WO2001016312A2 - Nucleic acid based modulators of gene expression - Google Patents

Abstract

Nucleic acid molecules (antisenses or ribozymes) useful as inhibitors of gene expression, especially of HER2, BACE, TERT, PTP-1B, MetAP-2, HBV, phospholamban, presenilin-2 and PKC-alpha. The nucleic acid molecules can be modified in various ways on the sugar and/or base moieties and/or on the phosphate backbone. They are used in pharmaceutical formulations for the treatment of diseases involving increased expression of the target genes. Also disclosed is a method for the synthesis of a modified pyrimidine nucleotide triphosphate and its incorporation into an oligonucleotide.

Description

NUCLEIC ACID BASED MODULATORS OF GENE EXPRESSION Background ofthe Invention

This invention relates to reagents useful as inhibitors of gene expression relating to diseases such as cancers, diabetes, obesity, Alzheimer's disease, cardiac diseases, age- related diseases, and/or hepatitis B infections and related conditions.

Summary of the Invention

The invention features novel nucleic acid-based techniques [e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, 2-5A antisense chimeras, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups (for example, Cook et al., U.S. Patent 5,359,051)] and methods for their use to modulate the expression of molecular targets impacting the development and progression of cancers, diabetes, obesity, Alzheimer's disease, cardiac diseases, age-related diseases, and or hepatitis B infections and related conditions In a preferred embodiment, the invention features novel nucleic acid-based techniques [e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, 2- 5A antisense chimeras, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups (for exaple, Cook et al., U.S. Patent 5,359,051)] and methods for their use for inhibiting the expression of disease related genes, e.g., Protein-Tyrosine-Phosphatase- lb (PTP-IB, Genbank accession No. NM_002827), Methionine Aminopeptidase (MetAP- 2, Genbank accession No. U29607), beta-Secretase (BACE, Genbank accession No. AF190725), Presenilin-1 (ps-1, Genbank accession No. L76517), Presenilin-2 (ps-2, Genbank accession No. L43964), Human Epidermal Growth Factor Receptor-2 (HER2/c- erb2/neu, Genbank accession No. X03363), Phosphola ban (PLN, Genbank accession No. NM_002667), Telomerase (TERT, Genbank accession No. NM_003219) and Hepatitis B virus genes (HBV, Genbank accession No. AF 100308.1). Such ribozymes can be used in a method for treatment of diseases caused by the expression of these genes in man and other animals, including other primates.

Thus, in an additional preferred embodiment, the invention features novel nucleic acid-based techniques such as enzymatic nucleic acid molecules and antisense molecules and methods for their use to down regulate or inhibit the expression of genes encoding Protein-Tyrosine-Phosphatase-lb (PTP-IB), Methionine Aminopeptidase (MetAP -2), beta-Secretase (BACE), Presenilin-1 (ps-1), Presenilin-2 (ps-2), Human Epidermal Growth Factor Receptor-2 (HER2/c-erb2/neu), Phospholamban (PLN), Telomerase (hTERT) PKC alpha, and Hepatitis B (HBV) proteins. In particular, applicant describes the selection and function of nucleic acid molecules capable of cleaving RNAs encoded by these genes and their use to reduce levels of PTP-IB, MetAP-2, BACE, ps-1 , ps-2, HER2, PLN, TERT, and/or HBV proteins in various tissues to treat the diseases discussed herein. Such nucleic acid molecules are also useful for diagnostic uses.

In a preferred embodiment, the invention features the use of one or more ofthe nucleic acid-based techniques independently or in combination to inhibit the expression of the genes encoding PTP-IB, MetAP-2, BACE, ps-1 , ps-2, HER2, PLN, TERT, and/or HBV. Specifically, the invention features the use of nucleic acid-based techniques to - specifically inhibit the expression of PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, PKC alpha, and/or HBV genes.

In yet another preferred embodiment, the invention features the use of an enzymatic nucleic acid molecule, preferably in the hammerhead, NCH (Inozyme), G-cleaver, amberzyme, zinzyme, and/or DNAzyme motif, to inhibit the expression of PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, PKC alpha and/or HBV RNA.

Applicant indicates that these nucleic acid molecules are able to inhibit expression of PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, PKC alpha, and/or HBV genes. Those of ordinary skill in the art, will find that it is clear from the examples described that other nucleic acid molecules that inhibit target PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV encoding mRNAs may be readily designed and are within the scope ofthe invention.

By "inhibit" it is meant that the activity of target genes or level of mRNAs or equivalent RNAs encoding target genes is reduced below that observed in the absence of the nucleic acid molecules of the instant invention (e.g., enzymatic nucleic acid molecules), antisense nucleic acids, 2-5A antisense chimeras, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups). In one embodiment, inhibition with an enzymatic nucleic acid molecule preferably is below that level observed in the presence of an enzymatically attenuated nucleic acid molecule that is able to bind to the same site on the mRNA, but is unable to cleave that RNA. In another embodiment, inhibition with nucleic acid molecules, including enzymatic nucleic acid and antisense molecules, is preferably greater than that observed in the presence of, for example, an oligonucleotide with scrambled sequence or with mismatches. In another embodiment, inhibition of target genes with the nucleic acid molecule ofthe instant invention is greater than in the presence ofthe nucleic acid molecule than in its absence. According to the invention, the activity of telomerase enzyme or the level of RNA encoding one or more portein subunits ofthe telomerase enzyme is inhibited if it is at least 10% less, 20% less, 50% less, 75% less or even not active or present at all, in the presence of a nucleic acid of the invention relative to the level in the absence of such a nucleic acid.

By "enzymatic nucleic acid molecule" it is meant a nucleic acid molecule which has complementarity in a substrate binding region to a specified gene target, and also has an enzymatic activity which is active to specifically cleave target RNA. That is, the enzymatic nucleic acid molecule is able to intermolecularly cleave RNA and thereby inactivate a target RNA molecule. These complementary regions allow sufficient hybridization ofthe enzymatic nucleic acid molecule to the target RNA and thus permit cleavage. One hundred percent complementarity is preferred, but complementarity as low as 50-75% may also be useful in this invention. The nucleic acids may be modified at the base, sugar, and/or phosphate groups. The term enzymatic nucleic acid is used interchangeably with phrases such as ribozymes, catalytic RNA, enzymatic RNA, catalytic DNA, aptazyme or aptamer-binding ribozyme, regulatable ribozyme, catalytic oligonucleotides, nucleozyme, DNAzyme, RNA enzyme, endoribonuclease, endonuclease, minizyme, leadzyme, oligozyme or DNA enzyme. All of these terminologies describe nucleic acid molecules with enzymatic activity. The specific enzymatic nucleic acid molecules described in the instant application are not meant to be limiting and those skilled in the art will recognize that all that is important in an enzymatic nucleic acid molecule of this invention is that it have a specific substrate binding site which is complementary to one or more ofthe target nucleic acid regions, and that it have nucleotide sequences within or surrounding that substrate binding site which impart a nucleic acid cleaving activity to the molecule (Cech et al., U.S. Patent No. 4,987,071 ; Cech et al., 1988, JAMA 260:20 3030-4). By "nucleic acid molecule" as used herein is meant a molecule having nucleotides.

The nucleic acid can be single, double, or multiple stranded and may comprise modified or unmodified nucleotides or non-nucleotides or various mixtures and combinations thereof. An example of a nucleic acid molecule according to the invention is a gene which encodes for a macromolecule such as a protein.

By "enzymatic portion" or "catalytic domain" is meant that portion/region ofthe enzymatic nucleic acid molecule essential for cleavage of a nucleic acid substrate (for example see Figures 1-5).

By "substrate binding arm" or "substrate binding domain" is meant that portion/region of a ribozyme which is complementary to (i.e., able to base-pair with) a portion of its substrate. Generally, such complementarity is 100%, but can be less if desired. For example, as few as 10 bases out of 14 may be base-paired. Such arms are shown generally in Figures 1-5. That is, these arms contain sequences within a ribozyme which are intended to bring ribozyme and target RNA together through complementary base-pairing interactions. The ribozyme ofthe invention may have binding arms that are contiguous or non-contiguous and may be of varying lengths. The length ofthe binding arm(s) are preferably greater than or equal to four nucleotides and of sufficient length to stably interact with the target RNA; specifically 12-100 nucleotides; more specifically 14- 24 nucleotides long. If two binding arms are chosen, the design is such that the length of the binding arms are symmetrical (i.e., each ofthe binding arms is ofthe same length; e.g., five and five nucleotides, six and six nucleotides or seven and seven nucleotides long) or asymmetrical (i.e., the binding arms are of different length; e.g., six and three nucleotides; three and six nucleotides long; four and five nucleotides long; four and six nucleotides long; four and seven nucleotides long; and the like). Binding arms can be complementary to the specified substrate, to a portion ofthe indicated substrate, to the indicated substrate sequence and additional adjacent sequence, or a portion ofthe indicated sequence and additional adjacent sequence. By "NCH" or "Inozyme" motif is meant, an enzymatic nucleic acid molecule comprising a motif as described in Ludwig et al, USSN No. 09/406,643, filed September 27, 1999, entitled "COMPOSITIONS HAVING RNA CLEAVING ACTIVITY", and International PCT publication Nos. WO 98/58058 and WO 98/58057, all incorporated by reference herein in their entirety, including the drawings. By "G-cleaver" motif is meant, an enzymatic nucleic acid molecule comprising a motif as described in Eckstein et al, International PCT publication No. WO 99/16871, incoφorated by reference herein in its entirety, including the drawings. By "zinzyme" motif is meant, a class II enzymatic nucleic acid molecule comprising a motif as described herein and in Beigelman et al, International PCT publication No. WO 99/55857, incoφorated by reference herein in its entirety, including the drawings. By "amberzyme" motif is meant, a class I enzymatic nucleic acid molecule comprising a motif as described herein and in Beigelman et al, International PCT publication No. WO 99/55857, incoφorated by reference herein in its entirety, including the drawings.

By 'DNAzyme' is meant, an enzymatic nucleic acid molecule lacking a ribonucleotide (2' -OH) group. In particular embodiments, the enzymatic nucleic acid molecule may have an attached linker(s) or other attached or associated groups, moieties, or chains containing one or more nucleotides with 2'-OH groups. A DNAzyme can be synthesized chemically or can be expressed by means of a single stranded DNA vector or equivalent thereof.

By "sufficient length" is meant an oligonucleotide of greater than or equal to 3 nucleotides that is of a length great enough to provide the intended function under the expected condition. For example, for binding arms of enzymatic nucleic acid "sufficient length" means that the binding arm sequence is long enough to provide stable binding to a target site under the expected binding conditions. Preferably, the binding arms are not so long as to prevent useful turnover. By "stably interact" is meant, interaction ofthe oligonucleotides with target nucleic acid (e.g., by forming hydrogen bonds with complementary nucleotides in the target under physiological conditions).

By "equivalent" RNA to PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV is meant to include those naturally occurring RNA molecules having homology (partial or complete) to PTP-IB, MetAP-2, BACE, ps-1 , ps-2, HER2, PLN, TERT, and/or HBV proteins or encoding for proteins with similar function as PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV in various organisms, including human, rodent, primate, rabbit, pig, protozoans, fungi, plants, and other microorganisms and parasites. The equivalent RNA sequence also includes in addition to the coding region, regions such as 5 '-untranslated region, 3 '-untranslated region, introns, intron-exon junction and the like in HBV. By "homology" is meant the nucleotide sequence of two or more nucleic acid molecules is partially or completely identical.

By "antisense nucleic acid", it is meant a non-enzymatic nucleic acid molecule that binds to target RNA by means of RNA-RNA or RNA-DNA or RNA-PNA (protein nucleic acid; Egholm et al, 1993 Nature 365, 566) interactions and alters the activity ofthe target RNA (for a review, see Stein and Cheng, 1993 Science 261, 1004 and Woolf et al, US patent No. 5,849,902). Typically, antisense molecules will be complementary to a target sequence along a single contiguous sequence ofthe antisense molecule. However, in certain embodiments, an antisense molecule may bind to substrate such that the substrate molecule forms a loop, and/or an antisense molecule may bind such that the antisense molecule forms a loop. Thus, the antisense molecule may be complementary to two (or even more) non-contiguous substrate sequences or two (or even more) non-contiguous sequence portions of an antisense molecule may be complementary to a target sequence or both. For a review of current antisense strategies, see Schmajuk et al, 1999, J. Biol. Chem., 27 A, 21783-21789, Delihas et al, 1997, Nature, 15, 751-753, Stein et al, 1997, Antisense N. A. Drug Dev., 7, 151, Crooke, 1998, Biotech. Genet. Eng. Rev., 15, 121-157, Crooke, 1997, Ad. Pharmacol, 40, 1-49. In addition, antisense DNA can be used to target RNA by means of DNA-RNA interactions, thereby activating RNase H, which digests the target RNA in the duplex. Antisense DNA can be synthesized chemically or can be expressed via the use of a single stranded DNA expression vector or the equivalent thereof.

By "2-5A antisense chimera" it is meant, an antisense oligonucleotide containing a 5'-phosphorylated 2'-5'-linked adenylate residue. These chimeras bind to target RNA in a sequence-specific manner and activate a cellular 2-5 A-dependent ribonuclease which, in turn, cleaves the target RNA (Torrence et al, 1993 Proc. Natl. Acad. Sci. USA 90, 1300). By "triplex DNA" it is meant an oligonucleotide that can bind to a double-stranded DNA in a sequence-specific manner to form a triple-strand helix. Formation of such triple helix structure has been shown to inhibit transcription ofthe targeted gene (Duval- Valentin et al, 1992, Proc. Natl. Acad. Sci.USA, 89, 504). By "gene" it is meant a nucleic acid that encodes a RNA. By "complementarity" is meant that a nucleic acid can form hydrogen bond(s) with another RNA sequence by either traditional Watson-Crick or other non-traditional types. In reference to the nucleic molecules ofthe present invention, the binding free energy for a nucleic acid molecule with its target or complementary sequence is sufficient to allow the relevant function ofthe nucleic acid to proceed, e.g., ribozyme cleavage, antisense or triple helix inhibition. Determination of binding free energies for nucleic acid molecules is well known in the art (see, e.g., Turner et al., 1987, CSH Symp. Quant. Biol. LJJ pp.123-133; Frier et al., 1986, Proc. Nat. Acad. Sci. USA 83:9373-9377; Turner et al., 1987, J. Am. Chem. Soc. 109:3783-3785). A percent complementarity indicates the percentage of contiguous residues in a nucleic acid molecule which can form hydrogen bonds (e.g.,

Watson-Crick base pairing) with a second nucleic acid sequence (e.g., 5, 6, 7, 8, 9, 10 out of 10 being 50%, 60%, 70%, 80%, 90%, and 100% complementary). "Perfectly complementary" means that all the contiguous residues of a nucleic acid sequence will hydrogen bond with the same number of contiguous residues in a second nucleic acid sequence.

At least seven basic varieties of naturally-occurring enzymatic RNAs are known presently. Each can catalyze the hydrolysis of RNA phosphodiester bonds in trans (and thus can cleave other RNA molecules) under physiological conditions. Table I summarizes some ofthe characteristics of these ribozymes. In general, enzymatic nucleic acids act by first binding to a target RNA. Such binding occurs through the target binding portion of a enzymatic nucleic acid which is held in close proximity to an enzymatic portion ofthe molecule that acts to cleave the target RNA. Thus, the enzymatic nucleic acid first recognizes and then binds a target RNA through complementary base-pairing, and once bound to the correct site, acts enzymatically to cut the target RNA. Strategic cleavage of such a target RNA will destroy its ability to direct synthesis of an encoded protein. After an enzymatic nucleic acid has bound and cleaved its RNA target, it is released from that RNA to search for another target and can repeatedly bind and cleave new targets. Thus, a single ribozyme molecule is able to cleave many molecules of target RNA. In addition, the ribozyme is a highly specific inhibitor of gene expression, with the specificity of inhibition depending not only on the base-pairing mechanism of binding to the target RNA, but also on the mechanism of target RNA cleavage. Single mismatches, or base-substitutions, near the site of cleavage can completely eliminate catalytic activity of a ribozyme.

The enzymatic nucleic acid molecule that cleave the specified sites in PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV-specific RNAs represent a novel therapeutic approach to treat a variety of pathologic indications, including, HBV infection, hepatitis, hepatocellular carcinoma, tumorigenesis, cirrhosis, liver failure, cancers including breast, ovarian, prostate, and esophogeal cancer, tumorigenesis, retinopathy, arthritis, psoriasis, female reproduction, restinosis, certain infectious diseases, transplant rejection and autoimmune disease such as multiple sclerosis, lupus, and AIDS, age related diseases such as macular degeneration and skin ulceration, Alzheimer's disease, dementia, diabetes, obesity and any other condition related to the level of PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and or HBV in a cell or tissue. In one ofthe preferred embodiments ofthe inventions described herein, the enzymatic nucleic acid molecule is formed in a hammerhead or haiφin motif, but may also be formed in the motif of a hepatitis delta virus, group I intron, group U intron or RNase P RNA (in association with an RNA guide sequence), Neurospora VS RNA, DNAzymes, NCH cleaving motifs, or G-cleavers. Examples of such hammerhead motifs are described by Dreyfus, supra, Rossi et al, 1992, AIDS Research and Human Retroviruses 8, 183. Examples of haiφin motifs are described by Hampel et al, EP0360257, Hampel and Tritz, 1989 Biochemistry 28, 4929, Feldstein et al, 1989, Gene 82, 53, Haseloff and Geriach, 1989, Gene, 82, 43, Hampel et al, 1990 Nucleic Acids Res. 18, 299; and Chowrira & McSwiggen, US. Patent No. 5,631,359. The hepatitis delta virus motif is described by Perrotta and Been, 1992 Biochemistry 31, 16. The RNase P motif is described by Guerrier-Takada et al, 1983 Cell 35, 849; Forster and Airman, 1990, Science 249, 783; and Li and Airman, 1996, Nucleic Acids Res. 24, 835. The Neurospora VS RNA ribozyme motif is described by Collins (Saville and Collins, 1990 Cell 61, 685-696; Saville and Collins, 1991 Proc. Natl. Acad. Sci. USA 88, 8826-8830; Collins and Olive, 1993 Biochemistry 32, 2795-2799; and Guo and Collins, 1995, EMBO. J. 14, 363). Group II introns are described by Griffin et al, 1995, Chem. Biol. 2, 761; Michels and Pyle, 1995, Biochemistry 34, 2965; and Pyle et al, International PCT Publication No. WO 96/22689. The Group I intron is described by Cech et al, U.S. Patent 4,987,071. DNAzymes are described by Usman et al, International PCT Publication No. WO 95/11304; Chartrand et al., 1995, NAR 23, 4092; Breaker et al, 1995, Chem. Bio. 2, 655; and Santoro et al, 1997, PNAS 94, 4262. NCH cleaving motifs are described in Ludwig & Sproat, International PCT Publication No. WO 98/58058; and G-cleavers are described in Kore et al, 1998, Nucleic Acids Research 26, 4116-4120 and Eckstein et al, International PCT Publication No. WO 99/16871. Additional motifs include the Aptazyme (Breaker et al, WO 98/43993), Amberzyme (Class I motif; Figure 3; Beigelman et al, International PCT publication No. WO 99/55857) and Zinzyme (Beigelman et al, International PCT publication No. WO 99/55857), all these references are incoφorated by reference herein in their totalities, including drawings and can also be used in the present invention. These specific motifs are not limiting in the invention and those skilled in the art will recognize that all that is important in an enzymatic nucleic acid molecule of this invention is that it has a specific substrate binding site which is complementary to one or more ofthe target gene RNA regions, and that it have nucleotide sequences within or surrounding that substrate binding site which impart an RNA cleaving activity to the molecule (Cech et al, U.S. Patent No. 4,987,071).

In preferred embodiments ofthe present invention, a nucleic acid molecule, e.g., an antisense molecule, a triplex DNA, or a ribozyme, is 13 to 100 nucleotides in length, e.g., in specific embodiments 35, 36, 37, or 38 nucleotides in length (e.g., for particular ribozymes or antisense). In particular embodiments, the nucleic acid molecule is 15-100, 17-100, 20-100, 21-100, 23-100, 25-100, 27-100, 30-100, 32-100, 35-100, 40-100, 50-100, 60-100, 70-100, or 80-100 nucleotides in length. Instead of 100 nucleotides being the upper limit on the length ranges specified above, the upper limit ofthe length range can be, for example, 30, 40, 50, 60, 70, or 80 nucleotides. Thus, for any ofthe length ranges, the length range for particular embodiments has lower limit as specified, with an upper limit as specified which is greater than the lower limit. For example, in a particular embodiment, the length range can be 35-50 nucleotides in length. All such ranges are expressly included. Also in particular embodiments, a nucleic acid molecule can have a length which is any ofthe lengths specified above, for example, 21 nucleotides in length. In a preferred embodiment, the invention provides a method for producing a class of nucleic acid-based gene inhibiting agents which exhibit a high degree of specificity for the RNA of a desired target. For example, the enzymatic nucleic acid molecule is preferably targeted to a highly conserved sequence region of target RNAs encoding PTP-IB, MetAP- 2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV proteins (specifically PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV RNA) such that specific treatment of a disease or condition can be provided with either one or several nucleic acid molecules ofthe invention. Such nucleic acid molecules can be delivered exogenously to specific tissue or cellular targets as required. Alternatively, the nucleic acid molecules (e.g., ribozymes and antisense) can be expressed from DNA and/or RNA vectors that are delivered to specific cells.

As used in herein "cell" is used in its usual biological sense, and does not refer to an entire multicellular organism, e.g., specifically does not refer to a human. The cell may be present in an organism which may be a human but is preferably a non-human multicellular organism, e.g., birds, plants and mammals such as cows, sheep, apes, monkeys, swine, dogs, and cats. The cell may be prokaryotic (e.g., bacterial cell) or eukaryotic (e.g., mammalian or plant cell).

By "PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV proteins" is meant, a protein or a mutant protein derivative thereof, comprising sequence expressed and/or encoded by PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, genes and/or the HBV genome respectively.

By "highly conserved sequence region" is meant a nucleotide sequence of one or more regions in a target gene does not vary significantly from one generation to the other or from one biological system to the other.

The enzymatic nucleic acid-based inhibitors of PTP-IB, MetAP-2, BACE, ps-1, ps- 2, HER2, PLN, TERT, and/or HBV expression are useful for the prevention ofthe diseases and conditions including HBV infection, hepatitis, hepatocellular carcinoma, tumorigenesis, cirrhosis, liver failure, cancers including breast, ovarian, prostate, and esophogeal cancer, tumorigenesis, retinopathy, arthritis, psoriasis, female reproduction, restinosis, certain infectious diseases, transplant rejection and autoimmune disease such as multiple sclerosis, lupus, and AIDS, age related diseases such as macular degeneration and skin ulceration, Alzheimer's disease, dementia, diabetes, obesity and any other condition related to the level of PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV in a cell or tissue, and any other diseases or conditions that are related to the levels of PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV in a cell or tissue. By "related" is meant that the reduction of PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV expression (specifically PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV genes) RNA levels and thus reduction in the level ofthe respective protein will relieve, to some extent, the symptoms ofthe disease or condition.

The nucleic acid-based inhibitors ofthe invention are added directly, or can be complexed with cationic lipids, packaged within liposomes, or otherwise delivered to target cells or tissues. The nucleic acid or nucleic acid complexes can be locally administered to relevant tissues ex vivo, or in vivo through injection, infusion pump or stent, with or without their incoφoration in biopolymers. In preferred embodiments, the enzymatic nucleic acid inhibitors comprise sequences, which are complementary to the subsfrate sequences in Tables 3-31, 33, 34, 36-43, 56, 58, 59, 62, 63. Examples of such enzymatic nucleic acid molecules also are shown in Tables 3-29, 31, 33, 34, 37-43, 56, 58, 59, 62, 63. Examples of such enzymatic nucleic acid molecules consist essentially of sequences defined in these tables. hi yet another embodiment, the invention features antisense nucleic acid molecules including sequences complementary to the substrate sequences shown in Tables 3-31, 33, 34, 36, 37-43, 56, 58, 59, 62, 63. Such nucleic acid molecules can include sequences as shown for the binding arms ofthe enzymatic nucleic acid molecules in Tables 3-29, 31, 33, 34, 37-43, 56, 58, 59, 62, 63. Similarly, triplex molecules can be provided targeted to the corresponding DNA target regions, and containing the DNA equivalent of a target sequence or a sequence complementary to the specified target (subsfrate) sequence. Typically, antisense molecules will be complementary to a target sequence along a single contiguous sequence ofthe antisense molecule. However, in certain embodiments, an antisense molecule may bind to subsfrate such that the subsfrate molecule forms a loop, and/or an antisense molecule may bind such that the antisense molecule forms a loop. Thus, the antisense molecule may be complementary to two (or even more) noncontiguous substrate sequences or two (or even more) non-contiguous sequence portions of an antisense molecule may be complementary to a target sequence or both. In another aspect, the invention provides mammalian cells containing one or more nucleic acid molecules and/or expression vectors of this invention. The one or more nucleic acid molecules may independently be targeted to the same or different sites. By "consists essentially of is meant that the active nucleic acid molecule ofthe invention, for example, an enzymatic nucleic acid molecule, contains an enzymatic center or core equivalent to those in the examples, and binding arms able to bind mRNA such that cleavage at the target site occurs. Other sequences may be present which do not interfere with such cleavage. Thus, a core region may, for example, include one or more loop or stem-loop structures, which do not prevent enzymatic activity. "X" in the sequences in Tables 3, 4, 9, 10, 13, 14, 18, 19, 24, 25, 33, 34, 37, 38, 63 can be such a loop. A core sequence for a hammerhead ribozyme can be CUGAUGAG X CGAA where X=GCCGUUAGGC or other stem II region as specifically or generally known in the art. In another aspect ofthe invention, ribozymes or antisense molecules that interact with target RNA molecules and inhibit PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV (specifically PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV RNA) activity are expressed from transcription units inserted into DNA or RNA vectors. The recombinant vectors are preferably DNA plasmids or viral vectors. Ribozyme or antisense expressing viral vectors could be constructed based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus. Preferably, the recombinant vectors capable of expressing the ribozymes or antisense are delivered as described above, and persist in target cells. Alternatively, viral vectors may be used that provide for transient expression of ribozymes or antisense. Such vectors might be repeatedly administered as necessary. Once expressed, the ribozymes or antisense bind to the target RNA and inhibit its function or expression. Delivery of ribozyme or antisense expressing vectors could be systemic, such as by intravenous or intramuscular administration, by administration to target cells ex -planted from the patient followed by reinfroduction into the patient, or by any other means that would allow for introduction into the desired target cell. Antisense DNA can be expressed via the use of a single stranded DNA intracellular expression vector.

By RNA is meant a molecule comprising at least one ribonucleotide residue. By "ribonucleotide" is meant a nucleotide with a hydroxyl group at the 2' position of a β-D- ribo-furanose moiety. By "vectors" is meant any nucleic acid- and/or viral-based technique used to deliver a desired nucleic acid. By "patient" is meant an organism, which is a donor or recipient of explanted cells or the cells themselves. "Patient" also refers to an organism to which the nucleic acid molecules ofthe invention can be administered. Preferably, a patient is a mammal or mammalian cells. More preferably, a patient is a human or human cells. The nucleic acid molecules ofthe instant invention, individually, or in combination or in conjunction with other drugs, can be used to treat diseases or conditions discussed above. For example, to treat a disease or condition associated with PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV, the patient may be treated, or other appropriate cells may be treated, as is evident to those skilled in the art, individually or in combination with one or more drugs under conditions suitable for the treatment.

In a further embodiment, the described molecules, such as antisense or ribozymes, can be used in combination with other known treatments to treat conditions or diseases discussed above. For example, the described molecules could be used in combination with one or more known therapeutic agents to treat HBV infection, hepatitis, hepatocellular carcinoma, tumorigenesis, cirrhosis, liver failure, cancers including breast, ovarian, prostate, and esophogeal cancer, tumorigenesis, retinopathy, arthritis, psoriasis, female reproduction, restinosis, certain infectious diseases, transplant rejection and autoimmune disease such as multiple sclerosis, lupus, and AIDS, age related diseases such as macular degeneration and skin ulceration, Alzheimer's disease, dementia, diabetes, and/or obesity. In another preferred embodiment, the invention features nucleic acid-based inhibitors (e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups) and methods for their use to down regulate or inhibit the expression of RNA (e.g., PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and or HBV) capable of progression and/or maintenance of HBV infection, hepatitis, hepatocellular carcinoma, tumorigenesis, cirrhosis, liver failure, cancers including breast, ovarian, prostate, and esophogeal cancer, tumorigenesis, retinopathy, arthritis, psoriasis, female reproduction, restinosis, certain infectious diseases, fransplant rejection and autoimmune disease such as multiple sclerosis, lupus, and ADDS, age related diseases such as macular degeneration and skin ulceration, Alzheimer's disease, dementia, diabetes, and/or obesity. In another preferred embodiment, the invention features nucleic acid-based techniques (e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups) and methods for their use to down regulate or inhibit the expression of PTP-IB, MetAP-2, BACE, ps- 1 , ps-2, HER2, PLN, TERT, and or HBV RNA expression.

By "comprising" is meant including, but not limited to, whatever follows the word "comprising". Thus, use ofthe term "comprising" indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present. By "consisting of is meant including, and limited to, whatever follows the phrase "consisting of. Thus, the phrase "consisting of indicates that the listed elements are required or mandatory, and that no other elements may be present. By "consisting essentially of is meant including any elements listed after the phrase, and limited to other elements that do not interfere with or contribute to the activity or action specified in the disclosure for the listed elements. Thus, the phrase "consisting essentially of indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present depending upon whether or not they affect the activity or action ofthe listed elements.

Other features and advantages ofthe invention will be apparent from the following description ofthe preferred embodiments thereof, and from the claims.

Description Of The Preferred Embodiments

The drawings will first briefly be described.

Drawings: Figure 1 shows the secondary structure model for seven different classes of enzymatic nucleic acid molecules. Arrow indicates the site of cleavage. indicate the target sequence. Lines interspersed with dots are meant to indicate tertiary interactions. - is meant to indicate base-paired interaction. Group I Intron: P1-P9.0 represent various stem-loop structures (Cech et al, 1994, Nature Struc. Bio., 1, 273). RNase P (M1RNA): EGS represents external guide sequence (Forster et al, 1990, Science, 249, 783; Pace et al, 1990, J. Biol. Chem., 265, 3587). Group II Intron: 5'SS means 5' splice site; 3'SS means 3 '-splice site; IBS means intron binding site; EBS means exon binding site (Pyle et al, 1994, Biochemistry, 33, 2716). VS RNA: I- VI are meant to indicate six stem-loop structures; shaded regions are meant to indicate tertiary interaction (Collins, International PCT Publication No. WO 96/19577). HDV Ribozyme: I-IV are meant to indicate four stem-loop structures (Been et al, US Patent No. 5,625,047). Hammerhead Ribozyme: I- HI are meant to indicate three stem- loop structures; stems I-HI can be of any length and may be symmetrical or asymmetrical (Usman et al, 1996, Curr. Op. Struct. Bio., 1, 527). Hairpin Ribozyme: Helix 1, 4 and 5 can be of any length; Helix 2 is between 3 and 8 base-pairs long; Y is a pyrimidine; Helix 2 (H2) is provided with a least 4 base pairs (i.e., n is 1, 2, 3 or 4) and helix 5 can be optionally provided of length 2 or more bases (preferably 3 - 20 bases, i.e., m is from 1 - 20 or more). Helix 2 and helix 5 may be covalently linked by one or more bases (i.e., r is > 1 base). Helix 1, 4 or 5 may also be extended by 2 or more base pairs (e.g., - 20 base pairs) to stabilize the ribozyme structure, and preferably is a protein binding site. In each instance, each N and N' independently is any normal or modified base and each dash represents a potential base- pairing interaction. These nucleotides may be modified at the sugar, base or phosphate.

Complete base-pairing is not required in the helices, but is preferred. Helix 1 and 4 can be of any size (i.e., o and p is each independently from 0 to any number, e.g., 20) as long as some base-pairing is maintained. Essential bases are shown as specific bases in the structure, but those in the art will recognize that one or more may be modified chemically (abasic, base, sugar and/or phosphate modifications) or replaced with another base without significant effect. Helix 4 can be formed from two separate molecules, i.e., without a connecting loop. The connecting loop when present may be a ribonucleotide with or without modifications to its base, sugar or phosphate, "q" > is 2 bases. The connecting loop can also be replaced with a non-nucleotide linker molecule. H refers to bases A, U, or C. Y refers to pyrimidine bases. " " refers to a covalent bond. (Burke et al, 1996,

Nucleic Acids & Mol Biol, 10, 129; Chowrira et al, US Patent No. 5,631,359).

Figure 2 shows examples of chemically stabilized ribozyme motifs. HH Rz, represents hammerhead ribozyme motif (Usman et al, 1996, Curr. Op. Struct. Bio., 1, 527); NCH Rz represents the NCH ribozyme motif (described herein and in Ludwig & Sproat, International PCT Publication No. WO 98/58058); G-Cleaver, represents G- cleaver ribozyme motif (Kore et α/., 1998, Nucleic Acids Research, 26, 4116-4120). N or n, represent independently a nucleotide which may be same or different and have complementarity to each other; rl, represents ribo-Inosine nucleotide; arrow indicates the site of cleavage within the target. Position 4 ofthe HH Rz and the NCH Rz is shown as having 2'-C-allyl modification, but those skilled in the art will recognize that this position can be modified with other modifications well known in the art, so long as such modifications do not significantly inhibit the activity ofthe ribozyme.

Figure 3 shows an example ofthe Amberzyme ribozyme motif that is chemically stabilized (see, for example, Beigelman et al, International PCT publication No. WO 99/55857; also referred to as Class I Motif). The Amberzyme motif is a class of enzymatic nucleic acid molecules that do not require the presence of a ribonucleotide (2'-OH) group for activity.

Figure 4 shows an example ofthe Zinzyme A ribozyme motif that is chemically stabilized (see, for example, International PCT publication No. WO 99/55857; also referred to as Class A Motif). The Zinzyme motif is a class of enzymatic nucleic acid molecules that do not require the presence of a ribonucleotide (2' -OH) group for activity. Figure 5 shows an example of a DNAzyme motif described by Santoro et al., 1997, PNAS, 94, 4262.

Figure 6 is a diagrammatic representation ofthe hammerhead ribozyme motif known in the art and the NCH motif. Stem JJ can be 2 base-pair long, preferably, 2, 3, 4, 5, 6, 7, 8, and 10 base-pairs long. Each N and N' is independently any base or non- nucleotide as used herein; X is adenosine, cytidine or uridine; Stem I-HI are meant to indicate three stem-loop structures; stems I-HI can be of any length and may be symmetrical or asymmetrical (Usman et al, 1996, Curr. Op. Struct. Bio., 1, 527); arrow indicates the site of cleavage in the target RNA; Rz refers to ribozyme; Loop II may be present or absent. If Loop II is present it is greater than or equal to three nucleotides, preferably four nucleotides. The Loop II sequence is preferably 5'-GAAA-3' or 5'- GUUA-3'.

Figure 7 shows examples of chemically stabilized ribozyme motifs. HH Rz, represents hammerhead ribozyme motif (Usman et al, 1996, Curr. Op. Struct. Bio., 1, 527); NCH-Inosine Rz represents the NCH ribozyme motif with riboinosine at 15.1 position; NCH-Xylo Rz represents the NCH ribozyme with xylo inosine at 15.1 position. N or n, represent independently a nucleotide which may be same or different and may have complementarity to each other; ri, represents ribo-Inosine nucleotide; xl represent xylo- inosine; arrow indicates the site of cleavage within the target. Position 4 ofthe HH Rz and the NCH Rzs is shown as having 2'-C-allyl modification, but those skilled in the art will recognize that this position can be modified with other modifications well known in the art, so long as such modifications do not significantly inhibit the activity ofthe ribozyme. Figure 8 is a graphical representation of data showing inhibition of cell proliferation mediated by NCH and HH ribozymes targeted against HER2/new/ErbB2 gene. Untreated, refers to cells not treated with ribozymes; HH RZ refers to hammerhead ribozyme; NCX RZ refers to the NCH ribozymes ofthe invention; LA refers to catalytically inactive or attenuated ribozyme used as a confrol.

Figure 9 is a schematic diagram ofthe process for the synthesis of beta-D- xylofuranosyl hypoxantine 3 '-phosphoramidite.

Figure 10 displays a schematic representation of NTP synthesis using nucleoside substrates. Figure 11 shows a scheme for an in vitro selection method. A pool of nucleic acid molecules is generated with a random core region and one or more region(s) with a defined sequence. These nucleic acid molecules are bound to a column containing immobilized oligonucleotide with a defined sequence, where the defined sequence is complementary to region(s) of defined sequence of nucleic acid molecules in the pool. Those nucleic acid molecules capable of cleaving the immobilized oligonucleotide (target) in the column are isolated and converted to complementary DNA (cDNA), followed by transcription using NTPs to form a new nucleic acid pool.

Figure 12 shows a scheme for a two column in vitro selection method. A pool of nucleic acid molecules is generated with a random core and two flanking regions (region A and region B) with defined sequences. The pool is passed through a column which has immobilized oligonucleotides with regions A' and B' that are complementary to regions A and B ofthe nucleic acid molecules in the pool, respectively. The column is subjected to conditions sufficient to facilitate cleavage ofthe immobilized oligonucleotide target. The molecules in the pool that cleave the target (active molecules) have A' region ofthe target bound to their A region, whereas the B region is free. The column is washed to isolate the active molecules with the bound A' region ofthe target. This pool of active molecules may also contain some molecules that are not active to cleave the target (inactive molecules) but have dissociated from the column. To separate the contaminating inactive molecules from the active molecules, the pool is passed through a second column (column 2) which contains immobilized oligonucleotides with the A' sequence but not the B' sequence. The inactive molecules will bind to column 2 but the active molecules will not bind to column 2 because their A region is occupied by the A' region ofthe target oligonucleotide from column 1. Column 2 is washed to isolate the active molecules for further processing as described in the scheme shown in Figure 11.

Figure 13 is a diagram of a novel 48 nucleotide enzymatic nucleic acid motif which was identified using in vitro methods described in the instant invention. The molecule shown is only exemplary. The 5' and 3' terminal nucleotides (referring to the nucleotides ofthe subsfrate binding arms rather than merely the single terminal nucleotide on the 5' and 3' ends) can be varied so long as those portions can base-pair with target substrate sequence. In addition, the guanosine (G) shown at the cleavage site ofthe subsfrate can be changed to other nucleotides so long as the change does not eliminate the ability of enzymatic nucleic acid molecules to cleave the target sequence. Substitutions in the nucleic acid molecule and/or in the subsfrate sequence can be readily tested, for example, as described herein.

Figure 14 is a schematic diagram of HCV luciferase assay used to demonstrate efficacy of class I enzymatic nucleic acid molecule motif. Figure 15 is a graph indicating the dose curve of an enzymatic nucleic acid molecule targeting site 146 on HCV RNA.

Figure 16 is a bar graph showing enzymatic nucleic acid molecules targeting 4 sites within the HCV RNA are able to reduce RNA levels in cells.

Figure 17 shows secondary structures and cleavage rates for characterized Class π enzymatic nucleic acid motifs.

Figure 18 is a diagram of a novel 35 nucleotide enzymatic nucleic acid motif which was identified using in vitro methods described in the instant invention. The molecule shown is only exemplary. The 5' and 3' terminal nucleotides (referring to the nucleotides ofthe subsfrate binding arms rather than merely the single terminal nucleotide on the 5' and 3' ends) can be varied so long as those portions can base-pair with target substrate sequence. In addition, the guanosine (G) shown at the cleavage site ofthe subsfrate can be changed to other nucleotides so long as the change does not eliminate the ability of enzymatic nucleic acid molecules to cleave the target sequence. Substitutions in the nucleic acid molecule and/or in the substrate sequence can be readily tested, for example, as described herein.

Figure 19 is a bar graph showing subsfrate specificities for Class π (zinzyme) ribozymes.

Figure 20 is a bar graph showing Class II enzymatic nucleic acid molecules targeting 10 representative sites within the HER2 RNA in a cellular proliferation screen.

Figure 21 is a synthetic scheme outlining the synthesis of 5-[3- aminopropynyl(propyl)]uridine 5'-triphosphates and 4-imidazoleaceticacid conjugates. Figure 22 is a synthetic scheme outlining the synthesis of 5-[3-(N-4- imidazoleacetyl)aminopropynyl(propyl)]uridine 5 '-triphosphates.

Figure 23 is a synthetic scheme outlining the synthesis of carboxylate tethered uridine 5'-triphosphoates.

Figure 24 is a synthetic scheme outlining the synthesis of 5-(3-aminoalkyl) and 5- [3(N-succinyl)aminopropyl] functionalized cytidines.

Figure 25 is a diagram of a class I ribozyme stem truncation and loop replacement analysis.

Figure 26 is a diagram of class I ribozymes with truncated stem(s) and/or non- nucleotide linkers used in loop structures. Figure 27 is a diagram of "no-ribo" class LI ribozymes.

Figure 28 is a graph showing cleavage reactions with class II ribozymes under differing divalent metal concentrations.

Figure 29 is a diagram of differing class π ribozymes with varying ribo content and their relative rates of catalysis. Figure 30 is a graph showing class II ribozyme (zinzyme) mediated reduction of

HER2 RNA in SKBR3 breast carcinoma cells. Cells were treated with 100 nm, and 200 nm of zinzyme (RPI 18656) targeting site 972 of HER2 RNA and a corresponding scrambled attenuated confrol complexed with 2.5 μg/ml of lipid. Active zinzymes and scrambled attenuated controls were compared to untreated cells after 24 hours post treatment. Figure 31 is a graph showing class II ribozyme (zinzyme) mediated dose response anti-prolferation assay in SKBR3 breast carcinoma cells. Cells were freated with 100 nm, and 200 nm of zinzyme (RPI 18656) targeting site 972 of HER2 RNA and a corresponding scrambled attenuated control complexed with 2.0 μg/ml of lipid. Active zinzymes and scrambled attenuated controls were compared to untreated cells after 24 hours post treatment.

Figure 32 is a graph which shows the dose dependent reduction of HER2 RNA in SKOV-3 cells treated with RPI 19293 from 0 to 100 nM with 5.0 μg/ml of cationic lipid.

Figure 33 is a graph which shows the dose dependent reduction of HER2 RNA and inhibition of cellular proliferation in SKBR-3 cells freated with RPI 19293 from 0 to 400 nM with 5.0 μg/ml of cationic lipid.

Figure 34 shows a non-limiting example ofthe replacement of a 2'-O-methyl 5'- CA-3' with a ribo G in the class LI (zinzyme) motif. The representative motif shown for the puφose ofthe figure is a "seven-ribo" zinzyme motif, however, the interchangeability of a G and a CA in the position shown in Figure 25 of the class II (zinzyme) motif extends to any combination of 2-O-methyl and ribo residues. For instance, a 2'-O-methyl G can replace the 2'-O-methyl 5'-CA-3' and vise versa.

Figure 35 is a graph which shows a screen of class II ribozymes (zinzymes) targeting site 972 of HER2 RNA which contain ribo-G reductions (RPI 19727 = no ribo, RPI 19728 = one ribo, RPI 19293 = two ribo, RPI 19729 = three ribo, RPI 19730 = four ribo, 19731 = five ribo, and RPI 19292 = seven ribo) for anti-proliferative activity in SKBR3 cells.

Figure 36 summarizes the results of functional group modification studies in which various nucleoside analogs were tested for activity in the NCH ribozyme motif. K_reι values describe the cleavage values of a given substituent at position 15.1 relative the Inosine at position 15.1 (1-15.1).

Figure 37 summarizes reported functional group modification studies performed at the A 15.1 residue in the A-15.1 »U-16.1 context of NUH cleaving ribozymes. K_reι values describe the cleavage values of a given substituent at position 15.1 relative the adenosine at position 15.1 (A-15.1). Mechanism of action of Nucleic Acid Molecules ofthe Invention

Antisense: Antisense molecules may be modified or unmodified RNA, DNA, or mixed polymer oligonucleotides and primarily function by specifically binding to matching sequences resulting in inhibition of peptide synthesis (Wu-Pong, Nov 1994, BioPharm, 20-33). The antisense oligonucleotide binds to target RNA by Watson Crick base-pairing and blocks gene expression by preventing ribosomal translation ofthe bound sequences either by steric blocking or by activating RNase H enzyme. Antisense molecules may also alter protein synthesis by interfering with RNA processing or transport from the nucleus into the cytoplasm (Mukhopadhyay & Roth, 1996, Crit. Rev. in Oncogenesis 7, 151 - 190).

In addition, binding of single stranded DNA to RNA may result in nuclease degradation ofthe heteroduplex (Wu-Pong, supra; Crooke, supra). To date, the only backbone modified DNA chemistry which will act as substrates for RNase H are phosphorothioates, phosphorodithioates, and borontrifluoridates. Recently, it has been reported that 2'-arabino and 2'-fluoro arabino- containing oligos can also activate RNase H activity.

A number of antisense molecules have been described that utilize novel configurations of chemically modified nucleotides, secondary structure, and/or RNase H substrate domains (Woolf et al., International PCT Publication No. WO 98/13526; Thompson et al, International PCT Publication No. WO 99/54459 ; Hartmann et al, International PCT Publication No. WO 00/17346) all of these are incoφorated by reference herein in their entirety.

Antisense DNA can be used to target RNA by means of DNA-RNA interactions, thereby activating RNase H, which digests the target RNA in the duplex. Antisense DNA can be chemically synthesized or can be expressed via the use of a single stranded DNA intracellular expression vector or the equivalent thereof.

Triplex Forming Oligonucleotides (TFO): Single stranded DNA may be designed to bind to genomic DNA in a sequence specific manner. TFOs are comprised of pyrimidine- rich oligonucleotides which bind DNA helices through Hoogsteen Base-pairing (Wu-Pong, supra). The resulting triple helix composed ofthe DNA sense, DNA antisense, and TFO disrupts RNA synthesis by RNA polymerase. The TFO mechanism may result in gene expression or cell death since binding may be irreversible (Mukhopadhyay & Roth, supra) 2'-5' Oligoadenylates: The 2-5 A system is an interferon-mediated mechanism for RNA degradation found in higher vertebrates (Mifra et al, 1996, Proc Nat Acad Sci USA 93, 6780-6785). Two types of enzymes, 2-5 A synthetase and RNase L, are required for RNA cleavage. The 2-5 A synthetases require double stranded RNA to form 2'-5' oligoadenylates (2-5 A). 2-5A then acts as an allosteric effector for utilizing RNase L which has the ability to cleave single stranded RNA. The ability to form 2-5 A structures with double stranded RNA makes this system particularly useful for inhibition of viral replication.

(2'-5') oligoadenylate structures may be covalently linked to antisense molecules to form chimeric oligonucleotides capable of RNA cleavage (Torrence, supra). These molecules putatively bind and activate a 2-5 A dependent RNase, the oligonucleotide/enzyme complex then binds to a target RNA molecule which can then be cleaved by the RNase enzyme. The covalent attachment of 2'-5' oligoadenylate structures is not limited to antisense applications, and can be further elaborated to include attachment to nucleic acid molecules ofthe instant invention.

Enzymatic Nucleic Acid: Seven basic varieties of naturally-occurring enzymatic RNAs are presently known. In addition, several in vitro selection (evolution) strategies (Orgel, 1979, Proc. R. Soc. London, B 205, 435) have been used to evolve new nucleic acid catalysts capable of catalyzing cleavage and ligation of phosphodi ester linkages (Joyce, 1989, Gene, 82, 83-87; Beaudry et al, 1992, Science 257, 635-641 ; Joyce, 1992, Scientific American 267, 90-97; Breaker et al, 1994, TIBTECH 12, 268; Bartel et al, 1993, Science 261:1411-1418; Szostak, 1993, TIBS 17, 89-93; Kumar et al, 1995, FASEB J., 9, 1183; Breaker, 1996, Curr. Op. Biotech., 7, 442; Santoro et al, 1997, Proc. Natl. Acad. Sci., 94, 4262; Tang et al, 1997, RNA 3, 914; Nakamaye & Eckstein, 1994, supra; Long & Uhlenbeck, 1994, supra; Ishizaka et al., 1995, supra; Vaish et al, 1997, Biochemistry 36, 6495; all of these are incoφorated by reference herein). Each can catalyze a series of reactions including the hydrolysis of phosphodiester bonds in trans (and thus can cleave other RNA molecules) under physiological conditions.

In general, enzymatic nucleic acids act by first binding to a target RNA. Such binding occurs through the target binding portion of an enzymatic nucleic acid which is held in close proximity to an enzymatic portion ofthe molecule that acts to cleave the target RNA. Thus, the enzymatic nucleic acid first recognizes and then binds a target RNA through complementary base-pairing, and once bound to the correct site, acts enzymatically to cut the target RNA. Strategic cleavage of such a target RNA will destroy its ability to direct synthesis of an encoded protein. After an enzymatic nucleic acid has bound and cleaved its RNA target, it is released from that RNA to search for another target and can repeatedly bind and cleave new targets.

Nucleic acid molecules of this invention will block to some extent PTP-IB, MetAP- 2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV protein expression and can be used to treat disease or diagnose disease associated with the levels of PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV. The enzymatic nature of a ribozyme has significant advantages, such as the concentration of ribozyme necessary to affect a therapeutic treatment is low. This advantage reflects the ability ofthe ribozyme to act enzymatically. Thus, a single ribozyme molecule is able to cleave many molecules of target RNA. In addition, the ribozyme is a highly specific inhibitor, with the specificity of inhibition depending not only on the base-pairing mechanism of binding to the target RNA, but also on the mechanism of target RNA cleavage. Single mismatches, or base-substitutions, near the site of cleavage can be chosen to completely eliminate catalytic activity of a ribozyme.

Nucleic acid molecules having an endonuclease enzymatic activity are able to repeatedly cleave other separate RNA molecules in a nucleotide base sequence-specific manner. Such enzymatic nucleic acid molecules can be targeted to virtually any RNA transcript, and achieve efficient cleavage in vitro (Zaug et al, 324, Nature, 429 1986 ; Uhlenbeck, 1987 Nature, 328, 596; Kim et al., 84 Proc. Natl. Acad. Sci. USA, 8788, 1987; Dreyfus, 1988, Einstein Quart. J. Bio. Med., 6, 92; Haseloff and Geriach, 334 Nature, 585, 1988; Cech, 260 JAMA, 3030, 1988; Jefferies et al., 17 Nucleic Acids Research, 1371, 1989; and Santoro et al, 1997 supra).

Because of their sequence specificity, trans-cleaving ribozymes show promise as therapeutic agents for human disease (Usman & McSwiggen, 1995 Ann. Rep. Med. Chem. 30, 285-294; Christoffersen and Marr, 1995 J. Med. Chem. 38, 2023-2037). Ribozymes can be designed to cleave specific RNA targets within the background of cellular RNA. Such a cleavage event renders the RNA non-functional and abrogates protein expression from that RNA. In this manner, synthesis of a protein associated with a disease state can be selectively inhibited (Warashina et al, 1999, Chemistry and Biology, 6, 237-250. The nucleic acid molecules ofthe instant invention are also referred to as GeneBloc™ reagents, which are essentially nucleic acid molecules (e.g.; ribozymes, antisense) capable of down-regulating gene expression.

Target sites

Targets for useful ribozymes and antisense nucleic acids can be determined as disclosed in Draper et al, WO 93/23569; Sullivan et al, WO 93/23057; Thompson et al, WO 94/02595; Draper et al, WO 95/04818; McSwiggen et al, US Patent No. 5,525,468, and all hereby incoφorated in their entireties by reference herein. Other examples include the following PCT applications, which concern inactivation of expression of disease- related genes: WO 95/23225, WO 95/13380, WO 94/02595, all incoφorated by reference herein. Rather than repeat the guidance provided in those documents here, below are provided specific examples of such methods, not limiting to those in the art. Ribozymes and antisense to such targets are designed as described in those applications and synthesized to be tested in vitro and in vivo, as also described. The sequence of human PTP-IB, MetAP-2, BACE, ps-1, ps-2, HER2, PLN, TERT, and/or HBV RNAs (for example, GenBank accession Nos. (PTP-IB,. NM_002827), (MetAP-2, U29607), (BACE, AF190725), (ps-1, L76517), (ps-2, L43964), (HER2/c-erb2/neu, X03363), (PLN, NM_002667), (TERT, NM_003219) and (HBV, AF100308.1, HBV strain 2-18; additionally, other HBV strains can be screened by one skilled in the art, see Table 35 for other possible strains) were screened for optimal enzymatic nucleic acid and antisense target sites using a computer-folding algorithm. Antisense, hammerhead, DNAzyme, NCH (Inozyme), amberzyme, zinzyme or G-Cleaver ribozyme binding/cleavage sites were identified. These sites are shown in Tables 3-29, 31, 33, 34, 37-43, 56, 58, 59, 62, 63 (all sequences are 5' to 3' in the tables; X can be any base-paired sequence, the actual sequence is not relevant here). The nucleotide base position is noted in the Tables as that site to be cleaved by the designated type of enzymatic nucleic acid molecule. Table 36 shows substrate positions selected from Renbo et al, 1987, Sci. Sin., 30, 507, used in Draper, US patent No. 6,017,756 entitled "METHOD AND REAGENT FOR INHIBITING HEPATITIS B VIRUS REPLICATION" and Draper et al., International PCT publication No. WO 93/23569, filed April 29, 1993, entitled "METHOD AND REAGENT FOR INHIBITING VIRAL REPLICATION". While human sequences can be screened and enzymatic nucleic acid molecule and/or antisense thereafter designed, as discussed in Stinchcomb et al, WO 95/23225, mouse targeted ribozymes may be useful to test efficacy of action ofthe enzymatic nucleic acid molecule and/or antisense prior to testing in humans. Antisense, hammerhead, DNAzyme, NCH (Inozyme), amberzyme, zinzyme or G-

Cleaver ribozyme binding/cleavage sites were identified, as discussed above. The nucleic acid molecules were individually analyzed by computer folding (Jaeger et al, 1989 Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether the sequences fold into the appropriate secondary structure. Those nucleic acid molecules with unfavorable intramolecular interactions such as between the binding arms and the catalytic core were eliminated from consideration. Varying binding arm lengths can be chosen to optimize activity.

Antisense, hammerhead, DNAzyme, NCH, amberzyme, zinzyme or G-Cleaver ribozyme binding/cleavage sites were identified and were designed to anneal to various sites in the RNA target. The binding arms are complementary to the target site sequences described above. The nucleic acid molecules were chemically synthesized. The method of synthesis used follows the procedure for normal DNA/RNA synthesis as described below and in Usman et al, 1987 J. Am. Chem. Soc, 109, 7845; Scaringe et al, 1990 Nucleic Acids Res., 18, 5433; Wincott et al, 1995 Nucleic Acids Res. 23, 2677-2684; and Caruthers et al, 1992, Methods in Enzymology 211,3-19.

Synthesis of Nucleic acid Molecules

Synthesis of nucleic acids greater than 100 nucleotides in length is difficult using automated methods, and the therapeutic cost of such molecules is prohibitive. In this invention, small nucleic acid motifs ("small refers to nucleic acid motifs no more than 100 nucleotides in length, preferably no more than 80 nucleotides in length, and most preferably no more than 50 nucleotides in length; e.g., antisense oligonucleotides, hammerhead or the NCH ribozymes) are preferably used for exogenous delivery. The simple structure of these molecules increases the ability ofthe nucleic acid to invade targeted regions of RNA structure. Exemplary molecules ofthe instant invention are chemically synthesized, and others can similarly be synthesized. Oligonucleotides (e.g.; antisense GeneBlocs) are synthesized using protocols known in the art as described in Caruthers et al, 1992, Methods in Enzymology 211, 3-19, Thompson et al, Intemational PCT Publication No. WO 99/54459, Wincott et al, 1995, Nucleic Acids Res. 23, 2677-2684, Wincott et al, 1997, Methods Mol. Bio., 74, 59, Brennan et al, 1998, Biotechnol Bioeng., 61, 33-45, and Brennan, US patent No.

6,001 ,311. All of these references are incoφorated herein by reference. The synthesis of oligonucleotides makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5'-end, and phosphoramidites at the 3'-end. In a non-limiting example, small scale syntheses are conducted on a 394 Applied Biosystems, Inc. synthesizer using a 0.2 μmol scale protocol with a 2.5 min coupling step for 2'-O- methylated nucleotides and a 45 sec coupling step for 2'-deoxy nucleotides. Table II outlines the amounts and the contact times ofthe reagents used in the synthesis cycle. Alternatively, syntheses at the 0.2 μmol scale can be performed on a 96-well plate synthesizer, such as the instrument produced by Protogene (Palo Alto, CA) with minimal modification to the cycle. A 33-fold excess (60 μL of 0.11 M = 6.6 μmol) of 2'-O-methyl phosphoramidite and a 105-fold excess of S-ethyl tefrazole (60 μL of 0.25 M = 15 μmol) can be used in each coupling cycle of 2'-O-methyl residues relative to polymer-bound 5'- hydroxyl. A 22-fold excess (40 μL of 0.11 M = 4.4 μmol) of deoxy phosphoramidite and a 70-fold excess of S-ethyl tefrazole (40 μL of 0.25 M = 10 μmol) can be used in each coupling cycle of deoxy residues relative to polymer-bound 5'-hydroxyl. Average coupling yields on the 394 Applied Biosystems, Inc. synthesizer, determined by colorimetric quantitation ofthe trityl fractions, are typically 97.5-99%. Other oligonucleotide synthesis reagents for the 394 Applied Biosystems, Inc. synthesizer include the following: detritylation solution is 3% TCA in methylene chloride (ABI); capping is performed with 16% N-methyl imidazole in THF (ABI) and 10% acetic anhydride/10% 2,6-lutidine in THF (ABI); and oxidation solution is 16.9 mM I2, 49 mM pyridine, 9% water in THF (PERSEPTIVE™). Burdick & Jackson Synthesis Grade acetonitrile is used directly from the reagent bottle. S-Ethyltefrazole solution (0.25 M in acetonitrile) is made up from the solid obtained from American International Chemical, Inc. Alternately, for the introduction of phosphorothioate linkages, Beaucage reagent (3H- l,2-Benzodithiol-3-one 1,1 -dioxide, 0.05 M in acetonitrile) is used. Deprotection ofthe antisense oligonucleotides is performed as follows: the polymer- bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 40% aq. methylamine (1 mL) at 65 °C for 10 min. After cooling to -20 °C, the supematant is removed from the polymer support. The support is washed three times with 1.0 mL of EtOH:MeCN:H2O/3 : 1 : 1 , vortexed and the supernatant is then added to the first supernatant. The combined supernatants, containing the oligoribonucleotide, are dried to a white powder.

The method of synthesis used for normal RNA including certain enzymatic nucleic acid molecules follows the procedure as described in Usman et al, 1987, J. Am. Chem. Soc, 109, 7845; Scaringe et al, 1990, Nucleic Acids Res., 18, 5433; and Wincott et al, 1995, Nucleic Acids Res. 23, 2677-2684 Wincott et al, 1997, Methods Mol. Bio., 74, 59, and makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5'-end, and phosphoramidites at the 3'-end. In a non-limiting example, small scale syntheses are conducted on a 394 Applied Biosystems, Inc. synthesizer using a 0.2 μmol scale protocol with a 7.5 min coupling step for alkylsilyl protected nucleotides and a 2.5 min coupling step for 2'-O-methylated nucleotides. Table II outlines the amounts and the contact times ofthe reagents used in the synthesis cycle. Alternatively, syntheses at the 0.2 μmol scale can be done on a 96-well plate synthesizer, such as the instrument produced by Protogene (Palo Alto, CA) with minimal modification to the cycle. A 33-fold excess (60 μL of 0.11 M = 6.6 μmol) of 2'-O-methyl phosphoramidite and a 75-fold excess of S-ethyl tefrazole (60 μL of 0.25 M = 15 μmol) can be used in each coupling cycle of 2'-O-methyl residues relative to polymer-bound 5'- hydroxyl. A 66-fold excess (120 μL of 0.11 M = 13.2 μmol) of alkylsilyl (ribo) protected phosphoramidite and a 150-fold excess of S-ethyl tefrazole (120 μL of 0.25 M = 30 μmol) can be used in each coupling cycle of ribo residues relative to polymer-bound 5'-hydroxyl. Average coupling yields on the 394 Applied Biosystems, Inc. synthesizer, determined by colorimetric quantitation ofthe trityl fractions, are typically 97.5-99%. Other oligonucleotide synthesis reagents for the 394 Applied Biosystems, Inc. synthesizer include the following: detritylation solution is 3% TCA in methylene chloride (ABI); capping is performed with 16% N-methyl imidazole in THF (ABI) and 10% acetic anhydride/10%. 2,6-lutidine in THF (ABI); oxidation solution is 16.9 mM I2, 49 mM pyridine, 9% water in THF (PERSEPTIVE™). Burdick & Jackson Synthesis Grade acetonitrile is used directly from the reagent bottle. S-Ethyltetrazole solution (0.25 M in acetonitrile) is made up from the solid obtained from American International Chemical, Inc. Alternately, for the introduction of phosphorothioate linkages, Beaucage reagent (3H- l,2-Benzodithiol-3-one l,l-dioxide0.05 M in acetonitrile) is used. Deprotection ofthe RNA is performed using either a two-pot or one-pot protocol.

For the two-pot protocol, the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 40% aq. methylamine (1 mL) at 65 °C for 10 min. After cooling to -20 °C, the supernatant is removed from the polymer support. The support is washed three times with 1.0 mL of EtOH:MeCN:H2O/3 : 1 : 1 , vortexed and the supernatant is then added to the first supematant. The combined supernatants, containing the oligoribonucleotide, are dried to a white powder. The base deprotected oligoribonucleotide is resuspended in anhydrous TEA/HF/NMP solution (300 μL of a solution of 1.5 mL N-methylpyrrolidinone, 750 μL TEA and 1 mL TEA»3HF to provide a 1.4 M HF concentration) and heated to 65 °C. After 1.5 h, the oligomer is quenched with 1.5 M NH₄HCO₃.

Alternatively, for the one-pot protocol, the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 33% ethanolic methylamine/DMSO: 1/1 (0.8 mL) at 65 °C for 15 min. The vial is brought to r.t. TEA*3HF (0.1 mL) is added and the vial is heated at 65 °C for 15 min. The sample is cooled at -20 °C and then quenched with 1.5 M NH₄HCO3.

For purification ofthe trityl-on oligomers, the quenched NH4HCO3 solution is loaded onto a C-18 containing cartridge that had been prewashed with acetonitrile followed by 50 mM TEAA. After washing the loaded cartridge with water, the RNA is detritylated with 0.5% TFA for 13 min. The cartridge is then washed again with water, salt exchanged with 1 M NaCl and washed with water again. The oligonucleotide is then eluted with 30% acetonitrile.

Inactive hammerhead ribozymes or binding attenuated confrol (B AC) oligonucleotides) are synthesized by substituting a U for G5 and a U for A14 (numbering from Hertel, K. J., et al, 1992, Nucleic Acids Res.. 20, 3252). Similarly, one or more nucleotide substitutions can be introduced in other enzymatic nucleic acid molecules to inactivate the molecule and such molecules can serve as a negative confrol. The average stepwise coupling yields are typically >98% (Wincott et al, 1995 Nucleic Acids Res. 23, 2677-2684). Those of ordinary skill in the art will recognize that the scale of synthesis can be adapted to be larger or smaller than the example described above including but not limited to 96-well format, all that is important is the ratio of chemicals used in the reaction.

Alternatively, the nucleic acid molecules ofthe present invention can be synthesized separately and joined together post-synthetically, for example, by ligation (Moore et al, 1992, Science 256, 9923; Draper et al, International PCT publication No. WO 93/23569; Shabarova et al, 1991, Nucleic Acids Research 19, 4247; Bellon et al, 1997, Nucleosides & Nucleotides, 16, 951; Bellon et al, 1997, Bioconjugate Chem. 8, 204).

The nucleic acid molecules ofthe present invention are modified extensively to enhance stability by modification with nuclease resistant groups, for example, 2'-amino, 2'- C-allyl, 2'-flouro, 2'-O-methyl, 2'-H (for a review see Usman and Cedergren, 1992, TIBS 17, 34; Usman et al, 1994, Nucleic Acids Symp. Ser. 31, 163). Ribozymes are purified by gel elecfrophoresis using general methods or are purified by high pressure liquid chromatography (HPLC; see Wincott et al, supra, the totality of which is hereby incoφorated herein by reference) and are re-suspended in water.

The sequences ofthe ribozymes and antisense constructs that are chemically synthesized, useful in this study, are shown in Tables 3-31, 33, 34, 37-43, 56, 58, 59, 62, 63. Those in the art will recognize that these sequences are representative only of many more such sequences where the enzymatic portion ofthe ribozyme (all but the binding arms) is altered to affect activity. The ribozyme and antisense construct sequences listed in Tables 3-31, 33, 34, 37-43, 56, 58, 59, 62, 63 maybe formed of ribonucleotides or other nucleotides or non-nucleotides. Such ribozymes with enzymatic activity are equivalent to the ribozymes described specifically in the Tables.

Optimizing Activity ofthe nucleic acid molecule ofthe invention.

Chemically synthesizing nucleic acid molecules with modifications (base, sugar and/or phosphate) that prevent their degradation by serum ribonucleases may increase their potency (see e.g., Eckstein et al, International Publication No. WO 92/07065; Perrault et al, 1990 Nature 344, 565; Pieken et al., 1991, Science 253, 314; Usman and Cedergren, 1992, Trends in Biochem. Sci. 17, 334; Usman et al, International Publication No. WO 93/15187; Rossi et al, International Publication No. WO 91/03162; Sproat, US Patent No. 5,334,711 ; and Burgin et al, supra; all of these describe various chemical modifications that can be made to the base, phosphate and/or sugar moieties ofthe nucleic acid molecules herein and are all hereby incoφorated by reference herein). Modifications which enhance their efficacy in cells, and removal of bases from nucleic acid molecules to shorten oligonucleotide synthesis times and reduce chemical requirements are desired. There are several examples in the art describing sugar, base and phosphate modifications that can be introduced into nucleic acid molecules (e.g., enzymatic nucleic acid molecules) without significantly effecting catalysis and with significant enhancement in their nuclease stability and efficacy. Enzymatic nucleic acid molecules are modified to enhance stability and/or enhance catalytic activity by modification with nuclease resistant groups, for example, 2'-amino, 2"-C-allyl, 2'-fluoro, 2'-O-methyl, 2'-O-allyl, 2'-H, nucleotide base modifications (for a review see Usman and Cedergren, 1992 TIBS 17, 34; Usman et al, 1994 Nucleic Acids Symp. Ser. 31, 163; Burgin et al, 1996 Biochemistry 35, 14090). Sugar modification of enzymatic nucleic acid molecules have been extensively described in the art (see Eckstein et al, International Publication PCT No. WΟ 92/07065; Perrault et al. Nature 1990, 344, 565-568; Pieken et al. Science 1991, 253, 314-317; Usman and Cedergren, Trends in Biochem. Sci. 1992, 17, 334-339; Usman et al. International Publication PCT No. WO 93/15187; Sproat, US Patent No. 5,334,711 and Beigelman et al, 1995 J. Biol. Chem. 270, 25702; all ofthe references are hereby incoφorated in their totality by reference herein). Such publications describe general methods and strategies to determine the location of incoφoration of sugar, base and/or phosphate modifications and the like into enzymatic nucleic acid molecules without inhibiting catalysis, and are incoφorated by reference herein. The 2'-position ofthe sugar in a nucleotide present in the nucleic acid molecules ofthe instant invention which tolerates substitution is selected from the group comprising -H, -OH, -COOH, -CONH , - CONHR¹, -CONR'R², -NΉ^ -NHR'. -NR'R², -NHCOR¹, -SH, SR¹, -F, -ONH₂, - ONHR¹, -ONR'R², -NHOH, -NHOR¹, -NR²OH, -NR²OR¹, substituted or unsubstituted C_I-C_ΪO straight chain or branched alkyl, substituted or unsubstituted C₂-Cιo straight chain or branched alkenyl, substituted or unsubstituted C₂-C₁₀ straight chain or branched alkynyl, substituted or unsubstituted Cr o straight chain or branched alkoxy, substituted or unsubstituted C₂-C₁₀ straight chain or branched alkenyloxy, and substituted or unsubstituted C₂-C₁₀ straight chain or branched alkynyloxy. The substituents for sugar 2' position preferably are independently halogen, cyano, amino, carboxy, ester, ether, carboxamide, hydroxy, or mercapto. R¹ and R² can be substituted or unsubstituted alkyl, alkenyl, or alkynyl groups, where the substituents are independently halogen, cyano, amino, carboxy, ester, ether, carboxamide, hydroxy, or mercapto. In view of such teachings, similar modifications can be used as described herein to modify the nucleic acid molecules ofthe instant invention. Such publications describe general methods and strategies to determine the location of incoφoration of sugar, base and/or phosphate modifications and the like into ribozymes without inhibiting catalysis, and are incoφorated by reference herein. In view of such teachings, similar modifications can be used as described herein to modify the nucleic acid molecules ofthe instant invention.

Some ofthe non-limiting examples of base modifications that can be introduced into enzymatic nucleic acids without significantly effecting their catalytic activity include, inosine, purine, pyridin-4-one, pyridin-2-one, phenyl, pseudouracil, 2, 4, 6-trimethoxy benzene, 3-methyluracil, dihydrouridine, naphthyl, aminophenyl, 5-alkylcytidines (e.g., 5-methylcytidine), 5-alkyluridines (e.g., ribothymidine), 5-halouridine (e.g., 5-bromouridine) or 6-azapyrimidines or 6-alkylpyrimidines (e.g. 6-methyluridine) and others (Burgin et al, 1996, Biochemistry, 35, 14090). By "modified bases" in this aspect is meant nucleotide bases other than adenine, guanine, cytosine and uracil at 1' position or their equivalents; such bases may be used within the catalytic core ofthe enzyme and/or in the substrate-binding regions.

The nucleic acid bases can be hypoxanthin-9-yl, or a functional equivalent thereof, in position¹⁵ 'of the ribozyme; the base at other positions may be guanin-9-yl, hypoxanthin-9-yl or 7-deazaguanin-9-yl in positions 5, 8 and 12 in the ribozyme; adenin-9- yl, 2,6-diaminopurin-9-yl, purin-9-yl or 7-deaza adenin-9-yl in positions 6, 9, 13 and 14; uracil-1-yl, uracil-5-yl, thymin-1-yl or 5-propynyluracil-l-yl in position 4; cytosin-1-yl, 5- methylcytosin-1-yl or 5-propynylcytosin-l-yl in position 3; and adenin-9-yl, cytosin-1-yl, guanin-9-yl, uracil-1-yl, uracil-5-yl, hypoxanthin-9-yl, thymin-1-yl, 5-methylcytosin-l-yl, 2,6-diaminopurin-9-yl, purin-9-yl, 7-deaza adenin-9-yl, 7-deazaguanin-9-yl, 5- propynylcytosin-1-yl, 5-propynyluracil-l-yl, isoguanin-9-yl, 2-aminopurin-9-yl, 6- methyluracil-1-yl, 4-thiouracil-l-yl, 2-pyrimidone-l-yl, quinazoline-2,4-dione-l-yl, xanthin-9-yl, N²-dimethylguanin-9-yl, or a functional equivalent thereof in position 7. The base at position 15.1 is preferably hypoxanthin-9-yl or an analog where no hydrogen bond can form between any group at the 2 position ofthe base and the 2-oxo group of C¹⁶'¹. Preferably, B is not guanin-9-yl in position 15.1.

In particular, the invention features modified ribozymes having a base substitution selected from pyridin-4-one, pyridin-2-one, phenyl, pseudouracil, 2, 4, 6-trimethoxy benzene, 3-methyluracil, dihydrouracil, naphthyl, 6-methyl-uracil and aminophenyl. While chemical modification of oligonucleotide intemucleotide linkages with phosphorothioate, phosphorothioate, and/or 5'-methylphosphonate linkages improves stability, too many of these modifications may cause some toxicity. Therefore, when designing nucleic acid molecules, the amount of these intemucleotide linkages should be minimized. The reduction in the concentration of these linkages should lower toxicity resulting in increased efficacy and higher specificity of these molecules.

Nucleic acid molecules having chemical modifications which maintain or enhance activity are provided. Such nucleic acid molecules are also generally more resistant to nucleases than unmodified nucleic acid. Thus, in a cell and/or in vivo the activity may not be significantly lowered. Therapeutic nucleic acid molecules delivered exogenously must optimally be stable within cells until translation ofthe target RNA has been inhibited long enough to reduce the levels ofthe undesirable protein. This period of time varies between hours to days depending upon the disease state. Clearly, nucleic acid molecules must be resistant to nucleases in order to function as effective infracellular therapeutic agents.

Improvements in the chemical synthesis of RNA and DNA (Wincott et al, 1995 Nucleic Acids Res. 23, 2677; Caruthers et al, 1992, Methods in Enzymology 211,3-19 (all are incoφorated by reference herein) have expanded the ability to modify nucleic acid molecules by introducing nucleotide modifications to enhance their nuclease stability as described above.

Use of these the nucleic acid-based molecules ofthe invention will lead to better treatment ofthe disease progression by affording the possibility of combination therapies (e.g., multiple antisense or enzymatic nucleic acid molecules targeted to different genes, nucleic acid molecules coupled with known small molecule inhibitors, or intermittent treatment with combinations of molecules (including different motifs) and/or other chemical or biological molecules). The treatment of patients with nucleic acid molecules may also include combinations of different types of nucleic acid molecules. Therapeutic nucleic acid molecules (e.g., enzymatic nucleic acid molecules and antisense nucleic acid molecules) delivered exogenously must optimally be stable within cells until translation ofthe target RNA has been inhibited long enough to reduce the levels ofthe undesirable protein. This period of time varies between hours to days depending upon the disease state. Clearly, these nucleic acid molecules must be resistant to nucleases in order to function as effective intracellular therapeutic agents. Improvements in the chemical synthesis of nucleic acid molecules described in the instant invention and in the art have expanded the ability to modify nucleic acid molecules by introducing nucleotide modifications to enhance their nuclease stability as described above.

By "enhanced enzymatic activity" is meant to include activity measured in cells and/or in vivo where the activity is a reflection of both catalytic activity and ribozyme stability. In this invention, the product of these properties is increased or not significantly (less than 10- fold) decreased in vivo compared to an all RNA ribozyme or all DNA enzyme.

In yet another preferred embodiment, nucleic acid catalysts having chemical modifications which maintain or enhance enzymatic activity are provided. Such nucleic acid catalysts are also generally more resistant to nucleases than unmodified nucleic acid. Thus, in a cell and/or in vivo the activity may not be significantly lowered. As exemplified herein such ribozymes are useful in a cell and/or in vivo even if activity over all is reduced 10 fold (Burgin et al, 1996, Biochemistry, 35, 14090). Such ribozymes herein are said to "maintain" the enzymatic activity of an all RNA ribozyme.

In another aspect the nucleic acid molecules comprise a 5' and/or a 3'- cap structure. By "cap structure" is meant chemical modifications, which have been incoφorated at either terminus ofthe oligonucleotide (see, for example, Wincott et al, WO 97/26270, incoφorated by reference herein). These terminal modifications protect the nucleic acid molecule from exonuclease degradation, and may help in delivery and/or localization within a cell. The cap may be present at the 5'-terminus (5'-cap) or at the 3'-terminal (3'- cap) or may be present on both termini. In non-limiting examples: the 5 '-cap is selected from the group comprising inverted abasic residue (moiety); 4',5'-methylene nucleotide; 1- (beta-D-erythrofuranosyl) nucleotide, 4'-thio nucleotide; carbocyclic nucleotide; 1,5- anhydrohexitol nucleotide; L-nucleotides; alpha-nucleotides; modified base nucleotide; phosphorodithioate linkage; tλreo-pentofuranosyl nucleotide; acyclic 3',4'-seco nucleotide; acyclic 3,4-dihydroxybutyl nucleotide; acyclic 3,5-dihydroxypentyl nucleotide, 3'-3'- inverted nucleotide moiety; 3'-3'-inverted abasic moiety; 3'-2'-inverted nucleotide moiety; 3'-2'-inverted abasic moiety; 1,4-butanediol phosphate; 3'-phosphoramidate; hexylphosphate; aminohexyl phosphate; 3'-phosphate; 3'-phosphorothioate; phosphorodithioate; or bridging or non-bridging methylphosphonate moiety (for more details, see Wincott et al, International PCT publication No. WO 97/26270, incoφorated by reference herein). Ln yet another preferred embodiment, the 3 '-cap is selected from a group comprising, 4',5'-methylene nucleotide; l-(beta-D-erythrofuranosyl) nucleotide; 4'-thio nucleotide, carbocyclic nucleotide; 5'-amino-alkyl phosphate; l,3-diamino-2 -propyl phosphate; 3-aminopropyl phosphate; 6-aminohexyl phosphate; 1,2-aminododecyl phosphate; hydroxypropyl phosphate; 1,5-anhydrohexitol nucleotide; L-nucleotide; alpha- nucleotide; modified base nucleotide; phosphorodithioate; t/zreo-pentofuranosyl nucleotide; acyclic 3',4'-seco nucleotide; 3,4-dihydroxybutyl nucleotide; 3,5- dihydroxypentyl nucleotide, 5'-5 '-inverted nucleotide moiety; 5'-5'-inverted abasic moiety; 5'-phosphoramidate; 5'-phosphorothioate; 1,4-butanediol phosphate; 5'-amino; bridging and/or non-bridging 5'-phosphoramidate, phosphorothioate and/or phosphorodithioate, bridging or non bridging methylphosphonate and 5'-mercapto moieties (for more details see Beaucage and Iyer, 1993, Tetrahedron 49, 1925; incoφorated by reference herein).

An "alkyl" group refers to a saturated aliphatic hydrocarbon, including straight- chain, branched-chain, and cyclic alkyl groups. Preferably, the alkyl group has 1 to 12 carbons. More preferably it is a lower alkyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkyl group may be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, =O, =S, NO2 or N(CH3)2, amino, or SH. The term also includes alkenyl groups which are unsaturated hydrocarbon groups containing at least one carbon-carbon double bond, including straight-chain, branched-chain, and cyclic groups. Preferably, the alkenyl group has 1 to 12 carbons. More preferably it is a lower alkenyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkenyl group may be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, =O, =S, NO2, halogen, N(CH3)2, amino, or SH. The term "alkyl" also includes alkynyl groups which have an unsaturated hydrocarbon group containing at least one carbon-carbon triple bond, including straight-chain, branched-chain, and cyclic groups. Preferably, the alkynyl group has 1 to 12 carbons. More preferably it is a lower alkynyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkynyl group may be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, =O, =S, NO2 or N(CH3)2, amino or SH.

Such alkyl groups may also include aryl, alkylaryl, carbocyclic aryl, heterocyclic aryl, amide and ester groups. An "aryl" group refers to an aromatic group which has at least one ring having a conjugated pi electron system and includes carbocyclic aryl, heterocyclic aryl and biaryl groups, all of which may be optionally substituted. The preferred substituent(s) of aryl groups are halogen, trihalomethyl, hydroxyl, SH, OH, cyano, alkoxy, alkyl, alkenyl, alkynyl, and amino groups. An "alkylaryl" group refers to an alkyl group (as described above) covalently joined to an aryl group (as described above). Carbocyclic aryl groups are groups wherein the ring atoms on the aromatic ring are all carbon atoms. The carbon atoms are optionally substituted. Heterocyclic aryl groups are groups having from 1 to 3 heteroatoms as ring atoms in the aromatic ring and the remainder ofthe ring atoms are carbon atoms. Suitable heteroatoms include oxygen, sulfur, and nifrogen, and include furanyl, thienyl, pyridyl, pyrrolyl, N-lower alkyl pyrrolo, pyrimidyl, pyrazinyl, imidazolyl and the like, all optionally substituted. An "amide" refers to an -C(O)-NH-R, where R is either alkyl, aryl, alkylaryl or hydrogen. An "ester" refers to an -C(O)-OR', where R is either alkyl, aryl, alkylaryl or hydrogen.

By "nucleotide" as used herein is as recognized in the art to include natural bases (standard), and modified bases well known in the art. Such bases are generally located at the 1' position of a nucleotide sugar moiety. Nucleotides generally comprise a base, sugar and a phosphate group. The nucleotides can be unmodified or modified at the sugar, phosphate and/or base moiety, (also referred to interchangeably as nucleotide analogs, modified nucleotides, non-natural nucleotides, non-standard nucleotides and other; see, for example, Usman and McSwiggen, supra; Eckstein et al, International PCT Publication No. WO 92/07065; Usman et al, International PCT Publication No. WO 93/15187; Uhlman & Peyman, supra, all are hereby incoφorated by reference herein). There are several examples of modified nucleic acid bases known in the art as summarized by Limbach et al, 1994, Nucleic Acids Res. 22, 2183. Some ofthe non-limiting examples of base modifications that can be introduced into nucleic acid molecules include, inosine, purine, pyridin-4-one, pyridin-2-one, phenyl, pseudouracil, 2, 4, 6-trimethoxy benzene, 3- methyl uracil, dihydrouridine, naphthyl, aminophenyl, 5-alkylcytidines (e.g., 5-methylcytidine), 5-alkyluridines (e.g., ribothymidine), 5-halouridine (e.g., 5-bromouridine) or 6-azapyrimidines or 6-alkylpyrimidines (e.g. 6-methyluridine), propyne, and others (Burgin et al, 1996, Biochemistry, 35, 14090; Uhlman & Peyman, supra).

By "modified bases" in this aspect is meant nucleotide bases other than adenine, guanine, cytosine and uracil at 1' position or their equivalents; such bases may be used at any position, for example, within the catalytic core of an enzymatic nucleic acid molecule and/or in the substrate-binding regions ofthe nucleic acid molecule. Such modified nucleotides include dideoxynucleotides which have pharmaceutical utility well known in the art, as well as utility in basic molecular biology methods such as sequencing. In a preferred embodiment, the invention features modified ribozymes with phosphate backbone modifications comprising one or more phosphorothioate, phosphorodithioate, methylphosphonate, moφholino, amidate carbamate, carboxymethyl, acetamidate, polyamide, sulfonate, sulfonamide, sulfamate, formacetal, thioformacetal, and/or alkylsilyl, substitutions. For a review of oligonucleotide backbone modifications, see Hunziker and Leumann, 1995, Nucleic Acid Analogues: Synthesis and Properties, in Modern Synthetic Methods, VCH, 331-417, and Mesmaeker et al, 1994, Novel Backbone Replacements for Oligonucleotides, in Carbohydrate Modifications in Antisense Research, ACS, 24-39. These references are hereby incoφorated by reference herein.

By "abasic" is meant sugar moieties lacking a base or having other chemical groups in place of a base at the 1' position, (for more details, see Wincott et al, International PCT publication No. WO 97/26270).

By "unmodified nucleoside" or "unmodified nucleotide" is meant one ofthe bases adenine, cytosine, guanine, thymine, uracil joined to the 1' carbon of β-D-ribo-furanose. By "modified nucleoside" or "modified nucleotide" is meant any nucleotide base which contains a modification in the chemical structure of an unmodified nucleotide base, sugar and/or phosphate.

In connection with 2'-modified nucleotides as described for the present invention, by "amino" is meant 2'-NH₂ or 2'-O- NH₂, which may be modified or unmodified. Such modified groups are described, for example, in Eckstein et al., U.S. Patent 5,672,695 and Matulic-Adamic et al., WΟ 98/28317, which are both incoφorated by reference in their entireties.

Various modifications to nucleic acid (e.g., antisense and ribozyme) structure can be made to enhance the utility of these molecules. Such modifications will enhance shelf-life, half-life in vitro, stability, and ease of introduction of such oligonucleotides to the target site, e.g., to enhance penetration of cellular membranes, and confer the ability to recognize and bind to targeted cells.

Use of these molecules will lead to better treatment ofthe disease progression by affording the possibility of combination therapies (e.g., multiple ribozymes targeted to different genes, ribozymes coupled with known small molecule inhibitors, or intermittent treatment with combinations of ribozymes (including different ribozyme motifs) and/or other chemical or biological molecules). The treatment of patients with nucleic acid molecules may also include combinations of different types of nucleic acid molecules. Therapies may be devised which include a mixture of ribozymes (including different ribozyme motifs), antisense and/or 2-5 A chimera molecules to one or more targets to alleviate symptoms of a disease.

Administration of Nucleic Acid Molecules Methods for the delivery of nucleic acid molecules are described in Akhtar et al,

1992, Trends Cell Bio., 2, 139; and Delivery Strategies for Antisense Oligonucleotide Therapeutics, ed. Akhtar, 1995 which are both incoφorated herein by reference. Sullivan et al, PCT WO 94/02595, further describes the general methods for delivery of enzymatic RNA molecules. These protocols may be utilized for the delivery of virtually any nucleic acid molecule. Nucleic acid molecules may be administered to cells by a variety of methods known to those familiar to the art, including, but not restricted to, encapsulation in liposomes, by iontophoresis, or by incoφoration into other vehicles, such as hydrogels, cyclodextrins, biodegradable nanocapsules, and bioadhesive microspheres. For some indications, nucleic acid molecules may be directly delivered ex vivo to cells or tissues with or without the aforementioned vehicles. Alternatively, the nucleic acid/vehicle combination is locally delivered by direct injection or by use of a catheter, infusion pump or stent. Many examples in the art describe CNS delivery methods of oligonucleotides by osmotic pump, (see Chun et al, 1998, Neuroscience Letters, 257, 135-138, D'Aldin et al, 1998, Mol. Brain Research, 55, 151-164, Dryden et α/., 1998, J. Endocrinol, 157, 169- 175, Ghirnikar et al, 1998, Neuroscience Letters, 247, 21-24) or direct infusion (Broaddus et al, 1997, Neurosurg. Focus, 3, article 4). Other routes of delivery include, but are not limited to oral (tablet or pill form) and/or intrathecal delivery (Gold, 1997, Neuroscience, 76, 1153-1158). For a comprehensive review on drug delivery strategies including broad coverage of CNS delivery, see Jain, Drug Delivery Systems: Technologies and Commercial Opportunities, Decision Resources, 1998. Other routes of delivery include, but are not limited to, infravascular, intramuscular, subcutaneous or joint injection, aerosol inhalation, oral (tablet or pill form), topical, systemic, ocular, intraperitoneal and/or intrathecal delivery. More detailed descriptions of nucleic acid delivery and administration are provided in Sullivan et al, supra, Draper et al, PCT WO93/23569; Beigelman et al, PCT WO99/05094, and Klimuk et al, PCT WO99/04819 all of which are incoφorated by reference herein. The molecules ofthe instant invention can be used as pharmaceutical agents.

Pharmaceutical agents prevent, inhibit the occurrence, or treat (alleviate a symptom to some extent, preferably all ofthe symptoms) of a disease state in a patient.

The negatively charged polynucleotides ofthe invention can be administered (e.g., RNA, DNA or protein) and introduced into a patient by any standard means, with or without stabilizers, buffers, and the like, to form a pharmaceutical composition. When it is desired to use a liposome delivery mechanism, standard protocols for formation of liposomes can be followed. The compositions ofthe present invention may also be formulated and used as tablets, capsules or elixirs for oral administration; suppositories for rectal administration; sterile solutions; suspensions for injectable administration; and the other compositions known in the art. The present invention also includes pharmaceutically acceptable formulations ofthe compounds described. These formulations include salts ofthe above compounds, e.g., acid addition salts, for example, salts of hydrochloric, hydrobromic, acetic acid, and benzene sulfonic acid. A pharmacological composition or formulation refers to a composition or formulation in a form suitable for administration, e.g., systemic administration, into a cell or patient, preferably a human. Suitable forms, in part, depend upon the use or the route of entry, for example, oral, transdermal, or by injection. Such forms should not prevent the composition or formulation from reaching a target cell (i.e., a cell to which the negatively charged polymer is desired to be delivered to). For example, pharmacological compositions injected into the blood stream should be soluble. Other factors are known in the art, and include considerations such as toxicity and forms which prevent the composition or formulation from exerting its effect.

By "systemic administration" is meant in vivo systemic absoφtion or accumulation of drugs in the blood stream followed by distribution throughout the entire body.

Administration routes which lead to systemic absoφtion include, without limitations: intravenous, subcutaneous, intraperitoneal, inhalation, oral, infrapulmonary and intramuscular. Each of these administration routes expose the desired negatively charged polymers, e.g., nucleic acids, to an accessible diseased tissue. The rate of entry of a drug into the circulation has been shown to be a function of molecular weight or size. The use of a liposome or other drug carrier comprising the compounds ofthe instant invention can potentially localize the drug, for example, in certain tissue types, such as the tissues ofthe reticular endothelial system (RES). A liposome formulation which can facilitate the association of drug with the surface of cells, such as, lymphocytes and macrophages is also useful. This approach may provide enhanced delivery ofthe drug to target cells by taking advantage ofthe specificity of macrophage and lymphocyte immune recognition of abnormal cells, such as cancer cells.

By pharmaceutically acceptable formulation is meant, a composition or formulation that allows for the effective distribution ofthe nucleic acid molecules ofthe instant invention in the physical location most suitable for their desired activity. Nonlimiting examples of agents suitable for formulation with the nucleic acid molecules ofthe instant invention include: P-glycoprotein inhibitors (such as Pluronic P85) which can enhance entry of drugs into the CNS (Jolliet-Riant and Tillement, 1999, Fundam. Clin. Pharmacol, 13, 16-26); biodegradable polymers, such as poly (DL-lactide-coglycolide) microspheres for sustained release delivery after intracerebral implantation (Emerich, DF et al, 1999, Cell Transplant, 8, 47-58) Alkermes, Inc. Cambridge, MA; and loaded nanoparticles, such as those made of polybutylcyanoacrylate, which can deliver drugs across the blood brain barrier and can alter neuronal uptake mechanisms (Prog Neuropsychopharmacol Biol Psychiatry, 23, 941-949, 1999). Other non-limiting examples of delivery strategies for the nucleic acid molecules ofthe instant invention include material described in Boado et al, 1998, J. Pharm. Sci., 87, 1308-1315; Tyler et al, 1999, FEBS Lett., 421, 280-284; Pardridge et al, 1995, PNAS USA., 92, 5592-5596; Boado, 1995, Adv. Drug Delivery Rev., 15, 73-107; Aldrian-Herrada et al, 1998, Nucleic Acids Res., 26, 4910-4916; and Tyler et al, 1999, PNAS USA., 96, 7053-7058.

The invention also features the use ofthe composition comprising surface-modified liposomes containing poly (ethylene glycol) lipids (PEG-modified, or long-circulating liposomes or stealth liposomes). These formulations offer a method for increasing the accumulation of drugs in target tissues. This class of drug carriers resists opsonization and elimination by the mononuclear phagocytic system (MPS or RES), thereby enabling longer blood circulation times and enhanced tissue exposure for the encapsulated drug (Lasic et al. Chem. Rev. 1995, 95, 2601-2627; Ishiwata et al, Chem. Pharm. Bull. 1995, 43, 1005- 1011). Such liposomes have been shown to accumulate selectively in tumors, presumably by extravasation and capture in the neovascularized target tissues (Lasic et al, Science 1995, 267, 1275-1276; Oku et al., 995, Biochim. Biophys. Acta, 1238, 86-90). The long- circulating liposomes enhance the pharmacokinetics and pharmacodynamics of DNA and RNA, particularly compared to conventional cationic liposomes which are known to accumulate in tissues ofthe MPS (Liu et al, J. Biol. Chem. 1995, 42, 24864-24870; Choi et al, International PCT Publication No. WO 96/10391; Ansell et al, Intemational PCT Publication No. WO 96/10390; Holland et al, International PCT Publication No. WO 96/10392; all of which are incoφorated herein by reference). Long-circulating liposomes are also likely to protect drugs from nuclease degradation to a greater extent compared to cationic liposomes, based on their ability to avoid accumulation in metabolically aggressive MPS tissues such as the liver and spleen. The present invention also includes compositions prepared for storage or administration which include a pharmaceutically effective amount ofthe desired compounds in a pharmaceutically acceptable carrier or diluent. Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (A.R.

Gennaro edit. 1985) hereby incoφorated by reference herein. For example, preservatives, stabilizers, dyes and flavoring agents may be provided. These include sodium benzoate, sorbic acid and esters ofp-hydroxybenzoic acid. In addition, antioxidants and suspending agents may be used. A pharmaceutically effective dose is that dose required to prevent, inhibit the occurrence, or treat (alleviate a symptom to some extent, preferably all ofthe symptoms) of a disease state. The pharmaceutically effective dose depends on the type of disease, the composition used, the route of administration, the type of mammal being freated, the physical characteristics ofthe specific mammal under consideration, concurrent medication, and other factors which those skilled in the medical arts will recognize. Generally, an amount between 0.1 mg/kg and 100 mg/kg body weight/day of active ingredients is administered dependent upon potency ofthe negatively charged polymer. The nucleic acid molecules ofthe present invention may also be administered to a patient in combination with other therapeutic compounds to increase the overall therapeutic effect. The use of multiple compounds to freat an indication may increase the beneficial effects while reducing the presence of side effects.

Alternatively, certain ofthe nucleic acid molecules ofthe instant invention can be expressed within cells from eukaryotic promoters (e.g., Izant and Weintraub, 1985, Science, 229, 345; McGarry and Lindquist, 1986, Proc. Natl. Acad. Sci., USA 83, 399; Scanlon et al, 1991, Proc. Natl. Acad. Sci. USA, 88, 10591-5; Kashani-Sabet et al, 1992, Antisense Res. Dev., 2, 3-15; Dropulic et al, 1992, J. Virol, 66, 1432-41; Weerasinghe et al, 1991, J. Virol, 65, 5531-4; Ojwang et α/., 1992, Proc. Natl. Acad. Sci. USA, 89, 10802-6; Chen et al, 1992, Nucleic Acids Res., 20, 4581-9; Sarver et α/., 1990 Science, 247, 1222-1225; Thompson et al, 1995, Nucleic Acids Res., 23, 2259; Good et al, 1997, Gene Therapy, 4, 45; all of these references are hereby incoφorated herein, in their totalities, by reference). Those skilled in the art realize that any nucleic acid can be expressed in eukaryotic cells from the appropriate DNA/RNA vector. The activity of such nucleic acids can be augmented by their release from the primary transcript by a ribozyme (Draper et al, PCT WO 93/23569, and Sullivan et al, PCT WO 94/02595; Ohkawa et al, 1992, Nucleic Acids Symp. Ser., 27, 15-6; Taira et α/., 1991, Nucleic Acids Res., 19, 5125- 30; Ventura et al, 1993, Nucleic Acids Res., 21, 3249-55; Chowrira et al, 1994, J. Biol. Chem., 269, 25856; all of these references are hereby incoφorated in their totality by reference herein).

In another aspect ofthe invention, RNA molecules ofthe present invention are preferably expressed from transcription units (see, for example, Couture et al, 1996, TIG., 12, 510) inserted into DNA or RNA vectors. The recombinant vectors are preferably DNA plasmids or viral vectors. Ribozyme expressing viral vectors could be constructed based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus. Preferably, the recombinant vectors capable of expressing the nucleic acid molecules are delivered as described above, and persist in target cells. Alternatively, viral vectors may be used that provide for transient expression of nucleic acid molecules. Such vectors might be repeatedly administered as necessary. Once expressed, the nucleic acid molecule binds to the target mRNA. Delivery of nucleic acid molecule expressing vectors could be systemic, such as by intravenous or intra-muscular administration, by administration to target cells ex-planted from the patient followed by reinfroduction into the patient, or by any other means that would allow for introduction into the desired target cell (for a review see Couture et al, 1996, TIG, 12, 510).

In one aspect, the invention features an expression vector comprising a nucleic acid sequence encoding at least one ofthe nucleic acid molecules ofthe instant invention is disclosed. The nucleic acid sequence encoding the nucleic acid molecule ofthe instant invention is operably linked in a manner which allows expression of that nucleic acid molecule.

In another aspect the invention features an expression vector comprising: a) a transcription initiation region (e.g., eukaryotic pol I, II or HI initiation region); b) a transcription termination region (e.g., eukaryotic pol I, LI or LU termination region); c) a nucleic acid sequence encoding at least one ofthe nucleic acid catalyst ofthe instant invention; and wherein said sequence is operably linked to said initiation region and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule. The vector may optionally include an open reading frame (ORF) for a protein operably linked on the 5' side or the 3'-side ofthe sequence encoding the nucleic acid catalyst ofthe invention; and/or an intron (intervening sequences).

Transcription ofthe nucleic acid molecule sequences are driven from a promoter for eukaryotic RNA polymerase I (pol I), RNA polymerase II (pol H), or RNA polymerase HI (pol HI). Transcripts from pol π or pol LU promoters will be expressed at high levels in all cells; the levels of a given pol LI promoter in a given cell type will depend on the nature of the gene regulatory sequences (enhancers, silencers, etc.) present nearby. Prokaryotic RNA polymerase promoters are also used, providing that the prokaryotic RNA polymerase enzyme is expressed in the appropriate cells (Elroy-Stein and Moss, 1990, Proc. Natl. Acad. Sci. USA, 87, 6743-7; Gao and Huang 1993, Nucleic Acids Res., 21, 2867-72;

Lieber et al., 1993, Methods Enzymol, 217, 47-66; Zhou et al., 1990, Mol. Cell. Biol, 10, 4529-37). All of these references are incoφorated by reference herein. Several investigators have demonstrated that nucleic acid molecules, such as ribozymes expressed from such promoters can function in mammalian cells (e.g. Kashani-Sabet et al., 1992, Antisense Res. Dev., 2, 3-15; Ojwang et al., 1992, Proc. Natl. Acad. Sci. USA, 89,

10802-6; Chen et al, 1992, Nucleic Acids Res., 20, 4581-9; Yu et al., 1993, Proc. Natl Acad. Sci. USA, 90, 6340-4; L'Huillier et α/., 992, EMBOJ., 11, 4411-8; Lisziewicz et al, 1993, Proc. Natl. Acad. Sci. U. S. A, 90, 8000-4; Thompson et al, 1995, Nucleic Acids Res., 23, 2259; Sullenger & Cech, 1993, Science, 262, 1566). More specifically, transcription units such as the ones derived from genes encoding U6 small nuclear

(snRNA), transfer RNA (tRNA) and adenovirus VA RNA are useful in generating high concentrations of desired RNA molecules such as ribozymes in cells (Thompson et al, supra; Couture and Stinchcomb, 1996, supra; Noonberg et al, 1994, Nucleic Acid Res., 22, 2830; Noonberg et al, US Patent No. 5,624,803; Good et al, 1997, Gene Ther., A, 45; Beigelman et al, International PCT Publication No. WO 96/18736; all of these publications are incoφorated by reference herein. The above ribozyme transcription units can be incoφorated into a variety of vectors for introduction into mammalian cells, including but not restricted to, plasmid DNA vectors, viral DNA vectors (such as adenovirus or adeno-associated virus vectors), or viral RNA vectors (such as retroviral or alphavirus vectors) (for a review see Couture and Stinchcomb, 1996, supra). In yet another aspect, the invention features an expression vector comprising nucleic acid sequence encoding at least one ofthe nucleic acid molecules ofthe invention, in a manner which allows expression of that nucleic acid molecule. The expression vector comprises in one embodiment; a) a transcription initiation region; b) a transcription termination region; c) a nucleic acid sequence encoding at least one said nucleic acid molecule; and wherein said sequence is operably linked to said initiation region and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule. In another preferred embodiment the expression vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an open reading frame; d) a nucleic acid sequence encoding at least one said nucleic acid molecule, wherein said sequence is operably linked to the 3 '-end of said open reading frame; and wherein said sequence is operably linked to said initiation region, said open reading frame and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule. In yet another embodiment, the expression vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an infron; d) a nucleic acid sequence encoding at least one said nucleic acid molecule; and wherein said sequence is operably linked to said initiation region, said intron and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule. In another embodiment, the expression vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an infron; d) an open reading frame; e) a nucleic acid sequence encoding at least one said nucleic acid molecule, wherein said sequence is operably linked to the 3'-end of said open reading frame; and wherein said sequence is operably linked to said initiation region, said infron, said open reading frame and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.

Examples:

The following are non-limiting examples showing the selection, isolation, synthesis and activity of nucleic acids ofthe instant invention. Example 1 : Telomerase

The ribonucleoprotein enzyme telomerase consists of an RNA template subunit and one or more protein subunits including telomerase reverse transcriptase (TERT), which function together to direct the synthesis of telomeres. Telomeres exist as non-nucleosome DNA/protein complexes at the physical ends of eukaryotic chromosomes. These capping structures maintain chromosome stability and replicative potential (Zakian, V. A., 1995, Science, 270, 1601-1607). Telomere structure is characterized by tandem repeats of conserved DNA sequences rich in G-C base pairs. Additional conserved telomere elements include a terminal 3 '-overhang in the G-rich strand and non-histone structural proteins that are complexed with telomeric DNA in the nucleus. (Blackburn, "E., 1990, JBC, 265, 5919-5921.). Observed shortening of telomeres coincides with the onset of cellular senescence in most somatic cell lines lacking significant levels of telomerase. This finding has had a profound impact on our views concerning the mechanisms of aging, age related disease, and cancer. Conventional DNA polymerases are unable to fully replicate the ends of linear chromosomes (Watson, J. D., 1972, Nature, 239, 197-201). This inability stems from the 3' G-rich overhang that is a product of ribonuclease cleavage ofthe RNA primer used in DNA replication. The overhang prevents DNA polymerase replication since the recessed C-rich parent strand cannot be used as a template. Telomerase overcomes this limitation by extending the 3' end ofthe chromosome using deoxyribonucleotides as substrates and a sequence within the telomerase RNA subunit as a template. (Lingner, J., 1995, Science, 269, 1533-1534). As such, telomerase is considered a reverse transcriptase that is responsible for telomere maintenance.

Telomerase was first discovered by in Tetrahymena thermophila in 1985 (Greider, C. W., 1995, Cell, 43, 405-413). The RNA subunits and their respective genes were later discovered and characterized in protozoa, budding yeast, and mammals. Genetic studies of these genes confirmed the role of telomerase RNA (TR) in determining telomere sequence by mutating genes which encode the telomeric RNA (Yu, G. L., 1990, Nature, 344, 126-132), (Singer, M. S., 1994, Science, 266, 404-409), (Blasco, M. A., 1995, Science, 269, 1267-1270). These studies showed that telomerase activity parallels TR expression in protozoa, yeast and mice. However, the expression of human telomerase RNA (hTR) does not correlate well with telomerase activity in mammalian cells. Many human tissues express hTR but are devoid of telomerase activity (Feng, J., 1995, Science, 269, 1236-1241). Knockout mice, in which the mTR gene has been deleted from germline cells, have been shown to be viable for at least six generations. Cells from later generations of these mice showed chromosomal abnormalities consistent with telomere degradation, indicating that mTR is necessary for telomere length maintenance, but is not required for embryonic development, oncogenic transformation, or tumor formation in mice (Blasco, M. A., 1997, Cell, 91, 25-34).

The first catalytically active subunit of telomerase (pi 23) was isolated from Euplotes aediculatus along with another subunit (p43) and a 66-kD RNA subunit (Linger, J., 1996, Proc. Natl. Acad. Sci., 93, 10712-10717). Subsequent studies revealed telomerase catalytic subunit homologs from fission yeast (Est2p) and human genes (TRT1). The human homolog, TRT1 encoding hTERT, expressed mRNA with a strong correlation to telomerase activity in human cells (Nakamura, T. M., 1997, Science, 277, 955-959). Reconstitution of telomerase activity with in vitro transcribed and translated hTERT and hTR, either co-synthesized or simply mixed, demonstrated that hTERT and hTR represent the minimal components of telomerase. Furthermore, transient expression of hTERT in normal diploid human cells restored telomerase activity, demonstrating that hTERT is the only component necessary to restore telomerase activity in normal human cells (Weinrich, S. L., 1997, Nature Genetics, 17, 498-502). The introduction of telomerase into normal human cells using hTERT expression via fransfection has resulted in the extension of life span in these cells. Such findings indicate that telomere loss in the absence of telomerase is the "mitotic clock" that controls the replicative potential of a cell prior to senescence (Bodnar, A. G., 1998, Science, 279, 349-352).

Expression of telomerase is observed in germ cell and most cancer cell lines. These "immortal" cell lines continue to divide without shortening of their telomeres (Kim, N. W., 1994, Science, 266, 2011-2015). A model of tumor progression has evolved from these findings, suggesting a role for telomerase expression in malignant transformation. Successful malignant transformation in human cells was accomplished for the first time by ectopic expression of hTERT in combination with two oncogenes, SV40 large-T and H- ras. Injection of nude mice with cells expressing these oncogenes and hTERT resulted in rapid growth of tumors. These observations indicate that hTERT mediated telomere maintenance is essential for the formation of human tumor cells (Hahn, W. C, 1999, Nature, 400, 464-468).

Various methods have been developed to assay telomerase activity in vitro. The most widely used method to characterize telomerase activity is the telomeric repeat amplification protocol (TRAP). TRAP utilizes RT-PCR of cellular exfracts to measure telomerase activity by making the amount of PCR target dependant upon the biochemical activity ofthe enzyme (Kim, N. W., 1997, Nucleic Acids Research, 25, 2595-2597, which is incoφorated by reference herein).

A method based on Kim is as follows. Briefly, for the telomerase assay, 2μg of protein exfract is used. The exfract is assayed in 50μl of reaction mixture containing 0.1 μg TS substrate primer (5^'-AATCCGTCGAGCAGAGTT-3', end-labeled using alpha-³²P- ATP and T4 polynucleotide kinase), 0.1 μg ACX return primer(5'-GCGCGG[CTTACC]₃ CTAACC-3'), 0.1 μg NT internal control primer (5*-ATCGCTTCTCGGCCTTTT-3'), 0.01 micromol TSNT internal confrol template (5'- AATCCGTCGAGCAGAGTTAAAAGGCCGAGAACGAT-3), 50 μM each deoxynucleoside triphosphate, 2 U of Taq DNA polymerase, and 2 μl CHAPS protein exfract, all in IX TRAP buffer (20 mM Tris (pH 8.3), 68 mM KC1, 1.5 mM MgCl₂, 1 mM EGTA, 0.05% Tween 20). Each reaction is placed in a thermocycler block preheated to 30 C and incubated at 30 C for 10 minutes, then cycled for 27 cycles of 94 degrees C for 30 seconds, 60 degrees C for 30 seconds. Reaction products are separated on a denaturing 8% polyacrylamide gel, followed by drying ofthe gel and autoradiography. The internal control (to control for possible Taq polymerase inhibition) generates a band of 36 nt. Comparison of radioactive signal integrated (e.g., by phoφhorimager analysis) for telomerase-extended bands with the radioactive signal from a reaction performed with a known amount of quantification standard template (termed R8; 5'-

AATCCGTCGAGCAGAGTTAG [GGTTAG]₇-3) allows expression of telomerase activity as an absolute value. The absolute value = TPG (total product generated) =[(TP- TPi)/TI]/[(R8-B)/RI)] x 100, where TP = telomerase products from test exfract, TPi = telomerase products from a heat-inactivated (75 C, 10 minutes) extract reaction, Tl = the signal from the internal control, R8 = the signal from the R8 qualification standard template reaction, B = signal from a lysis buffer-only blank reaction, and RI = the internal confrol value for the reaction containing R8 template and NT and TSNT confrol primers. TPG values of 0-10,000 are possible, with the linear range being from approximately 1 to 1000 TPG. The range of 1 to 1000 TPG encompasses the minimum and maximum levels of telomerase activity in most tumor samples tested, while non-tumor cells most often have no telomerase activity (TPG approximately zero). Telomerase activity may also be assayed as follows. Samples to be assayed for telomerase activity are prepared by extraction into CHAPS lysis buffer (lOmM Tris pH 7.5, ImM MgCl₂, ImM EGTA, 0.1 mM PMSF, 5mM -mercaptoethanol, ImM DTT, 0.5% 3-[(3-cholamidopropyl)-dimethyl-amino]-l- propanesulfonate (CHAPS), 10% glycerol and 40 U/ml RNAse inhibitor (Promega, Madison, WI, U.S.A.). Cells are suspended in CHAPS lysis buffer and incubated on ice for 30 minutes, which allows lysis of 90-100%) of cells. Lysate is then transferred to polyallomer centrifuge tubes and spun at 100,000 x g for 1 hour at 4 degrees C. The supernatant is the protein exfract, and concentration ranges of 4-10 μg/μl are suitable for telomerase assay. Extracts may be concentrated if necessary using a Microcon Microfilter 30 (Amicron, Beverly, MA U.S.A.) according to the manufactureris instructions. Exfracts may be stored frozen at -80 degrees C until assayed.

A variety of animal models have been designed to assay telomerase activity in vivo. Inhibition of telomerase activity has been analyzed in rats via cell proliferation studies with MNU (N-methyl-N-nitosurea) induced mammary carcinomas in response to treatment with 4-(hydroxyphenyl)retinamide (4-HPR), a known inhibitor of mammary carcinogenesis in animal models and premenopausal women (Bednarek, A., 1999, Carcinogenesis, 20, 879-883). Additional studies have focused on the up-regulation of telomerase in transformed cell lines from animal and human model systems (Zhang, P. B., 1998, Leuk. Res., 22, 509-516), (Chadeneau, C, 1995, Oncogene, 11, 893-898), (Greenberg, R., 1999, Oncogene, 18, 1219-1226).

Human cell culture studies have been established to assay inhibition of telomerase activity in human carcinomas responding to various therapeutics. A human breast cancer model for studying telomerase inhibitors is described (Raymond, E., 1999, Br. J. Cancer, 80, 1332-1341). Human studies of telomerase expression as related to various other cancers are described including cervical cancer (Nakano, K., 1998, Am. J. Pathol, 153, 857-864), endometrial cancer (Kyo, S., 1999, Int. J. Cancer, 80, 60-63), meningeal carcinoma (Kleinschmidt-DeMasters, B. K., 1998, J. Neurol. Sci., 161, 124-134), lung carcinoma (Yashima, K., 1997, Cancer Reseach, 57, 2372-2377), testicular cancer in response to cisplatin (Burger, A. M., 1997, Eur. J. Cancer, 33, 638-644), and ovarian carcinoma (Counter, C. M., 1994, Proc. Natl. Acad. Sci., 91, 2900-2904).

Particular degenerative and disease states that can be associated with telomerase expression modulation include but are not limited to:

Cancer: Almost all human tumors have detectable telomerase activity (Shay, J. W., 1997, Eur. J. Cancer, 33, 787-791). Treatment with telomerase inhibitors may provide effective cancer therapy with minimal side effects in normal somatic cells that lack telomerase activity. The therapeutic potential exists for the treatment of a wide variety of cancer types.

Restinosis: Telomerase inhibition in vascular smooth muscle cells may inhibit restinosis by limiting proliferation of these cells.

Infectious disease: Telomerase inhibition in infectious cell types that express telomerase activity may provide selective anti-infectious agent activity. Such treatment may prove especially effective in protozoan-based infection such as Giardia and Lesh Meniesis.

Transplant rejection: Telomerase inhibition in endothelial cell types may demonstrate selective immunnosuppressant activity. Activation of telomerase in transplant cells could benefit grafting success through increased proliferative potential. Autoimmune disease: Telomerase modulation in various immune cells may prove beneficial in treating diseases such as multiple sclerosis, lupus, and AIDS.

Age related disease: Activation of telomerase expression in cells at or nearing senescence as a result of advanced age or premature aging could benefit conditions such as macular degeneration, skin ulceration, and rheumatoid arthritis. The present body of knowledge in telomerase research indicates the need for methods to assay telomerase activity and for compounds that can regulate telomerase expression for research, diagnostic, trait alteration, animal health and therapeutic use.

Gemcytabine and cyclophosphamide are non-limiting examples of chemotherapeutic agents that can be combined with or used in conjunction with the nucleic acid molecules (e.g. ribozymes and antisense molecules) ofthe instant invention. Those skilled in the art will recognize that other drugs such as anti-cancer compounds and therapies can be similarly be readily combined with the nucleic acid molecules ofthe instant invention (e.g. ribozymes and antisense molecules) and are hence within the scope ofthe instant invention. Such compounds and therapies are well known in the art (see for example Cancer: Principles and Pranctice of Oncology, Volumes 1 and 2, eds Devita, V.T., Hellman, S., and Rosenberg, S.A., J.B. Lippincott Company, Philadelphia, USA; incoφorated herein by reference) and include, without limitations, antifolates; fluoropyrimidines; cytarabine; purine analogs; adenosine analogs; amsacrine; topoisomerase I inhibitors; anthrapyrazoles; retinoids; antibiotics such as bleomycin, anthacyclins, mitomycin C, dactinomycin, and mithramycin; hexamethylmelamine; dacarbazine; 1-asperginase; platinum analogs; alkylating agents such as nitrogen mustard, melphalan, chlorambucil, busulfan, ifosfamide, 4-hydroperoxycyclophosphamide, nifrosoureas, thiotepa; plant derived compounds such as vinca alkaloids, epipodophyllotoxins, taxol; Tomaxifen; radiation therapy; surgery; nutritional supplements; gene therapy; radiotherapy such as 3D-CRT; immunotoxin therapy such as ricin, monoclonal antibodies herceptin; and the like. For combination therapy, the nucleic acids ofthe invention are prepared in one of two ways. First, the agents are physically combined in a preparation of nucleic acid and chemotherapeutic agent, such as a mixture of a nucleic acid ofthe invention encapsulated in liposomes and ifosfamide in a solution for intravenous administration, wherein both agents are present in a therapeutically effective concentration (e.g., ifosfamide in solution to deliver 1000-1250 mg/m²/day and liposome-associated nucleic acid ofthe invention in the same solution to deliver 0.1-100 mg/kg/day). Alternatively, the agents are administered separately but simultaneously in their respective effective doses (e.g., 1000-1250 mg/m²/d ifosfamide and 0.1 to 100 mg/kg/day nucleic acid ofthe invention).

Gaeta et al, US patents No. 5,760,062; 5,767,278; 5,770,613 have described small molecule inhibitors of human telomerase RNA (hTR) subunit.

Blasco et al, 1995, Science, 269, 1267-1270 describe the synthesis and testing of antisense oligonucleotides targeted against a specific region ofthe mouse telomerase RNA (mTR) subunit and reported reduction in telomerase activity in mice.

Bisoffi et al, 1998, Eur. J. Cancer, 34, 1242-1249 have studied the down regulation of human telomerase activity by a refro virus vector expressing antisense RNA targeted against the hTR RNA. Norton et al, 1996, Nature Biotechnology, 14, 615-619 have reported the use of a peptide nucleic acid (PNA) molecule targeting hTR RNA to down regulate telomerase activity in human immortal breast epithelial cells.

Yokoyama et al, 1998, Cancer Research, 58, 5406-5410 have reported the synthesis and testing of hammerhead ribozyme constructs targeting hTR RNA resulting in a decrease in the telomerase activity in Ishikawa cells.

Henderson, European Patent Application No. 666,313-A2 describes methods of identifying and cloning hTR gene for use in gene therapy approaches for creating aberrant telomeric sequences in transfected human tumor cells. A ribozyme based gene therapy approach to inhibit the expression of hTR gene is described as well. The intended result of such therapies involves incurred genetic instability based on non-native telomeric sequences resulting in rapid cell death ofthe freated cells.

West et al, US patent No. 5,489,508 describe methods for determining telomere length and telomerase activity in cells. Inhibitors of hTR RNA, including oligonucleotides and/or small molecules are described.

These foregoing approaches of targeting the telomerase RNA subunit (TR) may not be very beneficial, because as demonstrated by Feng et al, (Feng, J., 1995, Science, 269, 1236-1241), telomerase activity in humans does not correlate well to hTR concentration.

Collins et al, International PCT publication No. WO 98/01542 describes assays for the detection of telomerase activity. Four human telomerase subunit proteins are described called pi 40, pi 05, p48 and p43. In addition, hybridization probes and primers are described as inhibitors of telomerase gene function. Antibody based inhibitors of telomerase protein subunits are described.

A more attractive approach to telomerase regulation would involve the regulation of human telomerase by modulating the expression ofthe protein subunits ofthe enzyme, preferably the reverse transcriptase (hTERT) subunit. Based of reconstitution experiments, hTERT and hTR represent the minimal components of telomerase. Since hTR expression does not correlate well with telomerase activity in human cells and since many human cells express hTR without telomerase activity, targeting hTERT may prove more beneficial than targeting hTR. hTERT is the only component necessary to restore telomerase activity in normal human cells. A study in which the three major subunits of telomerase (hTR, TPI, and hTERT were assayed in normal and malignant endometrial tissues determined that hTERT is a rate limiting determinant of enzymatic activity of human telomerase (Kyo, S., 1999, Int. J. Cancer, 80, 60-63). Additional protein subunits that have been isolated most likely serve only a structural role in telomerase activity, but may be important in enhancing the activity ofthe telomerase enzyme. As such, hTERT is one ofthe better targets for the ectopic regulation of telomerase activity.

Cech et al, International PCT publication No. WO 98/14593 describe compositions and methods related to hTERT for diagnosis, prognosis and treatment of human diseases, for altering proliferative capacity in cells and organisms, and for screening compounds and treatments with potential use as human therapeutics. Cech et al, International PCT publication No. WO 98/14592 describe nucleic acid and amino acid sequences encoding various telomerase protein subunits and motifs of Euplotes aediculatus, and related sequences from Schizosaccharomyces, Saccharomyces sequences, and human telomerase. The polypeptides comprising telomeric subunits and functional polypeptides and ribonucleoproteins that contain these subunits are described as well. Cech et al, International PCT Publication No. WO 98/14592, mentions in general terms the the possibility of using antisense and ribozymes to down regulate the expression of human telomerase reverse transcriptase enzyme.

Identification of Potential Target Sites in Human TERT RNA The sequence of human TERT was screened for accessible sites using a computer folding algorithm. Regions ofthe RNA that did not form secondary folding structures and contained potential ribozyme and/or antisense binding/cleavage sites were identified. The sequences of these cleavage sites are shown in Tables 13-17.

Selection of Enzymatic Nucleic Acid Cleavage Sites in Human TERT RNA

To test whether the sites predicted by the computer-based RNA folding algorithm corresponded to accessible sites in TERT RNA, 10 hammerhead ribozyme and three G- Cleaver ribozyme sites were selected for further analysis (Table 17). Ribozyme target sites were chosen by analyzing sequences of Human TERT (Nakamura et al, 1997 Science 277, 955-959; Genbank sequence accession number: NM 003219) and prioritizing the sites on the basis of folding. Ribozymes were designed that could bind each target and were individually analyzed by computer folding (Christoffersen et al, 1994 J. Mol. Struc. Theochem, 311, 273; Jaeger et al, 1989, Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether the ribozyme sequences fold into the appropriate secondary structure. Those ribozymes with unfavorable intramolecular interactions between the binding arms and the catalytic core were eliminated from consideration. As noted below, varying binding arm lengths can be chosen to optimize activity. Generally, at least 5 bases on each arm are able to bind to, or otherwise interact with, the target RNA.

Chemical Synthesis and Purification of Ribozymes for Efficient Cleavage of TERT RNA Ribozymes were designed to anneal to various sites in the RNA message. The binding arms are complementary to the target site sequences described above. The ribozymes were chemically synthesized. The method of synthesis used followed the procedure for normal RNA synthesis as described above and in Usman et al., (1987 J. Am. Chem. Soc, 109, 7845), Scaringe et al., (1990 Nucleic Acids Res., 18, 5433) and Wincott et al., supra, and made use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5'-end, and phosphoramidites at the 3'-end. The average stepwise coupling yields were >98%.

Ribozymes were also synthesized from DNA templates using bacteriophage T7 RNA polymerase (Milligan and Uhlenbeck, 1989, Methods Enzymol. 180, 51). Ribozymes were purified by gel electrophoresis using general methods or were purified by high pressure liquid chromatography (HPLC; See Wincott et al., supra; the totality of which is hereby incoφorated herein by reference) and were resuspended in water. The sequences of the chemically synthesized ribozymes used in this study are shown below in Table 13-17.

Ribozyme Cleavage of TERT RNA Target in vitro Ribozymes targeted to the human TERT RNA are designed and synthesized as described above. These ribozymes can be tested for cleavage activity in vitro, for example using the following procedure. The target sequences and the nucleotide location within the

TERT RNA are given in Tables 13-17.

Cleavage Reactions: Full-length or partially full-length, internally-labeled target RNA for ribozyme cleavage assay is prepared by in vitro transcription in the presence of

[_a.32p] CTP, passed over a G 50 Sephadex column by spin chromatography and used as substrate RNA without further purification. Alternately, substrates are 5'-32p-_en(i labeled using T4 polynucleotide kinase enzyme. Assays are performed by pre- warming 15 μl of a 2X concentration of purified ribozyme in ribozyme cleavage buffer (50 mM Tris-HCI, pH 7.5 at 37°C, 10 mM MgC ) and the cleavage reaction was initiated by adding the 2X ribozyme mix to an equal volume (15 μl) of subsfrate RNA (maximum of 1-5 nM; 5 x 10⁵ to 1 x 10⁷ cpm) that was also pre- warmed in cleavage buffer. As an initial screen, assays o are carried out for 1 hour at 37 C using a final concentration of either 40 nM or 1 mM ribozyme, i.e., ribozyme excess. The reaction is quenched by the addition of an equal volume (30 μl) of 95% formamide, 20 mM EDTA, 0.05% bromophenol blue and 0.05% o xylene cyanol after which the sample is heated to 95 C for 2 minutes, quick chilled and loaded onto a denaturing polyacrylamide gel. Subsfrate RNA and the specific RNA cleavage products generated by ribozyme cleavage are visualized on an autoradiograph of the gel. The percentage of cleavage is determined by Phosphor Imager® quantitation of bands representing the intact subsfrate and the cleavage products.

Example 2: PTP-IB

Protein tyrosine phosphorylation and dephosphorylation are important mechanisms in the regulation of signal transduction pathways that control the processes of cell growth, proliferation, and differentiation (Fantl, W. J., 1993, Annu. Rev. Biochem., 62, 453-481). Cooperative enzyme classes regulate protein tyrosine phosphorylation and dephosphorylation events. These broad classes of enzymes consist ofthe protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). PTKs and PTPs can exist as both receptor-type transmembrane proteins and as cytoplasmic protein enzymes. Receptor tyrosine kinases propagate signal transduction events via extracellular receptor-ligand interactions that result in the activation ofthe tyrosine kinase portion ofthe PTK in the cytoplasmic domain. Receptor-like transmembrane PTPs function through extracellular ligand binding that modulates dephosphorylation of infracellular phosphotyrosine proteins via cytoplasmic phosphatase domains. Cytoplasmic PTKs and PTPs exert enzymatic activity without receptor-mediated ligand interactions, however, phosphorylation can regulate the activity of these enzymes. Protein tyrosine phosphatase IB, a cytoplasmic PTP, was the first PTP to be isolated in homogeneous form (Tonks, N. K., 1988, J. Biol. Chem., 263, 6722-6730), characterized (Tonks, N. K., 1988, J. Biol. Chem., 263, 6731-6737), and sequenced (Charbonneau, H., 1989, Biochemistry, 86, 5252-5256). Cytoplasmic and receptor-like PTPs both share a catalytic domain characterized by eleven conserved amino acids containing cysteine and arginine residues that are critical for phosphatase activity (Streuli, M., 1990, EMBO, 9, 2399-2407). A cysteine residue at position 215 is responsible for the covalent attachment of phosphate to the enzyme (Guan, K, 1991, J. Biol. Chem., 266, 17026-17030). The crystal structure of human PTP IB defined the phosphate binding site ofthe enzyme as a glycine rich cleft at the surface of the molecule with cysteine 215 positioned at the base of this cleft. The location of cysteine 215 and the shape ofthe cleft provide specificity of PTPase activity for tyrosine residues but not for serine or threonine residues (Barford, D., 1994, Science, 263, 1397-1404).

Receptor tyrosine kinase and protein tyrosine phosphatase localization plays a key role in the regulation of phosphotyrosine mediated signal fransduction. PTP-IB activity and specificity against a panel of receptor tyrosine kinases demonstrated clear differences between substrates, suggesting that cellular comparrmentalization is a determinant in defining the activity and function ofthe enzyme (Lammers, R.,1993, J. Biol. Chem., 268, 22456-22462). Experiments have indicated that PTP-IB is localized predominantly in the endoplasmic reticulum via its 35 amino acid carboxyterminal sequence. PTP-IB is also tightly associated with microsomal membranes with its catalytic phosphatase domain oriented towards the cytoplasm (Frangioni, J. V., 1992, Cell, 68, 545-560).

PTP-IB has been identified as a negative regulator ofthe insulin response. PTP-IB is widely expressed in insulin sensitive tissues (Goldstein, B. J., 1993, Receptor, 3, 1-15). Isolated PTP-IB dephosphorylates the insulin receptor in vitro (Tonks, N. K., 1988, J. Biol. Chem., 263, 6731-6737). PTP-IB dephosphorylation of multiple phosphotyrosine residues ofthe insulin receptor proceeds sequentially and with specificity for the three tyrosine residues that are critical for receptor autoactivation (Ramachandran, C, 1992, Biochemistry, 31, 4232-4238). In addition to insulin receptor dephosphorylation, PTP-IB also dephosphorylates the insulin related subfrate 1 (IRS-1), a principal substrate ofthe insulin receptor (Lammers, R., 1993, J. Biol. Chem., 268, 22456-22462). Microinjection of PTP IB into Xenopus oocytes results in the inhibition of insulin stimulated tyrosine phosphorylation of endogenous proteins, including the β-subunit ofthe insulin and insulin-like growth factor receptor proteins. The resulting 3 to 5 fold increase over endogenous PTPase activity also blocks the activation of an S6 peptide kinase (Cicirelli, M. F., 1990, Proc, Natl. Acad. Sci., 87, 5514-5518). Inactivation of recombinant rat PTP-IB with antibody immunoprecipitation results in the dramatic increase in insulin stimulated DNA synthesis and phosphatidylinositol 3 '-kinase activity. Insulin stimulated receptor autophosphorylation and insulin receptor substrate 1 tyrosine phosphorylation are increased dramatically as well through PTP-IB inhibition (Ahmad, F., 1995, J. Biol. Chem., 270, 20503-20508).

Increased PTP-IB expression correlates with insulin resistance in hyperglycemic cultured fibroblasts. In this study, desensitized insulin receptor function was observed via impaired insulin-induced autophosphorylation ofthe receptor. Treatment with insulin sensitivity normalizing thiazolidine derivatives resulted in the amelioration ofthe hyperglycemic insulin resistance via a normalization in PTP-IB expression (Maegawa, H., 1995, J. Biol. Chem., 270, 7724-7730). A murine model of insulin resistance with a knockout of the hefrerotrimeric GTP-binding protein subunit Giα2 provides a type 2 diabetis phenotype that correlates with the increased expression of PTP-IB (Moxam, C. M., 1996, Nature, 379, 840-844). PTP-IB interacts directly with the activated insulin receptor β-subunit. An inactive homolog of PTP-IB was used to precipitate the activated insulin receptor in both purified receptor preparations and whole-cell lysates. Phosphorylation ofthe insulin receptor's triple tyrosine residues in the kinase domain is necessary for PTP-IB interaction. Furthermore, insulin stimulates tyrosine phosphorylation of PTP-IB (Seely, B. L., 1996, Diabetes, 45, 1379-1385). A similar study confirmed the direct interaction of PTP-IB with the insulin receptor β-subunit as well as the required multiple phosphorylation sites within the receptor and PTP-IB (Bandyopadhyay, D., J. Biol. Chem., 272, 1639-1645).

Knockout mice lacking the PTP-IB gene (both homozygous PTP-IB"''" and heterozygous PTP-1B^+/") have been used to study the specific role of PTP-IB relating to insulin action in vivo. The resulting PTP-IB deficient mice were healthy and, in the fed state, had lower blood glucose and circulating insulin levels that were half that of their PTP-1B^+/+ expressing littermates. These PTP-IB deficient mice demonstrated enhanced insulin sensitivity in glucose and insulin tolerance tests. At the physiological level, the PTP-IB deficient mice showed increased phosphorylation ofthe insulin receptor after insulin administration. When fed a high fat diet, the PTP-IB deficient mice were resistant to weight gain and remained insulin sensitive as opposed to normal PTP-IB expressing mice, who rapidly gained weight and become insulin resistant (Elchebly, M., 1999, Science, 283, 1544-1548). As such, modulation of PTP-IB expression could be used to regulate autophosphorylation ofthe insulin receptor and increase insulin sensitivity in vivo. This modulation could prove beneficial in the treatment of insulin related disease states. In light ofthe above findings, particular disease states that involve PTP-IB expression include but are not limited to:

Diabetes: Both type 1 and type 2 diabetes may be treated by modulation of PTP-IB expression. Type 2 diabetes correlates to desensitized insulin receptor function (White et al, 1994). Disruption ofthe PTP-IB dephosphorylation ofthe insulin receptor in vivo manifests in insulin sensitivity and increased insulin receptor autophosphorylation (Elchebly et al, 1999). Insulin dependant diabetes, type 1, may respond to PTP-IB modulation through increased insulin sensitivity.

Obesity: Elchebly et al, 1999, demonstrated that PTP-IB deficient mice were resistant to weight gain when fed a high fat diet compared to normal PTP-IB expressing mice. This finding suggests that PTP-IB modulation may be beneficial in the treatment of obesity. Ahmad et al, 1997, Metab. Clin. Exp., 46, 1140-1145, describe reduced PTPs in adipose tissue and improved insulin sensitivity in obese subjects following weight loss.

Troglitazone is a non-limiting example of a pharmaceutical agent that can be combined with or used in conjunction with the nucleic acid molecules (e.g. ribozymes and antisense molecules) ofthe instant invention. Those skilled in the art will recognize that other drugs such as anti-diabetes and anti-obesity compounds and therapies can be similarly be readily combined with the nucleic acid molecules ofthe instant invention (e.g. ribozymes and antisense molecules) are hence within the scope ofthe instant invention. Methods have been developed to assay PTP-IB activity.

Maegawa et al, 1995, J. Biol. Chem., 270, 7724-7730, describe a tissue culture model in which Rat 1 fibroblasts expressing human insulin receptors can be used to model hyperglycemia induced insulin resistance. Maegawa et al. also describe assays to measure PTPase activity using labeled phosphorylated insulin receptors and by immunoenzymatic techniques.

Moxham et al, 1996, Nature, 379, 840-844, describe a murine animal and tissue culture model employing Giα2 deficiency to study hyperinsulinaemia, impaired glucose tolerance and resistance to insulin in vivo. Assays for PTPase activity and tyrosine phosphorylation of insulin-receptor subsfrate 1 are described.

Khandelwal et al, 1995, Molecular and Cellular Biochemistry, 153, 87-94, describe four different animal models for studying insulin dependent and insulin resistant diabetes mellitus. These models were used to study the effect of vanadate, an insulin mimetic and PTPase inhibitor, on the insulin-stimulated phosphorylation ofthe insulin receptor and its tyrosine kinase acitivity.

Wang et al, 1999, Biochim. Biophys. Acta, 1431, 14-23, describe fluorescein monophosphates as fluorogenic substrates for PTPs. Various methods and compounds have been developed to inhibit protein tyrosine phosphatase activity.

Wrobel et al, 1999, J. Med. Chem., 42, 3199-3202, describe PTP-IB inhibition and antihyperglycemic activity in the ob/ob mouse model by 1 l-arylbenzo[b]naphtho[2,3- d]furans and arylbenzo[b]naphtho[2,3-d]thiophenes. Andersen et al, International PCT publication No. WO 98/DK407 describe the preparation of thienopyridzinones and thienochromenones as modulators of PTPases.

Taing et al, 1999, Biochemistry, 38, 3793-3803, describe potent and highly selective inhibitors of PTP-IB comprising an array of bis(aryldifluorophosphonates).

Ham et al, 1999, Bioorg. Med. Chem. Lett., 9, 185-186, describe selective inactivation of PTP- 1 B by a sulfone analog of naphthoquinone.

Desmarais et al, 1999, Biochem, J., 337, 219-223, describe [Difluro(phosphono)methyl]phenylalanine-containing peptide inhibitors of PTPs.

Taylor et al, 1998, Bioorg. Med. Chem., 6, 2235, describe potent non-peptidyl inhibitors of PTP-IB. Kotoris et al, 1998, Bioorg. Med. Chem. Lett., 8, 3275-3280, describe novel phosphate mimetics for the design of non-peptidyl inhibitors of PTPs. Groves et al, 1998, Biochemistry, 37, 17773-17783, describe the structural basis for PTP-IB inhibition by the phosphotyrosine peptide mimetics

(difluoronaphthylmethyl)phosphonic acid and the fluoromalonyl tyrosines with complexed crystal structures. Yao et al, 1998, Bioorgl Med. Chem., 6, 1799-1810, describe the structure-based design and synthesis of small molecule PTP-IB inhibitors comprising novel naphthyldifluoromethyl phosphonic acids 1 and 2.

Taylor et al, 1998, Bioorg. Med. Chem., 6, 1457-1468, describe potent non-peptidyl inhibitors of PTP-IB. Desmarais et al, 1998, Arch. Biochem. Biophys., 354, 225-231, describe inhibition of PTP-IB and CD45 by sulfotyrosyl peptides.

Mjalli et al, application US 96-766114, cont. in part of US patent No. 543,630, describe the preparation of heterocyclic compounds as modulators of proteins with phosphotyrosine recognition units. Wang et al, 1998, Bioorg. Med. Chem. Lett., 8, 345-350, describe naphthalenebis[α,α-difluoromethylenephosphonates] as potent inhibitors of PTPs.

Rice et al, 1997, Biochemistry, 36, 15965-15974, describe a targeted library of small molecule tyrosine and dual-specificity phosphatase inhibitors with random side chain variation from a rational core design. Olefsky, International PCT publication No. WO 97/US2752 describes a method and phosphopeptides used for the treatment of insulin resistance based on the association of PTP-IB with the activated insulin receptor. Also included is a method for determining whether a compound inhibits PTP-IB binding to the insulin receptor.

Huyer et al, 1997, J. Biol. Chem., 272, 843-851, describe the mechanism of inhibition of PTPases by vanadate and pervanadate.

Burke et al, 1996, Biochemistry, 35, 15989-15996, describe the structure-based design of PTP-IB inhibitors.

Tonks et al, International PCT publication No. WO 97/US13016, describe subsfrate-frapping protein PTPase mutants for identification of tyrosine-phosphorylated protein substrates and their clinical uses. The human genome is thought to contain up to 100 PTPases, each varying slightly in chemistry but vastly in function. Compounds designed to inhibit PTP-IB activity specifically by covalent binding to or modification of PTP-IB have the potential for multiple side effects. Conventional drug substances that will potently suppress PTP-IB activity with few or no side effects from interaction with other PTPs are difficult to envision. A more attractive approach to PTP-IB modulation would involve the specific regulation of PTP-IB expression with oligonucleotides.

Identification of Potential Target Sites in Human PTP-IB RNA The sequence of human PTP-IB was screened for accessible sites using a computer folding algorithm. Regions ofthe RNA that did not form secondary folding structures and contained potential ribozyme and/or antisense binding/cleavage sites were identified. The sequences of these cleavage sites are shown in Tables 3-8.

Selection of Enzymatic Nucleic Acid Cleavage Sites in Human PTP-IB RNA

To test whether the sites predicted by the computer-based RNA folding algorithm corresponded to accessible sites in PTP-IB RNA, 10 hammerhead ribozyme, five NCH and three G-Cleaver ribozyme sites were selected for further analysis (Table 8). Ribozyme target sites were chosen by analyzing sequences of Human PTP-IB (Genbank accession number M33689) and prioritizing the sites on the basis of folding. Ribozymes were designed that could bind each target and were individually analyzed by computer folding (Christoffersen et al, 1994 J. Mol. Struc. Theochem, 311, 273; Jaeger et al, 1989, Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether the ribozyme sequences fold into the appropriate secondary structure. Those ribozymes with unfavorable intramolecular interactions between the binding arms and the catalytic core were eliminated from consideration. As noted below, varying binding arm lengths can be chosen to optimize activity. Generally, at least 5 bases on each arm are able to bind to, or otherwise interact with, the target RNA. Chemical Synthesis and Purification of Ribozymes for Efficient Cleavage of PTP-IB RNA

Ribozymes were designed to anneal to various sites in the RNA message. The binding arms are complementary to the target site sequences described above. The ribozymes were chemically synthesized. The method of synthesis used followed the procedure for normal RNA synthesis as described above and in Usman et al., (1987 J. Am. Chem. Soc, 109, 7845), Scaringe et al., (1990 Nucleic Acids Res., 18, 5433) and Wincott et al., supra, and made use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5'-end, and phosphoramidites at the 3'-end. The average stepwise coupling yields were >98%. Ribozymes were also synthesized from DNA templates using bacteriophage T7

RNA polymerase (Milligan and Uhlenbeck, 1989, Methods Enzymol. 180, 51). Ribozymes were purified by gel electrophoresis using general methods or were purified by high pressure liquid chromatography (HPLC; see Wincott et al., supra; the totality of which is hereby incoφorated herein by reference) and were resuspended in water. The sequences of the chemically synthesized ribozymes used in this study are shown below in Tables 3-8.

Ribozyme Cleavage of PTP-IB RNA Target in vitro

Ribozymes targeted to the human PTP-IB RNA are designed and synthesized as described above. These ribozymes can be tested for cleavage activity in vitro, for example, using the following procedure. The target sequences and the nucleotide location within the PTP-IB RNA are given in Tables 3-8.

Cleavage Reactions: Full-length or partially full-length, internally-labeled target RNA for ribozyme cleavage assay is prepared by in vitro transcription in the presence of [α-³²p] CTP, passed over a G 50 Sephadex column by spin chromatography and used as subsfrate RNA without further purification. Alternately, substrates are 5'-32p-end labeled using T4 polynucleotide kinase enzyme. Assays are performed by pre-warming a 2X concentration of purified ribozyme in ribozyme cleavage buffer (50 mM Tris-HCI, pH 7.5 at 37°C, 10 mM MgCl2) and the cleavage reaction was initiated by adding the 2X ribozyme mix to an equal volume of substrate RNA (maximum of 1-5 nM) that was also pre-warmed in cleavage buffer. As an initial screen, assays are carried out for 1 hour at o

37 C using a final concentration of either 40 nM or 1 mM πbozyme, i.e., nbozyme excess. The reaction is quenched by the addition of an equal volume of 95% formamide, 20 mM EDTA, 0.05%) bromophenol blue and 0.05% xylene cyanol after which the sample is o heated to 95 C for 2 minutes, quick chilled and loaded onto a denatuπng polyacrylamide gel. Substrate RNA and the specific RNA cleavage products generated by ribozyme cleavage are visualized on an autoradiograph ofthe gel. The percentage of cleavage is determined by Phosphor Imager® quantitation of bands representing the intact subsfrate and the cleavage products.

Example 3: MetAP-2 Methionyl aminopeptidases are metalloproteases that are known to possess post- franslational enzymatic activity by hydrolytically cleaving amino-terminal methionine residues from nascent peptide substrates in a non-processive manner (Kendall, R. L., 1992, J. Biol. Chem., 267, 20667-20673). This family of enzymes is divided into two classes (type 1 and type 2) based on differences in sequence, although the overall structure ofthe two classes are similar (Liu, S., 1998, Science, 282, 1324-1327). Methionine aminopeptidase expression appears to be involved in the confrol of cellular proliferation. Deletion ofthe MetAP gene from E. Coli is lethal (Chang, S. Y., 1989, J. Bacteriol., 171, 4071-4072). In Saccharomyces cerevisiae, deletion ofthe gene that codes for either MetAP- 1 or 2 results in a slow growth phenotype while deletion of both genes is lethal (Li, X., 1995, Proc. Natl. Acad. Sci., 92, 12357-12361). (Human methionine aminopeptidase- 1, MetAP-1, accession No. P53582).

The aminopeptidase function of this class of enzymes may serve a regulatory role in activating signal peptides in conjunction with N-myristoyl transferase (NMT) activity. NMT is expressed from a lethal gene in yeast (Duronio, R. J., 1989, Science, 243, 796- 800). NMT is responsible for amino-terminal ligation of myristic acid onto nascent peptides and cannot act on peptides with an amino-terminal methionine residue (Resh, M. D., 1996, Cell. Signal., 8, 403-412). Myristoylation of proteins correlates to intracellular localization events that may determine why certain signaling proteins are dependent on NMT for activity (Taunton, J., 1997, Chemistry & Biology, 4, 493-496). Protein tyrosine kinase Src is dependant on myristoylation for activity and has been identified as an upstream regulator of human vascular endothelial growth factor (VEGF) expression through hypoxic induction in solid tumors (Mukhopadhyay, D., 1995, Nature, 375, 577- 581). MetAPs may therefore regulate the activation of signal peptides (such as VEGF) through cofranslational modification of nascent peptides with NMT. Disruption of protein myristoylation by MetAP inhibition could result in the improper localization of signaling proteins resulting in inhibition of cell growth. (Human N-myristoyltransferase, hNMT, accession No. AF043324.)

Fumagillin, a sesquiteφene diepoxide metabolite ofthe fungus Aspergillus fumigatus, and a related compound TNP-470, are strong inhibitors of growth in cultured endothelial cells. The antiproliferative and angiostatic activity of fumagillin was originally discovered by the serendipitous contamination of Aspergillus fumigatus in an endothelial cell culture dish in which cells closest to the fungal colony displayed growth inhibition. Synthetic analogs of fumagillin were later synthesized resulting in the discovery of TNP- 470, which is 50 times more potent of an inhibitor than fumagillin and is less toxic in mice (Ingber, D., 1990, Nature, 348, 555-557). Treatment of endothelial cells with these compounds results in late Gl phase arrest. TNP-470 inhibits the signaling pathway of retinoblastoma gene product phosphorylation, cyclin dependent kinases cdk2 and cdk4 activation, and cyclins E and A expression (Abe, J., 1994, Cancer Res., 54, 3407-3412). TNP-470 has also been shown to potently inhibit endothelial cell proliferation induced by the growth factors VEGF and bFGF (Toi, M., 1994, Oncology Reports, 1, 423-426). The bifunctional protein MetAP-2 has been identified as the molecular target for fumagillin and related compounds that demonstrate antiproliferative activity in endothelial cells. The use of affinity chromatography with a fumagillin-biotin conjugate resulted in the isolation of a 67-kDa mammalian protein through covalent interaction with the bound subsfrate. Analysis of digested peptide fragments from the isolated protein revealed MetAP-2 as the covalently bound substrate. Subsequent growth inhibition studies in yeast utilizing MetAP- 1 and MetAP-2 deletion strains determined that MetAP-2 is selectively inhibited by fumagillin in vivo (Sin, N., 1997, Proc. Natl. Acad. Sci., 94, 6099-6103). A similar study with TNP-470 and ovalicin, another potent inhibitor of neovascularization, determined that MetAP-2 is the molecular target for these fumagillin-related compounds (Griffith, E. C, 1997, Chemistry & Biology, 4, 461-471). MetAP-2 expression correlates with cellular growth. Non-dividing cells in culture have no detectable levels ofthe 67-kDa MetAP-2 protein by immunoassay. MetAP-2 has been shown to affect franslational initiation by association with eukaryotic initiation factor 2α (eIF-2 ) (Ray, M. K., 1992, Proc. Natl. Acad. Sci., 89, 539-543). The binding of MetAP-2 with eLF-2α inhibits the heme-regulated inhibitor kinase (HRI) phosphorylation of eLF-2α in vitro in reticulocyte lysates (Datta, B., 1988, Proc. Natl. Acad. Sci., 85, 3324- 3328). MetAP-2/eIF-2α binding results in the partial reversal of protein synthesis inhibition by double stranded RNA dependent kinase mediated phosphorylation in vivo (Wu, S., 1996, Biochemistry, 35, 8275-8280). Griffith et al. also determined that covalent binding of TNP-470 and ovalicin, while potently inhibiting methionine aminopeptidase type 2 activity specifically, did not affect the regulatory activity of MetAP-2 on eIF-2α. This finding by Griffith et al. rules out the possibility that confrol of eLF-2α phosphorylation by MetAP-2 is responsible for the inhibition of endothelial cell proliferation by fumagillin related compounds. Particular angiogenesis related degenerative and disease states that can be associated with MetAP expression modulation include but are not limited to: Cancer: Solid tumors are unable to grow or metastasize without the formation of new blood vessels (Hanahan, D., 1996, Cell, 86, 353-364). Inhibition of angiogenesis via MetAP modulation can potentially be used to freat a wide variety of cancers.

Diabetic retinopathy and age related macular degeneration: Ocular neovascularization is observed in diabetic retinopathy, which is mediated by up-regulation of VEGF (Adamis, A. P., 1994, Amer. J. Ophthal, 118, 445-450). The requirement of protein kinase Src in hypoxia induced VEGF expression (Mukhopadhyay, D., 1995, Nature, 375, 577-581) indicates that MetAP modulation of aminopeptidase activity can potentially be used to freat conditions involving ocular neovascularization.

Arthritis: The ingrowth of a vascular pannus in arthritis may be mediated by the overexpression of angiogenic factors from infiltrating inflammatory cells, macrophages, and immune cells (Peacock, D. J., 1992, J. exp. Med., 175, 1135-1138). Angiogenesis inhibition through MetAP modulation can potentially be used to freat arthritis. Psoriasis: Angiogenesis has been implicated in psoriasis due to overexpression of the angiogenic polypeptide interleukin-8 and decreased expression ofthe angiogenesis inhibitor thrombospondin (Nickoloff, B. J., 1994, Amer. J. Pathol. 44, 820-828). Angiogenesis inhibition through MetAP modulation can potentially be used to treat psoriasis.

Female reproduction: Angiogenesis in the female reproductive system has been implicated in several disorders ofthe reproductive tract (Reynolds, L. P., 1992, FASEB, 6, 886-892). Modulation of angiogenesis through confrol of MetAP may have various applications in the area of female reproduction and fertility. Various methods have been developed to assay MetAP activity.

Griffith et al, 1998, Proc. Natl. Acad. Sci., 95, 15183-15188, describe an enzymatic assay for MetAP-2 activity in vitro and an endothelial cell culture proliferation assay for MetAP-2 activity in vivo.

Weber et al, 1999, International PCT publication No. WO 98/US-21231 describe novel fluorescent reporter molecules and an enzymatic assay that can be used for determining the activity of MetAP-2 for drug screening and determining the chemosensitivity of human cancer cells to treatment with chemotherapeutic drugs.

Larrabee, J. A. et al, 1999, Anal. Biochem, 269, 194-198, describe the use of a high- pressure liquid chromatographic (HPLC) method for assaying MetAP-2 activity with application to the study of enzymic inactivation.

Quantitative methods have been developed to assay the efficacy of antiangiogenic therapies.

Wantanabe et al, 1992, Molec Biol. Cell, 3, 324a, describe the quantitation of angiogenic peptides (bFGF) in human serum as a prognostic test for breast cancer. Nguyen et al, 1994, J. Narn. Cancer Inst., 86, 356-361, describe the quantitation of angiogenic peptides (bFGF) in the urine of patients with a wide spectrum of cancers. Li et al, 1994, The Lancet, 344, 82-86, describe the quantitation of angiogenic peptides (bFGF) in the cerebrospinal fluid of children with brain tumors. This work also describes determining the extent of neovascularization in histological sections by utilizing microvessel count. The present body of knowledge in angiogenesis research indicates the need for compounds that can modulate MetAP activity for research, diagnostic, trait alteration, animal health and therapeutic use.

Griffith et al, International PCT publication No. WO 9856372 describe small molecule inhibitors of MetAP2 and uses thereof.

D'Amato et al, International PCT publication No. WO 9805293 describe the use of AGM-1470 (TNP-470) as an angiogenesis inhibitor for use in regulating the female reproductive system and for treating diseases ofthe reproductive tissue.

Davidson et al, US patent No. 5,801,146 describe a compound and method for inhibiting angiogenesis using mammalian kringle 5 protein.

Cao et al, US patent No. 5,854,221 describe a protein-based endothelial cell proliferation inhibitor and its method of use.

Chang et al, US patent No. 5,888,796 describe a clone of a nucleotide sequence encoding a protein having two functions comprising methionine aminopeptidase activity and anti eIF-2 phosphorylation activity.

Wang et al, 1998, Proc. Am. Assoc Cancer Res., 39, 98 (absfr.) describe blocked proliferation of human endothelial cells by human MetAP-2 antisense oligonucleotides.

A rat corneal model has been developed to study ribozyme inhibition of VEGF receptor-mediated angiogenesis (Pavco, P. A., 1999, Nucleic Acids Research, 27, 2569- 2577). A similar study employing MetAP-2 inhibition could be used to study ribozyme based inhibition of MetAP-2 induced angiogenesis in vivo.

Identification of Potential Target Sites in Human MetAP-2 RNA

The sequence of human MetAP-2 was screened for accessible sites using a computer- folding algorithm. Regions ofthe RNA that did not form secondary folding structures and contained potential ribozyme and/or antisense binding/cleavage sites were identified. The sequences of these cleavage sites are shown in Tables 9-12.

Selection of Enzymatic Nucleic Acid Cleavage Sites in Human MetAP-2 RNA To test whether the sites predicted by the computer-based RNA folding algorithm corresponded to accessible sites in MetAP-2 RNA, 11 hammerhead ribozyme, 4 NCH and three G-Cleaver ribozyme sites were selected for further analysis (Table 12). Ribozyme target sites were chosen by analyzing sequences of Human MetAP-2 (Genbank accession number HSU29607) and prioritizing the sites on the basis of folding. Ribozymes were designed that could bind each target and were individually analyzed by computer folding (Christoffersen et al, 1994 J. Mol. Struc. Theochem, 311, 273; Jaeger et al, 1989, Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether the ribozyme sequences fold into the appropriate secondary structure. Those ribozymes with unfavorable intramolecular interactions between the binding arms and the catalytic core were eliminated from consideration. As noted below, varying binding arm lengths can be chosen to optimize activity. Generally, at least 5 bases on each arm are able to bind to, or otherwise interact with, the target RNA.

Chemical Synthesis and Purification of Ribozymes for Efficient Cleavage of MetAP-2 RNA

Ribozymes were designed to anneal to various sites in the RNA message. The binding arms are complementary to the target site sequences described above. The ribozymes were chemically synthesized. The method of synthesis used followed the procedure for normal RNA synthesis as described above and in Usman et al., (1987 J. Am. Chem. Soc, 109, 7845), Scaringe et al., (1990 Nucleic Acids Res., 18, 5433) and Wincott et al., supra, and made use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5'-end, and phosphoramidites at the 3'-end. The average stepwise coupling yields were >98%.

Ribozymes were also synthesized from DNA templates using bacteriophage T7 RNA polymerase (Milligan and Uhlenbeck, 1989, Methods Enzymol. 180, 51). Ribozymes were purified by gel electrophoresis using general methods or were purified by high pressure liquid chromatography (HPLC; see Wincott et al, supra; the totality of which is hereby incoφorated herein by reference) and were resuspended in water. The sequences of the chemically synthesized ribozymes used in this study are shown below in Table 9-12.

Ribozyme Cleavage of MetAP-2 RNA Target in vitro Ribozymes targeted to the human MetAP-2 RNA are designed and synthesized as described above. These ribozymes can be tested for cleavage activity in vitro, for example, using the following procedure. The target sequences and the nucleotide location within the MetAP-2 RNA are given in Tables 9-12.

Cleavage Reactions: Full-length or partially full-length, internally-labeled target RNA for ribozyme cleavage assay is prepared by in vitro transcription in the presence of [a-³²p] CTP, passed over a G 50 Sephadex column by spin chromatography and used as subsfrate RNA without further purification. Alternately, substrates are 5'-32p-end labeled using T4 polynucleotide kinase enzyme. Assays are performed by pre-warming a 2X concentration of purified ribozyme in ribozyme cleavage buffer (50 mM Tris-HCI, pH 7.5 at 37°C, 10 mM MgC ) and the cleavage reaction was initiated by adding the 2X ribozyme mix to an equal volume of substrate RNA (maximum of 1 -5 nM) that was also pre-warmed in cleavage buffer. As an initial screen, assays are carried out for 1 hour at o

37 C using a final concentration of either 40 nM or 1 mM ribozyme, i.e., ribozyme excess. The reaction is quenched by the addition of an equal volume of 95% formamide, 20 mM EDTA, 0.05%) bromophenol blue and 0.05% xylene cyanol after which the sample is o heated to 95 C for 2 minutes, quick chilled and loaded onto a denaturing polyacrylamide gel. Subsfrate RNA and the specific RNA cleavage products generated by ribozyme cleavage are visualized on an autoradiograph ofthe gel. The percentage of cleavage is determined by Phosphor Imager® quantitation of bands representing the intact substrate and the cleavage products.

Example 4: BACE, ps-1, ps-2

Alzheimer's disease (AD) is a progressive, degenerative disease ofthe brain which affects approximately 4 million people in the United States alone. An estimated 14 million Americans will have Alzheimer's disease by the middle ofthe next century if no cure or definitive prevention ofthe disease is found. Nearly one out often people over age 65 and nearly half of those over 85 have Alzheimer's disease. Alzheimer's disease is not confined to the elderly, a small percentage of people in their 30' s and 40 's are afflicted with early onset AD. Alzheimer's disease is the most common form of dementia, and amounts to the third most expensive disease in the US following heart disease and cancer. An estimated 100 billion dollars are spent annually on Alzheimer's disease (National Alzheimer's Association, 1999). Alzheimer's disease is characterized by the progressive formation of insoluble plaques and vascular deposits in the brain consisting ofthe 4 kD amyloid β peptide (Aβ). These plaques are characterized by dysfrophic neurites that show profound synaptic loss, neurofibrillary tangle formation, and gliosis. Aβ arises from the proteolytic cleavage of the large type I transmembrane protein, β-amyloid precursor protein (APP) (Kang et al, 1987, Nature, 325, 733). Processing of APP to generate Aβ requires two sites of cleavage by a β-secretase and a γ-secretase. β-secretase cleavage of APP results in the cytoplasmic release of a 100 kD soluble amino-terminal fragment, APPsβ, leaving behind a 12 kD transmembrane carboxy-terminal fragment, C99. Alternately, APP can be cleaved by a α- secretase to generate cytoplasmic APPsα and transmembrane C83 fragments. Both remaining transmembrane fragments, C99 and C83, can be further cleaved by a γ- secretase, leading to the release and secretion of Alzheimer's related Aβ and a non- pathogenic peptide, p3, respectively (Vassar et al, 1999, Science, 286, 735-741). Early onset familial Alzheimer's disease is characterized by mutant APP protein with a Met to Leu substitution at position PI, characterized as the "Swedish" familial mutation (Mullan et al, 1992, Nature Genet., 1, 345). This APP mutation is characterized by a dramatic enhancement in β-secretase cleavage (Citron et al, 1992, Nature, 360, 672).

The identification of β-secretase, and γ-secretase constituents involved in the release of β-amyloid protein is of primary importance in the development of treatment strategies for Alzheimer's disease. Characterization of α-secretase is also important in this regard since α-secretase cleavage may compete with β-secretase cleavage resulting in non- pathogenic vs. pathogenic protein production. Involvement ofthe two metalloproteases, ADAM 10, and TACE has been demonstrated in α-cleavage of AAP (Buxbaum et al, 1999, J. Biol. Chem., 273, 27765, and Lammich et al, 1999, Proc. Natl. Acad. Sci. U.S.A., 96, 3922). Studies of γ-secretase activity have demonsfrated presenilin dependence (De Stooper et al, 1998, Nature, 391, 387, and De Stooper et al, 1999, Nature, 398, 518), and as such, presenilins have been proposed as γ-secretase even though presenilin does not present proteolytic activity (Wolfe et al, 1999, Nature, 398, 513). Recently, Vassar et al, 1999, supra reported β-secretase cleavage of AAP by the transmembrane aspartic protease beta site APP cleaving enzyme, BACE. While other potential candidates for β-secretase have been proposed (for review see Evin et al, 1999, Proc. Natl. Acad. Sci. U.S.A., 96, 3922), none have demonstrated the full range of characteristics expected from this enzyme. Vassar et al, supra, demonstrate that BACE expression and localization are as expected for β-secretase, that BACE overexpression in cells results in increased β-secretase cleavage of APP and Swedish APP, that isolated BACE demonstrates site specific proteolytic activity on APP derived peptide substrates, and that antisense mediated endogenous BACE inhibition results in dramatically reduced β-secretase activity.

Current treatment strategies for Alzheimer's disease rely on either the prevention or the alleviation of symptoms and/or the slowing down of disease progression. Two drugs approved in the treatment of Alzheimer's, donepezil (Aricept®) and tacrine (Cognex®), both cholinomimetics, attempt to slow the loss of cognitive ability by increasing the amount of acetylcholine available to the brain. Antioxidant therapy through the use of antioxidant compounds such as alpha-tocopherol (vitamin E), melatonin, and selegeline (Eldepryl®) attempt to slow disease progression by minimizing free radical damage. Estrogen replacement therapy is thought to incur a possible preventative benefit in the development of Alzheimer's disease based on limited data. The use of anti-inflammatory drugs may be associated with a reduced risk of Alzheimer's as well. Calcium channel blockers such as Nimodipine® are considered to have a potential benefit in treating Alzheimer's disease due to protection of nerve cells from calcium overload, thereby prolonging nerve cell survival. Nootropic compounds, such as acetyl-L-carnitine (Alcar®) and insulin, have been proposed to have some benefit in treating Alzheimer's due to enhancement of cognitive and memory function based on cellular metabolism.

Whereby the above treatment strategies may all improve quality of life in

Alzheimer's patients, there exists an unmet need in the comprehensive treatment and prevention of this disease. As such, there exists the need for therapeutics effective in reversing the physiological changes associated with Alzheimer's disease, specifically, therapeutics that can eliminate and/or reverse the deposition of amyloid β peptide. The use of compounds to modulate the expression of proteases that are instrumental in the release of amyloid β peptide, namely β-secretase (BACE), and γ-secretase (presenilin), is of therapeutic significance.

Tsai et al, 1999, Book of Absfrasts, 218^th ACS National Meeting, New Orleans, Aug 22-26, describe substrate-based alpha-aminoisobutyric acid derivatives of difluoro ketone peptidomimetic inhibitors of amyloid β peptide through γ-secretase inhibition.

Czech et al, International PCT publication No. WO/9921886, describe peptides capable of inhibiting the interaction between presenilins and the β-amyloid peptide or its precursor for therapeutic use.

Fournier et al, International PCT publication No. WO/9916874, describe human brain proteins capable of interacting with presenilins and cDNAs encoding them toward therapeutic use.

St. George-Hyslop et al, International PCT publication No. WO/9727296, describe genes for proteins that interact with presenilins and their role in Alzheimer's disease toward therapeutic use. Vassar et al, 1999, Science, 286, 735-741, describe specific antisense oligonucleotides targeting BACE, used for inhibition studies of endogenous BACE expression in 101 cells and APPsw cells via lipid mediated fransfection.

Vassar et al, 1999, Science, 286, 735-741, describe a cell culture model for studying BACE inhibition. Specific antisense nucleic acid molecules targeting BACE mRNA were used for inhibition studies of endogenous BACE expression in 101 cells and APPsw

(Swedish type amyloid precursor protein expressing) cells via lipid mediated transfection. Antisense treatment resulted in dramatic reduction of both BACE mRNA by Northern blot analysis, and APPsβsw ("Swedish" type β-secretase cleavage product) by ELISA, with maximum inhibition of both parameters at 75-80%. This model was also used to study the effect of BACE inhibition on amyloid β-peptide production in APPsw cells.

Games et al, 1995, Nature, 373, 523-527, describe a transgenic mouse model in which mutant human familial type APP (Phe 717 instead of Val) is overexpressed. This model results in mice that progressively develop many ofthe pathological hallmarks of Alzheimer's disease, and as such, provides a model for testing therapeutic drugs. Particular degenerative and disease states that can be associated with BACE expression modulation include but are not limited to Alzheimer's disease and dementia. Donepezil, tacrine, selegeline, and acetyl-L-carnitine are non-limiting examples of pharmaceutical agents that can be combined with or used in conjunction with the nucleic acid molecules (e.g. ribozymes and antisense molecules) ofthe instant invention. Those skilled in the art will recognize that other drugs such as diuretic and antihypertensive compounds and therapies can be similarly be readily combined with the nucleic acid molecules ofthe instant invention (e.g. ribozymes and antisense molecules) are hence within the scope ofthe instant invention.

Identification of Potential Target Sites in Human BACE RNA The sequence of human BACE was screened for accessible sites using a computer- folding algorithm. Regions ofthe RNA that did not form secondary folding structures and contained potential ribozyme and/or antisense binding/cleavage sites were identified. The sequences of these cleavage sites are shown in Tables 18-23.

Selection of Enzymatic Nucleic Acid Cleavage Sites in Human BACE RNA

Ribozyme target sites were chosen by analyzing sequences of Human BACE (Genbank sequence accession number: AF 190725) and prioritizing the sites on the basis of folding. Ribozymes were designed that could bind each target and were individually analyzed by computer folding (Christoffersen et al, 1994 J. Mol. Struc. Theochem, 311, 273; Jaeger et al, 1989, Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether the ribozyme sequences fold into the appropriate secondary structure. Those ribozymes with unfavorable intramolecular interactions between the binding arms and the catalytic core were eliminated from consideration. As noted below, varying binding arm lengths can be chosen to optimize activity. Generally, at least 5 bases on each arm are able to bind to, or otherwise interact with, the target RNA.

Chemical Synthesis and Purification of Ribozymes and Antisense for Efficient Cleavage and/or blocking of BACE RNA

Ribozymes and antisense constructs were designed to anneal to various sites in the RNA message. The binding arms ofthe ribozymes are complementary to the target site sequences described above, while the antisense constructs are fully complimentary to the target site sequences described above. The ribozymes and antisense constructs were chemically synthesized. The method of synthesis used followed the procedure for normal RNA synthesis as described above and in Usman et al., (1987 J. Am. Chem. Soc, 109, 7845), Scaringe et al., (1990 Nucleic Acids Res., 18, 5433) and Wincott et al., supra, and made use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5'-end, and phosphoramidites at the 3'-end. The average stepwise coupling yields were >98%.

Ribozymes and antisense constructs were also synthesized from DNA templates using bacteriophage T7 RNA polymerase (Milligan and Uhlenbeck, 1989, Methods Enzymo 180, 51). Ribozymes and antisense constructs were purified by gel elecfrophoresis using general methods or were purified by high pressure liquid chromatography (HPLC; See Wincott et al., supra; the totality of which is hereby incoφorated herein by reference) and were resuspended in water. The sequences ofthe chemically synthesized ribozymes and antisense constructs used in this study are shown below in Table 18-23.

Ribozyme Cleavage of BACE RNA Target in vitro

Ribozymes targeted to the human BACE RNA are designed and synthesized as described above. These ribozymes can be tested for cleavage activity in vitro, for example, using the following procedure. The target sequences and the nucleotide location within the BACE RNA are given in Tables 18-23.

Cleavage Reactions: Full-length or partially full-length, internally-labeled target RNA for ribozyme cleavage assay is prepared by in vitro transcription in the presence of [a-³²p] CTP, passed over a G 50 Sephadex column by spin chromatography and used as substrate RNA without further purification. Alternately, substrates are 5'-32p-end labeled using T4 polynucleotide kinase enzyme. Assays are performed by pre-warming a 2X concentration of purified ribozyme in ribozyme cleavage buffer (50 mM Tris-HCI, pH 7.5 at 37°C, 10 mM MgCl₂) and the cleavage reaction was initiated by adding the 2X ribozyme mix to an equal volume of substrate RNA (maximum of 1-5 nM) that was also pre-warmed in cleavage buffer. As an initial screen, assays are carried out for 1 hour at o 37 C using a final concentration of either 40 nM or 1 mM ribozyme, i.e., ribozyme excess. The reaction is quenched by the addition of an equal volume of 95% formamide, 20 mM EDTA, 0.05%) bromophenol blue and 0.05% xylene cyanol after which the sample is heated to 95 C for 2 minutes, quick chilled and loaded onto a denaturing polyacrylamide gel. Substrate RNA and the specific RNA cleavage products generated by ribozyme cleavage are visualized on an autoradiograph ofthe gel. The percentage of cleavage is determined by Phosphor Imager® quantitation of bands representing the intact subsfrate and the cleavage products.

Example 5: Phospholamban

Cardiac disease leading to heart failure is the leading cause of combined morbidity and mortality in the developed world. Nearly twenty million people worldwide suffer from heart failure related disease. An estimated five million Americans are afflicted with congestive heart failure (CHF), with 400,000 new cases diagnosed each year. In the US, cardiac disease associated failure results in approximately 40,000 deaths per year, and is associated with an additional 250,000 deaths (Harnish, 1999, Drug & Market Development, 10, 114-119). Heart failure related disease represents a major public health issue due to an overall increase in prevalence and incidence in aging populations with a greater proportion of survivors of acute myocardial infarction (AMI) (Kannel et al, 1994, Br. Heart. J., 72 (suppl), 3). Heart failure related disease represents the most common reason for hospitalization of elderly patients in the US. The resulting life expectancy of these patients is less than that of many common cancers, with five year survival rates for men and women at only 25% and 38% respectively, and with one year mortality rates for severe heart failure at 50% (Ho et al, 1993, Circulation, 88, 107).

Heart disease is characterized by a progressive decrease in cardiac output resulting from insufficient pumping activity ofthe diseased heart. The resulting venous back- pressure results in peripheral and pulmonary dysfunctional congestion. The heart responds to a variety of mechanical, hemodynamic, hormonal, and pathological stimuli by increasing muscle mass in response to an increased demand for cardiac output. The resulting transformation of heart tissue (myocardial hypertrophy) can arise as a result of genetic, physiologic, and environmental factors, and represents an early indication of clinical heart disease and an important risk factor for subsequent heart failure (Hunter and Chien, 1999, New England J. of Medicine, 99, 313-322). Coronary heart disease is a predominant factor in the development ofthe cardiac disease state, along with prior AMI, hypertension, diabetes mellitus, and valvular heart disease. Diagnosis of cardiac disease includes determination of coronary heart disease associated left ventricular systolic dysfunction (LVSD) and/or left ventricular diastolic dysfunction (LVDD) by echocaardiographic imaging (Cleland, 1997, Dis Management Health Outcomes, 1, 169). Promising diagnosis may also rely on assaying atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations. ANP and BNP levels are indicative ofthe level of ventricular dysfunction (Davidson et al, 1996, Am. J. Cardiol., 77, 828). Current treatment strategies for cardiac disease associated failure are varied.

Diuretics are often used to reduce pulmonary edema and dyspnea in patients with fluid overload, and are usually used in conjunction with angiotensin converting enzyme (ACE) inhibitors for vasodilation. Digoxin is another popular choice for treating cardiac disease as an ionofropic agent, however, doubts remain concerning the long-term efficacy and safety of Digoxin (Harnish, 1999, Drug & Market Development, 10, 114- 119). Carvedilol, a beta-blocker, has been introduced to complement the above treatments in order to slow down the progression of cardiac disease. Antiarrhythmic agents can be used in order to reduce the risk of sudden death in patients suffering from cardiac disease. Lastly, heart transplants have been effective in the treatment of patients with advanced stages of cardiac disease, however, the limited supply of donor hearts greatly limits the scope of this treatment to the broad population (Hamish, 1999, Drug & Market Development, 10, 114- 119).

Whereby the above treatment strategies can all improve morbidity and mortality associated with cardiac disease, the only existing definitive approach to curing the diseased heart is replacement by transplant. Even a healthy, fransplanted heart can become diseased in response to the various stresses of mechanical, hemodynamic, hormonal, and pathological stimuli associated with extrinsic risk factors. As such there exists the need for therapeutics effective in reversing the physiological changes associated with cardiac disease. Myocardial hypertrophy and apoptosis are the underlying degenerative process associated with cardiac hypertrophy and failure. A variety of signaling pathways are involved in the progression of myocardial hypertrophy and myocardial apoptosis. Genetic studies have been instrumental in elucidating these pathways and their involvement in cardiac disease through in vitro assays of cardiac muscle cells and in vivo studies of genetically engineered animals.

Studies in which the expression of specific genes have been altered in cardiac myocytes have shown that specific peptide hormones, growth factors, and cytokines can activate various features ofthe hyperfrophic response (Hunter and Chien, 1999, New England J of Medicine, 99, 313-322). Particular substances that have been characterized from these studies include potential therapeutic and molecular targets involved in heart failure. Hunter et al, in Chien, KR, ed. Molecular basis of heart disease: a companion to Braunwald 's Heart Disease, Philadelphia: W.B. Saunders, 1999:211 -250, describe classes of therapeutic and molecular targets involved in heart failure including:

1. Endothelin 1 and angiotensin π receptor antagonists, and antagonists of ras, p38, and c-jun Ν-terminal kinase (JΝK) for inhibition of pathologic hypertrophy.

2. Insulin like growth factor I and growth hormone receptor stimulation for promotion of physiologic hypertrophy.

3. beta- 1 -adrenergic receptor blockers for inhibition of neurohumoral over stimulation.

4. Phospholamban and Sarcolipin small molecule inhibitors for relief of sarcoplasmic reticulum calcium ATPase inhibition to provide enhancement of myocardial contractile and relaxation responses. 5. Small molecule inhibitors of β-adrenergic receptor kinase to counteract the desensitization of G protein coupled receptor kinases in order to provide enhancement of myocardial contractile and relaxation responses. 6. Enhancement of angiogenic growth factors (VEGF, FGF-5) for relief of energy deprivation in cardiac tissues. 7. Promoters of myocyte survival including gp 130 ligands (cardiofrophin 1), and

Νeuregulin for the inhibition of apoptosis of myocytes.

8. Inhibitors of apoptosis such as Caspase inhibitors for the inhibition of apoptosis of myocytes.

9. Inhibitors of cytokines such as TΝF-alpha for the inhibition of apoptosis of myocytes. Congestive heart failure, heart failure, dilated cardiomyopathy and pressure overload hypertrophy are nonlimiting examples of disorders and disease states that can be associated with the above classes of molecular targets. The failure of cardiac contractile performance leading to cardiac disorders and disease, governed by impairment of cardiac excitation/contraction coupling, points to the importance ofthe signaling pathways involved in this process. The release and uptake of cytosolic Ca²⁺ by the sarcoplasmic reticulum plays an integral role in each cycle of cardiac confraction and excitation (Minamisawa et al, 1999, Cell, 99, 313-322). The process of Ca²⁺ reuptake is mediated by the cardiac sarcoplasmic reticulum Ca²⁺ ATPase (SERCA2a). SERCA2a activity is regulated by phospholamban, a p52 muscle specific sarcoplasmic reticulum phosphoprotein (Koss et al, 1996, Circ. Res., 79, 1059-1063, and Simmerman et al, 1998, Physiol. Rev., 78, 921-947). In its active, unphosphorylated state, phospholamban is a potent inhibitor of SERCA2a activity. Phosphorylation of phospholamban at serine 16 by cyclic AMP-dependent protein kinase (PKA) or calmodulin kinase, results in the inhibition of phospholamban interaction with SERCA2a. This phosphorylation event is predominantly responsible for the proportional increase in the rate of Ca²⁺ uptake into the sarcoplasmic reticulum and resultant ventricular relaxation (Tada et al, 1982, Mol. Cell Biochem., 46, 73-95, and Luo et al, 1998, J. Biol. Chem., 273, 4734-4739).

Since a proportional decrease in Ca²⁺ uptake is a hallmark feature of heart failure (Sordahl et al, 1973, Am. J. Physiol, 224, 497-502) and since an increase in the relative ratio of phospholamban to SERCA2a is an important determinant of sarcoplasmic reticulum dysfunction in heart failure (Hasenfuss, 1998, Cardiovasc. Res., 37, 279-289), the targeting of phospholamban and related regulatory factors as therapeutic targets for heart disorders should prove valuable for cardiac indications.

Pystynen et al, International PCT publication No. WO 99/00132, describe bisethers of 1-oxa, aza and thianaphthalen-2-ones as small molecule inhibitors of phospholamban for increasing coronary flow via direct dilation ofthe coronary arteries.

Pystynen et al, International PCT publication No. WO 99/15523, describe bisethers of 1-oxa, aza and thianaphthalen-2-ones as small molecule inhibitors of phospholamban that are useful for treating heart failure.

The efficacy ofthe above mentioned treatment strategies is limited. Small molecule inhibition of a molecular target is often limited by toxicity, which can restrict dosing and overall efficacy. He et al, 1999, Circulation, 100, 974-980, describe endogenous expression of mutant phospholamban and phospholamban antisense RNA to investigate the corresponding effect on SERC A2a activity and cardiac myocyte contractility.

A more attractive approach to the treatment of heart disease would involve the use of ribozymes and/or antisense constructs to modulate the expression of target molecules involved in heart failure. The use of nucleic acid molecules ofthe instant invention permits highly specific regulation ofthe molecular targets of interest, including phospholamban (PLN) (GenBank accession No. NM_002667), sarcolipin (SLN) (GenBank accession No. NM_003063), angiotensin II receptor (GenBank accession No. U20860), endothelin 1 receptor (GenBank accession No. NM 001957), K-ras (GenBank accession No. NM 004985), p38 (GenBank accession No. AF092535), c-jun N-terminal kinase (GenBank accession No. NM_002750, L31951, NM_002753), growth hormone receptor (GenBank accession No. NM_000163), insulin- like growth factor I receptor (GenBank accession No. NM_000875), beta- 1 -adrenergic receptor (GenBank accession No. NM_000024), βl-adrenergic receptor kinase (GenBank accession No. NM_001619, NM_005160), VEGF receptor (GenBank accession No. U43368, M27281 X15997), fibroblast growth factor 5 (GenBank accession No. NM_004464), cardiofrophin I (GenBank accession No. NM_001330), neuregulin (GenBank accession No. AF009227), TNF-alpha (GenBank accession No. X02910 X02159), PI3 kinase (GenBank accession No. NM_006218, NM_006219, U86453, NM_002649, M61906), and AKT kinase (GenBank accession No. NM_005163, M77198).

Various methods have been developed to assay phospholamban activity in vitro and in vivo. Holt et al, 1999, J. Mol. Cell. Cardiol, 31, 645-656, describe a cell culture model in which thyroid hormone control of confraction and the Ca²⁺-ATPase/phospholamban complex is studied in adult rat ventricular myocytes. Slack et al. 1997, J. Biol. Chem., 272, 18862-18868, describe studies in which the ectopic expression of phospholamban in mouse fast-twitch skeletal muscle cells alters sarcoplasmic reticulum Ca²⁺ transport and muscle relaxation. MacLennan et al, 1996, Soc. Gen. Physiol. Ser., 51, 89-103, in a review of regulatory interactions between calcium ATPases and phospholamban describe phospholamban/ Ca²⁺- ATPase interactions in protein expressed in heterologous cell culture experiments. Comwell et al, 1991, Mol. Pharmacol, 40,923-931, describe the regulation of sarcoplasmic reticulum protein phosphorylation by localized cyclic GMP- dependent protein kinase in vascular smooth muscle cells.

Minamisawa et al, 1999, Cell, 99, 313-322, describe a phospholamban knockout mouse model which affords protection from induced dilated cardiomyopathy. Dillmann et al, 1999, Am. J. Cardiol, 83, 89H-91H, describe a fransgenic rat model for the study of altered expression of calcium regulatory proteins, including phospholamban, and their effect on myocyte contractile response. LekanneDeprez et al, 1998, J. Mol. Cell. Cardiol, 30, 1877-1888, describe a rat pressure-overload model to investigate alterations in gene expression of phospholamban, atrial natriuretic peptide (ANP), sarcoplasmic endoplasmic reticular calcium ATPase 2 (SERCA2), collagen LLIαl, and calsequestrin (CSQ). Jones et al, 1998, J. Clin. Invest., 101, 1385-1393, describe a mouse model for investigating the regulation of calcium signaling in transgenic mouse cardiac myocytes overexpressing calsequestrin. In this study, the upregulation and downregulation of calcium uptake and release proteins were determined, including phospholamban. Lorenz et al, 1997, Am J. Physiol, 273, 6, describe a mouse model for the study of regulatory effects of phospholamban on cardiac function in intact mice. This study makes use of animal models with altered levels of phospholamban to permit in vivo evaluation ofthe physiological role of phospholamban. Arai et al, 1996, Saishin Igaku, 51, 1095-1104, presents a review article of gene targeted animal models expressing cardiovascular abnormalities. The study of phospholamban and other protein expression modification effects in mice is presented. Wankerl et al, 1995, J. Mol. Med., 73, 487-496, presents a review article describing the study of calcium transport proteins in the nonfailing and failing heart. Animal models investigating the major calcium handling myocardial proteins, including phospholamban, are described. These models, as well as others, may be used to evaluate the effect of treatment with nucleic acid molecules ofthe instant invention on cardiac function. Endpoints may be, but are not limited to, left ventricular pressure, left ventricular pressure as a function of time (LVdP/dt), and mean arterial blood pressure. Endpoints will be evaluated under basal and stimulated (cardiac load) conditions. Particular degenerative and disease states that can be associated with phospholamban expression modulation include but are not limited to congestive heart failure, heart failure, dilated cardiomyopathy and pressure overload hypertrophy: Digoxin, Bendrofluazide, Dofetilide, and Carvedilol are non-limiting examples of pharmaceutical agents that can be combined with or used in conjunction with the nucleic acid molecules (e.g. ribozymes and antisense molecules) ofthe instant invention. Those skilled in the art will recognize that other drugs such as diuretic and antihypertensive compounds and therapies can be similarly be readily combined with the nucleic acid molecules ofthe instant invention (e.g. ribozymes and antisense molecules) are hence within the scope ofthe instant invention.

Identification of Potential Target Sites in Human phospholamban RNA The sequence of human phospholamban was screened for accessible sites using a computer folding algorithm. Regions ofthe RNA that did not form secondary folding structures and contained potential ribozyme and/or antisense binding/cleavage sites were identified. The sequences of these cleavage sites are shown in Tables 24-30.

Selection of Enzymatic Nucleic Acid Cleavage Sites in Human phospholamban RNA Ribozyme target sites were chosen by analyzing sequences of Human phospholamban (Genbank sequence accession number: NM 002667) and prioritizing the sites on the basis of folding. Ribozymes were designed that could bind each target and were individually analyzed by computer folding (Christoffersen et al, 1994 J. Mol. Struc. Theochem, 311, 273; Jaeger et al, 1989, Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether the ribozyme sequences fold into the appropriate secondary structure. Those ribozymes with unfavorable intramolecular interactions between the binding arms and the catalytic core were eliminated from consideration. As noted below, varying binding arm lengths can be chosen to optimize activity. Generally, at least 5 bases on each arm are able to bind to, or otherwise interact with, the target RNA.

Chemical Synthesis and Purification of Ribozymes and Antisense for Efficient Cleavage and/or blocking of phospholamban RNA

Ribozymes and antisense constructs were designed to anneal to various sites in the RNA message. The binding arms ofthe ribozymes are complementary to the target site sequences described above, while the antisense constructs are fully complimentary to the target site sequences described above. The ribozymes and antisense constructs were chemically synthesized. The method of synthesis used followed the procedure for normal RNA synthesis as described above and in Usman et al., (1987 J. Am. Chem. Soc, 109, 7845), Scaringe et al., (1990 Nucleic Acids Res., 18, 5433) and Wincott et al., supra, and made use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5 '-end, and phosphoramidites at the 3 '-end. The average stepwise coupling yields were >98%.

Ribozymes and antisense constructs were also synthesized from DNA templates using bacteriophage T7 RNA polymerase (Milligan and Uhlenbeck, 1989, Methods Enzymol. 180, 51). Ribozymes and antisense constructs were purified by gel elecfrophoresis using general methods or were purified by high pressure liquid chromatography (HPLC; see Wincott et al., supra; the totality of which is hereby incoφorated herein by reference) and were resuspended in water. The sequences ofthe chemically synthesized ribozymes and antisense constructs used in this study are shown below in Table 24-30.

Ribozyme Cleavage of phospholamban RNA Target in vitro

Ribozymes targeted to the human phospholamban RNA are designed and synthesized as described above. These ribozymes can be tested for cleavage activity in vitro, for example using the following procedure. The target sequences and the nucleotide location within the phospholamban RNA are given in Tables 24-30.

Cleavage Reactions: Full-length or partially full-length, internally-labeled target RNA for ribozyme cleavage assay is prepared by in vitro transcription in the presence of [a-³²p] CTP, passed over a G 50 Sephadex column by spin chromatography and used as substrate RNA without further purification. Alternately, substrates are 5'-32p_end labeled using T4 polynucleotide kinase enzyme. Assays are performed by pre-warming a 2X concenfration of purified ribozyme in ribozyme cleavage buffer (50 mM Tris-HCI, pH 7.5 at 37°C, 10 mM MgC ) and the cleavage reaction was initiated by adding the 2X ribozyme mix to an equal volume of substrate RNA (maximum of 1-5 nM) that was also pre-warmed in cleavage buffer. As an initial screen, assays are carried out for 1 hour at

O 37 C using a final concenfration of either 40 nM or 1 mM ribozyme, i.e., ribozyme excess. The reaction is quenched by the addition of an equal volume of 95% formamide, 20 mM EDTA, 0.05%o bromophenol blue and 0.05% xylene cyanol after which the sample is o heated to 95 C for 2 minutes, quick chilled and loaded onto a denaturing polyacrylamide gel. Subsfrate RNA and the specific RNA cleavage products generated by ribozyme cleavage are visualized on an autoradiograph ofthe gel. The percentage of cleavage is determined by Phosphor Imager® quantitation of bands representing the intact substrate and the cleavage products.

Tissue distribution of BrdU-labeled antisense in mice

CD1 mice were injected with a single bolus (30 mg/kg) of a BrdU-labeled antisense oligonucleotide or a similar molar amount of BrdU (as a control). At various time points (30 min, 2h and 6 h), mice were sacrificed and major tissues isolated and fixed. Distribution of antisense oligonucleotides was determined by probing with an anti-BrdU antibody and immunohistochemical staining. Tissue slices were probed with an anti-BrdU antibody followed by a reporter enzyme-conjugated second antibody and finally an enzyme subsfrate. Visualization ofthe colored product by microscopy indicated nuclear staining, demonstrating effective distribution of antisense oligonucleotide in cardiac tissue.

Tissue distribution of BrdU-labeled ribozymes in monkey

Rhesus monkeys were dosed with BrdU-labeled ribozyme by intravenous bolus injection at 0.1 , 1.0, and 10 mg/kg once daily over five days. Saline injection was used in control animals. Animals were sacrificed and major tissues isolated and fixed. Tissue samples were probed with an anti-BrdU antibody followed by a reporter enzyme- conjugated second antibody and finally an enzyme subsfrate. Significant quantities of chemically modified ribozyme are detected in cardiac tissue following this dosing regimen.

Example 6: HBV

Chronic hepatitis B is caused by an enveloped virus, commonly known as the hepatitis B virus or HBV. HBV is transmitted via infected blood or other body fluids, especially saliva and semen, during delivery, sexual activity, or sharing of needles contaminated by infected blood. Individuals may be "carriers" and transmit the infection to others without ever having experienced symptoms ofthe disease. Persons at highest risk are those with multiple sex partners, those with a history of sexually transmitted diseases, parenteral drug users, infants bom to infected mothers, "close" contacts or sexual partners of infected persons, and healthcare personnel or other service employees who have contact with blood. Transmission is also possible via tattooing, ear or body piercing,

5 and acupuncture; the virus is also stable on razors, toothbrushes, baby bottles, eating utensils, and some hospital equipment such as respirators, scopes and instruments. There is no evidence that HBsAg positive food handlers pose a health risk in an occupational setting, nor should they be excluded from work. Hepatitis B has never been documented as being a food-borne disease. The average incubation period is 60 to 90 days, with a

! 0 range of 45 to 180; the number of days appears to be related to the amount of virus to which the person was exposed. However, determining the length of incubation is difficult, since onset of symptoms is insidious. Approximately 50% of patients develop symptoms of acute hepatitis that last from 1 to 4 weeks. Two percent or less of these individuals develop fulminant hepatitis resulting in liver failure and death.

5 The determinants of severity include: (1) The size ofthe dose to which the person was exposed; (2) the person's age with younger patients experiencing a milder form ofthe disease; (3) the status ofthe immune system with those who are immunosuppressed experiencing milder cases; and (4) the presence or absence of co-infection with the Delta virus (hepatitis D), with more severe cases resulting from co-infection. In symptomatic

!0 cases, clinical signs include loss of appetite, nausea, vomiting, abdominal pain in the right upper quadrant, arthralgia, and tiredness/loss of energy. Jaundice is not experienced in all cases, however, jaundice is more likely to occur if the infection is due to transfusion or percutaneous serum transfer, and it is accompanied by mild pruritus in some patients. Bilirubin elevations are demonsfrated in dark urine and clay-colored stools, and liver

15 enlargement may occur accompanied by right upper-quadrant pain. The acute phase ofthe disease may be accompanied by severe depression, meningitis, Guillain-Barre syndrome, myelitis, encephalitis, agranulocytosis, and/or thrombocytopenia.

Hepatitis B is generally self-limiting and will resolve in approximately 6 months. Asymptomatic cases can be detected by serologic testing, since the presence ofthe virus

>0 leads to production of large amounts of HBsAg in the blood. This antigen is the first and most useful diagnostic marker for active infections. However, if HBsAg remains positive for 20 weeks or longer, the person is likely to remain positive indefinitely and is now a carrier. While only 10% of persons over age 6 who contract HBV become carriers, 90% of infants infected during the first year of life do so.

Hepatitis B virus (HBV) infects over 300 million people worldwide (Imperial, 1999, Gastroenterol. Hepatol, 14 (suppl), Sl-5). In the United States approximately 1.25 million individuals are chronic carriers of HBV as evidenced by the fact that they have measurable hepatitis B virus surface antigen HBsAg in their blood. The risk of becoming a chronic HBsAg carrier is dependent upon the mode of acquisition of infection as well as the age ofthe individual at the time of infection. For those individuals with high levels of viral replication, chronic active hepatitis with progression to cirrhosis, liver failure and hepatocellular carcinoma (HCC) is common, and liver transplantation is the only treatment option for patients with end-stage liver disease from HBV.

The natural progression of chronic HBV infection over a 10 to 20 year period leads to cirrhosis in 20-to-50% of patients and progression of HBV infection to hepatocellular carcinoma has been well documented. There have been no studies that have determined sub-populations that are most likely to progress to cirrhosis and/or hepatocellular carcinoma, thus all patients have equal risk of progression.

It is important to note that the survival for patients diagnosed with hepatocellular carcinoma is only 0.9 to 12.8 months from initial diagnosis (Takahashi et al, 1993, American Journal of Gastroenterology, 88, 240-243). Treatment of hepatocellular carcinoma with chemotherapeutic agents has not proven effective and only 10% of patients will benefit from surgery due to extensive tumor invasion ofthe liver (Trinchet et al, 1994, Presse Medicine, 23, 831-833). Given the aggressive nature of primary hepatocellular carcinoma, the only viable treatment alternative to surgery is liver transplantation (Pichlmayr et al, 1994, Hepatology., 20, 33S-40S). Upon progression to cirrhosis, patients with chronic HCV infection present with clinical features, which are common to clinical cirrhosis regardless ofthe initial cause (D'Amico et al, 1986, Digestive Diseases and Sciences, 31, 468-475). These clinical features may include: bleeding esophageal varices, ascites, jaundice, and encephalopathy (Zakim D, Boyer TD. Hepatology a textbook of liver disease, Second Edition Volume 1. 1990 W.B. Saunders Company. Philadelphia). In the early stages of cirrhosis, patients are classified as compensated, meaning that although liver tissue damage has occurred, the patient's liver is still able to detoxify metabolites in the blood-stream. In addition, most patients with compensated liver disease are asymptomatic and the minority with symptoms report only minor symptoms such as dyspepsia and weakness. Ln the later stages of cirrhosis, patients are classified as decompensated meaning that their ability to detoxify metabolites in the bloodstream is diminished and it is at this stage that the clinical features

5 described above will present.

In 1986, D'Amico et al. described the clinical manifestations and survival rates in 1155 patients with both alcoholic and viral associated cirrhosis (D'Amico supra). Ofthe 1155 patients, 435 (37%) had compensated disease although 70% were asymptomatic at the beginning ofthe study. The remaining 720 patients (63%) had decompensated liver

10 disease with 78% presenting with a history of ascites, 31 % with jaundice, 17% had bleeding and 16% had encephalopathy. Hepatocellular carcinoma was observed in six (0.5%)) patients with compensated disease and in 30 (2.6%) patients with decompensated disease.

Over the course of six years, the patients with compensated cirrhosis developed

5 clinical features of decompensated disease at a rate of 10% per year. In most cases, ascites was the first presentation of decompensation. In addition, hepatocellular carcinoma developed in 59 patients who initially presented with compensated disease by the end of the six-year study.

With respect to survival, the D'Amico study indicated that the five-year survival rate

!0 for all patients on the study was only 40%. The six-year survival rate for the patients who initially had compensated cirrhosis was 54% while the six-year survival rate for patients who initially presented with decompensated disease was only 21%. There were no significant differences in the survival rates between the patients who had alcoholic cirrhosis and the patients with viral related cirrhosis. The major causes of death for the

!5 patients in the D'Amico study were liver failure in 49%; hepatocellular carcinoma in 22%; and, bleeding in 13% (D'Amico supra).

Hepatitis B virus is a double-stranded circular DNA virus. It is a member ofthe Hepadnaviridae family. The virus consists of a central core that contains a core antigen (HBcAg) surrounded by an envelope containing a surface protein surface antigen (HBsAg)

»0 and is 42 nm in diameter. It also contains an e antigen (HBeAg) which, along with HBcAg and HBsAg, is helpful in identifying this disease In HBV virions, the genome is found in an incomplete double-stranded form. HBV uses a reverse transcriptase to transcribe a positive-sense full length RNA version of its genome back into DNA. This reverse transcriptase also contains DNA polymerase activity and thus begins replicating the newly synthesized minus-sense DNA strand. However, it appears that the core protein encapsidates the reverse-transcriptase/polymerase before it completes replication.

From the free-floating form, the virus must first attach itself specifically to a host cell membrane. Viral attachment is one ofthe crucial steps which determines host and tissue specificity. However, currently there are no in vitro cell-lines that can be infected by HBV. There are some cells lines, such as HepG2, which can support viral replication only upon transient or stable transfection using HBV DNA.

After attachment, fusion ofthe viral envelope and host membrane must occur to allow the viral core proteins containing the genome and polymerase to enter the cell. Once inside, the genome is translocated to the nucleus where it is repaired and cyclized. The complete closed circular DNA genome of HBV remains in the nucleus and gives rise to four transcripts. These transcripts initiate at unique sites but share the same 3'-ends. The 3.5-kb pregenomic RNA serves as a template for reverse transcription and also encodes the nucleocapsid protein and polymerase. A subclass of this transcript with a 5 '-end extension codes for the precore protein that, after processing, is secreted as HBV e antigen. The 2.4-kb RNA encompasses the pre-Sl open reading frame (ORF) that encodes the large surface protein. The 2.1-kb RNA encompasses the pre-S2 and S ORFs that encode the middle and small surface proteins, respectively. The smallest transcript (~0.8- kb) codes for the X protein, a transcriptional activator.

Multiplication ofthe HBV genome begins within the nucleus of an infected cell. RNA polymerase LI transcribes the circular HBV DNA into greater-than-full length mRNA. Since the mRNA is longer than the actual complete circular DNA, redundant ends are formed. Once produced, the pregenomic RNA exits the nucleus and enters the cytoplasm.

The packaging of pregenomic RNA into core particles is triggered by the binding of the HBV polymerase to the 5' epsilon stem-loop. RNA encapsidation is believed to occur as soon as binding occurs. The HBV polymerase also appears to require associated core protein in order to function. The HBV polymerase initiates reverse transcription from the 5' epsilon stem-loop three to four base pairs at which point the polymerase and attached nascent DNA are transferred to the 3' copy ofthe DR1 region. Once there, the (-)DNA is extended by the HBV polymerase while the RNA template is degraded by the HBV polymerase RNAse H activity. When the HBV polymerase reaches the 5' end, a small stretch of RNA is left undigested by the RNAse H activity. This segment of RNA is comprised of a small sequence just upstream and including the DR1 region. The RNA oligomer is then translocated and annealed to the DR2 region at the 5' end ofthe (-)DNA. It is used as a primer for the (+)DNA synthesis which is also generated by the HBV polymerase. It appears that the reverse transcription as well as plus strand synthesis may occur in the completed core particle.

Since the pregenomic RNA is required as a template for DNA synthesis, this RNA is an excellent target for ribozyme cleavage. Nucleoside analogues that have been documented to inhibit HBV replication target the reverse transcriptase activity needed to convert the pregenomic RNA into DNA. Ribozyme cleavage ofthe pregenomic RNA template would be expected to result in a similar inhibition of HBV replication. Further, targeting the 3 '-end ofthe pregenomic RNA that is common to all HBV transcripts could result in reduction of all HBV gene products and an additional level of inhibition of HBV replication.

As previously mentioned, HBV does not infect cells in culture. However, fransfection of HBV DNA (either as a head-to-tail dimer or as an "overlength" genome of >100%) into HuH7 or Hep G2 hepatocytes results in viral gene expression and production of HBV virions released into the media. Thus, HBV replication competent DNA would be co-fransfected with ribozymes in cell culture. Such an approach has been used to report infracellular ribozyme activity against HBV (zu Putlitz, et al, 1999, J. Virol, 73, 5381- 5387, and Kim et al, 1999, Biochem. Biophys. Res. Commun., 257, 759-765). In addition, stable hepatocyte cell lines have been generated that express HBV. In these cells only ribozyme would need to be delivered; however, a delivery screen would need to be performed. In addition, stable hepatocyte cell lines have been generated that express HBV. Infracellular HBV gene expression can be assayed by a Taqman® assay for HBV RNA or by ELISA for HBV protein. Exfracellular virus can be assayed by PCR for DNA or ELISA for protein. Antibodies are commercially available for HBV surface antigen and core protein. A secreted alkaline phosphatase expression plasmid can be used to normalize for differences in transfection efficiency and sample recovery.

There are several small animal models to study HBV replication. One is the fransplantation of HBV-infected liver tissue into irradiated mice. Viremia (as evidenced

5 by measuring HBV DNA by PCR) is first detected 8 days after fransplantation and peaks between 18 - 25 days (Ilan et al, 1999, Hepatology, 29, 553-562).

Transgenic mice that express HBV have also been used as a model to evaluate potential anti-virals. HBV DNA is detectable in both liver and serum (Morrey et al, 1999, Antiviral Res., 42, 97-108).

10 An additional model is to establish subcutaneous tumors in nude mice with Hep G2 cells transfected with HBV. Tumors develop in about 2 weeks after inoculation and express HBV surface and core antigens. HBV DNA and surface antigen is also detected in the circulation of tumor-bearing mice (Yao et al, 1996, J. Viral Hepat., 3, 19-22).

Woodchuck hepatitis virus (WHV) is closely related to HBV in its virus structure,

15 genetic organization, and mechanism of replication. As with HBV in humans, persistent WHV infection is common in natural woodchuck populations and is associated with chronic hepatitis and hepatocellular carcinoma (HCC). Experimental studies have established that WHV causes HCC in woodchucks and woodchucks chronically infected with WHV have been used as a model to test a number of anti-viral agents. For example,

!0 the nucleoside analogue 3T3 was observed to cause dose dependent reduction in virus (50% reduction after two daily treatments at the highest dose) (Hurwitz et al, 1998. Antimicrob. Agents Chemother., 42, 2804-2809).

Current therapeutic goals of treatment are three-fold: to eliminate infectivity and transmission of HBV to others, to arrest the progression of liver disease and improve the

!5 clinical prognosis, and to prevent the development of hepatocellular carcinoma (HCC). Interferon alpha use is the most common therapy for HBV; however, recently Lamivudine (3TC) has been approved by the FDA. Interferon alpha (IFN-alpha) is one treatment for chronic hepatitis B. The standard duration of IFN-alpha therapy is 16 weeks, however, the optimal treatment length is still poorly defined. A complete response (HBV

>0 DNA negative HBeAg negative) occurs in approximately 25% of patients. Several factors have been identified that predict a favorable response to therapy including: High ALT , low HBV DNA , being female, and heterosexual orientation. There is also a risk of reactivation ofthe hepatitis B virus even after a successful response, this occurs in around 5% of responders and normally occurs within 1 year.

Side effects resulting from treatment with type 1 interferons can be divided into four general categories including: Influenza-like symptoms, neuropsychiatric, laboratory abnormalities, and other miscellaneous side effects. Examples of influenza-like symptoms include, fatigue, fever; myalgia, malaise, appetite loss, tachycardia, rigors, headache and arthralgias. The influenza-like symptoms are usually short-lived and tend to abate after the first four weeks of dosing (Dusheiko et al, 1994, Journal of Viral Hepatitis, 1, 3-5). Neuropsychiatric side effects include irritability, apathy, mood changes, insomnia, cognitive changes, and depression. Laboratory abnormalities include the reduction of myeloid cells, including granulocytes, platelets and to a lesser extent, red blood cells. These changes in blood cell counts rarely lead to any significant clinical sequellae. In addition, increases in triglyceride concentrations and elevations in serum alaine and aspartate aminotransferase concentration have been observed. Finally, thyroid abnormalities have been reported. These thyroid abnormalities are usually reversible after cessation of interferon therapy and can be controlled with appropriate medication while on therapy. Miscellaneous side effects include nausea, diarrhea, abdominal and back pain, pruritus, alopecia, and rhinorrhea. In general, most side effects will abate after 4 to 8 weeks of therapy (Dushieko et al, supra ). Lamivudine (3TC) is a nucleoside analogue, which is a very potent and specific inhibitor of HBV DNA synthesis. Lamivudine has recently been approved for the treatment of chronic Hepatitis B. Unlike treatment with interferon, treatment with 3TC does not eliminate the HBV from the patient. Rather, viral replication is controlled and chronic administration results in improvements in liver histology in over 50%> of patients. Phase m studies with 3TC, showed that treatment for one year was associated with reduced liver inflammation and a delay in scarring ofthe liver. In addition, patients treated with Lamivudine (lOOmg per day) had a 98 percent reduction in hepatitis B DNA and a significantly higher rate of seroconversion, suggesting disease improvements after completion of therapy. However, stopping of therapy resulted in a reactivation of HBV replication in most patients. In addition recent reports have documented 3TC resistance in approximately 30% of patients. Particular degenerative and disease states that can be associated with HBV expression modulation include but are not limited to, HBV infection, hepatitis, cancer, tumorigenesis, cirrhosis, liver failure and others.

Lamivudine (3TC), L-FMAU, adefovir dipivoxil, type 1 Interferon, therapeutic 5 vaccines, steriods, and 2 '-5' Oligoadenylates are non- limiting examples of pharmaceutical agents that can be combined with or used in conjunction with the nucleic acid molecules (e.g. ribozymes and antisense molecules) ofthe instant invention. Those skilled in the art will recognize that other drugs such as diuretic and antihypertensive compounds or other therapies can similarly and readily be combined with the nucleic acid molecules ofthe

10 instant invention (e.g. ribozymes and antisense molecules) and are, therefore, within the scope ofthe instant invention.

Current therapies for treating HBV infection, including interferon and nucleoside analogues, are only partially effective. In addition, drug resistance to nucleoside analogues is now emerging, making freatment of chronic Hepatitis B more difficult. Thus, a need

15 exists for effective freatment of this disease which utilizes antiviral inhibitors which work by mechanisms other than those currently utilized in the freatment of both acute and chronic hepatitis B infections.

Draper, US patent No. 6,017,756, describes the use of ribozymes for the inhibition of Hepatitis B Virus.

10 Passman et al, 2000, Biochem. Biophys. Res. Commun., 268(3), 728-733.; Gan et al, 1998, J. Med. Coll. PLA, 13(3), 157-159.; Li et al, 1999, Jiefangjun Yixue Zazhi, 24(2), 99-101.; Puftitz et α/., 1999, J. Virol, 73(7), 5381-5387.; Kim et al, 1999, Biochem. Biophys. Res. Commun., 257(3), 759-765.; Xu et al, 1998, Bingdu Xuebao, 14(4), 365-369.; Welch et al, 1997, Gene Ther., 4(7), 736-743.; Goldenberg et al, 1997,

>5 International PCT publication No. WO 97/08309, Wands et al, 1997, J. of Gastroenterology and Hepatology, 12(suppl.), S354-S369.; Ruiz et al, 1997, BioTechniques, 22(2), 338-345.; Gan et al, 1996, J. Med. Coll. PLA, 11(3), 171-175.; Beck and Nassal, 1995, Nucleic Acids Res., 23(24), 4954-62.; Goldenberg, 1995, International PCT publication No. WO 95/22600.; Xu et al, 1993, Bingdu Xuebao, 9(4),

$0 331-6.; Wang et al, 1993, Bingdu Xuebao, 9(3), 278-80, all describe ribozymes that are targeted to cleave a specific HBV target site. The enzymatic nucleic acid molecules ofthe instant invention exhibit a high degree of specificity for only the viral mRNA in infected cells. Nucleic acid molecules ofthe instant invention targeted to highly conserved sequence regions allow the freatment of many strains of human HBV with a single compound. No freatment presently exists which specifically attacks expression ofthe viral gene(s) that are responsible for transformation of hepatocytes by HBV.

The methods of this invention can be used to treat human hepatitis B virus infections, which include productive virus infection, latent or persistent virus infection, and HBV-induced hepatocyte transformation. The utility can be extended to other species of HBV which infect non-human animals where such infections are of veterinary importance.

Preferred target sites are genes required for viral replication, a non-limiting example includes genes for protein synthesis, such as the 5' most 1500 nucleotides ofthe HBV pregenomic mRNAs. For sequence references, see Renbao et al, 1987, Sci. Sin., 30, 507. This region confrols the franslational expression ofthe core protein (C), X protein (X) and DNA polymerase (P) genes and plays a role in the replication ofthe viral DNA by serving as a template for reverse transcriptase. Disruption of this region in the RNA results in deficient protein synthesis as well as incomplete DNA synthesis (and inhibition of transcription from the defective genomes). Target sequences 5' ofthe encapsidation site can result in the inclusion ofthe disrupted 3' RNA within the core virion structure and targeting sequences 3' ofthe encapsidation site can result in the reduction in protein expression from both the 3' and 5' fragments.

Alternative regions outside ofthe 5' most 1500 nucleotides ofthe pregenomic mRNA also make suitable targets of enzymatic nucleic acid mediated inhibition of HBV replication. Such targets include the mRNA regions that encode the viral S gene.

Selection of particular target regions will depend upon the secondary structure ofthe pregenomic mRNA. Targets in the minor mRNAs can also be used, especially when folding or accessibility assays in these other RNAs reveal additional target sequences that are unavailable in the pregenomic mRNA species. A desirable target in the pregenomic RNA is a proposed bipartite stem-loop structure in the 3 '-end ofthe pregenomic RNA which is believed to be critical for viral replication (Kidd and Kidd-Ljunggren, 1996. Nuc. Acid Res. 24:3295-3302). The 5'end ofthe HBV pregenomic RNA carries a cw-acting encapsidation signal, which has inverted repeat sequences that are thought to form a bipartite stem-loop structure. Due to a terminal redundancy in the pregenomic RNA, the putative stem-loop also occurs at the 3'-end. While it is the 5' copy which functions in polymerase binding and encapsidation, reverse franscription actually begins from the 3' stem-loop. To start reverse transcription, a 4 nt primer which is covalently attached to the polymerase is made, using a bulge in the 5' encapsidation signal as template. This primer is then shifted, by an unknown mechanism, to the DR1 primer binding site in the 3' stem-loop structure, and reverse franscription proceeds from that point. The 3' stem-loop, and especially the DR1 primer binding site, appear to be highly effective targets for ribozyme intervention.

Sequences ofthe pregenomic RNA are shared by the mRNAs for surface, core, polymerase, and X proteins. Due to the overlapping nature ofthe HBV transcripts, all share a common 3'-end. Ribozyme targeting this common 3'-end will thus cleave the pregenomic RNA as well as all ofthe mRNAs for surface, core, polymerase and X proteins.

In preferred embodiments, the invention features a method for the analysis of HBV proteins. This method is useful in determining the efficacy of HBV inhibitors. Specifically, the instant invention features an assay for the analysis of HBsAg proteins and secreted alkaline phosphatase (SEAP) confrol proteins to determine the efficacy of agents used to modulate HBV expression.

The method consists of coating a micro-titer plate with an antibody such as anti- HBsAg Mab (for example, Biostride B88-95-31ad,ay) at 0.1 to 10 μg/ml in a buffer (for example, carbonate buffer, such as Na₂CO₃ 15 mM, NaHCO₃ 35 mM, pH 9.5) at 4°C overnight. The microtiter wells are then washed with PBST or the equivalent thereof, (for example, PBS, 0.05% Tween 20) and blocked for 0.1-24 hr at 37° C with PBST, 1% BSA or the equivalent thereof. Following washing as above, the wells are dried (for example, at 37° C for 30 min). Biotinylated goat anti-HBsAg or an equivalent antibody (for example, Accurate YVS1807) is diluted (for example at 1:1000) in PBST and incubated in the wells (for example, 1 hr. at 37° C). The wells are washed with PBST (for example, 4x). A conjugate, (for example, Streptavidin/ Alkaline Phosphatase Conjugate, Pierce 21324) is diluted to 10-10,000 ng/ml in PBST, and incubated in the wells (for example, 1 hr. at 37° C). After washing as above, a substrate (for example, p-nitrophenyl phosphate substrate, Pierce 37620) is added to the wells, which are then incubated (for example, 1 hr. at 37° C). The optical density is then determined (for example, at 405 nm). SEAP levels are then assayed, for example, using the Great EscAPe® Detection Kit (Clontech K2041-1), as per the manufacturers instructions. In the above example, incubation times and reagent

5 concentrations may be varied to achieve optimum results, a non-limiting example is described in Example 6.

Comparison of this HBsAg ELISA method to a commercially available assay from World Diagnostics, Inc. 15271 NW 60^th Ave, #201, Miami Lakes, FL 33014 (305) 827- 3304 (Cat. No. EL10018) demonstrates an increase in sensitivity (signal :noise) of 3-20

10 fold.

Identification of Potential Target Sites in Human HBV RNA

The sequence of human HBV was screened for accessible sites using a computer- folding algorithm. Regions ofthe RNA that did not form secondary folding structures and ! 5 contained potential ribozyme and/or antisense binding/cleavage sites were identified. The sequences of these cleavage sites are shown in Tables 36-43.

Selection of Enzymatic Nucleic Acid Cleavage Sites in Human HBV RNA

Ribozyme target sites were chosen by analyzing sequences of Human HBV

!0 (accession number: AF 100308.1) and prioritizing the sites on the basis of folding.

Ribozymes were designed that could bind each target and were individually analyzed by computer folding (Christoffersen et al, 1994 J. Mol. Struc. Theochem, 311, 273; Jaeger et al, 1989, Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether the ribozyme sequences fold into the appropriate secondary structure. Those ribozymes with unfavorable

!5 intramolecular interactions between the binding arms and the catalytic core were eliminated from consideration. As noted herein, varying binding arm lengths can be chosen to optimize activity. Generally, at least 5 bases on each arm are able to bind to, or otherwise interact with, the target RNA. Chemical Synthesis and Purification of Ribozymes and Antisense for Efficient Cleavage and/or blocking of HBV RNA

Ribozymes and antisense constructs were designed to anneal to various sites in the RNA message. The binding arms ofthe ribozymes are complementary to the target site sequences described above, while the antisense constructs are fully complementary to the target site sequences described above. The ribozymes and antisense constructs were chemically synthesized. The method of synthesis used followed the procedure for normal RNA synthesis as described above and in Usman et al., (1987 J. Am. Chem. Soc, 109, 7845), Scaringe et al., (1990 Nucleic Acids Res., 18, 5433) and Wincott et al., supra, and made use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5'-end, and phosphoramidites at the 3'-end. The average stepwise coupling yields were typically >98%.

Ribozymes and antisense constructs were also synthesized from DNA templates using bacteriophage T7 RNA polymerase (Milligan and Uhlenbeck, 1989, Methods Enzymol. 180, 51). Ribozymes and antisense constructs were purified by gel electrophoresis using general methods or were purified by high pressure liquid chromatography (HPLC; see Wincott et al., supra; the totality of which is hereby incoφorated herein by reference) and were resuspended in water. The sequences ofthe chemically synthesized ribozymes used in this study are shown below in Table 43.

!0

Ribozyme Cleavage of HBV RNA Target in vitro

Ribozymes targeted to the human HBV RNA are designed and synthesized as described above. These ribozymes can be tested for cleavage activity in vitro, for example using the following procedure. The target sequences and the nucleotide location within the !5 HBV RNA are given in Tables 36-43.

Cleavage Reactions: Full-length or partially full-length, internally-labeled target RNA for ribozyme cleavage assay is prepared by in vitro franscription in the presence of [α-³²p] CTP, passed over a G 50 Sephadex® column by spin chromatography and used as substrate RNA without further purification. Alternately, substrates are 5'-32p-end labeled 0 using T4 polynucleotide kinase enzyme. Assays are performed by pre-warming a 2X concentration of purified ribozyme in ribozyme cleavage buffer (50 mM Tris-HCI, pH 7.5 at 37°C, 10 mM MgCl2) and the cleavage reaction was initiated by adding the 2X ribozyme mix to an equal volume of substrate RNA (maximum of 1-5 nM) that was also pre-warmed in cleavage buffer. As an initial screen, assays are carried out for 1 hour at o

37 C using a final concentration of either 40 nM or 1 mM ribozyme, i.e., ribozyme excess. The reaction is quenched by the addition of an equal volume of 95% formamide, 20 mM EDTA, 0.05% bromophenol blue and 0.05% xylene cyanol after which the sample is o heated to 95 C for 2 minutes, quick chilled and loaded onto a denaturing polyacrylamide gel. Substrate RNA and the specific RNA cleavage products generated by ribozyme cleavage are visualized on an autoradiograph ofthe gel. The percentage of cleavage is determined by Phosphor Imager® quantitation of bands representing the intact substrate and the cleavage products.

Transfection of HepG2 Cells with psHBV-1 and Ribozymes

The human hepatocellular carcinoma cell line Hep G2 was grown in Dulbecco's modified Eagle media supplemented with 10% fetal calf serum, 2 mM glutamine, 0.1 mM nonessential amino acids, 1 mM sodium pyruvate, 25 mM Hepes, 100 units penicillin, and 100 μg/ml streptomycin. To generate a replication competent cDNA, prior to fransfection the HBV genomic sequences are excised from the bacterial plasmid sequence contained in the psHBV-1 vector (Those skilled in the art understand that other methods may be used to generate a replication competent cDNA). This was done with an EcoRI and Hind IU restriction digest. Following completion ofthe digest, a ligation was performed under dilute conditions (20 μg/ml) to favor intermolecular ligation. The total ligation mixture was then concentrated using Qiagen spin columns.

Secreted alkaline phosphatase (SEAP) was used to normalize the HBsAg levels to confrol for transfection variability. The pSEAP2-TK control vector was constructed by ligating a Bgl II-Hind HI fragment ofthe pRL-TK vector (Promega), containing the heφes simplex virus thymidine kinase promoter region, into Bgl HIHind HI digested pSEAP2- Basic (Clontech). Hep G2 cells were plated (3 x IO⁴ cells/well) in 96-well microtiter plates and incubated overnight. A lipid/DNA/ribozyme complex was formed containing (at final concentrations) cationic lipid (15 μg/ml), prepared psHBV-1 (4.5 μg/ml), pSEAP2-TK (0.5 μg/ml), and ribozyme (100 μM). Following a 15 min. incubation at 37° C, the complexes were added to the plated Hep G2 cells. Media was removed from the cells 96 hr. post-fransfection for HBsAg and SEAP analysis.

Transfection ofthe human hepatocellular carcinoma cell line, Hep G2, with replication competent HBV DNA results in the expression of HBV proteins and the production of virions. To investigate the potential use of ribozymes for the freatment of chronic HBV infection, a series of ribozymes that target the 3' terminus ofthe HBV genome have been synthesized. Ribozymes targeting this region have the potential to cleave all four major HBV RNA transcripts as well as the potential to block the production of HBV DNA by cleavage ofthe pregenomic RNA. To test the efficacy of these HBV ribozymes, they were co-transfected with HBV genomic DNA into Hep G2 cells, and the subsequent levels of secreted HBV surface antigen (HBsAg) were analyzed by ELISA. To confrol for variability in fransfection efficiency, a confrol vector which expresses secreted alkaline phosphatase (SEAP), was also co-transfected. The efficacy ofthe HBV ribozymes was determined by comparing the ratio of HBsAg: SEAP and/or HBeAg: SEAP to that of a scrambled attenuated confrol (SAC) ribozyme. Twenty-five ribozymes

(RPI18341, RPI18356, RPI18363, RPI18364, RPI18365, RPI18366, RPI18367, RPI18368, RPI18369, RPI18370, RPI18371, RPI18372, RPI18373, RPI18374, RPI18303, RPI18405, RPI18406, RPI18407, RPI18408, RPI18409, RPI18410, RPI18411, RPI18418, RPI18419, and RPI18422) have been identified which cause a reduction in the levels of HBsAg and/or HBeAg as compared to the corresponding SAC ribozyme.

Example 6: Analysis of HBsAg and SEAP Levels Following Ribozyme Treatment

Immulon 4 (Dynax) microtiter wells were coated overnight at 4° C with anti-HBsAg Mab (Biostride B88-95-31ad,ay) at 1 μg/ml in Carbonate Buffer (Na₂CO₃ 15 mM, NaHCO₃ 35 mM, pH 9.5). The wells were then washed 4x with PBST (PBS, 0.05%

Tween® 20) and blocked for 1 hr at 37° C with PBST, 1% BSA. Following washing as above, the wells were dried at 37° C for 30 min. Biotinylated goat ant-HBsAg (Accurate YVS1807) was diluted 1:1000 in PBST and incubated in the wells for 1 hr. at 37° C. The wells were washed 4x with PBST. Streptavidin Alkaline Phosphatase Conjugate (Pierce 21324) was diluted to 250 ng/ml in PBST, and incubated in the wells for 1 hr. at 37° C. After washing as above, p-nitrophenyl phosphate substrate (Pierce 37620) was added to the wells, which were then incubated for 1 hr. at 37° C. The optical density at 405 nm was then determined. SEAP levels were assayed using the Great EscAPe® Detection Kit (Clontech K2041-1), as per the manufacturers instructions.

Example 7: X-gene Reporter Assay The effect of ribozyme treatment on the level of fransactivation of a SV40 promoter driven firefly luciferase gene by the HBV X-protein was analyzed in transfected Hep G2 cells. As a confrol for variability in transfection efficiency, a Renilla luciferase reporter driven by the TK promoter, which is not transactivated by the X protein, was used. Hep G2 cells were plated (3 x IO⁴ cells/well) in 96-well microtiter plates and incubated overnight. A lipid/DNA ribozyme complex was formed containing (at final concentrations) cationic lipid (2.4 μg/ml), the X-gene vector pSBDR(2.5 μg/ml), the firefly reporter pSV40HCVluc (0.5 μg/ml), the Renilla luciferase control vector pRL-TK (0.5 μg/ml), and ribozyme (100 μM). Following a 15 min. incubation at 37° C, the complexes were added to the plated Hep G2 cells. Levels of firefly and Renilla luciferase were analyzed 48 hr. post transfection, using Promega' s Dual-Luciferase Assay System. The HBV X protein is a transactivator of a number of viral and cellular genes. Ribozymes which target the X region were tested for their ability to cause a reduction in X protein fransactivation of a firefly luciferase gene driven by the S V40 promoter in transfected Hep G2 cells. As a control for fransfection variability, a vector containing the Renilla luciferase gene driven by the TK promotor, which is not activated by the X protein, was included in the co-transfections. The efficacy ofthe HBV ribozymes was determined by comparing the ratio of firefly luciferase: Renilla luciferase to that of a scrambled attenuated confrol (SAC) ribozyme. Eleven ribozymes (RPI18365, RPI18367, RPI18368, RPI18371, RPI18372, RPI18373, RPI18405, RPI18406, RPI18411, RPI18418, RPI18423) were identified which cause a reduction in the level of fransactivation of a reporter gene by the X protein, as compared to the corresponding SAC ribozyme.

Example 8: HBV transgenic mouse study

A fransgenic mouse strain (founder strain 1.3.32 with a C57B1/6 background) that expresses HBV RNA and forms HBV viremia (Morrey et al, 1999, Antiviral Res., 42, 97- 108; Guidotti et al, 1995, J. Virology, 69, 10, 6158-6169) was utilized to study the in vivo activity of ribozymes ofthe instant invention. This model is predictive in screening for anti-HBV agents. Ribozyme or the equivalent volume of saline was administered via a continuous s.c infusion using Alzet® mini-osmotic pumps for 14 days. Alzet® pumps were filled with test material(s) in a sterile fashion according to the manufacturer's instructions. Prior to in vivo implantation, pumps were incubated at 37°C overnight (> 18 hours) to prime the flow modulators. On the day of surgery, animals were lightly anesthetized with a ketamine/xylazine cocktail (94 mg/kg and 6 mg/kg, respectively; 0.3 ml, IP). Baseline blood samples (200 μl) were obtained from each animal via a retro- orbital bleed. A 2 cm area near the base ofthe tail was shaved and cleansed with betadine surgical scrub and sequentially with 70%> alcohol. A 1 cm incision in the skin was made with a #15 scalpel blade or a blunt pair of scissors near the base ofthe tail. Forceps were used to open a pocket rosfrally (i.e., towards the head) by spreading apart the subcutaneous connective tissue. The pump was inserted with the delivery portal pointing away from the incision. Wounds were closed with sterile 9-mm stainless steel clips or with sterile 4-0 suture. Animals were then allowed to recover from anesthesia on a warm heating pad before being returned to their cage. Wounds were checked daily. Clips or sutures were replaced as needed. Incisions typically healed completely within 7 days post-op. Animals were then deeply anesthetized with the ketamine/xylazine cocktail (150 mg/kg and 10 mg/kg, respectively; 0.5 ml, IP) on day 14 post pump implantation. A midline thoracotomy/ laparatomy was performed to expose the abdominal cavity and the thoracic cavity. The left ventricle was cannulated at the base and animals exsanguinated using a 23G needle and 1 ml syringe. Serum was separated, frozen and analyzed for HBV DNA and antigen levels. Experimental groups were compared to the saline confrol group in respect to percent change from day 0 to day 14. HBV DNA was assayed by quantitative PCR

Results

Table 44 is a summary ofthe group designation and dosage levels used in the HBV fransgenic mouse study. Baseline blood samples were obtained via a refroorbital bleed and animals (N=10/group) received anti-HBV ribozymes (100 mg/kg/day) as a continuous SC infusion. After 14 days, animals treated with a ribozyme targeting site 273 (RPI.18341) of the HBV RNA showed a significant reduction in serum HBV DNA concenfration, compared to the saline treated animals as measured by a quantitative PCR assay. More specifically, the saline treated animals had a 69% increase in serum HBV DNA concentrations over this 2-week period while treatment with the 273 ribozyme (RPI.18341) resulted in a 60% decrease in serum HBV DNA concentrations. Ribozymes directed against sites 1833 (RPI.18371), 1873 (RPI.18418), and 1874 (RPI.18372) decreased serum HBV DNA concentrations by 49%, 15% and 16%, respectively.

Example 7: Activity of NCH Ribozyme to inhibit HER2 gene expression HER2 (also known as neu, erbB2 and c-erbB2) is an oncogene that encodes a 185- kDa transmembrane tyrosine kinase receptor. HER2 is a member ofthe epidermal growth factor receptor (EGFR) family and shares partial homology with other family members. In normal adult tissues HER2 expression is low. However, HER2 is overexpressed in at least 25-30% of breast (McGuire & Greene, 1989) and ovarian cancers (Berchuck, et al, 1990). Furthermore, overexpression of HER2 in malignant breast tumors has been correlated with increased metastasis, chemoresistance and poor survival rates (Slamon et al, 1987 Science 235: 177-182). Because HER2 expression is high in aggressive human breast and ovarian cancers, but low in normal adult tissues, it is an attractive target for ribozyme-mediated therapy (Thompson et al, supra). The greatest HER2 specific effects have been observed in cancer cell lines that express high levels of HER2 protein (as measured by ELISA). Specifically, in one study that freated five human breast cancer cell lines with the HER2 antibody (anti-erbB2-sFv), the greatest inhibition of cell growth was seen in three cell lines (MDA-MB-361, SKBR-3 and BT-474) that express high levels of HER2 protein. No inhibition of cell growth was observed in two cell lines (MDA-MB-231 and MCF-7) that express low levels of HER2 protein (Wright et al, 1997). Another group successfully used SKBR-3 cells to show HER2 antisense oligonucleotide-mediated inhibition of HER2 protein expression and HER2 RNA knockdown (Vaughn et al, 1995). Other groups have also demonstrated a decrease in the levels of HER2 protein, HER2 mRNA and/or cell proliferation in cultured cells using anti-HER2 ribozymes or antisense molecules (Suzuki, T. et al, 1997; Weichen, et al, 1997; Czubayko, F. et al, 1997; Colomer, et al, 1994; Befram et al, 1994). Because cell lines that express higher levels of HER2 have been more sensitive to anti- HER2 agents, we are pursuing several medium to high expressing cell lines, including SKBR-3 and T47D, for ribozyme screens in cell culture.

A variety of endpoints have been used in cell culture models to look at HER2- mediated effects after freatment with anti-HER2 agents. Phenotypic endpoints include

5 inhibition of cell proliferation, apoptosis assays and reduction of HER2 protein expression. Because overexpression of HER2 is directly associated with increased proliferation of breast and ovarian tumor cells, a proliferation endpoint for cell culture assays will be our primary screen. There are several methods by which this endpoint can be measured. Following treatment of cells with ribozymes, cells are allowed to grow (typically 5 days)

0 after which either the cell viability, the incoφoration of [³H] thymidine into cellular DNA and/or the cell density can be measured. The assay of cell density is very straightforward and can be done in a 96-well format using commercially available fluorescent nucleic acid stains (such as Syto 13 or CyQuant). The assay using CyQuant is in place at RPI and is currently being employed to screen -100 ribozymes targeting HER2 (details below).

5 As a secondary, confirmatory endpoint a ribozyme-mediated decrease in the level of

HER2 protein expression can be evaluated using a HER2-specific ELISA.

Validation of Cell Lines and Ribozyme Treatment Conditions

Two human breast cancer cell lines (T47D and SKBR-3) that are known to express

!0 medium to high levels of HER2 protein, respectively, were considered for ribozyme screening. In order to validate these cell lines for HER2-mediated sensitivity, both cell lines were freated with the HER2 specific antibody, Herceptin® (Genentech) and its effect on cell proliferation was determined. Herceptin was added to cells at concentrations ranging from 0-8 μM in medium containing either no serum (OptiMem), 0.1% or 0.5%>

!5 FBS and efficacy was determined via cell proliferation. Maximal inhibition of proliferation (-50%) in both cell lines was observed after addition of Herceptin at 0.5 nM in medium containing 0.1 %> or no FBS. The fact that both cell lines are sensitive to an anti-HER2 agent (Herceptin) supports their use in experiments testing anti-HER2 ribozymes.

0 Prior to ribozyme screening, the choice ofthe optimal lipid(s) and conditions for ribozyme delivery was determined empirically for each cell line. Applicant has established a panel of proprietary lipids that can be used to deliver ribozymes to cultured cells and are very useful for cell proliferation assays that are typically 3-5 days in length. Initially, this panel of proprietary lipid delivery vehicles was screened in SKBR-3 and T47D cells using previously established confrol oligonucleotides. Specific lipids and conditions for optimal delivery were selected for each cell line based on these screens. These conditions were used to deliver HER2 specific ribozymes to cells for primary (inhibition of cell proliferation) and secondary (decrease in HER2 protein) efficacy endpoints.

Primary Screen: Inhibition of Cell Proliferation

Although optimal ribozyme delivery conditions were determined for two cell lines, the SKBR-3 cell line were be used for the initial screen because it has the higher level of HER2 protein, and thus should be most susceptible to a HER2-specific ribozyme. Follow- up studies can be carried out in T47D cells to confirm leads as necessary.

Ribozyme screens were be performed using an automated, high throughput 96-well cell proliferation assay. Cell proliferation were measured over a 5-day freatment period using the nucleic acid stain CyQuant for determining cell density. The growth of cells treated with ribozyme/lipid complexes were compared to both untreated cells and to cells treated with Scrambled-arm attenuated core Confrols (SAC; or A; Figure 8). SACs can no longer bind to the target site due to the scrambled arm sequence and have nucleotide changes in the core that greatly diminish ribozyme cleavage. These SACs are used to determine non-specific inhibition of cell growth caused by ribozyme chemistry (i. e. multiple 2' O-Me modified nucleotides, a single 2'C-allyl uridine, 4 phosphorothioates and a 3' inverted abasic). Lead ribozymes are chosen from the primary screen based on their ability to inhibit cell proliferation in a specific manner. Dose response assays are carried out on these leads and a subset was advanced into a secondary screen using the level of HER2 protein as an endpoint.

Secondary Screen: Decrease in HER2 Protein

A secondary screen that measures the effect of anti-HER2 ribozymes on HER2 protein levels is used to support preliminary findings. A robust HER2 ELISA for both T47D and SKBR-3 cells has been established and is available for use as an additional endpoint. Ribozyme Mechanism Assays

A Taqman assay for measuring the ribozyme-mediated decrease in HER2 RNA has also been established. This assay is based on PCR technology and can measure in real time the production of HER2 mRNA relative to a standard cellular mRNA such as GAPDH. This RNA assay is used to establish proof that lead ribozymes are working through an RNA cleavage mechanism and result in a decrease in the level of HER2 mRNA, thus leading to a decrease in cell surface HER2 protein receptors and a subsequent decrease in tumor cell proliferation.

Animal Models

Evaluating the efficacy of anti-HER2 agents in animal models is an important prerequisite to human clinical trials. As in cell culture models, the most HER2 sensitive mouse tumor xenografts are those derived from human breast carcinoma cells that express high levels of HER2 protein. In a recent study, nude mice bearing BT-474 xenografts were sensitive to the anti-HER2 humanized monoclonal antibody Herceptin, resulting in an 80%) inhibition of tumor growth at a 1 mg kg dose (ip, 2 X week for 4-5 weeks). Tumor eradication was observed in 3 of 8 mice freated in this manner (Baselga et al, 1998). This same study compared the efficacy of Herceptin alone or in combination with the commonly used chemotherapeutics, paclitaxel or doxorubicin. Although, all three anti- HER2 agents caused modest inhibition of tumor growth, the greatest antitumor activity was produced by the combination of Herceptin and paclitaxel (93 % inhibition of tumor growth vs 35% with paclitaxel alone). The above studies provide proof that inhibition of HER2 expression by anti-HER2 agents causes inhibition of tumor growth in animals. Lead anti-HER2 ribozymes chosen from in vitro assays are further tested in mouse xenograft models. Ribozymes are first tested alone and then in combination with standard chemotherapies.

Animal Model Development

Three human breast tumor cell lines (T47D, SKBR-3 and BT-474) were characterized to establish their growth curves in mice. These three cell lines have been implanted into the mammary papillae of both nude and SCLD mice and primary tumor volumes are measured 3 times per week. Growth characteristics of these tumor lines using a Matrigel implantation format will also be established. In addition, the use of two other breast cell lines that have been engineered to express high levels of HER2 are also being used. The tumor cell line(s) and implantation method that supports the most consistent and reliable tumor growth is used in animal studies testing the lead HER2 ribozyme(s). Ribozyme are administered by daily subcutaneous injection or by continuous subcutaneous infusion from Alzet mini osmotic pumps beginning 3 days after tumor implantation and continuing for the duration ofthe study. Group sizes of at least 10 animals are employed. Efficacy is determined by statistical comparison of tumor volume of ribozyme-treated animals to a control group of animals freated with saline alone. Because the growth of these tumors is generally slow (45-60 days), an initial endpoint will be the time in days it takes to establish an easily measurable primary tumor (i.e. 50-100 mm³) in the presence or absence of ribozyme treatment.

Clinical Summary Breast cancer is a common cancer in women and also occurs in men to a lesser degree. The incidence of breast cancer in the United States is -180,000 cases per year and -46,000 die each year ofthe disease. In addition, 21,000 new cases of ovarian cancer per year lead to -13,000 deaths (data from Hung et al, 1995 and the Surveillance, Epidemiology and End Results Program, NCI). Ovarian cancer is a potential secondary indication for anti-HER2 ribozyme therapy.

A full review of breast cancer is given in the NCI PDQ for Breast Cancer. A brief overview is given here. Breast cancer is evaluated or "staged" on the basis of tumor size, and whether it has spread to lymph nodes and/or other parts ofthe body. In Stage I breast cancer, the cancer is no larger than 2 centimeters and has not spread outside ofthe breast. In Stage LI, the patient's tumor is 2-5 centimeters but cancer may have spread to the axillary lymph nodes. By Stage LU, metastasis to the lymph nodes is typical, and tumors are 5 centimeters. Additional tissue involvement (skin, chest wall, ribs, muscles etc.) may also be noted. Once cancer has spread to additional organs ofthe body, it is classed as Stage LV. Almost all breast cancers (>90%) are detected at Stage I or LI, but 31% of these are already lymph node positive. The 5-year survival rate for node negative patients (with standard surgery/radiation/chemotherapy /hormone regimens) is 97%; however, involvement ofthe lymph nodes reduces the 5-year survival to only 77%. Involvement of other organs ( Stage HI) drastically reduces the overall survival, to 22% at 5 years. Thus, chance of recovery from breast cancer is highly dependent on early detection. Because up to 10% of breast cancers are hereditary, those with a family history are considered to be at high risk for breast cancer and should be monitored very closely.

Breast cancer is highly treatable and often curable when detected in the early stages. (For a complete review of breast cancer treatments, see the NCI PDQ for Breast Cancer.) Common therapies include surgery, radiation therapy, chemotherapy and hormonal therapy. Depending upon many factors, including the tumor size, lymph node involvement and location ofthe lesion, surgical removal varies from lumpectomy (removal ofthe tumor and some surrounding tissue) to mastectomy (removal ofthe breast, lymph nodes and some or all ofthe underlying chest muscle). Even with successful surgical resection, as many as 21% ofthe patients may ultimately relapse (10-20 years). Thus, once local disease is controlled by surgery, adjuvant radiation treatments, chemotherapies and/or hormonal therapies are typically used to reduce the rate of recurrence and improve survival. The therapy regimen employed depends not only on the stage ofthe cancer at its time of removal, but other variables such the type of cancer (ductal or lobular), whether lymph nodes were involved and removed, age and general health ofthe patient and if other organs are involved. Common chemotherapies include various combinations cytotoxic drugs to kill the cancer cells. These drugs include paclitaxel (Taxol), docetaxel, cisplatin, methotrexate, cyclophosphamide, doxorubin, fluorouracil etc. Significant toxicities are associated with these cytotoxic therapies. Well-characterized toxicities include nausea and vomiting, myelosuppression, alopecia and mucosity. Serious cardiac problems are also associated with certain ofthe combinations, e.g. doxorubin and paclitaxel, but are less common.

Testing for esfrogen and progesterone receptors helps to determine whether certain anti-hormone therapies might be helpful in inhibiting tumor growth. If either or both receptors are present, therapies to interfere with the action ofthe hormone ligands, can be given in combination with chemotherapy and are generally continued for several years. These adjuvant therapies are called SERMs, selective esfrogen receptor modulators, and they can give beneficial estrogen-like effects on bone and lipid metabolism while antagonizing estrogen in reproductive tissues. Tamoxifen is one such compound. The primary toxic effect associated with the use of tamoxifen is a 2 to 7-fold increase in the rate of endometrial cancer. Blood clots in the legs and lung and the possibility of stroke are additional side effects. However, tamoxifen has been determined to reduce breast cancer incidence by 49% in high-risk patients and an extensive, somewhat controversial, clinical study is underway to expand the prophylactic use of tamoxifen. Another SERM, raloxifene, was also shown to reduce the incidence of breast cancer in a large clinical trial where it was being used to freat osteoporosis. In additional studies, removal ofthe ovaries and/or drugs to keep the ovaries from working are being tested.

Bone marrow fransplantation is being studied in clinical trials for breast cancers that have become resistant to traditional chemotherapies or where >3 lymph nodes are involved. Marrow is removed from the patient prior to high-dose chemotherapy to protect it from being destroyed, and then replaced after the chemotherapy. Another type of "fransplant" involves the exogenous freatment of peripheral blood stem cells with drugs to kill cancer cells prior to replacing the freated cells in the bloodstream. One biological freatment, a humanized monoclonal anti-HER2 antibody, Herceptin

(Genentech) has been approved by the FDA as an additional treatment for HER2 positive tumors. Herceptin binds with high affinity to the exfracellular domain of HER2 and thus blocks its signaling action. Herceptin can be used alone or in combination with chemotherapeutics (i.e. paclitaxel, docetaxel, cisplatin, etc.) (Pegram, et al, 1998). In Phase LTJ studies, Herceptin significantly improved the response rate to chemotherapy as well as improving the time to progression (Ross & Fletcher, 1998). The most common side effects attributed to Herceptin are fever and chills, pain, asthenia, nausea, vomiting, increased cough, diarrhea, headache, dyspnea, infection, rhinitis, and insomnia. Herceptin in combination with chemotherapy (paclitaxel) can lead to cardiotoxicity (Sparano, 1999), leukopenia, anemia, diarrhea, abdominal pain and infection.

HER2 Protein Levels for Patient Screening and as a Potential Endpoint

Because elevated HER2 levels can be detected in at least 30% of breast cancers, breast cancer patients can be pre-screened for elevated HER2 prior to admission to initial clinical trials testing an anti-HER2 ribozyme. Initial HER2 levels can be determined (by ELISA) from tumor biopsies or resected tumor samples. During clinical trials, it may be possible to monitor circulating HER2 protein by ELISA (Ross and Fletcher, 1998). Evaluation of serial blood/serum samples over the course ofthe anti-HER2 ribozyme freatment period could be useful in determining early indications of efficacy. In fact, the clinical course of Stage TV breast cancer was correlated

5 with shed HER2 protein fragment following a dose-intensified paclitaxel monotherapy. In all responders, the HER2 serum level decreased below the detection limit (Luftner et al). Two cancer-associated antigens, CA27.29 and CA15.3, can also be measured in the serum. Both of these glycoproteins have been used as diagnostic markers for breast cancer. CA27.29 levels are higher than CA15.3 in breast cancer patients; the reverse is

10 true in healthy individuals. Of these two markers, CA27.29 was found to better discriminate primary cancer from healthy subjects. In addition, a statistically significant and direct relationship was shown between CA27.29 and large vs small tumors and node postive vs node negative disease (Gion, et al, 1999). Moreover, both cancer antigens were found to be suitable for the detection of possible metastases during follow-up (Rodriguez

5 de Patema et al, 1999). Thus, blocking breast tumor growth may be reflected in lower CA27.29 and/or CA15.3 levels compared to a control group. FDA submissions for the use of CA27.29 and CA15.3 for monitoring metastatic breast cancer patients have been filed (reviewed in Beveridge, 1999). Fully automated methods for measurement of either of these markers are commercially available.

!0

References

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Weichen, K., Zimmer, C. and Dietel, M. (1997) Selection of a high activity c-erbB-2 ribozyme using a fusion gene of c-erbB-2 and the enhanced green fluorescent protein. Cancer Gene Therapy 5: 45-51.

Wright, M., Grim, J., Deshane, J., Kim, M., Strong, T.V., Siegel, G.P., Curiel, D.T. (1997) An intracellular anti-erbB-2 single-chain antibody is specifically cytotoxic to human breast carcinoma cells overexpressing erbB-2. Gene Therapy 4: 317-322.

Applicant has designed, synthesized and tested several NCH ribozymes and HH ribozymes targeted against HER2 RNA (see for example Tables 31 and 34) in cell proliferation assays.

Proliferation assay:

The model proliferation assay used in the study can require a cell plating density of 2000 cells/well in 96-well plates and at least 2 cell doublings over a 5-day freatment period. To calculate cell density for proliferation assays, the FFPS (fluoro-imaging processing system) method well in the art was used. This method allows for cell density measurements after nucleic acids are stained with CyQuant dye, and has the advantage of accurately measuring cell densities over a very wide range 1,000-100,000 cells/well in 96- well format.

Ribozymes (50-200 nM) were delivered in the presence of cationic lipid at 2.0 μg/mL and inhibition of proliferation was determined on day 5 post-treatment. Two full ribozyme screens were completed and 4 lead HH and 11 lead NCH ribozymes were chosen for further testing. Ofthe 15 lead Rzs chosen from primary screens, 4 NCH and 1 HH Rzs continued to inhibit cell proliferation in subsequent experiments. NCH Rzs against sites, 2001 (RPI No. 17236), 2783 (RPI No. 17249), 2939 (RPI No. 17251) or 3998 (RPI No. 17262) caused inhibition of proliferation ranging from 25-60% as compared to a scrambled confrol Rz (LA; RPI No. 17263). Ofthe five lead Rzs, the most efficacious is the NCH Rz (RPI No. 17251) against site 2939 of HER2 RNA. An example of results from cell culture assay is shown in Figure 8. Referring to Figure 8, NCH ribozymes and a HH ribozyme targeted against HER2 RNA, are shown to cause significant inhibition of proliferation of cells. This shows that ribozymes, for instance the NCH ribozymes are capable of inhibiting HER2 gene expression in mammalian cells.

Example 8: Activity of Class LI (Zinzyme) nucleic acid catalysts to inhibit HER2 gene expression

Applicant has designed, synthesized and tested several class π (zinzyme) ribozymes targeted against HER2 RNA (see, for example, Tables 58, 59, and 62) in cell proliferation RNA reduction assays.

Proliferation assay:

The model proliferation assay used in the study requires a cell-plating density of 2000-10000 cells/well in 96-well plates and at least 2 cell doublings over a 5-day treatment period. Cells used in proliferation studies were either human breast or ovarian cancer cells (SKBR-3 and SKOV-3 cells respectively). To calculate cell density for proliferation assays, the FLPS (fluoro-imaging processing system) method well known in the art was used. This method allows for cell density measurements after nucleic acids are stained with CyQuant® dye, and has the advantage of accurately measuring cell densities over a very wide range 1,000-100,000 cells/well in 96-well format. Ribozymes (50-200 nM) were delivered in the presence of cationic lipid at 2.0-5.0 μg/mL and inhibition of proliferation was determined on day 5 post-treatment. Two full ribozyme screens were completed resulting in the selection of 14 ribozymes. Class IL (zinzyme) ribozymes against sites, 314 (RPI No. 18653), 443 (RPI No. 18680), 597 (RPI No. 18697), 659 (RPI No. 18682), 878 (RPI Nos. 18683 and 18654), 881 (RPI Nos. 18684 and 18685) 934 (RPI No. 18651), 972 (RPI No. 18656, 19292, 19727, 19728, and 19293), 1292 (RPI No. 18726), 1541 (RPI No. 18687), 2116 (RPI No. 18729), 2932 (RPI No. 18678), 2540 (RPI No. 18715), and 3504 (RPI No. 18710) caused inhibition of proliferation ranging from 25-80% as compared to a scrambled control ribozyme. An example of results from a cell culture assay is shown in Figure 20. Referring to Figure 20, Class II ribozymes targeted against HER2 RNA are shown to cause significant inhibition of proliferation of cells. This shows that ribozymes, for instance the Class II (zinzyme) ribozymes are capable of inhibiting HER2 gene expression in mammalian cells.

RNA assay:

RNA was harvested 24 hours post-treatment using the Qiagen RNeasy® 96 procedure. Real time RT-PCR (TaqMan® assay) was performed on purified RNA samples using separate primer/probe sets specific for either target HER2 RNA or control actin RNA (to normalize for differences due to cell plating or sample recovery). Results are shown as the average of triplicate determinations of HER2 to actin RNA levels post- treatment. Figure 30 shows class LI ribozyme (zinzyme) mediated reduction in HER2 RNA targeting site 972 vs a scrambled attenuated confrol.

Dose response assays: Active ribozyme was mixed with binding arm-attenuated confrol (BAC) ribozyme to a final oligonucleotide concenfration of either 100, 200 or 400 nM and delivered to cells in the presence of cationic lipid at 5.0 μg/mL. Mixing active and BAC in this manner maintains the lipid to ribozyme charge ratio throughout the dose response curve. HER2 RNA reduction was measured 24 hours post-treatment and inhibition of proliferation was determined on day 5 post-treatment. The dose response antiproliferation results are summarized in Figure 31 and the dose-dependent reduction of HER2 RNA results are summarized in Figure 32. Figure 33 shows a combined dose response plot of both anti- proliferation and RNA reduction data for a class LI ribozyme targeting site 972 of HER2 RNA (RPI 19293).

Example 9: Compositions having RNA cleaving activity

Hammerhead ribozymes are an example of catalytic RNA molecules which are able to recognize and cleave a given specific RNA subsfrate (Hutchins et α/.,1986, Nucleic Acids Res. 14:3627; Keese and Symons, in Viroids and viroid-like pathogens (J.J. Semanchik, publ., CRC-Press, Boca Raton, Florida, 1987, pages 1-47). The catalytic center of hammerhead ribozymes is flanked by three stems and can be formed by adjacent sequence regions ofthe RNA or also by regions, which are separated from one another by many nucleotides. Figure 6 shows a diagram of such a catalytically active hammerhead structure. The stems have been denoted I, IL and ILI. The nucleotides are numbered according to the standard nomenclature for hammerhead ribozymes (Hertel et al, 1992, Nucleic Acids Res. 20:3252). In this nomenclature, bases are denoted by a number, which relates their position relative to the 5' side ofthe cleavage site. Furthermore, each base that is involved in a stem or loop region has an additional designation (which is denoted by a decimal point and then another number) that defines the position of that base within the stem or loop. A designation of A^{15 Λ} would indicate that this base is involved in a paired region and that it is the first nucleotide in that stem going away from the core region. This accepted convention for describing hammerhead-derived ribozymes allows for the nucleotides involved in the core ofthe enzyme to always have the same number relative to all ofthe other nucleotides. The size ofthe stems involved in substrate binding or core formation can be any size and of any sequence, and the position of A⁹, for example, will remain the same relative to all ofthe other core nucleotides. Nucleotides designated, for example, N^Λ12 or N^9Λ represent an inserted nucleotide where the position ofthe caret (^Λ) relative to the number denotes whether the insertion is before or after the indicated nucleotide. Thus, N^Λ represents a nucleotide inserted before nucleotide position 12, and N^9Λ represents a nucleotide inserted after nucleotide position 9. The consensus sequence ofthe catalytic core structure is described by Ruffher and

Uhlenbeck, 1990, Nucleic Acids Res. 18:6025-6029. Perriman et al, 1992, Gene 113:157- 163, have meanwhile shown that this structure can also contain variations, for example, naturally occurring nucleotide insertions such as N^9Λ and N^Λ12. Thus, the positive strand ofthe satellite RNA ofthe tobacco ring-spot virus does not contain any ofthe two nucleotide insertions while the +RNA strand ofthe virusoid ofthe lucerne transient streak virus (vLTSV) contains a N^9Λ = U insertion which can be mutated to C or G without loss ofactivity (Sheldon and Symons, 1989, Nucleic Acids Res. 17:5679-5685). Furthermore, in this special case, N⁷ = A and R^{15 1} = A. On the other hand, the minus strand ofthe carnation stunt associated viroid (-CarSV) is quite unusual since it contains both nucleotide insertions, that is N^Λ12 = A and N^9Λ = C (Hernandez et α/.,1992, Nucleic Acids Res. 20:6323-6329). In this viroid N⁷ = A and R^{15 1} = A. In addition, this special hammerhead structure exhibits a very effective self-catalytic cleavage despite the more open central stem.

Possible uses of hammerhead ribozymes include, for example, generation of RNA restriction enzymes and the specific inactivation ofthe expression of genes in, for example, animal, human or plant cells and prokaryotes, yeasts and plasmodia. A particular biomedical interest is based on the fact that many diseases, including many forms of tumors, are related to the overexpression of specific genes. Inactivating such genes by cleaving the associated mRNA represents a possible way to confrol and eventually treat such diseases. Moreover there is a great need to develop antiviral, antibacterial, and antifungal pharmaceutical agents. Ribozymes have potential as such anti-infective agents since RNA molecules vital to the survival ofthe organism can be selectively destroyed. In addition to needing the correct hybridizing sequences for subsfrate binding, substrates for hammerhead ribozymes have been shown to strongly prefer the triplet _N ⁱ⁶.² _Tj^i6.i _H ⁱ⁷ (NUH) _{where N can e my nuc}ieotide, U is uridine, and H is either adenosine, cytidine, or uridine (Koizumi et al, 1988, FEBS Lett. 228, 228-230; Ruffner et al, 1990, Biochemistry 29, 10695-10702 ; Perriman et al, 1992, Gene 113, 157-163). NUH is sometimes designated as NUX. The fact that changes to this general rule for substrate specificity result in non- functional substrates implies that there are "non core compatible" structures which are formed when substrates are provided which deviate from the stated requirements. Evidence along these lines was recently reported by Uhlenbeck and co-workers (Uhlenbeck et al, 1997, Biochemistry 36: 1108-1114) when they demonsfrated that the substitution of a G at position 17 caused a functionally catastrophic base pair between G¹⁷ and C³ to form, both preventing the correct orientation ofthe scissile bond for cleavage and the needed tertiary interactions of C³ (Murray et al, 1995, Biochem. J. 311 :487-494). The strong preference for a U at position 16.1 may exist for similar reasons. Many experiments have been done in an attempt to isolate ribozymes which are able to efficiently relieve the requirement of a U at position 16.1, however, attempts to find hammerhead type ribozymes which can cleave substrates having a base other than a U at position 16.1 have proven impossible (Perriman et al, 1992, Gene 113, 157-163).

Efficient catalytic molecules with reduced or altered requirements in the cleavage region are highly desirable because their isolation would greatly increase the number of available target sequences that molecules of this type could cleave. For example, it would be desirable to have a ribozyme variant that could efficiently cleave substrates containing triplets other than N U H since this would increase the number of potential target cleavage sites.

Chemically modified oligonucleotides which contain a block of deoxyribonucleotides in the middle region ofthe molecule have potential as pharmaceutical agents for the specific inactivation ofthe expression of genes (Giles et al, 1992, Nucleic Acids Res. 20:763-770). These oligonucleotides can form a hybrid DNA- RNA duplex in which the DNA bound RNA strand is degraded by RNase H. Such oligonucleotides are considered to promote cleavage ofthe RNA and so cannot be characterized as having an RNA-cleaving activity nor as cleaving an RNA molecule (the RNase H is cleaving). A significant disadvantage of these oligonucleotides for in vivo applications is their low specificity, since hybrid formation, and thus cleavage, can also take place at undesired positions on the RNA molecules.

Since, unmodified ribozymes are sensitive to degradation by RNases, chemically modified active substances have to be used in order to administer hammerhead ribozymes exogenously (discussed, for example, by Heidenreich et al, 1994, J. Biol. Chem. 269:2131-2138; Kiehntopf et al, \99A, EMBOJ. 13:4645-4652; Paolella et al, 1992, EMBOJ. 11:1913-1919; and Usman et al, \99 A, Nucleic Acids Symp. Ser. 31 :163-164). Sproat et al, U.S. Pat. No. 5,334,711, describe such chemically modified active substances based on synthetic catalytic oligonucleotide structures with a length of 35 to 40 nucleotides which are suitable for cleaving a nucleic acid target sequence and contain modified nucleotides that contain an optionally substituted alkyl, alkenyl or alkynyl group with 1 - 10 carbon atoms at the 2'-O atom ofthe ribose. These oligonucleotides contain modified nucleotide building blocks and form a structure resembling a hammerhead structure. These oligonucleotides are able to cleave specific RNA subsfrates.

Usman et al, U.S. Patent No. 5,891,684, describe enzymatic nucleic acid molecules with one or more nucleotide base modification(s) in a subsfrate binding arm.

Thompson et al, US Patent No. 5,599,704 describe enzymatic RNA molecules targeted against ErbB2/«ew/Her2 RNA.

Sullivan et al, US Patent No. 5,616,490 describe enzymatic RNA molecules targeted against protein kinase C (PKC) RNA. Sioud, International PCT publication No. WO 99/63066 describe hammerhead ribozymes targeted against specific sites within protein kinase C alpha (PKC alpha), VEGF, and TNF alpha RNA.

Jarvis et al, International PCT publication No. WO 98/505030, describe the synthesis of xylo-ribonucleosides and oligonucleotides comprising xylo modifications. This invention relates to novel enzymatic nucleic acid molecules having an RNA- cleavage activity, as well as their use for cleaving RNA substrates in vitro and in vivo. The compositions contain an active center, the subunits of which are selected from nucleotides and/or nucleotide analogues, as well as flanking regions contributing to the formation of a specific hybridization with an RNA subsfrate. Preferred compositions form, in combination with an RNA substrate, a structure resembling a hammerhead structure. The active center ofthe disclosed compositions is characterized by the presence of I¹⁵ ' which allows cleavage of RNA substrates having C^{16 -1}. It is therefore an object of the present invention to provide compositions that cleave RNA, and in particular to provide RNA- cleaving oligomers which at the same time have a high stability, activity, and specificity. This invention relates to novel nucleic acid molecules with catalytic activity, which are particularly useful for cleavage of RNA or DNA or combination thereof. The nucleic acid catalysts ofthe instant invention are distinct from other nucleic acid catalysts known in the art. Specifically, nucleic acid catalysts ofthe instant invention are capable of catalyzing an intermolecular or intramolecular endonuclease reaction. It is another object ofthe present invention to provide compositions that cleave RNA subsfrates having a cleavage site triplet other than N^16,2U^{16 1}H¹⁷ (NUH; Figure 6), where N is a nucleotide, U is uridine and H is adenosine, uridine or cytidine. H is used interchangably with X. Specifically, the enzymatic nucleic acid molecule ofthe instant invention has an endonuclease activity to cleave RNA substrates having a cleavage triplet _N ⁱ⁶.² .^i6.ι jjⁱ⁷ (Ncjj. Fig_Ure 6), where N is a nucleotide, C is cytidine and H is adenosine, uridine or cytidine. H is used interchangeably with X. In another aspect the invention features an enzymatic nucleic acid molecule ofthe instant invention has an endonuclease activity to cleave RNA substrates having a cleavage triplet N¹⁶²C^{16 1}N¹⁷ (NCN; Figure 6), where N is a nucleotide, C is cytidine.

In a preferred embodiment, the invention features an enzymatic nucleic acid molecule having formula 1 :

^ — G— A — A — I _D — ₃.

L

^ (N) n^~ (N)_p— A — G— N — A — G — TJ — C ^~ E^~ 5' where N represents independently a nucleotide or a non-nucleotide linker, which may be same or different; D and E are independently oligonucleotides of length sufficient to stably interact (e.g., by forming hydrogen bonds with complementary nucleotides in the target) with a target nucleic acid molecule (the target can be an RNA, DNA or mixed polymers), preferably, the length of D and E are independently between 3-20 nucleotides long, specifically, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17, and 20; o and n are integers independently greater than or equal to 1 and preferably less than about 100, specifically 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 50, wherein if (N)₀ and (N)n are nucleotides, (N)o and (N)n are optionally able to interact by hydrogen bond interaction, in particular if n =1 and o=l then (N)n is preferably a purine (e.g., G, and A) and (N)o is preferably a pyrimidine (e.g., C and U) and (N)n preferably forms; • indicates base-paired interaction; L is a linker which may be present or absent (i.e., the molecule may be assembled from two separate oligonucleotides), but when present, is a nucleotide and/or a non-nucleotide linker, which may be a single-stranded and/or double-stranded region; p is an integer 0 or 1, when p=l, (N)p is preferably A or U; and represents a chemical linkage (e.g. a phosphate ester linkage, amide linkage, phosphorothioate linkage or others known in the art). A, U, I, C and G represent adenosine, uridine, inosine, cytidine and guanosine nucleotides, respectively. The N in 5'-CUGANGA-3' region of formula 1 is preferably U. The nucleotides in the formula 1 are unmodified or modified at the sugar, base, and/or phosphate as known in the art.

In a preferred embodiment, the invention features an enzymatic nucleic acid molecule having formula 2:

G-A- A- I D- 3'

L

(N) _n G- (N)_P-A- G- N- A- G~ U- C~ E" 5'

where N represents independently a nucleotide or a non-nucleotide linker, which may be same or different; D and E are independently oligonucleotides of length sufficient to stably interact (e.g., by forming hydrogen bonds with complementary nucleotides in the target) with a target nucleic acid molecule (the target can be an RNA, DNA or mixed polymers), preferably, the length of D and E are independently between 3-20 nucleotides long, specifically, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17, and 20; o and n are integers independently greater than or equal to 0 and preferably less than about 100, specifically 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 50, wherein if (N)₀ and (N)_n are nucleotides, (N)o and (N)n are optionally able to interact by hydrogen bond interaction; • indicates base- paired interaction; L is a linker which may be present or absent (i.e., the molecule may be assembled from two separate oligonucleotides), but when present, is a nucleotide and/or a non-nucleotide linker, which may be a single-stranded and/or double-stranded region; p is an integer 0 or 1, when p=l, (N)p is preferably A, C or U; and represents a chemical linkage (e.g. a phosphate ester linkage, amide linkage, phosphorothioate linkage or others known in the art). A, U, I, C and G represent adenosine, uridine, inosine, cytidine and guanosine nucleotides, respectively. The N in 5'-CUGANGA-3' region of formula 2 is preferably U. The nucleotides in the formula 2 are unmodified or modified at the sugar, base, and/or phosphate as known in the art. In a preferred embodiment, the I (inosine) in formula 1 and 2 is preferably a riboinosine or a xylo-inosine. In yet another embodiment, the nucleotide linker (L) is a nucleic acid aptamer, such as an ATP aptamer, HIV Rev aptamer (RRE), HIV Tat aptamer (TAR) and others (for a review see Gold et al, 1995, Annu. Rev. Biochem., 64, 763; and Szostak & Ellington, 1993, in The RNA World, ed. Gesteland and Atkins, pp 511, CSH Laboratory Press). A "nucleic acid aptamer" as used herein is meant to indicate nucleic acid sequence capable of interacting with a ligand. The ligand can be any natural or a synthetic molecule, including but not limited to a resin, metabolites, nucleosides, nucleotides, drugs, toxins, transition state analogs, peptides, lipids, proteins, amino acids, nucleic acid molecules, hormones, carbohydrates, receptors, cells, viruses, bacteria and others. In a preferred embodiment L has the sequence 5 '-GAAA-3 ' or 5 '-GUUA-3 ' .

In yet another embodiment, the non-nucleotide linker (L) is as defined herein. The term "non-nucleotide", as used herein, includes either abasic nucleotide, polyether, polyamine, polyamide, peptide, carbohydrate, lipid, or polyhydrocarbon compounds. Specific examples include those described by Seela and Kaiser, Nucleic Acids Res. 1990, 75:6353 and Nucleic Acids Res. 1987, 75:3113; Cload and Schepartz, J. Am. Chem. Soc. 1991, 773:6324; Richardson and Schepartz, J. Am. Chem. Soc. 1991, 775:5109; Ma et al., Nucleic Acids Res. 1993, 27:2585 and Biochemistry 1993, 52:1751; Durand et al., Nucleic Acids Res. 1990, 75:6353; McCurdy et al., Nucleosides & Nucleotides 1991, 70:287; Jschke et al., Tetrahedron Lett. 1993, 34:301; Ono et al., Biochemistry 1991, 50:9914; Arnold et al, International Publication No. WO 89/02439; Usman et al, International Publication No. WO 95/06731 ; Dudycz et al, International Publication No. WO 95/11910 and Ferentz and Verdine, J. Am. Chem. Soc. 1991, 775:4000, all hereby incoφorated by reference herein. Non-nucleotide linkers can be any molecule, which is not an oligomeric sequence, that can be covalently coupled to an oligomeric sequence. Preferred non-nucleotide linkers are oligomeric molecules formed of non-nucleotide subunits. Examples of such non-nucleotide linkers are described by Letsinger and Wu, (J. Am. Chem. Soc. 117:7323-7328 (1995)), Benseler et al, (J. Am. Chem. Soc. 115:8483-8484 (1993)) and Fu et al. , (J. Am. Chem. Soc. 116:4591-4598 (1994)). Prefeπed non-nucleotide linkers, or subunits for non-nucleotide linkers, include substituted or unsubstituted Ci-Cio straight chain or branched alkyl, substituted or unsubstituted C₂-C₁₀ straight chain or branched alkenyl, substituted or unsubstituted C₂- C₁₀ straight chain or branched alkynyl, substituted or unsubstituted C do straight chain or branched alkoxy, substituted or unsubstituted C₂-C₁₀ straight chain or branched alkenyloxy, and substituted or unsubstituted C₂-Cι₀ straight chain or branched alkynyloxy. The substituents for these prefeπed non-nucleotide linkers (or subunits) can be halogen, cyano, amino, carboxy, ester, ether, carboxamide, hydroxy, or mercapto. Thus, in a prefeπed embodiment, the invention features an enzymatic nucleic acid molecule having one or more non-nucleotide moieties, and having enzymatic activity to cleave an RNA or DNA molecule. By the term "non-nucleotide" is meant any group or compound which can be incoφorated into a nucleic acid chain in the place of one or more nucleotide units, including either sugar and/or phosphate substitutions, and allows the remaining bases to exhibit their enzymatic activity. The group or compound is abasic in that it does not contain a commonly recognized nucleotide base, such as adenosine, guanine, cytosine, uracil or thymine. The terms "abasic" or "abasic nucleotide" as used herein encompass sugar moieties lacking a base or having other chemical groups in place of nucleotide base at the 1' position. In a prefeπed embodiment, the invention features modified ribozymes with phosphate backbone modifications comprising one or more phosphorothioate, phosphorodithioate, methylphosphonate, moφholino, amidate carbamate, carboxymethyl, acetamidate, polyamide, sulfonate, sulfonamide, sulfamate, formacetal, thioformacetal, and/or alkylsilyl, substitutions. For a review of oligonucleotide backbone modifications see Hunziker and Leumann, 1995, Nucleic Acid Analogues: Synthesis and Properties, in Modern Synthetic Methods, VCH, 331-417, and Mesmaeker et al, 1994, Novel Backbone Replacements for Oligonucleotides, in Carbohydrate Modifications in Antisense Research, ACS, 24-39.

In a further prefeπed embodiment ofthe instant invention, an inverted deoxy abasic moiety is utilized at the 3' end ofthe enzymatic nucleic acid molecule.

By "pyrimidines" is meant nucleotides comprising modified or unmodified derivatives of a six membered pyrimidine ring. An example of a pyrimidine is modified or unmodified uridine.

In a prefeπed embodiment, the nucleosides ofthe instant invention include, 2'-O- methyl-2,6-diaminopurine riboside; 2'-deoxy-2'amino-2,6-diaminopurine riboside; 2'-(N- alanyl) amino-2'-deoxy-uridine; 2'-(N-phenylalanyl)amino-2'-deoxy-uridine; 2'-deoxy -2'- (N-beta-alanyl) amino ; 2'-deoxy-2'-(lysiyl) amino uridine; 2'-C-allyl uridine; 2'-O-amino- uridine; 2'-O-methylthiomethyl adenosine; 2'-O-methylthiomethyl cytidine ; 2'-O- methylthiomethyl guanosine; 2'-O-methylthiomethyl-uridine; 2'-Deoxy-2'-(N-histidyl) amino uridine; 2'-deoxy-2'-amino-5-methyl cytidine; 2'-(N-β-carboxamidine-beta- alanyl)amino-2 '-deoxy-uridine; 2 ' -deoxy-2 ' -(Ν-beta-alanyl)-guanosine; 2 '-O-amino- adenosine; 2'-(N-lysyl)amino -2'-deoxy-cytidine; 2'-Deoxy -2'-(L-histidine) amino Cytidine; and 5-Imidazoleacetic acid 2'-deoxy-5'-triphosphate uridine.

By "oligonucleotide" as used herein is meant a molecule having two or more nucleotides. The polynucleotide can be single, double or multiple stranded and may have modified or unmodified nucleotides or non-nucleotides or various mixtures and combinations thereof.

In a prefeπed embodiment, the enzymatic nucleic acid molecule of formula 1 or 2 include at least three ribonucleotide residues, preferably 4, 5, 6, 7, 8, 9, and 10 ribonucleotide residues.

In prefeπed embodiments, the enzymatic nucleic acid ofthe instant invention includes one or more stretches of RΝA, which provide the enzymatic activity ofthe molecule, linked to the non-nucleotide moiety. The necessary RΝA components are known in the art (see for e.g., Usman et al, supra).

Thus, in one prefeπed embodiment, the invention features enzymatic nucleic acid molecules that inhibit gene expression and/or cell proliferation in vitro or in vivo (e.g. in patients). These chemically or enzymatically synthesized nucleic acid molecules contain substrate binding domains that bind to accessible regions of specific target nucleic acid molecules. The nucleic acid molecules also contain domains that catalyze the cleavage of target. Upon binding, the enzymatic nucleic acid molecules cleave the target molecules, preventing for example, translation and protein accumulation. In the absence ofthe expression ofthe target gene, cell proliferation, for example, is inhibited.

In another prefeπed embodiment, catalytic activity ofthe molecules described in the instant invention can be optimized as described by Draper et al., supra. The details will not be repeated here, but include altering the length ofthe ribozyme binding arms, or chemically synthesizing ribozymes with modifications (base, sugar and/or phosphate) that prevent their degradation by serum ribonucleases and/or enhance their enzymatic activity (see e.g., Eckstein et al, International Publication No. WO 92/07065; Peπault et al, 1990 Nature 344, 565; Pieken et al., 1991 Science 253, 314; Usman and Cedergren, 1992 Trends in Biochem. Sci. 17, 334; Usman et al, International Publication No. WO 93/15187; and Rossi et al, International Publication No. WO 91/03162; Sproat, US Patent No. 5,334,711; and Burgin et al, supra; all of these describe various chemical modifications that can be made to the base, phosphate and/or sugar moieties of enzymatic RNA molecules). Modifications which enhance their efficacy in cells, and removal of bases from stem loop structures to shorten RNA synthesis times and reduce chemical requirements are desired. (All these publications are hereby incoφorated by reference herein.).

By "nucleic acid catalyst" as used herein is meant a nucleic acid molecule (e.g., the molecule of formulae 1 and 2) capable of catalyzing (altering the velocity and/or rate of) a variety of reactions including the ability to repeatedly cleave other separate nucleic acid molecules (endonuclease activity) in a nucleotide base sequence-specific manner. Such a molecule with endonuclease activity may have complementarity in a subsfrate binding region to a specified gene target, and also has an enzymatic activity that specifically cleaves RNA or DNA in that target. That is, the nucleic acid molecule with endonuclease activity is able to inframolecularly or intermolecularly cleave RNA or DNA and thereby inactivate a target RNA or DNA molecule. This complementarity functions to allow sufficient hybridization ofthe enzymatic RNA molecule to the target RNA or DNA to allow the cleavage to occur. 100%> complementarity is prefeπed, but complementarity as low as 50-75%) may also be useful in this invention. The nucleic acids may be modified at the base, sugar, and/or phosphate groups. The term enzymatic nucleic acid as used herein is used interchangeably with phrases such as ribozymes, catalytic RNA, enzymatic RNA, catalytic oligonucleotides, nucleozyme, RNA enzyme, endoribonuclease, endonuclease, minizyme, oligozyme, finderon or nucleic acid catalyst. All of these terminologies describe nucleic acid molecules ofthe instant invention with enzymatic activity. The specific examples of enzymatic nucleic acid molecules described in the instant application are not limiting in the invention and those skilled in the art will recognize that all that is important in an enzymatic nucleic acid molecule of this invention is that it has a specific substrate binding site which is complementary to one or more ofthe target nucleic acid regions, and that it have nucleotide sequences within or suπounding that substrate binding site which impart a nucleic acid cleaving activity to the molecule (Cech et al., U.S. Patent No. 4,987,071; Cech et al, 1988, 260 JAMA 3030). The enzymatic nucleic acid molecule of Formula 1 or 2 may independently comprise a cap structure which may independently be present or absent.

By "chimeric nucleic acid molecule" or "mixed polymer" is meant that, the molecule maybe comprised of both modified or unmodified nucleotides. In yet another prefeπed embodiment, the 3 '-cap is selected from a group comprising,

4', 5 '-methylene nucleotide; l-(beta-D-erythrofuranosyl) nucleotide; 4'-thio nucleotide, carbocyclic nucleotide; 5'-amino-alkyl phosphate; l,3-diamino-2-propyl phosphate, 3- aminopropyl phosphate; 6-aminohexyl phosphate; 1,2-aminododecyl phosphate; hydroxypropyl phosphate; 1,5-anhydrohexitol nucleotide; L-nucleotide; alpha-nucleotide; modified base nucleotide; phosphorodithioate; tλreσ-pentofuranosyl nucleotide; acyclic

3',4'-seco nucleotide; 3,4-dihydroxybutyl nucleotide; 3,5-dihydroxypentyl nucleotide, 5'-5'- inverted nucleotide moiety; 5'-5'-inverted abasic moiety; 5'-phosphoramidate; 5'- phosphorothioate; 1,4-butanediol phosphate; 5'-amino; bridging and/or non-bridging 5'- phosphoramidate, phosphorothioate and/or phosphorodithioate, bridging or non bridging methylphosphonate and 5'-mercapto moieties (for more details, see Beaucage and Iyer, 1993, Tetrahedron 49, 1925; incoφorated by reference herein). By the term "non- nucleotide" is meant any group or compound which can be incoφorated into a nucleic acid chain in the place of one or more nucleotide units, including either sugar and/or phosphate substitutions, and allows the remaining bases to exhibit their enzymatic activity. The group or compound is abasic in that it does not contain a commonly recognized nucleotide base, such as adenosine, guanine, cytosine, uracil or thymine. The terms "abasic" or "abasic nucleotide" as used herein encompass sugar moieties lacking a base or having other chemical groups in place of a base at the 1' position.

In a prefeπed embodiment, the invention features l-(beta-D-xylofuranosyl)- xypoxanthine phosphoramidite and a process for the synthesis thereof and incoφoration into oligonucleotides, such as enzymatic nucleic acid molecule.

In yet another prefeπed embodiment, the invention features enzymatic nucleic acid molecules targeted against HER2 RNA, specifically, ribozymes in the hammerhead and NCH motifs. In a prefeπed embodiment, the invention features enzymatic nucleic acid molecules targeted against PKC alpha RNA, specifically, ribozymes in the hammerhead and NCH motifs. Targets, for example PKC alpha RNA, for useful ribozymes and antisense nucleic acids can be determined, for example, as described in Draper et al, WO 95/04818; McSwiggen et al, U.S. Patent Nos. 5,525,468 and 5,646,042, all are hereby incoφorated by reference herein in their totality. Other examples include the following PCT applications, which concern inactivation of expression of disease-related genes: WO 95/23225, WO 95/13380, WO 94/02595, all incoφorated by reference herein.

The specific enzymatic nucleic acid molecules described in the instant application are not limiting in the invention and those skilled in the art will recognize that all that is important in an enzymatic nucleic acid molecule of this invention is that it has a specific subsfrate binding site (e.g., D and E of Formula 1 above) which is complementary to one or more ofthe target nucleic acid regions, and that it have nucleotide sequences within or suπounding that substrate binding site which impart a nucleic acid cleaving activity to the molecule.

All naturally occurring hammerhead ribozymes have an A¹⁵ '-U^{16 Λ} base pair. In addition, it is known that subsfrates for ribozymes based on the consensus hammerhead sequence strongly prefer a substrate that contains an N^16'2U^{16 1}H¹⁷ triplet in which H¹⁷ is not a guanosine (Koizumi et al, FEBS Lett. 228, 228-230 (1988); Ruffner et al, Biochemistry 29, 10695-10702 (1990); Perriman et al, Gene 113, 157-163 (1992)). Many experiments have been done in an attempt to isolate ribozymes which are able to efficiently relieve the requirement of a U at position 16.1, however, attempts to find ribozymes which can cleave subsfrates having a base other than a U at position 16.1 have proven largely unsuccessful (Perriman et al, Gene 113, 157-163 1992, Singh et al, Antisense and Nucleic Acid Drug Development 6:165-168 (1996)).

However, examination ofthe recently published X-ray crystal structures (Pley et al, Nαtwre 372:68-74 (1994), Scott et al, Cell 81 :991-1002 (1995), and Scott et al, Science 274:2065-2069 (1996)) led to the realization that the A¹⁵ '-U^{16 Λ} interaction is a non- standard base pair with a single hydrogen bond between the exocyclic amine (Ν6) ofthe adenosine and the 4-oxo group ofthe uridine. Modeling studies (based on the crystal structure) then led to the discovery that the interaction ofthe wild-type A^{15 1}-U^{16 1} base pair can be spatially mimicked by replacement with an ι^{15 1}-C^16,1 base pair that adopts an isostructural orientation and which preserves the required contact ofthe 2-keto group of C^{16 -1} with A⁶ ofthe uridine turn. In the model, the polarity ofthe stabilizing hydrogen bond between positions 15.1 and 16.1 is reversed in the ι^{15 1}_c^{16 1} interaction, but the coπect orientation ofthe bases around this bond is maintained.

It has been discovered that hammerhead ribozyme analogues containing an inosine at position 15.1 readily cleave RNA substrates containing an

triplet. Based on this, disclosed are compositions, preferably synthetic oligomers, which cleave a nucleic acid target sequence containing the triplet N¹⁶'²C^{16 1}H¹⁷. It is prefeπed that H¹⁷ is not guanosine, however, under certain circumstances, NCG triplet containing RNA can be cleaved by the ribozymes ofthe instant invention. The ability to cleave subsfrates having

1 Λ 7 1 Λ 1 17

N C X triplets effectively doubles the number of targets available for cleavage by compositions ofthe type disclosed.

Example 10: Synthesis of l-(beta-D-xylofuranosyl)-xypoxanthine phosphoramidite Referring to Figure 9, Inosine (1) was 5'-O-monomethoxyfritylated and 2'-O- silylated under standard conditions to afford 2 (Charubala, R; Pfleiderer, W. Heterocycles 1990, 30, 1141). Oxidation/reduction procedure afforded 3 in moderate yield (Matulic- Adamic, J.; Daniher, A.T.; Gonzalez, C; Beigelman, L. Bioorg. Med. Chem. Lett.. 1999, 9, 157): !H NMR (CDC1₃) δ 12.80 (br s, IH, NH), 8.11 (s, IH, H-8), 8.08 (s, IH, H-2), 7.45-6.80 (m, 14H, trityl), 5.85 (d, J_{r 2}>= 1.6, IH, H-l'), 4.83 (d, J_2',3_'=7.2, IH, H-2'), 4.46 (br s, IH, 3'-OH), 4.34 (m, IH, H-4'), 4.06 (m, IH, H-3'), 3.77 (s, 6H, 2 x OMe), 3.60 (app d, 2H, H-5', H-5"), 0.89 (s, 9H, t-Bu), 0.07 (s, 3H, Me), 0.06 (s, 3H, Me). Standard phosphitylation of 3 afforded the desired phosphoramidite 4. More acid stable 5'-O-MMT group is used in this particular case because applicant found that 5'-O-DMT protection is more labile in xylo nucleoside series than in ribo nucleoside series. The xylo-inosine was incoφorated into oligonucleotides using the standard procedures known in the art and as described herein.

Example 11 : Activity ofthe xylo-Inosine-modified NCH Ribozyme

Several NCH ribozymes with xylo-inosine at position 15.1 were designed (Figure 7) to cleave RNA containing GCA, ACA, UCA or the CCA triplet. These ribozymes were synthesized and purified as described herein and tested using standard RNA cleavage reaction conditions (see Table 31, for example, and see below).

The ribozymes were chemically synthesized. The method of synthesis used followed the procedure for normal RNA synthesis as described above and in Usman et al., (1987 J. Am. Chem. Soc, 109, 7845), Scaringe et al., (1990 Nucleic Acids Res., 18, 5433) and

Wincott et al., supra, and made use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5'-end, and phosphoramidites at the 3'-end. The average stepwise coupling yields were >98%>.

Ribozymes were purified by gel elecfrophoresis using general methods or were purified by high pressure liquid chromatography (HPLC; See Wincott et al., supra; the totality of which is hereby incoφorated herein by reference) and were resuspended in water. The sequences ofthe chemically synthesized ribozymes used in this study are shown below in Table 33.

Cleavage Reactions: Full-length or partially full-length, internally-labeled target RNA for ribozyme cleavage assay is prepared by in vitro transcription in the presence of

[alpha-³²p] CTP, passed over a G 50 Sephadex column by spin chromatography and used as substrate RNA without further purification. Alternately, substrates were 5'-32p-end labeled using T4 polynucleotide kinase enzyme. Assays are performed by pre-warming a 2X concentration of purified ribozyme in ribozyme cleavage buffer (50 mM Tris-HCI, pH 7.5 at 37°C, 10 mM MgCtø) and the cleavage reaction was initiated by adding the 2X ribozyme mix to an equal volume of substrate RNA (maximum of 1-5 nM) that was also pre-warmed in cleavage buffer. As an initial screen, assays are carried out for 1 hour at o

37 C using a final concentration of 40 nM or 1 mM ribozyme, i.e., ribozyme excess. The reaction is quenched by the addition of an equal volume of 95% formamide, 20 mM EDTA, 0.05% bromophenol blue and 0.05% xylene cyanol after which the sample is heated to 95 C for 2 minutes, quick chilled and loaded onto a denaturing polyacrylamide gel. Substrate RNA and the specific RNA cleavage products generated by ribozyme cleavage are visualized on an autoradiograph ofthe gel. The percentage of cleavage is determined by Phosphor hnager® quantitation of bands representing the intact subsfrate and the cleavage products. The results ofthe experiments are summarized in Table 32, which shows that NCH- xylo ribozymes are catalytically active to cleave target RNA.

Example 12: Activity of NCH Ribozyme variants The nucleic acid molecules ofthe instant invention allow for the ability to cleave a new set of 12 NCH triplets. Determination of single turnover rate constants at pH 6 of these ribozymes in the all ribo form show that with NCA type triplets, the cleavage rate is higher than at NUA sites. NCC and NUC site rates are similar, and NCU sites are slightly lower than NUU sites. Additional measurements of multiple turnover parameters ofthe all ribo ribozymes performed under non-saturating conditions using 5nM ribozyme and changing the substrate concentration from 50 to 500 nM at pH 7.4 with 10 mM Mg ⁺⁺ at 37 °C gave Km= 100 nM and kcat=6.5 min -¹ for GCA vs Km -30 nM and kcat =2.0 min ^_1 for GUA cleaving all ribo ribozymes. These data verify that the ribozymes with an I^»C base pair are efficient catalysts in multiple turnover reactions and the relative order of activity between NCH and NUH cleavers established at pH 6 (Ludwig et al, 1998, Nucleic Acids Res., 26, 2279-2285) remains unchanged.

To gain more insight into the structural requirements ofthe 15.1- 16.1 base pair of the ribozymes ofthe instant invention, applicant synthesized several variants ofthe active 1-15.1 ^»C-16.1 structure and tested these ribozyme analogues with their coπesponding subsfrates. The influence of several core stabilization strategies on the activity ofthe NCH cleaving ribozymes was also investigated.

Various nucleoside analogs were incoφorated at position 15.1 ofthe ribozyme. Cleavage activity was tested with the complementary Fl* labeled substrates at pH 7.4 in the presence of 10 mM Mg ⁺⁺ under conditions of ribozyme excess (i.e. single turnover conditions). The modified oligonucleotides were synthesized by standard oligonucleotide synthesis procedures. Xanthosine was protected using O-2 ,0-4pivaloyloxymethyl groups; N,N-dimethylguanosine with 6-O-( 2-nitrophenyl-)ethyl and 6-thio-inosine with S- cyanoethyl protecting groups. The cleavage activity ofthe ribozymes containing the 15.1 analogs is summarized in Figure 36. For comparison Figure 37 summarizes reported functional group modification studies performed at the A 15.1 residue in the A-15.1 ^»U- 16.1 context of NUH cleaving ribozymes. Modifications at the purine 15.1 Nl and/or C6 positions (Figure 36 A, B, C)

In the 6-thio-inosine (A) (si) 15.1 substituted ribozyme, the original (1-15.1) position 6 O^»H-N (C-16.1) bonds are replaced by weaker (sl-15.1) position 6 SΗ-N (C-16.1) hydrogen bonds while all other functional groups remain unchanged. Ribozymes with an adenosine (B) at position 15.1 (A- 15.1 ) are inactive with C-16.1 substrates since the ribozyme geometry requires the [A-15.1] position 6 amino group and the [C-16.1] position 4 amino group hydrogen-bond donor functional groups to be in close proximity. Similarly, low activity is observed with 1-15.1 ribozymes and U-16.1 subsfrates, where the [1-15.1] position 6 keto and [C-16.1] position 4 keto hydrogen-bond acceptor groups are opposed (Figure 37, B). Although inosine can form stable mismatch pairs with uridine in RNA duplexes or in tRNA anticodon-mRNA interactions, these results suggest that the geometry in the MJ mismatches differ from that ofthe A^»U (or I*C) base pair in the active NUH ribozyme. Substitution of Nl-Methyl-inosine (C) in place of inosine at position 15.1 leads to complete loss of cleavage activity.

Modifications at the purine 15.1 C2 and/or N3 position (Figure 36 D, E, F)

The extremely low activity observed with the G-15.1 (D) substituted analog may be explained by the formation of a G-C Watson-Crick base pair. The replacement ofthe I^«C pair with a G»C pair can significantly distort the geometry at the 15.1-16.1 position. G- 15.1 N2-alkylation (E) gives only minimal recovery of catalytic activity compared to G- 15.1, suggesting that the steric problems introduced by the bulky N-methyl groups may interfere with stacking interactions. The activity of this construct is significantly less than that of iso-G-15.1 (Figure 37, E) containing ribozymes in the standard A-U context. Xanthosine 15.1 (F) contains the same functional groups as inosine at the Nl and C6 sites but contains an additional hydrogen-bond donor site at position N3 along with a C2 carbonyl group. The complete lack ofactivity seen with this construct reinforces the importance ofthe purine N3 acceptor functionality in transition state formation. Similarly, 3-deaza-adenosine (Figure 37, F) containing ribozymes were also inactive. The C2 carbonyl ofthe 15.1 purine shows no significant negative interference in iso-guanosine containing 15.1 ribozymes. Activity of modified core variants

To complete the characterization ofthe I*C pair containing ribozymes, the acceptance of various core substitution patterns was tested. Short subsfrates containing GCH and GUH (H= non G) triplets were compared using 3 different modified ribozymes. The acceptance of the U-42 '-O-alkyl substituent is the greatest with GCA triplets while U- 4 = 2'-deoxy-2'-amino uridine and U-4 = ribo uridine substituted ribozymes show a similar level of activity with NCH and NUH triplets. The results of this comparison are summarized in Table 64. In addition, a ribozyme construct in which ribo inosine replaces adenosine at positions 14 and 15.1 was tested which demonsfrated cleavage activity. Apart from the A-15.1 *U-16.1 to 1-15 .1 ^»C-16.1 change that reverses the polarity of an important H-bond in the ribozyme structure, no other functional group changes at the 15.1 purine residue seem to be compatible with the requirements of efficient catalysis. The 1-15.1 and A-15.1 ribozymes are equally suitable for practical applications because there are only minor differences in the acceptance of stabilizing residues.

Example 13: Activity of NCH Ribozyme to inhibit HER2 gene expression

Applicant has designed, synthesized and tested several NCH ribozymes and HH ribozymes targeted against HER2 RNA (see, for example, Tables 31 and 34) in cell proliferation assays.

Proliferation assay: The model proliferation assay used in the study can require a cell plating density of 2000 cells/well in 96-well plates and at least 2 cell doublings over a

5-day treatment period. To calculate cell density for proliferation assays, the FIPS (fluoro- imaging processing system) method well in the art was used. This method allows for cell density measurements after nucleic acids are stained with CyQuant® dye, and has the advantage of accurately measuring cell densities over a very wide range 1,000-100,000 cells/well in 96-well format.

Ribozymes (50-200 nM) were delivered in the presence of cationic lipid at 2.0 μg/mL and inhibition of proliferation was determined on day 5 post- treatment. Two full ribozyme screens were completed and 4 lead HH and 11 lead NCH ribozymes were chosen for further testing. Ofthe 15 lead Rzs chosen from primary screens, 4 NCH and 1 HHRzs continued to inhibit cell proliferation in subsequent experiments. NCH Rzs against sites, 2001 (RPI No. 17236), 2783 (RPI No. 17249), 2939 (RPI No. 17251) or 3998 (RPI No. 17262) caused inhibition of proliferation ranging from 25-60%) as compared to a scrambled confrol Rz (LA; RPI No. 17263). Ofthe five lead Rzs, the most efficacious is the NCH Rz (RPI No. 17251) against site 2939 of ΗER2 RNA. An example of results from cell culture assay is shown in Figure 3. Referring to Figure 3, NCH ribozymes and a HH ribozyme targeted against HER2 RNA are shown to cause significant inhibition of proliferation of cells. This shows that ribozymes, for instance, the NCH ribozymes are capable of inhibiting HER2 gene expression in mammalian cells.

Example 14: Activity of NCH Ribozyme to inhibit PKC alpha gene expression

The Protein Kinase C family contains twelve cuπently known isozymes divided into three classes: the classic, Ca^ dependent (PKCα, βl, βH, γ), the novel, non-Ca** dependent (PKCδ, ε, μ, η, θ) and the atypical (PKC ξ, i/λ); all of which are serine/threonine kinases. These isozymes show distinct and overlapping tissue, cellular, and subcellular distribution. They aid in the regulation of cell growth and differentiation through their response to second messenger products of lipid metabolism (Blobe, et al, 1996, Cancer Surveys, 27, 213-248). These second messengers include diacylglyceral (DAG), inositol-friphosphate (LP3), lysophospholipids, free fatty acids, and phosphatidate which act directly or in addition to changes in the Ca** concenfration. A simple model for PKCα activation follows a two step mechanism. First, membrane association of PKCα is through Ca*^4" and phospholipid interactions and second, the kinase is activated by interaction with DAG. An example of a signal cascade subsequent to PKC activation is PKC's phosphorylation of c-Raf, which phosphorylates MEK, which phosphorylates MAP, which phosphorylates transcription factors such as Jun and thereby activates a mitogenic program in the nucleus. There are numerous substrates for the various PKC's, one which for PKCα ultimately stimulates franscription factors that activate P- glycoprotein (P-gp) causing the multi-drug resistant phenotype (MDR) (Blobe, et al, 1994, Cancer and Metastasis Reviews, 13, 411-431). Cell Culture Review

PKC's have been implicated in tumor promotion since the discovery that these molecules can serve as receptors for tumor-promoting phorbol esters. An increase in PKC overexpression in numerous tumor cell lines and tumor tissues has also been demonsfrated. PKC overexpression has been shown to be associated with increased invasion and metastasis in mouse Lewis lung carcinoma, mouse B16 melanoma (Lee et al, 1997, Molecular Carcinogenesis, 18, 44-53), mouse mammary adenocarcinoma, mouse fibrosarcoma, human lung carcinoma (Wang and Liu, 1998, Acta Pharmacologica Sinica, 19, 265-268), human bladder carcinoma, human pancreatic cancer (Denham et al., 1998, Surgery, 124, 218-223), and human gastric cancer (Dean et al, 1996, Cancer Research, 56, 3499-3507). Mounting evidence suggests PKCα can stimulate adhesion molecule expression and can directly act on these membrane bound species as subsfrates, thereby modulating cellular adhesion to the extracellular matrix and increasing metastic potential. Furthermore, human surgical specimens have demonsfrated elevated PKC in breast tumors, thyroid carcinomas and melanomas (Becker et al, 1990, Oncogene, 5, 1133- 1139).

Utz et al, 1994, Int. J. Cancer, 57, 104-110, describe a cell proliferation assay in which small molecule inhibitors of PKC demonstrate anti-pro liferative activity in CCRF- VCR 1000 and KB-8511 cells with the multidrug resistant (MDR) phenotype. PKCα is overexpressed in tumor tissues that express the MDR phenotype. This phenotype is associated with the expression of a 170 kDa broad specificity drug efflux pump, P-gp. PKCα phosphorylation of P-gp has been shown in vitro. In addition, PKC expression coπelates with resistance to doxorubicin and high P-gp levels in human renal carcinoma and non-small cell lung carcinoma, inhibitors of PKC partially reverse the MDR phenotype and decrease phosphorylation of P-gp (Caponigro et al, 1997, Anti-Cancer Drugs, 8, 26-33).

Dean et al, 1994, Journal of Biological Chemistry, 269, 16416-24, describe cell culture studies in which antisense targeting of PKC α resulted in the potent inhibition of mRNA and protein expression in human lung carcinoma (A549) cells. In this study, PKC α inhibition resulted in the reduced induction of intercellular adhesion molecule 1 (ICAM- 1) mRNA by phorbol esters. Yano et al, 1999, Endocrinology, 140, 4622-4632, describe a cell proliferation study in which down regulation of different PKC isoforms, including PKCα, results in the inhibition of insulin like growth factor I induced vascular smooth muscle cell proliferation, migration, and gene expression. Wang et al, 1999, Experimental Cell Research, 250, 253-263, describe cell culture studies in which antisense inhibition of PKCα results in the reversal ofthe transformed phenotype in human lung carcinoma (LTEPa-2) cells. In this study, the amounts of PKCα protein and total PKC activity were decreased when compared to control cells. Sioud and Sorensen, 1998, Nature Biotechnology, 16, 556-561, describe hammerhead ribozyme inhibition of PKCα in rat glioma cell lines (BT4C and BT4Cn). This study demonsfrated inhibition of malignant glioma cell proliferation along with the inhibition of regulatory Bcl-x_L protein expression. BC1-XL is overexpressed in glioma cells and is an apoptosis inhibitor. The ribozyme mediated inhibition of cell proliferation presumably results from apoptosis induction of transformed glioma cells through suppression of PKCα and Bcl-x_L (Leirdal and Sioud, 1999, British J. of Cancer, 80, 1558- 1564). Animal Models

Evaluating the efficacy of anti-PKCα agents in animal models is an important prerequisite to human clinical trials. A variety of mouse xenograft models using human tumor cell lines have been developed using cell lines which express high levels of PKCα protein. McGraw et α/, 1997 ', Anti-Cancer Drug Design, 12, 315-326, describe mouse xenograft models using human breast (MDA MB-321), prostate (Du-145), colon (Colo 205, WiDr), lung (NCI H69, H209, J460, H520, A549), bladder (T-24), and melanoma (SK-mel 1) carcinoma cells. Antisense oligonucleotides targeting PKCα administered infravenously following s.c. transplanted tumor cells resulted in dose dependant decreases in tumor size when compared to confrols in most cases. Similar studies using T-24 bladder carcinoma, non-small cell lung carcinoma (A549), and Colo 205 colon carcinoma mouse xenografts are described in Dean et al, 1996, Biochemical Society Transactions, 24, 623. Sioud and Sorensen, 1998, Nature Biotechnology, 16, 556-561, describe a rat model in which inbred syngeneic BDLX rats were inoculated subcutaneously with BT4Cn glioma cells. After approximately three weeks, rats were freated with a single injection of ribozyme targeting PKCα resulting in inhibition of tumor growth as determined by tumor size and/or weight when compared to confrols. The above studies provide proof that inhibition of PKCα expression by anti-PKCα agents causes inhibition of tumor growth in animals. Lead anti-PKCα ribozymes chosen from in vitro assays can be further tested in mouse xenograft models. Ribozymes can be first tested alone and then in combination with standard chemotherapies. Animal Model Development

Human lung (A549, NCI H520) tumor and breast (MDA-MB 231) cell lines can be characterized to establish their growth curves in mice. These cell lines are been implanted into both nude and SCLD mice and primary tumor volumes are measured 3 times per week. Growth characteristics of these tumor lines using a Matrigel implantation format can also be established. In addition, the use of other cell lines that have been engineered to express high levels of PKCα can also be used. The tumor cell line(s) and implantation method that supports the most consistent and reliable tumor growth can be used in animal studies to test promising PKCα ribozyme(s). Ribozymes can be administered by daily subcutaneous injection or by continuous subcutaneous infusion from Alzet mini osmotic pumps beginning 3 days after tumor implantation and continuing for the duration ofthe study. Group sizes of at least 10 animals are employed. Efficacy is determined by statistical comparison of tumor volume of ribozyme-freated animals to a control group of animals freated with saline alone. Because the growth of these tumors is generally slow (45-60 days), an initial endpoint will be the time in days it takes to establish an easily measurable primary tumor (i.e. 50-100 mm³) in the presence or absence of ribozyme treatment. Clinical Summary Overview

Ribozymes targeting PKCα have strong potential to develop into useful therapeutics directed towards numerous cancer types. Lung cancer is the leading cause of cancer deaths for both men and women in the USA. The incidence of lung cancer in the United States is -172,000 cases per year, accounting for 14% of cancer diagnoses. Approximately 158,000 die each year of lung cancer, accounting for 28% of all cancer deaths. Numerous other indications exist including cancers ofthe bladder, colon, breast, prostate, and ovary in addition to melanoma and glioblastoma.

McGraw et α/., 1997 , Anti-Cancer Drug Design, 12, 315-326, describe a Phase I trial for ISIS 3521/CGP 64128A, a PKC alpha antisense construct. In this trial, ISIS 3521/CGP 64128A was administered as either a two-hour i.v. infusion three times per week for three consecutive weeks, or as a continuous i.v. infusion for twenty-one consecutive days. The authors report that patients demonstrated excellent tolerance to the antisense compound when administered at doses of up to 2.5 mg/kg by the two-hour i.v. infusion and at 1.5 mg/kg/day by continuous i.v. infusion. In patients receiving the two-hour i.v. infusion schedule, the post-infusion plasma concenfration ofthe compound increased proportional to the dose, and metabolites were determined to have been cleared rapidly from plasma with a half-life of thirty to forty- five minutes. These metabolites were composed of chain- shortened oligonucleotides, consistent with exonuclease-mediated degradation. No evidence of accumulation, induction, or inhibition of metabolism was found after the administration of repetitive doses. Therapy

Treatment options for lung cancer are determined by the type and stage ofthe cancer and include surgery, radiation therapy, and chemotherapy. For many localized cancers, surgery is usually the treatment of choice. Because the disease has usually spread by the time it is discovered, radiation therapy and chemotherapy are often needed in combination with surgery. Chemotherapy alone or combined with radiation has replaced surgery as the treatment of choice for small cell lung cancer; on this regimen, a large percentage of patients experience remission, which in some cases is long-lasting. The 1-year relative survival rates for lung cancer have increased from 32% in 1973 to 41% in 1994, largely due to improvements in surgical techniques. The 5-year relative survival rate for all stages combined is only 14%. The survival rate is 50% for cases detected when the disease is still localized, but only 15% of lung cancers are discovered that early.

Common chemotherapies include various combinations of cytotoxic drugs to kill the cancer cells. These drugs include paclitaxel (Taxol), docetaxel, cisplatin, methofrexate, cyclophosphamide, doxorubin, fluorouracil etc. Significant toxicities are associated with these cytotoxic therapies. Well-characterized toxicities include nausea and vomiting, myelosuppression, alopecia and mucosity. Serious cardiac problems are also associated with certain ofthe combinations, e.g. doxorubin and paclitaxel, but are less common.

Applicant has designed several NCH ribozymes targeted against PKCα RNA (Genebank accession No NM_002737) (see, for example, Table 63). These ribozymes are used first in a proliferation assay that is used to select ribozyme leads.

Proliferation assay: The model proliferation assay useful in the study can require a cell plating density of 2000 cells/well in 96-well plates and at least 2 cell doublings over a 5-day freatment period. To calculate cell density for proliferation assays, the FLPS (fluoro- imaging processing system) method well known in the art can be used. This method allows for cell density measurements after nucleic acids are stained with CyQuant® dye, and has the advantage of accurately measuring cell densities over a very wide range 1,000-100,000 cells/well in 96-well format.

Ribozymes (50-200 nM) are delivered in the presence of cationic lipid at 2.0 μg/mL and inhibition of proliferation is determined on day 5 post-treatment. Two full ribozyme screens are usually completed and lead ribozymes are chosen for further testing. Ofthe lead ribozymes chosen from primary screens, ribozymes which continue to inhibit cell proliferation in subsequent experiments are selected for PKCα RNA and protein inhibition studies.

Example 15: Nucleoside Triphosphates and their incoφoration into oligonucleotides

The synthesis of nucleotide triphosphates and their incoφoration into nucleic acids using polymerase enzymes has greatly assisted in the advancement of nucleic acid research. The polymerase enzyme utilizes nucleotide triphosphates as precursor molecules to assemble oligonucleotides. Each nucleotide is attached by a phosphodiester bond formed through nucleophilic attack by the 3' hydroxyl group ofthe oligonucleotide 's last nucleotide onto the 5' triphosphate ofthe next nucleotide. Nucleotides are incoφorated one at a time into the oligonucleotide in a 5' to 3' direction. This process allows RNA to be produced and amplified from virtually any DNA or RNA templates.

Most natural polymerase enzymes incoφorate standard nucleotide triphosphates into nucleic acid. For example, a DNA polymerase incoφorates dATP, dTTP, dCTP, and dGTP into DNA and an RNA polymerase generally incoφorates ATP, CTP, UTP, and GTP into RNA. There are however, certain polymerases that are capable of incoφorating non-standard nucleotide triphosphates into nucleic acids (Joyce, 1997, PNAS 94, 1619- 1622, Huang et al., Biochemistry 36, 8231-8242).

Before nucleosides can be incoφorated into RNA transcripts using polymerase enzymes they must first be converted into nucleotide triphosphates which can be recognized by these enzymes. Phosphorylation of unblocked nucleosides by treatment with POCl and trialkyl phosphates was shown to yield nucleoside 5'- phosphorodichloridates (Yoshikawa et al, 1969, Bull. Chem. Soc. (Japan) 42, 3505). Adenosine or 2'-deoxyadenosine 5 '-triphosphate was synthesized by adding an additional step consisting of freatment with excess tri-n-butylammonium pyrophosphate in DMF followed by hydrolysis (Ludwig, 1981, Acta Biochim. et Biophys. Acad. Sci. Hung. 16, 131-133).

Non-standard nucleotide triphosphates are not readily incoφorated into RNA transcripts by traditional RNA polymerases. Mutations have been introduced into RNA polymerase to facilitate incoφoration of deoxyribonucleotides into RNA (Sousa & Padilla, 1995, EMBO J. 14,4609-4621, Bonner et al, 1992, EMBO J. 11, 3767-3775, Bonner et al., 1994, J. Biol. Chem. 42, 25120-25128, Aurup et al, 1992, Biochemistry 31, 9636-9641).

McGee et al, International PCT Publication No. WO 95/35102, describes the incoφoration of 2'-NH₂-NTP's, 2'-F-NTP's, and 2'-deoxy-2'-benzyloxyamino UTP into RNA using bacteriophage T7 polymerase.

Wieczorek et al, 1994, Bioorganic & Medicinal Chemistry Letters A, 987-994, describes the incoφoration of 7-deaza-adenosine triphosphate into an RNA transcript using bacteriophage T7 RNA polymerase.

Lin et al, 1994, Nucleic Acids Research 22, 5229-5234, reports the incoφoration of 2'-NH₂-CTP and 2'-NH₂-UTP into RNA using bacteriophage T7 RNA polymerase and polyethylene glycol containing buffer. The article describes the use ofthe polymerase synthesized RNA for in vitro selection of aptamers to human neutrophil elastase (HNE).

This invention relates to novel nucleotide triphosphate (NTP) molecules, and their incoφoration into nucleic acid molecules, including nucleic acid catalysts. The NTPs of the instant invention are distinct from other NTPs known in the art. The invention further relates to incoφoration of these nucleotide triphosphates into oligonucleotides using an RNA polymerase; the invention further relates to novel transcription conditions for the incoφoration of modified (non-standard) and unmodified NTP's, into nucleic acid molecules. Further, the invention relates to methods for synthesis of novel NTP's

In a first aspect, the invention features NTP's having the formula triphosphate-OR, for example the following formula 3:

where R is any nucleoside; specifically the nucleosides 2'-O-methyl-2,6- diaminopurine riboside; 2'-deoxy-2'amino-2,6-diaminopurine riboside; 2'-(N-alanyl) amino-2'-deoxy-uridine; 2'-(N-phenylalanyl)amino-2'-deoxy-uridine; 2'-deoxy -2'-(N-β- alanyl) amino ; 2'-deoxy-2'-(lysiyl) amino uridine; 2'-C-allyl uridine; 2'-O-amino-uridine; 2'-O-methylthiomethyl adenosine; 2'-O-methylthiomethyl cytidine ; 2'-O- methylthiomethyl guanosine; 2'-O-methylthiomethyl-uridine; 2'-deoxy-2'-(N-histidyl) amino uridine; 2'-deoxy-2'-amino-5-methyl cytidine; 2'-(N-β-carboxamidine-β- alanyl)amino-2 ' -deoxy-uridine; 2 ' -deoxy-2 ' -(Ν- β -alanyl)-guanosine; 2 ' -O-amino- adenosine; 2'-(N-lysyl)amino-2'-deoxy-cytidine; 2'-Deoxy -2'-(L-histidine) amino Cytidine; 5-Imidazoleacetic acid 2'-deoxy uridine, 5-[3-(Ν-4- imidazoleacetyl)aminopropynyl] -2 '-O-methyl uridine, 5-(3-aminopropynyl)-2'-O-methyl uridine, 5-(3-aminopropyl)-2'-O-methyl uridine, 5-[3-(N-4-imidazoleacetyl)aminopropyl]- 2'-O-methyl uridine, 5-(3-aminopropyl)-2'-deoxy-2-fluoro uridine, 2'-Deoxy-2'-(β-alanyl- L-histidyl)amino uridine, 2'-deoxy-2'-β-alaninamido-uridine, 3 -(2 '-deoxy-2' -fluoro- β-D- ribofuranosyl)piperazino[2,3-D]pyrimidine-2-one, 5-[3-(N-4- imidazoleacetyl)aminopropyl]-2'-deoxy-2'-fluoro uridine, 5-[3-(N-4- imidazoleacetyl)aminopropynyl] -2 ' -deoxy-2 ' -fluoro uridine, 5 -E-(2-carbox yvinyl-2 ' - deoxy-2 '-fluoro uridine, 5-[3-(N-4-aspartyl)aminopropynyl-2'-fluoro uridine, 5-(3- aminopropyl)-2'-deoxy-2-fluoro cytidine, and 5-[3-(N-4-succynyl)aminopropyl-2'-deoxy- 2-fluoro cytidine.

In a second aspect, the invention features inorganic and organic salts ofthe nucleoside triphosphates ofthe instant invention. In a third aspect, the invention features a process for the synthesis of pyrimidine nucleotide triphosphate (such as UTP, 2'-O-MTM-UTP, dUTP and the like) including the steps of monophosphorylation where the pyrimidine nucleoside is contacted with a mixture having a phosphorylating agent (such as phosphorus oxychloride, phospho-tris-

5 triazolides, phospho-tris-triimidazolides and the like), trialkyl phosphate (such as triethylphosphate or trimethylphosphate or the like) and a hindered base (such as dimethylaminopyridine, DMAP and the like) under conditions suitable for the formation of pyrimidine monophosphate; and pyrophosphorylation where the pyrimidine monophosphate is contacted with a pyrophosphorylating reagent (such as

10 tributylammonium pyrophosphate) under conditions suitable for the formation of pyrimidine triphosphates.

By "nucleotide triphosphate" or "NTP" is meant a nucleoside bound to three inorganic phosphate groups at the 5' hydroxyl group ofthe modified or unmodified ribose or deoxyribose sugar where the 1 ' position ofthe sugar may comprise a nucleic acid base

15 or hydrogen. The triphosphate portion may be modified to include chemical moieties which do not destroy the functionality ofthe group (i.e., allow incoφoration into an RNA molecule).

In another prefeπed embodiment, nucleotide triphosphates (NTPs) ofthe instant invention are incoφorated into an oligonucleotide using an RNA polymerase enzyme.

!0 RNA polymerases include but are not limited to mutated and wild type versions of bacteriophage T7, SP6, or T3 RNA polymerases. Applicant has also found that the NTPs ofthe present invention can be incoφorated into oligonucleotides using certain DNA polymerases, such as Taq polymerase.

In yet another prefeπed embodiment, the invention features a process for

!5 incoφorating modified NTP's into an oligonucleotide including the step of incubating a mixture having a DNA template, RNA polymerase, NTP, and an enhancer of modified NTP incoφoration under conditions suitable for the incoφoration ofthe modified NTP into the oligonucleotide.

By "enhancer of modified NTP incoφoration" is meant a reagent which facilitates

SO the incoφoration of modified nucleotides into a nucleic acid transcript by an RNA polymerase. Such reagents include, but are not limited to, methanol, LiCl, polyethylene glycol (PEG), diethyl ether, propanol, methyl amine, ethanol, and the like. In another prefeπed embodiment, the modified nucleotide triphosphates can be incoφorated by franscription into a nucleic acid molecules including enzymatic nucleic acid, antisense, 2-5A antisense chimera, oligonucleotides, triplex forming oligonucleotide (TFO), aptamers and the like (Stull et al, 1995 Pharmaceutical Res. 12, 465). By "triplex forming oligonucleotides (TFO)" it is meant an oligonucleotide that can bind to a double-stranded DNA in a sequence-specific manner to form a triple-strand helix. Formation of such triple helix structure has been shown to inhibit transcription of the targeted gene (Duval- Valentin et al, 1992 Proc. Natl. Acad. Sci. USA 89, 504).

In yet another prefeπed embodiment, the modified nucleotide triphosphates ofthe instant invention can be used for combinatorial chemistry or in vitro selection of nucleic acid molecules with novel function. Modified oligonucleotides can be enzymatically synthesized to generate libraries for screening.

In another prefeπed embodiment, the invention features nucleic acid based techniques (e.g., enzymatic nucleic acid molecules), antisense nucleic acids, 2-5 A antisense chimeras, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups) isolated using the methods described in this invention and methods for their use to diagnose, down regulate or inhibit gene expression.

In yet another prefeπed embodiment, the invention features enzymatic nucleic acid molecules targeted against HER2 RNA, specifically including ribozymes in the class II (zinzyme) motif.

Targets, for example HER2 RNA, for useful ribozymes and antisense nucleic acids can be determined, for example, as described in Draper et al, WO 93/23569; Sullivan et al, WO 93/23057; Thompson et al, WO 94/02595; Draper et al, WO 95/04818; McSwiggen et al, US Patent Nos. 5,525,468 and 5,646,042, all are hereby incoφorated by reference herein in their totalities. Other examples include the following PCT applications, which concern inactivation of expression of disease-related genes: WO 95/23225, and WO 95/13380; all of which are incoφorated by reference herein.

In yet another prefeπed embodiment, the invention features a process for incoφorating a plurality of compounds of formula 3. In yet another embodiment, the invention features a nucleic acid molecule with catalytic activity having formula 4:

In the formula shown above X, Y, and Z represent independently a nucleotide or a non-nucleotide linker, which may be same or different; • indicates hydrogen bond formation between two adjacent nucleotides which may or may not be present; Y' is a nucleotide complementary to Y; Z' is a nucleotide complementary to Z; 1 is an integer greater than or equal to 3 and preferably less than 20, more specifically 4, 5, 6, 7, 8, 9, 10, 11, 12, or 15; m is an integer greater than 1 and preferably less than 10, more specifically 2, 3, 4, 5, 6, or 7; n is an integer greater than 1 and preferably less than 10, more specifically 3, 4, 5, 6, or 7; o is an integer greater than or equal to 3 and preferably less than 20, more specifically 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 15; 1 and o may be the same length (1 = o) or different lengths (1 ≠ o); each X(l) and X(o) are oligonucleotides which are of sufficient length to stably interact independently with a target nucleic acid sequence (the target can be an RNA, DNA or RNA/DNA mixed polymers); W is a linker of > 2 nucleotides in length or may be a non-nucleotide linker; A, U, C, and G represent the nucleotides; G is a nucleotide, preferably 2'-O-methyl or ribo; A is a nucleotide, preferably 2'-O-methyl or ribo; U is a nucleotide, preferably 2'-amino (e.g., 2'-NH₂ or 2'-O- NH₂), 2'-O-methyl or ribo; C represents a nucleotide, preferably 2'-amino (e.g., 2'-NH₂ or 2'-O- NH₂), and represents a chemical linkage (e.g. a phosphate ester linkage, amide linkage, phosphorothioate, phosphorodithioate or others known in the art).

In yet another embodiment, the invention features a nucleic acid molecule with catalytic activity having formula 5:

In the formula shown above X, Y, and Z represent independently a nucleotide or a non-nucleotide linker, which may be same or different; • indicates hydrogen bond formation between two adjacent nucleotides which may or may not be present; Z' is a nucleotide complementary to Z; 1 is an integer greater than or equal to 3 and preferably less than 20, more specifically 4, 5, 6, 7, 8, 9, 10, 11, 12, or 15; n is an integer greater than 1 and preferably less than 10, more specifically 3, 4, 5, 6, or 7; o is an integer greater than or equal to 3 and preferably less than 20, more specifically 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or

15; 1 and o may be the same length (1 = o) or different lengths (1 ≠ o); each Xm and X(_o) are oligonucleotides which are of sufficient length to stably interact independently with a target nucleic acid sequence (the target can be an RNA, DNA or RNA/DNA mixed polymers); preferably has a G at the 3 '-end, XQ) preferably has a G at the 5 '-end; W is a linker of ≥ 2 nucleotides in length or may be a non-nucleotide linker; Y is a linker of > 1 nucleotides in length, preferably G, 5' -CA-3', or 5' -CAA-3', or may be a non-nucleotide linker; A, U, C, and G represent nucleotides; G is a nucleotide, preferably 2'-O-methyl, 2'-deozy-2'-fluoro, or 2'-OH; A is a nucleotide, preferably 2'-O-methyl, 2'-deozy-2'- fluoro, or 2'-OH; U is a nucleotide, preferably 2'-O-methyl, 2 '-deozy-2' -fluoro, or 2'-OH;

C represents a nucleotide, preferably 2'-amino (e.g., 2'-NH₂ or 2'-O- NH₂, and represents a chemical linkage (e.g. a phosphate ester linkage, amide linkage, phosphorothioate, phosphorodithioate or others known in the art). The enzymatic nucleic acid molecules of Formula 4 and Formula 5 may independently comprise a cap structure which may independently be present or absent.

In yet another prefeπed embodiment, the 3 '-cap is selected from a group comprising,

4',5'-methylene nucleotide; l-(beta-D-erythrofuranosyl) nucleotide; 4'-thio nucleotide; carbocyclic nucleotide; 5'-amino-alkyl phosphate; l,3-diamino-2-propyl phosphate; 3- aminopropyl phosphate; 6-aminohexyl phosphate; 1,2-aminododecyl phosphate; hydroxypropyl phosphate; 1,5-anhydrohexitol nucleotide; L-nucleotide; alpha-nucleotide; modified base nucleotide; phosphorodithioate; tΛreo-pentofuranosyl nucleotide; acyclic

3',4'-seco nucleotide; 3,4-dihydroxybutyl nucleotide; 3,5-dihydroxypentyl nucleotide; 5'-5'- inverted nucleotide moiety; 5'-5'-inverted abasic moiety; 5'-phosphoramidate; 5'- phosphorothioate; 1,4-butanediol phosphate 5'-amino; bridging and/or non-bridging 5'- phosphoramidate, phosphorothioate and/or hosphorodithioate; bridging or non bridging methylphosphonate and 5'-mercapto moieties (for more details, see Beaucage and Iyer,

1993, Tetrahedron 49, 1925; incoφorated by reference herein).

In another aspect, the invention provides mammalian cells containing one or more nucleic acid molecules and/or expression vectors of this invention. The one or more nucleic acid molecules may independently be targeted to the same or different sites.

Nucleotide Synthesis

Addition of dimethylaminopyridine (DMAP) to the phosphorylation protocols known in the art can greatly increase the yield of nucleotide monophosphates while decreasing the reaction time. Synthesis ofthe nucleosides ofthe invention have been described in several publications and Applicants previous applications (Beigelman et al, Intemational PCT publication No. WO 96/18736; Dudzcy et al, Int. PCT Pub. No. WO 95/11910; Usman et al, Int. PCT Pub. No. WO 95/13378; Matulic-Adamic et al, 1997, Tetrahedron Lett. 38, 203; Matulic-Adamic et al, 1997, Tetrahedron Lett. 38, 1669; all of which are incoφorated herein by reference). These nucleosides are dissolved in triethyl phosphate and chilled in an ice bath. Phosphorus oxychloride (POCl₃) is then added followed by the introduction of DMAP. The reaction is then warmed to room temperature and allowed to proceed for 5 hours. This reaction allows the formation of nucleotide monophosphates which can then be used in the formation of nucleotide triphosphates. Tributylamine is added followed by the addition of anhydrous acetonitrile and tributylammonium pyrophosphate. The reaction is then quenched with TEAB and stiπed overnight at room temperature (about 20°C). The triphosphate is purified using Sephadex® column purification or equivalent and/or HPLC and the chemical structure is confirmed using NMR analysis. Those skilled in the art will recognize that the reagents, temperatures ofthe reaction, and purification methods can easily be alternated with substitutes and equivalents and still obtain the desired product.

Nucleotide Triphosphates

The invention provides nucleotide triphosphates which can be used for a number of different functions. The nucleotide triphosphates formed from nucleosides found in Table 45 are unique and distinct from other nucleotide triphosphates known in the art.

Incoφoration of modified nucleotides into DNA or RNA oligonucleotides can alter the properties ofthe molecule. For example, modified nucleotides can hinder binding of nucleases, thus increasing the chemical half-life ofthe molecule. This is especially important if the molecule is to be used for cell culture or in vivo. It is known in the art that the introduction of modified nucleotides into these molecules can greatly increase the stability and thereby the effectiveness ofthe molecules (Burgin et al, 1996, Biochemistry 35, 14090-14097; Usman et al, 1996, Curr. Opin. Struct. Biol. 6, 527-533).

Modified nucleotides are incoφorated using either wild type or mutant polymerases. For example, mutant T7 polymerase is used in the presence of modified nucleotide triphosphate(s), DNA template and suitable buffers. Those skilled in the art will recognize that other polymerases and their respective mutant versions can also be utilized for the incoφoration of NTP's ofthe invention. Nucleic acid transcripts were detected by incoφorating radiolabelled nucleotides (α-³²P NTP). The radiolabeled NTP contained the same base as the modified triphosphate being tested. The effects of methanol, PEG and LiCl were tested by adding these compounds independently or in combination. Detection and quantitation ofthe nucleic acid transcripts was performed using a Molecular Dynamics Phosphorlmager. Efficiency of franscription was assessed by comparing modified nucleotide triphosphate incoφoration with all-ribonucleotide incoφoration control. Wild- type polymerase was used to incoφorate NTP's using the manufacturer's buffers and instructions (Boehringer Mannheim).

Transcription Conditions

Incoφoration rates of modified nucleotide triphosphates into oligonucleotides can be increased by adding to traditional buffer conditions, several different enhancers of modified NTP incoφoration. Applicant has utilized methanol and LiCl in an attempt to increase incoφoration rates of dNTP using RNA polymerase. These enhancers of modified NTP incoφoration can be used in different combinations and ratios to optimize transcription. Optimal reaction conditions differ between nucleotide triphosphates and can readily be determined by standard experimentation. Overall, however, Applicant has found that inclusion of enhancers of modified NTP incoφoration such as methanol or inorganic compound such as lithium chloride increase the mean transcription rates. Applicant synthesized pyrimidine nucleotide triphosphates using DMAP in the reaction. For purines, applicant utilized standard protocols previously described in the art (Yoshikawa et al supra;. Ludwig, supra). Described below is one example of a pyrimdine nucleotide triphosphate and one purine nucleotide triphosphate synthesis.

Synthesis of purine nucleotide triphosphates: 2'-O-methyl-guanosine-5 '-triphosphate

2'-O-methyl guanosine nucleoside (0.25 grams, 0.84 mmol) was dissolved in triethyl phosphate (5.0) ml by heating to 100°C for 5 minutes. The resulting clear, colorless solution was cooled to 0°C using an ice bath under an argon atmosphere. Phosphorous oxychloride (1.8 eq., 0.141 ml) was then added to the reaction mixture with vigorous stirring. The reaction was monitored by HPLC, using a sodium perchlorate gradient. After 5 hours at 0°C, tributylamine (0.65 ml) was added followed by the addition of anhydrous acetonitrile (10.0 ml), and after 5 minutes (reequilibration to 0°C) tributylammonium pyrophosphate (4.0 eq., 1.53 g) was added. The reaction mixture was quenched with 20 ml of 2M TEAB after 15 minutes at 0°C (HPLC analysis with above conditions showed consumption of monophosphate at 10 minutes) then stiπed overnight at room temperature, the mixture was evaporated in vacuo with methanol co-evaporation (4x) then diluted in 50 ml 0.05M TEAB. DEAE sephadex purification was used with a gradient of 0.05 to 0.6 M TEAB to obtain pure triphosphate (0.52 g, 66.0% yield) (elutes around 0.3M TEAB); the purity was confirmed by HPLC and NMR analysis.

Synthesis of Pyrimidine nucleotide triphosphates: 2'-O-methylthiomethyl-uridine-5'- triphosphate

2'-O-methylthiomethyl uridine nucleoside (0.27 grams, 1.0 mmol) was dissolved in triethyl phosphate (5.0 ml). The resulting clear, colorless solution was cooled to 0°C with an ice bath under an argon atmosphere. Phosphorus oxychloride (2.0 eq., 0.190 ml) was then added to the reaction mixture with vigorous stirring. Dimethylaminopyridine

(DMAP, 0.2eq., 25 mg) was added, the solution warmed to room temperature and the reaction was monitored by HPLC, using a sodium perchlorate gradient. After 5 hours at 20°C, tributylamine (1.0 ml) was added followed by anhydrous acetonitrile (10.0 ml), and after 5 minutes tributylammonium pyrophosphate (4.0 eq., 1.8 g) was added. The reaction mixture was quenched with 20 ml of 2M TEAB after 15 minutes at 20°C (HPLC analysis with above conditions showed consumption of monophosphate at 10 minutes) then stiπed overnight at room temperature. The mixture was evaporated in vacuo with methanol co- evaporation (4x) then diluted in 50 ml 0.05M TEAB. DEAE fast flow Sepharose purification with a gradient of 0.05 to 1.0 M TEAB was used to obtain pure triphosphate (0.40 g, 44%) yield) (elutes around 0.3M TEAB) as determined by HPLC and NMR analysis.

Utilization of DMAP in Uridine 5 '-Triphosphate Synthesis

The reactions were performed on 20 mg aliquots of nucleoside dissolved in 1 ml of triethyl phosphate and 19 ul of phosphorus oxychloride. The reactions were monitored at 40 minute intervals automatically by HPLC to generate yield-of-product curves at times up to 18 hours. A reverse phase column and ammonium acetate/ sodium acetate buffer system (50mM & lOOmM respectively at pH 4.2) was used to separate the 5', 3', 2' monophosphates (the monophosphates elute in that order) from the 5 '-triphosphate and the starting nucleoside. The data is shown in Table 46. These conditions doubled the product yield and resulted in a 10-fold improvement in the reaction time to maximum yield (1200 minutes down to 120 minutes for a 90%> yield). Selectivity for 5'-monophosphorylation was observed for all reactions. Subsequent triphosphorylation occuπed in nearly quantitative yield.

Materials Used in Bacteriophage T7 RNA Polymerase Reactions Buffer 1: Reagents are mixed together to form a 10X stock solution of buffer 1

(400 mM Tris-Cl [pH 8.1], 200 mM MgCl₂, 100 mM DTT, 50 mM spermidine, and 0.1% triton® X-100). Prior to initiation ofthe polymerase reaction methanol, LiCl is added and the buffer is diluted such that the final reaction conditions for condition 1 consisted of : 40mM tris (pH 8.1), 20mM MgCl₂, 10 mM DTT, 5 mM spermidine, 0.01% triton® X- 100, 10% methanol, and 1 mM LiCl.

BUFFER 2: Reagents are mixed together to form a 10X stock solution of buffer 2 (400 mM Tris-Cl [pH 8.1], 200 mM MgCl₂, 100 mM DTT, 50 mM spermidine, and 0.1% triton® X-100). Prior to initiation ofthe polymerase reaction PEG, LiCl is added and the buffer is diluted such that the final reaction conditions for buffer 2 consisted of : 40mM tris (pH 8.1), 20mM MgCl₂, 10 mM DTT, 5 mM spermidine, 0.01% triton® X-100, 4% PEG, and 1 mM LiCl.

BUFFER 3: Reagents are mixed together to form a 10X stock solution of buffer 3 (400 mM Tris-Cl [pH 8.0], 120 mM MgCl₂, 50 mM DTT, 10 mM spermidine and 0.02% triton® X-100). Prior to initiation ofthe polymerase reaction PEG is added and the buffer is diluted such that the final reaction conditions for buffer 3 consisted of : 40mM tris (pH 8.0), 12 mM MgCl₂, 5 mM DTT, 1 mM spermidine, 0.002% triton® X-100, and 4% PEG.

BUFFER 4: Reagents are mixed together to form a 10X stock solution of buffer 4 (400 mM Tris-Cl [pH 8.0], 120 mM MgCl₂, 50 mM DTT, 10 mM spermidine and 0.02% triton® X-100). Prior to initiation ofthe polymerase reaction PEG, methanol is added and the buffer is diluted such that the final reaction conditions for buffer 4 consisted of :

40mM tris (pH 8.0), 12 mM MgCl₂, 5 mM DTT, 1 mM spermidine, 0.002% triton® X- 100, 10% methanol, and 4%> PEG.

BUFFER 5: Reagents are mixed together to form a 10X stock solution of buffer 5 (400 mM Tris-Cl [pH 8.0], 120 mM MgCl₂, 50 mM DTT, 10 mM spermidine and 0.02% triton® X-100). Prior to initiation ofthe polymerase reaction PEG, LiCl is added and the buffer is diluted such that the final reaction conditions for buffer 5 consisted of : 40mM tris (pH 8.0), 12 mM MgCl₂, 5 mM DTT, 1 mM spermidine, 0.002% triton® X-100, 1 mM LiCl and 4% PEG.

BUFFER 6: Reagents are mixed together to form a 10X stock solution of buffer 6 (400 mM Tris-Cl [pH 8.0], 120 mM MgCl₂, 50 mM DTT, 10 mM spermidine and 0.02% triton® X-100). Prior to initiation ofthe polymerase reaction PEG, methanol is added and the buffer is diluted such that the final reaction conditions for buffer 6 consisted of : 40mM tris (pH 8.0), 12 mM MgCl₂, 5 mM DTT, 1 mM spermidine, 0.002% triton® X- 100, 10% methanol, and 4% PEG.

BUFFER 7: Reagents are mixed together to form a 10X stock solution of buffer 6 (400 mM Tris-Cl [pH 8.0], 120 mM MgCl₂, 50 mM DTT, 10 mM spermidine and 0.02% triton® X-100). Prior to initiation ofthe polymerase reaction PEG, methanol and LiCl is added and the buffer is diluted such that the final reaction conditions for buffer 6 consisted of : 40mM tris (pH 8.0), 12 mM MgCl₂, 5 mM DTT, 1 mM spermidine, 0.002% triton® X-100, 10% methanol, 4% PEG, and 1 mM LiCl.

Screening of Modified nucleotide triphosphates with Mutant T7 RNA Polymerase

Modified nucleotide triphosphates were tested in buffers 1 through 6 at two different temperatures (25 and 37°C). Buffers 1-6 tested at 25°C were designated conditions 1-6 and buffers 1-6 tested at 37°C were designated conditions 7-12 (Table 47). In each condition, Y639F mutant T7 polymerase (Sousa and Padilla, supra) (0.3-2 mg/20 ml reaction), NTP's (2 mM each), DNA template (10 pmol), inorganic pyrophosphatase (5U/ml) and α-³²P NTP (0.8 mCi/pmol template) were combined and heated at the designated temperatures for 1-2 hours. The radiolabeled NTP used was different from the modified triphosphate being testing. The samples were resolved by polyacrylamide gel elecfrophoresis. Using a Phosphorhnager (Molecular Dynamics, Sunnyvale, CA), the amount of full-length transcript was quantified and compared with an all-RNA confrol reaction. The data is presented in Table 48; results in each reaction are expressed as a percent compared to the all-ribonucleotide triphosphate (rNTP) control. The confrol was run with the mutant T7 polymerase using commercially available polymerase buffer (Boehringer Mannheim, Indianapolis, LN). Incoφoration of Modified NTP's using Wild-type T7 RNA polymerase

Bacteriophage T7 RNA polymerase was purchased from Boehringer Mannheim at 0.4 U/μL concentration. Applicant used the commercial buffer supplied with the enzyme and 0.2 μCi alpha-³²P NTP in a 50 μL reaction with nucleotides triphosphates at 2 mM each. The template was a double-stranded PCR fragment, which was used in previous screens. Reactions were carried out at 37°C for 1 hour. Ten μL ofthe sample was run on a 7.5%o analytical PAGE and bands were quantitated using a Phosphorhnager. Results are calculated as a comparison to an "all ribo" control (non-modified nucleotide triphosphates) and the results are in Table 49. Incoφoration of Multiple Modified nucleotide triphosphates Into Oligonucleotides Combinations of modified nucleotide triphosphates were tested with the transcription protocol described above, to determine the rates of incoφoration of two or more of these triphosphates. Incoφoration of 2 '-Deoxy-2 '-(L-histidine) amino uridine (2'- his-NH₂-UTP) was tested with unmodified cytidine nucleotide triphosphates, rATP and rGTP in reaction condition number 9. The data is presented as a percentage of incoφoration of modified NTP's compared to the all rNTP control and is shown in Table 50a.

Two modified cytidines (2'-NH₂-CTP or 2'dCTP) were incoφorated along with 2'- his-NH₂-UTP with identical efficiencies. 2'-his-NH₂-UTP and 2'-NH₂-CTP were then tested with various unmodified and modified adenosine triphosphates in the same buffer (Table 50b). The best modified adenosine triphosphate for incoφoration with both 2'-his- NH₂-UTP and 2'-NH₂-CTP was 2'-NH₂-DAPTP.

Optimization of Reaction conditions for Incoφoration of Modified Nucleotide Triphosphate

The combination of 2'-his-NH₂-UTP, 2'-NH₂-CTP, 2'-NH₂-DAP, and rGTP was tested in several reaction conditions (Table 51) using the incoφoration protocol described above. The results demonstrate that ofthe buffer conditions tested, incoφoration of these modified nucleotide triphosphates occur in the presence of both methanol and LiCl. Selection of Novel Enzymatic nucleic acid molecule Motifs using 2'-deoxy-2'amino Modified GTP and CTP

For selection of new enzymatic nucleic acid molecule motifs, pools of enzymatic nucleic acid molecules were designed to have two substrate binding arms (5 and 16 nucleotides long) and a random region in the middle. The subsfrate has a biotin on the 5' end, 5 nucleotides complementary to the short binding arm ofthe pool, an unpaired G (the desired cleavage site), and 16 nucleotides complementary to the long binding arm ofthe pool. The subsfrate was bound to column resin through an avidin-biotin complex. The general process for selection is shown in Figure 11. The protocols described below represent one possible method that may be utilized for selection of enzymatic nucleic acid molecules and are given as a non-limiting example of enzymatic nucleic acid molecule selection with combinatorial libraries.

Construction of Libraries: The oligonucleotides listed below were synthesized by Operon Technologies

(Alameda, CA). Templates were gel purified and then run through a Sep-Pak™ cartridge

(Waters, Millford, MA) using the manufacturers protocol. Primers (MST3, MST7c,

MST3del) were used without purification.

Primers: MST3 (30 mer): 5'- CAC TTA GCA TTA ACC CTC ACT AAA GGC CGT-3'

MST7c (33 mer): 5'-TAA TAC GAC TCA CTA TAG GAA AGG TGT GCA ACC-3'

MST3del (18 mer): 5'-ACC CTC ACT AAA GGC CGT-3'

Templates:

MSN60c (93 mer): 5'-ACC CTC ACT AAA GGC CGT (N)₆₀ GGT TGC ACA CCT TTG-3'

MSN40c (73 mer): 5'-ACC CTC ACT AAA GGC CGT (N)₄₀ GGT TGC ACA CCT

TTG-3'

MSN20c (53 mer): 5'-ACC CTC ACT AAA GGC CGT (N)₂₀ GGT TGC ACA CCT

TTG-3' N60 library was constructed using MSN60c as a template and MST3/MST7c as primers. N40 and N20 libraries were constructed using MSN40c (or MSN20c) as template and MST3del/MST7c as primers. Single-stranded templates were converted into double-sfranded DNA by the following protocol: 5 nmol template, 10 nmol each primer, in 10 ml reaction volume using standard PCR buffer, dNTP's, and taq DNA polymerase (all reagents from Boerhinger Mannheim). Synthesis cycle conditions were 94°C, 4 minutes; (94°C, 1 minute; 42°C, 1 minute; 72°C, 2 minutes) x 4; 72°C, 10 minutes. Products were checked on agarose gel to confirm the length of each fragment (N60=123 bp, N40=91 bp, N20=71 bp) and then were phenol/chloroform extracted and ethanol precipitated. The concenfration ofthe double-sfranded product was 25 μM.

Transcription ofthe initial pools was performed in a 1 ml volume comprising: 500 pmol double-sfranded template (3 x IO¹⁴ molecules), 40 mM tris-HCl (pH 8.0), 12 mM MgCl₂, 1 mM spermidine, 5 mM DTT, 0.002% triton X-100, 1 mM LiCl, 4% PEG 8000, 10% methanol, 2 mM ATP (Pharmacia), 2 mM GTP (Pharmacia), 2 mM 2'-deoxy-2'- amino-CTP (USB), 2 mM 2' -deoxy-2 '-amino-UTP (USB), 5 U/ml inorganic pyrophosphatase (Sigma), 5 U/μl T7 RNA polymerase (USB; Y639F mutant was used in some cases at 0.1 mg/ml (Sousa and Padilla, supra)), 37°C, 2 hours. Transcribed libraries were purified by denaturing PAGE (N60=106 ntds, N40=74, N20=54) and the resulting product was desalted using Sep-Pak™ columns and then ethanol precipitated.

Initial column-Selection: The following biotinylated substrate was synthesized using standard protocols

(Usman et al, 1987 J. Am. Chem. Soc, 109, 7845; Scaringe et al, 1990 Nucleic Acids Res., 18, 5433; and Wincott et al, 1995 Nucleic Acids Res. 23, 2677-2684):

5'-biotin-C18 spacer-GCC GUG GGU UGC ACA CCU UUC C-C18 spacer-thiol- modifier C6 S-S-inverted abasic-3' Subsfrate was purified by denaturing PAGE and ethanol precipitated. 10 nmol of subsfrate was linked to a NeutrAvidin™ column using the following protocol: 400 μl UlfraLink Immobilized NeutrAvidin™ slurry (200 μl beads, Pierce, Rockford, LL) were loaded into a polystyrene column (Pierce). The column was washed twice with 1 ml of binding buffer (20 mM NaPO₄ (pH 7.5), 150 mM NaCl) and then capped off (i.e., a cap was put on the bottom ofthe column to stop the flow). 200 μl ofthe subsfrate suspended in binding buffer was applied and allowed to incubate at room temperature for 30 minutes with occasional vortexing to ensure even linking and distribution ofthe solution to the resin. After the incubation, the cap was removed and the column was washed with 1 ml binding buffer followed by 1 ml column buffer (50 mM tris-HCL (pH 8.5), 100 mM NaCl, 50 mM KC1). The column was then ready for use and capped off. 1 nmol ofthe initial pool RNA was loaded on the column in a volume of 200 μl column buffer. It was allowed to bind the substrate by incubating for 30 minutes at room temperature with occasional vortexing. After the incubation, the cap was removed and the column was washed twice with 1 ml column buffer and capped off. 200 μl of elution buffer (50 mM tris-HCl (pH 8.5), 100 mM NaCl, 50 mM KC1, 25 mM MgCl₂) was applied to the column followed by 30 minute incubation at room temperature with occasional vortexing. The cap was removed and four 200 μl fractions were collected using elution buffer.

Second column (counter selection):

A diagram for events in the second column is generally shown in Figure 12 and subsfrate oligonucleotide used is shown below:

5'-GGU UGC ACA CCU UUC C-C18 spacer-biotin-inverted abasic-3' This column subsfrate was linked to UltraLink NeutrAvidin™ resin as previously described (40 pmol) which was washed twice with elution buffer. The eluent from the first column purification was then run on the second column. The use of this column allowed for binding of RNA that non-specifically diluted from the first column, while RNA that performed a catalytic event and had product bound to it, flowed through the second column. The fractions were ethanol precipitated using glycogen as carrier and rehydrated in sterile water for amplification.

Amplification:

RNA and primer MST3 (10-100 pmol) were denatured at 90°C for 3 minutes in water and then snap-cooled on ice for one minute. The following reagents were added to the tube (final concentrations given): IX PCR buffer (Boerhinger Mannheim), 1 mM dNTP's (for PCR, Boerhinger Mannheim), 2 U/μl RNase-Inhibitor (Boerhinger Mannheim), 10 U/μl Superscript™ LI Reverse Transcriptase (BRL). The reaction was incubated for 1 hour at 42°C, then at 95 °C for 5 minutes in order to destroy the Superscript™. The following reagents were then added to the tube to increase the volume five-fold for the PCR step (final concentrations/amounts given): MST7c primer (10-100 pmol, same amount as in RT step), IX PCR buffer, taq DNA polymerase (0.025-0.05 U/μl, Boerhinger Mannheim). The reaction was cycled as follows: 94°C, 4minutes; (94°C, 30s; 42-54°C, 30s; 72°C, lminute) x 4-30 cycles; 72°C, 5minutes; 30°C, 30 minutes. Cycle number and annealing temperature were decided on a round by round basis. In cases where heteroduplex was observed, the reaction was diluted five-fold with fresh reagents and allowed to progress through 2 more amplification cycles. Resulting products were analyzed for size on an agarose gel (N60=123 bp, N40=103 bp, N20=83 bp) and then ethanol precipitated.

Transcriptions:

Transcription of amplified products was done using the conditions described above with the following modifications: 10-20% ofthe amplification reaction was used as template, reaction volume was 100-500 μl, and the products sizes varied slightly (N60=106 ntds, N40=86, N20=66). A small amount of ³²P-GTP was added to the reactions for quantitation puφoses.

Subsequent rounds: Subsequent rounds of selection used 20 pmols of input RNA and 40 pmol ofthe 22 nucleotide substrate on the column.

Activity of pools:

Pools were assayed for activity under single turnover conditions every three to four rounds. Activity assay conditions were as follows: 50 mM tris-HCl (pH 8.5), 25 mM MgCl₂, 100 mM NaCl, 50 mM KC1, trace ³²P-labeled substrate, 10 nM RNA pool. 2X pool in buffer and, separately, 2X substrate in buffer were incubated at 90°C for 3 minutes, then at 37°C for 3 minutes. Equal volume 2X subsfrate was then added the 2X pool tube (t=0). Initial assay time points were taken at 4 and 24 hours: 5 μl was removed and quenched in 8 μl cold Stop buffer (96% formamide, 20 mM EDTA, 0.05% bromphenyl blue/xylene cyanol). Samples were heated 90°C, 3 minutes, and loaded on a 20% sequencing gel. Quantitation was performed using a Molecular Dynamics Phosphorimager and ImageQuaNT™ software. The data is shown in Table 52.

Samples from the pools of oligonucleotide were cloned into vectors and sequenced using standard protocols (Sambrook et al, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press). The enzymatic nucleic acid molecules were transcribed from a representative number of these clones using methods described in this application. Individuals from each pool were tested for RNA cleavage from N60 and N40 by incubating the enzymatic nucleic acid molecules from the clones with 5/16 substrate in 2mM MgC12, pH 7.5, lOmM KCl at 37°C. The data in Table 54 shows that the enzymatic nucleic acid molecules isolated from the pool are individually active.

Kinetic Activity:

Kinetic activity ofthe enzymatic nucleic acid molecule shown in Table 54, was determined by incubating enzymatic nucleic acid molecule (10 nM) with substrate in a cleavage buffer (pH 8.5, 25 mM MgCl₂, 100 mM NaCl, 50 mM KCl) at 37°C.

Magnesium Dependence:

Magnesium dependence of round 15 of N20 was tested by varying MgCl₂ while other conditions were held constant (50 mM tris [pH 8.0], 100 mM NaCl, 50 mM KCl, single turnover, 10 nM pool). The data is shown in Table 55, which demonstrates increased activity with increased magnesium concentrations.

Selection of Novel Enzymatic nucleic acid molecule Motifs using 2 '-Deoxy-2 '-(N- histidyl) amino UTP. 2 '-Fluoro- ATP, and 2'-deoxy-2'-amino CTP and GTP The method used for selection of novel enzymatic nucleic acid molecule motifs using 2 '-deoxy-2 'amino modified GTP and CTP was repeated using 2'-Deoxy-2'-(N- histidyl) amino UTP, 2'-Fluoro-ATP, and 2 '-deoxy-2 '-amino CTP and GTP. However, rather than causing cleavage on the initial column with MgCl₂, the initial random modified-RΝA pool was loaded onto substrate-resin in the following buffer; 5 mM ΝaOAc pH 5.2, 1 M ΝaCl at 4° C. After ample washing, the resin was moved to 22 ° C and the buffer switch 20 mM HEPES pH 7.4, 140 mM KCl, 10 mM ΝaCl, 1 mM CaCl₂, 1 mM MgCl₂. In one selection of Ν60 oligonucleotides, no divalent cations (MgCl₂, CaCl₂) was used. The resin was incubated for 10 minutes to allow reaction and the eluant collected.

The enzymatic nucleic acid molecule pools were capable of cleaving l-3%> ofthe present subsfrate even in the absence of divalent cations, the background (in the absence of modified pools) was 0.2 - 0.4 %.

Synthesis of 5-substituted 2^,-modified nucleosides

When designing monomeric nucleoside triphosphates for selection of therapeutic catalytic RNAs, one has to take into account nuclease stability of such molecules in biological sera. A common approach to increase RNA stability is to replace the sugar 2'- OH group with other groups like 2'-fluoro, 2'-O-methyl or 2'-amino. Fortunately such 2'- modified pyrimidine 5 'triphosphates are shown to be subsfrates for RNA polymerases. (Aurup, H.; Williams, D.M.; Eckstein, F. Biochemistry 1992, 57, 9637; and Padilla, R.; Sousa, R. Nucleic Acids Res. 1999, 27, 1561.) On the other hand it was shown that variety of substituents at pyrimidine 5-position is well tolerated by T7 RNA polymerase (Tarasow, T.M.; Eaton, B.E. Biopolymers 1998, 48, 29), most likely because the natural hydrogen-bonding pattern of these nucleotides is preserved. We have chosen 2'-fluoro and 2'-O-methyl pyrimidine nucleosides as starting materials for attachment of different functionalities to the 5-position ofthe base. Both rigid (alkynyl) and flexible (alkyl) spacers are used. The choice of imidazole, amino and carboxylate pendant groups is based on their ability to act as general acids, general bases, nucleophiles and metal ligands, all of which can improve the catalytic effectiveness of selected nucleic acids. Figures 21 - 24 relate to the synthesis of these compounds.

2'-O-methyluridine was 3',5'-bis-acetylated using acetic anhydride in pyridine and then converted to its 5-iodo derivative la using ceric ammonium nitrate reagent

(Asakura, J.; Robins, M.J. J. Org. Chem. 1990, 55, 4928) (Scheme 1). Both reactions proceeded in a quantitative yield and no chromatographic purifications were needed. Coupling between 1 and N-trifluoroacetyl propargylamine using copper(I) iodide and tefrakis(triphenylphosphine)palladium(0) catalyst as described by Hobbs (Hobbs, F.W., Jr. J. Org. Chem. 1989, 54, 3420) yielded 2a in 89% yield. Selective O-deacylation with aqueous ΝaOH afforded 3a which was phosphorylated with POClβ/triethylphosphate (TEP) in the presence of l,8-bis(dimethylamino)naphthalene (Proton-Sponge) (Method A) (Kovacz, T; Otvδs, L. Tetrahedron Lett. 1988, 29, 4525). The intermediate nucleoside phosphorodichloridate was condensed in situ with tri-n-butylammonium pyrophosphate. At the end, the N-TFA group was removed with concentrated ammonia. 5'- Triphosphate was purified on Sephadex® DEAE A-25 ion exchange column using a linear gradient of 0.1-0.8M triethylammonium bicarbonate (TEAB) for elution. Traces of contaminating inorganic pyrophosphate are removed using C-18 RP HPLC to afford analytically pure material. Conversion into Νa-salt was achieved by passing the aqueous solution of triphosphate through Dowex 50WX8 ion exchange resin in Νa⁺ form to afford 4a in 45% yield. When Proton-Sponge was omitted in the first phosphorylation step, yields were reduced to 10-20%. Catalytic hydrogenation of 3a yielded 5-aminopropyl derivative 5a which was phosphorylated under conditions identical to those described for propynyl derivative 3a to afford triphosphate 6a in 50% yield.

For the preparation of imidazole derivatized triphosphates 9a and Ila, we developed an efficient synthesis of N-diphenylcarbamoyl 4-imidazoleacetic acid (ImAA^DPC): Transient protection of carboxyl group as TMS-ester using TMS- Cl/pyridine followed by DPC-C1 allowed for a clean and quantitative conversion of 4- imidazoleacetic acid (LmAA) to its N-DPC protected derivative.

Complete deacylation of 2a afforded 5-(3-aminopropynyl) derivative 8a which was condensed with 4-imidazoleacetic acid in the presence of 1 -(3- dimethylaminopropyl)-3-ethylcarbodiimide (EDC) to afford 9a in 68% yield. Catalytic hydrogenation of 8a yielded 5-(3-aminopropyl) derivative 10a which was condensed with ImAA^DPC to yield conjugate Ila in 32% yield. Yields in these couplings were greatly improved when 5' -OH was protected with DMT group (not shown) thus efficientlypreventing undesired 5 '-O-esterification. Both 9a and Ila failed to yield triphosphate products in reaction with POCl_β/TEP/Proton-Sponge.

On the contrary, phosphorylation of 3'-O-acetylated derivatives 12a and 13a using 2-chloro-4H-l,3,2-benzodioxaphosphorin-4-one followed by pyrophosphate addition and oxidation (Method B, Scheme 2; Ludwig, J., Eckstein, F., J. Org. Chem. 1989, 54, 631) afforded the desired triphosphates 14a and 15a in 57% yield, respectively. 2 '-Deoxy-2 '-fluoro nucleoside 5 '-triphosphates containing amino- (4b, 6b) and imidazole- (14b, 15b) linked groups were synthesized in a manner analogous to that described for the preparation of 2'-O-methyl nucleoside 5 '-triphosphates (Schemes 1 and 2). Again, only Ludwig-Eckstein's phosphorylation worked for the preparation of 4- imidazoleacetyl derivatized triphosphates.

It is worth noting that when "one-pot-two-steps" phosphorylation reaction (Kovacz, T; Otvδs, L. Tetrahedron Lett. 1988, 29, 4525) of 5b was quenched with 40% aqueous methylamine instead of TEAB or H2O, the γ-amidate 7b was generated as the only detectable product. Similar reaction was reported recently for the preparation ofthe γ-amidate of pppA2'p5'A2'p5'A.¹²

Carboxylate group was introduced into 5-position of uridine both on the nucleoside level and post-synthetically (Method C) (Scheme 3). 5-Iodo-2'-deoxy-2'-fluorouridine (16) was coupled with methyl acrylate using modified Heck reaction¹³ to yield 17 in 85% yield. 5'-O-Dimethoxytritylation, followed by in situ 3'-O-acetylation and subsequent detritylation afforded 3 '-protected derivative 18. Phosphorylation using 2-chloro-4H- l,3,2-benzodioxa-phosphorin-4-one followed by pyrophosphate addition and oxidation (Ludwig, J.; Eckstein, F. J. Org. Chem. 1989, 54, 631) afforded the desired triphosphate in 54% yield. On the other hand, 5-(3-aminopropyl)uridine 5 '-triphosphate 6b was coupled with N-hydroxysuccinimide ester of Fmoc-Asp-OFm to afford, after removal of Fmoc and Fm groups with diethylamine, the desired aminoacyl conjugate 20 in 50% yield.

Cytidine derivatives comprising 3-aminopropyl and 3(N-succinyl)aminopropyl groups were synthesized according to Scheme 4. Peracylated 5-(3-aminopropynyl)uracil derivative 2b is reduced using catalytic hydrogenation and then converted in seven steps and 5%ι overall yield into 3'-acetylated cytidine derivative 25. This synthesis was plagued by poor solubility of intermediates and formation ofthe Ν⁴-cyclized byproduct during ammonia freatment ofthe 4-triazolyl intermediate. Phosphorylation of 25 as described in reference 11 yielded triphosphate 26 and N -cyclized product 27 in 1 : 1 ratio. They were easily separated on Sephadex DEAE A-25 ion exchange column using 0.1-0.8M TEAB gradient. It appears that under basic conditions the free primary amine can displace any remaining intact 4-NΗBz group leading to the cyclized product. This is similar to displacement of 4-triazolyl group by primary amine as mentioned above. We reasoned that utilization of N⁴-unprotected cytidine will solve this problem. This lead to an improved synthesis of 26: Iodination of 2'-deoxy-2'-fluorocytidine (28) provided the 5-iodo derivative 29 in 58%> yield. This compound was then smoothly converted into 5-(3-aminopropynyl) derivative 30. Hydrogenation afforded 5-(3- aminopropyl) derivative 31 which was phosphorylated directly with POCI3/ PPi to afford

26 in 37%) yield. Coupling ofthe 5 '-triphosphate 26 with succinic anhydride yielded succinylated derivative 32 in 36% yield.

Synthesis of 5-Imidazoleacetic acid 2'-deoxy-5'-triphosphate uridine

5-dintrophenylimidazoleacetic acid 2'-deoxy uridine nucleoside (80 mg) was dissolved in 5 ml of triethylphosphate while stirring under argon, and the reaction mixture was cooled to 0°C. Phosphorous oxychloride (1.8 eq, 22 ml) was added to the reaction mixture at 0°C, three more aliquots were added over the course of 48 hours at room temperature. The reaction mixture was then diluted with anhydrous MeCΝ (5 ml) and cooled to 0°C, followed by the addition of tributylamine (0.65 ml) and tributylammonium pyrophosphate (4.0 eq, 0.24 g). After 45 minutes, the reaction was quenched with 10 ml aq. methyl amine for four hours. After co-evaporation with MeOH (3x), purified material on DEAE Sephadex followed by RP chromatography to afford 15 mg of triphosphate. Synthesis of 2'-(N-lvsyl)-amino-2'-deoxy-cytidine Triphosphate

2'-(Ν-lysyl)-amino-2'-deoxy cytidine (0.180 g, 0.22 mmol) was dissolved in triethyl phosphate (2.00 ml) under Ar. The solution was cooled to 0 °C in an ice bath.

Phosphorus oxychloride (99.999%, 3 eq., 0.0672 mL) was added to the solution and the reaction was stiπed for two hours at 0 °C. Tributylammonium pyrophosphate (4 eq., 0.400 g) was dissolved in 3.42 mL of acetonitrile and tribuytylamine (0.165 mL). Acetonitrile (1 mL) was added to the monophosphate solution followed by the pyrophosphate solution which was added dropwise. The resulting solution was clear. The reaction was allowed to warm up to room temperature. After stirring for 45 minutes, methylamine (5 mL) was added and the reaction and stiπed at room temperature for 2 hours. A biphasic mixture appeared (little beads at the bottom ofthe flask). TLC (7:1:2 iPrOH:NH4OH:H2O) showed the appearance of triphosphate material. The solution was concentrated, dissolved in water and loaded on a newly prepared DEAE Sephadex A-25 column. The column was washed with a gradient up to 0.6 M TEAB buffer and the product eluted off in fractions 90-95. The fractions were analyzed by ion exchange HPLC. Each fraction showed one triphosphate peak that eluted at -4.000 minutes. The fractions were combined and pumped down from methanol to remove buffer salt to yield 15.7 mg of product. Synthesis of 2'-deoxy-2'-(L-histidine)amino Cytidine Triphosphate 2'-[N-Fmoc, Nimid -dinifrophenyl-histidyl]amino-2' -cytidine (0.310 g, 4.04 mmol) was dissolved in triethyl phosphate (3 ml) under Ar. The solution was cooled to 0 °C. Phosphorus oxychloride (1.8 eq., 0.068 mL) was added to the solution and stored overnight in the freezer. The next morning TLC (10% MeOH in CH2CI2) showed significant starting material, one more equivalent of POCI3 was added. After two hours, TLC still showed starting material. Tributylamine (0.303 mL) and Tributylammonium pyrophosphate (4 eq., 0.734 g) dissolved in 6.3 mL of acetonitrile (added dropwise) were added to the monophosphate solution. The reaction was allowed to warm up to room temperature. After stirring for 15 min, methylamine (10 mL) was added at room temperature and stirring continued for 2 hours. TLC (7:1:2 iPrOH:ΝH4θH:H2θ) showed the appearance of triphosphate material. The solution was concenfrated, dissolved in water and loaded on a DEAE Sephadex A-25 column. The column was washed with a gradient up to 0.6 M TEAB buffer and the product eluted off in fractions 170-179. The fractions were analyzed by ion exchange HPLC. Each fraction showed one triphosphate peak that eluted at ~6.77 minutes. The fractions were combined and pumped down from methanol to remove buffer salt to afford 17 mg of product.

Screening for Novel Enzymatic nucleic acid molecule Motifs Using Modified NTPs (Class I Motif)

Our initial pool contained 3 x IO¹⁴ individual sequences of 2'-amino-dCTP/2'- amino-dUTP RNA. We optimized franscription conditions in order to increase the amount of RNA product by inclusion of methanol and lithium chloride. 2'-amino-2'- deoxynucleotides do not interfere with the reverse transcription and amplification steps of selection and confer nuclease resistance. We designed the pool to have two binding arms complementary to the substrate, separated by the random 40 nucleotide region. The 16- mer subsfrate had two domains, 5 and 10 nucleotides long, that bind the pool, separated by an unpaired guanosine. On the 5' end ofthe substrate was a biotin attached by a C18 linker. This enabled us to link the subsfrate to a NeutrAvidin™ resin in a column format. The desired reaction would be cleavage at the unpaired G upon addition of magnesium cofactor followed by dissociation from the column due to instability ofthe 5 base pair helix. A detailed protocol follows:

Enzymatic nucleic acid molecule Pool Prep: The initial pool DNA was prepared by converting the following template oligonucleotides into double-sfranded DNA by filling in with taq polymerase. (template=5'-ACC CTC ACT AAA GGC CGT (N)₄₀ GGT TGC ACA CCT TTC-3'; primer 1=5'- CAC TTA GCA TTA ACC CTC ACT AAA GGC CGT-3'; primer 2=5'-TAA TAC GAC TCA CTA TAG GAA AGG TGT GCA ACC-3'.) All DNA oligonucleotides were synthesized by Operon technologies. Template oligos were purified by denaturing PAGE and Sep-pak chromatography columns (Waters). RNA subsfrate oligos were using standard solid phase chemistry and purified by denaturing PAGE followed by ethanol precipitation. Substrates for in vitro cleavage assays were 5'- end labeled with gamma-³²P-ATP and T4 polynucleotide kinase followed by denaturing PAGE purification and ethanol precipitation. 5 nmole of template, 10 nmole of each primer and 250 U taq polymerase were incubated in a 10 ml volume with IX PCR buffer (10 mM tris-HCl (pH 8.3), 1.5 mM MgCl₂, 50 mM KCl) and 0.2 mM each dNTP as follows: 94°C, 4 minutes; (94°C, 1 min; 42°C, 1 min; 72°C, 2 min) through four cycles; and then 72°C, for 10 minutes. The product was analyzed on 2% Separide™ agarose gel for size and then was extracted twice with buffered phenol, then chloroform-isoamyl alcohol, and ethanol precipitated. The initial RNA pool was made by franscription of 500 pmole (3 x IO¹⁴ molecules) of this DNA as follows. Template DNA was added to 40 mM tris-HCl (pH 8.0), 12 mM MgCl₂, 5 mM dithiothreitol (DTT), 1 mM spermidine, 0.002% triton X-100, 1 mM LiCl, 4% PEG-8000, 10% methanol, 2 mM ATP, 2 mM GTP, 2 mM 2'-amino-dCTP, 2 mM 2'- amino-dUTP, 5 U/ml inorganic pyrophosphatase, and 5 U/μl T7 RNA polymerase at room temperature for a total volume of 1 ml. A separate reaction contained a trace amount of

^7 alpha- P-GTP for detection. Transcriptions were incubated at 37°C for 2 hours followed by addition of equal volume STOP buffer (94% formamide, 20 mM EDTA, 0.05% bromophenol blue). The resulting RNA was purified by 6% denaturing PAGE gel, Sep- pak™ chromatography, and ethanol precipitated.

INITIAL SELECTION: 2 nmole of 16 mer 5 '-biotinylated substrate (5'-biotin-C18 linker-GCC GUG GGU UGC ACA C-3') was linked to 200 μl UltraLink Immobilized NeutrAvidin™ resin (400 μl slurry, Pierce) in binding buffer (20 mM NaPO₄ (pH 7.5), 150 mM NaCl) for 30 minutes at room temperature. The resulting subsfrate column was washed with 2 ml binding buffer followed by 2 ml column buffer (50 mM tris-HCl (pH 8.5), 100 mM NaCl, 50 mM KCl). The flow was capped off and 1000 pmole of initial pool RNA in 200 μl column buffer was added to the column and incubated 30 minutes at room temperature. The column was uncapped and washed with 2 ml column buffer, then capped off. 200 μl elution buffer (=column buffer + 25 mM MgCl₂) was added to the column and allowed to incubate 30 minutes at room temperature. The column was uncapped and eluent collected followed by three 200 μl elution buffer washes. The eluent washes were ethanol precipitated using glycogen as carrier and rehydrated in 50 μl sterile H O. The eluted RNA was amplified by standard reverse transcription/PCR amplification techniques. 5-31 μl RNA was incubated with 20 pmol of primer 1 in 14 μl volume 90° for 3 min then placed on ice for 1 minute. The following reagent were added (final concentrations noted): IX PCR buffer, 1 mM each dNTP, 2 U/μl RNase Inhibitor, 10 U/μl Superscript™ IL reverse transcriptase. The reaction was incubated 42° for 1 hour followed by 95° for 5 min in order to inactivate the reverse transcriptase. The volume was then increased to 100 μl by adding water and reagents for PCR: IX PCR buffer, 20 pmol primer 2, and 2.5 U taq DNA polymerase. The reaction was cycled in a Hybaid thermocycler: 94°, 4 min; (94°C, 30 sec; 54°C, 30 sec; 72°C, 1 min) X 25; 72°C, 5 min. Products were analyzed on agarose gel for size and ethanol precipitated. One-third to one- fifth ofthe PCR DNA was used to transcribe the next generation, in 100 μl volume, as described above. Subsequent rounds used 20 pmol RNA for the column with 40 pmol substrate.

TWO COLUMN SELECTION: At generation 8 (G8), the column selection was changed to the two column format. 200 pmoles of 22 mer 5 '-biotinylated subsfrate (5'- biotin-C18 linker-GCC GUG GGU UGC ACA CCU UUC C-C18 linker-thiol modifier C6 S-S-inverted abasic-3') was used in the selection column as described above. Elution was in 200 μl elution buffer followed by a 1 ml elution buffer wash. The 1200 μl eluent was passed through a product trap column by gravity. The product trap column was prepared as follows: 200 pmol 16 mer 5 '-biotinylated "product" (5'-GGU UGC ACA CCU UUC C-C18 linker-biotin-3') was linked to the column as described above and the column was equilibrated in elution buffer. Eluent from the product column was precipitated as previously described. The products were amplified as above only with 2.5-fold more volume and 100 pmol each primer. 100 μl ofthe PCR reaction was used to do a cycle course; the remaining fraction was amplified the minimal number of cycles needed for product. After 3 rounds (Gl 1), there was visible activity in a single turnover cleavage assay. By generation 13, 45% ofthe substrate was cleaved at 4 hours; k_obS ofthe pool was 0.037 min^"1 in 25 mM MgCl₂. We subcloned and sequenced generation 13; the pool was still very diverse. Since our goal was a enzymatic nucleic acid molecule that would work in a physiological environment, we decided to change selection pressure rather than exhaustively catalog G13. Reselection of the N40 pool was started from Gl 2 DNA. Part of the Gl 2 DNA was subjected to hypermutagenic PCR (Vartanian et al, 1996, Nucleic Acids Research 24, 2627-2631) to introduce a 10% per position mutation frequency and was designated N40H. At round 19, part ofthe DNA was hypermutagenized again, giving N40M and N40HM (a total of 4 parallel pools). The column subsfrates remained the same; buffers were changed and temperature of binding and elution was raised to 37°C. Column buffer was replaced by physiological buffer (50 mM tris-HCl (pH 7.5), 140 mM KCl, 10 mM NaCl) and elution buffer was replaced by 1 mM Mg buffer (physiological buffer + 1 mM MgCl₂). Amount of time allowed for the pool to bind the column was eventually reduced to 10 min and elution time was gradually reduced from 30 min to 20 sec. Between rounds 18 and 23, k^_s for the N40 pool stayed relatively constant at 0.035-0.04 min^"1. Generation 22 from each ofthe 4 pools was cloned and sequenced.

CLONING AND SEQUENCING: Generations 13 and 22 were cloned using Novagen's Perfectly Blunt™ Cloning kit (pT7Blue-3 vector) following the kit protocol. Clones were screened for insert by PCR amplification using vector-specific primers. Positive clones were sequenced using ABI Prism 7700 sequence detection system and vector-specific primer. Sequences were aligned using Mac Vector software; two- dimensional folding was performed using Mulfold software ( Zuker,, 1989, Science 244, 48-52; Jaeger et al, 1989, Biochemistry 86, 7706-7710; Jaeger et al, 1989, R. F. Doolittle ed., Methods in Enzymology, 183, 281-306). Individual clone transcription units were constructed by PCR amplification with 50 pmol each primer 1 and primer 2 in IX PCR buffer, 0.2 mM each dNTP, and 2.5 U of taq polymerase in 100 μl volume cycled as follows: 94°C, 4 min; (94°C, 30 sec; 54°C, 30 sec; 72°C, 1 min) X 20; 72°C, 5 min. Transcription units were ethanol precipitated, rehydrated in 30 μl H2O, and 10 μl was transcribed in 100 μl volume and purified as previously described.

Thirty-six clones from each pool were sequenced and were found to be variations of the same consensus motif. Unique clones were assayed for activity in 1 mM MgCl₂ and physiological conditions; nine clones represented the consensus sequence and were used in subsequent experiments. There were no mutations that significantly increased activity; most ofthe mutations were in regions believed to be duplex, based on the proposed secondary structure. In order to make the motif shorter, we deleted the 3 '-terminal 25 nucleotides necessary to bind the primer for amplification. The measured rates ofthe full length and truncated molecules were both 0.04 min^"1 ; thus we were able reduce the size of the motif from 86 to 61 nucleotides. The molecule was shortened even further by truncating base pairs in the stem loop structures as well as the substrate recognition arms to yield a 48 nucleotide molecule. In addition, many ofthe ribonucleotides were replaced with 2-O-methyl modified nucleotides to stabilize the molecule. An example ofthe new motif is given in Figure 13. Those of ordinary skill in the art will recognize that the molecule is not limited to the chemical modifications shown in the figure and that it represents only one possible chemically modified molecule.

Kinetic Analysis: Single turnover kinetics were performed with trace amounts of 5 '-³²P-labeled subsfrate and 10-1000 nM pool of enzymatic nucleic acid molecule. 2X substrate in IX buffer and 2X pool enzymatic nucleic acid molecule in IX buffer were incubated separately 90° for 3 min followed by equilibration to 37° for 3 min. Equal volume of 2X subsfrate was added to pool/enzymatic nucleic acid molecule at to and the reaction was incubated at 37°C. Time points were quenched in 1.2 vol STOP buffer on ice. Samples were heated to 90°C for 3 min prior to separation on 15% sequencing gels. Gels were imaged using a Phosphorimager and quantitated using ImageQuant™ software (Molecular Dynamics). Curves were fit to double-exponential decay in most cases, although some of the curves required linear fits. STABILITY: Serum stability assays were performed as previously described

(Beigelman et al., 1995, J. Biol. Chem. 270, 25702-25708). 1 μg of 5'-³²P-labeled synthetic enzymatic nucleic acid molecule was added to 13 μl cold and assayed for decay in human serum. Gels and quantitation were as described in kinetics section.

SUBSTRATE REQUIREMENTS: Table 60 outlines the substrate requirements for Class I motif. Subsfrates maintained Watson-Crick or wobble base pairing with mutant Class I constructs. Activity in single turnover kinetic assay is shown relative to wild type Class I and 22 mer substrate (50 mM Tris-HCL (pH 7.5), 140 mM KCl, 10 mM NaCl, 1 mM MgCl₂ , 100 nM ribozyme, 5 nM substrate, 37°C).

RANDOM REGION MUTATION ALIGNMENT: Table 61 outlines the random region alignment of 134 clones from generation 22 (1.x = N40, 2.x = N40M, 3.x = N40H, 4.x = N40HM). The number of copies of each mutant is in parenthesis in the table, deviations from consensus are shown. Mutations that maintain base pair U19:A34 are shown in italic. Activity in single turnover kinetic assay is shown relative to the G22 pool rate (50 mM Tris-HCL pH 7.5, 140 mM KCl, 10 mM NaCl, 1 mM MgCl₂ , 100 nM ribozyme, trace subsfrate, 37°C). STEM TRUNCATION AND LOOP REPLACEMENT ANALYSIS: Figure 25 shows a representation of Class I ribozyme stem truncation and loop replacement analysis. The K_rej is compared to a 61 mer Class I ribozyme measured as described above. Figure 26 shows examples of Class I ribozymes with truncated stem(s) and/or non-nucleotide linker replaced loop structures.

Inhibition of HCV Using Class I (Amberzyme) Motif

During HCV infection, viral RNA is present as a potential target for enzymatic nucleic acid molecule cleavage at several processes: uncoating, translation, RNA replication and packaging. Target RNA may be more or less accessible to enzymatic nucleic acid molecule cleavage at any one of these steps. Although the association between the HCV initial ribosome entry site (LRES) and the translation apparatus is mimicked in the HCV 5'UTR luciferase reporter system, these other viral processes are not represented in the OST7 system. The resulting RNA/protein complexes associated with the target viral RNA are also absent. Moreover, these processes may be coupled in an HCV-infected cell which could further impact target RNA accessibility. Therefore, we tested whether enzymatic nucleic acid molecules designed to cleave the HCV 5'UTR could effect a replicating viral system.

Recently, Lu and Wimmer characterized an HCV-poliovirus chimera in which the poliovirus LRES was replaced by the IRES from HCV (Lu & Wimmer, 1996, Proc. Natl. Acad. Sci. USA. 93, 1412-1417). Poliovirus (PV) is a positive strand RNA virus like HCV, but unlike HCV is non-enveloped and replicates efficiently in cell culture. The HCV-PV chimera expresses a stable, small plaque phenotype relative to wild type PV. The capability ofthe new enzymatic nucleic acid molecule motifs to inhibit HCV RNA intracellularly was tested using a dual reporter system that utilizes both firefly and Renilla luciferase (Figure 14). A number of enzymatic nucleic acid molecules having the new class I motif (Amberzyme) were designed and tested (Table 56). The Amberzyme ribozymes were targeted to the 5' HCV UTR region, which when cleaved, would prevent the translation ofthe transcript into luciferase. OST-7 cells were plated at 12,500 cells per well in black walled 96-well plates (Packard) in medium DMEM containing 10%> fetal bovine serum, 1%> pen/strep, and 1% L-glutamine and incubated at 37°C overnight. A plasmid containing T7 promoter expressing 5' HCV UTR and firefly luciferase (T7C1-341 (Wang et al, 1993, J. of Virol. 67, 3338-3344)) was mixed with a pRLSV40 Renilla confrol plasmid (Promega Coφoration) followed by enzymatic nucleic acid molecule, and cationic lipid to make a 5X concentration ofthe reagents (T7C 1-341 (4 μg/ml), pRLSV40 renilla luciferase confrol (6 μg/ml), enzymatic nucleic acid molecule (250 nM), fransfection reagent (28.5 μg/ml). o

The complex mixture was incubated at 37 C for 20 minutes. The media was removed from the cells and 120 μl of Opti-mem media was added to the well followed by 30 μl ofthe 5X complex mixture. 150 μl of Opti-mem was added to the wells holding the untreated cells. The complex mixture was incubated on OST-7 cells for 4 hours, lysed with passive lysis buffer (Promega Coφoration) and luminescent signals were quantified using the Dual Luciferase Assay Kit using the manufacturer's protocol (Promega Coφoration). The data shown in Figure 15 is a dose curve of enzymatic nucleic acid molecule targeting site 146 ofthe HCV RNA and is presented as a ratio between the firefly and Renilla luciferase fluorescence. The enzymatic nucleic acid molecule was able to reduce the quantity of HCV RNA at all enzymatic nucleic acid molecule concentrations yielding an IC₅₀ of approximately 5 nM. Other sites were also efficacious (Figure 16), in particular enzymatic nucleic acid molecules targeting sites 133, 209, and 273 were also able to reduce HCV RNA compared to the iπelevant (LRR) confrols.

Cleavage of Subsfrates Using Completely Modified class I (Amberzyme) enzymatic nucleic acid molecule

The ability of an enzymatic nucleic acid, which is modified at every 2' position to cleave a target RNA was tested to determine if any ribonucleotide positions are necessary in the Amberzyme motif. Enzymatic nucleic acid molecules were constructed with 2'-O- methyl, and 2'-amino (NH₂) nucleotides and included no ribonucleotides (Table 56; gene name: no ribo) and kinetic analysis was performed as described in example 13. 100 nM enzymatic nucleic acid was mixed with trace amounts of substrate in the presence of 1 mM MgCl₂ at physiological conditions (37°C). The Amberzyme with no ribonucleotide present in it has a K_reι of 0.13 compared to the enzymatic nucleic acid with a few ribonucleotides present in the molecule shown in Table 56 (ribo). This shows that Amberzyme enzymatic nucleic acid molecule may not require the presence of 2' -OH groups within the molecule for activity.

Substrate Recognition Rules for Class II (zinzyme) enzymatic nucleic acid molecules Class LI (zinzyme) ribozymes were tested for their ability to cleave base-paired subsfrates with all sixteen possible combinations of bases immediately 5' and 3' proximal to the bulged cleavage site G. Ribozymes were identical in all remaining positions of their 7 base pair binding arms. Activity was assessed at two and twenty- four hour time points under standard reaction conditions [20 mM HEPES pH 7.4, 140 mM KCl, 10 mM NaCl, 1 mM MgCl₂, 1 mM CaCl₂ - 37° C]. Figure 19 shows the results of this study. Base paired subsfrate UGG (not shown in the figure) cleaved as poorly as CGG shown in the figure. The figure shows the cleavage site substrate triplet in the 5'- 3' direction and 2 and 24 hour time points are shown top to bottom respectively. The results indicate the cleavage site triplet is most active with a 5'- Y-G-H -3' (where Y is C or U and H is A, C or U with cleavage between G and H); however, activity is detected particularly with the 24 hour time point for most paired subsfrates. All positions outside ofthe cleavage triplet were found to tolerate any base pairings (data not shown). All possible mispairs immediately 5' and 3' proximal to the bulged cleavage site G were tested to a class II ribozyme designed to cleave a 5'-C-G-C -3'. It was observed the 5' and 3' proximal sites are as active with G:U wobble pairs, in addition, the 5' proximal site will tolerate a mismatch with only a slight reduction in activity [data not shown].

Screening for Novel Enzymatic nucleic acid molecule Motifs (Class LI Motifs)

The selections were initiated with pools of > IO¹⁴ modified RNA's ofthe following sequence: S'-GGGAGGAGGAAGUGCCU (N)₃₅ UGCCGCGCUCGCUCCCAGUCC-3'. The RNA was enzymatically generated using the mutant T7 Y639F RNA polymerase prepared by Rui Souza. The following modified NTP's were incoφorated: 2 '-deoxy-2 '-fluoro- adenine triphosphate, 2' -deoxy-2 '-fluoro-uridine triphosphate or 2'-deoxy-2'-fluoro-5-[(N- imidazole-4acetyl)propyl amine] uridine triphosphate, and 2' -deoxy-2 '-amino-cytidine triphosphate; natural guanidine triphosphate was used in all selections so that alpha - P- GTP could be used to label pool RNA's. RNA pools were purified by denaturing gel elecfrophoresus 8% polyacrilamide 7 M Urea. The following target RNA (resin A) was synthesized and coupled to Iodoacetyl

Ulfralink™ resin (Pierce) by the supplier's proceedure:5' -b-L- GGACUGGGAGCGAGCGCGGCGCAGGCACU GAAG-L-S-B-3'; where b is biotin (Glenn Research cat# 10-1953-nn), L is polyethylene glycol spacer (Glenn Research cat# 10-1918- nn), S is thiol-modifier C6 S-S (Glenn Research cat# 10-1936-nn), B is a standard inverted deoxy abasic.

RNA pools were added to 100 μl of 5 uM Resin A in the buffer A (20 mM HEPES pH 7.4, 140 mM KCL, 10 mM NaCl) and incubated at 22°C for 5 minutes. The temperature was then raised to 37°C for 10 minutes. The resin was washed with 5 ml buffer A. Reaction was triggered by the addition of buffer B(20 mM HEPES pH 7.4, 140 mM KCL, 10 mM NaCl, 1 mM MgCl₂, 1 mM CaCl₂). Incubation proceeded for 20 minutes in the first generation and was reduced progressively to 1 minute in the final generations; with 13 total generations. The reaction eluent was collected in 5 M NaCl to give a final concenfration of 2 M NaCl. To this was added 100 μl of 50% slurry Ultralink NeufraAvidin™ (Pierce). Binding of cleaved biotin product to the avidin resin was allowed by 20 minute incubation at 22° C. The resin was subsequently washed with 5 ml of 20 mM HEPES pH 7.4, 2 M NaCl. Desired RNA's were removed by a 1.2 ml denaturing wash IM NaCl, 10 M Urea at 94° C over 10 minutes. RNA's were double precipitated in 0.3 M sodium acetate to remove CI^" ions inhibitory to reverse franscription. Standard protocols of reverse transcription and PCR amplification were performed. RNA's were again transcribed with the modified NTP's described above. After 13 generations cloning and sequencing provided 14 sequences which were able to cleave the target subsfrate. Six sequences were characterized to determine secondary structure and kinetic cleavage rates. The structures and kinetic data are given in Figure 17. The sequences of eight other enzymatic nucleic acid molecule sequences are given in Table 57. The size, sequence, and chemical compositions of these molecules can be modified as described below or using other techniques well known in the art.

Nucleic Acid Catalyst Engineering

Sequence, chemical and structural variants of Class I and Class LI enzymatic nucleic acid molecule can be engineered and re-engineered using the techniques shown in this application and known in the art. For example, the size of class I and class II enzymatic nucleic acid molecules can, be reduced or increased using the techniques known in the art (Zaug et al, 1986, Nature, 324, 429; Ruffher et al, 1990, Biochem., 29, 10695; Beaudry et al, 1990, Biochem., 29, 6534; McCall et al, 1992, Proc. Natl. Acad. Sci., USA., 89, 5710; Long et α/., 199A, supra; Hendry et al, 1994, BBA 1219, 405; Benseler et α/., 1993, JACS, 115, 8483; Thompson et al, 1996, Nucl. Acids Res., 24, 4401; Michels et al, 1995, Biochem., 34, 2965; Been et al, 1992, Biochem., 31, 11843; Guo et α/., 1995, EMBO. J, 14, 368; Pan et al, 1994, Biochem., 33, 9561; Cech, 1992, Cwrr. Op. Struc. Bio., 2, 605; Sugiyama et al, 1996, FEBS Lett., 392, 215; Beigelman et α/., 199A, Bioorg. Med. Chem., A, 1715; Santoro et α/., 1997, PN4S 94, 4262; all are incoφorated in their totality by reference herein), to the extent that the overall catalytic activity ofthe ribozyme is not significantly decreased. Further rounds of in vitro selection strategies described herein and variations thereof can be readily used by a person skilled in the art to evolve additional nucleic acid catalysts and such new catalysts are within the scope ofthe instant invention.

Example 16: Activity of Class TJ (zinzyme) nucleic acid catalysts to inhibit HER2 gene expression

Applicant has designed, synthesized and tested several class LI (zinzyme) ribozymes targeted against HER2 RNA (see, for example, Tables 58, 59, and 62) in cell proliferation

RNA reduction assays.

Proliferation assay: The model proliferation assay used in the study can require a cell-plating density of

2000-10000 cells/well in 96-well plates and at least 2 cell doublings over a 5-day freatment period. Cells used in proliferation studies were either human breast or ovarian cancer cells

(SKBR-3 and SKOV-3 cells respectively). To calculate cell density for proliferation assays, the FLPS (fluoro-imaging processing system) method well known in the art was used. This method allows for cell density measurements after nucleic acids are stained with CyQuant® dye, and has the advantage of accurately measuring cell densities over a very wide range 1,000-100,000 cells/well in 96-well format.

Ribozymes (50-200 nM) were delivered in the presence of cationic lipid at 2.0-5.0 μg/mL and inhibition of proliferation was determined on day 5 post-treatment. Two full ribozyme screens were completed resulting in the selection of 14 ribozymes. Class LI

(zinzyme) ribozymes against sites, 314 (RPI No. 18653), 443 (RPI No. 18680), 597 (RPI No. 18697), 659 (RPI No. 18682), 878 (RPI Nos. 18683 and 18654), 881 (RPI Nos. 18684 and 18685) 934 (RPI No. 18651), 972 (RPI No. 18656, 19292, 19727, 19728, and 19293), 1292 (RPI No. 18726), 1541 (RPI No. 18687), 2116 (RPI No. 18729), 2932 (RPI No. 18678), 2540 (RPI No. 18715), and 3504 (RPI No. 18710) caused inhibition of proliferation ranging from 25-80% as compared to a scrambled control ribozyme. An example of results from a cell culture assay is shown in Figure 20. Referring to Figure 20, Class II ribozymes targeted against HER2 RNA are shown to cause significant inhibition of proliferation of cells. This shows that ribozymes, for instance the Class π (zinzyme) ribozymes are capable of inhibiting HER2 gene expression in mammalian cells.

RNA assay:

RNA was harvested 24 hours post-treatment using the Qiagen RNeasy® 96 procedure. Real time RT-PCR (TaqMan® assay) was performed on purified RNA samples using separate primer/probe sets specific for either target HER2 RNA or confrol actin RNA (to normalize for differences due to cell plating or sample recovery). Results are shown as the average of triplicate determinations of HER2 to actin RNA levels post- treatment. Figure 30 shows class II ribozyme (zinzyme) mediated reduction in HER2 RNA targeting site 972 vs a scrambled attenuated control.

Dose response assays:

Active ribozyme was mixed with binding arm-attenuated control (BAC) ribozyme to a final oligonucleotide concenfration of either 100, 200 or 400 nM and delivered to cells in the presence of cationic lipid at 5.0 μg/mL. Mixing active and BAC in this manner maintains the lipid to ribozyme charge ratio throughout the dose response curve. HER2 RNA reduction was measured 24 hours post-freatment and inhibition of proliferation was determined on day 5 post-freatment. The dose response antiproliferation results are summarized in Figure 31 and the dose-dependent reduction of HER2 RNA results are summarized in Figure 32. Figure 33 shows a combined dose response plot of both anti- proliferation and RNA reduction data for a class LI ribozyme targeting site 972 of HER2 RNA (RPI 19293). Example 17: Reduction of ribose residues in Class LI (zinzyme) nucleic acid catalysts

Class LI (zinzyme) nucleic acid catalysts were tested for their activity as a function ribonucleotide content. A Zinzyme having no ribonucleotide residue (ie., no 2'-OH group at the 2' position ofthe nucleotide sugar) against the K-Ras site 521 was designed. This molecules were tested utilizing the chemistry shown in Figure 27a. The in vitro catalytic activity zinzyme construct was not significantly effected (the cleavage rate reduced only 10 fold).

The Kras zinzyme shown in Figure 27a was tested in physiological buffer with the divalent concentrations as indicated in the legend (high NaCl is an altered monovalent condition shown) of Figure 28. The 1 mM Ca*^* condition yielded a rate of 0.005 min^"1 while the 1 mM Mg^""^" condition yielded a rate of 0.002 min^"1. The ribose containing wild type yields a rate of 0.05 min while subsfrate in the absence of zinzyme demonstrates less than 2% degradation at the longest time point under reaction conditions shown. This illustrates a well-behaved cleavage reaction done by a non-ribose containing catalyst with only a 10-fold reduced cleavage as compared to ribonucleotide-containing zinzyme and vastly above non-catalyzed degradation.

A more detailed investigation into the role of ribose positions in the Class π (zinzyme) motif was carried out in the context ofthe HER2 site 972 (Applicant has further designed a fully modified Zinzyme as shown in Figure 27b targeting the HER2 RNA site 972). Figure 29 is a diagram ofthe alternate formats tested and their relative rates of catalysis. The effect of substitution of ribose G for the 2'-O-methyl C-2'-O-methyl A in the loop of Zinzyme (see Figure 34) was insignificant when assayed with the Kras target but showed a modest rate enhancement in the HER2 assays. The activity of all Zinzyme motifs, including the fully stabilized "0 ribose" (RPI 19727) are well above background noise level degradation. Zinzyme with only two ribose positions (RPI 19293) are sufficient to restore "wild-type" activity. Motifs containing 3 (RPI 19729), 4 (RPI 19730) or 5 ribose (RPI 19731) positions demonsfrated a greater extent of cleavage and profiles almost identical to the 2 ribose motif. Applicant has thus demonsfrated that a Zinzyme with no ribonucleotides present at any position can catalyze efficient RNA cleavage activity. Thus, Zinzyme enzymatic nucleic acid molecules do not require the presence of 2'-ΟH group within the molecule for catalytic activity. Example 18: Activity of reduced ribose containing Class II (zinzyme) nucleic acid catalysts to inhibit HER2 gene expression

A cell proliferation assay for testing reduced ribo class LI (zinzyme) nucleic acid catalysts (50-400 nM) targeting HER2 site 972 was performed as described in example 19. The results of this study are summarized in Figure 35. These results indicate significant inhibition of HER2 gene expression using stabilized Class II (zinzyme) motifs, including two ribo (RPI 19293), one ribo (RPI 19728), and non-ribo (RPI 19727) containing nucleic acid catalysts.

Applications

The use of NTP's described in this invention have several research and commercial applications. These modified nucleotide triphosphates can be used for in vitro selection (evolution) of oligonucleotides with novel functions. Examples of in vitro selection protocols are incoφorated herein by reference (Joyce, 1989, Gene, 82, 83-87; Beaudry et al, 1992, Science 257, 635-641; Joyce, 1992, Scientific American 267, 90-97; Breaker et al, 1994, TIBTECH 12, 268; Bartel et α/.,1993, Science 261:1411-1418; Szostak, 1993, TIBS 17, 89-93; Kumar et al, 1995, FASEB , 9, 1183; Breaker, 1996, Curr. Op. Biotech., 7, 442).

Additionally, these modified nucleotide triphosphates can be employed to generate modified oligonucleotide combinatorial chemistry libraries. Several references for this technology exist (Brenner et al, 1992, PNAS 89, 5381-5383, Eaton, 1997, Curr. Opin. Chem. Biol. 1, 10-16), which are all incoφorated herein by reference.

Diagnostic uses Enzymatic nucleic acid molecules of this invention may be used as diagnostic tools to examine genetic drift and mutations within diseased cells or to detect the presence of specific RNA in a cell. The close relationship between enzymatic nucleic acid molecule activity and the structure ofthe target RNA allows the detection of mutations in any region ofthe molecule which alters the base-pairing and three-dimensional structure ofthe target RNA. By using multiple enzymatic nucleic acid molecules described in this invention, one may map nucleotide changes which are important to RNA structure and function in vitro, as well as in cells and tissues. Cleavage of target RNAs with enzymatic nucleic acid molecules may be used to inhibit gene expression and define the role (essentially) of specified gene products in the progression of disease. In this manner, other genetic targets may be defined as important mediators ofthe disease. These experiments will lead to better treatment ofthe disease progression by affording the possibility of combinational therapies (e.g., multiple enzymatic nucleic acid molecules targeted to different genes, enzymatic nucleic acid molecules coupled with known small molecule inhibitors, radiation or intermittent freatment with combinations of enzymatic nucleic acid molecules and/or other chemical or biological molecules). Other in vitro uses of enzymatic nucleic acid molecules of this invention are well known in the art, and include detection ofthe presence of mRNAs associated with related conditions. Such RNA is detected by determimng the presence of a cleavage product after treatment with a enzymatic nucleic acid molecule using standard methodology.

In a specific example, enzymatic nucleic acid molecules which can cleave only wild- type or mutant forms ofthe target RNA are used for the assay. The first enzymatic nucleic acid molecule is used to identify wild-type RNA present in the sample and the second enzymatic nucleic acid molecule will be used to identify mutant RNA in the sample. As reaction confrols, synthetic subsfrates of both wild-type and mutant RNA will be cleaved by both enzymatic nucleic acid molecules to demonstrate the relative enzymatic nucleic acid molecule efficiencies in the reactions and the absence of cleavage ofthe "non- targeted" RNA species. The cleavage products from the synthetic subsfrates will also serve to generate size markers for the analysis of wild type and mutant RNAs in the sample population. Thus each analysis can involve two enzymatic nucleic acid molecules, two subsfrates and one unknown sample which can be combined into six reactions. The presence of cleavage products can be determined using an RNAse protection assay so that full-length and cleavage fragments of each RNA can be analyzed in one lane of a polyacrylamide gel. It is not absolutely required to quantify the results to gain insight into the expression of mutant RNAs and putative risk ofthe desired phenotypic changes in target cells. The expression of mRNA whose protein product is implicated in the development ofthe phenotype is adequate to establish risk. If probes of comparable specific activity are used for both franscripts, then a qualitative comparison of RNA levels will be adequate and will decrease the cost ofthe initial diagnosis. Higher mutant form to wild-type ratios will be coπelated with higher risk whether RNA levels are compared qualitatively or quantitatively.

Additional Uses Potential usefulness of sequence-specific enzymatic nucleic acid molecules ofthe instant invention can have many ofthe same applications for the study of RNA that DNA restriction endonucleases have for the study of DNA (Nathans et al, 1975 Ann. Rev. Biochem. 44:273). For example, the pattern of restriction fragments can be used to establish sequence relationships between two related RNAs, and large RNAs could be specifically cleaved to fragments of a size more useful for study. The ability to engineer sequence specificity ofthe enzymatic nucleic acid molecule is ideal for cleavage of RNAs of unknown sequence. Applicant describes the use of nucleic acid molecules to down- regulate gene expression of target genes in bacterial, microbial, fungal, viral, and eukaryotic systems including plant, or mammalian cells. All patents and publications mentioned in the specification are indicative ofthe levels of skill of those skilled in the art to which the invention pertains. All references cited in this disclosure are incoφorated by reference to the same extent as if each reference had been incoφorated by reference in its entirety individually.

One skilled in the art would readily appreciate that the present invention is well adapted to carry out the objects and obtain the ends and advantages mentioned, as well as those inherent therein. The methods and compositions described herein as presently representative of prefeπed embodiments are exemplary and are not intended as limitations on the scope ofthe invention. Changes therein and other uses will occur to those skilled in the art, which are encompassed within the spirit ofthe invention, are defined by the scope ofthe claims.

It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit ofthe invention. Thus, such additional embodiments are within the scope ofthe present invention and the following claims. The invention illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein. Thus, for example, in each instance herein any ofthe terms "comprising", "consisting essentially of and "consisting of may be replaced with either ofthe other two terms. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents ofthe features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope ofthe invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by prefeπed embodiments, optional features, modification and variation ofthe concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the description and the appended claims.

In addition, where features or aspects ofthe invention are described in terms of Markush groups or other grouping of alternatives, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members ofthe Markush group or other group. Thus, additional embodiments are within the scope ofthe invention and within the following claims

Table 1

TABLE 1

Characteristics of naturally occurring ribozymes Group I Introns

Size: -150 to >1000 nucleotides.

• Requires a U in the target sequence immediately 5' of the cleavage site.

• Binds 4-6 nucleotides at the 5'-side of the cleavage site.

• Reaction mechanism: attack by the 3' -OH of guanosine to generate cleavage products with 3'-OH and 5'-guanosine.

• Additional protein cofactors required in some cases to help folding and maintainance of the active structure.

• Over 300 known members of this class. Found as an intervening sequence in Tetrahymena tliermophila rRNA, fungal mitochondria, chloroplasts, phage T4, blue-green algae, and others.

• Major structural features largely established through phylogenetic comparisons, mutagenesis, and biochemical studies [',"].

• Complete kinetic framework established for one ribozyme ["V^vΛ^vi]-

• Studies of ribozyme folding and substrate docking underway [^vii,^viii,^ix]-

• Chemical modification investigation of important residues well established [^x,^xi].

• The small (4-6 nt) binding site may make this ribozyme too non-specific for targeted RNA cleavage, however, the Tetrahymena group I intron has been used to repair a "defective" β-galactosidase message by the ligation of new β-galactosidase sequences onto the defective message [^xii].

RNAse P RNA (M1 RNA)

Size: -290 to 400 nucleotides.

• RNA portion of a ubiquitous ribonucleoprotein enzyme.

• Cleaves tRNA precursors to form mature tRNA [^xiii].

2+

• Reaction mechanism: possible attack by M -OH to generate cleavage products with 3'- OH and 5' -phosphate.

• RNAse P is found throughout the prokaryotes and eukaryotes. The RNA subunit has been sequenced from bacteria, yeast, rodents, and primates.

• Recruitment of endogenous RNAse P for therapeutic applications is possible through hybridization of an External Guide Sequence (EGS) to the target RNA [^xiv,^χv]

• Important phosphate and 2' OH contacts recently identified ["^{vi vii}j

Group II Introns

• Size: >1000 nucleotides.

• Trans cleavage of target RNAs recently demonstrated [^xvπ^^xix]. Table 1

• Sequence requirements not fully determined.

• Reaction mechanism: 2'-OH of an internal adenosine generates cleavage products with 3'- OH and a "lariat" RNA containing a 3' -5' and a 2' -5' branch point.

• Only natural ribozyme with demonstrated participation in DNA cleavage [^x ,^{x i}] in addition to RNA cleavage and ligation.

• Major structural features largely established through phylogenetic comparisons [^xxϋ].

• Important 2' OH contacts beginning to be identified [^xxiii]

• Kinetic framework under development [^xxiv]

Neurospora VS RNA

• Size: -144 nucleotides.

• Trans cleavage of hairpin target RNAs recently demonstrated [^xxv].

• Sequence requirements not fully determined.

• Reaction mechanism: attack by 2' -OH 5' to the scissile bond to generate cleavage products with 2',3'-cyclic phosphate and 5' -OH ends.

• Binding sites and structural requirements not fully determined.

• Only 1 known member of this class. Found in Neurospora VS RNA.

Hammerhead Ribozyme

(see text for references)

• Size: -13 to 40 nucleotides.

• Requires the target sequence UH immediately 5' of the cleavage site.

• Binds a variable number nucleotides on both sides of the cleavage site.

• Reaction mechanism: attack by 2'-OH 5' to the scissile bond to generate cleavage products with 2',3'-cyclic phosphate and 5'-OH ends.

• 14 known members of this class. Found in a number of plant pathogens (virusoids) that use RNA as the infectious agent.

• Essential structural features largely defined, including 2 crystal structures [^xx ^ ^xvϋj

• Minimal ligation activity demonstrated (for engineering through in vitro selection) [ ^xviii]

• Complete kinetic framework established for two or more ribozymes [^xxix].

• Chemical modification investigation of important residues well established [^xxx].

Hairpin Ribozyme

• Size: -50 nucleotides.

• Requires the target sequence GUC immediately 3' of the cleavage site.

• Binds 4-6 nucleotides at the 5'-side of the cleavage site and a variable number to the 3'- side of the cleavage site.

• Reaction mechanism: attack by 2' -OH 5' to the scissile bond to generate cleavage products with 2',3'-cyclic phosphate and 5' -OH ends.

• 3 known members of this class. Found in three plant pathogen (satellite RNAs of the tobacco ringspot virus, arabis mosaic virus and chicory yellow mottle virus) which uses RNA as the infectious agent.

• Essential structural features largely defined [ ^χi _/ ^χχχii _/ ^χχχ»ⁱ _/ ^χχχiv] Table 1

• Ligation activity (in addition to cleavage activity) makes ribozyme amenable to engineering through in vitro selection [^{xx v}]

• Complete kinetic framework established for one ribozyme [^χχχvι].

• Chemical modification investigation of important residues begun [ ^χχ u xxx^vmj

Hepatitis Delta Virus (HDV) Ribozyme

• Size: -60 nucleotides.

• Trans cleavage of target RNAs demonstrated [^xχχι ].

• Binding sites and structural requirements not fully determined, although no sequences 5' of cleavage site are required. Folded ribozyme contains a pseudoknot structure [^x1].

• Reaction mechanism: attack by 2' -OH 5' to the scissile bond to generate cleavage products with 2',3' -cyclic phosphate and 5'-OH ends.

• Only 2 known members of this class. Found in human HDV.

• Circular form of HDV is active and shows increased nuclease stability [^xh]

Michel, Francois; Westhof, Eric. Slippery substrates. Nat. Struct. Biol. (1994), 1(1), 5-7. ^u . Lisacek, Frederique; Diaz, Yolande; Michel, Francois. Automatic identification of group I intron cores in genomic DNA sequences. J. Mol. Biol. (1994), 235(4), 1206-17. ^m . Herschlag, Daniel; Cech, Thomas R.. Catalysis of RNA cleavage by the Tetrahymena thermophila ribozyme. 1. Kinetic description of the reaction of an RNA substrate complementary to the active site. Biochemistry (1990), 29(44), 10159-71.

^1V . Herschlag, Daniel; Cech, Thomas R.. Catalysis of RNA cleavage by the Tetrahymena thermophila ribozyme. 2. Kinetic description of the reaction of an RNA substrate that forms a mismatch at the active site. Biochemistry (1990), 29(44), 10172-80. ^v . Knitt, Deborah S.; Herschlag, Daniel. pH Dependencies of the Tetrahymena Ribozyme Reveal an

Unconventional Origin of an Apparent pKa. Biochemistry (1996), 35(5), 1560-70.

^V1 . Bevilacqua, Philip C; Sugimoto, Naoki; Turner, Douglas H.. A mechanistic framework for the second step of splicing catalyzed by the Tetrahymena ribozyme. Biochemistry (1996), 35(2), 648-58. ^vu . Li, Yi; Bevilacqua, Philip C; Mathews, David; Turner, Douglas H.. Thermodynamic and activation parameters for binding of a pyrene-labeled substrate by the Tetrahymena ribozyme: docking is not diffusion-controlled and is driven by a favorable entropy change. Biochemistry (1995), 34(44), 14394-9. ^vm . Banerjee, Aloke Raj; Turner, Douglas H.. The time dependence of chemical modification reveals slow steps in the folding of a group I ribozyme. Biochemistry (1995), 34(19), 6504-12. ^■* . Zarrinkar, Patrick P.; Williamson, James R.. The P9.1-P9.2 peripheral extension helps guide folding of the Tetrahymena ribozyme. Nucleic Acids Res. (1996), 24(5), 854-8.

* . Strobel, Scott A.; Cech, Thomas R.. Minor groove recognition of the conserved G.cntdot.U pair at the Tetrahymena ribozyme reaction site. Science (Washington, D. C.) (1995), 267(5198), 675-9. "• . Strobel, Scott A.; Cech, Thomas R.. Exocyclic Amine of the Conserved G.cntdo U Pair at the

Cleavage Site of the Tetrahymena Ribozyme Contributes to 5'-Splice Site Selection and Transition State Stabilization. Biochemistry (1996), 35(4), 1201-11. ^xu. Sullenger, Bruce A.; Cech, Thomas R.. Ribozyme-mediated repair of defective mRNA by targeted trans-splicing. Nature (London) (1994), 371(6498), 619-22.

Robertson, H.D.; Altaian, S.; Smith, J.D. J. Biol. Chem., 247, 5243-5251 (1972). *^1V. Forster, Anthony C; Altaian, Sidney. External guide sequences for an RNA enzyme. Science

(Washington, D. C, 1883-) (1990), 249(4970), 783-6.

*^v. Yuan, Y.; Hwang, E. S.; Altaian, S. Targeted cleavage of mRNA by human RNase P. Proc. Natl.

Acad. Sci. USA (1992) 89, 8006-10. *^V1 . Harris, Michael E.; Pace, Norman R.. Identification of phosphates involved in catalysis by the Table 1

ribozyme RNase P RNA. RNA (1995), 1(2), 210-18. ^xvu . Pan, Tao; Loria, Andrew; Zhong, Kun. Probing of tertiary interactions in RNA: 2'-hydroxyl-base contacts between the RNase P RNA and pre-tRNA. Proc. Natl. Acad. Sci. U. S. A. (1995), 92(26), 12510-14. ^xvm Pyle, Anna Marie; Green, Justin B.. Building a Kinetic Framework for Group II Intron Ribozyme

Activity: Quantitation of Interdomain Binding and Reaction Rate. Biochemistry (1994), 33(9), 2716-25. ^X1X . Michels, William J. Jr.; Pyle, Anna Marie. Conversion of a Group II Intron into a New Multiple-

Turnover Ribozyme that Selectively Cleaves Oligonucleotides: Elucidation of Reaction Mechanism and Structure/ Function Relationships. Biochemistry (1995), 34(9), 2965-77. ^xx . Zimmerly, Steven; Guo, Huatao; Eskes, Robert; Yang, Jian; Perlman, Philip S.; Lambowitz, Alan

M.. A group II intron RNA is a catalytic component of a DNA endonuclease involved in intron mobility. Cell (Cambridge, Mass.) (1995), 83(4), 529-38.

*^X1 . Griffin, Edmund A., Jr.; Qin, Zhifeng; Michels, Williams J., Jr.; Pyle, Anna Marie. Group II intron ribozymes that cleave DNA and RNA linkages with similar efficiency, and lack contacts with substrate 2'- hydroxyl groups. Chem. Biol. (1995), 2(11), 761-70. ^xu . Michel, Francois; Ferat, Jean Luc. Structure and activities of group II introns. Annu. Rev. Biochem. (1995), 64, 435-61. ^xx . Abramovitz, Dana L.; Friedman, Richard A.; Pyle, Anna Marie. Catalytic role of 2'-hydroxyl groups within a group II intron active site. Science (Washington, D. C.) (1996), 271(5254), 1410-13. ^X!αv . Daniels, Danette L.; Michels, William J., Jr.; Pyle, Anna Marie. Two competing pathways for self- splicing by group II introns: a quantitative analysis of in vitro reaction rates and products. J. Mol. Biol. (1996), 256(1), 31-49. ^XV . Guo, Hans C. T.; Collins, Richard A.. Efficient trans-cleavage of a stem-loop RNA substrate by a ribozyme derived from Neurospora VS RNA. EMBO J. (1995), 14(2), 368-76. ^XXVI . Scott, W.G., Finch, J.T., Aaron,K. The crystal structure of an all RNA hammerhead ribozyme:Aproposed mechanism for RNA catalytic cleavage. Cell, (1995), 81, 991-1002. ^xxvu McKay, Structure and function of the hammerhead ribozyme: an unfinished story. RNA, (1996), 2, 395-403. ^xxvώ . Long, D., Uhlenbeck, O., Hertel, K. Ligation with hammerhead ribozymes. US Patent No. 5,633,133.

^XX1X . Hertel, K.J., Herschlag, D., Uhlenbeck, O. A kinetic and thermodynamic framework for the hammerhead ribozyme reaction. Biochemistry, (1994) 33, 3374-3385.Beigelman, L., et al., Chemical modifications of hammerhead ribozymes. J. Biol. Chem., (1995) 270, 25702-25708. ^xxx Beigelman, L., et al., Chemical modifications of hammerhead ribozymes. J. Biol. Chem., (1995)

270, 25702-25708.

^{X XI} . Hampel, Arnold; Tritz, Richard; Hicks, Margaret; Cruz, Phillip. 'Hairpin' catalytic RNA model: evidence for helixes and sequence requirement for substrate RNA. Nucleic Acids Res. (1990), 18(2), 299- 304. ^u Chowrira, Bharat M.; Berzal-Herranz, Alfredo; Burke, John M.. Novel guanosine requirement for catalysis by the hairpin ribozyme. Nature (London) (1991), 354(6351), 320-2. ^{xx ui} Berzal-Herranz, Alfredo; Joseph, Simpson; Chowrira, Bharat M.; Butcher, Samuel E.; Burke, John M.. Essential nucleotide sequences and secondary structure elements of the hairpin ribozyme. EMBO J. (1993), 12(6), 2567-73. ^{xx iv} Joseph, Simpson; Berzal-Herranz, Alfredo; Chowrira, Bharat M.; Butcher, Samuel E.. Substrate selection rules for the hairpin ribozyme determined by in vitro selection, mutation, and analysis of mismatched substrates. Genes Dev. (1993), 7(1), 130-8. ^{x v} Berzal-Herranz, Alfredo; Joseph, Simpson; Burke, John M.. In vitro selection of active hairpin ribozymes by sequential RNA-catalyzed cleavage and ligation reactions. Genes Dev. (1992), 6(1), 129-34. ^{xx vi} Hegg, Lisa A.; Fedor, Martha J.. Kinetics and Thermodynamics of Intermolecular Catalysis by Hairpin Ribozymes. Biochemistry (1995), 34(48), 15813-28. ^xxxvu Grasby, Jane A.; Mersmann, Karin; Singh, Mohinder; Gait, Michael J.. Purine Functional Groups in Essential Residues of the Hairpin Ribozyme Required for Catalytic Cleavage of RNA. Biochemistry Table 1

(1995), 34(12), 4068-76. ^xxvui Schmidt, Sabine; Beigelman, Leonid; Karpeisky, Alexander; Usman, Nassim; Sorensen, Ulrik S.; Gait, Michael J.. Base and sugar requirements for RNA cleavage of essential nucleoside residues in internal loop B of the hairpin ribozyme: implications for secondary structure. Nucleic Acids Res. (1996), 24(4), 573-81. ^{xx ix} Perrotta, Anne T.; Been, Michael D.. Cleavage of oligoribonucleotides by a ribozyme derived from the hepatitis .delta, virus RNA sequence. Biochemistry (1992), 31(1), 16-21. ^xl . Perrotta, Anne T.; Been, Michael D.. A pseudoknot-like structure required for efficient self- cleavage of hepatitis delta virus RNA. Nature (London) (1991), 350(6317), 434-6. ^xU . Puttaraju, M.; Perrotta, Anne T.; Been, Michael D.. A circular trans-acting hepatitis delta virus ribozyme. Nucleic Acids Res. (1993), 21(18), 4253-8.

Table 2

Table 2:

A. 2.5 μmol Synthesis Cycle ABI 394 Instrument

Reagent Equivalents Amount Wait Time* DNA Wait Time* 2'- Wait Time' O-methyl RNA

Phosphoramidites 6.5 163 μL 45 sec 2.5 min 7.5 min S-Ethyl Tetrazole 23.8 238 μL 45 sec 2.5 min 7.5 min Acetic Anhydride 100 233 μL 5 sec 5 sec 5 sec Λ/-Methyl Imidazole 186 233 μL 5 sec 5 sec 5 sec TCA 176 2.3 mL 21 sec 21 sec 21 sec Iodine 11.2 1.7 mL 45 sec 45 sec 45 sec Beaucage 12.9 645 μL 100 sec 300 sec 300 sec Acetonitrile NA 6.67 mL NA NA NA

B. 0.2 μmol Synthesis Cycle ABI 394 Instrument

Reagent Equivalents Amount Wait Time* DNA Wait Time* 2'- Wait Time* O-methyl RNA

Phosphoramidites 15 31 μL 45 sec 233 sec 465 sec

S-Ethyl Tetrazole 38.7 31 μL 45 sec 233 min 465 sec

Acetic Anhydride 655 124 μL 5 sec 5 sec 5 sec

Λ/-Methyl Imidazole 1245 124 μL 5 sec 5 sec 5 sec

TCA 700 732 μL 10 sec 10 sec 10 sec

Iodine 20.6 244 μL 15 sec 15 sec 15 sec

Beaucage 71 232 μL 100 sec 300 sec 300 sec

Table 2

Acetonitrile NA 2.64 mL NA NA NA

C. 0.2 μmol Synthesis Cycle 96 well Instrument

Reagent Equivalents Amount Wait Time* Wait Time* 2'-0- Wait Time* Ribo

DNA 2'-0-me thyl/Ribo DNA/2'-0-methyl/Ribo DNA methyl

Phosphoramidites 22/33/66 40/60/120 μL 60 sec 180 sec 360sec

S-Ethyl Tetrazole 70/105/210 40/60/120 μL 60 sec 180 min 360 sec

Acetic Anhydride 265/265/265 50/50/50 μL 10 sec 10 sec 10 sec

Λ/-Methyl Imidazole 502/502/502 50/50/50 μL 10 sec 10 sec 10 sec

TCA 238/475/475 250/500/500 μL 15 sec 15 sec 15 sec

Iodine 6.8/6.8/6.8 80/80/80 μL 30 sec 30 sec 30 sec

Beaucage 34/51/51 80/120/120 100 sec 200 sec 200 sec

Acetonitrile NA 1150/1150/1150 μL NA NA NA

* Wait time does not include contact time during delivery.

Table 3 Table 3: Human PTP-IB Hammerhead Ribozyme and Target Sequence

Nt. Ribozyme Sequence Seq. ID Substrate Sequence Seq. ID Position Nos. Nos.

15 UGCCGCUC CUGAUGAG X CGAA AGGCCGCG 1 CGCGGCCT A GAGCGGCA 529

72 AUCUCCAU CUGAUGAG X CGAA ACGGGCCA 2 TGGCCCGT C ATGGAGAT 530

92 UCUGCUCG CUGAUGAG X CGAA ACUCCUUU 3 AAAGGAGT T CGAGCAGA 531

93 AUCUGCUC CUGAUGAG X CGAA AACUCCUU 4 AAGGAGTT C GAGCAGAT 532

102 GACUUGUC CUGAUGAG X CGAA AUCUGCUC 5 GAGCAGAT C GACAAGTC 533

110 AGCUCCCG CUGAUGAG X CGAA ACUUGUCG 6 CGACAAGT c CGGGAGCT 534

129 UCCUGGUA CUGAUGAG X CGAA AUGGCCGC 7 GCGGCCAT T TACCAGGA 535

130 AUCCUGGU CUGAUGAG X CGAA AAUGGCCG 8 CGGCCATT T ACCAGGAT 536

131 UAUCCUGG CUGAUGAG X CGAA AAAUGGCC 9 GGCCATTT A CCAGGATA 537

139 AUGUCGGA CUGAUGAG X CGAA AUCCUGGU 10 ACCAGGAT A TCCGACAT 538

141 UCAUGUCG CUGAUGAG X CGAA AUAUCCUG 11 CAGGATAT c CGACATGA 539

161 UACAUGGG CUGAUGAG X CGAA AGUCACUG 12 CAGTGACT T CCCATGTA 540

162 CUACAUGG CUGAUGAG X CGAA AAGUCACU 13 AGTGACTT c CCATGTAG 541

169 GGCCACUC CUGAUGAG X CGAA ACAUGGGA 14 TCCCATGT A GAGTGGCC 542

183 UUCUUAGG CUGAUGAG X CGAA AGCUUGGC 15 GCCAAGCT T CCTAAGAA 543

184 GUUCUUAG CUGAUGAG X CGAA AAGCUUGG 16 CCAAGCTT c CTAAGAAC 544

187 UUUGUUCU CUGAUGAG X CGAA AGGAAGCU 17 AGCTTCCT A AGAACAAA 545

205 UCUGUACC CUGAUGAG X CGAA AUUUCGGU 18 ACCGAAAT A GGTACAGA 546

209 CGUCUCUG CUGAUGAG X CGAA ACCUAUUU 19 AAATAGGT A CAGAGACG 547

219 AAGGGACU CUGAUGAG X CGAA ACGUCUCU 20 AGAGACGT C AGTCCCTT 548

223 GUCAAAGG CUGAUGAG X CGAA ACUGACGU 21 ACGTCAGT C CCTTTGAC 549

227 UAUGGUCA CUGAUGAG X CGAA AGGGACUG 22 CAGTCCCT T TGACCATA 550

228 CUAUGGUC CUGAUGAG X CGAA AAGGGACU 23 AGTCCCTT T GACCATAG 551

235 AAUCCGAC CUGAUGAG X CGAA AUGGUCAA 24 TTGACCAT A GTCGGATT 552

238 UUUAAUCC CUGAUGAG X CGAA ACUAUGGU 25 ACCATAGT C GGATTAAA 553

243 UGUAGUUU CUGAUGAG X CGAA AUCCGACU 26 AGTCGGAT T AAACTACA 554

244 AUGUAGUU CUGAUGAG X CGAA AAUCCGAC 27 GTCGGATT A AACTACAT 555

249 UCUUGAUG CUGAUGAG X CGAA AGUUUAAU 28 ATTAAACT A CATCAAGA 556

253 AUCUUCUU CUGAUGAG X CGAA AUGUAGUU 29 AACTACAT C AAGAAGAT 557

262 AUAGUCAU CUGAUGAG X CGAA AUCUUCUU 30 AAGAAGAT A ATGACTAT 558

269 CGUUGAUA CUGAUGAG X CGAA AGUCAUUA 31 TAATGACT A TATCAACG 559

271 AGCGUUGA CUGAUGAG X CGAA AUAGUCAU 32 ATGACTAT A TCAACGCT 560

273 CUAGCGUU CUGAUGAG X CGAA AUAUAGUC 33 GACTATAT C AACGCTAG 561

280 UAUCAAAC CUGAUGAG X CGAA AGCGUUGA 34 TCAACGCT A GTTTGATA 562

283 UUUUAUCA CUGAUGAG X CGAA ACUAGCGU 35 ACGCTAGT T TGATAAAA 563

284 UUUUUAUC CUGAUGAG X CGAA AACUAGCG 36 CGCTAGTT T GATAAAAA 564

288 UCCAUUUU CUGAUGAG X CGAA AUCAAACU 37 AGTTTGAT A AAAATGGA 565

313 AAGAAUGU CUGAUGAG X CGAA ACUCCUUU 38 AAAGGAGT T ACATTCTT 566

314 UAAGAAUG CUGAUGAG X CGAA AACUCCUU 39 AAGGAGTT A CATTCTTA 567

318 UGGGUAAG CUGAUGAG X CGAA AUGUAACU 40 AGTTACAT T CTTACCCA 568

319 CUGGGUAA CUGAUGAG X CGAA AAUGUAAC 41 GTTACATT C TTACCCAG 569

321 CCCUGGGU CUGAUGAG X CGAA AGAAUGUA 42 TACATTCT T ACCCAGGG 570

322 GCCCUGGG CUGAUGAG X CGAA AAGAAUGU 43 ACATTCTT A CCCAGGGC 571

334 GUUAGGCA CUGAUGAG X CGAA AGGGCCCU 44 AGGGCCCT T TGCCTAAC 572 Table 3

335 UGUUAGGC CUGAUGAG X CGAA AAGGGCCC 45 GGGCCCTT T GCCTAACA 573

340 GCAUGUGU CUGAUGAG X CGAA AGGCAAAG 46 CTTTGCCT A ACACATGC 574

352 CCAAAAGU CUGAUGAG X CGAA ACCGCAUG 47 CATGCGGT C ACTTTTGG 575

356 UCUCCCAA CUGAUGAG X CGAA AGUGACCG 48 CGGTCACT T TTGGGAGA 576

357 AUCUCCCA CUGAUGAG X CGAA AAGUGACC 49 GGTCACTT T TGGGAGAT 577

358 CAUCUCCC CUGAUGAG X CGAA AAAGUGAC 50 GTCACTTT T GGGAGATG 578

393 AGCAUGAC CUGAUGAG X CGAA ACACCCCU 51 AGGGGTGT C GTCATGCT 579

396 UUGAGCAU CUGAUGAG X CGAA ACGACACC 52 GGTGTCGT c ATGCTCAA 580

402 ACUCUGUU CUGAUGAG X CGAA AGCAUGAC 53 GTCATGCT c AACAGAGT 581

424 UUUUAACG CUGAUGAG X CGAA ACCUUUCU 54 AGAAAGGT T CGTTAAAA 582

425 AUUUUAAC CUGAUGAG X CGAA AACCUUUC 55 GAAAGGTT C GTTAAAAT 583

428 CGCAUUUU CUGAUGAG X CGAA ACGAACCU 56 AGGTTCGT T AAAATGCG 584

429 GCGCAUUU CUGAUGAG X CGAA AACGAACC 57 GGTTCGTT A AAATGCGC 585

443 GUGGCCAG CUGAUGAG X CGAA AUUGUGCG 58 CGCACAAT A CTGGCCAC 586

474 UCUUCAAA CUGAUGAG X CGAA AUCAUCUC 59 GAGATGAT C TTTGAAGA 587

476 UGUCUUCA CUGAUGAG X CGAA AGAUCAUC 60 GATGATCT T TGAAGACA 588

477 GUGUCUUC CUGAUGAG X CGAA AAGAUCAU 61 ATGATCTT T GAAGACAC 589

490 UAAUUUCA CUGAUGAG X CGAA AUUUGUGU 62 ACACAAAT T TGAAATTA 590

491 UUAAUUUC CUGAUGAG X CGAA AAUUUGUG 63 CACAAATT T GAAATTAA 591

497 UCAAUGUU CUGAUGAG X CGAA AUUUCAAA 64 TTTGAAAT T AACATTGA 592

498 AUCAAUGU CUGAUGAG X CGAA AAUUUCAA 65 TTGAAATT A ACATTGAT 593

503 CAGAGAUC CUGAUGAG X CGAA AUGUUAAU 66 ATTAACAT T GATCTCTG 594

507 UCUUCAGA CUGAUGAG X CGAA AUCAAUGU 67 ACATTGAT c TCTGAAGA 595

509 UAUCUUCA CUGAUGAG X CGAA AGAUCAAU 68 ATTGATCT C TGAAGATA 596

517 UGACUUGA CUGAUGAG X CGAA AUCUUCAG 69 CTGAAGAT A TCAAGTCA 597

519 UAUGACUU CUGAUGAG X CGAA AUAUCUUC 70 GAAGATAT C AAGTCATA 598

524 UAUAAUAU CUGAUGAG X CGAA ACUUGAUA 71 TATCAAGT C ATATTATA 599

527 CUGUAUAA CUGAUGAG X CGAA AUGACUUG 72 CAAGTCAT A TTATACAG 600

529 CACUGUAU CUGAUGAG X CGAA AUAUGACU 73 AGTCATAT T ATACAGTG 601

530 GCACUGUA CUGAUGAG X CGAA AAUAUGAC 74 GTCATATT A TACAGTGC 602

532 UCGCACUG CUGAUGAG X CGAA AUAAUAUG 75 CATATTAT A CAGTGCGA 603

546 UCCAAUUC CUGAUGAG X CGAA AGCUGUCG 76 CGACAGCT A GAATTGGA 604

551 GGUUUUCC CUGAUGAG X CGAA AUUCUAGC 77 GCTAGAAT T GGAAAACC 605

561 UGGGUUGU CUGAUGAG X CGAA AGGUUUUC 78 GAAAACCT T ACAACCCA 606

562 UUGGGUUG CUGAUGAG X CGAA AAGGUUUU 79 AAAACCTT A CAACCCAA 607

577 GAUCUCUC CUGAUGAG X CGAA AGUUUCUU 80 AAGAAACT C GAGAGATC 608

585 AAAUGUAA CUGAUGAG X CGAA AUCUCUCG 81 CGAGAGAT C TTACATTT 609

587 GGAAAUGU CUGAUGAG X CGAA AGAUCUCU 82 AGAGATCT T ACATTTCC 610

588 UGGAAAUG CUGAUGAG X CGAA AAGAUCUC 83 GAGATCTT A CATTTCCA 611

592 AUAGUGGA CUGAUGAG X CGAA AUGUAAGA 84 TCTTACAT T TCCACTAT 612

593 UAUAGUGG CUGAUGAG X CGAA AAUGUAAG 85 CTTACATT T CCACTATA 613

594 GUAUAGUG CUGAUGAG X CGAA AAAUGUAA 86 TTACATTT C CACTATAC 614

599 AUGUGGUA CUGAUGAG X CGAA AGUGGAAA 87 TTTCCACT A TACCACAT 615

601 CCAUGUGG CUGAUGAG X CGAA AUAGUGGA 88 TCCACTAT A CCACATGG 616

617 GGACUCCA CUGAUGAG X CGAA AGUCAGGC 89 GCCTGACT T TGGAGTCC 617

618 GGGACUCC CUGAUGAG X CGAA AAGUCAGG 90 CCTGACTT T GGAGTCCC 618

624 GAUUCAGG CUGAUGAG X CGAA ACUCCAAA 91 TTTGGAGT C CCTGAATC 619 Table 3

632 AGGCUGGU CUGAUGAG X CGAA AUUCAGGG 92 CCCTGAAT C ACCAGCCT 620

641 UCAAGAAU CUGAUGAG X CGAA AGGCUGGU 93 ACCAGCCT C ATTCTTGA 621

644 AGUUCAAG CUGAUGAG X CGAA AUGAGGCU 94 AGCCTCAT T CTTGAACT 622

645 AAGUUCAA CUGAUGAG X CGAA AAUGAGGC 95 GCCTCATT C TTGAACTT 623

647 GAAAGUUC CUGAUGAG X CGAA AGAAUGAG 96 CTCATTCT T GAACTTTC 624

653 UGAAAAGA CUGAUGAG X CGAA AGUUCAAG 97 CTTGAACT T TCTTTTCA 625

654 UUGAAAAG CUGAUGAG X CGAA AAGUUCAA 98 TTGAACTT T CTTTTCAA 626

655 UUUGAAAA CUGAUGAG X CGAA AAAGUUCA 99 TGAACTTT C TTTTCAAA 627

657 ACUUUGAA CUGAUGAG X CGAA AGAAAGUU 100 AACTTTCT T TTCAAAGT 628

658 GACUUUGA CUGAUGAG X CGAA AAGAAAGU 101 ACTTTCTT T TCAAAGTC 629

659 GGACUUUG CUGAUGAG X CGAA AAAGAAAG 102 CTTTCTTT T CAAAGTCC 630

660 CGGACUUU CUGAUGAG X CGAA AAAAGAAA 103 TTTCTTTT C AAAGTCCG 631

666 GACUCUCG CUGAUGAG X CGAA ACUUUGAA 104 TTCAAAGT C CGAGAGTC 632

674 GUGACCCU CUGAUGAG X CGAA ACUCUCGG 105 CCGAGAGT C AGGGTCAC 633

680 GGCUGAGU CUGAUGAG X CGAA ACCCUGAC 106 GTCAGGGT C ACTCAGCC 634

684 UCCGGGCU CUGAUGAG X CGAA AGUGACCC 107 GGGTCACT C AGCCCGGA 635

705 UGCACCAC CUGAUGAG X CGAA ACGGGCCC 108 GGGCCCGT T GTGGTGCA 636

729 GACCUGCC CUGAUGAG X CGAA AUGCCUGC 109 GCAGGCAT C GGCAGGTC 637

737 AGGUUCCA CUGAUGAG X CGAA ACCUGCCG 110 CGGCAGGT C TGGAACCT 638

746 CCAGACAG CUGAUGAG X CGAA AGGUUCCA 111 TGGAACCT T CTGTCTGG 639

747 GCCAGACA CUGAUGAG X CGAA AAGGUUCC 112 GGAACCTT C TGTCTGGC 640

751 AUCAGCCA CUGAUGAG X CGAA ACAGAAGG 113 CCTTCTGT C TGGCTGAT 641

760 GAGGCAGG CUGAUGAG X CGAA AUCAGCCA 114 TGGCTGAT A CCTGCCTC 642

768 AUCAGCAA CUGAUGAG X CGAA AGGCAGGU 115 ACCTGCCT C TTGCTGAT 643

770 CCAUCAGC CUGAUGAG X CGAA AGAGGCAG 116 CTGCCTCT T GCTGATGG 644

796 AACGGAAG CUGAUGAG X CGAA AGGGUCUU 117 AAGACCCT T CTTCCGTT 645

797 CAACGGAA CUGAUGAG X CGAA AAGGGUCU 118 AGACCCTT c TTCCGTTG 646

799 AUCAACGG CUGAUGAG X CGAA AGAAGGGU 119 ACCCTTCT T CCGTTGAT 647

800 UAUCAACG CUGAUGAG X CGAA AAGAAGGG 120 CCCTTCTT c CGTTGATA 648

804 UUGAUAUC CUGAUGAG X CGAA ACGGAAGA 121 TCTTCCGT T GATATCAA 649

808 UUUCUUGA CUGAUGAG X CGAA AUCAACGG 122 CCGTTGAT A TCAAGAAA 650

810 ACUUUCUU CUGAUGAG X CGAA AUAUCAAC 123 GTTGATAT c AAGAAAGT 651

824 UCAUUUCU CUGAUGAG X CGAA ACAGCACU 124 AGTGCTGT T AGAAATGA 652

825 CUCAUUUC CUGAUGAG X CGAA AACAGCAC 125 GTGCTGTT A GAAATGAG 653

839 CCAUCCGA CUGAUGAG X CGAA ACUUCCUC 126 GAGGAAGT T TCGGATGG 654

840 CCCAUCCG CUGAUGAG X CGAA AACUUCCU 127 AGGAAGTT T CGGATGGG 655

841 CCCCAUCC CUGAUGAG X CGAA AAACUUCC 128 GGAAGTTT c GGATGGGG 656

855 GCUGUCUG CUGAUGAG X CGAA AUCAGCCC 129 GGGCTGAT c CAGACAGC 657

878 GGUAGGAG CUGAUGAG X CGAA AGCGCAGC 130 GCTGCGCT T CTCCTACC 658

879 AGGUAGGA CUGAUGAG X CGAA AAGCGCAG 131 CTGCGCTT c TCCTACCT 659

881 CCAGGUAG CUGAUGAG X CGAA AGAAGCGC 132 GCGCTTCT c CTACCTGG 660

884 CAGCCAGG CUGAUGAG X CGAA AGGAGAAG 133 CTTCTCCT A CCTGGCTG 661

897 GCACCUUC CUGAUGAG X CGAA AUCACAGC 134 GCTGTGAT C GAAGGTGC 662

911 CCAUGAUG CUGAUGAG X CGAA AUUUGGCA 135 TGCCAAAT T CATCATGG 663

912 CCCAUGAU CUGAUGAG X CGAA AAUUUGGC 136 GCCAAATT c ATCATGGG 664

915 UCCCCCAU CUGAUGAG X CGAA AUGAAUUU 137 AAATTCAT c ATGGGGGA 665

926 GCACGGAA CUGAUGAG X CGAA AGUCCCCC 138 GGGGGACT c TTCCGTGC 666 Table 3

928 CUGCACGG CUGAUGAG X CGAA AGAGUCCC 139 GGGACTCT T CCGTGCAG 667

929 CCUGCACG CUGAUGAG X CGAA AAGAGUCC 140 GGACTCTT C CGTGCAGG 668

940 CUUCCACU CUGAUGAG X CGAA AUCCUGCA 141 TGCAGGAT C AGTGGAAG 669

954 UCGUGGGA CUGAUGAG X CGAA AGCUCCUU 142 AAGGAGCT T TCCCACGA 670

955 CUCGUGGG CUGAUGAG X CGAA AAGCUCCU 143 AGGAGCTT T CCCACGAG 671

956 CCUCGUGG CUGAUGAG X CGAA AAAGCUCC 144 GGAGCTTT C CCACGAGG 672

988 UGGGGGGA CUGAUGAG X CGAA AUGCUCGG 145 CCGAGCAT A TCCCCCCA 673

990 GGUGGGGG CUGAUGAG X CGAA AUAUGCUC 146 GAGCATAT C CCCCCACC 674

1000 UGGCCGGG CUGAUGAG X CGAA AGGUGGGG 147 CCCCACCT C CCCGGCCA 675

1020 GGCUCCAG CUGAUGAG X CGAA AUUCGUUU 148 AAACGAAT C CTGGAGCC 676

1052 UUGGGAAG CUGAUGAG X CGAA ACUCCCUG 149 CAGGGAGT T CTTCCCAA 677

1053 UUUGGGAA CUGAUGAG X CGAA AACUCCCU 150 AGGGAGTT C TTCCCAAA 678

1055 GAUUUGGG CUGAUGAG X CGAA AGAACUCC 151 GGAGTTCT T CCCAAATC 679

1056 UGAUUUGG CUGAUGAG X CGAA AAGAACUC 152 GAGTTCTT C CCAAATCA 680

1063 CCACUGGU CUGAUGAG X CGAA AUUUGGGA 153 TCCCAAAT C ACCAGTGG 681

1096 GCAGUCUU CUGAUGAG X CGAA AUCCUCCU 154 AGGAGGAT A AAGACTGC 682

1110 UCUUCCUU CUGAUGAG X CGAA AUGGGGCA 155 TGCCCCAT C AAGGAAGA 683

1133 CGGCAUUU CUGAUGAG X CGAA AGGGGCUU 156 AAGCCCCT T AAATGCCG 684

1134 GCGGCAUU CUGAUGAG X CGAA AAGGGGCU 157 AGCCCCTT A AATGCCGC 685

1148 CGAUGCCG CUGAUGAG X CGAA AGGGUGCG 158 CGCACCCT A CGGCATCG 686

1155 AUGCUUUC CUGAUGAG X CGAA AUGCCGUA 159 TACGGCAT C GAAAGCAT 687

1168 AGUGUCUU CUGAUGAG X CGAA ACUCAUGC 160 GCATGAGT C AAGACACT 688

1182 CGACUUCU CUGAUGAG X CGAA ACUUCAGU 161 ACTGAAGT T AGAAGTCG 689

1183 CCGACUUC CUGAUGAG X CGAA AACUUCAG 162 CTGAAGTT A GAAGTCGG 690

1189 CACGACCC CUGAUGAG X CGAA ACUUCUAA 163 TTAGAAGT C GGGTCGTG 691

1194 CCCCCCAC CUGAUGAG X CGAA ACCCGACU 164 AGTCGGGT C GTGGGGGG 692

1207 ACCUCGAA CUGAUGAG X CGAA ACUUCCCC 165 GGGGAAGT C TTCGAGGT 693

1209 GCACCUCG CUGAUGAG X CGAA AGACUUCC 166 GGAAGTCT T CGAGGTGC 694

1210 GGCACCUC CUGAUGAG X CGAA AAGACUUC 167 GAAGTCTT C GAGGTGCC 695

1229 UGGCUGGG CUGAUGAG X CGAA AGGCAGCC 168 GGCTGCCT C CCCAGCCA 696

1250 CGGGCAGU CUGAUGAG X CGAA ACGGCUCC 169 GGAGCCGT C ACTGCCCG 697

1285 CUUCCAGU CUGAUGAG X CGAA ACUCAGUG 170 CACTGAGT T ACTGGAAG 698

1286 GCUUCCAG CUGAUGAG X CGAA AACUCAGU 171 ACTGAGTT A CTGGAAGC 699

1298 UGACCAGG CUGAUGAG X CGAA AGGGCUUC 172 GAAGCCCT T CCTGGTCA 700

1299 UUGACCAG CUGAUGAG X CGAA AAGGGCUU 173 AAGCCCTT C CTGGTCAA 701

1305 CACAUGUU CUGAUGAG X CGAA ACCAGGAA 174 TTCCTGGT C AACATGTG 702

1321 GAGGACCG CUGAUGAG X CGAA AGCCACGC 175 GCGTGGCT A CGGTCCTC 703

1326 GCCGUGAG CUGAUGAG X CGAA ACCGUAGC 176 GCTACGGT C CTCACGGC 704

1329 CCGGCCGU CUGAUGAG X CGAA AGGACCGU 177 ACGGTCCT C ACGGCCGG 705

1342 GCAGAGGU CUGAUGAG X CGAA AGCGCCGG 178 CCGGCGCT T ACCTCTGC 706

1343 AGCAGAGG CUGAUGAG X CGAA AAGCGCCG 179 CGGCGCTT A CCTCTGCT 707

1347 CUGUAGCA CUGAUGAG X CGAA AGGUAAGC 180 GCTTACCT C TGCTACAG 708

1352 GGAACCUG CUGAUGAG X CGAA AGCAGAGG 181 CCTCTGCT A CAGGTTCC 709

1358 UGAACAGG CUGAUGAG X CGAA ACCUGUAG 182 CTACAGGT T CCTGTTCA 710

1359 UUGAACAG CUGAUGAG X CGAA AACCUGUA 183 TACAGGTT C CTGTTCAA 711

1364 UGCUGUUG CUGAUGAG X CGAA ACAGGAAC 184 GTTCCTGT T CAACAGCA 712

1365 UUGCUGUU CUGAUGAG X CGAA AACAGGAA 185 TTCCTGTT C AACAGCAA 713 Table 3

1379 GGUCAGGC CUGAUGAG X CGAA AUGUGUUG 186 CAACACAT A GCCTGACC 714

1390 GAGUGGAG CUGAUGAG X CGAA AGGGUCAG 187 CTGACCCT C CTCCACTC 715

1393 GUGGAGUG CUGAUGAG X CGAA AGGAGGGU 188 ACCCTCCT C CACTCCAC 716

1398 UGGAGGUG CUGAUGAG X CGAA AGUGGAGG 189 CCTCCACT C CACCTCCA 717

1404 AGUGGGUG CUGAUGAG X CGAA AGGUGGAG 190 CTCCACCT C CACCCACT 718

1415 CAGAGGCG CUGAUGAG X CGAA ACAGUGGG 191 CCCACTGT C CGCCTCTG 719

1421 UGCGGGCA CUGAUGAG X CGAA AGGCGGAC 192 GTCCGCCT C TGCCCGCA 720

1446 AUGCCUGC CUGAUGAG X CGAA AGUCGGGC 193 GCCCGACT A GCAGGCAT 721

1463 CCCUUACC CUGAUGAG X CGAA ACCGCGGC 194 GCCGCGGT A GGTAAGGG 722

1467 GCGGCCCU CUGAUGAG X CGAA ACCUACCG 195 CGGTAGGT A AGGGCCGC 723

1486 CGGCUCUC CUGAUGAG X CGAA ACGCGGUC 196 GACCGCGT A GAGAGCCG 724

1511 GCAGAACC CUGAUGAG X CGAA ACGUCCGU 197 ACGGACGT T GGTTCTGC 725

1515 UAGUGCAG CUGAUGAG X CGAA ACCAACGU 198 ACGTTGGT T CTGCACTA 726

1516 UUAGUGCA CUGAUGAG X CGAA AACCAACG 199 CGTTGGTT C TGCACTAA 727

1523 AUGGGUUU CUGAUGAG X CGAA AGUGCAGA 200 TCTGCACT A AAACCCAT 728

1532 CCGGGGAA CUGAUGAG X CGAA AUGGGUUU 201 AAACCCAT C TTCCCCGG 729

1534 AUCCGGGG CUGAUGAG X CGAA AGAUGGGU 202 ACCCATCT T CCCCGGAT 730

1535 CAUCCGGG CUGAUGAG X CGAA AAGAUGGG 203 CCCATCTT c CCCGGATG 731

1549 AGGGGUGA CUGAUGAG X CGAA ACACACAU 204 ATGTGTGT c TCACCCCT 732

1551 UGAGGGGU CUGAUGAG X CGAA AGACACAC 205 GTGTGTCT c ACCCCTCA 733

1558 AAAAGGAU CUGAUGAG X CGAA AGGGGUGA 206 TCACCCCT c ATCCTTTT 734

1561 AGUAAAAG CUGAUGAG X CGAA AUGAGGGG 207 CCCCTCAT c CTTTTACT 735

1564 AAAAGUAA CUGAUGAG X CGAA AGGAUGAG 208 CTCATCCT T TTACTTTT 736

1565 AAAAAGUA CUGAUGAG X CGAA AAGGAUGA 209 TCATCCTT T TACTTTTT 737

1566 CAAAAAGU CUGAUGAG X CGAA AAAGGAUG 210 CATCCTTT T ACTTTTTG 738

1567 GCAAAAAG CUGAUGAG X CGAA AAAAGGAU 211 ATCCTTTT A CTTTTTGC 739

1570 GGGGCAAA CUGAUGAG X CGAA AGUAAAAG 212 CTTTTACT T TTTGCCCC 740

1571 AGGGGCAA CUGAUGAG X CGAA AAGUAAAA 213 TTTTACTT T TTGCCCCT 741

1572 AAGGGGCA CUGAUGAG X CGAA AAAGUAAA 214 TTTACTTT T TGCCCCTT 742

1573 GAAGGGGC CUGAUGAG X CGAA AAAAGUAA 215 TTACTTTT T GCCCCTTC 743

1580 CAAAGUGG CUGAUGAG X CGAA AGGGGCAA 216 TTGCCCCT T CCACTTTG 744

1581 UCAAAGUG CUGAUGAG X CGAA AAGGGGCA 217 TGCCCCTT c CACTTTGA 745

1586 GGUACUCA CUGAUGAG X CGAA AGUGGAAG 218 CTTCCACT T TGAGTACC 746

1587 UGGUACUC CUGAUGAG X CGAA AAGUGGAA 219 TTCCACTT T GAGTACCA 747

1592 GGAUUUGG CUGAUGAG X CGAA ACUCAAAG 220 CTTTGAGT A CCAAATCC 748

1599 GGCUUGUG CUGAUGAG X CGAA AUUUGGUA 221 TACCAAAT C CACAAGCC 749

1610 CCUCAAAA CUGAUGAG X CGAA AUGGCUUG 222 CAAGCCAT T TTTTGAGG 750

1611 UCCUCAAA CUGAUGAG X CGAA AAUGGCUU 223 AAGCCATT T TTTGAGGA 751

1612 CUCCUCAA CUGAUGAG X CGAA AAAUGGCU 224 AGCCATTT T TTGAGGAG 752

1613 UCUCCUCA CUGAUGAG X CGAA AAAAUGGC 225 GCCATTTT T TGAGGAGA 753

1614 CUCUCCUC CUGAUGAG X CGAA AAAAAUGG 226 CCATTTTT T GAGGAGAG 754

1634 CAGCAUGG CUGAUGAG X CGAA ACUCUCUU 227 AAGAGAGT A CCATGCTG 755

1665 GACGGGUG CUGAUGAG X CGAA AGGCCCCU 228 AGGGGCCT A CACCCGTC 756

1673 AGCCCCAA CUGAUGAG X CGAA ACGGGUGU 229 ACACCCGT C TTGGGGCT 757

1675 CGAGCCCC CUGAUGAG X CGAA AGACGGGU 230 ACCCGTCT T GGGGCTCG 758

1682 GGUGGGGC CUGAUGAG X CGAA AGCCCCAA 231 TTGGGGCT C GCCCCACC 759

1698 CCAGGAGG CUGAUGAG X CGAA AGCCCUGG 232 CCAGGGCT C CCTCCTGG 760 Table 3

1702 UGCUCCAG CUGAUGAG X CGAA AGGGAGCC 233 GGCTCCCT C CTGGAGCA 761

1712 CCGCCUGG CUGAUGAG X CGAA AUGCUCCA 234 TGGAGCAT C CCAGGCGG 762

1746 GCAGAUUC CUGAUGAG X CGAA AGGGGGGG 235 CCCCCCCT T GAATCTGC 763

1751 UCCCUGCA CUGAUGAG X CGAA AUUCAAGG 236 CCTTGAAT C TGCAGGGA 764

1766 GGAGUGGA CUGAUGAG X CGAA AGUUGCUC 237 GAGCAACT C TCCACTCC 765

1768 AUGGAGUG CUGAUGAG X CGAA AGAGUUGC 238 GCAACTCT C CACTCCAT 766

1773 UAAAUAUG CUGAUGAG X CGAA AGUGGAGA 239 TCTCCACT C CATATTTA 767

1777 UAAAUAAA CUGAUGAG X CGAA AUGGAGUG 240 CACTCCAT A TTTATTTA 768

1779 UUUAAAUA CUGAUGAG X CGAA AUAUGGAG 241 CTCCATAT T TATTTAAA 769

1780 GUUUAAAU CUGAUGAG X CGAA AAUAUGGA 242 TCCATATT T ATTTAAAC 770

1781 UGUUUAAA CUGAUGAG X CGAA AAAUAUGG 243 CCATATTT A TTTAAACA 771

1783 AUUGUUUA CUGAUGAG X CGAA AUAAAUAU 244 ATATTTAT T TAAACAAT 772

1784 AAUUGUUU CUGAUGAG X CGAA AAUAAAUA 245 TATTTATT T AAACAATT 773

1785 AAAUUGUU CUGAUGAG X CGAA AAAUAAAU 246 ATTTATTT A AACAATTT 774

1792 GGGGAAAA CUGAUGAG X CGAA AUUGUUUA 247 TAAACAAT T TTTTCCCC 775

1793 UGGGGAAA CUGAUGAG X CGAA AAUUGUUU 248 AAACAATT T TTTCCCCA 776

1794 UUGGGGAA CUGAUGAG X CGAA AAAUUGUU 249 AACAATTT T TTCCCCAA 777

1795 UUUGGGGA CUGAUGAG X CGAA AAAAUUGU 250 ACAATTTT T TCCCCAAA 778

1796 CUUUGGGG CUGAUGAG X CGAA AAAAAUUG 251 CAATTTTT T CCCCAAAG 779

1797 CCUUUGGG CUGAUGAG X CGAA AAAAAAUU 252 AATTTTTT C CCCAAAGG 780

1809 GCACUAUG CUGAUGAG X CGAA AUGCCUUU 253 AAAGGCAT C CATAGTGC 781

1813 UAGUGCAC CUGAUGAG X CGAA AUGGAUGC 254 GCATCCAT A GTGCACTA 782

1821 GAAAAUGC CUGAUGAG X CGAA AGUGCACU 255 AGTGCACT A GCATTTTC 783

1826 UUCAAGAA CUGAUGAG X CGAA AUGCUAGU 256 ACTAGCAT T TTCTTGAA 784

1827 GUUCAAGA CUGAUGAG X CGAA AAUGCUAG 257 CTAGCATT T TCTTGAAC 785

1828 GGUUCAAG CUGAUGAG X CGAA AAAUGCUA 258 TAGCATTT T CTTGAACC 786

1829 UGGUUCAA CUGAUGAG X CGAA AAAAUGCU 259 AGCATTTT C TTGAACCA 787

1831 AUUGGUUC CUGAUGAG X CGAA AGAAAAUG 260 CATTTTCT T GAACCAAT 788

1840 UAAUACAU CUGAUGAG X CGAA AUUGGUUC 261 GAACCAAT A ATGTATTA 789

1845 AAUUUUAA CUGAUGAG X CGAA ACAUUAUU 262 AATAATGT A TTAAAATT 790

1847 AAAAUUUU CUGAUGAG X CGAA AUACAUUA 263 TAATGTAT T AAAATTTT 791

1848 AAAAAUUU CUGAUGAG X CGAA AAUACAUU 264 AATGTATT A AAATTTTT 792

1853 CAUCAAAA CUGAUGAG X CGAA AUUUUAAU 265 ATTAAAAT T TTTTGATG 793

1854 ACAUCAAA CUGAUGAG X CGAA AAUUUUAA 266 TTAAAATT T TTTGATGT 794

1855 GACAUCAA CUGAUGAG X CGAA AAAUUUUA 267 TAAAATTT T TTGATGTC 795

1856 UGACAUCA CUGAUGAG X CGAA AAAAUUUU 268 AAAATTTT T TGATGTCA 796

1857 CUGACAUC CUGAUGAG X CGAA AAAAAUUU 269 AAATTTTT T GATGTCAG 797

1863 GCAAGGCU CUGAUGAG X CGAA ACAUCAAA 270 TTTGATGT C AGCCTTGC 798

1869 CUUGAUGC CUGAUGAG X CGAA AGGCUGAC 271 GTCAGCCT T GCATCAAG 799

1874 AAGCCCUU CUGAUGAG X CGAA AUGCAAGG 272 CCTTGCAT c AAGGGCTT 800

1882 UUUUGAUA CUGAUGAG X CGAA AGCCCUUG 273 CAAGGGCT T TATCAAAA 801

1883 UUUUUGAU CUGAUGAG X CGAA AAGCCCUU 274 AAGGGCTT T ATCAAAAA 802

1884 CUUUUUGA CUGAUGAG X CGAA AAAGCCCU 275 AGGGCTTT A TCAAAAAG 803

1886 UACUUUUU CUGAUGAG X CGAA AUAAAGCC 276 GGCTTTAT C AAAAAGTA 804

1894 UAUUAUUG CUGAUGAG X CGAA ACUUUUUG 277 CAAAAAGT A CAATAATA 805

1899 GGAUUUAU CUGAUGAG X CGAA AUUGUACU 278 AGTACAAT A ATAAATCC 806

1902 UGAGGAUU CUGAUGAG X CGAA AUUAUUGU 279 ACAATAAT A AATCCTCA 807 Table 3

1906 UACCUGAG CUGAUGAG X CGAA AUUUAUUA 280 TAATAAAT C CTCAGGTA 808

1909 UACUACCU CUGAUGAG X CGAA AGGAUUUA 281 TAAATCCT C AGGTAGTA 809

1914 CCCAGUAC CUGAUGAG X CGAA ACCUGAGG 282 CCTCAGGT A GTACTGGG 810

1917 AUUCCCAG CUGAUGAG X CGAA ACUACCUG 283 CAGGTAGT A CTGGGAAT 811

1934 CCAUGGCA CUGAUGAG X CGAA AGCCUUCC 284 GGAAGGCT T TGCCATGG 812

1935 CCCAUGGC CUGAUGAG X CGAA AAGCCUUC 285 GAAGGCTT T GCCATGGG 813

1954 ACUGGUCU CUGAUGAG X CGAA ACGCAGCA 286 TGCTGCGT C AGACCAGT 814

1963 CUUCCCAG CUGAUGAG X CGAA ACUGGUCU 287 AGACCAGT A CTGGGAAG 815

1981 CUGCUUAC CUGAUGAG X CGAA ACCGUCCU 288 AGGACGGT T GTAAGCAG 816

1984 CAACUGCU CUGAUGAG X CGAA ACAACCGU 289 ACGGTTGT A AGCAGTTG 817

1991 UAAAUAAC CUGAUGAG X CGAA ACUGCUUA 290 TAAGCAGT T GTTATTTA 818

1994 CACUAAAU CUGAUGAG X CGAA ACAACUGC 291 GCAGTTGT T ATTTAGTG 819

1995 UCACUAAA CUGAUGAG X CGAA AACAACUG 292 CAGTTGTT A TTTAGTGA 820

1997 UAUCACUA CUGAUGAG X CGAA AUAACAAC 293 GTTGTTAT T TAGTGATA 821

1998 AUAUCACU CUGAUGAG X CGAA AAUAACAA 294 TTGTTATT T AGTGATAT 822

1999 AAUAUCAC CUGAUGAG X CGAA AAAUAACA 295 TGTTATTT A GTGATATT 823

2005 ACCCACAA CUGAUGAG X CGAA AUCACUAA 296 TTAGTGAT A TTGTGGGT 824

2007 UUACCCAC CUGAUGAG X CGAA AUAUCACU 297 AGTGATAT T GTGGGTAA 825

2014 UCUCACGU CUGAUGAG X CGAA ACCCACAA 298 TTGTGGGT A ACGTGAGA 826

2027 CAUUGUUC CUGAUGAG X CGAA AUCUUCUC 299 GAGAAGAT A GAACAATG 827

2038 AUAUAUUA CUGAUGAG X CGAA AGCAUUGU 300 ACAATGCT A TAATATAT 828

2040 UUAUAUAU CUGAUGAG X CGAA AUAGCAUU 301 AATGCTAT A ATATATAA 829

2043 UCAUUAUA CUGAUGAG X CGAA AUUAUAGC 302 GCTATAAT A TATAATGA 830

2045 GUUCAUUA CUGAUGAG X CGAA AUAUUAUA 303 TATAATAT A TAATGAAC 831

2047 GUGUUCAU CUGAUGAG X CGAA AUAUAUUA 304 TAATATAT A ATGAACAC 832

2062 UUAUUAAA CUGAUGAG X CGAA ACCCACGU 305 ACGTGGGT A TTTAATAA 833

2064 UCUUAUUA CUGAUGAG X CGAA AUACCCAC 306 GTGGGTAT T TAATAAGA 834

2065 UUCUUAUU CUGAUGAG X CGAA AAUACCCA 307 TGGGTATT T AATAAGAA 835

2066 UUUCUUAU CUGAUGAG X CGAA AAAUACCC 308 GGGTATTT A ATAAGAAA 836

2069 AUGUUUCU CUGAUGAG X CGAA AUUAAAUA 309 TATTTAAT A AGAAACAT 837

2088 GACAAAGU CUGAUGAG X CGAA AUCUCACA 310 TGTGAGAT T ACTTTGTC 838

2089 GGACAAAG CUGAUGAG X CGAA AAUCUCAC 311 GTGAGATT A CTTTGTCC 839

2092 GCGGGACA CUGAUGAG X CGAA AGUAAUCU 312 AGATTACT T TGTCCCGC 840

2093 AGCGGGAC CUGAUGAG X CGAA AAGUAAUC 313 GATTACTT T GTCCCGCT 841

2096 AUAAGCGG CUGAUGAG X CGAA ACAAAGUA 314 TACTTTGT C CCGCTTAT 842

2102 AGCAGAAU CUGAUGAG X CGAA AGCGGGAC 315 GTCCCGCT T ATTCTGCT 843

2103 GAGCAGAA CUGAUGAG X CGAA AAGCGGGA 316 TCCCGCTT A TTCTGCTC 844

2105 GGGAGCAG CUGAUGAG X CGAA AUAAGCGG 317 CCGCTTAT T CTGCTCCC 845

2106 AGGGAGCA CUGAUGAG X CGAA AAUAAGCG 318 CGCTTATT C TGCTCCCT 846

2111 AUAACAGG CUGAUGAG X CGAA AGCAGAAU 319 ATTCTGCT C CCTGTTAT 847

2117 UAGCAGAU CUGAUGAG X CGAA ACAGGGAG 320 CTCCCTGT T ATCTGCTA 848

2118 CUAGCAGA CUGAUGAG X CGAA AACAGGGA 321 TCCCTGTT A TCTGCTAG 849

2120 AUCUAGCA CUGAUGAG X CGAA AUAACAGG 322 CCTGTTAT C TGCTAGAT 850

2125 ACUAGAUC CUGAUGAG X CGAA AGCAGAUA 323 TATCTGCT A GATCTAGT 851

2129 GAGAACUA CUGAUGAG X CGAA AUCUAGCA 324 TGCTAGAT C TAGTTCTC 852

2131 UUGAGAAC CUGAUGAG X CGAA AGAUCUAG 325 CTAGATCT A GTTCTCAA 853

2134 UGAUUGAG CUGAUGAG X CGAA ACUAGAUC 326 GATCTAGT T CTCAATCA 854 Table 3

2135 GUGAUUGA CUGAUGAG X CGAA AACUAGAU 327 ATCTAGTT C TCAATCAC 855

2137 CAGUGAUU CUGAUGAG X CGAA AGAACUAG 328 CTAGTTCT C AATCACTG 856

2141 GGAGCAGU CUGAUGAG X CGAA AUUGAGAA 329 TTCTCAAT C ACTGCTCC 857

2148 ACACGGGG CUGAUGAG X CGAA AGCAGUGA 330 TCACTGCT C CCCCGTGT 858

2159 CAUUCUAA CUGAUGAG X CGAA ACACACGG 331 CCGTGTGT A TTAGAATG 859

2161 UGCAUUCU CUGAUGAG X CGAA AUACACAC 332 GTGTGTAT T AGAATGCA 860

2162 AUGCAUUC CUGAUGAG X CGAA AAUACACA 333 TGTGTATT A GAATGCAT 861

2173 GAAGACCU CUGAUGAG X CGAA ACAUGCAU 334 ATGCATGT A AGGTCTTC 862

2178 CACAAGAA CUGAUGAG X CGAA ACCUUACA 335 TGTAAGGT C TTCTTGTG 863

2180 GACACAAG CUGAUGAG X CGAA AGACCUUA 336 TAAGGTCT T CTTGTGTC 864

2181 GGACACAA CUGAUGAG X CGAA AAGACCUU 337 AAGGTCTT C TTGTGTCC 865

2183 CAGGACAC CUGAUGAG X CGAA AGAAGACC 338 GGTCTTCT T GTGTCCTG 866

2188 UUCAUCAG CUGAUGAG X CGAA ACACAAGA 339 TCTTGTGT C CTGATGAA 867

2201 CAAGCACA CUGAUGAG X CGAA AUUUUUCA 340 TGAAAAAT A TGTGCTTG 868

2208 CUCAUUUC CUGAUGAG X CGAA AGCACAUA 341 TATGTGCT T GAAATGAG 869

2222 AGAGAUCA CUGAUGAG X CGAA AGUUUCUC 342 GAGAAACT T TGATCTCT 870

2223 CAGAGAUC CUGAUGAG X CGAA AAGUUUCU 343 AGAAACTT T GATCTCTG 871

2227 UAAGCAGA CUGAUGAG X CGAA AUCAAAGU 344 ACTTTGAT c TCTGCTTA 872

2229 AGUAAGCA CUGAUGAG X CGAA AGAUCAAA 345 TTTGATCT c TGCTTACT 873

2234 ACAUUAGU CUGAUGAG X CGAA AGCAGAGA 346 TCTCTGCT T ACTAATGT 874

2235 CACAUUAG CUGAUGAG X CGAA AAGCAGAG 347 CTCTGCTT A CTAATGTG 875

2238 GGGCACAU CUGAUGAG X CGAA AGUAAGCA 348 TGCTTACT A ATGTGCCC 876

2252 UGGACUUG CUGAUGAG X CGAA ACAUGGGG 349 CCCCATGT C CAAGTCCA 877

2258 GCAGGUUG CUGAUGAG X CGAA ACUUGGAC 350 GTCCAAGT C CAACCTGC 878

2283 CAUGUAAU CUGAUGAG X CGAA AUCAGGUC 351 GACCTGAT C ATTACATG 879

2286 AGCCAUGU CUGAUGAG X CGAA AUGAUCAG 352 CTGATCAT T ACATGGCT 880

2287 CAGCCAUG CUGAUGAG X CGAA AAUGAUCA 353 TGATCATT A CATGGCTG 881

2300 GGCUUAGG CUGAUGAG X CGAA ACCACAGC 354 GCTGTGGT T CCTAAGCC 882

2301 AGGCUUAG CUGAUGAG X CGAA AACCACAG 355 CTGTGGTT c CTAAGCCT 883

2304 AACAGGCU CUGAUGAG X CGAA AGGAACCA 356 TGGTTCCT A AGCCTGTT 884

2312 ACUUCAGC CUGAUGAG X CGAA ACAGGCUU 357 AAGCCTGT T GCTGAAGT 885

2321 GCGACAAU CUGAUGAG X CGAA ACUUCAGC 358 GCTGAAGT C ATTGTCGC 886

2324 UGAGCGAC CUGAUGAG X CGAA AUGACUUC 359 GAAGTCAT T GTCGCTCA 887

2327 UGCUGAGC CUGAUGAG X CGAA ACAAUGAC 360 GTCATTGT C GCTCAGCA 888

2331 CUAUUGCU CUGAUGAG X CGAA AGCGACAA 361 TTGTCGCT c AGCAATAG 889

2338 CUGCACCC CUGAUGAG X CGAA AUUGCUGA 362 TCAGCAAT A GGGTGCAG 890

2348 UCCUGGAA CUGAUGAG X CGAA ACUGCACC 363 GGTGCAGT T TTCCAGGA 891

2349 UUCCUGGA CUGAUGAG X CGAA AACUGCAC 364 GTGCAGTT T TCCAGGAA 892

2350 AUUCCUGG CUGAUGAG X CGAA AAACUGCA 365 TGCAGTTT T CCAGGAAT 893

2351 UAUUCCUG CUGAUGAG X CGAA AAAACUGC 366 GCAGTTTT c CAGGAATA 894

2359 CAAAUGCC CUGAUGAG X CGAA AUUCCUGG 367 CCAGGAAT A GGCATTTG 895

2365 AUUAGGCA CUGAUGAG X CGAA AUGCCUAU 368 ATAGGCAT T TGCCTAAT 896

2366 AAUUAGGC CUGAUGAG X CGAA AAUGCCUA 369 TAGGCATT T GCCTAATT 897

- 2371 CCAGGAAU CUGAUGAG X CGAA AGGCAAAU 370 ATTTGCCT A ATTCCTGG 898

2374 AUGCCAGG CUGAUGAG X CGAA AUUAGGCA 371 TGCCTAAT T CCTGGCAT 899

2375 CAUGCCAG CUGAUGAG X CGAA AAUUAGGC 372 GCCTAATT C CTGGCATG 900

2389 AGUCACUA CUGAUGAG X CGAA AGUGUCAU 373 ATGACACT C TAGTGACT 901 Table 3

2391 GAAGUCAC CUGAUGAG X CGAA AGAGUGUC 374 GACACTCT A GTGACTTC 902

2398 UCACCAGG CUGAUGAG X CGAA AGUCACUA 375 TAGTGACT T CCTGGTGA 903

2399 CUCACCAG CUGAUGAG X CGAA AAGUCACU 376 AGTGACTT C CTGGTGAG 904

2419 UGUACCAG CUGAUGAG X CGAA ACAGGCUG 377 CAGCCTGT C CTGGTACA 905

2425 CCCUGCUG CUGAUGAG X CGAA ACCAGGAC 378 GTCCTGGT A CAGCAGGG 906

2435 UACAGCAA CUGAUGAG X CGAA ACCCUGCU 379 AGCAGGGT C TTGCTGTA 907

2437 GUUACAGC CUGAUGAG X CGAA AGACCCUG 380 CAGGGTCT T GCTGTAAC 908

2443 GUCUGAGU CUGAUGAG X CGAA ACAGCAAG 381 CTTGCTGT A ACTCAGAC 909

2447 GAAUGUCU CUGAUGAG X CGAA AGUUACAG 382 CTGTAACT C AGACATTC 910

2454 ACCCUUGG CUGAUGAG X CGAA AUGUCUGA 383 TCAGACAT T CCAAGGGT 911

2455 UACCCUUG CUGAUGAG X CGAA AAUGUCUG 384 CAGACATT c CAAGGGTA 912

2463 GCUUCCCA CUGAUGAG X CGAA ACCCUUGG 385 CCAAGGGT A TGGGAAGC 913

2475 GGUGUGAA CUGAUGAG X CGAA AUGGCUUC 386 GAAGCCAT A TTCACACC 914

2477 GAGGUGUG CUGAUGAG X CGAA AUAUGGCU 387 AGCCATAT T CACACCTC 915

2478 UGAGGUGU CUGAUGAG X CGAA AAUAUGGC 388 GCCATATT c ACACCTCA 916

2485 CAGAGCGU CUGAUGAG X CGAA AGGUGUGA 389 TCACACCT c ACGCTCTG 917

2491 CAUGUCCA CUGAUGAG X CGAA AGCGUGAG 390 CTCACGCT C TGGACATG 918

2502 CUUCCCUA CUGAUGAG X CGAA AUCAUGUC 391 GACATGAT T TAGGGAAG 919

2503 GCUUCCCU CUGAUGAG X CGAA AAUCAUGU 392 ACATGATT T AGGGAAGC 920

2504 UGCUUCCC CUGAUGAG X CGAA AAAUCAUG 393 CATGATTT A GGGAAGCA 921

2536 UGAUCCCA CUGAUGAG X CGAA AGGUGGGG 394 CCCCACCT T TGGGATCA 922

2537 CUGAUCCC CUGAUGAG X CGAA AAGGUGGG 395 CCCACCTT T GGGATCAG 923

2543 CGGAGGCU CUGAUGAG X CGAA AUCCCAAA 396 TTTGGGAT c AGCCTCCG 924

2549 GAAUGGCG CUGAUGAG X CGAA AGGCUGAU 397 ATCAGCCT c CGCCATTC 925

2556 CGACUUGG CUGAUGAG X CGAA AUGGCGGA 398 TCCGCCAT T CCAAGTCG 926

2557 UCGACUUG CUGAUGAG X CGAA AAUGGCGG 399 CCGCCATT c CAAGTCGA 927

2563 AGAGUGUC CUGAUGAG X CGAA ACUUGGAA 400 TTCCAAGT c GACACTCT 928

2570 CUCAAGAA CUGAUGAG X CGAA AGUGUCGA 401 TCGACACT c TTCTTGAG 929

2572 UGCUCAAG CUGAUGAG X CGAA AGAGUGUC 402 GACACTCT T CTTGAGCA 930

2573 CUGCUCAA CUGAUGAG X CGAA AAGAGUGU 403 ACACTCTT c TTGAGCAG 931

2575 GUCUGCUC CUGAUGAG X CGAA AGAAGAGU 404 ACTCTTCT T GAGCAGAC 932

2590 CUCUUCCA CUGAUGAG X CGAA AUCACGGU 405 ACCGTGAT T TGGAAGAG 933

2591 UCUCUUCC CUGAUGAG X CGAA AAUCACGG 406 CCGTGATT T GGAAGAGA 934

2622 GUUUCAAG CUGAUGAG X CGAA AGUGUGGU 407 ACCACACT T CTTGAAAC 935

2623 UGUUUCAA CUGAUGAG X CGAA AAGUGUGG 408 CCACACTT c TTGAAACA 936

2625 GCUGUUUC CUGAUGAG X CGAA AGAAGUGU 409 ACACTTCT T GAAACAGC 937

2646 GCCUAAAG CUGAUGAG X CGAA ACCGUCAC 410 GTGACGGT c CTTTAGGC 938

2649 GCUGCCUA CUGAUGAG X CGAA AGGACCGU 411 ACGGTCCT T TAGGCAGC 939

2650 GGCUGCCU CUGAUGAG X CGAA AAGGACCG 412 CGGTCCTT T AGGCAGCC 940

2651 AGGCUGCC CUGAUGAG X CGAA AAAGGACC 413 GGTCCTTT A GGCAGCCT 941

2668 GGGACAGA CUGAUGAG X CGAA ACGGCGGC 414 GCCGCCGT c TCTGTCCC 942

2^"670 CCGGGACA CUGAUGAG X CGAA AGACGGCG 415 CGCCGTCT c TGTCCCGG 943

2674 UGAACCGG CUGAUGAG X CGAA ACAGAGAC 416 GTCTCTGT c CCGGTTCA 944

2680 GCAAGGUG CUGAUGAG X CGAA ACCGGGAC 417 GTCCCGGT T CACCTTGC 945

2681 GGCAAGGU CUGAUGAG X CGAA AACCGGGA 418 TCCCGGTT c ACCTTGCC 946

2686 CUCUCGGC CUGAUGAG X CGAA AGGUGAAC 419 GTTCACCT T GCCGAGAG 947

2703 GUGGGGCA CUGAUGAG X CGAA ACGCGCCU 420 AGGCGCGT c TGCCCCAC 948 Table 3

2715 CAGGGUUU CUGAUGAG X CGAA AGGGUGGG 421 CCCACCCT C AAACCCTG 949

2741 AGAGUCGU CUGAUGAG X CGAA AGCACCAU 422 ATGGTGCT C ACGACTCT 950

2748 UGCAGGAA CUGAUGAG X CGAA AGUCGUGA 423 TCACGACT C TTCCTGCA 951

2750 UUUGCAGG CUGAUGAG X CGAA AGAGUCGU 424 ACGACTCT T CCTGCAAA 952

2751 CUUUGCAG CUGAUGAG X CGAA AAGAGUCG 425 CGACTCTT C CTGCAAAG 953

2774 UUAAUGUG CUGAUGAG X CGAA AGGUCUUC 426 GAAGACCT C CACATTAA 954

2780 AGCCACUU CUGAUGAG X CGAA AUGUGGAG 427 CTCCACAT T AAGTGGCT 955

2781 AAGCCACU CUGAUGAG X CGAA AAUGUGGA 428 TCCACATT A AGTGGCTT 956

2789 AUGUUAAA CUGAUGAG X CGAA AGCCACUU 429 AAGTGGCT T TTTAACAT 957

2790 CAUGUUAA CUGAUGAG X CGAA AAGCCACU 430 AGTGGCTT T TTAACATG 958

2791 UCAUGUUA CUGAUGAG X CGAA AAAGCCAC 431 GTGGCTTT T TAACATGA 959

2792 UUCAUGUU CUGAUGAG X CGAA AAAAGCCA 432 TGGCTTTT T AACATGAA 960

2793 UUUCAUGU CUGAUGAG X CGAA AAAAAGCC 433 GGCTTTTT A ACATGAAA 961

2816 UCGGGAGC CUGAUGAG X CGAA ACAGCUGC 434 GCAGCTGT A GCTCCCGA 962

2820 UAGCUCGG CUGAUGAG X CGAA AGCUACAG 435 CTGTAGCT C CCGAGCTA 963

2828 CAAGAGAG CUGAUGAG X CGAA AGCUCGGG 436 CCCGAGCT A CTCTCTTG 964

2831 UGGCAAGA CUGAUGAG X CGAA AGUAGCUC 437 GAGCTACT C TCTTGCCA 965

2833 GCUGGCAA CUGAUGAG X CGAA AGAGUAGC 438 GCTACTCT C TTGCCAGC 966

2835 AUGCUGGC CUGAUGAG X CGAA AGAGAGUA 439 TACTCTCT T GCCAGCAT 967

2844 AAUGUGAA CUGAUGAG X CGAA AUGCUGGC 440 GCCAGCAT T TTCACATT 968

2845 AAAUGUGA CUGAUGAG X CGAA AAUGCUGG 441 CCAGCATT T TCACATTT 969

2846 AAAAUGUG CUGAUGAG X CGAA AAAUGCUG 442 CAGCATTT T CACATTTT 970

2847 CAAAAUGU CUGAUGAG X CGAA AAAAUGCU 443 AGCATTTT C ACATTTTG 971

2852 AAAGGCAA CUGAUGAG X CGAA AUGUGAAA 444 TTTCACAT T TTGCCTTT 972

2853 GAAAGGCA CUGAUGAG X CGAA AAUGUGAA 445 TTCACATT T TGCCTTTC 973

2854 AGAAAGGC CUGAUGAG X CGAA AAAUGUGA 446 TCACATTT T GCCTTTCT 974

2859 CCACGAGA CUGAUGAG X CGAA AGGCAAAA 447 TTTTGCCT T TCTCGTGG 975

2860 ACCACGAG CUGAUGAG X CGAA AAGGCAAA 448 TTTGCCTT T CTCGTGGT 976

2861 UACCACGA CUGAUGAG X CGAA AAAGGCAA 449 TTGCCTTT c TCGTGGTA 977

2863 UCUACCAC CUGAUGAG X CGAA AGAAAGGC 450 GCCTTTCT c GTGGTAGA 978

2869 CUGGCUUC CUGAUGAG X CGAA ACCACGAG 451 CTCGTGGT A GAAGCCAG 979

2879 UUUCUCUG CUGAUGAG X CGAA ACUGGCUU 452 AAGCCAGT A CAGAGAAA 980

2889 CACCACAG CUGAUGAG X CGAA AUUUCUCU 453 AGAGAAAT T CTGTGGTG 981

2890 CCACCACA CUGAUGAG X CGAA AAUUUCUC 454 GAGAAATT C TGTGGTGG 982

2905 ACACCUCG CUGAUGAG X CGAA AUGUUCCC 455 GGGAACAT T CGAGGTGT 983

2906 GACACCUC CUGAUGAG X CGAA AAUGUUCC 456 GGAACATT C GAGGTGTC 984

2914 UGCAGGGU CUGAUGAG X CGAA ACACCUCG 457 CGAGGTGT C ACCCTGCA 985

2928 CCUCACCA CUGAUGAG X CGAA AGCUCUGC 458 GCAGAGCT A TGGTGAGG 986

2944 CUAAGCCU CUGAUGAG X CGAA AUCCACAC 459 GTGTGGAT A AGGCTTAG 987

2950 UGGCACCU CUGAUGAG X CGAA AGCCUUAU 460 ATAAGGCT T AGGTGCCA 988

2951 CUGGCACC CUGAUGAG X CGAA AAGCCUUA 461 TAAGGCTT A GGTGCCAG 989

2965 AGAAUGCU CUGAUGAG X CGAA ACAGCCUG 462 CAGGCTGT A AGCATTCT 990

2971 CAGCUCAG CUGAUGAG X CGAA AUGCUUAC 463 GTAAGCAT T CTGAGCTG 991

2972 CCAGCUCA CUGAUGAG X CGAA AAUGCUUA 464 TAAGCATT C TGAGCTGG 992

2983 AAAACAAC CUGAUGAG X CGAA AGCCAGCU 465 AGCTGGCT T GTTGTTTT 993

2986 UUAAAAAC CUGAUGAG X CGAA ACAAGCCA 466 TGGCTTGT T GTTTTTAA 994

2989 GACUUAAA CUGAUGAG X CGAA ACAACAAG 467 CTTGTTGT T TTTAAGTC 995 Table 3

2990 GGACUUAA CUGAUGAG X CGAA AACAACAA 468 TTGTTGTT T TTAAGTCC 996

2991 AGGACUUA CUGAUGAG X CGAA AAACAACA 469 TGTTGTTT T TAAGTCCT 997

2992 CAGGACUU CUGAUGAG X CGAA AAAACAAC 470 GTTGTTTT T AAGTCCTG 998

2993 ACAGGACU CUGAUGAG X CGAA AAAAACAA 471 TTGTTTTT A AGTCCTGT 999

2997 AUAUACAG CUGAUGAG X CGAA ACUUAAAA 472 TTTTAAGT C CTGTATAT 1000

3002 CAUACAUA CUGAUGAG X CGAA ACAGGACU 473 AGTCCTGT A TATGTATG 1001

3004 UACAUACA CUGAUGAG X CGAA AUACAGGA 474 TCCTGTAT A TGTATGTA 1002

3008 CUACUACA CUGAUGAG X CGAA ACAUAUAC 475 GTATATGT A TGTAGTAG 1003

3012 CAAACUAC CUGAUGAG X CGAA ACAUACAU 476 ATGTATGT A GTAGTTTG 1004

3015 ACCCAAAC CUGAUGAG X CGAA ACUACAUA 477 TATGTAGT A GTTTGGGT 1005

3018 CACACCCA CUGAUGAG X CGAA ACUACUAC 478 GTAGTAGT T TGGGTGTG 1006

3019 ACACACCC CUGAUGAG X CGAA AACUACUA 479 TAGTAGTT T GGGTGTGT 1007

3028 ACUAUAUA CUGAUGAG X CGAA ACACACCC 480 GGGTGTGT A TATATAGT 1008

3030 CUACUAUA CUGAUGAG X CGAA AUACACAC 481 GTGTGTAT A TATAGTAG 1009

3032 UGCUACUA CUGAUGAG X CGAA AUAUACAC 482 GTGTATAT A TAGTAGCA 1010

3034 AAUGCUAC CUGAUGAG X CGAA AUAUAUAC 483 GTATATAT A GTAGCATT 1011

3037 UGAAAUGC CUGAUGAG X CGAA ACUAUAUA 484 TATATAGT A GCATTTCA 1012

3042 CAUUUUGA CUGAUGAG X CGAA AUGCUACU 485 AGTAGCAT T TCAAAATG 1013

3043 CCAUUUUG CUGAUGAG X CGAA AAUGCUAC 486 GTAGCATT T CAAAATGG 1014

3044 UCCAUUUU CUGAUGAG X CGAA AAAUGCUA 487 TAGCATTT c AAAATGGA 1015

3056 UAAACCAG CUGAUGAG X CGAA ACGUCCAU 488 ATGGACGT A CTGGTTTA 1016

3062 GGAGGUUA CUGAUGAG X CGAA ACCAGUAC 489 GTACTGGT T TAACCTCC 1017

3063 AGGAGGUU CUGAUGAG X CGAA AACCAGUA 490 TACTGGTT T AACCTCCT 1018

3064 UAGGAGGU CUGAUGAG X CGAA AAACCAGU 491 ACTGGTTT A ACCTCCTA 1019

3069 AAGGAUAG CUGAUGAG X CGAA AGGUUAAA 492 TTTAACCT C CTATCCTT 1020

3072 UCCAAGGA CUGAUGAG X CGAA AGGAGGUU 493 AACCTCCT A TCCTTGGA 1021

3074 UCUCCAAG CUGAUGAG X CGAA AUAGGAGG 494 CCTCCTAT C CTTGGAGA 1022

3077 UGCUCUCC CUGAUGAG X CGAA AGGAUAGG 495 CCTATCCT T GGAGAGCA 1023

3093 AAGGUGGA CUGAUGAG X CGAA AGCCAGCU 496 AGCTGGCT C TCCACCTT 1024

3095 ACAAGGUG CUGAUGAG X CGAA AGAGCCAG 497 CTGGCTCT C CACCTTGT 1025

3101 UGUGUAAC CUGAUGAG X CGAA AGGUGGAG 498 CTCCACCT T GTTACACA 1026

3104 UAAUGUGU CUGAUGAG X CGAA ACAAGGUG 499 CACCTTGT T ACACATTA 1027

3105 AUAAUGUG CUGAUGAG X CGAA AACAAGGU 500 ACCTTGTT A CACATTAT 1028

3111 UCUAACAU CUGAUGAG X CGAA AUGUGUAA 501 TTACACAT T ATGTTAGA 1029

3112 CUCUAACA CUGAUGAG X CGAA AAUGUGUA 502 TACACATT A TGTTAGAG 1030

3116 ACCUCUCU CUGAUGAG X CGAA ACAUAAUG 503 CATTATGT T AGAGAGGT 1031

3117 UACCUCUC CUGAUGAG X CGAA AACAUAAU 504 ATTATGTT A GAGAGGTA 1032

3125 CAGCUCGC CUGAUGAG X CGAA ACCUCUCU 505 AGAGAGGT A GCGAGCTG 1033

3136 ACAUAGCA CUGAUGAG X CGAA AGCAGCUC 506 GAGCTGCT C TGCTATGT 1034

3141 UAAGGACA CUGAUGAG X CGAA AGCAGAGC 507 GCTCTGCT A TGTCCTTA 1035

3145 GGCUUAAG CUGAUGAG X CGAA ACAUAGCA 508 TGCTATGT C CTTAAGCC 1036

3148 AUUGGCUU CUGAUGAG X CGAA AGGACAUA 509 TATGTCCT T AAGCCAAT 1037

3149 UAUUGGCU CUGAUGAG X CGAA AAGGACAU 510 ATGTCCTT A AGCCAATA 1038

3157 UGAGUAAA CUGAUGAG X CGAA AUUGGCUU 511 AAGCCAAT A TTTACTCA 1039

3159 GAUGAGUA CUGAUGAG X CGAA AUAUUGGC 512 GCCAATAT T TACTCATC 1040

3160 UGAUGAGU CUGAUGAG X CGAA AAUAUUGG 513 CCAATATT T ACTCATCA 1041

3161 CUGAUGAG CUGAUGAG X CGAA AAAUAUUG 514 CAATATTT A CTCATCAG 1042 Table 3

3164 GACCUGAU CUGAUGAG X CGAA AGUAAAUA 515 TATTTACT C ATCAGGTC 1043

3167 AAUGACCU CUGAUGAG X CGAA AUGAGUAA 516 TTACTCAT C AGGTCATT 1044

3172 AAAAUAAU CUGAUGAG X CGAA ACCUGAUG 517 CATCAGGT C ATTATTTT 1045

3175 UAAAAAAU CUGAUGAG X CGAA AUGACCUG 518 CAGGTCAT T ATTTTTTA 1046

3176 GUAAAAAA CUGAUGAG X CGAA AAUGACCU 519 AGGTCATT A TTTTTTAC 1047

3178 UUGUAAAA CUGAUGAG X CGAA AUAAUGAC 520 GTCATTAT T TTTTACAA 1048

3179 AUUGUAAA CUGAUGAG X CGAA AAUAAUGA 521 TCATTATT T TTTACAAT 1049

3180 CAUUGUAA CUGAUGAG X CGAA AAAUAAUG 522 CATTATTT T TTACAATG 1050

3181 CCAUUGUA CUGAUGAG X CGAA AAAAUAAU 523 ATTATTTT T TACAATGG 1051

3182 GCCAUUGU CUGAUGAG X CGAA AAAAAUAA 524 TTATTTTT T ACAATGGC 1052

3183 GGCCAUUG CUGAUGAG X CGAA AAAAAAUA 525 TATTTTTT A CAATGGCC 1053

3199 AAAUGGUU CUGAUGAG X CGAA AUUCCAUG 525 CATGGAAT A AACCATTT 1054

320S UUUGUAAA CUGAUGAG X CGAA AUGGUUUA 527 TAAACCAT T TTTACAAA 1055

3207 UUUUGUAA CUGAUGAG X CGAA AAUGGUUU 528 AAACCATT T TTACAAAA 1056

Input Sequence PTPNl (Homo sapiens protein tyrosine phosphatase, non-receptor type 1 (PTPNl) 3215 bp)

Cut Site UH.

Table 4

Table 4: Human PTP-IB NCH Ribozyme and Target Sequence

Nt. Ribozyme Sequence Seq. ID Substrate Sequence Seq. ID Position Nos. Nos.

13 CCGCUCUA CUGAUGAG X CGAA ICCGCGUC 1057 GACGCGGC C TAGAGCGG 1781

14 GCCGCUCU CUGAUGAG X CGAA IGCCGCGU 1058 ACGCGGCC T AGAGCGGC 1782

23 GCGCCGUC CUGAUGAG X CGAA ICCGCUCU 1059 AGAGCGGC A GACGGCGC 1783

32 CGGCCCAC CUGAUGAG X CGAA ICGCCGUC 1060 GACGGCGC A GTGGGCCG 1784

39 UCCUUCUC CUGAUGAG X CGAA ICCCACUG 1061 CAGTGGGC C GAGAAGGA 1785

53 GCGGCUGC CUGAUGAG X CGAA ICGCCUCC 1062 GGAGGCGC A GCAGCCGC 1786

56 AGGGCGGC CUGAUGAG X CGAA ICUGCGCC 1063 GGCGCAGC A GCCGCCCT 1787

59 GCCAGGGC CUGAUGAG X CGAA ICUGCUGC 1064 GCAGCAGC C GCCCTGGC 1788

62 CGGGCCAG CUGAUGAG X CGAA ICGGCUGC 1065 GCAGCCGC C CTGGCCCG 1789

63 ACGGGCCA CUGAUGAG X CGAA IGCGGCUG 1066 CAGCCGCC C TGGCCCGT 1790

64 GACGGGCC CUGAUGAG X CGAA IGGCGGCU 1067 AGCCGCCC T GGCCCGTC 1791

68 CCAUGACG CUGAUGAG X CGAA ICCAGGGC 1068 GCCCTGGC C CGTCATGG 1792

69 UCCAUGAC CUGAUGAG X CGAA IGCCAGGG 1069 CCCTGGCC C GTCATGGA 1793

73 CAUCUCCA CUGAUGAG X CGAA IACGGGCC 1070 GGCCCGTC A TGGAGATG 1794

98 UGUCGAUC CUGAUGAG X CGAA ICUCGAAC 1071 GTTCGAGC A GATCGACA 1795

106 CCCGGACU CUGAUGAG X CGAA IUCGAUCU 1072 AGATCGAC A AGTCCGGG 1796

111 CAGCUCCC CUGAUGAG X CGAA IACUUGUC 1073 GACAAGTC C GGGAGCTG 1797

118 GGCCGCCC CUGAUGAG X CGAA ICUCCCGG 1074 CCGGGAGC T GGGCGGCC 1798

126 UGGUAAAU CUGAUGAG X CGAA ICCGCCCA 1075 TGGGCGGC C ATTTACCA 1799

127 CUGGUAAA CUGAUGAG X CGAA IGCCGCCC 1076 GGGCGGCC A TTTACCAG 1800

133 GAUAUCCU CUGAUGAG X CGAA IUAAAUGG 1077 CCATTTAC C AGGATATC 1801

134 GGAUAUCC CUGAUGAG X CGAA IGUAAAUG 1078 CATTTACC A GGATATCC 1802

142 UUCAUGUC CUGAUGAG X CGAA IAUAUCCU 1079 AGGATATC C GACATGAA 1803

146 UGGCUUCA CUGAUGAG X CGAA IUCGGAUA 1080 TATCCGAC A TGAAGCCA 1804

153 AAGUCACU CUGAUGAG X CGAA ICUUCAUG 1081 CATGAAGC C AGTGACTT 1805

154 GAAGUCAC CUGAUGAG X CGAA IGCUUCAU 1082 ATGAAGCC A GTGACTTC 1806

160 ACAUGGGA CUGAUGAG X CGAA IUCACUGG 1083 CCAGTGAC T TCCCATGT 1807

163 UCUACAUG CUGAUGAG X CGAA IAAGUCAC 1084 GTGACTTC C CATGTAGA 1808

164 CUCUACAU CUGAUGAG X CGAA IGAAGUCA 1085 TGACTTCC C ATGTAGAG 1809

165 ACUCUACA CUGAUGAG X CGAA IGGAAGUC 1086 GACTTCCC A TGTAGAGT 1810

177 GGAAGCUU CUGAUGAG X CGAA ICCACUCU 1087 AGAGTGGC C AAGCTTCC 1811

178 AGGAAGCU CUGAUGAG X CGAA IGCCACUC 1088 GAGTGGCC A AGCTTCCT 1812

182 UCUUAGGA CUGAUGAG X CGAA ICUUGGCC 1089 GGCCAAGC T TCCTAAGA 1813

185 UGUUCUUA CUGAUGAG X CGAA IAAGCUUG 1090 CAAGCTTC C TAAGAACA 1814

186 UUGUUCUU CUGAUGAG X CGAA IGAAGCUU 1091 AAGCTTCC T AAGAACAA 1815

193 UCGGUUUU CUGAUGAG X CGAA IUUCUUAG 1092 CTAAGAAC A AAAACCGA 1816

199 CCUAUUUC CUGAUGAG X CGAA IUUUUUGU 1093 ACAAAAAC C GAAATAGG 1817

211 GACGUCUC CUGAUGAG X CGAA IUACCUAU 1094 ATAGGTAC A GAGACGTC 1818

220 AAAGGGAC CUGAUGAG X CGAA IACGUCUC 1095 GAGACGTC A GTCCCTTT 1819

224 GGUCAAAG CUGAUGAG X CGAA IACUGACG 1096 CGTCAGTC C CTTTGACC 1820

225 UGGUCAAA CUGAUGAG X CGAA IGACUGAC 1097 GTCAGTCC C TTTGACCA 1821

226 AUGGUCAA CUGAUGAG X CGAA IGGACUGA 1098 TCAGTCCC T TTGACCAT 1822

232 CCGACUAU CUGAUGAG X CGAA IUCAAAGG 1099 CCTTTGAC C ATAGTCGG 1823 Table 4

233 UCCGACUA CUGAUGAG X CGAA IGUCAAAG 1100 CTTTGACC A TAGTCGGA 1824

248 CUUGAUGU CUGAUGAG X CGAA IUUUAAUC 1101 GATTAAAC T ACATCAAG 1825

251 CUUCUUGA CUGAUGAG X CGAA IUAGUUUA 1102 TAAACTAC A TCAAGAAG 1826

254 UAUCUUCU CUGAUGAG X CGAA IAUGUAGU 1103 ACTACATC A AGAAGATA 1827

268 GUUGAUAU CUGAUGAG X CGAA IUCAUUAU 1104 ATAATGAC T ATATCAAC 1828

274 ACUAGCGU CUGAUGAG X CGAA IAUAUAGU 1105 ACTATATC A ACGCTAGT 1829

279 AUCAAACU CUGAUGAG X CGAA ICGUUGAU 1106 ATCAACGC T AGTTTGAT 1830

303 CUCCUUUG CUGAUGAG X CGAA ICUUCUUC 1107 GAAGAAGC C CAAAGGAG 1831

304 ACUCCUUU CUGAUGAG X CGAA IGCUUCUU 1108 AAGAAGCC C AAAGGAGT 1832

305 AACUCCUU CUGAUGAG X CGAA IGGCUUCU 1109 AGAAGCCC A AAGGAGTT 1833

316 GGUAAGAA CUGAUGAG X CGAA IUAACUCC 1110 GGAGTTAC A TTCTTACC 1834

320 CCUGGGUA CUGAUGAG X CGAA IAAUGUAA llll TTACATTC T TACCCAGG 1835

324 GGGCCCUG CUGAUGAG X CGAA IUAAGAAU 1112 ATTCTTAC c CAGGGCCC 1836

325 AGGGCCCU CUGAUGAG X CGAA IGUAAGAA 1113 TTCTTACC c AGGGCCCT 1837

326 AAGGGCCC CUGAUGAG X CGAA IGGUAAGA 1114 TCTTACCC A GGGCCCTT 1838

331 AGGCAAAG CUGAUGAG X CGAA ICCCUGGG 1115 CCCAGGGC C CTTTGCCT 1839

332 UAGGCAAA CUGAUGAG X CGAA IGCCCUGG 1116 CCAGGGCC C TTTGCCTA 1840

333 UUAGGCAA CUGAUGAG X CGAA IGGCCCUG 1117 CAGGGCCC T TTGCCTAA 1841

338 AUGUGUUA CUGAUGAG X CGAA ICAAAGGG 1118 CCCTTTGC c TAACACAT 1842

339 CAUGUGUU CUGAUGAG X CGAA IGCAAAGG 1119 CCTTTGCC T AACACATG 1843

343 ACCGCAUG CUGAUGAG X CGAA IUUAGGCA 1120 TGCCTAAC A CATGCGGT 1844

345 UGACCGCA CUGAUGAG X CGAA IUGUUAGG 1121 CCTAACAC A TGCGGTCA 1845

353 CCCAAAAG CUGAUGAG X CGAA IACCGCAU 1122 ATGCGGTC A CTTTTGGG 1846

355 CUCCCAAA CUGAUGAG X CGAA IUGACCGC 1123 GCGGTCAC T TTTGGGAG 1847

377 UGCUUUUC CUGAUGAG X CGAA ICUCCCAC 1124 GTGGGAGC A GAAAAGCA 1848

385 GACACCCC CUGAUGAG X CGAA ICUUUUCU 1125 AGAAAAGC A GGGGTGTC 1849

397 GUUGAGCA CUGAUGAG X CGAA IACGACAC 1126 GTGTCGTC A TGCTCAAC 1850

401 CUCUGUUG CUGAUGAG X CGAA ICAUGACG 1127 CGTCATGC T CAACAGAG 1851

403 CACUCUGU CUGAUGAG X CGAA IAGCAUGA 1128 TCATGCTC A ACAGAGTG 1852

406 CAUCACUC CUGAUGAG X CGAA IUUGAGCA 1129 TGCTCAAC A GAGTGATG 1853

438 CAGUAUUG CUGAUGAG X CGAA ICGCAUUU 1130 AAATGCGC A CAATACTG 1854

440 GCCAGUAU CUGAUGAG X CGAA IUGCGCAU 1131 ATGCGCAC A ATACTGGC 1855

445 UUGUGGCC CUGAUGAG X CGAA IUAUUGUG 1132 CACAATAC T GGCCACAA 1856

449 CUUUUUGU CUGAUGAG X CGAA ICCAGUAU 1133 ATACTGGC c ACAAAAAG 1857

450 UCUUUUUG CUGAUGAG X CGAA IGCCAGUA 1134 TACTGGCC A CAAAAAGA 1858

452 CUUCUUUU CUGAUGAG X CGAA IUGGCCAG 1135 CTGGCCAC A AAAAGAAG 1859

475 GUCUUCAA CUGAUGAG X CGAA IAUCAUCU 1136 AGATGATC T TTGAAGAC 1860

484 CAAAUUUG CUGAUGAG X CGAA IUCUUCAA 1137 TTGAAGAC A CAAATTTG 1861

486 UUCAAAUU CUGAUGAG X CGAA IUGUCUUC 1138 GAAGACAC A AATTTGAA 1862

501 GAGAUCAA CUGAUGAG X CGAA IUUAAUUU 1139 AAATTAAC A TTGATCTC 1863

508 AUCUUCAG CUGAUGAG X CGAA IAUCAAUG 1140 CATTGATC T CTGAAGAT 1864

510 AUAUCUUC CUGAUGAG X CGAA lAGAUCAA 1141 TTGATCTC T GAAGATAT 1865

520 AUAUGACU CUGAUGAG X CGAA IAUAUCUU 1142 AAGATATC A AGTCATAT 1866

525 GUAUAAUA CUGAUGAG X CGAA IACUUGAU 1143 ATCAAGTC A TATTATAC 1867

534 UGUCGCAC CUGAUGAG X CGAA IUAUAAUA 1144 TATTATAC A GTGCGACA 1868

542 AUUCUAGC CUGAUGAG X CGAA lUCGCACU 1145 AGTGCGAC A GCTAGAAT 1869

545 CCAAUUCU CUGAUGAG X CGAA ICUGUCGC 1146 GCGACAGC T AGAATTGG 1870 Table 4

559 GGUUGUAA CUGAUGAG X CGAA IUUUUCCA 1147 TGGAAAAC C TTACAACC 1871

560 GGGUUGUA CUGAUGAG X CGAA IGUUUUCC 1148 GGAAAACC T TACAACCC 1872

564 UCUUGGGU CUGAUGAG X CGAA IUAAGGUU 1149 AACCTTAC A ACCCAAGA 1873

567 GUUUCUUG CUGAUGAG X CGAA IUUGUAAG 1150 CTTACAAC C CAAGAAAC 1874

568 AGUUUCUU CUGAUGAG X CGAA IGUUGUAA 1151 TTACAACC C AAGAAACT 1875

569 GAGUUUCU CUGAUGAG X CGAA IGGUUGUA 1152 TACAACCC A AGAAACTC 1876

576 AUCUCUCG CUGAUGAG X CGAA IUUUCUUG 1153 CAAGAAAC T CGAGAGAT 1877

586 GAAAUGUA CUGAUGAG X CGAA IAUCUCUC 1154 GAGAGATC T TACATTTC 1878

590 AGUGGAAA CUGAUGAG X CGAA IUAAGAUC 1155 GATCTTAC A TTTCCACT 1879

595 GGUAUAGU CUGAUGAG X CGAA IAAAUGUA 1156 TACATTTC C ACTATACC 1880

596 UGGUAUAG CUGAUGAG X CGAA IGAAAUGU 1157 ACATTTCC A CTATACCA 1881

598 UGUGGUAU CUGAUGAG X CGAA IUGGAAAU 1158 ATTTCCAC T ATACCACA 1882

603 GGCCAUGU CUGAUGAG X CGAA IUAUAGUG 1159 CACTATAC C ACATGGCC 1883

604 AGGCCAUG CUGAUGAG X CGAA IGUAUAGU 1160 ACTATACC A CATGGCCT 1884

606 UCAGGCCA CUGAUGAG X CGAA IUGGUAUA 1161 TATACCAC A TGGCCTGA 1885

611 CAAAGUCA CUGAUGAG X CGAA ICCAUGUG 1162 CACATGGC C TGACTTTG 1886

612 CCAAAGUC CUGAUGAG X CGAA IGCCAUGU 1163 ACATGGCC T GACTTTGG 1887

616 GACUCCAA CUGAUGAG X CGAA IUCAGGCC 1164 GGCCTGAC T TTGGAGTC 1888

625 UGAUUCAG CUGAUGAG X CGAA IACUCCAA 1165 TTGGAGTC C CTGAATCA 1889 -

626 GUGAUUCA CUGAUGAG X CGAA IGACUCCA 1166 TGGAGTCC C TGAATCAC 1890

627 GGUGAUUC CUGAUGAG X CGAA IGGACUCC 1167 GGAGTCCC T GAATCACC 1891

633 GAGGCUGG CUGAUGAG X CGAA IAUUCAGG 1168 CCTGAATC A CCAGCCTC 1892

635 AUGAGGCU CUGAUGAG X CGAA lUGAUUCA 1169 TGAATCAC C AGCCTCAT 1893

636 AAUGAGGC CUGAUGAG X CGAA IGUGAUUC 1170 GAATCACC A GCCTCATT 1894

639 AAGAAUGA CUGAUGAG X CGAA ICUGGUGA 1171 TCACCAGC C TCATTCTT 1895

640 CAAGAAUG CUGAUGAG X CGAA IGCUGGUG 1172 CACCAGCC T CATTCTTG 1896

642 UUCAAGAA CUGAUGAG X CGAA IAGGCUGG 1173 CCAGCCTC A TTCTTGAA 1897

646 AAAGUUCA CUGAUGAG X CGAA IAAUGAGG 1174 CCTCATTC T TGAACTTT 1898

652 GAAAAGAA CUGAUGAG X CGAA IUUCAAGA 1175 TCTTGAAC T TTCTTTTC 1899

656 CUUUGAAA CUGAUGAG X CGAA IAAAGUUC 1176 GAACTTTC T TTTCAAAG 1900

661 UCGGACUU CUGAUGAG X CGAA IAAAAGAA 1177 TTCTTTTC A AAGTCCGA 1901

667 UGACUCUC CUGAUGAG X CGAA IACUUUGA 1178 TCAAAGTC C GAGAGTCA 1902

675 AGUGACCC CUGAUGAG X CGAA IACUCUCG 1179 CGAGAGTC A GGGTCACT 1903

681 GGGCUGAG CUGAUGAG X CGAA IACCCUGA 1180 TCAGGGTC A CTCAGCCC 1904

683 CCGGGCUG CUGAUGAG X CGAA IUGACCCU 1181 AGGGTCAC T CAGCCCGG 1905

685 CUCCGGGC CUGAUGAG X CGAA IAGUGACC 1182 GGTCACTC A GCCCGGAG 1906

688 GUGCUCCG CUGAUGAG X CGAA ICUGAGUG 1183 CACTCAGC C CGGAGCAC 1907

689 CGUGCUCC CUGAUGAG X CGAA IGCUGAGU 1184 ACTCAGCC C GGAGCACG 1908

695 CGGGCCCG CUGAUGAG X CGAA ICUCCGGG 1185 CCCGGAGC A CGGGCCCG 1909

701 CCACAACG CUGAUGAG X CGAA ICCCGUGC 1186 GCACGGGC C CGTTGTGG 1910

702 ACCACAAC CUGAUGAG X CGAA IGCCCGUG 1187 CACGGGCC C GTTGTGGT 1911

713 CACUGCAG CUGAUGAG X CGAA ICACCACA 1188 TGTGGTGC A CTGCAGTG 1912

715 UGCACUGC CUGAUGAG X CGAA lUGCACCA 1189 TGGTGCAC T GCAGTGCA 1913

718 GCCUGCAC CUGAUGAG X CGAA ICAGUGCA 1190 TGCACTGC A GTGCAGGC 1914

723 CCGAUGCC CUGAUGAG X CGAA ICACUGCA 1191 TGCAGTGC A GGCATCGG 1915

727 CCUGCCGA CUGAUGAG X CGAA ICCUGCAC 1192 GTGCAGGC A TCGGCAGG 1916

733 UCCAGACC CUGAUGAG X CGAA ICCGAUGC 1193 GCATCGGC A GGTCTGGA 1917 Table 4

738 AAGGUUCC CUGAUGAG X CGAA IACCUGCC 1194 GGCAGGTC T GGAACCTT 1918

744 AGACAGAA CUGAUGAG X CGAA lUUCCAGA 1195 TCTGGAAC C TTCTGTCT 1919

745 CAGACAGA CUGAUGAG X CGAA IGUUCCAG 1196 CTGGAACC T TCTGTCTG 1920

748 AGCCAGAC CUGAUGAG X CGAA IAAGGUUC 1197 GAACCTTC T GTCTGGCT 1921

752 UAUCAGCC CUGAUGAG X CGAA IACAGAAG 1198 CTTCTGTC T GGCTGATA 1922

756 CAGGUAUC CUGAUGAG X CGAA ICCAGACA 1199 TGTCTGGC T GATACCTG 1923

762 AAGAGGCA CUGAUGAG X CGAA IUAUCAGC 1200 GCTGATAC C TGCCTCTT 1924

763 CAAGAGGC CUGAUGAG X CGAA IGUAUCAG 1201 CTGATACC T GCCTCTTG 1925

766 CAGCAAGA CUGAUGAG X CGAA ICAGGUAU 1202 ATACCTGC C TCTTGCTG 1926

767 UCAGCAAG CUGAUGAG X CGAA IGCAGGUA 1203 TACCTGCC T CTTGCTGA 1927

769 CAUCAGCA CUGAUGAG X CGAA IAGGCAGG 1204 CCTGCCTC T TGCTGATG 1928

773 UGUCCAUC CUGAUGAG X CGAA ICAAGAGG 1205 CCTCTTGC T GATGGACA 1929

781 UUUCCUCU CUGAUGAG X CGAA lUCCAUCA 1206 TGATGGAC A AGAGGAAA 1930

793 GGAAGAAG CUGAUGAG X CGAA IUCUUUCC 1207 GGAAAGAC C CTTCTTCC 1931

794 CGGAAGAA CUGAUGAG X CGAA IGUCUUUC 1208 GAAAGACC C TTCTTCCG 1932

795 ACGGAAGA CUGAUGAG X CGAA IGGUCUUU 1209 AAAGACCC T TCTTCCGT 1933

798 UCAACGGA CUGAUGAG X CGAA IAAGGGUC 1210 GACCCTTC T TCCGTTGA 1934

801 AUAUCAAC CUGAUGAG X CGAA IAAGAAGG 1211 CCTTCTTC C GTTGATAT 1935

811 CACUUUCU CUGAUGAG X CGAA IAUAUCAA 1212 TTGATATC A AGAAAGTG 1936

821 UUUCUAAC CUGAUGAG X CGAA ICACUUUC 1213 GAAAGTGC T GTTAGAAA 1937

851 UCUGGAUC CUGAUGAG X CGAA ICCCCAUC 1214 GATGGGGC T GATCCAGA 1938

856 GGCUGUCU CUGAUGAG X CGAA IAUCAGCC 1215 GGCTGATC C AGACAGCC 1939

857 CGGCUGUC CUGAUGAG X CGAA IGAUCAGC 1216 GCTGATCC A GACAGCCG 1940

861 UGGUCGGC CUGAUGAG X CGAA IUCUGGAU 1217 ATCCAGAC A GCCGACCA 1941

864 AGCUGGUC CUGAUGAG X CGAA ICUGUCUG 1218 CAGACAGC C GACCAGCT 1942

868 GCGCAGCU CUGAUGAG X CGAA IUCGGCUG 1219 CAGCCGAC C AGCTGCGC 1943

869 AGCGCAGC CUGAUGAG X CGAA IGUCGGCU 1220 AGCCGACC A GCTGCGCT 1944

872 AGAAGCGC CUGAUGAG X CGAA ICUGGUCG 1221 CGACCAGC T GCGCTTCT 1945

877 GUAGGAGA CUGAUGAG X CGAA ICGCAGCU 1222 AGCTGCGC T TCTCCTAC 1946

880 CAGGUAGG CUGAUGAG X CGAA IAAGCGCA 1223 TGCGCTTC T CCTACCTG 1947

882 GCCAGGUA CUGAUGAG X CGAA IAGAAGCG 1224 CGCTTCTC C TACCTGGC 1948

883 AGCCAGGU CUGAUGAG X CGAA IGAGAAGC 1225 GCTTCTCC T ACCTGGCT 1949

886 CACAGCCA CUGAUGAG X CGAA IUAGGAGA 1226 TCTCCTAC C TGGCTGTG 1950

887 UCACAGCC CUGAUGAG X CGAA IGUAGGAG 1227 CTCCTACC T GGCTGTGA 1951

891 UCGAUCAC CUGAUGAG X CGAA ICCAGGUA 1228 TACCTGGC T GTGATCGA 1952

906 AUGAAUUU CUGAUGAG X CGAA ICACCUUC 1229 GAAGGTGC C AAATTCAT 1953

907 GAUGAAUU CUGAUGAG X CGAA IGCACCUU 1230 AAGGTGCC A AATTCATC 1954

913 CCCCAUGA CUGAUGAG X CGAA IAAUUUGG 1231 CCAAATTC A TCATGGGG 1955

916 GUCCCCCA CUGAUGAG X CGAA IAUGAAUU 1232 AATTCATC A TGGGGGAC 1956

925 CACGGAAG CUGAUGAG X CGAA IUCCCCCA 1233 TGGGGGAC T CTTCCGTG 1957

927 UGCACGGA CUGAUGAG X CGAA IAGUCCCC 1234 GGGGACTC T TCCGTGCA 1958

930 UCCUGCAC CUGAUGAG X CGAA IAAGAGUC 1235 GACTCTTC C GTGCAGGA 1959

935 ACUGAUCC CUGAUGAG X CGAA ICACGGAA 1236 TTCCGTGC A GGATCAGT 1960

941 CCUUCCAC CUGAUGAG X CGAA IAUCCUGC 1237 GCAGGATC A GTGGAAGG 1961

953 CGUGGGAA CUGAUGAG X CGAA ICUCCUUC 1238 GAAGGAGC T TTCCCACG 1962

957 UCCUCGUG CUGAUGAG X CGAA IAAAGCUC 1239 GAGCTTTC C CACGAGGA 1963

958 GUCCUCGU CUGAUGAG X CGAA IGAAAGCU 1240 AGCTTTCC C ACGAGGAC 1964 Table 4

959 GGUCCUCG CUGAUGAG X CGAA IGGAAAGC 1241 GCTTTCCC A CGAGGACC 1965

967 GGGCUCCA CUGAUGAG X CGAA IUCCUCGU 1242 ACGAGGAC C TGGAGCCC 1966

968 GGGGCUCC CUGAUGAG X CGAA IGUCCUCG 1243 CGAGGACC T GGAGCCCC 1967

974 CGGGUGGG CUGAUGAG X CGAA ICUCCAGG 1244 CCTGGAGC C CCCACCCG 1968

975 UCGGGUGG CUGAUGAG X CGAA IGCUCCAG 1245 CTGGAGCC C CCACCCGA 1969

976 CUCGGGUG CUGAUGAG X CGAA IGGCUCCA 1246 TGGAGCCC C CACCCGAG 1970

977 GCUCGGGU CUGAUGAG X CGAA IGGGCUCC 1247 GGAGCCCC C ACCCGAGC 1971

978 UGCUCGGG CUGAUGAG X CGAA IGGGGCUC 1248 GAGCCCCC A CCCGAGCA 1972

980 UAUGCUCG CUGAUGAG X CGAA IUGGGGGC 1249 GCCCCCAC C CGAGCATA 1973

981 AUAUGCUC CUGAUGAG X CGAA IGUGGGGG 1250 CCCCCACC C GAGCATAT 1974

986 GGGGGAUA CUGAUGAG X CGAA ICUCGGGU 1251 ACCCGAGC A TATCCCCC 1975

991 AGGUGGGG CUGAUGAG X CGAA lAUAUGCU 1252 AGCATATC C CCCCACCT 1976

992 GAGGUGGG CUGAUGAG X CGAA IGAUAUGC 1253 GCATATCC C CCCACCTC 1977

993 GGAGGUGG CUGAUGAG X CGAA IGGAUAUG 1254 CATATCCC C CCACCTCC 1978

994 GGGAGGUG CUGAUGAG X CGAA IGGGAUAU 1255 ATATCCCC C CACCTCCC 1979

995 GGGGAGGU CUGAUGAG X CGAA IGGGGAUA 1256 TATCCCCC C ACCTCCCC 1980

996 CGGGGAGG CUGAUGAG X CGAA IGGGGGAU 1257 ATCCCCCC A CCTCCCCG 1981

998 GCCGGGGA CUGAUGAG X CGAA IUGGGGGG 1258 CCCCCCAC C TCCCCGGC 1982

999 GGCCGGGG CUGAUGAG X CGAA IGUGGGGG 1259 CCCCCACC T CCCCGGCC 1983

1001 GUGGCCGG CUGAUGAG X CGAA IAGGUGGG 1260 CCCACCTC C CCGGCCAC 1984

1002 GGUGGCCG CUGAUGAG X CGAA IGAGGUGG 1261 CCACCTCC C CGGCCACC 1985

1003 GGGUGGCC CUGAUGAG X CGAA IGGAGGUG 1262 CACCTCCC C GGCCACCC 1986

1007 GUUUGGGU CUGAUGAG X CGAA ICCGGGGA 1263 TCCCCGGC C ACCCAAAC 1987

1008 CGUUUGGG CUGAUGAG X CGAA IGCCGGGG 1264 CCCCGGCC A CCCAAACG 1988

1010 UUCGUUUG CUGAUGAG X CGAA IUGGCCGG 1265 CCGGCCAC C CAAACGAA 1989

1011 AUUCGUUU CUGAUGAG X CGAA IGUGGCCG 1266 CGGCCACC C AAACGAAT 1990

1012 GAUUCGUU CUGAUGAG X CGAA IGGUGGCC 1267 GGCCACCC A AACGAATC 1991

1021 UGGCUCCA CUGAUGAG X CGAA IAUUCGUU 1268 AACGAATC C TGGAGCCA 1992

1022 GUGGCUCC CUGAUGAG X CGAA IGAUUCGU 1269 ACGAATCC T GGAGCCAC 1993

1028 CAUUGUGU CUGAUGAG X CGAA ICUCCAGG 1270 CCTGGAGC C ACACAATG 1994

1029 CCAUUGUG CUGAUGAG X CGAA IGCUCCAG 1271 CTGGAGCC A CACAATGG 1995

1031 UCCCAUUG CUGAUGAG X CGAA IUGGCUCC 1272 GGAGCCAC A CAATGGGA 1996

1033 UUUCCCAU CUGAUGAG X CGAA IUGUGGCU 1273 AGCCACAC A ATGGGAAA 1997

1045 GAACUCCC CUGAUGAG X CGAA ICAUUUCC 1274 GGAAATGC A GGGAGTTC 1998

1054 AUUUGGGA CUGAUGAG X CGAA IAACUCCC 1275 GGGAGTTC T TCCCAAAT 1999

1057 GUGAUUUG CUGAUGAG X CGAA IAAGAACU 1276 AGTTCTTC C CAAATCAC 2000

1058 GGUGAUUU CUGAUGAG X CGAA IGAAGAAC 1277 GTTCTTCC C AAATCACC 2001

1059 UGGUGAUU CUGAUGAG X CGAA IGGAAGAA 1278 TTCTTCCC A AATCACCA 2002

1064 CCCACUGG CUGAUGAG X CGAA IAUUUGGG 1279 CCCAAATC A CCAGTGGG 2003

1066 CACCCACU CUGAUGAG X CGAA IUGAUUUG 1280 CAAATCAC C AGTGGGTG 2004

1067 UCACCCAC CUGAUGAG X CGAA IGUGAUUU 1281 AAATCACC A GTGGGTGA 2005

1086 UCCUCCUG CUGAUGAG X CGAA IUCUCUUC 1282 GAAGAGAC C CAGGAGGA 2006

1087 AUCCUCCU CUGAUGAG X CGAA IGUCUCUU 1283 AAGAGACC C AGGAGGAT 2007

1088 UAUCCUCC CUGAUGAG X CGAA IGGUCUCU 1284 AGAGACCC A GGAGGATA 2008

1102 GAUGGGGC CUGAUGAG X CGAA IUCUUUAU 1285 ATAAAGAC T GCCCCATC 2009

1105 CUUGAUGG CUGAUGAG X CGAA ICAGUCUU 1286 AAGACTGC C CCATCAAG 2010

1106 CCUUGAUG CUGAUGAG X CGAA IGCAGUCU 1287 AGACTGCC C CATCAAGG 2011 Table 4

1107 UCCUUGAU CUGAUGAG X CGAA IGGCAGUC 1288 GACTGCCC C ATCAAGGA 2012

1108 UUCCUUGA CUGAUGAG X CGAA IGGGCAGU 1289 ACTGCCCC A TCAAGGAA 2013 llll UUCUUCCU CUGAUGAG X CGAA IAUGGGGC 1290 GCCCCATC A AGGAAGAA 2014

1129 AUUUAAGG CUGAUGAG X CGAA ICUUCCUU 1291 AAGGAAGC C CCTTAAAT 2015

1130 CAUUUAAG CUGAUGAG X CGAA IGCUUCCU 1292 AGGAAGCC C CTTAAATG 2016

1131 GCAUUUAA CUGAUGAG X CGAA IGGCUUCC 1293 GGAAGCCC C TTAAATGC 2017

1132 GGCAUUUA CUGAUGAG X CGAA IGGGCUUC 1294 GAAGCCCC T TAAATGCC 2018

1140 UAGGGUGC CUGAUGAG X CGAA ICAUUUAA 1295 TTAAATGC C GCACCCTA 2019

1143 CCGUAGGG CUGAUGAG X CGAA ICGGCAUU 1296 AATGCCGC A CCCTACGG 2020

1145 UGCCGUAG CUGAUGAG X CGAA IUGCGGCA 1297 TGCCGCAC C CTACGGCA 2021

1146 AUGCCGUA CUGAUGAG X CGAA IGUGCGGC 1298 GCCGCACC c TACGGCAT 2022

1147 GAUGCCGU CUGAUGAG X CGAA IGGUGCGG 1299 CCGCACCC T ACGGCATC 2023

1153 GCUUUCGA CUGAUGAG X CGAA ICCGUAGG 1300 CCTACGGC A TCGAAAGC 2024

1162 UUGACUCA CUGAUGAG X CGAA ICUUUCGA 1301 TCGAAAGC A TGAGTCAA 2025

1169 CAGUGUCU CUGAUGAG X CGAA IACUCAUG 1302 CATGAGTC A AGACACTG 2026

1174 AACUUCAG CUGAUGAG X CGAA IUCUUGAC 1303 GTCAAGAC A CTGAAGTT 2027

1176 CUAACUUC CUGAUGAG X CGAA IUGUCUUG 1304 CAAGACAC T GAAGTTAG 2028

1208 CACCUCGA CUGAUGAG X CGAA IACUUCCC 1305 GGGAAGTC T TCGAGGTG 2029

1218 GCAGCCUG CUGAUGAG X CGAA ICACCUCG 1306 CGAGGTGC c CAGGCTGC 2030

1219 GGCAGCCU CUGAUGAG X CGAA IGCACCUC 1307 GAGGTGCC C AGGCTGCC 2031

1220 AGGCAGCC CUGAUGAG X CGAA IGGCACCU 1308 AGGTGCCC A GGCTGCCT 2032

1224 GGGGAGGC CUGAUGAG X CGAA ICCUGGGC 1309 GCCCAGGC T GCCTCCCC 2033

1227 GCUGGGGA CUGAUGAG X CGAA ICAGCCUG 1310 CAGGCTGC C TCCCCAGC 2034

1228 GGCUGGGG CUGAUGAG X CGAA IGCAGCCU 1311 AGGCTGCC T CCCCAGCC 2035

1230 UUGGCUGG CUGAUGAG X CGAA IAGGCAGC 1312 GCTGCCTC C CCAGCCAA 2036

1231 UUUGGCUG CUGAUGAG X CGAA IGAGGCAG 1313 CTGCCTCC C CAGCCAAA 2037

1232 CUUUGGCU CUGAUGAG X CGAA IGGAGGCA 1314 TGCCTCCC C AGCCAAAG 2038

1233 CCUUUGGC CUGAUGAG X CGAA IGGGAGGC 1315 GCCTCCCC A GCCAAAGG 2039

1236 UCCCCUUU CUGAUGAG X CGAA ICUGGGGA 1316 TCCCCAGC C AAAGGGGA 2040

1237 CUCCCCUU CUGAUGAG X CGAA IGCUGGGG 1317 CCCCAGCC A AAGGGGAG 2041

1247 GCAGUGAC CUGAUGAG X CGAA ICUCCCCU 1318 AGGGGAGC C GTCACTGC 2042

1251 UCGGGCAG CUGAUGAG X CGAA IACGGCUC 1319 GAGCCGTC A CTGCCCGA 2043

1253 UCUCGGGC CUGAUGAG X CGAA IUGACGGC 1320 GCCGTCAC T GCCCGAGA 2044

1256 CCUUCUCG CUGAUGAG X CGAA ICAGUGAC 1321 GTCACTGC C CGAGAAGG 2045

1257 UCCUUCUC CUGAUGAG X CGAA IGCAGUGA 1322 TCACTGCC C GAGAAGGA 2046

1273 CAGUGCAU CUGAUGAG X CGAA IUCCUCGU 1323 ACGAGGAC C ATGCACTG 2047

1274 UCAGUGCA CUGAUGAG X CGAA IGUCCUCG 1324 CGAGGACC A TGCACTGA 2048

1278 UAACUCAG CUGAUGAG X CGAA ICAUGGUC 1325 GACCATGC A CTGAGTTA 2049

1280 AGUAACUC CUGAUGAG X CGAA IUGCAUGG 1326 CCATGCAC T GAGTTACT 2050

1288 GGGCUUCC CUGAUGA rG X CGAA lUAACUCA 1327 TGAGTTAC T GGAAGCCC 2051

1295 CCAGGAAG CUGAUGAG X CGAA ICUUCCAG 1328 CTGGAAGC C CTTCCTGG 2052

1296 ACCAGGAA CUGAUGAG X CGAA IGCUUCCA 1329 TGGAAGCC C TTCCTGGT 2053

1297 GACCAGGA CUGAUGAG X CGAA IGGCUUCC 1330 GGAAGCCC T TCCTGGTC 2054

1300 GUUGACCA CUGAUGAG X CGAA IAAGGGCU 1331 AGCCCTTC C TGGTCAAC 2055

1301 UGUUGACC CUGAUGAG X CGAA IGAAGGGC 1332 GCCCTTCC T GGTCAACA 2056

1306 GCACAUGU CUGAUGAG X CGAA IACCAGGA 1333 TCCTGGTC A ACATGTGC 2057

1309 CACGCACA CUGAUGAG X CGAA IUUGACCA 1334 TGGTCAAC A TGTGCGTG 2058 Table 4

1320 AGGACCGU CUGAUGAG X CGAA ICCACGCA 1335 TGCGTGGC T ACGGTCCT 2059

1327 GGCCGUGA CUGAUGAG X CGAA IACCGUAG 1336 CTACGGTC C TCACGGCC 2060

1328 CGGCCGUG CUGAUGAG X CGAA IGACCGUA 1337 TACGGTCC T CACGGCCG 2061

1330 GCCGGCCG CUGAUGAG X CGAA IAGGACCG 1338 CGGTCCTC A CGGCCGGC 2062

1335 UAAGCGCC CUGAUGAG X CGAA ICCGUGAG 1339 CTCACGGC C GGCGCTTA 2063

1341 CAGAGGUA CUGAUGAG X CGAA ICGCCGGC 1340 GCCGGCGC T TACCTCTG 2064

1345 GUAGCAGA CUGAUGAG X CGAA IUAAGCGC 1341 GCGCTTAC C TCTGCTAC 2065

1346 UGUAGCAG CUGAUGAG X CGAA IGUAAGCG 1342 CGCTTACC T CTGCTACA 2066

1348 CCUGUAGC CUGAUGAG X CGAA IAGGUAAG 1343 CTTACCTC T GCTACAGG 2067

1351 GAACCUGU CUGAUGAG X CGAA ICAGAGGU 1344 ACCTCTGC T ACAGGTTC 2068

1354 CAGGAACC CUGAUGAG X CGAA IUAGCAGA 1345 TCTGCTAC A GGTTCCTG 2069

1360 GUUGAACA CUGAUGAG X CGAA IAACCUGU 1346 ACAGGTTC C TGTTCAAC 2070

1361 UGUUGAAC CUGAUGAG X CGAA IGAACCUG 1347 CAGGTTCC T GTTCAACA 2071

1366 GUUGCUGU CUGAUGAG X CGAA IAACAGGA 1348 TCCTGTTC A ACAGCAAC 2072

1369 UGUGUUGC CUGAUGAG X CGAA IUUGAACA 1349 TGTTCAAC A GCAACACA 2073

1372 CUAUGUGU CUGAUGAG X CGAA ICUGUUGA 1350 TCAACAGC A ACACATAG 2074

1375 AGGCUAUG CUGAUGAG X CGAA lUUGCUGU 1351 ACAGCAAC A CATAGCCT 2075

1377 UCAGGCUA CUGAUGAG X CGAA IUGUUGCU 1352 AGCAACAC A TAGCCTGA 2076

1382 GAGGGUCA CUGAUGAG X CGAA ICUAUGUG 1353 CACATAGC C TGACCCTC 2077

1383 GGAGGGUC CUGAUGAG X CGAA IGCUAUGU 1354 ACATAGCC T GACCCTCC 2078

1387 UGGAGGAG CUGAUGAG X CGAA IUCAGGCU 1355 AGCCTGAC c CTCCTCCA 2079

1388 GUGGAGGA CUGAUGAG X CGAA IGUCAGGC 1356 GCCTGACC c TCCTCCAC 2080

1389 AGUGGAGG CUGAUGAG X CGAA IGGUCAGG 1357 CCTGACCC T CCTCCACT 2081

1391 GGAGUGGA CUGAUGAG X CGAA IAGGGUCA 1358 TGACCCTC c TCCACTCC 2082

1392 UGGAGUGG CUGAUGAG X CGAA IGAGGGUC 1359 GACCCTCC T CCACTCCA 2083

1394 GGUGGAGU CUGAUGAG X CGAA IAGGAGGG 1360 CCCTCCTC c ACTCCACC 2084

1395 AGGUGGAG CUGAUGAG X CGAA IGAGGAGG 1361 CCTCCTCC A CTCCACCT 2085

1397 GGAGGUGG CUGAUGAG X CGAA IUGGAGGA 1362 TCCTCCAC T CCACCTCC 2086

1399 GUGGAGGU CUGAUGAG X CGAA IAGUGGAG 1363 CTCCACTC c ACCTCCAC 2087

1400 GGUGGAGG CUGAUGAG X CGAA IGAGUGGA 1364 TCCACTCC A CCTCCACC 2088

1402 UGGGUGGA CUGAUGAG X CGAA IUGGAGUG 1365 CACTCCAC C TCCACCCA 2089

1403 GUGGGUGG CUGAUGAG X CGAA IGUGGAGU 1366 ACTCCACC T CCACCCAC 2090

1405 CAGUGGGU CUGAUGAG X CGAA IAGGUGGA 1367 TCCACCTC C ACCCACTG 2091

1406 ACAGUGGG CUGAUGAG X CGAA IGAGGUGG 1368 CCACCTCC A CCCACTGT 2092

1408 GGACAGUG CUGAUGAG X CGAA IUGGAGGU 1369 ACCTCCAC C CACTGTCC 2093

1409 CGGACAGU CUGAUGAG X CGAA IGUGGAGG 1370 CCTCCACC C ACTGTCCG 2094

1410 GCGGACAG CUGAUGAG X CGAA IGGUGGAG 1371 CTCCACCC A CTGTCCGC 2095

1412 AGGCGGAC CUGAUGAG X CGAA IUGGGUGG 1372 CCACCCAC T GTCCGCCT 2096

1416 GCAGAGGC CUGAUGAG X CGAA IACAGUGG 1373 CCACTGTC C GCCTCTGC 2097

1419 CGGGCAGA CUGAUGAG X CGAA ICGGACAG 1374 CTGTCCGC C TCTGCCCG 2098

1420 GCGGGCAG CUGAUGAG X CGAA IGCGGACA 1375 TGTCCGCC T CTGCCCGC 2099

1422 CUGCGGGC CUGAUGAG X CGAA IAGGCGGA 1376 TCCGCCTC T GCCCGCAG 2100

1425 GCUCUGCG CUGAUGAG X CGAA ICAGAGGC 1377 GCCTCTGC C CGCAGAGC 2101

1426 GGCUCUGC CUGAUGAG X CGAA IGCAGAGG 1378 CCTCTGCC C GCAGAGCC 2102

1429 GUGGGCUC CUGAUGAG X CGAA ICGGGCAG 1379 CTGCCCGC A GAGCCCAC 2103

1434 CGGGCGUG CUGAUGAG X CGAA ICUCUGCG 1380 CGCAGAGC C CACGCCCG 2104

1435 UCGGGCGU CUGAUGAG X CGAA IGCUCUGC 1381 GCAGAGCC C ACGCCCGA 2105 Table 4

1436 GUCGGGCG CUGAUGAG X CGAA IGGCUCUG 1382 CAGAGCCC A CGCCCGAC 2106

1440 GCUAGUCG CUGAUGAG X CGAA ICGUGGGC 1383 GCCCACGC C CGACTAGC 2107

1441 UGCUAGUC CUGAUGAG X CGAA IGCGUGGG 1384 CCCACGCC C GACTAGCA 2108

1445 UGCCUGCU CUGAUGAG X CGAA IUCGGGCG 1385 CGCCCGAC T AGCAGGCA 2109

1449 GGCAUGCC CUGAUGAG X CGAA ICUAGUCG 1386 CGACTAGC A GGCATGCC 2110

1453 CCGCGGCA CUGAUGAG X CGAA ICCUGCUA 1387 TAGCAGGC A TGCCGCGG 2111

1457 CCUACCGC CUGAUGAG X CGAA ICAUGCCU 1388 AGGCATGC C GCGGTAGG 2112

1473 GGUCCGGC CUGAUGAG X CGAA ICCCUUAC 1389 GTAAGGGC C GCCGGACC 2113

1476 CGCGGUCC CUGAUGAG X CGAA ICGGCCCU 1390 AGGGCCGC C GGACCGCG 2114

1481 CUCUACGC CUGAUGAG X CGAA IUCCGGCG 1391 CGCCGGAC C GCGTAGAG 2115

1493 CGGGGCCC CUGAUGAG X CGAA ICUCUCUA 1392 TAGAGAGC C GGGCCCCG 2116

1498 CCGUCCGG CUGAUGAG X CGAA ICCCGGCU 1393 AGCCGGGC C CCGGACGG 2117

1499 UCCGUCCG CUGAUGAG X CGAA IGCCCGGC 1394 GCCGGGCC C CGGACGGA 2118

1500 GUCCGUCC CUGAUGAG X CGAA IGGCCCGG 1395 CCGGGCCC C GGACGGAC 2119

1517 UUUAGUGC CUGAUGAG X CGAA IAACCAAC 1396 GTTGGTTC T GCACTAAA 2120

1520 GGUUUUAG CUGAUGAG X CGAA ICAGAACC 1397 GGTTCTGC A CTAAAACC 2121

1522 UGGGUUUU CUGAUGAG X CGAA lUGCAGAA 1398 TTCTGCAC T AAAACCCA 2122

1528 GGAAGAUG CUGAUGAG X CGAA IUUUUAGU 1399 ACTAAAAC C CATCTTCC 2123

1529 GGGAAGAU CUGAUGAG X CGAA IGUUUUAG 1400 CTAAAACC C ATCTTCCC 2124

1530 GGGGAAGA CUGAUGAG X CGAA IGGUUUUA 1401 TAAAACCC A TCTTCCCC 2125

1533 UCCGGGGA CUGAUGAG X CGAA IAUGGGUU 1402 AACCCATC T TCCCCGGA 2126

1536 ACAUCCGG CUGAUGAG X CGAA IAAGAUGG 1403 CCATCTTC C CCGGATGT 2127

1537 CACAUCCG CUGAUGAG X CGAA IGAAGAUG 1404 CATCTTCC C CGGATGTG 2128

1538 ACACAUCC CUGAUGAG X CGAA IGGAAGAU 1405 ATCTTCCC C GGATGTGT 2129

1550 GAGGGGUG CUGAUGAG X CGAA IACACACA 1406 TGTGTGTC T CACCCCTC 2130

1552 AUGAGGGG CUGAUGAG X CGAA lAGACACA 1407 TGTGTCTC A CCCCTCAT 2131

1554 GGAUGAGG CUGAUGAG X CGAA IUGAGACA 1408 TGTCTCAC C CCTCATCC 2132

1555 AGGAUGAG CUGAUGAG X CGAA IGUGAGAC 1409 GTCTCACC C CTCATCCT 2133

1556 AAGGAUGA CUGAUGAG X CGAA IGGUGAGA 1410 TCTCACCC C TCATCCTT 2134

1557 AAAGGAUG CUGAUGAG X CGAA IGGGUGAG 1411 CTCACCCC T CATCCTTT 2135

1559 UAAAAGGA CUGAUGAG X CGAA IAGGGGUG 1412 CACCCCTC A TCCTTTTA 2136

1562 AAGUAAAA CUGAUGAG X CGAA IAUGAGGG 1413 CCCTCATC C TTTTACTT 2137

1563 AAAGUAAA CUGAUGAG X CGAA IGAUGAGG 1414 CCTCATCC T TTTACTTT 2138

1569 GGGCAAAA CUGAUGAG X CGAA IUAAAAGG 1415 CCTTTTAC T TTTTGCCC 2139

1576 GUGGAAGG CUGAUGAG X CGAA ICAAAAAG 1416 CTTTTTGC C CCTTCCAC 2140

1577 AGUGGAAG CUGAUGAG X CGAA IGCAAAAA 1417 TTTTTGCC C CTTCCACT 2141

1578 AAGUGGAA CUGAUGAG X CGAA IGGCAAAA 1418 TTTTGCCC C TTCCACTT 2142

1579 AAAGUGGA CUGAUGAG X CGAA IGGGCAAA 1419 TTTGCCCC T TCCACTTT 2143

1582 CUCAAAGU CUGAUGAG X CGAA IAAGGGGC 1420 GCCCCTTC C ACTTTGAG 2144

1583 ACUCAAAG CUGAUGAG X CGAA IGAAGGGG 1421 CCCCTTCC A CTTTGAGT 2145

1585 GUACUCAA CUGAUGAG X CGAA IUGGAAGG 1422 CCTTCCAC T TTGAGTAC 2146

1594 GUGGAUUU CUGAUGAG X CGAA IUACUCAA 1423 TTGAGTAC C AAATCCAC 2147

1595 UGUGGAUU CUGAUGAG X CGAA IGUACUCA 1424 TGAGTACC A AATCCACA 2148

1600 UGGCUUGU CUGAUGAG X CGAA IAUUUGGU 1425 ACCAAATC C ACAAGCCA 2149

1601 AUGGCUUG CUGAUGAG X CGAA IGAUUUGG 1426 CCAAATCC A CAAGCCAT 2150

1603 AAAUGGCU CUGAUGAG X CGAA IUGGAUUU 1427 AAATCCAC A AGCCATTT 2151

1607 CAAAAAAU CUGAUGAG X CGAA ICUUGUGG 1428 CCACAAGC C ATTTTTTG 2152 Table 4

1608 UCAAAAAA CUGAUGAG X CGAA IGCUUGUG 1429 CACAAGCC A TTTTTTGA 2153

1636 GCCAGCAU CUGAUGAG X CGAA IUACUCUC 1430 GAGAGTAC C ATGCTGGC 2154

1637 CGCCAGCA CUGAUGAG X CGAA IGUACUCU 1431 AGAGTACC A TGCTGGCG 2155

1641 GCGCCGCC CUGAUGAG X CGAA ICAUGGUA 1432 TACCATGC T GGCGGCGC 2156

1650 CUUCCCUC CUGAUGAG X CGAA ICGCCGCC 1433 GGCGGCGC A GAGGGAAG 2157

1663 CGGGUGUA CUGAUGAG X CGAA ICCCCUUC 1434 GAAGGGGC C TACACCCG 2158

1664 ACGGGUGU CUGAUGAG X CGAA IGCCCCUU 1435 AAGGGGCC T ACACCCGT 2159

1667 AAGACGGG CUGAUGAG X CGAA IUAGGCCC 1436 GGGCCTAC A CCCGTCTT 2160

1669 CCAAGACG CUGAUGAG X CGAA IUGUAGGC 1437 GCCTACAC C CGTCTTGG 2161

1670 CCCAAGAC CUGAUGAG X CGAA IGUGUAGG 1438 CCTACACC C GTCTTGGG 2162

1674 GAGCCCCA CUGAUGAG X CGAA IACGGGUG 1439 CACCCGTC T TGGGGCTC 2163

1681 GUGGGGCG CUGAUGAG X CGAA ICCCCAAG 1440 CTTGGGGC T CGCCCCAC 2164

1685 CUGGGUGG CUGAUGAG X CGAA ICGAGCCC 1441 GGGCTCGC C CCACCCAG 2165

1686 CCUGGGUG CUGAUGAG X CGAA IGCGAGCC 1442 GGCTCGCC C CACCCAGG 2166

1687 CCCUGGGU CUGAUGAG X CGAA IGGCGAGC 1443 GCTCGCCC C ACCCAGGG 2167

1688 GCCCUGGG CUGAUGAG X CGAA IGGGCGAG 1444 CTCGCCCC A CCCAGGGC 2168

1690 GAGCCCUG CUGAUGAG X CGAA IUGGGGCG 1445 CGCCCCAC C CAGGGCTC 2169

1691 GGAGCCCU CUGAUGAG X CGAA IGUGGGGC 1446 GCCCCACC C AGGGCTCC 2170

1692 GGGAGCCC CUGAUGAG X CGAA IGGUGGGG 1447 CCCCACCC A GGGCTCCC ^• 2171

1697 CAGGAGGG CUGAUGAG X CGAA ICCCUGGG 1448 CCCAGGGC T CCCTCCTG 2172

1699 UCCAGGAG CUGAUGAG X CGAA IAGCCCUG 1449 CAGGGCTC C CTCCTGGA 2173

1700 CUCCAGGA CUGAUGAG X CGAA IGAGCCCU 1450 AGGGCTCC C TCCTGGAG 2174

1701 GCUCCAGG CUGAUGAG X CGAA IGGAGCCC 1451 GGGCTCCC T CCTGGAGC 2175

1703 AUGCUCCA CUGAUGAG X CGAA IAGGGAGC 1452 GCTCCCTC c TGGAGCAT 2176

1704 GAUGCUCC CUGAUGAG X CGAA IGAGGGAG 1453 CTCCCTCC T GGAGCATC 2177

1710 GCCUGGGA CUGAUGAG X CGAA ICUCCAGG 1454 CCTGGAGC A TCCCAGGC 2178

1713 CCCGCCUG CUGAUGAG X CGAA IAUGCUCC 1455 GGAGCATC C CAGGCGGG 2179

1714 GCCCGCCU CUGAUGAG X CGAA IGAUGCUC 1456 GAGCATCC C AGGCGGGC 2180

1715 CGCCCGCC CUGAUGAG X CGAA IGGAUGCU 1457 AGCATCCC A GGCGGGCG 2181

1726 GUCUGGCG CUGAUGAG X CGAA ICCGCCCG 1458 CGGGCGGC A CGCCAGAC 2182

1730 GGCUGUCU CUGAUGAG X CGAA ICGUGCCG 1459 CGGCACGC C AGACAGCC 2183

1731 GGGCUGUC CUGAUGAG X CGAA IGCGUGCC 1460 GGCACGCC A GACAGCCC 2184

1735 GGGGGGGC CUGAUGAG X CGAA IUCUGGCG 1461 CGCCAGAC A GCCCCCCC 2185

1738 AAGGGGGG CUGAUGAG X CGAA ICUGUCUG 1462 CAGACAGC C CCCCCCTT 2186

1739 CAAGGGGG CUGAUGAG X CGAA IGCUGUCU 1463 AGACAGCC C CCCCCTTG 2187

1740 UCAAGGGG CUGAUGAG X CGAA IGGCUGUC 1464 GACAGCCC C CCCCTTGA 2188

1741 UUCAAGGG CUGAUGAG X CGAA IGGGCUGU 1465 ACAGCCCC C CCCTTGAA 2189

1742 AUUCAAGG CUGAUGAG X CGAA IGGGGCUG 1466 CAGCCCCC C CCTTGAAT 2190

1743 GAUUCAAG CUGAUGAG X CGAA IGGGGGCU 1467 AGCCCCCC C CTTGAATC 2191

1744 AGAUUCAA CUGAUGAG X CGAA IGGGGGGC 1468 GCCCCCCC C TTGAATCT 2192

1745 CAGAUUCA CUGAUGAG X CGAA IGGGGGGG 1469 CCCCCCCC T TGAATCTG 2193

1752 CUCCCUGC CUGAUGAG X CGAA IAUUCAAG 1470 CTTGAATC T GCAGGGAG 2194

1755 UUGCUCCC CUGAUGAG X CGAA ICAGAUUC 1471 GAATCTGC A GGGAGCAA 2195

1762 UGGAGAGU CUGAUGAG X CGAA ICUCCCUG 1472 CAGGGAGC A ACTCTCCA 2196

1765 GAGUGGAG CUGAUGAG X CGAA IUUGCUCC 1473 GGAGCAAC T CTCCACTC 2197

1767 UGGAGUGG CUGAUGAG X CGAA IAGUUGCU 1474 AGCAACTC T CCACTCCA 2198

1769 UAUGGAGU CUGAUGAG X CGAA IAGAGUUG 1475 CAACTCTC C ACTCCATA 2199 Table 4

1770 AUAUGGAG CUGAUGAG X CGAA IGAGAGUU 1476 AACTCTCC A CTCCATAT 2200

1772 AAAUAUGG CUGAUGAG X CGAA IUGGAGAG 1477 CTCTCCAC T CCATATTT 2201

1774 AUAAAUAU CUGAUGAG X CGAA IAGUGGAG 1478 CTCCACTC C ATATTTAT 2202

1775 AAUAAAUA CUGAUGAG X CGAA IGAGUGGA 1479 TCCACTCC A TATTTATT 2203

1789 GAAAAAAU CUGAUGAG X CGAA IUUUAAAU 1480 ATTTAAAC A ATTTTTTC 2204

1798 GCCUUUGG CUGAUGAG X CGAA IAAAAAAU 1481 ATTTTTTC C CCAAAGGC 2205

1799 UGCCUUUG CUGAUGAG X CGAA IGAAAAAA 1482 TTTTTTCC C CAAAGGCA 2206

1800 AUGCCUUU CUGAUGAG X CGAA IGGAAAAA 1483 TTTTTCCC C AAAGGCAT 2207

1801 GAUGCCUU CUGAUGAG X CGAA IGGGAAAA 1484 TTTTCCCC A AAGGCATC 2208

1807 ACUAUGGA CUGAUGAG X CGAA ICCUUUGG 1485 CCAAAGGC A TCCATAGT 2209

1810 UGCACUAU CUGAUGAG X CGAA IAUGCCUU 1486 AAGGCATC C ATAGTGCA 2210

1811 GUGCACUA CUGAUGAG X CGAA IGAUGCCU 1487 AGGCATCC A TAGTGCAC 2211

1818 AAUGCUAG CUGAUGAG X CGAA ICACUAUG 1488 CATAGTGC A CTAGCATT 2212

1820 AAAAUGCU CUGAUGAG X CGAA IUGCACUA 1489 TAGTGCAC T AGCATTTT 2213

1824 CAAGAAAA CUGAUGAG X CGAA ICUAGUGC 1490 GCACTAGC A TTTTCTTG 2214

1830 UUGGUUCA CUGAUGAG X CGAA IAAAAUGC 1491 GCATTTTC T TGAACCAA 2215

1836 ACAUUAUU CUGAUGAG X CGAA IUUCAAGA 1492 TCTTGAAC C AATAATGT 2216

1837 UACAUUAU CUGAUGAG X CGAA IGUUCAAG 1493 CTTGAACC A ATAATGTA 2217

1864 UGCAAGGC CUGAUGAG X CGAA IACAUCAA 1494 TTGATGTC A GCCTTGCA 2218

1867 UGAUGCAA CUGAUGAG X CGAA ICUGACAU 1495 ATGTCAGC C TTGCATCA 2219

1868 UUGAUGCA CUGAUGAG X CGAA IGCUGACA 1496 TGTCAGCC T TGCATCAA 2220

1872 GCCCUUGA CUGAUGAG X CGAA ICAAGGCU 1497 AGCCTTGC A TCAAGGGC 2221

1875 AAAGCCCU CUGAUGAG X CGAA IAUGCAAG 1498 CTTGCATC A AGGGCTTT 2222

1881 UUUGAUAA CUGAUGAG X CGAA ICCCUUGA 1499 TCAAGGGC T TTATCAAA 2223

1887 GUACUUUU CUGAUGAG X CGAA IAUAAAGC 1500 GCTTTATC A AAAAGTAC 2224

1896 UUUAUUAU CUGAUGAG X CGAA IUACUUUU 1501 AAAAGTAC A ATAATAAA 2225

1907 CUACCUGA CUGAUGAG X CGAA IAUUUAUU 1502 AATAAATC C TCAGGTAG 2226

1908 ACUACCUG CUGAUGAG X CGAA IGAUUUAU 1503 ATAAATCC T CAGGTAGT 2227

1910 GUACUACC CUGAUGAG X CGAA IAGGAUUU 1504 AAATCCTC A GGTAGTAC 2228

1919 CCAUUCCC CUGAUGAG X CGAA IUACUACC 1505 GGTAGTAC T GGGAATGG 2229

1933 CAUGGCAA CUGAUGAG X CGAA ICCUUCCA 1506 TGGAAGGC T TTGCCATG 2230

1938 AGGCCCAU CUGAUGAG X CGAA ICAAAGCC 1507 GGCTTTGC C ATGGGCCT 2231

1939 CAGGCCCA CUGAUGAG X CGAA IGCAAAGC 1508 GCTTTGCC A TGGGCCTG 2232

1945 ACGCAGCA CUGAUGAG X CGAA ICCCAUGG 1509 CCATGGGC C TGCTGCGT 2233

1946 GACGCAGC CUGAUGAG X CGAA IGCCCAUG 1510 CATGGGCC T GCTGCGTC 2234

1949 UCUGACGC CUGAUGAG X CGAA ICAGGCCC 1511 GGGCCTGC T GCGTCAGA 2235

1955 UACUGGUC CUGAUGAG X CGAA IACGCAGC 1512 GCTGCGTC A GACCAGTA 2236

1959 CCAGUACU CUGAUGAG X CGAA IUCUGACG 1513 CGTCAGAC C AGTACTGG 2237

1960 CCCAGUAC CUGAUGAG X CGAA IGUCUGAC 1514 GTCAGACC A GTACTGGG 2238

1965 UCCUUCCC CUGAUGAG X CGAA IUACUGGU 1515 ACCAGTAC T GGGAAGGA 2239

1988 AUAACAAC CUGAUGAG X CGAA ICUUACAA 1516 TTGTAAGC A GTTGTTAT 2240

2032 UAUAGCAU CUGAUGAG X CGAA IUUCUAUC 1517 GATAGAAC A ATGCTATA 2241

2037 UAUAUUAU CUGAUGAG X CGAA ICAUUGUU 1518 AACAATGC T ATAATATA 2242

2054 UACCCACG CUGAUGAG X CGAA lUUCAUUA 1519 TAATGAAC A CGTGGGTA 2243

2076 UCACAUCA CUGAUGAG X CGAA IUUUCUUA 1520 TAAGAAAC A TGATGTGA 2244

2091 CGGGACAA CUGAUGAG X CGAA IUAAUCUC 1521 GAGATTAC T TTGTCCCG 2245

2097 AAUAAGCG CUGAUGAG X CGAA lACAAAGU 1522 ACTTTGTC C CGCTTATT 2246 Table 4

2098 GAAUAAGC CUGAUGAG X CGAA IGACAAAG 1523 CTTTGTCC C GCTTATTC 2247

2101 GCAGAAUA CUGAUGAG X CGAA ICGGGACA 1524 TGTCCCGC T TATTCTGC 2248

2107 CAGGGAGC CUGAUGAG X CGAA IAAUAAGC 1525 GCTTATTC T GCTCCCTG 2249

2110 UAACAGGG CUGAUGAG X CGAA ICAGAAUA 1526 TATTCTGC T CCCTGTTA 2250

2112 GAUAACAG CUGAUGAG X CGAA IAGCAGAA 1527 TTCTGCTC C CTGTTATC 2251

2113 AGAUAACA CUGAUGAG X CGAA IGAGCAGA 1528 TCTGCTCC C TGTTATCT 2252

2114 CAGAUAAC CUGAUGAG X CGAA IGGAGCAG 1529 CTGCTCCC T GTTATCTG 2253

2121 GAUCUAGC CUGAUGAG X CGAA IAUAACAG 1530 CTGTTATC T GCTAGATC 2254

2124 CUAGAUCU CUGAUGAG X CGAA ICAGAUAA 1531 TTATCTGC T AGATCTAG 2255

2130 UGAGAACU CUGAUGAG X CGAA IAUCUAGC 1532 GCTAGATC T AGTTCTCA 2256

2136 AGUGAUUG CUGAUGAG X CGAA IAACUAGA 1533 TCTAGTTC T CAATCACT 2257

2138 GCAGUGAU CUGAUGAG X CGAA IAGAACUA 1534 TAGTTCTC A ATCACTGC 2258

2142 GGGAGCAG CUGAUGAG X CGAA IAUUGAGA 1535 TCTCAATC A CTGCTCCC 2259

2144 GGGGGAGC CUGAUGAG X CGAA IUGAUUGA 1536 TCAATCAC T GCTCCCCC 2260

2147 CACGGGGG CUGAUGAG X CGAA ICAGUGAU 1537 ATCACTGC T CCCCCGTG 2261

2149 CACACGGG CUGAUGAG X CGAA IAGCAGUG 1538 CACTGCTC C CCCGTGTG 2262

2150 ACACACGG CUGAUGAG X CGAA IGAGCAGU 1539 ACTGCTCC C CCGTGTGT 2263

2151 UACACACG CUGAUGAG X CGAA IGGAGCAG 1540 CTGCTCCC C CGTGTGTA 2264

2152 AUACACAC CUGAUGAG X CGAA IGGGAGCA 1541 TGCTCCCC C GTGTGTAT 2265

2169 ACCUUACA CUGAUGAG X CGAA ICAUUCUA 1542 TAGAATGC A TGTAAGGT 2266

2179 ACACAAGA CUGAUGAG X CGAA IACCUUAC 1543 GTAAGGTC T TCTTGTGT 2267

2182 AGGACACA CUGAUGAG X CGAA IAAGACCU 1544 AGGTCTTC T TGTGTCCT 2268

2189 UUUCAUCA CUGAUGAG X CGAA IACACAAG 1545 CTTGTGTC c TGATGAAA 2269

2190 UUUUCAUC CUGAUGAG X CGAA IGACACAA 1546 TTGTGTCC T GATGAAAA 2270

2207 UCAUUUCA CUGAUGAG X CGAA ICACAUAU 1547 ATATGTGC T TGAAATGA 2271

2221 GAGAUCAA CUGAUGAG X CGAA IUUUCUCA 1548 TGAGAAAC T TTGATCTC 2272

2228 GUAAGCAG CUGAUGAG X CGAA IAUCAAAG 1549 CTTTGATC T CTGCTTAC 2273

2230 UAGUAAGC CUGAUGAG X CGAA lAGAUCAA 1550 TTGATCTC T GCTTACTA 2274

2233 CAUUAGUA CUGAUGAG X CGAA ICAGAGAU 1551 ATCTCTGC T TACTAATG 2275

2237 GGCACAUU CUGAUGAG X CGAA IUAAGCAG 1552 CTGCTTAC T AATGTGCC 2276

2245 GGACAUGG CUGAUGAG X CGAA ICACAUUA 1553 TAATGTGC c CCATGTCC 2277

2246 UGGACAUG CUGAUGAG X CGAA IGCACAUU 1554 AATGTGCC c CATGTCCA 2278

2247 UUGGACAU CUGAUGAG X CGAA IGGCACAU 1555 ATGTGCCC c ATGTCCAA 2279

2248 CUUGGACA CUGAUGAG X CGAA IGGGCACA 1556 TGTGCCCC A TGTCCAAG 2280

2253 UUGGACUU CUGAUGAG X CGAA IACAUGGG 1557 CCCATGTC c AAGTCCAA 2281

2254 GUUGGACU CUGAUGAG X CGAA IGACAUGG 1558 CCATGTCC A AGTCCAAC 2282

2259 GGCAGGUU CUGAUGAG X CGAA IACUUGGA 1559 TCCAAGTC C AACCTGCC 2283

2260 AGGCAGGU CUGAUGAG X CGAA IGACUUGG 1560 CCAAGTCC A ACCTGCCT 2284

2263 CACAGGCA CUGAUGAG X CGAA IUUGGACU 1561 AGTCCAAC C TGCCTGTG 2285

2264 GCACAGGC CUGAUGAG X CGAA IGUUGGAC 1562 GTCCAACC T GCCTGTGC 2286

2267 CAUGCACA CUGAUGAG X CGAA ICAGGUUG 1563 CAACCTGC C TGTGCATG 2287

2268 UCAUGCAC CUGAUGAG X CGAA IGCAGGUU 1564 AACCTGCC T GTGCATGA 2288

2273 UCAGGUCA CUGAUGAG X CGAA ICACAGGC 1565 GCCTGTGC A TGACCTGA 2289

2278 AAUGAUCA CUGAUGAG X CGAA lUCAUGCA 1566 TGCATGAC C TGATCATT 2290

2279 UAAUGAUC CUGAUGAG X CGAA IGUCAUGC 1567 GCATGACC T GATCATTA 2291

2284 CCAUGUAA CUGAUGAG X CGAA IAUCAGGU 1568 ACCTGATC A TTACATGG 2292

2289 CACAGCCA CUGAUGAG X CGAA IUAAUGAU 1569 ATCATTAC A TGGCTGTG 2293 Table 4

2294 GGAACCAC CUGAUGAG X CGAA ICCAUGUA 1570 TACATGGC T GTGGTTCC 2294

2302 CAGGCUUA CUGAUGAG X CGAA IAACCACA 1571 TGTGGTTC C TAAGCCTG 2295

2303 ACAGGCUU CUGAUGAG X CGAA IGAACCAC 1572 GTGGTTCC T AAGCCTGT 2296

2308 CAGCAACA CUGAUGAG X CGAA ICUUAGGA 1573 TCCTAAGC C TGTTGCTG 2297

2309 UCAGCAAC CUGAUGAG X CGAA IGCUUAGG 1574 CCTAAGCC T GTTGCTGA 2298

2315 AUGACUUC CUGAUGAG X CGAA ICAACAGG 1575 CCTGTTGC T GAAGTCAT 2299

2322 AGCGACAA CUGAUGAG X CGAA IACUUCAG 1576 CTGAAGTC A TTGTCGCT 2300

2330 UAUUGCUG CUGAUGAG X CGAA ICGACAAU 1577 ATTGTCGC T CAGCAATA 2301

2332 CCUAUUGC CUGAUGAG X CGAA IAGCGACA 1578 TGTCGCTC A GCAATAGG 2302

2335 CACCCUAU CUGAUGAG X CGAA ICUGAGCG 1579 CGCTCAGC A ATAGGGTG 2303

2345 UGGAAAAC CUGAUGAG X CGAA ICACCCUA 1580 TAGGGTGC A GTTTTCCA 2304

2352 CUAUUCCU CUGAUGAG X CGAA IAAAACUG 1581 CAGTTTTC C AGGAATAG 2305

2353 CCUAUUCC CUGAUGAG X CGAA IGAAAACU 1582 AGTTTTCC A GGAATAGG 2306

2363 UAGGCAAA CUGAUGAG X CGAA ICCUAUUC 1583 GAATAGGC A TTTGCCTA 2307

2369 AGGAAUUA CUGAUGAG X CGAA ICAAAUGC 1584 GCATTTGC C TAATTCCT 2308

2370 CAGGAAUU CUGAUGAG X CGAA IGCAAAUG 1585 CATTTGCC T AATTCCTG 2309

2376 UCAUGCCA CUGAUGAG X CGAA IAAUUAGG 1586 CCTAATTC C TGGCATGA 2310

2377 GUCAUGCC CUGAUGAG X CGAA IGAAUUAG 1587 CTAATTCC T GGCATGAC 2311

2381 GAGUGUCA CUGAUGAG X CGAA ICCAGGAA 1588 TTCCTGGC A TGACACTC 2312

2386 CACUAGAG CUGAUGAG X CGAA IUCAUGCC 1589 GGCATGAC A CTCTAGTG 2313

2388 GUCACUAG CUGAUGAG X CGAA IUGUCAUG 1590 CATGACAC T CTAGTGAC 2314

2390 AAGUCACU CUGAUGAG X CGAA lAGUGUCA 1591 TGACACTC T AGTGACTT 2315

2397 CACCAGGA CUGAUGAG X CGAA IUCACUAG 1592 CTAGTGAC T TCCTGGTG 2316

2400 CCUCACCA CUGAUGAG X CGAA IAAGUCAC 1593 GTGACTTC C TGGTGAGG 2317

2401 GCCUCACC CUGAUGAG X CGAA IGAAGUCA 1594 TGACTTCC T GGTGAGGC 2318

2410 ACAGGCUG CUGAUGAG X CGAA ICCUCACC 1595 GGTGAGGC C CAGCCTGT 2319

2411 GACAGGCU CUGAUGAG X CGAA IGCCUCAC 1596 GTGAGGCC C AGCCTGTC 2320

2412 GGACAGGC CUGAUGAG X CGAA IGGCCUCA 1597 TGAGGCCC A GCCTGTCC 2321

2415 CCAGGACA CUGAUGAG X CGAA ICUGGGCC 1598 GGCCCAGC C TGTCCTGG 2322

2416 ACCAGGAC CUGAUGAG X CGAA IGCUGGGC 1599 GCCCAGCC T GTCCTGGT 2323

2420 CUGUACCA CUGAUGAG X CGAA IACAGGCU 1600 AGCCTGTC C TGGTACAG 2324

2421 GCUGUACC CUGAUGAG X CGAA IGACAGGC 1601 GCCTGTCC T GGTACAGC 2325

2427 GACCCUGC CUGAUGAG X CGAA IUACCAGG 1602 CCTGGTAC A GCAGGGTC 2326

2430 CAAGACCC CUGAUGAG X CGAA ICUGUACC 1603 GGTACAGC A GGGTCTTG 2327

2436 UUACAGCA CUGAUGAG X CGAA IACCCUGC 1604 GCAGGGTC T TGCTGTAA 2328

2440 UGAGUUAC CUGAUGAG X CGAA ICAAGACC 1605 GGTCTTGC T GTAACTCA 2329

2446 AAUGUCUG CUGAUGAG X CGAA IUUACAGC 1606 GCTGTAAC T CAGACATT 2330

2448 GGAAUGUC CUGAUGAG X CGAA lAGUUACA 1607 TGTAACTC A GACATTCC 2331

2452 CCUUGGAA CUGAUGAG X CGAA IUCUGAGU 1608 ACTCAGAC A TTCCAAGG 2332

2456 AUACCCUU CUGAUGAG X CGAA IAAUGUCU 1609 AGACATTC C AAGGGTAT 2333

2457 CAUACCCU CUGAUGAG X CGAA IGAAUGUC 1610 GACATTCC A AGGGTATG 2334

2472 GUGAAUAU CUGAUGAG X CGAA ICUUCCCA 1611 TGGGAAGC C ATATTCAC 2335

2473 UGUGAAUA CUGAUGAG X CGAA IGCUUCCC 1612 GGGAAGCC A TATTCACA 2336

2479 GUGAGGUG CUGAUGAG X CGAA IAAUAUGG 1613 CCATATTC A CACCTCAC 2337

2481 GCGUGAGG CUGAUGAG X CGAA IUGAAUAU 1614 ATATTCAC A CCTCACGC 2338

2483 GAGCGUGA CUGAUGAG X CGAA IUGUGAAU 1615 ATTCACAC C TCACGCTC 2339

2484 AGAGCGUG CUGAUGAG X CGAA IGUGUGAA 1616 TTCACACC T CACGCTCT 2340 Table 4

2486 CCAGAGCG CUGAUGAG X CGAA IAGGUGUG 1617 CACACCTC A CGCTCTGG 2341

2490 AUGUCCAG CUGAUGAG X CGAA ICGUGAGG 1618 CCTCACGC T CTGGACAT 2342

2492 UCAUGUCC CUGAUGAG X CGAA IAGCGUGA 1619 TCACGCTC T GGACATGA 2343

2497 CUAAAUCA CUGAUGAG X CGAA IUCCAGAG 1620 CTCTGGAC A TGATTTAG 2344

2512 GGUGUCCC CUGAUGAG X CGAA ICUUCCCU 1621 AGGGAAGC A GGGACACC 2345

2518 GCGGGGGG CUGAUGAG X CGAA IUCCCUGC 1622 GCAGGGAC A CCCCCCGC 2346

2520 GGGCGGGG CUGAUGAG X CGAA IUGUCCCU 1623 AGGGACAC C CCCCGCCC 2347

2521 GGGGCGGG CUGAUGAG X CGAA IGUGUCCC 1624 GGGACACC C CCCGCCCC 2348

2522 GGGGGCGG CUGAUGAG X CGAA IGGUGUCC 1625 GGACACCC C CCGCCCCC 2349

2523 GGGGGGCG CUGAUGAG X CGAA IGGGUGUC 1626 GACACCCC C CGCCCCCC 2350

2524 UGGGGGGC CUGAUGAG X CGAA IGGGGUGU 1627 ACACCCCC C GCCCCCCA 2351

2527 AGGUGGGG CUGAUGAG X CGAA ICGGGGGG 1628 CCCCCCGC C CCCCACCT 2352

2528 AAGGUGGG CUGAUGAG X CGAA IGCGGGGG 1629 CCCCCGCC C CCCACCTT 2353

2529 AAAGGUGG CUGAUGAG X CGAA IGGCGGGG 1630 CCCCGCCC C CCACCTTT 2354

2530 CAAAGGUG CUGAUGAG X CGAA IGGGCGGG 1631 CCCGCCCC C CACCTTTG 2355

2531 CCAAAGGU CUGAUGAG X CGAA IGGGGCGG 1632 CCGCCCCC C ACCTTTGG 2356

2532 CCCAAAGG CUGAUGAG X CGAA IGGGGGCG 1633 CGCCCCCC A CCTTTGGG 2357

2534 AUCCCAAA CUGAUGAG X CGAA IUGGGGGG 1634 CCCCCCAC C TTTGGGAT 2358

2535 GAUCCCAA CUGAUGAG X CGAA IGUGGGGG 1635 CCCCCACC T TTGGGATC 2359

2544 GCGGAGGC CUGAUGAG X CGAA IAUCCCAA 1636 TTGGGATC A GCCTCCGC 2360

2547 AUGGCGGA CUGAUGAG X CGAA ICUGAUCC 1637 GGATCAGC C TCCGCCAT 2361

2548 AAUGGCGG CUGAUGAG X CGAA IGCUGAUC 1638 GATCAGCC T CCGCCATT 2362

2550 GGAAUGGC CUGAUGAG X CGAA IAGGCUGA 1639 TCAGCCTC C GCCATTCC 2363

2553 CUUGGAAU CUGAUGAG X CGAA ICGGAGGC 1640 GCCTCCGC C ATTCCAAG 2364

2554 ACUUGGAA CUGAUGAG X CGAA IGCGGAGG 1641 CCTCCGCC A TTCCAAGT 2365

2558 GUCGACUU CUGAUGAG X CGAA IAAUGGCG 1642 CGCCATTC C AAGTCGAC 2366

2559 UGUCGACU CUGAUGAG X CGAA IGAAUGGC 1643 GCCATTCC A AGTCGACA 2367

2567 AAGAAGAG CUGAUGAG X CGAA IUCGACUU 1644 AAGTCGAC A CTCTTCTT 2368

2569 UCAAGAAG CUGAUGAG X CGAA IUGUCGAC 1645 GTCGACAC T CTTCTTGA 2369

2571 GCUCAAGA CUGAUGAG X CGAA IAGUGUCG 1646 CGACACTC T TCTTGAGC 2370

2574 UCUGCUCA CUGAUGAG X CGAA IAAGAGUG 1647 CACTCTTC T TGAGCAGA 2371

2580 UCACGGUC CUGAUGAG X CGAA ICUCAAGA 1648 TCTTGAGC A GACCGTGA 2372

2584 CAAAUCAC CUGAUGAG X CGAA IUCUGCUC 1649 GAGCAGAC C GTGATTTG 2373

2603 CCAGCAGG CUGAUGAG X CGAA ICCUCUCU 1650 AGAGAGGC A CCTGCTGG 2374

2605 UUCCAGCA CUGAUGAG X CGAA IUGCCUCU 1651 AGAGGCAC C TGCTGGAA 2375

2606 UUUCCAGC CUGAUGAG X CGAA IGUGCCUC 1652 GAGGCACC T GCTGGAAA 2376

2609 UGGUUUCC CUGAUGAG X CGAA ICAGGUGC 1653 GCACCTGC T GGAAACCA 2377

2616 AGAAGUGU CUGAUGAG X CGAA IUUUCCAG 1654 CTGGAAAC C ACACTTCT 2378

2617 AAGAAGUG CUGAUGAG X CGAA IGUUUCCA 1655 TGGAAACC A CACTTCTT 2379

2619 UCAAGAAG CUGAUGAG X CGAA IUGGUUUC 1656 GAAACCAC A CTTCTTGA 2380

2621 UUUCAAGA CUGAUGAG X CGAA IUGUGGUU 1657 AACCACAC T TCTTGAAA 2381

2624 CUGUUUCA CUGAUGAG X CGAA IAAGUGUG 1658 CACACTTC T TGAAACAG 2382

2631 ACCCAGGC CUGAUGAG X CGAA IUUUCAAG 1659 CTTGAAAC A GCCTGGGT 2383

2634 GUCACCCA CUGAUGAG X CGAA ICUGUUUC 1660 GAAACAGC C TGGGTGAC 2384

2635 CGUCACCC CUGAUGAG X CGAA IGCUGUUU 1661 AAACAGCC T GGGTGACG 2385

2647 UGCCUAAA CUGAUGAG X CGAA IACCGUCA 1662 TGACGGTC C TTTAGGCA 2386

2648 CUGCCUAA CUGAUGAG X CGAA IGACCGUC 1663 GACGGTCC T TTAGGCAG 2387 Table 4

2655 CGGCAGGC CUGAUGAG X CGAA ICCUAAAG 1664 CTTTAGGC A GCCTGCCG 2388

2658 CGGCGGCA CUGAUGAG X CGAA ICUGCCUA 1665 TAGGCAGC C TGCCGCCG 2389

2659 ACGGCGGC CUGAUGAG X CGAA IGCUGCCU 1666 AGGCAGCC T GCCGCCGT 2390

2662 GAGACGGC CUGAUGAG X CGAA ICAGGCUG 1667 CAGCCTGC C GCCGTCTC 2391

2665 ACAGAGAC CUGAUGAG X CGAA ICGGCAGG 1668 CCTGCCGC C GTCTCTGT 2392

2669 CGGGACAG CUGAUGAG X CGAA IACGGCGG 1669 CCGCCGTC T CTGTCCCG 2393

2671 ACCGGGAC CUGAUGAG X CGAA IAGACGGC 1670 GCCGTCTC T GTCCCGGT 2394

2675 GUGAACCG CUGAUGAG X CGAA IACAGAGA 1671 TCTCTGTC c CGGTTCAC 2395

2676 GGUGAACC CUGAUGAG X CGAA IGACAGAG 1672 CTCTGTCC c GGTTCACC 2396

2682 CGGCAAGG CUGAUGAG X CGAA IAACCGGG 1673 CCCGGTTC A CCTTGCCG 2397

2684 CUCGGCAA CUGAUGAG X CGAA IUGAACCG 1674 CGGTTCAC c TTGCCGAG 2398

2685 UCUCGGCA CUGAUGAG X CGAA IGUGAACC 1675 GGTTCACC T TGCCGAGA 2399

2689 CCUCUCUC CUGAUGAG X CGAA ICAAGGUG 1676 CACCTTGC C GAGAGAGG 2400

2704 GGUGGGGC CUGAUGAG X CGAA IACGCGCC 1677 GGCGCGTC T GCCCCACC 2401

2707 GAGGGUGG CUGAUGAG X CGAA ICAGACGC 1678 GCGTCTGC C CCACCCTC 2402

2708 UGAGGGUG CUGAUGAG X CGAA IGCAGACG 1679 CGTCTGCC C CACCCTCA 2403

2709 UUGAGGGU CUGAUGAG X CGAA IGGCAGAC 1680 GTCTGCCC c ACCCTCAA 2404

2710 UUUGAGGG CUGAUGAG X CGAA IGGGCAGA 1681 TCTGCCCC A CCCTCAAA 2405

2712 GGUUUGAG CUGAUGAG X CGAA IUGGGGCA 1682 TGCCCCAC C CTCAAACC 2406

2713 GGGUUUGA CUGAUGAG X CGAA IGUGGGGC 1683 GCCCCACC C TCAAACCC 2407

2714 AGGGUUUG CUGAUGAG X CGAA IGGUGGGG 1684 CCCCACCC T CAAACCCT 2408

2716 ACAGGGUU CUGAUGAG X CGAA IAGGGUGG 1685 CCACCCTC A AACCCTGT 2409

2720 CCCCACAG CUGAUGAG X CGAA IUUUGAGG 1686 CCTCAAAC C CTGTGGGG 2410

2721 GCCCCACA CUGAUGAG X CGAA IGUUUGAG 1687 CTCAAACC C TGTGGGGC 2411

2722 GGCCCCAC CUGAUGAG X CGAA IGGUUUGA 1688 TCAAACCC T GTGGGGCC 2412

2730 CACCAUCA CUGAUGAG X CGAA ICCCCACA 1689 TGTGGGGC C TGATGGTG 2413

2731 GCACCAUC CUGAUGAG X CGAA IGCCCCAC 1690 GTGGGGCC T GATGGTGC 2414

2740 GAGUCGUG CUGAUGAG X CGAA ICACCAUC 1691 GATGGTGC T CACGACTC 2415

2742 AAGAGUCG CUGAUGAG X CGAA IAGCACCA 1692 TGGTGCTC A CGACTCTT 2416

2747 GCAGGAAG CUGAUGAG X CGAA IUCGUGAG 1693 CTCACGAC T CTTCCTGC 2417

2749 UUGCAGGA CUGAUGAG X CGAA IAGUCGUG 1694 CACGACTC T TCCTGCAA 2418

2752 CCUUUGCA CUGAUGAG X CGAA IAAGAGUC 1695 GACTCTTC C TGCAAAGG 2419

2753 CCCUUUGC CUGAUGAG X CGAA IGAAGAGU 1696 ACTCTTCC T GCAAAGGG 2420

2756 GUUCCCUU CUGAUGAG X CGAA ICAGGAAG 1697 CTTCCTGC A AAGGGAAC 2421

2765 AGGUCUUC CUGAUGAG X CGAA IUUCCCUU 1698 AAGGGAAC T GAAGACCT 2422

2772 AAUGUGGA CUGAUGAG X CGAA IUCUUCAG 1699 CTGAAGAC C TCCACATT 2423

2773 UAAUGUGG CUGAUGAG X CGAA IGUCUUCA 1700 TGAAGACC T CCACATTA 2424

2775 CUUAAUGU CUGAUGAG X CGAA IAGGUCUU 1701 AAGACCTC C ACATTAAG 2425

2776 ACUUAAUG CUGAUGAG X CGAA IGAGGUCU 1702 AGACCTCC A CATTAAGT 2426

2778 CCACUUAA CUGAUGAG X CGAA IUGGAGGU 1703 ACCTCCAC A TTAAGTGG 2427

2788 UGUUAAAA CUGAUGAG X CGAA ICCACUUA 1704 TAAGTGGC T TTTTAACA 2428

2796 GUUUUUCA CUGAUGAG X CGAA IUUAAAAA 1705 TTTTTAAC A TGAAAAAC 2429

2805 AGCUGCCG CUGAUGAG X CGAA IUUUUUCA 1706 TGAAAAAC A CGGCAGCT 2430

2810 GCUACAGC CUGAUGAG X CGAA ICCGUGUU 1707 AACACGGC A GCTGTAGC 2431

2813 GGAGCUAC CUGAUGAG X CGAA ICUGCCGU 1708 ACGGCAGC T GTAGCTCC 2432

2819 AGCUCGGG CUGAUGAG X CGAA ICUACAGC 1709 GCTGTAGC T CCCGAGCT 2433

2821 GUAGCUCG CUGAUGAG X CGAA IAGCUACA 1710 TGTAGCTC C CGAGCTAC 2434 Table 4

2822 AGUAGCUC CUGAUGAG X CGAA IGAGCUAC 1711 GTAGCTCC C GAGCTACT 2435

2827 AAGAGAGU CUGAUGAG X CGAA ICUCGGGA 1712 TCCCGAGC T ACTCTCTT 2436

2830 GGCAAGAG CUGAUGAG X CGAA IUAGCUCG 1713 CGAGCTAC T CTCTTGCC 2437

2832 CUGGCAAG CUGAUGAG X CGAA IAGUAGCU 1714 AGCTACTC T CTTGCCAG 2438

2834 UGCUGGCA CUGAUGAG X CGAA IAGAGUAG 1715 CTACTCTC T TGCCAGCA 2439

2838 AAAAUGCU CUGAUGAG X CGAA ICAAGAGA 1716 TCTCTTGC c AGCATTTT 2440

2839 GAAAAUGC CUGAUGAG X CGAA IGCAAGAG 1717 CTCTTGCC A GCATTTTC 2441

2842 UGUGAAAA CUGAUGAG X CGAA ICUGGCAA 1718 TTGCCAGC A TTTTCACA 2442

2848 GCAAAAUG CUGAUGAG X CGAA IAAAAUGC 1719 GCATTTTC A CATTTTGC 2443

2850 AGGCAAAA CUGAUGAG X CGAA IUGAAAAU 1720 ATTTTCAC A TTTTGCCT 2444

2857 ACGAGAAA CUGAUGAG X CGAA ICAAAAUG 1721 CATTTTGC C TTTCTCGT 2445

2858 CACGAGAA CUGAUGAG X CGAA IGCAAAAU 1722 ATTTTGCC T TTCTCGTG 2446

2862 CUACCACG CUGAUGAG X CGAA IAAAGGCA 1723 TGCCTTTC T CGTGGTAG 2447

2875 UCUGUACU CUGAUGAG X CGAA ICUUCUAC 1724 GTAGAAGC c AGTACAGA 2448

2876 CUCUGUAC CUGAUGAG X CGAA IGCUUCUA 1725 TAGAAGCC A GTACAGAG 2449

2881 AAUUUCUC CUGAUGAG X CGAA IUACUGGC 1726 GCCAGTAC A GAGAAATT 2450

2891 CCCACCAC CUGAUGAG X CGAA IAAUUUCU 1727 AGAAATTC T GTGGTGGG 2451

2903 ACCUCGAA CUGAUGAG X CGAA IUUCCCAC 1728 GTGGGAAC A TTCGAGGT 2452

2915 CUGCAGGG CUGAUGAG X CGAA IACACCUC 1729 GAGGTGTC A CCCTGCAG 2453

2917 CUCUGCAG CUGAUGAG X CGAA IUGACACC 1730 GGTGTCAC c CTGCAGAG 2454

2918 GCUCUGCA CUGAUGAG X CGAA IGUGACAC 1731 GTGTCACC C TGCAGAGC 2455

2919 AGCUCUGC CUGAUGAG X CGAA IGGUGACA 1732 TGTCACCC T GCAGAGCT 2456

2922 CAUAGCUC CUGAUGAG X CGAA ICAGGGUG 1733 CACCCTGC A GAGCTATG 2457

2927 CUCACCAU CUGAUGAG X CGAA ICUCUGCA 1734 TGCAGAGC T ATGGTGAG 2458

2949 GGCACCUA CUGAUGAG X CGAA ICCUUAUC 1735 GATAAGGC T TAGGTGCC 2459

2957 UACAGCCU CUGAUGAG X CGAA ICACCUAA 1736 TTAGGTGC C AGGCTGTA 2460

2958 UUACAGCC CUGAUGAG X CGAA IGCACCUA 1737 TAGGTGCC A GGCTGTAA 2461

2962 AUGCUUAC CUGAUGAG X CGAA ICCUGGCA 1738 TGCCAGGC T GTAAGCAT 2462

2969 GCUCAGAA CUGAUGAG X CGAA ICUUACAG 1739 CTGTAAGC A TTCTGAGC 2463

2973 GCCAGCUC CUGAUGAG X CGAA IAAUGCUU 1740 AAGCATTC T GAGCTGGC 2464

2978 AACAAGCC CUGAUGAG X CGAA ICUCAGAA 1741 TTCTGAGC T GGCTTGTT 2465

2982 AAACAACA CUGAUGAG X CGAA ICCAGCUC 1742 GAGCTGGC T TGTTGTTT 2466

2998 CAUAUACA CUGAUGAG X CGAA IACUUAAA 1743 TTTAAGTC C TGTATATG 2467

2999 ACAUAUAC CUGAUGAG X CGAA IGACUUAA 1744 TTAAGTCC T GTATATGT 2468

3040 UUUUGAAA CUGAUGAG X CGAA ICUACUAU 1745 ATAGTAGC A TTTCAAAA 2469

3045 GUCCAUUU CUGAUGAG X CGAA IAAAUGCU 1746 AGCATTTC A AAATGGAC 2470

3058 GUUAAACC CUGAUGAG X CGAA IUACGUCC 1747 GGACGTAC T GGTTTAAC 2471

3067 GGAUAGGA CUGAUGAG X CGAA IUUAAACC 1748 GGTTTAAC C TCCTATCC 2472

3068 AGGAUAGG CUGAUGAG X CGAA IGUUAAAC 1749 GTTTAACC T CCTATCCT 2473

3070 CAAGGAUA CUGAUGAG X CGAA IAGGUUAA 1750 TTAACCTC C TATCCTTG 2474

3071 CCAAGGAU CUGAUGAG X CGAA IGAGGUUA 1751 TAACCTCC T ATCCTTGG 2475

3075 CUCUCCAA CUGAUGAG X CGAA IAUAGGAG 1752 CTCCTATC C TTGGAGAG 2476

3076 GCUCUCCA CUGAUGAG X CGAA IGAUAGGA 1753 TCCTATCC T TGGAGAGC 2477

3085 GAGCCAGC CUGAUGAG X CGAA ICUCUCCA 1754 TGGAGAGC A GCTGGCTC 2478

3088 GGAGAGCC CUGAUGAG X CGAA ICUGCUCU 1755 AGAGCAGC T GGCTCTCC 2479

3092 AGGUGGAG CUGAUGAG X CGAA ICCAGCUG 1756 CAGCTGGC T CTCCACCT 2480

3094 CAAGGUGG CUGAUGAG X CGAA IAGCCAGC 1757 GCTGGCTC T CCACCTTG 2481 Table 4

3096 AACAAGGU CUGAUGAG X CGAA lAGAGCCA 1758 TGGCTCTC C ACCTTGTT 2482

3097 UAACAAGG CUGAUGAG X CGAA IGAGAGCC 1759 GGCTCTCC A CCTTGTTA 2483

3099 UGUAACAA CUGAUGAG X CGAA IUGGAGAG 1760 CTCTCCAC C TTGTTACA 2484

3100 GUGUAACA CUGAUGAG X CGAA IGUGGAGA 1761 TCTCCACC T TGTTACAC 2485

3107 ACAUAAUG CUGAUGAG X CGAA IUAACAAG 1762 CTTGTTAC A CATTATGT 2486

3109 UAACAUAA CUGAUGAG X CGAA IUGUAACA 1763 TGTTACAC A TTATGTTA 2487

3132 AGCAGAGC CUGAUGAG X CGAA ICUCGCUA . 1764 TAGCGAGC T GCTCTGCT 2488

3135 CAUAGCAG CUGAUGAG X CGAA ICAGCUCG 1765 CGAGCTGC T CTGCTATG 2489

3137 GACAUAGC CUGAUGAG X CGAA IAGCAGCU 1766 AGCTGCTC T GCTATGTC 2490

3140 AAGGACAU CUGAUGAG X CGAA ICAGAGCA 1767 TGCTCTGC T ATGTCCTT 2491

3146 UGGCUUAA CUGAUGAG X CGAA IACAUAGC 1768 GCTATGTC c TTAAGCCA 2492

3147 UUGGCUUA CUGAUGAG X CGAA IGACAUAG 1769 CTATGTCC T TAAGCCAA 2493

3153 UAAAUAUU CUGAUGAG X CGAA ICUUAAGG 1770 CCTTAAGC c AATATTTA 2494

3154 GUAAAUAU CUGAUGAG X CGAA IGCUUAAG 1771 CTTAAGCC A ATATTTAC 2495

3163 ACCUGAUG CUGAUGAG X CGAA IUAAAUAU 1772 ATATTTAC T CATCAGGT 2496

3165 UGACCUGA CUGAUGAG X CGAA IAGUAAAU 1773 ATTTACTC A TCAGGTCA 2497

3168 UAAUGACC CUGAUGAG X CGAA IAUGAGUA 1774 TACTCATC A GGTCATTA 2498

3173 AAAAAUAA CUGAUGAG X CGAA IACCUGAU 1775 ATCAGGTC A TTATTTTT 2499

3185 AUGGCCAU CUGAUGAG X CGAA IUAAAAAA 1776 TTTTTTAC A ATGGCCAT 2500

3191 UAUUCCAU CUGAUGAG X CGAA ICCAUUGU 1777 ACAATGGC c ATGGAATA 2501

3192 UUAUUCCA CUGAUGAG X CGAA IGCCAUUG 1778 CAATGGCC A TGGAATAA 2502

3203 GUAAAAAU CUGAUGAG X CGAA IUUUAUUC 1779 GAATAAAC c ATTTTTAC 2503

3204 UGUAAAAA CUGAUGAG X CGAA IGUUUAUU 1780 AATAAACC A TTTTTACA 2504

Table 5

Table 5: Human PTP-IB G-Cleaver Ribozyme and Target Sequence

Nt. Ribozyme Sequence Seq. ID Substrate Sequence Seq. ID position Nos. Nos.

25 CACUG UGAUG GCAUGCACUAUGC GCG GCCGUCUGCC 2505 GGCAGACGGC G CAGTG 2670

35 CUUCU UGAUG GCAUGCACUAUGC GCG GGCCCACUGC 2506 GCAGTGGGCC G AGAAG 2671

46 UGCUG UGAUG GCAUGCACUAUGC GCG GCCUCCUUCU 2507 AGAAGGAGGC G CAGCA 2672

55 CAGGG UGAUG GCAUGCACUAUGC GCG GGCUGCUGCG 2508 CGCAGCAGCC G CCCTG 2673

89 CUGCU UGAUG GCAUGCACUAUGC GCG GAACUCCUUU 2509 AAAGGAGTTC G AGCAG 2674

98 CUUGU UGAUG GCAUGCACUAUGC GCG GAUCUGCUCG 2510 CGAGCAGATC G ACAAG 2675

138 CAUGU UGAUG GCAUGCACUAUGC GCG GGAUAUCCUG 2511 CAGGATATCC G ACATG 2676

143 GGCUU UGAUG GCAUGCACUAUGC GCG AUGUCGGAUA 2512 TATCCGACAT G AAGCC 2677

152 GAAGU UGAUG GCAUGCACUAUGC GCG ACUGGCUUCA 2513 TGAAGCCAGT G ACTTC 2678

195 UAUUU UGAUG GCAUGCACUAUGC GCG GGUUUUUGUU 2514 AACAAAAACC G AAATA 2679

224 AUGGU UGAUG GCAUGCACUAUGC GCG AAAGGGACUG 2515 CAGTCCCTTT G ACCAT 2680

260 AUAGU UGAUG GCAUGCACUAUGC GCG AUUAUCUUCU 2516 AGAAGATAAT G ACTAT 2681

272 ACUAG UGAUG GCAUGCACUAUGC GCG GUUGAUAUAG 2517 CTATATCAAC G CTAGT 2682

280 UUUAU UGAUG GCAUGCACUAUGC GCG AAACUAGCGU 2518 ACGCTAGTTT G ATAAA 2683

331 UUAGG UGAUG GCAUGCACUAUGC GCG AAAGGGCCCU 2519 AGGGCCCTTT G CCTAA 2684

342 GACCG UGAUG GCAUGCACUAUGC GCG AUGUGUUAGG 2520 CCTAACACAT G CGGTC 2685

394 UUGAG UGAUG GCAUGCACUAUGC GCG AUGACGACAC 2521 GTGTCGTCAT G CTCAA 2686

406 UCCAU UGAUG GCAUGCACUAUGC GCG ACUCUGUUGA 2522 TCAACAGAGT G ATGGA 2687

429 GUGCG UGAUG GCAUGCACUAUGC GCG AUUUUAACGA 2523 TCGTTAAAAT G CGCAC 2688

431 UUGUG UGAUG GCAUGCACUAUGC GCG GCAUUUUAAC 2524 GTTAAAATGC G CACAA 2689

466 AAGAU UGAUG GCAUGCACUAUGC GCG AUCUCUUUUU 2525 AAAAAGAGAT G ATCTT 2690

473 GUCUU UGAUG GCAUGCACUAUGC GCG AAAGAUCAUC 2526 GATGATCTTT G AAGAC 2691

487 AAUUU UGAUG GCAUGCACUAUGC GCG AAAUUUGUGU 2527 ACACAAATTT G AAATT 2692

499 GAGAU UGAUG GCAUGCACUAUGC GCG AAUGUUAAUU 2528 AATTAACATT G ATCTC 2693

506 AUCUU UGAUG GCAUGCACUAUGC GCG AGAGAUCAAU 2529 ATTGATCTCT G AAGAT 2694

532 UGUCG UGAUG GCAUGCACUAUGC GCG ACUGUAUAAU 2530 ATTATACAGT G CGACA 2695

534 GCUGU UGAUG GCAUGCACUAUGC GCG GCACUGUAUA 2531 TATACAGTGC G ACAGC 2696

573 UCUCU UGAUG GCAUGCACUAUGC GCG GAGUUUCUUG 2532 CAAGAAACTC G AGAGA 2697

Table 5

608 AAAGU UGAUG GCAUGCACUAUGC GCG AGGCCAUGUG 2533 CACATGGCCT G ACTTT 2698

623 UGAUU UGAUG GCAUGCACUAUGC GCG AGGGACUCCA 2534 TGGAGTCCCT G AATCA 2699

643 AAGUU UGAUG GCAUGCACUAUGC GCG AAGAAUGAGG 2535 CCTCATTCTT G AACTT 2700

663 ACUCU UGAUG GCAUGCACUAUGC GCG GGACUUUGAA 2536 TTCAAAGTCC G AGAGT 2701

706 CAGUG UGAUG GCAUGCACUAUGC GCG ACCACAACGG 2537 CCGTTGTGGT G CACTG 2702

711 CACUG UGAUG GCAUGCACUAUGC GCG AGUGCACCAC 2538 GTGGTGCACT G CAGTG 2703

716 GCCUG UGAUG GCAUGCACUAUGC GCG ACUGCAGUGC 2539 GCACTGCAGT G CAGGC 2704

752 GGUAU UGAUG GCAUGCACUAUGC GCG AGCCAGACAG 2540 CTGTCTGGCT G ATACC 2705

759 AGAGG UGAUG GCAUGCACUAUGC GCG AGGUAUCAGC 2541 GCTGATACCT G CCTCT 2706

766 AUCAG UGAUG GCAUGCACUAUGC GCG AAGAGGCAGG 2542 CCTGCCTCTT G CTGAT 2707

769 UCCAU UGAUG GCAUGCACUAUGC GCG AGCAAGAGGC 2543 GCCTCTTGCT G ATGGA 2708

800 GAUAU UGAUG GCAUGCACUAUGC GCG AACGGAAGAA 2544 TTCTTCCGTT G ATATC 2709

814 AACAG UGAUG GCAUGCACUAUGC GCG ACUUUCUUGA 2545 TCAAGAAAGT G CTGTT 2710

826 UUCCU UGAUG GCAUGCACUAUGC GCG AUUUCUAACA 2546 TGTTAGAAAT G AGGAA 2711

847 UGGAU UGAUG GCAUGCACUAUGC GCG AGCCCCAUCC 2547 GGATGGGGCT G ATCCA 2712

860 CUGGU UGAUG GCAUGCACUAUGC GCG GGCUGUCUGG 2548 CCAGACAGCC G ACCAG 2713

868 AAGCG UGAUG GCAUGCACUAUGC GCG AGCUGGUCGG 2549 CCGACCAGCT G CGCTT 2714

870 AGAAG UGAUG GCAUGCACUAUGC GCG GCAGCUGGUC 2550 GACCAGCTGC G CTTCT 2715

889 UCGAU UGAUG GCAUGCACUAUGC GCG ACAGCCAGGU 2551 ACCTGGCTGT G ATCGA 2716

893 ACCUU UGAUG GCAUGCACUAUGC GCG GAUCACAGCC 2552 GGCTGTGATC G AAGGT 2717

899 UUUGG UGAUG GCAUGCACUAUGC GCG ACCUUCGAUC 2553 GATCGAAGGT G CCAAA 2718

928 UCCUG UGAUG GCAUGCACUAUGC GCG ACGGAAGAGU 2554 ACTCTTCCGT G CAGGA 2719

956 GUCCU UGAUG GCAUGCACUAUGC GCG GUGGGAAAGC 2555 GCTTTCCCAC G AGGAC 2720

977 AUGCU UGAUG GCAUGCACUAUGC GCG GGGUGGGGGC 2556 GCCCCCACCC G AGCAT 2721

1011 GGAUU UGAUG GCAUGCACUAUGC GCG GUUUGGGUGG 2557 CCACCCAAAC G AATCC 2722

1038 CCCUG UGAUG GCAUGCACUAUGC GCG AUUUCCCAUU 2558 AATGGGAAAT G CAGGG 2723

1069 UCCUU UGAUG GCAUGCACUAUGC GCG ACCCACUGGU 2559 ACCAGTGGGT G AAGGA 2724

1098 UGGGG UGAUG GCAUGCACUAUGC GCG AGUCUUUAUC 2560 GATAAAGACT G CCCCA 2725

1133 UGCGG UGAUG GCAUGCACUAUGC GCG AUUUAAGGGG 2561 CCCCTTAAAT G CCGCA 2726

1136 GGGUG UGAUG GCAUGCACUAUGC GCG GGCAUUUAAG 2562 CTTAAATGCC G CACCC 2727

1151 GCUUU UGAUG GCAUGCACUAUGC GCG GAUGCCGUAG 2563 CTACGGCATC G AAAGC 2728

Table 5

1159 UGACU UGAUG GCAUGCACUAUGC GCG AUGCUUUCGA 2564 TCGAAAGCAT G AGTCA 2729

1172 AACUU UGAUG GCAUGCACUAUGC GCG AGUGUCUUGA 2565 TCAAGACACT G AAGTT 2730

1206 CACCU UGAUG GCAUGCACUAUGC GCG GAAGACUUCC 2566 GGAAGTCTTC G AGGTG 2731

1211 CUGGG UGAUG GCAUGCACUAUGC GCG ACCUCGAAGA 2567 TCTTCGAGGT G CCCAG 2732

1220 GGAGG UGAUG GCAUGCACUAUGC GCG AGCCUGGGCA 2568 TGCCCAGGCT G CCTCC 2733

1249 UCGGG UGAUG GCAUGCACUAUGC GCG AGUGACGGCU 2569 AGCCGTCACT G CCCGA 2734

1253 CUUCU UGAUG GCAUGCACUAUGC GCG GGGCAGUGAC 2570 GTCACTGCCC G AGAAG 2735

1262 GUCCU UGAUG GCAUGCACUAUGC GCG GUCCUUCUCG 2571 CGAGAAGGAC G AGGAC 2736

1271 CAGUG UGAUG GCAUGCACUAUGC GCG AUGGUCCUCG 2572 CGAGGACCAT G CACTG 2737

1276 UAACU UGAUG GCAUGCACUAUGC GCG AGUGCAUGGU 2573 ACCATGCACT G AGTTA 2738

1308 CCACG UGAUG GCAUGCACUAUGC GCG ACAUGUUGAC 2574 GTCAACATGT G CGTGG 2739

1334 GUAAG UGAUG GCAUGCACUAUGC GCG GCCGGCCGUG 2575 CACGGCCGGC G CTTAC 2740

1344 UGUAG UGAUG GCAUGCACUAUGC GCG AGAGGUAAGC 2576 GCTTACCTCT G CTACA 2741

1379 AGGGU UGAUG GCAUGCACUAUGC GCG AGGCUAUGUG 2577 CACATAGCCT G ACCCT 2742

1412 AGAGG UGAUG GCAUGCACUAUGC GCG GGACAGUGGG 2578 CCCACTGTCC G CCTCT 2743

1418 GCGGG UGAUG GCAUGCACUAUGC GCG AGAGGCGGAC 2579 GTCCGCCTCT G CCCGC 2744

1422 CUCUG UGAUG GCAUGCACUAUGC GCG GGGCAGAGGC 2580 GCCTCTGCCC G CAGAG 2745

1433 UCGGG UGAUG GCAUGCACUAUGC GCG GUGGGCUCUG 2581 CAGAGCCCAC G CCCGA 2746

1437 CUAGU UGAUG GCAUGCACUAUGC GCG GGGCGUGGGC 2582 GCCCACGCCC G ACTAG 2747

1450 CGCGG UGAUG GCAUGCACUAUGC GCG AUGCCUGCUA 2583 TAGCAGGCAT G CCGCG 2748

1453 UACCG UGAUG GCAUGCACUAUGC GCG GGCAUGCCUG 2584 CAGGCATGCC G CGGTA 2749

1469 UCCGG UGAUG GCAUGCACUAUGC GCG GGCCCUUACC 2585 GGTAAGGGCC G CCGGA 2750

1477 CUACG UGAUG GCAUGCACUAUGC GCG GGUCCGGCGG 2586 CCGCCGGACC G CGTAG 2751

1513 UAGUG UGAUG GCAUGCACUAUGC GCG AGAACCAACG 2587 CGTTGGTTCT G CACTA 2752

1569 AGGGG UGAUG GCAUGCACUAUGC GCG AAAAAGUAAA 2588 TTTACTTTTT G CCCCT 2753

1583 GUACU UGAUG GCAUGCACUAUGC GCG AAAGUGGAAG 2589 CTTCCACTTT G AGTAC 2754

1610 CUCCU UGAUG GCAUGCACUAUGC GCG AAAAAAUGGC 2590 GCCATTTTTT G AGGAG 2755

1619 UCUUU UGAUG GCAUGCACUAUGC GCG ACUCUCCUCA 2591 TGAGGAGAGT G AAAGA 2756

1634 GCCAG UGAUG GCAUGCACUAUGC GCG AUGGUACUCU 2592 AGAGTACCAT G CTGGC 2757

1643 CUCUG UGAUG GCAUGCACUAUGC GCG GCCGCCAGCA 2593 TGCTGGCGGC G CAGAG 2758

1678 UGGGG UGAUG GCAUGCACUAUGC GCG GAGCCCCAAG 2594 CTTGGGGCTC G CCCCA 2759

Table 5

1723 UCUGG UGAUG GCAUGCACUAUGC GCG GUGCCGCCCG 2595 CGGGCGGCAC G CCAGA 2760

1742 AGAUU , UGAUG GCAUGCACUAUGC GCG AAGGGGGGGG 2596 CCCCCCCCTT G AATCT 2761

1748 CCCUG UGAUG GCAUGCACUAUGC GCG AGAUUCAAGG 2597 CCTTGAATCT G CAGGG 2762

1811 UAGUG UGAUG GCAUGCACUAUGC GCG ACUAUGGAUG 2598 CATCCATAGT G CACTA 2763

1827 UGGUU UGAUG GCAUGCACUAUGC GCG AAGAAAAUGC 2599 GCATTTTCTT G AACCA 2764

1853 GACAU UGAUG GCAUGCACUAUGC GCG AAAAAAUUUU 2600 AAAATTTTTT G ATGTC 2765

1865 UGAUG UGAUG GCAUGCACUAUGC GCG AAGGCUGACA 2601 TGTCAGCCTT G CATCA 2766

1931 CAUGG UGAUG GCAUGCACUAUGC GCG AAAGCCUUCC 2602 GGAAGGCTTT G CCATG 2767

1942 CGCAG UGAUG GCAUGCACUAUGC GCG AGGCCCAUGG 2603 CCATGGGCCT G CTGCG 2768

1945 UGACG UGAUG GCAUGCACUAUGC GCG AGCAGGCCCA 2604 TGGGCCTGCT G CGTCA 2769

1997 AAUAU UGAUG GCAUGCACUAUGC GCG ACUAAAUAAC 2605 GTTATTTAGT G ATATT 2770

2014 CUUCU UGAUG GCAUGCACUAUGC GCG ACGUUACCCA 2606 TGGGTAACGT G AGAAG 2771

2030 UAUAG UGAUG GCAUGCACUAUGC GCG AUUGUUCUAU 2607 ATAGAACAAT G CTATA 2772

2045 GUGUU UGAUG GCAUGCACUAUGC GCG AUUAUAUAUU 2608 AATATATAAT G AACAC 2773

2073 CACAU UGAUG GCAUGCACUAUGC GCG AUGUUUCUUA 2609 TAAGAAACAT G ATGTG 2774

2078 AAUCU UGAUG GCAUGCACUAUGC GCG ACAUCAUGUU 2610 AACATGATGT G AGATT 2775

2094 AUAAG UGAUG GCAUGCACUAUGC GCG GGGACAAAGU 2611 ACTTTGTCCC G CTTAT 2776

2103 GGGAG UGAUG GCAUGCACUAUGC GCG AGAAUAAGCG 2612 CGCTTATTCT G CTCCC 2777

2117 UCUAG UGAUG GCAUGCACUAUGC GCG AGAUAACAGG 2613 CCTGTTATCT G CTAGA 2778

2140 GGGAG UGAUG GCAUGCACUAUGC GCG AGUGAUUGAG 2614 CTCAATCACT G CTCCC 2779

2162 ACAUG UGAUG GCAUGCACUAUGC GCG AUUCUAAUAC 2615 GTATTAGAAT G CATGT 2780

2186 UUCAU UGAUG GCAUGCACUAUGC GCG AGGACACAAG 2616 CTTGTGTCCT G ATGAA 2781

2189 UUUUU UGAUG GCAUGCACUAUGC GCG AUCAGGACAC 2617 GTGTCCTGAT G AAAAA 2782

2200 UCAAG UGAUG GCAUGCACUAUGC GCG ACAUAUUUUU 2618 AAAAATATGT G CTTGA 2783

2204 CAUUU UGAUG GCAUGCACUAUGC GCG AAGCACAUAU 2619 ATATGTGCTT G AAATG 2784

2209 UUUCU UGAUG GCAUGCACUAUGC GCG AUUUCAAGCA 2620 TGCTTGAAAT G AGAAA 2785

2219 GAGAU UGAUG GCAUGCACUAUGC GCG AAAGUUUCUC 2621 GAGAAACTTT G ATCTC 2786

2226 GUAAG UGAUG GCAUGCACUAUGC GCG AGAGAUCAAA 2622 TTTGATCTCT G CTTAC 2787

2238 UGGGG UGAUG GCAUGCACUAUGC GCG ACAUUAGUAA 2623 TTACTAATGT G CCCCA 2788

2260 ACAGG UGAUG GCAUGCACUAUGC GCG AGGUUGGACU 2624 AGTCCAACCT G CCTGT 2789

2266 UCAUG UGAUG GCAUGCACUAUGC GCG ACAGGCAGGU 2625 ACCTGCCTGT G CATGA 2790

Table 5

2270 CAGGU UGAUG GCAUGCACUAUGC GCG AUGCACAGGC 2626 GCCTGTGCAT G ACCTG 2791

2275 AUGAU UGAUG GCAUGCACUAUGC GCG AGGUCAUGCA 2627 TGCATGACCT G ATCAT 2792

2308 UUCAG UGAUG GCAUGCACUAUGC GCG AACAGGCUUA 2628 TAAGCCTGTT G CTGAA 2793

2311 GACUU UGAUG GCAUGCACUAUGC GCG AGCAACAGGC 2629 GCCTGTTGCT G AAGTC 2794

2323 CUGAG UGAUG GCAUGCACUAUGC GCG GACAAUGACU 2630 AGTCATTGTC G CTCAG 2795

2338 AACUG UGAUG GCAUGCACUAUGC GCG ACCCUAUUGC 2631 GCAATAGGGT G CAGTT 2796

2362 UUAGG UGAUG GCAUGCACUAUGC GCG AAAUGCCUAU 2632 ATAGGCATTT G CCTAA 2797

2378 AGUGU UGAUG GCAUGCACUAUGC GCG AUGCCAGGAA 2633 TTCCTGGCAT G ACACT 2798

2389 GAAGU UGAUG GCAUGCACUAUGC GCG ACUAGAGUGU 2634 ACACTCTAGT G ACTTC 2799

2400 GGCCU UGAUG GCAUGCACUAUGC GCG ACCAGGAAGU 2635 ACTTCCTGGT G AGGCC 2800

2433 UACAG UGAUG GCAUGCACUAUGC GCG AAGACCCUGC 2636 GCAGGGTCTT G CTGTA 2801

2483 CAGAG UGAUG GCAUGCACUAUGC GCG GUGAGGUGUG 2637 CACACCTCAC G CTCTG 2802

2494 UAAAU UGAUG GCAUGCACUAUGC GCG AUGUCCAGAG 2638 CTCTGGACAT G ATTTA 2803

2520 GGGGG UGAUG GCAUGCACUAUGC GCG GGGGGGUGUC 2639 GACACCCCCC G CCCCC 2804

2546 AAUGG UGAUG GCAUGCACUAUGC GCG GGAGGCUGAU 2640 ATCAGCCTCC G CCATT 2805

2559 AGUGU UGAUG GCAUGCACUAUGC GCG GACUUGGAAU 2641 ATTCCAAGTC G ACACT 2806

2571 CUGCU UGAUG GCAUGCACUAUGC GCG AAGAAGAGUG 2642 CACTCTTCTT G AGCAG 2807

2582 CAAAU UGAUG GCAUGCACUAUGC GCG ACGGUCUGCU 2643 AGCAGACCGT G ATTTG 2808

2602 UCCAG UGAUG GCAUGCACUAUGC GCG AGGUGCCUCU 2644 AGAGGCACCT G CTGGA 2809

2621 UGUUU UGAUG GCAUGCACUAUGC GCG AAGAAGUGUG 2645 CACACTTCTT G AAACA 2810

2635 ACCGU UGAUG GCAUGCACUAUGC GCG ACCCAGGCUG 2646 CAGCCTGGGT G ACGGT 2811

2655 GGCGG UGAUG GCAUGCACUAUGC GCG AGGCUGCCUA 2647 TAGGCAGCCT G CCGCC 2812

2658 GACGG UGAUG GCAUGCACUAUGC GCG GGCAGGCUGC 2648 GCAGCCTGCC G CCGTC 2813

2682 CUCGG UGAUG GCAUGCACUAUGC GCG AAGGUGAACC 2649 GGTTCACCTT G CCGAG 2814

2685 UCUCU UGAUG GCAUGCACUAUGC GCG GGCAAGGUGA 2650 TCACCTTGCC G AGAGA 2815

2694 AGACG UGAUG GCAUGCACUAUGC GCG GCCUCUCUCG 2651 CGAGAGAGGC G CGTCT 2816

2700 UGGGG UGAUG GCAUGCACUAUGC GCG AGACGCGCCU 2652 AGGCGCGTCT G CCCCA 2817

2727 ACCAU UGAUG GCAUGCACUAUGC GCG AGGCCCCACA 2653 TGTGGGGCCT G ATGGT 2818

2733 GUGAG UGAUG GCAUGCACUAUGC GCG ACCAUCAGGC 2654 GCCTGATGGT G CTCAC 2819

2739 AGAGU UGAUG GCAUGCACUAUGC GCG GUGAGCACCA 2655 TGGTGCTCAC G ACTCT 2820

2749 CUUUG UGAUG GCAUGCACUAUGC GCG AGGAAGAGUC 2656 GACTCTTCCT G CAAAG 2821

Table 5

2761 GUCUU UGAUG GCAUGCACUAUGC GCG AGUUCCCUUU 2657 AAAGGGAACT G AAGAC 2822

2793 UUUUU UGAUG GCAUGCACUAUGC GCG AUGUUAAAAA 2658 TTTTTAACAT G AAAAA 2823

2818 UAGCU UGAUG GCAUGCACUAUGC GCG GGGAGCUACA 2659 TGTAGCTCCC G AGCTA 2824

2831 GCUGG UGAUG GCAUGCACUAUGC GCG AAGAGAGUAG 2660 CTACTCTCTT G CCAGC 2825

2850 AAAGG UGAUG GCAUGCACUAUGC GCG AAAAUGUGAA 2661 TTCACATTTT G CCTTT 2826

2902 CACCU UGAUG GCAUGCACUAUGC GCG GAAUGUUCCC 2662 GGGAACATTC G AGGTG 2827

2915 CUCUG UGAUG GCAUGCACUAUGC GCG AGGGUGACAC 2663 GTGTCACCCT G CAGAG 2828

2928 CACCU UGAUG GCAUGCACUAUGC GCG ACCAUAGCUC 2664 GAGCTATGGT G AGGTG 2829

2950 CCUGG UGAUG GCAUGCACUAUGC GCG ACCUAAGCCU 2665 AGGCTTAGGT G CCAGG 2830

2969 CAGCU UGAUG GCAUGCACUAUGC GCG AGAAUGCUUA 2666 TAAGCATTCT G AGCTG 2831

3123 CAGCU UGAUG GCAUGCACUAUGC GCG GCUACCUCUC 2667 GAGAGGTAGC G AGCTG 2832

3128 CAGAG UGAUG GCAUGCACUAUGC GCG AGCUCGCUAC 2668 GTAGCGAGCT G CTCTG 2833

3133 CAUAG UGAUG GCAUGCACUAUGC GCG AGAGCAGCUC 2669 GAGCTGCTCT G CTATG 2834

Table 6

Table 6: Human PTP-IB DNAzyme and Target Sequence

Table 6

Table 6

275 AACTAGCG GGCTAGCTACAACGA TGATATAG 2894 CUAUAUCA A CGCUAGUU 3604

277 CAAACTAG GGCTAGCTACAACGA GTTGATAT 2895 AUAUCAAC G CUAGUUUG 3605

281 TTATCAAA GGCTAGCTACAACGA TAGCGTTG 2896 CAACGCUA G UUUGAUAA 3606

286 CATTTTTA GGCTAGCTACAACGA CAAACTAG 2897 CUAGUUUG A UAAAAAUG 3607

292 TTCTTCCA GGCTAGCTACAACGA TTTTATCA 2898 UGAUAAAA A UGGAAGAA 3608

301 CCTTTGGG GGCTAGCTACAACGA TTCTTCCA 2899 UGGAAGAA G CCCAAAGG 3609

311 GAATGTAA GGCTAGCTACAACGA TCCTTTGG 2900 CCAAAGGA G UUACAUUC 3610

314 TAAGAATG GGCTAGCTACAACGA AACTCCTT 2901 AAGGAGUU A CAUUCUUA 3611

316 GGTAAGAA GGCTAGCTACAACGA GTAACTCC 2902 GGAGUUAC A UUCUUACC 3612

322 GCCCTGGG GGCTAGCTACAACGA AAGAATGT 2903 ACAUUCUU A CCCAGGGC 3613

329 GCAAAGGG GGCTAGCTACAACGA CCTGGGTA 2904 UACCCAGG G CCCUUUGC 3614

336 GTGTTAGG GGCTAGCTACAACGA AAAGGGCC 2905 GGCCCUUU G CCUAACAC 3615

341 CGCATGTG GGCTAGCTACAACGA TAGGCAAA 2906 UUUGCCUA A CACAUGCG 3616

343 ACCGCATG GGCTAGCTACAACGA GTTAGGCA 2907 UGCCUAAC A CAUGCGGU 3617

345 TGACCGCA GGCTAGCTACAACGA GTGTTAGG 2908 CCUAACAC A UGCGGUCA 3618

347 AGTGACCG GGCTAGCTACAACGA ATGTGTTA 2909 UAACACAU G CGGUCACU 3619

350 AAAAGTGA GGCTAGCTACAACGA CGCATGTG 2910 CACAUGCG G UCACUUUU 3620

353 CCCAAAAG GGCTAGCTACAACGA GACCGCAT 2911 AUGCGGUC A CUUUUGGG 3621

364 CCACACCA GGCTAGCTACAACGA CTCCCAAA 2912 UUUGGGAG A UGGUGUGG 3622

367 CTCCCACA GGCTAGCTACAACGA CATCTCCC 2913 GGGAGAUG G UGUGGGAG 3623

369 TGCTCCCA GGCTAGCTACAACGA ACCATCTC 2914 GAGAUGGU G UGGGAGCA 3624

375 CTTTTCTG GGCTAGCTACAACGA TCCCACAC 2915 GUGUGGGA G CAGAAAAG 3625

383 CACCCCTG GGCTAGCTACAACGA TTTTCTGC 2916 GCAGAAAA G CAGGGGUG 3626

389 TGACGACA GGCTAGCTACAACGA CCCTGCTT 2917 AAGCAGGG G UGUCGUCA 3627

391 CATGACGA GGCTAGCTACAACGA ACCCCTGC 2918 GCAGGGGU G UCGUCAUG 3628

394 GAGCATGA GGCTAGCTACAACGA GACACCCC 2919 GGGGUGUC G UCAUGCUC 3629

397 GTTGAGCA GGCTAGCTACAACGA GACGACAC 2920 GUGUCGUC A UGCUCAAC 3630

399 CTGTTGAG GGCTAGCTACAACGA ATGACGAC 2921 GUCGUCAU G CUCAACAG 3631

404 TCACTCTG GGCTAGCTACAACGA TGAGCATG 2922 CAUGCUCA A CAGAGUGA 3632

409 CTCCATCA GGCTAGCTACAACGA TCTGTTGA 2923 UCAACAGA G UGAUGGAG ^' 3633

412 TTTCTCCA GGCTAGCTACAACGA CACTCTGT 2924 ACAGAGUG A UGGAGAAA 3634

Table 6

422 TTAACGAA GGCTAGCTACAACGA CTTTCTCC 2925 GGAGAAAG G UUCGUUAA 3635

426 CATTTTAA GGCTAGCTACAACGA GAACCTTT 2926 AAAGGUUC G UUAAAAUG 3636

432 TGTGCGCA GGCTAGCTACAACGA TTTAACGA 2927 UCGUUAAA A UGCGCACA 3637

434 ATTGTGCG GGCTAGCTACAACGA ATTTTAAC 2928 GUUAAAAU G CGCACAAU 3638

436 GTATTGTG GGCTAGCTACAACGA GCATTTTA 2929 UAAAAUGC G CACAAUAC 3639

438 CAGTATTG GGCTAGCTACAACGA GCGCATTT 2930 AAAUGCGC A CAAUACUG 3640

441 GGCCAGTA GGCTAGCTACAACGA TGTGCGCA 2931 UGCGCACA A UACUGGCC 3641

443 GTGGCCAG GGCTAGCTACAACGA ATTGTGCG 2932 CGCACAAU A CUGGCCAC 3642

447 TTTTGTGG GGCTAGCTACAACGA CAGTATTG 2933 CAAUACUG G CCACAAAA 3643

450 TCTTTTTG GGCTAGCTACAACGA GGCCAGTA 2934 UACUGGCC A CAAAAAGA 3644

469 AAAGATCA GGCTAGCTACAACGA CTCTTTTT 2935 AAAAAGAG A UGAUCUUU 3645

472 TTCAAAGA GGCTAGCTACAACGA CATCTCTT 2936 AAGAGAUG A UCUUUGAA 3646

482 AATTTGTG GGCTAGCTACAACGA CTTCAAAG 2937 CUUUGAAG A CACAAAUU 3647

484 CAAATTTG GGCTAGCTACAACGA GTCTTCAA 2938 UUGAAGAC A CAAAUUUG 3648

488 ATTTCAAA GGCTAGCTACAACGA TTGTGTCT 2939 AGACACAA A UUUGAAAU 3649

495 AATGTTAA GGCTAGCTACAACGA TTCAAATT 2940 AAUUUGAA A UUAACAUU 3650

499 GATCAATG GGCTAGCTACAACGA TAATTTCA 2941 UGAAAUUA A CAUUGAUC 3651

501 GAGATCAA GGCTAGCTACAACGA GTTAATTT 2942 AAAUUAAC A UUGAUCUC 3652

505 TTCAGAGA GGCTAGCTACAACGA CAATGTTA 2943 UAACAUUG A UCUCUGAA 3653

515 ACTTGATA GGCTAGCTACAACGA CTTCAGAG 2944 CUCUGAAG A UAUCAAGU 3654

517 TGACTTGA GGCTAGCTACAACGA ATCTTCAG 2945 CUGAAGAU A UCAAGUCA 3655

522 TAATATGA GGCTAGCTACAACGA TTGATATC 2946 GAUAUCAA G UCAUAUUA 3656

525 GTATAATA GGCTAGCTACAACGA GACTTGAT 2947 AUCAAGUC A UAUUAUAC 3657

527 CTGTATAA GGCTAGCTACAACGA ATGACTTG 2948 CAAGUCAU A UUAUACAG 3658

530 GCACTGTA GGCTAGCTACAACGA AATATGAC 2949 GUCAUAUU A UACAGUGC 3659

532 TCGCACTG GGCTAGCTACAACGA ATAATATG 2950 CAUAUUAU A CAGUGCGA 3660

535 CTGTCGCA GGCTAGCTACAACGA TGTATAAT 2951 AUUAUACA G UGCGACAG 3661

537 AGCTGTCG GGCTAGCTACAACGA ACTGTATA 2952 UAUACAGU G CGACAGCU 3662

540 TCTAGCTG GGCTAGCTACAACGA CGCACTGT 2953 ACAGUGCG A CAGCUAGA 3663

543 AATTCTAG GGCTAGCTACAACGA TGTCGCAC 2954 GUGCGACA G CUAGAAUU 3664

549 TTTTCCAA GGCTAGCTACAACGA TCTAGCTG 2955 CAGCUAGA A UUGGAAAA 3665

Table 6

557 TTGTAAGG GGCTAGCTACAACGA TTTCCAAT 2956 AUUGGAAA A CCUUACAA 3666

562 TTGGGTTG GGCTAGCTACAACGA AAGGTTTT 2957 AAAACCUU A CAACCCAA 3667

565 TTCTTGGG GGCTAGCTACAACGA TGTAAGGT 2958 ACCUUACA A CCCAAGAA 3668

574 CTCTCGAG GGCTAGCTACAACGA TTCTTGGG 2959 CCCAAGAA A CUCGAGAG 3669

583 ATGTAAGA GGCTAGCTACAACGA CTCTCGAG 2960 CUCGAGAG A UCUUACAU 3670

588 TGGAAATG GGCTAGCTACAACGA AAGATCTC 2961 GAGAUCUU A CAUUUCCA 3671

590 AGTGGAAA GGCTAGCTACAACGA GTAAGATC 2962 GAUCUUAC A UUUCCACU 3672

596 TGGTATAG GGCTAGCTACAACGA GGAAATGT 2963 ACAUUUCC A CUAUACCA 3673

599 ATGTGGTA GGCTAGCTACAACGA AGTGGAAA 2964 UUUCCACU A UACCACAU 3674

601 CCATGTGG GGCTAGCTACAACGA ATAGTGGA 2965 UCCACUAU A CCACAUGG 3675

604 AGGCCATG GGCTAGCTACAACGA GGTATAGT 2966 ACUAUACC A CAUGGCCU 3676

606 TCAGGCCA GGCTAGCTACAACGA GTGGTATA 2967 UAUACCAC A UGGCCUGA 3677

609 AAGTCAGG GGCTAGCTACAACGA CATGTGGT 2968 ACCACAUG G CCUGACUU 3678

614 CTCCAAAG GGCTAGCTACAACGA CAGGCCAT 2969 AUGGCCUG A CUUUGGAG 3679

622 TTCAGGGA GGCTAGCTACAACGA TCCAAAGT 2970 ACUUUGGA G UCCCUGAA 3680

630 GCTGGTGA GGCTAGCTACAACGA TCAGGGAC 2971 GUCCCUGA A UCACCAGC 3681

633 GAGGCTGG GGCTAGCTACAACGA GATTCAGG 2972 CCUGAAUC A CCAGCCUC 3682

637 GAATGAGG GGCTAGCTACAACGA TGGTGATT 2973 AAUCACCA G CCUCAUUC 3683

642 TTCAAGAA GGCTAGCTACAACGA GAGGCTGG 2974 CCAGCCUC A UUCUUGAA 3684

650 AAAGAAAG GGCTAGCTACAACGA TCAAGAAT 2975 AUUCUUGA A CUUUCUUU 3685

664 CTCTCGGA GGCTAGCTACAACGA TTTGAAAA 2976 UUUUCAAA G UCCGAGAG 3686

672 GACCCTGA GGCTAGCTACAACGA TCTCGGAC 2977 GUCCGAGA G UCAGGGUC 3687

678 CTGAGTGA GGCTAGCTACAACGA CCTGACTC 2978 GAGUCAGG G UCACUCAG 3688

681 GGGCTGAG GGCTAGCTACAACGA GACCCTGA 2979 UCAGGGUC A CUCAGCCC 3689

686 GCTCCGGG GGCTAGCTACAACGA TGAGTGAC 2980 GUCACUCA G CCCGGAGC 3690

693 GGCCCGTG GGCTAGCTACAACGA TCCGGGCT 2981 AGCCCGGA G CACGGGCC 3691

695 CGGGCCCG GGCTAGCTACAACGA GCTCCGGG 2982 CCCGGAGC A CGGGCCCG 3692

699 ACAACGGG GGCTAGCTACAACGA CCGTGCTC 2983 GAGCACGG G CCCGUUGU 3693

703 CACCACAA GGCTAGCTACAACGA GGGCCCGT 2984 ACGGGCCC G UUGUGGUG 3694

706 GTGCACCA GGCTAGCTACAACGA AACGGGCC 2985 GGCCCGUU G UGGUGCAC 3695

709 GCAGTGCA GGCTAGCTACAACGA CACAACGG 2986 CCGUUGUG G UGCACUGC 3696

Table 6

711 CTGCAGTG GGCTAGCTACAACGA ACCACAAC 2987 GUUGUGGU G CACUGCAG 3697

713 CACTGCAG GGCTAGCTACAACGA GCACCACA 2988 UGUGGUGC A CUGCAGUG 3698

716 CTGCACTG GGCTAGCTACAACGA AGTGCACC 2989 GGUGCACU G CAGUGCAG 3699

719 TGCCTGCA GGCTAGCTACAACGA TGCAGTGC 2990 GCACUGCA G UGCAGGCA 3700

721 GATGCCTG GGCTAGCTACAACGA ACTGCAGT 2991 ACUGCAGU G CAGGCAUC 3701

725 TGCCGATG GGCTAGCTACAACGA CTGCACTG 2992 CAGUGCAG G CAUCGGCA 3702

727 CCTGCCGA GGCTAGCTACAACGA GCCTGCAC 2993 GUGCAGGC A UCGGCAGG 3703

731 CAGACCTG GGCTAGCTACAACGA CGATGCCT 2994 AGGCAUCG G CAGGUCUG 3704

735 GTTCCAGA GGCTAGCTACAACGA CTGCCGAT 2995 AUCGGCAG G UCUGGAAC 3705

742 ACAGAAGG GGCTAGCTACAACGA TCCAGACC 2996 GGUCUGGA A CCUUCUGU 3706

749 CAGCCAGA GGCTAGCTACAACGA AGAAGGTT 2997 AACCUUCU G UCUGGCUG 3707

754 GGTATCAG GGCTAGCTACAACGA CAGACAGA 2998 UCUGUCUG G CUGAUACC 3708

758 GGCAGGTA GGCTAGCTACAACGA CAGCCAGA 2999 UCUGGCUG A UACCUGCC 3709

760 GAGGCAGG GGCTAGCTACAACGA ATCAGCCA 3000 UGGCUGAU A CCUGCCUC 3710

764 GCAAGAGG GGCTAGCTACAACGA AGGTATCA 3001 UGAUACCU G CCUCUUGC 3711

771 TCCATCAG GGCTAGCTACAACGA AAGAGGCA 3002 UGCCUCUU G CUGAUGGA 3712

775 CTTGTCCA GGCTAGCTACAACGA CAGCAAGA 3003 UCUUGCUG A UGGACAAG 3713

779 TCCTCTTG GGCTAGCTACAACGA CCATCAGC 3004 GCUGAUGG A CAAGAGGA 3714

791 AAGAAGGG GGCTAGCTACAACGA CTTTCCTC 3005 GAGGAAAG A CCCUUCUU 3715

802 GATATCAA GGCTAGCTACAACGA GGAAGAAG 3006 CUUCUUCC G UUGAUAUC 3716

806 TCTTGATA GGCTAGCTACAACGA CAACGGAA 3007 UUCCGUUG A UAUCAAGA 3717

808 TTTCTTGA GGCTAGCTACAACGA ATCAACGG 3008 CCGUUGAU A UCAAGAAA 3718

817 TAACAGCA GGCTAGCTACAACGA TTTCTTGA 3009 UCAAGAAA G UGCUGUUA 3719

819 TCTAACAG GGCTAGCTACAACGA ACTTTCTT 3010 AAGAAAGU G CUGUUAGA 3720

822 ATTTCTAA GGCTAGCTACAACGA AGCACTTT 3011 AAAGUGCU G UUAGAAAU 3721

829 CTTCCTCA GGCTAGCTACAACGA TTCTAACA 3012 UGUUAGAA A UGAGGAAG 3722

837 ATCCGAAA GGCTAGCTACAACGA TTCCTCAT 3013 AUGAGGAA G UUUCGGAU 3723

844 CAGCCCCA GGCTAGCTACAACGA CCGAAACT 3014 AGUUUCGG A UGGGGCUG 3724

849 TGGATCAG GGCTAGCTACAACGA CCCATCCG 3015 CGGAUGGG G CUGAUCCA 3725

853 TGTCTGGA GGCTAGCTACAACGA CAGCCCCA 3016- UGGGGCUG A UCCAGACA 3726

859 GTCGGCTG GGCTAGCTACAACGA CTGGATCA 3017 UGAUCCAG A CAGCCGAC 3727

Table 6

Table 6

1018 CTCCAGGA GGCTAGCTACAACGA TCGTTTGG 3049 CCAAACGA A UCCUGGAG 3759

1026 TTGTGTGG GGCTAGCTACAACGA TCCAGGAT 3050 AUCCUGGA G CCACACAA 3760

1029 CCATTGTG GGCTAGCTACAACGA GGCTCCAG 3051 CUGGAGCC A CACAAUGG 3761

1031 TCCCATTG GGCTAGCTACAACGA GTGGCTCC 3052 GGAGCCAC A CAAUGGGA 3762

1034 ATTTCCCA GGCTAGCTACAACGA TGTGTGGC 3053 GCCACACA A UGGGAAAU 3763

1041 TCCCTGCA GGCTAGCTACAACGA TTCCCATT 3054 AAUGGGAA A UGCAGGGA 3764

1043 ACTCCCTG GGCTAGCTACAACGA ATTTCCCA 3055 UGGGAAAU G CAGGGAGU 3765

1050 GGGAAGAA GGCTAGCTACAACGA TCCCTGCA 3056 UGCAGGGA G UUCUUCCC 3766

1061 ACTGGTGA GGCTAGCTACAACGA TTGGGAAG 3057 CUUCCCAA A UCACCAGU 3767

1064 CCCACTGG GGCTAGCTACAACGA GATTTGGG 3058 CCCAAAUC A CCAGUGGG 3768

1068 TTCACCCA GGCTAGCTACAACGA TGGTGATT 3059 AAUCACCA G UGGGUGAA 3769

1072 TTCCTTCA GGCTAGCTACAACGA CCACTGGT 3060 ACCAGUGG G UGAAGGAA 3770

1084 CTCCTGGG GGCTAGCTACAACGA CTCTTCCT 3061 AGGAAGAG A CCCAGGAG 3771

1094 AGTCTTTA GGCTAGCTACAACGA CCTCCTGG 3062 CCAGGAGG A UAAAGACU 3772

1100 TGGGGCAG GGCTAGCTACAACGA CTTTATCC 3063 GGAUAAAG A CUGCCCCA 3773

1103 TGATGGGG GGCTAGCTACAACGA AGTCTTTA 3064 UAAAGACU G CCCCAUCA 3774

1108 TTCCTTGA GGCTAGCTACAACGA GGGGCAGT 3065 ACUGCCCC A UCAAGGAA 3775

1127 TTAAGGGG GGCTAGCTACAACGA TTCCTTTT 3066 AAAAGGAA G CCCCUUAA 3776

1136 GTGCGGCA GGCTAGCTACAACGA TTAAGGGG 3067 CCCCUUAA A UGCCGCAC 3777

1138 GGGTGCGG GGCTAGCTACAACGA ATTTAAGG 3068 CCUUAAAU G CCGCACCC 3778

1141 GTAGGGTG GGCTAGCTACAACGA GGCATTTA 3069 UAAAUGCC G CACCCUAC 3779

1143 CCGTAGGG GGCTAGCTACAACGA GCGGCATT 3070 AAUGCCGC A CCCUACGG 3780

1148 CGATGCCG GGCTAGCTACAACGA AGGGTGCG 3071 CGCACCCU A CGGCAUCG 3781

1151 TTTCGATG GGCTAGCTACAACGA CGTAGGGT 3072 ACCCUACG G CAUCGAAA 3782

1153 GCTTTCGA GGCTAGCTACAACGA GCCGTAGG 3073 CCUACGGC A UCGAAAGC 3783

1160 GACTCATG GGCTAGCTACAACGA TTTCGATG 3074 CAUCGAAA G CAUGAGUC 3784

1162 TTGACTCA GGCTAGCTACAACGA GCTTTCGA 3075 UCGAAAGC A UGAGUCAA 3785

1166 TGTCTTGA GGCTAGCTACAACGA TCATGCTT 3076 AAGCAUGA G UCAAGACA 3786

1172 CTTCAGTG GGCTAGCTACAACGA CTTGACTC 3077 GAGUCAAG A CACUGAAG 3787

1174 AACTTCAG GGCTAGCTACAACGA GTCTTGAC 3078 GUCAAGAC A CUGAAGUU 3788

1180 ACTTCTAA GGCTAGCTACAACGA TTCAGTGT 3079 ACACUGAA G UUAGAAGU 3789

Table 6

1187 CGACCCGA GGCTAGCTACAACGA TTCTAACT 3080 AGUUAGAA G UCGGGUCG 3790

1192 CCCCACGA GGCTAGCTACAACGA CCGACTTC 3081 GAAGUCGG G UCGUGGGG 3791

1195 TCCCCCCA GGCTAGCTACAACGA GACCCGAC 3082 GUCGGGUC G UGGGGGGA 3792

1205 CTCGAAGA GGCTAGCTACAACGA TTCCCCCC 3083 GGGGGGAA G UCUUCGAG 3793

1214 CCTGGGCA GGCTAGCTACAACGA CTCGAAGA 3084 UCUUCGAG G UGCCCAGG 3794

1216 AGCCTGGG GGCTAGCTACAACGA ACCTCGAA 3085 UUCGAGGU G CCCAGGCU 3795

1222 GGAGGCAG GGCTAGCTACAACGA CTGGGCAC 3086 GUGCCCAG G CUGCCUCC 3796

1225 TGGGGAGG GGCTAGCTACAACGA AGCCTGGG 3087 CCCAGGCU G CCUCCCCA 3797

1234 CCCTTTGG GGCTAGCTACAACGA TGGGGAGG 3088 CCUCCCCA G CCAAAGGG 3798

1245 AGTGACGG GGCTAGCTACAACGA TCCCCTTT 3089 AAAGGGGA G CCGUCACU 3799

1248 GGCAGTGA GGCTAGCTACAACGA GGCTCCCC 3090 GGGGAGCC G UCACUGCC 3800

1251 TCGGGCAG GGCTAGCTACAACGA GACGGCTC 3091 GAGCCGUC A CUGCCCGA 3801

1254 TTCTCGGG GGCTAGCTACAACGA AGTGACGG 3092 CCGUCACU G CCCGAGAA 3802

1265 GGTCCTCG GGCTAGCTACAACGA CCTTCTCG 3093 CGAGAAGG A CGAGGACC 3803

1271 GTGCATGG GGCTAGCTACAACGA CCTCGTCC 3094 GGACGAGG A CCAUGCAC 3804

1274 TCAGTGCA GGCTAGCTACAACGA GGTCCTCG 3095 CGAGGACC A UGCACUGA 3805

1276 ACTCAGTG GGCTAGCTACAACGA ATGGTCCT 3096 AGGACCAU G CACUGAGU 3806

1278 TAACTCAG GGCTAGCTACAACGA GCATGGTC 3097 GACCAUGC A CUGAGUUA 3807

1283 TCCAGTAA GGCTAGCTACAACGA TCAGTGCA 3098 UGCACUGA G UUACUGGA 3808

1286 GCTTCCAG GGCTAGCTACAACGA AACTCAGT 3099 ACUGAGUU A CUGGAAGC 3809

1293 AGGAAGGG GGCTAGCTACAACGA TTCCAGTA 3100 UACUGGAA G CCCUUCCU 3810

1303 CATGTTGA GGCTAGCTACAACGA CAGGAAGG 3101 CCUUCCUG G UCAACAUG 3811

1307 CGCACATG GGCTAGCTACAACGA TGACCAGG 3102 CCUGGUCA A CAUGUGCG 3812

1309 CACGCACA GGCTAGCTACAACGA GTTGACCA 3103 UGGUCAAC A UGUGCGUG 3813

1311 GCCACGCA GGCTAGCTACAACGA ATGTTGAC 3104 GUCAACAU G UGCGUGGC 3814

1313 TAGCCACG GGCTAGCTACAACGA ACATGTTG 3105 CAACAUGU G CGUGGCUA 3815

1315 CGTAGCCA GGCTAGCTACAACGA GCACATGT 3106 ACAUGUGC G UGGCUACG 3816

1318 GACCGTAG GGCTAGCTACAACGA CACGCACA 3107 UGUGCGUG G CUACGGUC 3817

1321 GAGGACCG GGCTAGCTACAACGA AGCCACGC 3108 GCGUGGCU A CGGUCCUC 3818

1324 CGTGAGGA GGCTAGCTACAACGA CGTAGCCA 3109 UGGCUACG G UCCUCACG 3819

1330 GCCGGCCG GGCTAGCTACAACGA GAGGACCG 3110 CGGUCCUC A CGGCCGGC 3820

Table 6

1333 AGCGCCGG GGCTAGCTACAACGA CGTGAGGA 3111 UCCUCACG G CCGGCGCU 3821

1337 GGTAAGCG GGCTAGCTACAACGA CGGCCGTG 3112 CACGGCCG G CGCUUACC 3822

1339 GAGGTAAG GGCTAGCTACAACGA GCCGGCCG 3113 CGGCCGGC G CUUACCUC 3823

1343 AGCAGAGG GGCTAGCTACAACGA AAGCGCCG 3114 CGGCGCUU A CCUCUGCU 3824

1349 ACCTGTAG GGCTAGCTACAACGA AGAGGTAA 3115 UUACCUCU G CUACAGGU 3825

1352 GGAACCTG GGCTAGCTACAACGA AGCAGAGG 3116 CCUCUGCU A CAGGUUCC 3826

1356 AACAGGAA GGCTAGCTACAACGA CTGTAGCA 3117 UGCUACAG G UUCCUGUU 3827

1362 CTGTTGAA GGCTAGCTACAACGA AGGAACCT 3118 AGGUUCCU G UUCAACAG 3828

1367 TGTTGCTG GGCTAGCTACAACGA TGAACAGG 3119 CCUGUUCA A CAGCAACA 3829

1370 ATGTGTTG GGCTAGCTACAACGA TGTTGAAC 3120 GUUCAACA G CAACACAU 3830

1373 GCTATGTG GGCTAGCTACAACGA TGCTGTTG 3121 CAACAGCA A CACAUAGC 3831

1375 AGGCTATG GGCTAGCTACAACGA GTTGCTGT 3122 ACAGCAAC A CAUAGCCU 3832

1377 TCAGGCTA GGCTAGCTACAACGA GTGTTGCT 3123 AGCAACAC A UAGCCUGA 3833

1380 GGGTCAGG GGCTAGCTACAACGA TATGTGTT 3124 AACACAUA G CCUGACCC 3834

1385 GAGGAGGG GGCTAGCTACAACGA CAGGCTAT 3125 AUAGCCUG A CCCUCCUC 3835

1395 AGGTGGAG GGCTAGCTACAACGA GGAGGAGG 3126 CCUCCUCC A CUCCACCU 3836

1400 GGTGGAGG GGCTAGCTACAACGA GGAGTGGA 3127 UCCACUCC A CCUCCACC 3837

1406 ACAGTGGG GGCTAGCTACAACGA GGAGGTGG 3128 CCACCUCC A CCCACUGU 3838

1410 GCGGACAG GGCTAGCTACAACGA GGGTGGAG 3129 CUCCACCC A CUGUCCGC 3839

1413 GAGGCGGA GGCTAGCTACAACGA AGTGGGTG 3130 CACCCACU G UCCGCCUC 3840

1417 GGCAGAGG GGCTAGCTACAACGA GGACAGTG 3131 CACUGUCC G CCUCUGCC 3841

1423 TCTGCGGG GGCTAGCTACAACGA AGAGGCGG 3132 CCGCCUCU G CCCGCAGA 3842

1427 GGGCTCTG GGCTAGCTACAACGA GGGCAGAG 3133 CUCUGCCC G CAGAGCCC 3843

1432 GGCGTGGG GGCTAGCTACAACGA TCTGCGGG 3134 CCCGCAGA G CCCACGCC 3844

1436 GTCGGGCG GGCTAGCTACAACGA GGGCTCTG 3135 CAGAGCCC A CGCCCGAC 3845

1438 TAGTCGGG GGCTAGCTACAACGA GTGGGCTC 3136 GAGCCCAC G CCCGACUA 3846

1443 CCTGCTAG' GGCTAGCTACAACGA CGGGCGTG 3137 CACGCCCG A CUAGCAGG 3847

1447 CATGCCTG GGCTAGCTACAACGA TAGTCGGG 3138 CCCGACUA G CAGGCAUG 3848

1451 GCGGCATG GGCTAGCTACAACGA CTGCTAGT 3139 ACUAGCAG G CAUGCCGC 3849

1453 CCGCGGCA GGCTAGCTACAACGA GCCTGCTA 3140 UAGCAGGC A UGCCGCGG 3850

1455 TACCGCGG GGCTAGCTACAACGA ATGCCTGC 3141 GCAGGCAU G CCGCGGUA 3851

Table 6

1458 ACCTACCG GGCTAGCTACAACGA GGCATGCC 3142 GGCAUGCC G CGGUAGGU 3852

1461 CTTACCTA GGCTAGCTACAACGA CGCGGCAT 3143 AUGCCGCG G UAGGUAAG 3853

1465 GGCCCTTA GGCTAGCTACAACGA CTACCGCG 3144 CGCGGUAG G UAAGGGCC 3854

1471 TCCGGCGG GGCTAGCTACAACGA CCTTACCT 3145 AGGUAAGG G CCGCCGGA 3855

1474 CGGTCCGG GGCTAGCTACAACGA GGCCCTTA 3146 UAAGGGCC G CCGGACCG 3856

1479 CTACGCGG GGCTAGCTACAACGA CCGGCGGC 3147 GCCGCCGG A CCGCGUAG 3857

1482 TCTCTACG GGCTAGCTACAACGA GGTCCGGC 3148 GCCGGACC G CGUAGAGA 3858

1484 GCTCTCTA GGCTAGCTACAACGA GCGGTCCG 3149 CGGACCGC G UAGAGAGC 3859

1491 GGGCCCGG GGCTAGCTACAACGA TCTCTACG 3150 CGUAGAGA G CCGGGCCC 3860

1496 GTCCGGGG GGCTAGCTACAACGA CCGGCTCT 3151 AGAGCCGG G CCCCGGAC 3861

1503 AACGTCCG GGCTAGCTACAACGA CCGGGGCC 3152 GGCCCCGG A CGGACGUU 3862

1507 AACCAACG GGCTAGCTACAACGA CCGTCCGG 3153 CCGGACGG A CGUUGGUU 3863

1509 AGAACCAA GGCTAGCTACAACGA GTCCGTCC 3154 GGACGGAC G UUGGUUCU 3864

1513 GTGCAGAA GGCTAGCTACAACGA CAACGTCC 3155 GGACGUUG G UUCUGCAC 3865

1518 TTTTAGTG GGCTAGCTACAACGA AGAACCAA 3156 UUGGUUCU G CACUAAAA 3866

1520 GGTTTTAG GGCTAGCTACAACGA GCAGAACC 3157 GGUUCUGC A CUAAAACC 3867

1526 AAGATGGG GGCTAGCTACAACGA TTTAGTGC 3158 GCACUAAA A CCCAUCUU 3868

1530 GGGGAAGA GGCTAGCTACAACGA GGGTTTTA 3159 UAAAACCC A UCUUCCCC 3869

1541 GACACACA GGCTAGCTACAACGA CCGGGGAA 3160 UUCCCCGG A UGUGUGUC 3870

1543 GAGACACA GGCTAGCTACAACGA ATCCGGGG 3161 CCCCGGAU G UGUGUCUC 3871

1545 GTGAGACA GGCTAGCTACAACGA ACATCCGG 3162 CCGGAUGU G UGUCUCAC 3872

1547 GGGTGAGA GGCTAGCTACAACGA ACACATCC 3163 GGAUGUGU G UCUCACCC 3873

1552 ATGAGGGG GGCTAGCTACAACGA GAGACACA 3164 UGUGUCUC A CCCCUCAU 3874

1559 TAAAAGGA GGCTAGCTACAACGA GAGGGGTG 3165 CACCCCUC A UCCUUUUA 3875

1567 GCAAAAAG GGCTAGCTACAACGA AAAAGGAT 3166 AUCCUUUU A CUUUUUGC 3876

1574 GGAAGGGG GGCTAGCTACAACGA AAAAAGTA 3167 UACUUUUU G CCCCUUCC 3877

1583 ACTCAAAG GGCTAGCTACAACGA GGAAGGGG 3168 CCCCUUCC A CUUUGAGU 3878

1590 ATTTGGTA GGCTAGCTACAACGA TCAAAGTG 3169 CACUUUGA G UACCAAAU 3879

1592 GGATTTGG GGCTAGCTACAACGA ACTCAAAG 3170 CUUUGAGU A CCAAAUCC 3880

1597 CTTGTGGA GGCTAGCTACAACGA TTGGTACT 3171 AGUACCAA A UCCACAAG 3881

1601 ATGGCTTG GGCTAGCTACAACGA GGATTTGG 3172 CCAAAUCC A CAAGCCAU 3882

Table b

1605 AAAAATGG GGCTAGCTACAACGA TTGTGGAT 3173 AUCCACAA G CCAUUUUU 3883

1608 TCAAAAAA GGCTAGCTACAACGA GGCTTGTG 3174 CACAAGCC A UUUUUUGA 3884

1622 CTCTTTCA GGCTAGCTACAACGA TCTCCTCA 3175 UGAGGAGA G UGAAAGAG 3885

1632 GCATGGTA GGCTAGCTACAACGA TCTCTTTC 3176 GAAAGAGA G UACCAUGC 3886

1634 CAGCATGG GGCTAGCTACAACGA ACTCTCTT 3177 AAGAGAGU A CCAUGCUG 3887

1637 CGCCAGCA GGCTAGCTACAACGA GGTACTCT 3178 AGAGUACC A UGCUGGCG 3888

1639 GCCGCCAG GGCTAGCTACAACGA ATGGTACT 3179 AGUACCAU G CUGGCGGC 3889

1643 CTGCGCCG GGCTAGCTACAACGA CAGCATGG 3180 CCAUGCUG G CGGCGCAG 3890

1646 CCTCTGCG GGCTAGCTACAACGA CGCCAGCA 3181 UGCUGGCG G CGCAGAGG 3891

1648 TCCCTCTG GGCTAGCTACAACGA GCCGCCAG 3182 CUGGCGGC G CAGAGGGA 3892

1661 GGTGTAGG GGCTAGCTACAACGA CCCTTCCC 3183 GGGAAGGG G CCUACACC 3893

1665 GACGGGTG GGCTAGCTACAACGA AGGCCCCT 3184 AGGGGCCU A CACCCGUC 3894

1667 AAGACGGG GGCTAGCTACAACGA GTAGGCCC 3185 GGGCCUAC A CCCGUCUU 3895

1671 CCCCAAGA GGCTAGCTACAACGA GGGTGTAG 3186 CUACACCC G UCUUGGGG 3896

1679 GGGGCGAG GGCTAGCTACAACGA CCCAAGAC 3187 GUCUUGGG G CUCGCCCC 3897

1683 GGGTGGGG GGCTAGCTACAACGA GAGCCCCA 3188 UGGGGCUC G CCCCACCC 3898

1688 GCCCTGGG GGCTAGCTACAACGA GGGGCGAG 3189 CUCGCCCC A CCCAGGGC 3899

1695 GGAGGGAG GGCTAGCTACAACGA CCTGGGTG 3190 CACCCAGG G CUCCCUCC 3900

1708 CTGGGATG GGCTAGCTACAACGA TCCAGGAG 3191 CUCCUGGA G CAUCCCAG 3901

1710 GCCTGGGA GGCTAGCTACAACGA GCTCCAGG 3192 CCUGGAGC A UCCCAGGC 3902

1717 GCCGCCCG GGCTAGCTACAACGA CTGGGATG 3193 CAUCCCAG G CGGGCGGC 3903

1721 GCGTGCCG GGCTAGCTACAACGA CCGCCTGG 3194 CCAGGCGG G CGGCACGC 3904

1724 CTGGCGTG GGCTAGCTACAACGA CGCCCGCC 3195 GGCGGGCG G CACGCCAG 3905

1726 GTCTGGCG GGCTAGCTACAACGA GCCGCCCG 3196 CGGGCGGC A CGCCAGAC 3906

1728 CTGTCTGG GGCTAGCTACAACGA GTGCCGCC 3197 GGCGGCAC G CCAGACAG 3907

1733 GGGGGCTG GGCTAGCTACAACGA CTGGCGTG 3198 CACGCCAG A CAGCCCCC 3908

1736 GGGGGGGG GGCTAGCTACAACGA TGTCTGGC 3199 GCCAGACA G CCCCCCCC 3909

1749 CCTGCAGA GGCTAGCTACAACGA TCAAGGGG 3200 CCCCUUGA A UCUGCAGG 3910

1753 GCTCCCTG GGCTAGCTACAACGA AGATTCAA 3201 UUGAAUCU G CAGGGAGC 3911

1760 GAGAGTTG GGCTAGCTACAACGA TCCCTGCA 3202 UGCAGGGA G CAACUCUC 3912

1763 GTGGAGAG GGCTAGCTACAACGA TGCTCCCT 3203 AGGGAGCA A CUCUCCAC 3913

Table 6

1770 ATATGGAG GGCTAGCTACAACGA GGAGAGTT 3204 AACUCUCC A CUCCAUAU 3914

1775. AATAAATA GGCTAGCTACAACGA GGAGTGGA 3205 UCCACUCC A UAUUUAUU 3915

1777 TAAATAAA GGCTAGCTACAACGA ATGGAGTG 3206 CACUCCAU A UUUAUUUA 3916

1781 TGTTTAAA GGCTAGCTACAACGA AAATATGG 3207 CCAUAUUU A UUUAAACA 3917

1787 AAAAATTG GGCTAGCTACAACGA TTAAATAA 3208 UUAUUUAA A CAAUUUUU 3918

1790 GGAAAAAA GGCTAGCTACAACGA TGTTTAAA 3209 UUUAAACA A UUUUUUCC 3919

1805 TATGGATG GGCTAGCTACAACGA CTTTGGGG 3210 CCCCAAAG G CAUCCAUA 3920

1807 ACTATGGA GGCTAGCTACAACGA GCCTTTGG 3211 CCAAAGGC A UCCAUAGU 3921

1811 GTGCACTA GGCTAGCTACAACGA GGATGCCT 3212 AGGCAUCC A UAGUGCAC 3922

1814 CTAGTGCA GGCTAGCTACAACGA TATGGATG 3213 CAUCCAUA G UGCACUAG 3923

1816 TGCTAGTG GGCTAGCTACAACGA ACTATGGA 3214 UCCAUAGU G CACUAGCA 3924

1818 AATGCTAG GGCTAGCTACAACGA GCACTATG 3215 CAUAGUGC A CUAGCAUU 3925

1822 AGAAAATG GGCTAGCTACAACGA TAGTGCAC 3216 GUGCACUA G CAUUUUCU 3926

1824 CAAGAAAA GGCTAGCTACAACGA GCTAGTGC 3217 GCACUAGC A UUUUCUUG 3927

1834 ATTATTGG GGCTAGCTACAACGA TCAAGAAA 3218 UUUCUUGA A CCAAUAAU 3928

1838 ATACATTA GGCTAGCTACAACGA TGGTTCAA 3219 UUGAACCA A UAAUGUAU 3929

1841 TTAATACA GGCTAGCTACAACGA TATTGGTT 3220 AACCAAUA A UGUAUUAA 3930

1843 TTTTAATA GGCTAGCTACAACGA ATTATTGG 3221 CCAAUAAU G UAUUAAAA 3931

1845 AATTTTAA GGCTAGCTACAACGA ACATTATT 3222 AAUAAUGU A UUAAAAUU 3932

1851 TCAAAAAA GGCTAGCTACAACGA TTTAATAC 3223 GUAUUAAA A UUUUUUGA 3933

1859 GGCTGACA GGCTAGCTACAACGA CAAAAAAT 3224 AUUUUUUG A UGUCAGCC 3934

1861 AAGGCTGA GGCTAGCTACAACGA ATCAAAAA 3225 UUUUUGAU G UCAGCCUU 3935

1865 ATGCAAGG GGCTAGCTACAACGA TGACATCA 3226 UGAUGUCA G CCUUGCAU 3936

1870 CCTTGATG GGCTAGCTACAACGA AAGGCTGA 3227 UCAGCCUU G CAUCAAGG 3937

1872 GCCCTTGA GGCTAGCTACAACGA GCAAGGCT 3228 AGCCUUGC A UCAAGGGC 3938

1879 TGATAAAG GGCTAGCTACAACGA CCTTGATG 3229 CAUCAAGG G CUUUAUCA 3939

1884 CTTTTTGA GGCTAGCTACAACGA AAAGCCCT 3230 AGGGCUUU A UCAAAAAG 3940

1892 TTATTGTA GGCTAGCTACAACGA TTTTTGAT 3231 AUCAAAAA G UACAAUAA 3941

1894 TATTATTG GGCTAGCTACAACGA ACTTTTTG 3232 CAAAAAGU A CAAUAAUA 3942

1897 ATTTATTA GGCTAGCTACAACGA TGTACTTT 3233 AAAGUACA A UAAUAAAU 3943

1900 AGGATTTA GGCTAGCTACAACGA TATTGTAC 3234 GUACAAUA A UAAAUCCU 3944

Table 6

1904 CCTGAGGA GGCTAGCTACAACGA TTATTATT 3235 AAUAAUAA A UCCUCAGG 3945

1912 CAGTACTA GGCTAGCTACAACGA CTGAGGAT 3236 AUCCUCAG G UAGUACUG 3946

1915 TCCCAGTA GGCTAGCTACAACGA TACCTGAG 3237 CUCAGGUA G UACUGGGA 3947

1917 ATTCCCAG GGCTAGCTACAACGA ACTACCTG 3238 CAGGUAGU A CUGGGAAU 3948

1924 GCCTTCCA GGCTAGCTACAACGA TCCCAGTA 3239 UACUGGGA A UGGAAGGC 3949

1931 TGGCAAAG GGCTAGCTACAACGA CTTCCATT 3240 AAUGGAAG G CUUUGCCA 3950

1936 GCCCATGG GGCTAGCTACAACGA AAAGCCTT 3241 AAGGCUUU G CCAUGGGC 3951

1939 CAGGCCCA GGCTAGCTACAACGA GGCAAAGC 3242 GCUUUGCC A UGGGCCUG 3952

1943 GCAGCAGG GGCTAGCTACAACGA CCATGGCA 3243 UGCCAUGG G CCUGCUGC 3953

1947 TGACGCAG GGCTAGCTACAACGA AGGCCCAT 3244 AUGGGCCU G CUGCGUCA 3954

1950 GTCTGACG GGCTAGCTACAACGA AGCAGGCC 3245 GGCCUGCU G CGUCAGAC 3955

1952 TGGTCTGA GGCTAGCTACAACGA GCAGCAGG 3246 CCUGCUGC G UCAGACCA 3956

1957 AGTACTGG GGCTAGCTACAACGA CTGACGCA 3247 UGCGUCAG A CCAGUACU 3957

1961 TCCCAGTA GGCTAGCTACAACGA TGGTCTGA 3248 UCAGACCA G UACUGGGA 3958

1963 CTTCCCAG GGCTAGCTACAACGA ACTGGTCT 3249 AGACCAGU A CUGGGAAG 3959

1976 TACAACCG GGCTAGCTACAACGA CCTCCTTC 3250 GAAGGAGG A CGGUUGUA 3960

1979 GCTTACAA GGCTAGCTACAACGA CGTCCTCC 3251 GGAGGACG G UUGUAAGC 3961

1982 ACTGCTTA GGCTAGCTACAACGA AACCGTCC 3252 GGACGGUU G UAAGCAGU 3962

1986 AACAACTG GGCTAGCTACAACGA TTACAACC 3253 GGUUGUAA G CAGUUGUU 3963

1989 AATAACAA GGCTAGCTACAACGA TGCTTACA 3254 UGUAAGCA G UUGUUAUU 3964

1992 CTAAATAA GGCTAGCTACAACGA AACTGCTT 3255 AAGCAGUU G UUAUUUAG 3965

1995 TCACTAAA GGCTAGCTACAACGA AACAACTG 3256 CAGUUGUU A UUUAGUGA 3966

2000 CAATATCA GGCTAGCTACAACGA TAAATAAC 3257 GUUAUUUA G UGAUAUUG 3967

2003 CCACAATA GGCTAGCTACAACGA CACTAAAT 3258 AUUUAGUG A UAUUGUGG 3968

2005 ACCCACAA GGCTAGCTACAACGA ATCACTAA 3259 UUAGUGAU A UUGUGGGU 3969

2008 GTTACCCA GGCTAGCTACAACGA AATATCAC 3260 GUGAUAUU G UGGGUAAC 3970

2012 TCACGTTA GGCTAGCTACAACGA CCACAATA 3261 UAUUGUGG G UAACGUGA 3971

2015 TTCTCACG GGCTAGCTACAACGA TACCCACA 3262 UGUGGGUA A CGUGAGAA 3972

2017 TCTTCTCA GGCTAGCTACAACGA GTTACCCA 3263 UGGGUAAC G UGAGAAGA 3973

2025 TTGTTCTA GGCTAGCTACAACGA CTTCTCAC 3264 GUGAGAAG A UAGAACAA 3974

2030 TAGCATTG GGCTAGCTACAACGA TCTATCTT 3265 AAGAUAGA A CAAUGCUA 3975

Table 6

2033 TTATAGCA GGCTAGCTACAACGA TGTTCTAT 3266 AUAGAACA A UGCUAUAA 3976

2035 TATTATAG GGCTAGCTACAACGA ATTGTTCT 3267 AGAACAAU G CUAUAAUA 3977

2038 ATATATTA GGCTAGCTACAACGA AGCATTGT 3268 ACAAUGCU A UAAUAUAU 3978

2041 ATTATATA GGCTAGCTACAACGA TATAGCAT 3269 AUGCUAUA A UAUAUAAU 3979

2043 TCATTATA GGCTAGCTACAACGA ATTATAGC 3270 GCUAUAAU A UAUAAUGA 3980

2045 GTTCATTA GGCTAGCTACAACGA ATATTATA 3271 UAUAAUAU A UAAUGAAC 3981

2048 CGTGTTCA GGCTAGCTACAACGA TATATATT 3272 AAUAUAUA A UGAACACG 3982

2052 CCCACGTG GGCTAGCTACAACGA TCATTATA 3273 UAUAAUGA A CACGUGGG 3983

2054 TACCCACG GGCTAGCTACAACGA GTTCATTA 3274 UAAUGAAC A CGUGGGUA 3984

2056 AATACCCA GGCTAGCTACAACGA GTGTTCAT 3275 AUGAACAC G UGGGUAUU 3985

2060 ATTAAATA GGCTAGCTACAACGA CCACGTGT 3276 ACACGUGG G UAUUUAAU 3986

2062 TTATTAAA GGCTAGCTACAACGA ACCCACGT 3277 ACGUGGGU A UUUAAUAA 3987

2067 GTTTCTTA GGCTAGCTACAACGA TAAATACC 3278 GGUAUUUA A UAAGAAAC 3988

2074 ACATCATG GGCTAGCTACAACGA TTCTTATT 3279 AAUAAGAA A CAUGAUGU 3989

2076 TCACATCA GGCTAGCTACAACGA GTTTCTTA 3280 UAAGAAAC A UGAUGUGA 3990

2079 ATCTCACA GGCTAGCTACAACGA CATGTTTC 3281 GAAACAUG A UGUGAGAU 3991

2081 TAATCTCA GGCTAGCTACAACGA ATCATGTT 3282 AACAUGAU G UGAGAUUA 3992

2086 CAAAGTAA GGCTAGCTACAACGA CTCACATC 3283 GAUGUGAG A UUACUUUG 3993

2089 GGACAAAG GGCTAGCTACAACGA AATCTCAC ^• 3284 GUGAGAUU A CUUUGUCC 3994

2094 AAGCGGGA GGCTAGCTACAACGA AAAGTAAT 3285 AUUACUUU G UCCCGCUU 3995

2099 AGAATAAG GGCTAGCTACAACGA GGGACAAA 3286 UUUGUCCC G CUUAUUCU 3996

2103 GAGCAGAA GGCTAGCTACAACGA AAGCGGGA 3287 UCCCGCUU A UUCUGCUC 3997

2108 ACAGGGAG GGCTAGCTACAACGA AGAATAAG 3288 CUUAUUCU G CUCCCUGU 3998

2115 GCAGATAA GGCTAGCTACAACGA AGGGAGCA 3289 UGCUCCCU G UUAUCUGC 3999

2118 CTAGCAGA GGCTAGCTACAACGA AACAGGGA 3290 UCCCUGUU A UCUGCUAG 4000

2122 AGATCTAG GGCTAGCTACAACGA AGATAACA 3291 UGUUAUCU G CUAGAUCU 4001

2127 GAACTAGA GGCTAGCTACAACGA CTAGCAGA 3292 UCUGCUAG A UCUAGUUC 4002

2132 ATTGAGAA GGCTAGCTACAACGA TAGATCTA 3293 UAGAUCUA G UUCUCAAU 4003

2139 AGCAGTGA GGCTAGCTACAACGA TGAGAACT 3294 AGUUCUCA A UCACUGCU 4004

2142 GGGAGCAG GGCTAGCTACAACGA GATTGAGA 3295 UCUCAAUC A CUGCUCCC 4005

2145 CGGGGGAG GGCTAGCTACAACGA AGTGATTG 3296 CAAUCACU G CUCCCCCG 4006

Table 6

2153 AATACACA GGCTAGCTACAACGA GGGGGAGC 3297 GCUCCCCC G UGUGUAUU 4007

2155 CTAATACA GGCTAGCTACAACGA ACGGGGGA 3298 UCCCCCGU G UGUAUUAG 4008

2157 TTCTAATA GGCTAGCTACAACGA ACACGGGG 3299 CCCCGUGU G UAUUAGAA 4009

2159 CATTCTAA GGCTAGCTACAACGA ACACACGG 3300. CCGUGUGU A UUAGAAUG 4010

2165 TACATGCA GGCTAGCTACAACGA TCTAATAC 3301 GUAUUAGA A UGCAUGUA 4011

2167 CTTACATG GGCTAGCTACAACGA ATTCTAAT 3302 AUUAGAAU G CAUGUAAG 4012

2169 ACCTTACA GGCTAGCTACAACGA GCATTCTA 3303 UAGAAUGC A UGUAAGGU 4013

2171 AGACCTTA GGCTAGCTACAACGA ATGCATTC 3304 GAAUGCAU G UAAGGUCU 4014

2176 CAAGAAGA GGCTAGCTACAACGA CTTACATG 3305 CAUGUAAG G UCUUCUUG 4015

2184 TCAGGACA GGCTAGCTACAACGA AAGAAGAC 3306 GUCUUCUU G UGUCCUGA 4016

2186 CATCAGGA GGCTAGCTACAACGA ACAAGAAG 3307 CUUCUUGU G UCCUGAUG 4017

2192 ATTTTTCA GGCTAGCTACAACGA CAGGACAC 3308 GUGUCCUG A UGAAAAAU 4018

2199 AGCACATA GGCTAGCTACAACGA TTTTCATC 3309 GAUGAAAA A UAUGUGCU 4019

2201 CAAGCACA GGCTAGCTACAACGA ATTTTTCA 3310 UGAAAAAU A UGUGCUUG 4020

2203 TTCAAGCA GGCTAGCTACAACGA ATATTTTT 3311 AAAAAUAU G UGCUUGAA 4021

2205 ATTTCAAG GGCTAGCTACAACGA ACATATTT 3312 AAAUAUGU G CUUGAAAU 4022

2212 GTTTCTCA GGCTAGCTACAACGA TTCAAGCA 3313 UGCUUGAA A UGAGAAAC 4023

2219 GATCAAAG GGCTAGCTACAACGA TTCTCATT 3314 AAUGAGAA A CUUUGAUC 4024

2225 AGCAGAGA GGCTAGCTACAACGA CAAAGTTT 3315 AAACUUUG A UCUCUGCU 4025

2231 TTAGTAAG GGCTAGCTACAACGA AGAGATCA 3316 UGAUCUCU G CUUACUAA 4026

2235 CACATTAG GGCTAGCTACAACGA AAGCAGAG 3317 CUCUGCUU A CUAAUGUG 4027

2239 GGGGCACA GGCTAGCTACAACGA TAGTAAGC 3318 GCUUACUA A UGUGCCCC 4028

2241 ATGGGGCA GGCTAGCTACAACGA ATTAGTAA 3319 UUACUAAU G UGCCCCAU 4029

2243 ACATGGGG GGCTAGCTACAACGA ACATTAGT 3320 ACUAAUGU G CCCCAUGU 4030

2248 CTTGGACA GGCTAGCTACAACGA GGGGCACA 3321 UGUGCCCC A UGUCCAAG 4031

2250 GACTTGGA GGCTAGCTACAACGA ATGGGGCA 3322 UGCCCCAU G UCCAAGUC 4032

2256 AGGTTGGA GGCTAGCTACAACGA TTGGACAT 3323 AUGUCCAA G UCCAACCU 4033

2261 CAGGCAGG GGCTAGCTACAACGA TGGACTTG 3324 CAAGUCCA A CCUGCCUG 4034

2265 TGCACAGG GGCTAGCTACAACGA AGGTTGGA 3325 UCCAACCU G CCUGUGCA 4035

2269 GTCATGCA GGCTAGCTACAACGA AGGCAGGT 3326 ACCUGCCU G UGCAUGAC 4036

2271 AGGTCATG GGCTAGCTACAACGA ACAGGCAG 3327 CUGCCUGU G CAUGACCU 4037

Table 6

2273 TCAGGTCA GGCTAGCTACAACGA GCACAGGC 3328 GCCUGUGC A UGACCUGA 4038

2276 TGATCAGG GGCTAGCTACAACGA CATGCACA 3329 UGUGCAUG A CCUGAUCA 4039

2281 TGTAATGA GGCTAGCTACAACGA CAGGTCAT 3330 AUGACCUG A UCAUUACA 4040

2284 CCATGTAA GGCTAGCTACAACGA GATCAGGT 3331 ACCUGAUC A UUACAUGG 4041

2287 CAGCCATG GGCTAGCTACAACGA AATGATCA 3332 UGAUCAUU A CAUGGCUG 4042

2289 CACAGCCA GGCTAGCTACAACGA GTAATGAT 3333 AUCAUUAC A UGGCUGUG 4043

2292 AACCACAG GGCTAGCTACAACGA CATGTAAT 3334 AUUACAUG G CUGUGGUU 4044

2295 AGGAACCA GGCTAGCTACAACGA AGCCATGT 3335 ACAUGGCU G UGGUUCCU 4045

2298 CTTAGGAA GGCTAGCTACAACGA CACAGCCA 3336 UGGCUGUG G UUCCUAAG 4046

2306 GCAACAGG GGCTAGCTACAACGA TTAGGAAC 3337 GUUCCUAA G CCUGUUGC 4047

2310 TTCAGCAA GGCTAGCTACAACGA AGGCTTAG 3338 CUAAGCCU G UUGCUGAA 4048

2313 GACTTCAG GGCTAGCTACAACGA AACAGGCT 3339 AGCCUGUU G CUGAAGUC 4049

2319 GACAATGA GGCTAGCTACAACGA TTCAGCAA 3340 UUGCUGAA G UCAUUGUC 4050

2322 AGCGACAA GGCTAGCTACAACGA GACTTCAG 3341 CUGAAGUC A UUGUCGCU 4051

2325 CTGAGCGA GGCTAGCTACAACGA AATGACTT 3342 AAGUCAUU G UCGCUCAG 4052

2328 TTGCTGAG GGCTAGCTACAACGA GACAATGA 3343 UCAUUGUC G CUCAGCAA 4053

2333 CCCTATTG GGCTAGCTACAACGA TGAGCGAC 3344 GUCGCUCA G CAAUAGGG 4054

2336 GCACCCTA GGCTAGCTACAACGA TGCTGAGC 3345 GCUCAGCA A UAGGGUGC 4055

2341 AAACTGCA GGCTAGCTACAACGA CCTATTGC 3346 GCAAUAGG G UGCAGUUU 4056

2343 GAAAACTG GGCTAGCTACAACGA ACCCTATT 3347 AAUAGGGU G CAGUUUUC 4057

2346 CTGGAAAA GGCTAGCTACAACGA TGCACCCT 3348 AGGGUGCA G UUUUCCAG 4058

2357 AATGCCTA GGCTAGCTACAACGA TCCTGGAA 3349 UUCCAGGA A UAGGCAUU 4059

2361 GGCAAATG GGCTAGCTACAACGA CTATTCCT 3350 AGGAAUAG G CAUUUGCC 4060

2363 TAGGCAAA GGCTAGCTACAACGA GCCTATTC 3351 GAAUAGGC A UUUGCCUA 4061

2367 GAATTAGG GGCTAGCTACAACGA AAATGCCT 3352 AGGCAUUU G CCUAAUUC 4062

2372 GCCAGGAA GGCTAGCTACAACGA TAGGCAAA 3353 UUUGCCUA A UUCCUGGC 4063

2379 GTGTCATG GGCTAGCTACAACGA CAGGAATT 3354 AAUUCCUG G CAUGACAC 4064

2381 GAGTGTCA GGCTAGCTACAACGA GCCAGGAA 3355 UUCCUGGC A UGACACUC 4065

2384 CTAGAGTG GGCTAGCTACAACGA CATGCCAG 3356 CUGGCAUG A CACUCUAG 4066

2386 CACTAGAG GGCTAGCTACAACGA GTCATGCC 3357 GGCAUGAC A CUCUAGUG 4067

2392 GGAAGTCA GGCTAGCTACAACGA TAGAGTGT 3358 ACACUCUA G UGACUUCC 4068

Table 6

Table 6

2541 GAGGCTGA GGCTAGCTACAACGA CCCAAAGG 3390 CCUUUGGG A UCAGCCUC 4100

2545 GGCGGAGG GGCTAGCTACAACGA TGATCCCA 3391 UGGGAUCA G CCUCCGCC 4101

2551 TGGAATGG GGCTAGCTACAACGA GGAGGCTG 3392 CAGCCUCC G CCAUUCCA 4102

2554 ACTTGGAA GGCTAGCTACAACGA GGCGGAGG 3393 CCUCCGCC A UUCCAAGU 4103

2561 AGTGTCGA GGCTAGCTACAACGA TTGGAATG 3394 CAUUCCAA G UCGACACU 4104

2565 GAAGAGTG GGCTAGCTACAACGA CGACTTGG 3395 CCAAGUCG A CACUCUUC 4105

2567 AAGAAGAG GGCTAGCTACAACGA GTCGACTT 3396 AAGUCGAC A CUCUUCUU 4106

2578 ACGGTCTG GGCTAGCTACAACGA TCAAGAAG 3397 CUUCUUGA G CAGACCGU 4107

2582 AATCACGG GGCTAGCTACAACGA CTGCTCAA 3398 UUGAGCAG A CCGUGAUU 4108

2585 CCAAATCA GGCTAGCTACAACGA GGTCTGCT 3399 AGCAGACC G UGAUUUGG 4109

2588 CTTCCAAA GGCTAGCTACAACGA CACGGTCT 3400 AGACCGUG A UUUGGAAG 4110

2601 AGCAGGTG GGCTAGCTACAACGA CTCTCTTC 3401 GAAGAGAG G CACCUGCU 4111

2603 CCAGCAGG GGCTAGCTACAACGA GCCTCTCT 3402 AGAGAGGC A CCUGCUGG 4112

2607 GTTTCCAG GGCTAGCTACAACGA AGGTGCCT 3403 AGGCACCU G CUGGAAAC 4113

2614 AAGTGTGG GGCTAGCTACAACGA TTCCAGCA 3404 UGCUGGAA A CCACACUU 4114

2617 AAGAAGTG GGCTAGCTACAACGA GGTTTCCA 3405 UGGAAACC A CACUUCUU 4115

2619 TCAAGAAG GGCTAGCTACAACGA GTGGTTTC 3406 GAAACCAC A CUUCUUGA 4116

2629 CCAGGCTG GGCTAGCTACAACGA TTCAAGAA 3407 UUCUUGAA A CAGCCUGG 4117

2632 CACCCAGG GGCTAGCTACAACGA TGTTTCAA 3408 UUGAAACA G CCUGGGUG 4118

2638 GACCGTCA GGCTAGCTACAACGA CCAGGCTG 3409 CAGCCUGG G UGACGGUC 4119

2641 AAGGACCG GGCTAGCTACAACGA CACCCAGG 3410 CCUGGGUG A CGGUCCUU 4120

2644 CTAAAGGA GGCTAGCTACAACGA CGTCACCC 3411 GGGUGACG G UCCUUUAG 4121

2653 GCAGGCTG GGCTAGCTACAACGA CTAAAGGA 3412 UCCUUUAG G CAGCCUGC 4122

2656 GCGGCAGG GGCTAGCTACAACGA TGCCTAAA 3413 UUUAGGCA G CCUGCCGC 4123

2660 GACGGCGG GGCTAGCTACAACGA AGGCTGCC 3414 GGCAGCCU G CCGCCGUC 4124

2663 AGAGACGG GGCTAGCTACAACGA GGCAGGCT 3415 AGCCUGCC G CCGUCUCU 4125

2666 GACAGAGA GGCTAGCTACAACGA GGCGGCAG 3416 CUGCCGCC G UCUCUGUC 4126

2672 AACCGGGA GGCTAGCTACAACGA AGAGACGG 3417 CCGUCUCU G UCCCGGUU 4127

2678 AAGGTGAA GGCTAGCTACAACGA CGGGACAG 3418 CUGUCCCG G UUCACCUU 4128

2682 CGGCAAGG GGCTAGCTACAACGA GAACCGGG 3419 CCCGGUUC A CCUUGCCG 4129

2687 TCTCTCGG GGCTAGCTACAACGA AAGGTGAA 3420 UUCACCUU G CCGAGAGA 4130

Table 6

2697 CAGACGCG GGCTAGCTACAACGA CTCTCTCG 3421 CGAGAGAG G CGCGUCUG 4131

2699 GGCAGACG GGCTAGCTACAACGA GCCTCTCT 3422 AGAGAGGC G CGUCUGCC 4132

2701 GGGGCAGA GGCTAGCTACAACGA GCGCCTCT 3423 AGAGGCGC G UCUGCCCC 4133

2705 GGGTGGGG GGCTAGCTACAACGA AGACGCGC 3424 GCGCGUCU G CCCCACCC 4134

2710 TTTGAGGG GGCTAGCTACAACGA GGGGCAGA 3425 UCUGCCCC A CCCUCAAA 4135

2718 CCACAGGG GGCTAGCTACAACGA TTGAGGGT 3426 ACCCUCAA A CCCUGUGG 4136

2723 AGGCCCCA GGCTAGCTACAACGA AGGGTTTG 3427 CAAACCCU G UGGGGCCU 4137

2728 CCATCAGG GGCTAGCTACAACGA CCCACAGG 3428 CCUGUGGG G CCUGAUGG 4138

2733 GAGCACCA GGCTAGCTACAACGA CAGGCCCC 3429 GGGGCCUG A UGGUGCUC 4139

2736 CGTGAGCA GGCTAGCTACAACGA CATCAGGC 3430 GCCUGAUG G UGCUCACG 4140

2738 GTCGTGAG GGCTAGCTACAACGA ACCATCAG 3431 CUGAUGGU G CUCACGAC 4141

2742 AAGAGTCG GGCTAGCTACAACGA GAGCACCA 3432 UGGUGCUC A CGACUCUU 4142

2745 AGGAAGAG GGCTAGCTACAACGA CGTGAGCA 3433 UGCUCACG A CUCUUCCU 4143

2754 TCCCTTTG GGCTAGCTACAACGA AGGAAGAG 3434 ^■ CUCUUCCU G CAAAGGGA 4144

2763 GTCTTCAG GGCTAGCTACAACGA TCCCTTTG 3435 CAAAGGGA A CUGAAGAC 4145

2770 TGTGGAGG GGCTAGCTACAACGA CTTCAGTT 3436 AACUGAAG A CCUCCACA 4146

2776 ACTTAATG GGCTAGCTACAACGA GGAGGTCT 3437 AGACCUCC A CAUUAAGU 4147

2778 CCACTTAA GGCTAGCTACAACGA GTGGAGGT 3438 ACCUCCAC A UUAAGUGG 4148

2783 AAAAGCCA GGCTAGCTACAACGA TTAATGTG 3439 CACAUUAA G UGGCUUUU 4149

2786 TTAAAAAG GGCTAGCTACAACGA CACTTAAT 3440 AUUAAGUG G CUUUUUAA 4150

2794 TTTTCATG GGCTAGCTACAACGA TAAAAAGC 3441 GCUUUUUA A CAUGAAAA 4151

2796 GTTTTTCA GGCTAGCTACAACGA GTTAAAAA 3442 UUUUUAAC A UGAAAAAC 4152

2803 CTGCCGTG GGCTAGCTACAACGA TTTTCATG 3443 CAUGAAAA A CACGGCAG 4153

2805 AGCTGCCG GGCTAGCTACAACGA GTTTTTCA 3444 UGAAAAAC A CGGCAGCU 4154

2808 TACAGCTG GGCTAGCTACAACGA CGTGTTTT 3445 AAAACACG G CAGCUGUA 4155

2811 AGCTACAG GGCTAGCTACAACGA TGCCGTGT 3446 ACACGGCA G CUGUAGCU 4156

2814 GGGAGCTA GGCTAGCTACAACGA AGCTGCCG 3447 CGGCAGCU G UAGCUCCC 4157

2817 CTCGGGAG GGCTAGCTACAACGA TACAGCTG 3448 CAGCUGUA G CUCCCGAG 4158

2825 GAGAGTAG GGCTAGCTACAACGA TCGGGAGC 3449 GCUCCCGA G CUACUCUC 4159

2828 CAAGAGAG GGCTAGCTACAACGA AGCTCGGG 3450 CCCGAGCU A CUCUCUUG 4160

2836 AATGCTGG GGCTAGCTACAACGA AAGAGAGT 3451 ACUCUCUU G CCAGCAUU 4161

Table 6

2840 TGAAAATG GGCTAGCTACAACGA TGGCAAGA 3452 UCUUGCCA G CAUUUUCA 4162

2842 TGTGAAAA GGCTAGCTACAACGA GCTGGCAA 3453 UUGCCAGC A UUUUCACA 4163

2848 GCAAAATG GGCTAGCTACAACGA GAAAATGC 3454 GCAUUUUC A CAUUUUGC 4164

2850 AGGCAAAA GGCTAGCTACAACGA GTGAAAAT 3455 AUUUUCAC A UUUUGCCU 4165

2855 GAGAAAGG GGCTAGCTACAACGA AAAATGTG 3456 CACAUUUU G CCUUUCUC 4166

2864 TTCTACCA GGCTAGCTACAACGA GAGAAAGG 3457 CCUUUCUC G UGGUAGAA 4167

2867 GGCTTCTA GGCTAGCTACAACGA CACGAGAA 3458 UUCUCGUG G UAGAAGCC 4168

2873 TGTACTGG GGCTAGCTACAACGA TTCTACCA 3459 UGGUAGAA G CCAGUACA 4169

2877 TCTCTGTA GGCTAGCTACAACGA TGGCTTCT 3460 AGAAGCCA G UACAGAGA 4170

2879 TTTCTCTG GGCTAGCTACAACGA ACTGGCTT 3461 AAGCCAGU A CAGAGAAA 4171

2887 CCACAGAA GGCTAGCTACAACGA TTCTCTGT 3462 ACAGAGAA A UUCUGUGG 4172

2892 TCCCACCA GGCTAGCTACAACGA AGAATTTC 3463 GAAAUUCU G UGGUGGGA 4173

2895 TGTTCCCA GGCTAGCTACAACGA CACAGAAT 3464 AUUCUGUG G UGGGAACA 4174

2901 CTCGAATG GGCTAGCTACAACGA TCCCACCA 3465 UGGUGGGA A CAUUCGAG 4175

2903 ACCTCGAA GGCTAGCTACAACGA GTTCCCAC 3466 GUGGGAAC A UUCGAGGU 4176

2910 GGGTGACA GGCTAGCTACAACGA CTCGAATG 3467 CAUUCGAG G UGUCACCC 4177

2912 CAGGGTGA GGCTAGCTACAACGA ACCTCGAA 3468 UUCGAGGU G UCACCCUG 4178

2915 CTGCAGGG GGCTAGCTACAACGA GACACCTC 3469 GAGGUGUC A CCCUGCAG 4179

2920 TAGCTCTG GGCTAGCTACAACGA AGGGTGAC 3470 GUCACCCU G CAGAGCUA 4180

2925 CACCATAG GGCTAGCTACAACGA TCTGCAGG 3471 CCUGCAGA G CUAUGGUG 4181

2928 CCTCACCA GGCTAGCTACAACGA AGCTCTGC 3472 GCAGAGCU A UGGUGAGG 4182

2931 ACACCTCA GGCTAGCTACAACGA CATAGCTC 3473 GAGCUAUG G UGAGGUGU 4183

2936 TATCCACA GGCTAGCTACAACGA CTCACCAT 3474 AUGGUGAG G UGUGGAUA 4184

2938 CTTATCCA GGCTAGCTACAACGA ACCTCACC 3475 GGUGAGGU G UGGAUAAG 4185

2942 AAGCCTTA GGCTAGCTACAACGA CCACACCT 3476 AGGUGUGG A UAAGGCUU 4186

2947 CACCTAAG GGCTAGCTACAACGA CTTATCCA 3477 UGGAUAAG G CUUAGGUG 4187

2953 GCCTGGCA GGCTAGCTACAACGA CTAAGCCT 3478 AGGCUUAG G UGCCAGGC 4188

2955 CAGCCTGG GGCTAGCTACAACGA ACCTAAGC 3479 GCUUAGGU G CCAGGCUG 4189

2960 GCTTACAG GGCTAGCTACAACGA CTGGCACC 3480 GGUGCCAG G CUGUAAGC 4190

2963 AATGCTTA GGCTAGCTACAACGA AGCCTGGC 3481 GCCAGGCU G UAAGCAUU 4191

2967 TCAGAATG GGCTAGCTACAACGA TTACAGCC 3482 GGCUGUAA G CAUUCUGA 4192

Table 6

2969 GCTCAGAA GGCTAGCTACAACGA GCTTACAG 3483 CUGUAAGC A UUCUGAGC 4193

2976 CAAGCCAG GGCTAGCTACAACGA TCAGAATG 3484 CAUUCUGA G CUGGCUUG 4194

2980 ACAACAAG GGCTAGCTACAACGA CAGCTCAG 3485 CUGAGCUG G CUUGUUGU 4195

2984 AAAAACAA GGCTAGCTACAACGA AAGCCAGC 3486 GCUGGCUU G UUGUUUUU 4196

2987 CTTAAAAA GGCTAGCTACAACGA AACAAGCC 3487 GGCUUGUU G UUUUUAAG 4197

2995 ATACAGGA GGCTAGCTACAACGA TTAAAAAC 3488 GUUUUUAA G UCCUGUAU 4198

3000 TACATATA GGCTAGCTACAACGA AGGACTTA 3489 UAAGUCCU G UAUAUGUA 4199

3002 CATACATA GGCTAGCTACAACGA ACAGGACT 3490 AGUCCUGU A UAUGUAUG 4200

3004 TACATACA GGCTAGCTACAACGA ATACAGGA 3491 UCCUGUAU A UGUAUGUA 4201

3006 ACTACATA GGCTAGCTACAACGA ATATACAG 3492 CUGUAUAU G UAUGUAGU 4202

3008 CTACTACA GGCTAGCTACAACGA ACATATAC 3493 GUAUAUGU A UGUAGUAG 4203

3010 AACTACTA GGCTAGCTACAACGA ATACATAT 3494 AUAUGUAU G UAGUAGUU 4204

3013 CCAAACTA GGCTAGCTACAACGA TACATACA 3495 UGUAUGUA G UAGUUUGG 4205

3016 CACCCAAA GGCTAGCTACAACGA TACTACAT 3496 AUGUAGUA G UUUGGGUG 4206

3022 TATACACA GGCTAGCTACAACGA CCAAACTA 3497 UAGUUUGG G UGUGUAUA 4207

3024 TATATACA GGCTAGCTACAACGA ACCCAAAC 3498 GUUUGGGU G UGUAUAUA 4208

3026 TATATATA GGCTAGCTACAACGA ACACCCAA 3499 UUGGGUGU G UAUAUAUA 4209

3028 ACTATATA GGCTAGCTACAACGA ACACACCC 3500 GGGUGUGU A UAUAUAGU 4210

3030 CTACTATA GGCTAGCTACAACGA ATACACAC 3501 GUGUGUAU A UAUAGUAG 4211

3032 TGCTACTA GGCTAGCTACAACGA ATATACAC 3502 GUGUAUAU A UAGUAGCA 4212

3035 AAATGCTA GGCTAGCTACAACGA TATATATA 3503 UAUAUAUA G UAGCAUUU 4213

3038 TTGAAATG GGCTAGCTACAACGA TACTATAT 3504 AUAUAGUA G CAUUUCAA 4214

3040 TTTTGAAA GGCTAGCTACAACGA GCTACTAT 3505 AUAGUAGC A UUUCAAAA 4215

3048 TACGTCCA GGCTAGCTACAACGA TTTGAAAT 3506 AUUUCAAA A UGGACGUA 4216

3052 CCAGTACG GGCTAGCTACAACGA CCATTTTG 3507 CAAAAUGG A CGUACUGG 4217

3054 AACCAGTA GGCTAGCTACAACGA GTCCATTT 3508 AAAUGGAC G UACUGGUU 4218

3056 TAAACCAG GGCTAGCTACAACGA ACGTCCAT 3509 AUGGACGU A CUGGUUUA 4219

3060 AGGTTAAA GGCTAGCTACAACGA CAGTACGT 3510 ACGUACUG G UUUAACCU 4220

3065 ATAGGAGG GGCTAGCTACAACGA TAAACCAG 3511 CUGGUUUA A CCUCCUAU 4221

3072 TCCAAGGA GGCTAGCTACAACGA AGGAGGTT 3512 AACCUCCU A UCCUUGGA 4222

3083 GCCAGCTG GGCTAGCTACAACGA TCTCCAAG 3513 CUUGGAGA G CAGCUGGC 4223

Table 6

3086 AGAGCCAG GGCTAGCTACAACGA TGCTCTCC 3514 GGAGAGCA G CUGGCUCU 4224

3090 GTGGAGAG GGCTAGCTACAACGA CAGCTGCT 3515 AGCAGCUG G CUCUCCAC 4225

3097 TAACAAGG GGCTAGCTACAACGA GGAGAGCC 3516 GGCUCUCC A CCUUGUUA 4226

3102 ATGTGTAA GGCTAGCTACAACGA AAGGTGGA 3517 UCCACCUU G UUACACAU 4227

3105 ATAATGTG GGCTAGCTACAACGA AACAAGGT 3518 ACCUUGUU A CACAUUAU 4228

3107 ACATAATG GGCTAGCTACAACGA GTAACAAG 3519 CUUGUUAC A CAUUAUGU 4229

3109 TAACATAA GGCTAGCTACAACGA GTGTAACA 3520 UGUUACAC A UUAUGUUA 4230

3112 CTCTAACA GGCTAGCTACAACGA AATGTGTA 3521 UACACAUU A UGUUAGAG 4231

3114 CTCTCTAA GGCTAGCTACAACGA ATAATGTG 3522 CACAUUAU G UUAGAGAG 4232

3123 GCTCGCTA GGCTAGCTACAACGA CTCTCTAA 3523 UUAGAGAG G UAGCGAGC 4233

3126 GCAGCTCG GGCTAGCTACAACGA TACCTCTC 3524 GAGAGGUA G CGAGCUGC 4234

3130 CAGAGCAG GGCTAGCTACAACGA TCGCTACC 3525 GGUAGCGA G CUGCUCUG 4235

3133 TAGCAGAG GGCTAGCTACAACGA AGCTCGCT 3526 AGCGAGCU G CUCUGCUA 4236

3138 GGACATAG GGCTAGCTACAACGA AGAGCAGC 3527 GCUGCUCU G CUAUGUCC 4237

3141 TAAGGACA GGCTAGCTACAACGA AGCAGAGC 3528 GCUCUGCU A UGUCCUUA 4238

3143 CTTAAGGA GGCTAGCTACAACGA ATAGCAGA 3529 UCUGCUAU G UCCUUAAG 4239

3151 AATATTGG GGCTAGCTACAACGA TTAAGGAC 3530 GUCCUUAA G CCAAUAUU 4240

3155 AGTAAATA GGCTAGCTACAACGA TGGCTTAA 3531 UUAAGCCA A UAUUUACU 4241

3157 TGAGTAAA GGCTAGCTACAACGA ATTGGCTT 3532 AAGCCAAU A UUUACUCA 4242

3161 CTGATGAG GGCTAGCTACAACGA AAATATTG 3533 CAAUAUUU A CUCAUCAG 4243

3165 TGACCTGA GGCTAGCTACAACGA GAGTAAAT 3534 AUUUACUC A UCAGGUCA 4244

3170 AATAATGA GGCTAGCTACAACGA CTGATGAG 3535 CUCAUCAG G UCAUUAUU 4245

3173 AAAAATAA GGCTAGCTACAACGA GACCTGAT 3536 AUCAGGUC A UUAUUUUU 4246

3176 GTAAAAAA GGCTAGCTACAACGA AATGACCT 3537 AGGUCAUU A UUUUUUAC 4247

3183 GGCCATTG GGCTAGCTACAACGA AAAAAATA 3538 UAUUUUUU A CAAUGGCC 4248

3186 CATGGCCA GGCTAGCTACAACGA TGTAAAAA 3539 UUUUUACA A UGGCCAUG 4249

3189 TTCCATGG GGCTAGCTACAACGA CATTGTAA 3540 UUACAAUG G CCAUGGAA 4250

3192 TTATTCCA GGCTAGCTACAACGA GGCCATTG 3541 CAAUGGCC A UGGAAUAA 4251

3197 ATGGTTTA GGCTAGCTACAACGA TCCATGGC 3542 GCCAUGGA A UAAACCAU 4252

3201 AAAAATGG GGCTAGCTACAACGA TTATTCCA 3543 UGGAAUAA A CCAUUUUU 4253

3204 TGTAAAAA GGCTAGCTACAACGA GGTTTATT 3544 AAUAAACC A UUUUUACA 4254

Table 7

Table 7: Human PTP-IB Hairpin Ribozyme and Target Sequence

Nt. Ribozyme sequence Seq. ID Substrate Sequence Seq. ID Position Nos. Nos.

10 GCUCUA AGAA GCGU ACCAGAGAAACA X GUACAUUACCUGGUA 4255 ACGC GGCC TAGAGC 4331

23 UGCGCC AGAA GCCG ACCAGAGAAACA X GUACAUUACCUGGUA 4256 CGGC AGAC GGCGCA 4332

56 CAGGGC AGAA GCUG ACCAGAGAAACA X GUACAUUACCUGGUA 4257 CAGC AGCC GCCCTG 4333

59 GGCCAG AGAA GCUG ACCAGAGAAACA X GUACAUUACCUGGUA 4258 CAGC CGCC CTGGCC 4334

98 UUGUCG AGAA GCUC ACCAGAGAAACA X GUACAUUACCUGGUA 4259 GAGC AGAT CGACAA 4335

220 CAAAGG AGAA GACG ACCAGAGAAACA X GUACAUUACCUGGUA 4260 CGTC AGTC CCTTTG 4336

239 AGUUUA AGAA GACU ACCAGAGAAACA X GUACAUUACCUGGUA 4261 AGTC GGAT TAAACT 4337

612 UCCAAA AGAA GGCC ACCAGAGAAACA X GUACAUUACCUGGUA 4262 GGCC TGAC TTTGGA 4338

636 GAAUGA AGAA GGUG ACCAGAGAAACA X GUACAUUACCUGGUA 4263 CACC AGCC TCATTC 4339

685 GCUCCG AGAA GAGU ACCAGAGAAACA X GUACAUUACCUGGUA 4264 ACTC AGCC CGGAGC 4340

702 CACCAC AGAA GGCC ACCAGAGAAACA X GUACAUUACCUGGUA 4265 GGCC CGTT GTGGTG 4341

748 CAGCCA AGAA GAAG ACCAGAGAAACA X GUACAUUACCUGGUA 4266 CTTC TGTC TGGCTG 4342

763 GCAAGA AGAA GGUA ACCAGAGAAACA X GUACAUUACCUGGUA 4267 TACC TGCC TCTTGC 4343

773 UUGUCC AGAA GCAA ACCAGAGAAACA X GUACAUUACCUGGUA 4268 TTGC TGAT GGACAA 4344

801 GAUAUC AGAA GAAG ACCAGAGAAACA X GUACAUUACCUGGUA 4269 CTTC CGTT GATATC 4345

842 AGCCCC AGAA GAAA ACCAGAGAAACA X GUACAUUACCUGGUA 4270 TTTC GGAT GGGGCT 4346

851 GUCUGG AGAA GCCC ACCAGAGAAACA X GUACAUUACCUGGUA 4271 GGGC TGAT CCAGAC 4347

861 CUGGUC AGAA GUCU ACCAGAGAAACA X GUACAUUACCUGGUA 4272 AGAC AGCC GACCAG 4348

864 CAGCUG AGAA GCUG ACCAGAGAAACA X GUACAUUACCUGGUA 4273 CAGC CGAC CAGCTG 4349

869 AAGCGC AGAA GGUC ACCAGAGAAACA X GUACAUUACCUGGUA 4274 GACC AGCT GCGCTT 4350

1102 UGAUGG AGAA GUCU ACCAGAGAAACA X GUACAUUACCUGGUA 4275 AGAC TGCC CCATCA 4351

1224 UGGGGA AGAA GCCU ACCAGAGAAACA X GUACAUUACCUGGUA 4276 AGGC TGCC TCCCCA 4352

1253 UUCUCG AGAA GUGA ACCAGAGAAACA X GUACAUUACCUGGUA 4277 TCAC TGCC CGAGAA 4353

1323 CGUGAG AGAA GUAG ACCAGAGAAACA X GUACAUUACCUGGUA 4278 CTAC GGTC CTCACG 4354

1332 AGCGCC AGAA GUGA ACCAGAGAAACA X GUACAUUACCUGGUA 4279 TCAC GGCC GGCGCT 4355

1361 CUGUUG AGAA GGAA ACCAGAGAAACA X GUACAUUACCUGGUA 4280 TTCC TGTT CAACAG 4356

1383 AGGAGG AGAA GGCU ACCAGAGAAACA X GUACAUUACCUGGUA 4281 AGCC TGAC CCTCCT 4357

1412 GAGGCG AGAA GUGG ACCAGAGAAACA X GUACAUUACCUGGUA 4282 CCAC TGTC CGCCTC 4358

Table 7

1416 GGCAGA AGAA GACA ACCAGAGAAACA X GUACAUUACCUGGUA 4283 TGTC CGCC TCTGCC 4359

1422 UCUGCG AGAA GAGG ACCAGAGAAACA X GUACAUUACCUGGUA 4284 CCTC TGCC CGCAGA 4360

1441 CUGCUA AGAA GGCG ACCAGAGAAACA X GUACAUUACCUGGUA 4285 CGCC CGAC TAGCAG 4361

1460 CUUACC AGAA GCGG ACCAGAGAAACA X GUACAUUACCUGGUA 4286 CCGC GGTA GGTAAG 4362

1473 CGGUCC AGAA GCCC ACCAGAGAAACA X GUACAUUACCUGGUA 4287 GGGC CGCC GGACCG 4363

1477 UACGCG AGAA GGCG ACCAGAGAAACA X GUACAUUACCUGGUA 4288 CGCC GGAC CGCGTA 4364

1501 ACGUCC AGAA GGGG ACCAGAGAAACA X GUACAUUACCUGGUA 4289 CCCC GGAC GGACGT 4365

1505 ACCAAC AGAA GUCC ACCAGAGAAACA X GUACAUUACCUGGUA 4290 GGAC GGAC GTTGGT 4366

1539 ACACAC AGAA GGGG ACCAGAGAAACA X GUACAUUACCUGGUA 4291 CCCC GGAT GTGTGT 4367

1670 CCCCAA AGAA GGUG ACCAGAGAAACA X GUACAUUACCUGGUA 4292 CACC CGTC TTGGGG 4368

1735 GGGGGG AGAA GUCU ACCAGAGAAACA X GUACAUUACCUGGUA 4293 AGAC AGCC CCCCCC 4369

1864 AUGCAA AGAA GACA ACCAGAGAAACA X GUACAUUACCUGGUA 4294 TGTC AGCC TTGCAT 4370

1946 UGACGC AGAA GGCC ACCAGAGAAACA X GUACAUUACCUGGUA 4295 GGCC TGCT GCGTCA 4371

1955 GUACUG AGAA GACG ACCAGAGAAACA X GUACAUUACCUGGUA 4296 CGTC AGAC CAGTAC 4372

1960 UCCCAG AGAA GGUC ACCAGAGAAACA X GUACAUUACCUGGUA 4297 GACC AGTA CTGGGA 4373

1978 GCUUAC AGAA GUCC ACCAGAGAAACA X GUACAUUACCUGGUA 4298 GGAC GGTT GTAAGC 4374

1988 AAUAAC AGAA GCUU ACCAGAGAAACA X GUACAUUACCUGGUA 4299 AAGC AGTT GTTATT 4375

2098 AGAAUA AGAA GGAC ACCAGAGAAACA X GUACAUUACCUGGUA 4300 GTCC CGCT TATTCT 4376

2107 ACAGGG AGAA GAAU ACCAGAGAAACA X GUACAUUACCUGGUA 4301 ATTC TGCT CCCTGT 4377

2144 CGGGGG AGAA GUGA ACCAGAGAAACA X GUACAUUACCUGGUA 4302 TCAC TGCT CCCCCG 4378

2190 UUUUUC AGAA GGAC ACCAGAGAAACA X GUACAUUACCUGGUA 4303 GTCC TGAT GAAAAA 4379

2230 UUAGUA AGAA GAGA ACCAGAGAAACA X GUACAUUACCUGGUA 4304 TCTC TGCT TACTAA 4380

2264 UGCACA AGAA GGUU ACCAGAGAAACA X GUACAUUACCUGGUA 4305 AACC TGCC TGTGCA 4381

2279 GUAAUG AGAA GGUC ACCAGAGAAACA X GUACAUUACCUGGUA 4306 GACC TGAT CATTAC 4382

2309 UUCAGC AGAA GGCU ACCAGAGAAACA X GUACAUUACCUGGUA 4307 AGCC TGTT GCTGAA 4383

2345 CUGGAA AGAA GCAC ACCAGAGAAACA X GUACAUUACCUGGUA 4308 GTGC AGTT TTCCAG 4384

2412 AGGACA AGAA GGGC ACCAGAGAAACA X GUACAUUACCUGGUA 4309 GCCC AGCC TGTCCT 4385

2416 UACCAG AGAA GGCU ACCAGAGAAACA X GUACAUUACCUGGUA 4310 AGCC TGTC CTGGTA - 4386

2524 GUGGGG AGAA GGGG ACCAGAGAAACA X GUACAUUACCUGGUA 4311 CCCC CGCC CCCCAC 4387

2544 GGCGGA AGAA GAUC ACCAGAGAAACA X GUACAUUACCUGGUA 4312 GATC AGCC TCCGCC 4388

2580 AUCACG AGAA GCUC ACCAGAGAAACA X GUACAUUACCUGGUA 4313 GAGC AGAC CGTGAT 4389

Table 7

2606 GUUUCC AGAA GGUG ACCAGAGAAACA X GUACAUUACCUGGUA 4314 CACC TGCT GGAAAC 4390

2631 CACCCA AGAA GUUU ACCAGAGAAACA X GUACAUUACCUGGUA 4315 AAAC AGCC TGGGTG 4391

2643 CUAAAG AGAA GUCA ACCAGAGAAACA X GUACAUUACCUGGUA 4316 TGAC GGTC CTTTAG 4392

2655 GCGGCA AGAA GCCU ACCAGAGAAACA X GUACAUUACCUGGUA 4317 AGGC AGCC TGCCGC 4393

2659 GACGGC AGAA GGCU ACCAGAGAAACA X GUACAUUACCUGGUA 4318 AGCC TGCC GCCGTC 4394

2662 AGAGAC AGAA GCAG ACCAGAGAAACA X GUACAUUACCUGGUA 4319 CTGC CGCC GTCTCT 4395

2665 GACAGA AGAA GCGG ACCAGAGAAACA X GUACAUUACCUGGUA 4320 CCGC CGTC TCTGTC 4396

2671 AACCGG AGAA GAGA ACCAGAGAAACA X GUACAUUACCUGGUA 4321 TCTC TGTC CCGGTT 4397

2677 AAGGUG AGAA GGGA ACCAGAGAAACA X GUACAUUACCUGGUA 4322 TCCC GGTT CACCTT 4398

2704 GGGUGG AGAA GACG ACCAGAGAAACA X GUACAUUACCUGGUA 4323 CGTC TGCC CCACCC 4399

2731 AGCACC AGAA GGCC ACCAGAGAAACA X GUACAUUACCUGGUA 4324 GGCC TGAT GGTGCT 4400

2810 AGCUAC AGAA GCCG ACCAGAGAAACA X GUACAUUACCUGGUA 4325 CGGC AGCT GTAGCT 4401

2813 GGGAGC AGAA GCUG ACCAGAGAAACA X GUACAUUACCUGGUA 4326 CAGC TGTA GCTCCC 4402

2876 UCUCUG AGAA GGCU ACCAGAGAAACA X GUACAUUACCUGGUA 4327 AGCC AGTA CAGAGA 4403

2999 UACAUA AGAA GGAC ACCAGAGAAACA X GUACAUUACCUGGUA 4328 GTCC TGTA TATGTA 4404

3085 AGAGCC AGAA GCUC ACCAGAGAAACA X GUACAUUACCUGGUA 4329 GAGC AGCT GGCTCT 4405

3132 UAGCAG AGAA GCUC ACCAGAGAAACA X GUACAUUACCUGGUA 4330 GAGC TGCT CTGCTA 4406

Table 8

Table 8: Anti Human PTP-IB HH, NCH, and G Cleaver Ribozymes

Table 9

Table 9: Human methionine aminopeptidase type 2 (Met AP-2) Hammerhead Ribozyme and Target Sequence

Table 9

528 CUUCUCGA CUGAUGAG X CGAA AAUCAUUC 43 GAATGATT T TCGAGAAG 455

529 GCUUCUCG CUGAUGAG X CGAA AAAUCAUU 44 AATGATTT T CGAGAAGC 456

530 AGCUUCUC CUGAUGAG X CGAA AAAAUCAU 45 ATGATTTT c GAGAAGCT 457

551 AACUUGUC CUGAUGAG X CGAA AUGUGCUU 46 AAGCACAT c GACAAGTT 458

559 UAUUUUCU CUGAUGAG X CGAA ACUUGUCG 47 CGACAAGT T AGAAAATA 459

560 GUAUUUUC CUGAUGAG X CGAA AACUUGUC 48 GACAAGTT A GAAAATAC 460

567 UCAUUACG CUGAUGAG X CGAA AUUUUCUA 49 TAGAAAAT A CGTAATGA 461

571 CAGCUCAU CUGAUGAG X CGAA ACGUAUUU 50 AAATACGT A ATGAGCTG 462

583 CCAGGCUU CUGAUGAG X CGAA AUCCAGCU 51 AGCTGGAT C AAGCCTGG 463

604 CAGAUUUC CUGAUGAG X CGAA AUCAUUGU 52 ACAATGAT A GAAATCTG 464

610 UUUUCACA CUGAUGAG X CGAA AUUUCUAU 53 ATAGAAAT C TGTGAAAA 465

621 AGUCUUCC CUGAUGAG X CGAA ACUUUUCA 54 TGAAAAGT T GGAAGACT 466

632 CUUGCGUG CUGAUGAG X CGAA ACAGUCUU 55 AAGACTGT T CACGCAAG 467

633 ACUUGCGU CUGAUGAG X CGAA AACAGUCU 56 AGACTGTT C ACGCAAGT 468

642 CUUUUAUU CUGAUGAG X CGAA ACUUGCGU 57 ACGCAAGT T AATAAAAG 469

643 UCUUUUAU CUGAUGAG X CGAA AACUUGCG 58 CGCAAGTT A ATAAAAGA 470

646 UUCUCUUU CUGAUGAG X CGAA AUUAACUU 59 AAGTTAAT A AAAGAGAA 471

660 CUGCAUUU CUGAUGAG X CGAA AUCCAUUC 60 GAATGGAT T AAATGCAG 472

661 CCUGCAUU CUGAUGAG X CGAA AAUCCAUU 61 AATGGATT A AATGCAGG 473

678 CAGUAGGA CUGAUGAG X CGAA AUGCCAGG 62 CCTGGCAT T TCCTACTG 474

679 CCAGUAGG CUGAUGAG X CGAA AAUGCCAG 63 CTGGCATT T CCTACTGG 475

680 UCCAGUAG CUGAUGAG X CGAA AAAUGCCA 64 TGGCATTT c CTACTGGA 476

683 ACAUCCAG CUGAUGAG X CGAA AGGAAAUG 65 CATTTCCT A CTGGATGT 477

692 AUUGAGAG CUGAUGAG X CGAA ACAUCCAG 66 CTGGATGT T CTCTCAAT 478

693 UAUUGAGA CUGAUGAG X CGAA AACAUCCA 67 TGGATGTT C TCTCAATA 479

695 AUUAUUGA CUGAUGAG X CGAA AGAACAUC 68 GATGTTCT C TCAATAAT 480

697 CAAUUAUU CUGAUGAG X CGAA AGAGAACA 69 TGTTCTCT C AATAATTG 481

701 AGCACAAU CUGAUGAG X CGAA AUUGAGAG 70 CTCTCAAT A ATTGTGCT 482

704 GGCAGCAC CUGAUGAG X CGAA AUUAUUGA 71 TCAATAAT T GTGCTGCC 483

716 GGGAGUAU CUGAUGAG X CGAA AUGGGCAG 72 CTGCCCAT T ATACTCCC 484

717 UGGGAGUA CUGAUGAG X CGAA AAUGGGCA 73 TGCCCATT A TACTCCCA 485

719 AUUGGGAG CUGAUGAG X CGAA AUAAUGGG 74 CCCATTAT A CTCCCAAT 486

722 GGCAUUGG CUGAUGAG X CGAA AGUAUAAU 75 ATTATACT C CCAATGCC 487

745 UACUGUAA CUGAUGAG X CGAA ACUGUUGU 76 ACAACAGT A TTACAGTA 488

747 CAUACUGU CUGAUGAG X CGAA AUACUGUU 77 AACAGTAT T ACAGTATG 489

748 UCAUACUG CUGAUGAG X CGAA AAUACUGU 78 ACAGTATT A CAGTATGA 490

753 UGUCAUCA CUGAUGAG X CGAA ACUGUAAU 79 ATTACAGT A TGATGACA 491

763 AUUUUACA CUGAUGAG X CGAA AUGUCAUC 80 GATGACAT C TGTAAAAT 492

767 GUCUAUUU CUGAUGAG X CGAA ACAGAUGU 81 ACATCTGT A AAATAGAC 493

772 CCAAAGUC CUGAUGAG X CGAA AUUUUACA 82 TGTAAAAT A GACTTTGG 494

777 GUGUUCCA CUGAUGAG X CGAA AGUCUAUU 83 AATAGACT T TGGAACAC 495

778 UGUGUUCC CUGAUGAG X CGAA AAGUCUAU 84 ATAGACTT T GGAACACA 496

788 ACCACUUA CUGAUGAG X CGAA AUGUGUUC 85 GAACACAT A TAAGTGGT 497

790 CUACCACU CUGAUGAG X CGAA AUAUGUGU 86 ACACATAT A AGTGGTAG 498

797 AAUAAUCC CUGAUGAG X CGAA ACCACUUA 87 TAAGTGGT A GGATTATT 499

802 CAGUCAAU CUGAUGAG X CGAA AUCCUACC 88 GGTAGGAT T ATTGACTG 500

803 ACAGUCAA CUGAUGAG X CGAA AAUCCUAC 89 GTAGGATT A TTGACTGT 501 Table 9

805 GCACAGUC CUGAUGAG X CGAA AUAAUCCU 90 AGGATTAT T GACTGTGC 502

815 GACAGUAA CUGAUGAG X CGAA AGCACAGU 91 ACTGTGCT T TTACTGTC 503

816 UGACAGUA CUGAUGAG X CGAA AAGCACAG 92 CTGTGCTT T TACTGTCA 504

817 GUGACAGU CUGAUGAG X CGAA AAAGCACA 93 TGTGCTTT T ACTGTCAC 505

818 AGUGACAG CUGAUGAG X CGAA AAAAGCAC 94 GTGCTTTT A CTGTCACT 506

823 UUAAAAGU CUGAUGAG X CGAA ACAGUAAA 95 TTTACTGT C ACTTTTAA 507

827 GGGAUUAA CUGAUGAG X CGAA AGUGACAG 96 CTGTCACT T TTAATCCC 508

828 UGGGAUUA CUGAUGAG X CGAA AAGUGACA 97 TGTCACTT T TAATCCCA 509

829 UUGGGAUU CUGAUGAG X CGAA AAAGUGAC 98 GTCACTTT T AATCCCAA 510

830 UUUGGGAU CUGAUGAG X CGAA AAAAGUGA 99 TCACTTTT A ATCCCAAA 511

833 AUAUUUGG CUGAUGAG X CGAA AUUAAAAG 100 CTTTTAAT C CCAAATAT 512

840 ACGUAUCA CUGAUGAG X CGAA AUUUGGGA 101 TCCCAAAT A TGATACGT 513

845 UAAUAACG CUGAUGAG X CGAA AUCAUAUU 102 AATATGAT A CGTTATTA 514

849 CUUUUAAU CUGAUGAG X CGAA ACGUAUCA 103 TGATACGT T ATTAAAAG 515

850 GCUUUUAA CUGAUGAG X CGAA AACGUAUC 104 GATACGTT A TTAAAAGC 516

852 CAGCUUUU CUGAUGAG X CGAA AUAACGUA 105 TACGTTAT T AAAAGCTG 517

853 ACAGCUUU CUGAUGAG X CGAA AAUAACGU 106 ACGTTATT A AAAGCTGT 518

862 GCAUCUUU CUGAUGAG X CGAA ACAGCUUU 107 AAAGCTGT A AAAGATGC 519

872 AGUGUUAG CUGAUGAG X CGAA AGCAUCUU 108 AAGATGCT A CTAACACT 520

875 UCCAGUGU CUGAUGAG X CGAA AGUAGCAU 109 ATGCTACT A ACACTGGA 521

886 GCACACUU CUGAUGAG X CGAA AUUCCAGU 110 ACTGGAAT A AAGTGTGC 522

901 CGAACAUC CUGAUGAG X CGAA AUUCCAGC 111 GCTGGAAT T GATGTTCG 523

907 CACAGACG CUGAUGAG X CGAA ACAUCAAU 112 ATTGATGT T CGTCTGTG 524

908 ACACAGAC CUGAUGAG X CGAA AACAUCAA 113 TTGATGTT C GTCTGTGT 525

911 AUCACACA CUGAUGAG X CGAA ACGAACAU 114 ATGTTCGT C TGTGTGAT 526

922 GCCUCACC CUGAUGAG X CGAA ACAUCACA 115 TGTGATGT T GGTGAGGC 527

934 ACUUCUUG CUGAUGAG X CGAA AUGGCCUC 116 GAGGCCAT C CAAGAAGT 528

943 GACUCCAU CUGAUGAG X CGAA ACUUCUUG 117 CAAGAAGT T ATGGAGTC 529

944 GGACUCCA CUGAUGAG X CGAA AACUUCUU 118 AAGAAGTT A TGGAGTCC 530

951 CUUCAUAG CUGAUGAG X CGAA ACUCCAUA 119 TATGGAGT C CTATGAAG 531

954 CAACUUCA CUGAUGAG X CGAA AGGACUCC 120 GGAGTCCT A TGAAGTTG 532

961 UCUAUUUC CUGAUGAG X CGAA ACUUCAUA 121 TATGAAGT T GAAATAGA 533

967 UUCCCAUC CUGAUGAG X CGAA AUUUCAAC 122 GTTGAAAT A GATGGGAA 534

981 UCACUUGA CUGAUGAG X CGAA AUGUCUUC 123 GAAGACAT A TCAAGTGA 535

983 UUUCACUU CUGAUGAG X CGAA AUAUGUCU 124 AGACATAT C AAGTGAAA 536

997 AGAUUACG CUGAUGAG X CGAA AUUGGUUU 125 AAACCAAT C CGTAATCT 537

1001 AUUUAGAU CUGAUGAG X CGAA ACGGAUUG 126 CAATCCGT A ATCTAAAT 538

1004 UCCAUUUA CUGAUGAG X CGAA AUUACGGA 127 TCCGTAAT C TAAATGGA 539

1006 UGUCCAUU CUGAUGAG X CGAA AGAUUACG 128 CGTAATCT A AATGGACA 540

1016 CCCAAUUG CUGAUGAG X CGAA AUGUCCAU 129 ATGGACAT T CAATTGGG 541

1017 GCCCAAUU CUGAUGAG X CGAA AAUGUCCA 130 TGGACATT C AATTGGGC 542

1021 UAUUGCCC CUGAUGAG X CGAA AUUGAAUG 131 CATTCAAT T GGGCAATA 543

1029 GUAUUCUA CUGAUGAG X CGAA AUUGCCCA 132 TGGGCAAT A TAGAATAC 544

1031 AUGUAUUC CUGAUGAG X CGAA AUAUUGCC 133 GGCAATAT A GAATACAT 545

1036 CCAGCAUG CUGAUGAG X CGAA AUUCUAUA 134 TATAGAAT A CATGCTGG 546

1060 CCUUUCAC CUGAUGAG X CGAA AUCGGCAC 135 GTGCCGAT T GTGAAAGG 547

1102 AUUGCAUA CUGAUGAG X CGAA ACUUCUCC 136 GGAGAAGT A TATGCAAT 548 Table 9

1104 CAAUUGCA CUGAUGAG X CGAA AUACUUCU 137 AGAAGTAT A TGCAATTG 549 llll AAGGUUUC CUGAUGAG X CGAA AUUGCAUA 138 TATGCAAT T GAAACCTT 550

1119 UACUACCA CUGAUGAG X CGAA AGGUUUCA 139 TGAAACCT T TGGTAGTA 551

1120 GUACUACC CUGAUGAG X CGAA AAGGUUUC 140 GAAACCTT T GGTAGTAC 552

1124 UCCUGUAC CUGAUGAG X CGAA ACCAAAGG 141 CCTTTGGT A GTACAGGA 553

1127 UUUUCCUG CUGAUGAG X CGAA ACUACCAA 142 TTGGTAGT A CAGGAAAA 554

1141 UCAUGAAC CUGAUGAG X CGAA ACACCUUU 143 AAAGGTGT T GTTCATGA 555

1144 UCAUCAUG CUGAUGAG X CGAA ACAACACC 144 GGTGTTGT T CATGATGA 556

1145 AUCAUCAU CUGAUGAG X CGAA AACAACAC 145 GTGTTGTT C ATGATGAT 557

1154 ACAUUCCA CUGAUGAG X CGAA AUCAUCAU 146 ATGATGAT A TGGAATGT 558

1163 GUAAUGUG CUGAUGAG X CGAA ACAUUCCA 147 TGGAATGT T CACATTAC 559

1164 UGUAAUGU CUGAUGAG X CGAA AACAUUCC 148 GGAATGTT C ACATTACA 560

1169 UUUCAUGU CUGAUGAG X CGAA AUGUGAAC 149 GTTCACAT T ACATGAAA 561

1170 UUUUCAUG CUGAUGAG X CGAA AAUGUGAA 150 TTCACATT A CATGAAAA 562

1181 AACAUCAA CUGAUGAG X CGAA AUUUUUCA 151 TGAAAAAT T TTGATGTT 563

1182 CAACAUCA CUGAUGAG X CGAA AAUUUUUC 152 GAAAAATT T TGATGTTG 564

1183 CCAACAUC CUGAUGAG X CGAA AAAUUUUU 153 AAAAATTT T GATGTTGG 565

1189 ACAUGUCC CUGAUGAG X CGAA ACAUCAAA 154 TTTGATGT T GGACATGT 566

1204 GGAAGCCU CUGAUGAG X CGAA AUUGGCAC 155 GTGCCAAT A AGGCTTCC 567

1210 GUUCUUGG CUGAUGAG X CGAA AGCCUUAU 156 ATAAGGCT T CCAAGAAC 568

1211 UGUUCUUG CUGAUGAG X CGAA AAGCCUUA 157 TAAGGCTT C CAAGAACA 569

1227 CAUUUAAC CUGAUGAG X CGAA AGUGUUUU 158 AAAACACT T GTTAAATG 570

1230 UGACAUUU CUGAUGAG X CGAA ACAAGUGU 159 ACACTTGT T AAATGTCA 571

1231 AUGACAUU CUGAUGAG X CGAA AACAAGUG 160 CACTTGTT A AATGTCAT 572

1237 UCAUUGAU CUGAUGAG X CGAA ACAUUUAA 161 TTAAATGT C ATCAATGA 573

1240 UUUUCAUU CUGAUGAG X CGAA AUGACAUU 162 AATGTCAT C AATGAAAA 574

1251 GGGUUCCA CUGAUGAG X CGAA AGUUUUCA 163 TGAAAACT T TGGAACCC 575

1252 AGGGUUCC CUGAUGAG X CGAA AAGUUUUC 164 GAAAACTT T GGAACCCT 576

1261 CAGAAGGC CUGAUGAG X CGAA AGGGUUCC 165 GGAACCCT T GCCTTCTG 577

1266 UGCGGCAG CUGAUGAG X CGAA AGGCAAGG 166 CCTTGCCT T CTGCCGCA 578

1267 CUGCGGCA CUGAUGAG X CGAA AAGGCAAG 167 CTTGCCTT c TGCCGCAG 579

1286 UCCCAAGC CUGAUGAG X CGAA AUCCAGCC 168 GGCTGGAT c GCTTGGGA 580

1290 UUUCUCCC CUGAUGAG X CGAA AGCGAUCC 169 GGATCGCT T GGGAGAAA 581

1301 CAAGUAUU CUGAUGAG X CGAA ACUUUCUC 170 GAGAAAGT A AATACTTG 582

1305 CCAUCAAG CUGAUGAG X CGAA AUUUACUU 171 AAGTAAAT A CTTGATGG 583

1308 GAGCCAUC CUGAUGAG X CGAA AGUAUUUA 172 TAAATACT T GATGGCTC 584

1316 AUUCUUCA CUGAUGAG X CGAA AGCCAUCA 173 TGATGGCT c TGAAGAAT 585

1325 GUCACACA CUGAUGAG X CGAA AUUCUUCA 174 TGAAGAAT c TGTGTGAC 586

1335 CAAUGCCC CUGAUGAG X CGAA AGUCACAC 175 GTGTGACT T GGGCATTG 587

1342 GGAUCUAC CUGAUGAG X CGAA AUGCCCAA 176 TTGGGCAT T GTAGATCC 588

1345 UAUGGAUC CUGAUGAG X CGAA ACAAUGCC 177 GGCATTGT A GATCCATA 589

1349 UGGAUAUG CUGAUGAG X CGAA AUCUACAA 178 TTGTAGAT C CATATCCA 590

1353 AUGGUGGA CUGAUGAG X CGAA AUGGAUCU 179 AGATCCAT A TCCACCAT 591

1355 UAAUGGUG CUGAUGAG X CGAA AUAUGGAU 180 ATCCATAT C CACCATTA 592

1362 UGUCACAU CUGAUGAG X CGAA AUGGUGGA 181 TCCACCAT T ATGTGACA 593

1363 AUGUCACA CUGAUGAG X CGAA AAUGGUGG 182 CCACCATT A TGTGACAT 594

1372 GAUCCUUU CUGAUGAG X CGAA AUGUCACA 183 TGTGACAT T AAAGGATC 595 Table 9

1373 UGAUCCUU CUGAUGAG X CGAA AAUGUCAC 184 GTGACATT A AAGGATCA 596

1380 CUGUAUAU CUGAUGAG X CGAA AUCCUUUA 185 TAAAGGAT C ATATACAG 597

1383 GCGCUGUA CUGAUGAG X CGAA AUGAUCCU 186 AGGATCAT A TACAGCGC 598

1385 UUGCGCUG CUGAUGAG X CGAA AUAUGAUC 187 GATCATAT A CAGCGCAA 599

1395 UAUGUUCA CUGAUGAG X CGAA AUUGCGCU 188 AGCGCAAT T TGAACATA 600

1396 GUAUGUUC CUGAUGAG X CGAA AAUUGCGC 189 GCGCAATT T GAACATAC 601

1403 CAGGAUGG CUGAUGAG X CGAA AUGUUCAA 190 TTGAACAT A CCATCCTG 602

1408 CGCAACAG CUGAUGAG X CGAA AUGGUAUG 191 CATACCAT C CTGTTGCG 603

1413 UUGGACGC CUGAUGAG X CGAA ACAGGAUG 192 CATCCTGT T GCGTCCAA 604

1418 ACAUGUUG CUGAUGAG X CGAA ACGCAACA 193 TGTTGCGT C CAACATGT 605

1427 AACUUCUU CUGAUGAG X CGAA ACAUGUUG 194 CAACATGT A AAGAAGTT 606

1435 CUGCUGAC CUGAUGAG X CGAA ACUUCUUU 195 AAAGAAGT T GTCAGCAG 607

1438 CCUCUGCU CUGAUGAG X CGAA ACAACUUC 196 GAAGTTGT C AGCAGAGG 608

1455 AAGUUUAA CUGAUGAG X CGAA AGUCAUCU 197 AGATGACT A TTAAACTT 609

1457 CUAAGUUU CUGAUGAG X CGAA AUAGUCAU 198 ATGACTAT T AAACTTAG 610

1458 ACUAAGUU CUGAUGAG X CGAA AAUAGUCA 199 TGACTATT A AACTTAGT 611

1463 UUUGGACU CUGAUGAG X CGAA AGUUUAAU 200 ATTAAACT T AGTCCAAA 612

1464 CUUUGGAC CUGAUGAG X CGAA AAGUUUAA 201 TTAAACTT A GTCCAAAG 613

1467 UGGCUUUG CUGAUGAG X CGAA ACUAAGUU 202 AACTTAGT C CAAAGCCA 614

1479 AAGGUGUU CUGAUGAG X CGAA AGGUGGCU 203 AGCCACCT C AACACCTT 615

1487 AGAAAAUA CUGAUGAG X CGAA AGGUGUUG 204 CAACACCT T TATTTTCT 616

1488 CAGAAAAU CUGAUGAG X CGAA AAGGUGUU 205 AACACCTT T ATTTTCTG 617

1489 UCAGAAAA CUGAUGAG X CGAA AAAGGUGU 206 ACACCTTT A TTTTCTGA 618

1491 GCUCAGAA CUGAUGAG X CGAA AUAAAGGU 207 ACCTTTAT T TTCTGAGC 619

1492 AGCUCAGA CUGAUGAG X CGAA AAUAAAGG 208 CCTTTATT T TCTGAGCT 620

1493 AAGCUCAG CUGAUGAG X CGAA AAAUAAAG 209 CTTTATTT T CTGAGCTT 621

1494 AAAGCUCA CUGAUGAG X CGAA AAAAUAAA 210 TTTATTTT C TGAGCTTT 622

1501 UUCCAACA CUGAUGAG X CGAA AGCUCAGA 211 TCTGAGCT T TGTTGGAA 623

1502 UUUCCAAC CUGAUGAG X CGAA AAGCUCAG 212 CTGAGCTT T GTTGGAAA 624

1505 UGUUUUCC CUGAUGAG X CGAA ACAAAGCU 213 AGCTTTGT T GGAAAACA 625

1518 AAUUCUGG CUGAUGAG X CGAA AUCAUGUU 214 AACATGAT A CCAGAATT 626

1526 GGCAAAUU CUGAUGAG X CGAA AUUCUGGU 215 ACCAGAAT T AATTTGCC 627

1527 UGGCAAAU CUGAUGAG X CGAA AAUUCUGG 216 CCAGAATT A ATTTGCCA 628

1530 AUGUGGCA CUGAUGAG X CGAA AUUAAUUC 217 GAATTAAT T TGCCACAT 629

1531 CAUGUGGC CUGAUGAG X CGAA AAUUAAUU 218 AATTAATT T GCCACATG 630

1541 AAACAGAC CUGAUGAG X CGAA ACAUGUGG 219. CCACATGT T GTCTGTTT 631

1544 UUAAAACA CUGAUGAG X CGAA ACAACAUG 220 CATGTTGT c TGTTTTAA 632

1548 ACUGUUAA CUGAUGAG X CGAA ACAGACAA 221 TTGTCTGT T TTAACAGT 633

1549 CACUGUUA CUGAUGAG X CGAA AACAGACA 222 TGTCTGTT T TAACAGTG 634

1550 CCACUGUU CUGAUGAG X CGAA AAACAGAC 223 GTCTGTTT T AACAGTGG 635

1551 UCCACUGU CUGAUGAG X CGAA AAAACAGA 224 TCTGTTTT A ACAGTGGA 636

1567 AAAAGUAU CUGAUGAG X CGAA ACAUGGGU 225 ACCCATGT A ATACTTTT 637

1570 GAUAAAAG CUGAUGAG X CGAA AUUACAUG 226 CATGTAAT A CTTTTATC 638

1573 AUGGAUAA CUGAUGAG X CGAA AGUAUUAC 227 GTAATACT T TTATCCAT 639

1574 CAUGGAUA CUGAUGAG X CGAA AAGUAUUA 228 TAATACTT T TATCCATG 640

1575 ACAUGGAU CUGAUGAG X CGAA AAAGUAUU 229 AATACTTT T ATCCATGT 641

1576 AACAUGGA CUGAUGAG X CGAA AAAAGUAU 230 ATACTTTT A TCCATGTT 642 Table 9

1578 UAAACAUG CUGAUGAG X CGAA AUAAAAGU 231 ACTTTTAT C CATGTTTA 643

1584 CUUUUUUA CUGAUGAG X CGAA ACAUGGAU 232 ATCCATGT T TAAAAAAG 644

1585 UCUUUUUU CUGAUGAG X CGAA AACAUGGA 233 TCCATGTT T AAAAAAGA 645

1586 UUCUUUUU CUGAUGAG X CGAA AAACAUGG 234 CCATGTTT A AAAAAGAA 646

1600 UUUGUCCA CUGAUGAG X CGAA AUUCCUUC 235 GAAGGAAT T TGGACAAA 647

1601 CUUUGUCC CUGAUGAG X CGAA AAUUCCUU 236 AAGGAATT T GGACAAAG 648

1619 UUACAUUA CUGAUGAG X CGAA ACGGUUUG 237 CAAACCGT C TAATGTAA 649

1621 AAUUACAU CUGAUGAG X CGAA AGACGGUU 238 AACCGTCT A ATGTAATT 650

1626 UGGUUAAU CUGAUGAG X CGAA ACAUUAGA 239 TCTAATGT A ATTAACCA 651

1629 CGUUGGUU CUGAUGAG X CGAA AUUACAUU 240 AATGTAAT T AACCAACG 652

1630 UCGUUGGU CUGAUGAG X CGAA AAUUACAU 241 ATGTAATT A ACCAACGA 653

1646 AGUCCGGA CUGAUGAG X CGAA AGCUUUUU 242 AAAAAGCT T TCCGGACT 654

1647 AAGUCCGG CUGAUGAG X CGAA AAGCUUUU 243 AAAAGCTT T CCGGACTT 655

, 1648 AAAGUCCG CUGAUGAG X CGAA AAAGCUUU 244 AAAGCTTT c CGGACTTT 656

1655 GCAUUUAA CUGAUGAG X CGAA AGUCCGGA 245 TCCGGACT T TTAAATGC 657

1656 AGCAUUUA CUGAUGAG X CGAA AAGUCCGG 246 CCGGACTT T TAAATGCT 658

1657 UAGCAUUU CUGAUGAG X CGAA AAAGUCCG 247 CGGACTTT T AAATGCTA 659

1658 UUAGCAUU CUGAUGAG X CGAA AAAAGUCC 248 GGACTTTT A AATGCTAA 660

1665 AAAACAGU CUGAUGAG X CGAA AGCAUUUA 249 TAAATGCT A ACTGTTTT 661

1671 AGGGGAAA CUGAUGAG X CGAA ACAGUUAG 250 CTAACTGT T TTTCCCCT 662

1672 AAGGGGAA CUGAUGAG X CGAA AACAGUUA 251 TAACTGTT T TTCCCCTT 663

1673 GAAGGGGA CUGAUGAG X CGAA AAACAGUU 252 AACTGTTT T TCCCCTTC 664

1674 GGAAGGGG CUGAUGAG X CGAA AAAACAGU 253 ACTGTTTT T CCCCTTCC 665

1675 AGGAAGGG CUGAUGAG X CGAA AAAAACAG 254 CTGTTTTT c CCCTTCCT 666

1680 UAGACAGG CUGAUGAG X CGAA AGGGGAAA 255 TTTCCCCT T CCTGTCTA 667

1681 CUAGACAG CUGAUGAG X CGAA AAGGGGAA 256 TTCCCCTT c CTGTCTAG 668

1686 UUUUCCUA CUGAUGAG X CGAA ACAGGAAG 257 CTTCCTGT c TAGGAAAA 669

1688 CAUUUUCC CUGAUGAG X CGAA AGACAGGA 258 TCCTGTCT A GGAAAATG 670

1699 GAGCUUUA CUGAUGAG X CGAA AGCAUUUU 259 AAAATGCT A TAAAGCTC 671

1701 UUGAGCUU CUGAUGAG X CGAA AUAGCAUU 260 AATGCTAT A AAGCTCAA 672

1707 ACUAAUUU CUGAUGAG X CGAA AGCUUUAU 261 ATAAAGCT C AAATTAGT 673

1712 UCCUAACU CUGAUGAG X CGAA AUUUGAGC 262 GCTCAAAT T AGTTAGGA 674

1713 UUCCUAAC CUGAUGAG X CGAA AAUUUGAG 263 CTCAAATT A GTTAGGAA 675

1716 UCAUUCCU CUGAUGAG X CGAA ACUAAUUU 264 AAATTAGT T AGGAATGA 676

1717. GUCAUUCC CUGAUGAG X CGAA AACUAAUU 265 AATTAGTT A GGAATGAC 677

1727 AAACGUAU CUGAUGAG X CGAA AGUCAUUC 266 GAATGACT T ATACGTTT 678

1728 AAAACGUA CUGAUGAG X CGAA AAGUCAUU 267 AATGACTT A TACGTTTT 679

1730 ACAAAACG CUGAUGAG X CGAA AUAAGUCA 268 TGACTTAT A CGTTTTGT 680

1734 CAAAACAA CUGAUGAG X CGAA ACGUAUAA 269 TTATACGT T TTGTTTTG 681

1735 UCAAAACA CUGAUGAG X CGAA AACGUAUA 270 TATACGTT T TGTTTTGA 682

1736 UUCAAAAC CUGAUGAG X CGAA AAACGUAU 271 "^~ ATACGTTT T GTTTTGAA 683

1739 GUAUUCAA CUGAUGAG X CGAA ACAAAACG 272 CGTTTTGT T TTGAATAC 684

1740 GGUAUUCA CUGAUGAG X CGAA AACAAAAC 273 GTTTTGTT T TGAATACC 685

1741 AGGUAUUC CUGAUGAG X CGAA AAACAAAA 274 TTTTGTTT T GAATACCT 686

1746 CUCUUAGG CUGAUGAG X CGAA AUUCAAAA 275 TTTTGAAT A CCTAAGAG 687

1750 GUAUCUCU CUGAUGAG X CGAA AGGUAUUC 276 GAATACCT A AGAGATAC 688

1757 CCAAAAAG CUGAUGAG X CGAA AUCUCUUA 277 TAAGAGAT A CTTTTTGG 689 Table 9

1760 UAUCCAAA CUGAUGAG X CGAA AGUAUCUC 278 GAGATACT T TTTGGATA 690

1761 AUAUCCAA CUGAUGAG X CGAA AAGUAUCU 279 AGATACTT T TTGGATAT 691

1762 AAUAUCCA CUGAUGAG X CGAA AAAGUAUC 280 GATACTTT T TGGATATT 692

1763 AAAUAUCC CUGAUGAG X CGAA AAAAGUAU 281 ATACTTTT T GGATATTT 693

1768 AAUAUAAA CUGAUGAG X CGAA AUCCAAAA 282 TTTTGGAT A TTTATATT 694

1770 GCAAUAUA CUGAUGAG X CGAA AUAUCCAA 283 TTGGATAT T TATATTGC 695

1771 GGCAAUAU CUGAUGAG X CGAA AAUAUCCA 284 TGGATATT T ATATTGCC 696

1772 UGGCAAUA CUGAUGAG X CGAA AAAUAUCC 285 GGATATTT A TATTGCCA 697

1774 UAUGGCAA CUGAUGAG X CGAA AUAAAUAU 286 ATATTTAT A TTGCCATA 698

1776 AAUAUGGC CUGAUGAG X CGAA AUAUAAAU 287 ATTTATAT T GCCATATT 699

1782 AGUAAGAA CUGAUGAG X CGAA AUGGCAAU 288 ATTGCCAT A TTCTTACT 700

1784 CAAGUAAG CUGAUGAG X CGAA AUAUGGCA 289 TGCCATAT T CTTACTTG 701

1785 UCAAGUAA CUGAUGAG X CGAA AAUAUGGC 290 GCCATATT C TTACTTGA 702

1787 AUUCAAGU CUGAUGAG X CGAA AGAAUAUG 291 CATATTCT T ACTTGAAT 703

1788 CAUUCAAG CUGAUGAG X CGAA AAGAAUAU 292 ATATTCTT A CTTGAATG 704

1791 AAGCAUUC CUGAUGAG X CGAA AGUAAGAA 293 TTCTTACT T GAATGCTT 705

1799 GUCAUUCA CUGAUGAG X CGAA AGCAUUCA 294 TGAATGCT T TGAATGAC 706

1800 AGUCAUUC CUGAUGAG X CGAA AAGCAUUC 295 GAATGCTT T GAATGACT 707

1809 ACUGGAUG CUGAUGAG X CGAA AGUCAUUC 296 GAATGACT A CATCCAGT 708

1813 CAGAACUG CUGAUGAG X CGAA AUGUAGUC 297 GACTACAT C CAGTTCTG 709

1818 AGGUGCAG CUGAUGAG X CGAA ACUGGAUG 298 CATCCAGT T CTGCACCT 710

1819 UAGGUGCA CUGAUGAG X CGAA AACUGGAU 299 ATCCAGTT C TGCACCTA 711

1827 AGAGGGUA CUGAUGAG X CGAA AGGUGCAG 300 CTGCACCT A TACCCTCT 712

1829 CCAGAGGG CUGAUGAG X CGAA AUAGGUGC 301 GCACCTAT A CCCTCTGG 713

1834 CAACACCA CUGAUGAG X CGAA AGGGUAUA 302 TATACCCT C TGGTGTTG 714

1841 UAAAAAGC CUGAUGAG X CGAA ACACCAGA 303 TCTGGTGT T GCTTTTTA 715

1845 AGGUUAAA CUGAUGAG X CGAA AGCAACAC 304 GTGTTGCT T TTTAACCT 716

1846 AAGGUUAA CUGAUGAG X CGAA AAGCAACA 305 TGTTGCTT T TTAACCTT 717

1847 GAAGGUUA CUGAUGAG X CGAA AAAGCAAC 306 GTTGCTTT T TAACCTTC 718

1848 GGAAGGUU CUGAUGAG X CGAA AAAAGCAA 307 TTGCTTTT T AACCTTCC 719

1849 AGGAAGGU CUGAUGAG X CGAA AAAAAGCA 308 TGCTTTTT A ACCTTCCT 720

1854 AUUCCAGG CUGAUGAG X CGAA AGGUUAAA 309 TTTAACCT T CCTGGAAT 721

1855 GAUUCCAG CUGAUGAG X CGAA AAGGUUAA 310 TTAACCTT c CTGGAATC 722

1863 AGAAAAUG CUGAUGAG X CGAA AUUCCAGG 311 CCTGGAAT c CATTTTCT 723

1867 UUUUAGAA CUGAUGAG X CGAA AUGGAUUC 312 GAATCCAT T TTCTAAAA 724

1868 UUUUUAGA CUGAUGAG X CGAA AAUGGAUU 313 AATCCATT T TCTAAAAA 725

1869 UUUUUUAG CUGAUGAG X CGAA AAAUGGAU 314 ATCCATTT T CTAAAAAA 726

1870 AUUUUUUA CUGAUGAG X CGAA AAAAUGGA 315 TCCATTTT c TAAAAAAT 727

1872 UUAUUUUU CUGAUGAG X CGAA AGAAAAUG 316 CATTTTCT A AAAAATAA 728

1879 UGUGUCUU CUGAUGAG X CGAA AUUUUUUA 317 TAAAAAAT A AAGACACA 729

1889 CUGAGAAG CUGAUGAG X CGAA AUGUGUCU 318 AGACACAT T CTTCTCAG 730

1890 GCUGAGAA CUGAUGAG X CGAA AAUGUGUC 319 GACACATT C TTCTCAGC 731

1892 GUGCUGAG CUGAUGAG X CGAA AGAAUGUG 320 CACATTCT T CTCAGCAC 732

1893 GGUGCUGA CUGAUGAG X CGAA AAGAAUGU 321 ACATTCTT C TCAGCACC 733

1895 GUGGUGCU CUGAUGAG X CGAA AGAAGAAU 322 ATTCTTCT C AGCACCAC 734

1913 UUUUGGAA CUGAUGAG X CGAA AGGUGUUG 323 CAACACCT A TTCCAAAA 735

1915 GAUUUUGG CUGAUGAG X CGAA AUAGGUGU 324 ACACCTAT T CCAAAATC 736 Table 9

1916 CGAUUUUG CUGAUGAG X CGAA AAUAGGUG 325 CACCTATT C CAAAATCG 737

1923 AUGUGGUC CUGAUGAG X CGAA AUUUUGGA 326 TCCAAAAT C GACCACAT 738

1932 CUUCCAAA CUGAUGAG X CGAA AUGUGGUC 327 GACCACAT A TTTGGAAG 739

1934 UACUUCCA CUGAUGAG X CGAA AUAUGUGG 328 CCACATAT T TGGAAGTA 740

1935 UUACUUCC CUGAUGAG X CGAA AAUAUGUG 329 CACATATT T GGAAGTAA 741

1942 GAGAGCUU CUGAUGAG X CGAA ACUUCCAA 330 TTGGAAGT A AAGCTCTC 742

1948 GCUGAGGA CUGAUGAG X CGAA AGCUUUAC 331 GTAAAGCT C TCCTCAGC 743

1950 UUGCUGAG CUGAUGAG X CGAA AGAGCUUU 332 AAAGCTCT C CTCAGCAA 744

1953 CAUUUGCU CUGAUGAG X CGAA AGGAGAGC 333 GCTCTCCT C AGCAAATG 745

1963 UGUUCUUU CUGAUGAG X CGAA ACAUUUGC 334 GCAAATGT A AAAGAACA 746

1977 UUUGUUAU CUGAUGAG X CGAA AUUUCUGU 335 ACAGAAAT T ATAACAAA 747

1978 GUUUGUUA CUGAUGAG X CGAA AAUUUCUG 336 CAGAAATT A TAACAAAC 748

1980 CAGUUUGU CUGAUGAG X CGAA AUAAUUUC 337 GAAATTAT A ACAAACTG 749

1990 GUCUGAGA CUGAUGAG X CGAA ACAGUUUG 338 CAAACTGT C TCTCAGAC 750

1992 UGGUCUGA CUGAUGAG X CGAA AGACAGUU 339 ^' AACTGTCT C TCAGACCA 751

1994 UGUGGUCU CUGAUGAG X CGAA AGAGACAG 340 CTGTCTCT C AGACCACA 752

2005 UUUGGUUA CUGAUGAG X CGAA ACUGUGGU 341 ACCACAGT A TAACCAAA 753

2007 AGUUUGGU CUGAUGAG X CGAA AUACUGUG 342 CACAGTAT A ACCAAACT 754

2016 CUGAGUUC CUGAUGAG X CGAA AGUUUGGU 343 ACCAAACT A GAACTCAG 755

2022 UUAAUCCU CUGAUGAG X CGAA AGUUCUAG 344 CTAGAACT C AGGATTAA 756

2028 AGUUUCUU CUGAUGAG X CGAA AUCCUGAG 345 CTCAGGAT T AAGAAACT 757

2029 GAGUUUCU CUGAUGAG X CGAA AAUCCUGA 346 TCAGGATT A AGAAACTC 758

2037 UUUUGAGU CUGAUGAG X CGAA AGUUUCUU 347 AAGAAACT C ACTCAAAA 759

2041 GUGGUUUU CUGAUGAG X CGAA AGUGAGUU 348 AACTCACT C AAAACCAC 760

2056 UUUCCAUG CUGAUGAG X CGAA AGUUGUGU 349 ACACAACT A CATGGAAA 761

2079 UCAUUCAG CUGAUGAG X CGAA AGCAGGUU 350 AACCTGCT C CTGAATGA 762

2090 GUAUCCAG CUGAUGAG X CGAA AGUCAUUC 351 GAATGACT A CTGGATAC 763

2097 UUGUUAUG CUGAUGAG X CGAA AUCCAGUA 352 TACTGGAT A CATAACAA 764

2101 CAUUUUGU CUGAUGAG X CGAA AUGUAUCC 353 GGATACAT A ACAAAATG 765

2121 AACAUCUU CUGAUGAG X CGAA AUUUCUGC 354 GCAGAAAT A AAGATGTT 766

2129 UUUUAAAG CUGAUGAG X CGAA ACAUCUUU 355 AAAGATGT T CTTTAAAA 767

2130 GUUUUAAA CUGAUGAG X CGAA AACAUCUU 356 AAGATGTT C TTTAAAAC 768

2132 UGGUUUUA CUGAUGAG X CGAA AGAACAUC 357 GATGTTCT T TAAAACCA 769

2133 UUGGUUUU CUGAUGAG X CGAA AAGAACAU 358 ATGTTCTT T AAAACCAA 770

2134 AUUGGUUU CUGAUGAG X CGAA AAAGAACA 359 TGTTCTTT A AAACCAAT 771

2162 GAUUCUGG CUGAUGAG X CGAA AUGUUGUG 360 CACAACAT A CCAGAATC 772

2170 GUCCCAGA CUGAUGAG X CGAA AUUCUGGU 361 ACCAGAAT C TCTGGGAC 773

2172 GUGUCCCA CUGAUGAG X CGAA AGAUUCUG 362 CAGAATCT C TGGGACAC 774

2183 CUGCUUUG CUGAUGAG X CGAA AUGUGUCC 363 GGACACAT T CAAAGCAG 775

2184 ACUGCUUU CUGAUGAG X CGAA AAUGUGUC 364 GACACATT C AAAGCAGT 776

2197 UUUCCCUC CUGAUGAG X CGAA ACACACUG 365 CAGTGTGT A GAGGGAAA 777

2207 GUGCUAUA CUGAUGAG X CGAA AUUUCCCU 366 AGGGAAAT T TATAGCAC 778

2208 AGUGCUAU CUGAUGAG X CGAA AAUUUCCC 367 GGGAAATT T ATAGCACT 779

2209 UAGUGCUA CUGAUGAG X CGAA AAAUUUCC 368 GGAAATTT A TAGCACTA 780

2211 UUUAGUGC CUGAUGAG X CGAA AUAAAUUU 369 AAATTTAT A GCACTAAA 781

2217 UGGGCAUU CUGAUGAG X CGAA AGUGCUAU 370 ATAGCACT A AATGCCCA 782

2244 AUUUUAGA CUGAUGAG X CGAA AUUUCCUG 371 CAGGAAAT A TCTAAAAT 783 Table 9

2246 CAAUUUUA CUGAUGAG X CGAA AUAUUUCC 372 GGAAATAT C TAAAATTG 784

2248 GUCAAUUU CUGAUGAG X CGAA AGAUAUUU 373 AAATATCT A AAATTGAC 785

2253 AGGGUGUC CUGAUGAG X CGAA AUUUUAGA 374 TCTAAAAT T GACACCCT 786

2262 UGUGAUGU CUGAUGAG X CGAA AGGGUGUC 375 GACACCCT A ACATCACA 787

2267 UUAAUUGU CUGAUGAG X CGAA AUGUUAGG 376 CCTAACAT C ACAATTAA 788

2273 GUUCUUUU CUGAUGAG X CGAA AUUGUGAU 377 ATCACAAT T AAAAGAAC 789

2274 AGUUCUUU CUGAUGAG X CGAA AAUUGUGA 378 TCACAATT A AAAGAACT 790

2283 UGCUUCUC CUGAUGAG X CGAA AGUUCUUU 379 AAAGAACT A GAGAAGCA 791

2305 AGCUUUUC CUGAUGAG X CGAA AUGUGUUU 380 AAACACAT T GAAAAGCT 792

2314 CCUUCUCU CUGAUGAG X CGAA AGCUUUUC 381 GAAAAGCT A AGAGAAGG 793

2331 AUCUUAGU CUGAUGAG X CGAA AUUUCUUG 382 CAAGAAAT A ACTAAGAT 794

2335 UCUGAUCU CUGAUGAG X CGAA AGUUAUUU 383 AAATAACT A AGATCAGA 795

2340 UCUGCUCU CUGAUGAG X CGAA AUCUUAGU 384 ACTAAGAT C AGAGCAGA 796

2361 UGUGUCUC CUGAUGAG X CGAA AUUUCCUU 385 AAGGAAAT A GAGACACA 797

2377 UUUUUGAA CUGAUGAG X CGAA AGUUUUUU 386 AAAAAACT C TTCAAAAA 798

2379 AUUUUUUG CUGAUGAG X CGAA AGAGUUUU 387 AAAACTCT T CAAAAAAT 799

2380 GAUUUUUU CUGAUGAG X CGAA AAGAGUUU 388 AAACTCTT C AAAAAATC 800

2388 GAUUCAUU CUGAUGAG X CGAA AUUUUUUG 389 CAAAAAAT C AATGAATC 801

2396 AGCUCCUG CUGAUGAG X CGAA AUUCAUUG 390 CAATGAAT C CAGGAGCT 802

2408 UUUCAAAA CUGAUGAG X CGAA ACCAGCUC 391 GAGCTGGT T TTTTGAAA 803

2409 GUUUCAAA CUGAUGAG X CGAA AACCAGCU 392 AGCTGGTT T TTTGAAAC 804

2410 CGUUUCAA CUGAUGAG X CGAA AAACCAGC 393 GCTGGTTT T TTGAAACG 805

2411 UCGUUUCA CUGAUGAG X CGAA AAAACCAG 394 CTGGTTTT T TGAAACGA 806

2412 AUCGUUUC CUGAUGAG X CGAA AAAAACCA 395 TGGTTTTT T GAAACGAT 807

2421 AUUUUGUU CUGAUGAG X CGAA AUCGUUUC 396 GAAACGAT C AACAAAAT 808

2430 UGUCUAUC CUGAUGAG X CGAA AUUUUGUU 397 AACAAAAT T GATAGACA 809

2434 CUAGUGUC CUGAUGAG X CGAA AUCAAUUU 398 AAATTGAT A GACACTAG 810

2441 AGUCUUGC CUGAUGAG X CGAA AGUGUCUA 399 TAGACACT A GCAAGACT 811

2450 . UUCUUUAU CUGAUGAG X CGAA AGUCUUGC 400 GCAAGACT A ATAAAGAA 812

2453 UUCUUCUU CUGAUGAG X CGAA AUUAGUCU 401 AGACTAAT A AAGAAGAA 813

2475 UUCUAUUU CUGAUGAG X CGAA AUUCUUCU 402 AGAAGAAT C AAATAGAA 814

2480 AUUGCUUC CUGAUGAG X CGAA AUUUGAUU 403 AATCAAAT A GAAGCAAT 815

2489 UCAUUUUU CUGAUGAG X CGAA AUUGCUUC 404 GAAGCAAT A AAAAATGA 816

2499 AUCCCCUU CUGAUGAG X CGAA AUCAUUUU 405 AAAATGAT A AAGGGGAT 817

2508 GGUGGUGA CUGAUGAG X CGAA AUCCCCUU 406 AAGGGGAT A TCACCACC 818

2510 UUGGUGGU CUGAUGAG X CGAA AUAUCCCC 407 GGGGATAT C ACCACCAA 819

2520 UUCUGUGG CUGAUGAG X CGAA AUUGGUGG 408 CCACCAAT C CCACAGAA 820

2531 UGGUGGUU CUGAUGAG X CGAA AUUUCUGU 409 ACAGAAAT A AACCACCA 821

2541 UAUUCUCU CUGAUGAG X CGAA AUGGUGGU 410 ACCACCAT C AGAGAATA 822

2549 GUUUGUAG CUGAUGAG X CGAA AUUCUCUG 411 CAGAGAAT A CTACAAAC 823

2552 GGUGUUUG CUGAUGAG X CGAA AGUAUUCU 412 AGAATACT A CAAACACC 824

Input Sequence = HSU29607. Cut Site = UH/.

Stem Length = 8 . Core Sequence = CUGAUGAG X CGAA (X = GCCGUUAGGC or other stem II)

Seql = HSU29607 (Human methionine aminopeptidase mRNA, complete eds., 2569 bp) Table 10

Table 10: Human methionine aminopeptidase type 2 (MetAP-2) NCH Ribozyme and Target Sequence

Nt. Ribozyme Sequence Seq. ID Substrate Sequence Seq. ID Nos. position Nos.

10 CCCGAGAG CUGAUGAG X CGAA IACGAGGG 825 CCCTCGTC T CTCTCGGG 1255

12 UGCCCGAG CUGAUGAG X CGAA IAGACGAG 826 CTCGTCTC T CTCGGGCA 1256

14 GUUGCCCG CUGAUGAG X CGAA IAGAGACG 827 CGTCTCTC T CGGGCAAC 1257

20 CGCCAUGU CUGAUGAG X CGAA ICCCGAGA 828 TCTCGGGC A ACATGGCG 1258

23 GCCCGCCA CUGAUGAG X CGAA IUUGCCCG 829 CGGGCAAC A TGGCGGGC 1259

49 CUCCCGGA CUGAUGAG X CGAA ICCGCUAC 830 GTAGCGGC C TCCGGGAG 1260

50 GCUCCCGG CUGAUGAG X CGAA IGCCGCUA 831 TAGCGGCC T CCGGGAGC 1261

52 UGGCUCCC CUGAUGAG X CGAA IAGGCCGC 832 GCGGCCTC C GGGAGCCA 1262

59 AUUCAGGU CUGAUGAG X CGAA ICUCCCGG 833 CCGGGAGC C ACCTGAAT 1263

60 CAUUCAGG CUGAUGAG X CGAA IGCUCCCG 834 CGGGAGCC A CCTGAATG 1264

62 GCCAUUCA CUGAUGAG X CGAA IUGGCUCC 835 GGAGCCAC C TGAATGGC 1265

63 CGCCAUUC CUGAUGAG X CGAA IGUGGCUC 836 GAGCCACC T GAATGGCG 1266

74 UGGAUCCA CUGAUGAG X CGAA IUCGCCAU 837 ATGGCGAC C TGGATCCA 1267

75 CUGGAUCC CUGAUGAG X CGAA IGUCGCCA 838 TGGCGACC T GGATCCAG 1268

81 UGUCGUCU CUGAUGAG X CGAA IAUCCAGG 839 CCTGGATC C AGACGACA 1269

82 CUGUCGUC CUGAUGAG X CGAA IGAUCCAG 840 CTGGATCC A GACGACAG 1270

89 UUCUUCCC CUGAUGAG X CGAA IUCGUCUG 841 CAGACGAC A GGGAAGAA 1271

103 GUAGAGGC CUGAUGAG X CGAA ICUCCUUC 842 GAAGGAGC T GCCTCTAC 1272

106 GCCGUAGA CUGAUGAG X CGAA ICAGCUCC 843 GGAGCTGC C TCTACGGC 1273

107 AGCCGUAG CUGAUGAG X CGAA IGCAGCUC 844 GAGCTGCC T CTACGGCT 1274

109 UCAGCCGU CUGAUGAG X CGAA IAGGCAGC 845 GCTGCCTC T ACGGCTGA 1275

115 GCUUCCUC CUGAUGAG X CGAA ICCGUAGA 846 TCTACGGC T GAGGAAGC 1276

124 UUCUUGGC CUGAUGAG X CGAA ICUUCCUC 847 GAGGAAGC A GCCAAGAA 1277

127 UUUUUCUU CUGAUGAG X CGAA ICUGCUUC 848 GAAGCAGC C AAGAAAAA 1278

128 UUUUUUCU CUGAUGAG X CGAA IGCUGCUU 849 AAGCAGCC A AGAAAAAA 1279

158 AGGCCCUU CUGAUGAG X CGAA ICUCUUCU 850 AGAAGAGC A AAGGGCCT 1280

165 CUGCAGAA CUGAUGAG X CGAA ICCCUUUG 851 CAAAGGGC C TTCTGCAG 1281

166 GCUGCAGA CUGAUGAG X CGAA IGCCCUUU 852 AAAGGGCC T TCTGCAGC 1282

169 CCUGCUGC CUGAUGAG X CGAA IAAGGCCC 853 GGGCCTTC T GCAGCAGG 1283

172 UCCCCUGC CUGAUGAG X CGAA ICAGAAGG 854 CCTTCTGC A GCAGGGGA 1284

175 UGUUCCCC CUGAUGAG X CGAA ICUGCAGA 855 TCTGCAGC A GGGGAACA 1285

183 CAGGUUCC CUGAUGAG X CGAA IUUCCCCU 856 AGGGGAAC A GGAACCTG 1286

189 CUUUAUCA CUGAUGAG X CGAA IUUCCUGU 857 ACAGGAAC C TGATAAAG 1287

190 UCUUUAUC CUGAUGAG X CGAA IGUUCCUG 858 CAGGAACC T GATAAAGA 1288

202 GAGGCUCC CUGAUGAG X CGAA IAUUCUUU 859 AAAGAATC A GGAGCCTC 1289

208 UCCACUGA CUGAUGAG X CGAA ICUCCUGA 860 TCAGGAGC C TCAGTGGA 1290

209 AUCCACUG CUGAUGAG X CGAA IGCUCCUG 861 CAGGAGCC T CAGTGGAT 1291

211 UCAUCCAC CUGAUGAG X CGAA IAGGCUCC 862 GGAGCCTC A GTGGATGA 1292

226 AACUGUCU CUGAUGAG X CGAA ICUACUUC 863 GAAGTAGC A AGACAGTT 1293

231 UUUCCAAC CUGAUGAG X CGAA IUCUUGCU 864 AGCAAGAC A GTTGGAAA 1294

244 UCCAAUGC CUGAUGAG X CGAA IAUCUUUC 865 GAAAGATC A GCATTGGA 1295

247 UCUUCCAA CUGAUGAG X CGAA ICUGAUCU 866 AGATCAGC A TTGGAAGA 1296 Table 10

307 UUUCCAGU CUGAUGAG X CGAA ICUCCAUC 867 GATGGAGC A ACTGGAAA 1297

310 UUCUUUCC CUGAUGAG X CGAA IUUGCUCC 868 GGAGCAAC T GGAAAGAA 1298

348 GAACUUUU CUGAUGAG X CGAA IUCCUCUC 869 GAGAGGAC C AAAAGTTC 1299

349 UGAACUUU CUGAUGAG X CGAA IGUCCUCU 870 AGAGGACC A AAAGTTCA 1300

357 GGUCUGUU CUGAUGAG X CGAA IAACUUUU 871 AAAAGTTC A AACAGACC 1301

361 GGAGGGUC CUGAUGAG X CGAA IUUUGAAC 872 GTTCAAAC A GACCCTCC 1302

365 UGAGGGAG CUGAUGAG X CGAA IUCUGUUU 873 AAACAGAC C CTCCCTCA 1303

366 CUGAGGGA CUGAUGAG X CGAA IGUCUGUU 874 AACAGACC C TCCCTCAG 1304

367 ACUGAGGG CUGAUGAG X CGAA IGGUCUGU 875 ACAGACCC T CCCTCAGT 1305

369 GAACUGAG CUGAUGAG X CGAA IAGGGUCU 876 AGACCCTC C CTCAGTTC 1306

370 GGAACUGA CUGAUGAG X CGAA IGAGGGUC 877 GACCCTCC C TCAGTTCC 1307

371 UGGAACUG CUGAUGAG X CGAA IGGAGGGU 878 ACCCTCCC T CAGTTCCA 1308

373 AUUGGAAC CUGAUGAG X CGAA IAGGGAGG 879 CCTCCCTC A GTTCCAAT 1309

378 CACAUAUU CUGAUGAG X CGAA IAACUGAG 880 CTCAGTTC C AATATGTG 1310

379 UCACAUAU CUGAUGAG X CGAA IGAACUGA 881 TCAGTTCC A ATATGTGA 1311

389 AGGAUACA CUGAUGAG X CGAA lUCACAUA 882 TATGTGAC C TGTATCCT 1312

390 UAGGAUAC CUGAUGAG X CGAA IGUCACAU 883 ATGTGACC T GTATCCTA 1313

396 CACCAUUA CUGAUGAG X CGAA IAUACAGG 884 CCTGTATC C TAATGGTG 1314

397 ACACCAUU CUGAUGAG X CGAA IGAUACAG 885 CTGTATCC T AATGGTGT 1315

411 GUCCUUUG CUGAUGAG X CGAA lAAAUACA 886 TGTATTTC C CAAAGGAC 1316

412 UGUCCUUU CUGAUGAG X CGAA IGAAAUAC 887 GTATTTCC C AAAGGACA 1317

413 UUGUCCUU CUGAUGAG X CGAA IGGAAAUA 888 TATTTCCC A AAGGACAA 1318

420 CGCAUUCU CUGAUGAG X CGAA IUCCUUUG 889 CAAAGGAC A AGAATGCG 1319

434 UGUGGGUG CUGAUGAG X CGAA IUAUUCGC 890 GCGAATAC C CACCCACA 1320

435 GUGUGGGU CUGAUGAG X CGAA IGUAUUCG 891 CGAATACC C ACCCACAC 1321

436 UGUGUGGG CUGAUGAG X CGAA IGGUAUUC 892 GAATACCC A CCCACACA 1322

438 CUUGUGUG CUGAUGAG X CGAA IUGGGUAU 893 ATACCCAC C CACACAAG 1323

439 UCUUGUGU CUGAUGAG X CGAA IGUGGGUA 894 TACCCACC C ACACAAGA 1324

440 AUCUUGUG CUGAUGAG X CGAA IGGUGGGU 895 ACCCACCC A CACAAGAT 1325

442 CCAUCUUG CUGAUGAG X CGAA IUGGGUGG 896 CCACCCAC A CAAGATGG 1326

444 GCCCAUCU CUGAUGAG X CGAA IUGUGGGU 897 ACCCACAC A AGATGGGC 1327

457 CAAGCAGC CUGAUGAG X CGAA IUUCGCCC 898 GGGCGAAC A GCTGCTTG 1328

460 CUCCAAGC CUGAUGAG X CGAA ICUGUUCG 899 CGAACAGC T GCTTGGAG 1329

463 GUUCUCCA CUGAUGAG X CGAA ICAGCUGU 900 ACAGCTGC T TGGAGAAC 1330

472 UCACUUGU CUGAUGAG X CGAA lUUCUCCA 901 TGGAGAAC T ACAAGTGA 1331

475 UCUUCACU CUGAUGAG X CGAA IUAGUUCU 902 AGAACTAC A AGTGAAGA 1332

493 UGAUCUAA CUGAUGAG X CGAA ICUUUCUU 903 AAGAAAGC A TTAGATCA 1333

501 CACUUGCC CUGAUGAG X CGAA IAUCUAAU 904 ATTAGATC A GGCAAGTG 1334

505 UCUUCACU CUGAUGAG X CGAA ICCUGAUC 905 GATCAGGC A AGTGAAGA 1335

538 GCUUCUGC CUGAUGAG X CGAA ICUUCUCG 906 CGAGAAGC T GCAGAAGC 1336

541 UGUGCUUC CUGAUGAG X CGAA ICAGCUUC 907 GAAGCTGC A GAAGCACA 1337

547 UGUCGAUG CUGAUGAG X CGAA ICUUCUGC 908 GCAGAAGC A CATCGACA 1338

549 CUUGUCGA CUGAUGAG X CGAA IUGCUUCU 909 AGAAGCAC A TCGACAAG 1339

555 UUCUAACU CUGAUGAG X CGAA IUCGAUGU 910 ACATCGAC A AGTTAGAA 1340

578 CUUGAUCC CUGAUGAG X CGAA ICUCAUUA 911 TAATGAGC T GGATCAAG 1341

584 CCCAGGCU CUGAUGAG X CGAA IAUCCAGC 912 GCTGGATC A AGCCTGGG 1342

588 UCAUCCCA CUGAUGAG X CGAA ICUUGAUC 913 GATCAAGC C TGGGATGA 1343 Table 10

589 GUCAUCCC CUGAUGAG X CGAA IGCUUGAU 914 ATCAAGCC T GGGATGAC 1344

598 UCUAUCAU CUGAUGAG X CGAA IUCAUCCC 915 GGGATGAC A ATGATAGA 1345

611 CUUUUCAC CUGAUGAG X CGAA IAUUUCUA 916 TAGAAATC T GTGAAAAG 1346

629 GCGUGAAC CUGAUGAG X CGAA IUCUUCCA 917 TGGAAGAC T GTTCACGC 1347

634 AACUUGCG CUGAUGAG X CGAA IAACAGUC 918 GACTGTTC A CGCAAGTT 1348

638 UAUUAACU CUGAUGAG X CGAA ICGUGAAC 919 GTTCACGC A AGTTAATA 1349

667 GCCAGGCC CUGAUGAG X CGAA ICAUUUAA 920 TTAAATGC A GGCCTGGC 1350

671 AAAUGCCA CUGAUGAG X CGAA ICCUGCAU 921 ATGCAGGC C TGGCATTT 1351

672 GAAAUGCC CUGAUGAG X CGAA IGCCUGCA 922 TGCAGGCC T GGCATTTC 1352

676 GUAGGAAA CUGAUGAG X CGAA ICCAGGCC 923 GGCCTGGC A TTTCCTAC 1353

681 AUCCAGUA CUGAUGAG X CGAA IAAAUGCC 924 GGCATTTC C TACTGGAT 1354

682 CAUCCAGU CUGAUGAG X CGAA IGAAAUGC 925 GCATTTCC T ACTGGATG 1355

685 GAACAUCC CUGAUGAG X CGAA IUAGGAAA 926 TTTCCTAC T GGATGTTC 1356

694 UUAUUGAG CUGAUGAG X CGAA IAACAUCC 927 GGATGTTC T CTCAATAA 1357

696 AAUUAUUG CUGAUGAG X CGAA IAGAACAU 928 ATGTTCTC T CAATAATT 1358

698 ACAAUUAU CUGAUGAG X CGAA IAGAGAAC 929 GTTCTCTC A ATAATTGT 1359

709 UAAUGGGC CUGAUGAG X CGAA ICACAAUU 930 AATTGTGC T GCCCATTA 1360

712 GUAUAAUG CUGAUGAG X CGAA ICAGCACA 931 TGTGCTGC C CATTATAC 1361

713 AGUAUAAU CUGAUGAG X CGAA IGCAGCAC 932 GTGCTGCC C ATTATACT 1362

714 GAGUAUAA CUGAUGAG X CGAA IGGCAGCA 933 TGCTGCCC A TTATACTC 1363

721 GCAUUGGG CUGAUGAG X CGAA IUAUAAUG 934 CATTATAC T CCCAATGC 1364

723 CGGCAUUG CUGAUGAG X CGAA IAGUAUAA 935 TTATACTC C CAATGCCG 1365

724 CCGGCAUU CUGAUGAG X CGAA IGAGUAUA 936 TATACTCC C AATGCCGG 1366

725 ACCGGCAU CUGAUGAG X CGAA IGGAGUAU 937 ATACTCCC A ATGCCGGT 1367

730 GUGUCACC CUGAUGAG X CGAA ICAUUGGG 938 CCCAATGC C GGTGACAC 1368

737 UACUGUUG CUGAUGAG X CGAA IUCACCGG 939 CCGGTGAC A CAACAGTA 1369

739 AAUACUGU CUGAUGAG X CGAA IUGUCACC 940 GGTGACAC A ACAGTATT 1370

742 UGUAAUAC CUGAUGAG X CGAA IUUGUGUC 941 GACACAAC A GTATTACA 1371

750 CAUCAUAC CUGAUGAG X CGAA IUAAUACU 942 AGTATTAC A GTATGATG 1372

761 UUUACAGA CUGAUGAG X CGAA IUCAUCAU 943 ATGATGAC A TCTGTAAA 1373

764 UAUUUUAC CUGAUGAG X CGAA IAUGUCAU 944 ATGACATC T GTAAAATA 1374

776 UGUUCCAA CUGAUGAG X CGAA IUCUAUUU 945 AAATAGAC T TTGGAACA 1375

784 CUUAUAUG CUGAUGAG X CGAA IUUCCAAA 946 TTTGGAAC A CATATAAG 1376

786 CACUUAUA CUGAUGAG X CGAA IUGUUCCA 947 TGGAACAC A TATAAGTG 1377

809 AAAAGCAC CUGAUGAG X CGAA lUCAAUAA 948 TTATTGAC T GTGCTTTT 1378

814 ACAGUAAA CUGAUGAG X CGAA ICACAGUC 949 GACTGTGC T TTTACTGT 1379

820 AAAGUGAC CUGAUGAG X CGAA lUAAAAGC 950 GCTTTTAC T GTCACTTT 1380

824 AUUAAAAG CUGAUGAG X CGAA IACAGUAA 951 TTACTGTC A CTTTTAAT 1381

• 826 GGAUUAAA CUGAUGAG X CGAA IUGACAGU 952 ACTGTCAC T TTTAATCC 1382

834 CAUAUUUG CUGAUGAG X CGAA IAUUAAAA 953 TTTTAATC C CAAATATG 1383

835 UCAUAUUU CUGAUGAG X CGAA IGAUUAAA 954 TTTAATCC C AAATATGA 1384

836 AUCAUAUU CUGAUGAG X CGAA IGGAUUAA 955 TTAATCCC A AATATGAT 1385

859 UCUUUUAC CUGAUGAG X CGAA ICUUUUAA 956 TTAAAAGC T GTAAAAGA 1386

871 GUGUUAGU CUGAUGAG X CGAA ICAUCUUU 957 AAAGATGC T ACTAACAC 1387

874 CCAGUGUU CUGAUGAG X CGAA IUAGCAUC 958 GATGCTAC T AACACTGG 1388

878 UAUUCCAG CUGAUGAG X CGAA IUUAGUAG 959 CTACTAAC A CTGGAATA 1389

880 UUUAUUCC CUGAUGAG X CGAA IUGUUAGU 960 ACTAACAC T GGAATAAA 1390 Table 10

895 UCAAUUCC CUGAUGAG X CGAA ICACACUU 961 AAGTGTGC T GGAATTGA 1391

912 CAUCACAC CUGAUGAG X CGAA IACGAACA 962 TGTTCGTC T GTGTGATG ^" 1392

931 UCUUGGAU CUGAUGAG X CGAA ICCUCACC 963 GGTGAGGC c ATCCAAGA 1393

932 UUCUUGGA CUGAUGAG X CGAA IGCCUCAC 964 GTGAGGCC A TCCAAGAA 1394

935 AACUUCUU CUGAUGAG X CGAA IAUGGCCU 965 AGGCCATC C AAGAAGTT 1395

936 UAACUUCU CUGAUGAG X CGAA IGAUGGCC 966 GGCCATCC A AGAAGTTA 1396

952 ACUUCAUA CUGAUGAG X CGAA IACUCCAU 967 ATGGAGTC C TATGAAGT 1397

953 AACUUCAU CUGAUGAG X CGAA IGACUCCA 968 TGGAGTCC T ATGAAGTT 1398

979 ACUUGAUA CUGAUGAG X CGAA IUCUUCCC 969 GGGAAGAC A TATCAAGT 1399

984 GUUUCACU CUGAUGAG X CGAA IAUAUGUC 970 GACATATC A AGTGAAAC 1400

993 UACGGAUU CUGAUGAG X CGAA IUUUCACU 971 AGTGAAAC C AATCCGTA 1401

994 UUACGGAU CUGAUGAG X CGAA IGUUUCAC 972 GTGAAACC A ATCCGTAA 1402

998 UAGAUUAC CUGAUGAG X CGAA IAUUGGUU 973 AACCAATC C GTAATCTA 1403

1005 GUCCAUUU CUGAUGAG X CGAA IAUUACGG 974 CCGTAATC T AAATGGAC 1404

1014 CAAUUGAA CUGAUGAG X CGAA IUCCAUUU 975 AAATGGAC A TTCAATTG 1405

1018 UGCCCAAU CUGAUGAG X CGAA IAAUGUCC 976 GGACATTC A ATTGGGCA 1406

1026 UUCUAUAU CUGAUGAG X CGAA ICCCAAUU 977 AATTGGGC A ATATAGAA 1407

1038 UUCCAGCA CUGAUGAG X CGAA IUAUUCUA 978 TAGAATAC A TGCTGGAA 1408

1042 GUUUUUCC CUGAUGAG X CGAA ICAUGUAU 979 ATACATGC T GGAAAAAC 1409

1051 AUCGGCAC CUGAUGAG X CGAA IUUUUUCC 980 GGAAAAAC A GTGCCGAT 1410

1056 UCACAAUC CUGAUGAG X CGAA ICACUGUU 981 AACAGTGC C GATTGTGA 1411

1078 AUUCUUGU CUGAUGAG X CGAA ICCUCCCC 982 GGGGAGGC A ACAAGAAT 1412

1081 UCCAUUCU CUGAUGAG X CGAA IUUGCCUC 983 GAGGCAAC A AGAATGGA 1413

1108 GUUUCAAU CUGAUGAG X CGAA ICAUAUAC 984 GTATATGC A ATTGAAAC 1414

1117 CUACCAAA CUGAUGAG X CGAA IUUUCAAU 985 ATTGAAAC C TTTGGTAG 1415

1118 ACUACCAA CUGAUGAG X CGAA IGUUUCAA 986 TTGAAACC T TTGGTAGT 1416

1129 CCUUUUCC CUGAUGAG X CGAA IUACUACC 987 GGTAGTAC A GGAAAAGG 1417

1146 UAUCAUCA CUGAUGAG X CGAA lAACAACA 988 TGTTGTTC A TGATGATA 1418

1165 AUGUAAUG CUGAUGAG X CGAA IAACAUUC 989 GAATGTTC A CATTACAT 1419

1167 UCAUGUAA CUGAUGAG X CGAA IUGAACAU 990 ATGTTCAC A TTACATGA 1420

1172 AUUUUUCA CUGAUGAG X CGAA IUAAUGUG 991 CACATTAC A TGAAAAAT 1421

1194 UUGGCACA CUGAUGAG X CGAA IUCCAACA 992 TGTTGGAC A TGTGCCAA 1422

1200 GCCUUAUU CUGAUGAG X CGAA ICACAUGU 993 ACATGTGC C AATAAGGC 1423

1201 AGCCUUAU CUGAUGAG X CGAA IGCACAUG 994 CATGTGCC A ATAAGGCT 1424

1209 UUCUUGGA CUGAUGAG X CGAA ICCUUAUU 995 AATAAGGC T TCCAAGAA 1425

1212 UUGUUCUU CUGAUGAG X CGAA IAAGCCUU 996 AAGGCTTC C AAGAACAA 1426

1213 UUUGUUCU CUGAUGAG X CGAA IGAAGCCU 997 AGGCTTCC A AGAACAAA 1427

1219 AAGUGUUU CUGAUGAG X CGAA IUUCUUGG 998 CCAAGAAC A AAACACTT 1428

1224 UUAACAAG CUGAUGAG X CGAA IUUUUGUU 999 AACAAAAC A CTTGTTAA 1429

1226 AUUUAACA CUGAUGAG X CGAA IUGUUUUG 1000 CAAAACAC T TGTTAAAT 1430

1238 UUCAUUGA CUGAUGAG X CGAA IACAUUUA 1001 TAAATGTC A TCAATGAA 1431

1241 GUUUUCAU CUGAUGAG X CGAA IAUGACAU 1002 ATGTCATC A ATGAAAAC 1432

1250 GGUUCCAA CUGAUGAG X CGAA IUUUUCAU 1003 ATGAAAAC T TTGGAACC 1433

1258 AAGGCAAG CUGAUGAG X CGAA IUUCCAAA 1004 TTTGGAAC C CTTGCCTT 1434

1259 GAAGGCAA CUGAUGAG X CGAA IGUUCCAA 1005 TTGGAACC C TTGCCTTC 1435

1260 AGAAGGCA CUGAUGAG X CGAA IGGUUCCA 1006 TGGAACCC T TGCCTTCT 1436

1264 CGGCAGAA CUGAUGAG X CGAA ICAAGGGU 1007 ACCCTTGC C TTCTGCCG 1437 Table 10

1265 GCGGCAGA CUGAUGAG X CGAA IGCAAGGG 1008 CCCTTGCC T TCTGCCGC 1438

1268 UCUGCGGC CUGAUGAG X CGAA IAAGGCAA 1009 TTGCCTTC T GCCGCAGA 1439

1271 CCAUCUGC CUGAUGAG X CGAA ICAGAAGG 1010 CCTTCTGC C GCAGATGG 1440

1274 CAGCCAUC CUGAUGAG X CGAA ICGGCAGA 1011 TCTGCCGC A GATGGCTG 1441

1281 AGCGAUCC CUGAUGAG X CGAA ICCAUCUG 1012 CAGATGGC T GGATCGCT 1442

1289 UUCUCCCA CUGAUGAG X CGAA ICGAUCCA 1013 TGGATCGC T TGGGAGAA 1443

1307 AGCCAUCA CUGAUGAG X CGAA IUAUUUAC 1014 GTAAATAC T TGATGGCT 1444

1315 UUCUUCAG CUGAUGAG X CGAA ICCAUCAA 1015 TTGATGGC T CTGAAGAA 1445

1317 GAUUCUUC CUGAUGAG X CGAA IAGCCAUC 1016 GATGGCTC T GAAGAATC 1446

1326 AGUCACAC CUGAUGAG X CGAA IAUUCUUC 1017 GAAGAATC T GTGTGACT 1447

1334 AAUGCCCA CUGAUGAG X CGAA IUCACACA 1018 TGTGTGAC T TGGGCATT 1448

1340 AUCUACAA CUGAUGAG X CGAA ICCCAAGU 1019 ACTTGGGC A TTGTAGAT 1449

1350 GUGGAUAU CUGAUGAG X CGAA IAUCUACA 1020 TGTAGATC C ATATCCAC 1450

1351 GGUGGAUA CUGAUGAG X CGAA IGAUCUAC 1021 GTAGATCC A TATCCACC 1451

1356 AUAAUGGU CUGAUGAG X CGAA IAUAUGGA 1022 TCCATATC C ACCATTAT 1452

1357 CAUAAUGG CUGAUGAG X CGAA IGAUAUGG 1023 CCATATCC A CCATTATG 1453

1359 CACAUAAU CUGAUGAG X CGAA IUGGAUAU 1024 ATATCCAC C ATTATGTG 1454

1360 UCACAUAA CUGAUGAG X CGAA IGUGGAUA 1025 TATCCACC A TTATGTGA 1455

1370 UCCUUUAA CUGAUGAG X CGAA lUCACAUA 1026 TATGTGAC A TTAAAGGA 1456

1381 GCUGUAUA CUGAUGAG X CGAA IAUCCUUU 1027 AAAGGATC A TATACAGC 1457

1387 AAUUGCGC CUGAUGAG X CGAA IUAUAUGA 1028 TCATATAC A GCGCAATT 1458

1392 GUUCAAAU CUGAUGAG X CGAA ICGCUGUA 1029 TACAGCGC A ATTTGAAC 1459

1401 GGAUGGUA CUGAUGAG X CGAA IUUCAAAU 1030 ATTTGAAC A TACCATCC 1460

1405 AACAGGAU CUGAUGAG X CGAA IUAUGUUC 1031 GAACATAC C ATCCTGTT 1461

1406 CAACAGGA CUGAUGAG X CGAA IGUAUGUU 1032 AACATACC A TCCTGTTG 1462

1409 ACGCAACA CUGAUGAG X CGAA IAUGGUAU 1033 ATACCATC C TGTTGCGT 1463

1410 GACGCAAC CUGAUGAG X CGAA IGAUGGUA 1034 TACCATCC T GTTGCGTC 1464

1419 UACAUGUU CUGAUGAG X CGAA IACGCAAC 1035 GTTGCGTC C AACATGTA 1465

1420 UUACAUGU CUGAUGAG X CGAA IGACGCAA 1036 TTGCGTCC A ACATGTAA 1466

1423 UCUUUACA CUGAUGAG X CGAA IUUGGACG 1037 CGTCCAAC A TGTAAAGA 1467

1439 UCCUCUGC CUGAUGAG X CGAA IACAACUU 1038 AAGTTGTC A GCAGAGGA 1468

1442 AUCUCCUC CUGAUGAG X CGAA ICUGACAA 1039 TTGTCAGC A GAGGAGAT 1469

1454 AGUUUAAU CUGAUGAG X CGAA IUCAUCUC 1040 GAGATGAC T ATTAAACT 1470

1462 UUGGACUA CUGAUGAG X CGAA IUUUAAUA 1041 TATTAAAC T TAGTCCAA 1471

1468 GUGGCUUU CUGAUGAG X CGAA IACUAAGU 1042 ACTTAGTC C AAAGCCAC 1472

1469 GGUGGCUU CUGAUGAG X CGAA IGACUAAG 1043 CTTAGTCC A AAGCCACC 1473

1474 GUUGAGGU CUGAUGAG X CGAA ICUUUGGA 1044 TCCAAAGC C ACCTCAAC 1474

1475 UGUUGAGG CUGAUGAG X CGAA IGCUUUGG 1045 CCAAAGCC A CCTCAACA 1475

1477 GGUGUUGA CUGAUGAG X CGAA IUGGCUUU 1046 AAAGCCAC C TCAACACC 1476

1478 AGGUGUUG CUGAUGAG X CGAA IGUGGCUU 1047 AAGCCACC T CAACACCT 1477

1480 AAAGGUGU CUGAUGAG X CGAA IAGGUGGC 1048 GCCACCTC A ACACCTTT 1478

1483 AAUAAAGG CUGAUGAG X CGAA IUUGAGGU 1049 ACCTCAAC A CCTTTATT 1479

1485 AAAAUAAA CUGAUGAG X CGAA lUGUUGAG 1050 CTCAACAC C TTTATTTT 1480

1486 GAAAAUAA CUGAUGAG X CGAA IGUGUUGA 1051 TCAACACC T TTATTTTC 1481

1495 CAAAGCUC CUGAUGAG X CGAA IAAAAUAA 1052 TTATTTTC T GAGCTTTG 1482

1500 UCCAACAA CUGAUGAG X CGAA ICUCAGAA 1053 TTCTGAGC T TTGTTGGA 1483

1513 UGGUAUCA CUGAUGAG X CGAA lUUUUCCA 1054 TGGAAAAC A TGATACCA 1484 Table 10

1520 UUAAUUCU CUGAUGAG X CGAA IUAUCAUG 1055 CATGATAC C AGAATTAA 1485

1521 AUUAAUUC CUGAUGAG X CGAA IGUAUCAU 1056 ATGATACC A GAATTAAT 1486

1534 CAACAUGU CUGAUGAG X CGAA ICAAAUUA 1057 TAATTTGC C ACATGTTG 1487

1535 ACAACAUG CUGAUGAG X CGAA IGCAAAUU 1058 AATTTGCC A CATGTTGT 1488

1537 AGACAACA CUGAUGAG X CGAA IUGGCAAA 1059 TTTGCCAC A TGTTGTCT 1489

1545 GUUAAAAC CUGAUGAG X CGAA IACAACAU 1060 ATGTTGTC T GTTTTAAC 1490

1554 GGGUCCAC CUGAUGAG X CGAA IUUAAAAC 1061 GTTTTAAC A GTGGACCC 1491

1561 AUUACAUG CUGAUGAG X CGAA IUCCACUG 1062 CAGTGGAC C CATGTAAT 1492

1562 UAUUACAU CUGAUGAG X CGAA IGUCCACU 1063 AGTGGACC C ATGTAATA 1493

1563 GUAUUACA CUGAUGAG X CGAA IGGUCCAC 1064 GTGGACCC A TGTAATAC 1494

1572 UGGAUAAA CUGAUGAG X CGAA IUAUUACA 1065 TGTAATAC T TTTATCCA 1495

1579 UUAAACAU CUGAUGAG X CGAA IAUAAAAG 1066 CTTTTATC C ATGTTTAA 1496

1580 UUUAAACA CUGAUGAG X CGAA IGAUAAAA 1067 TTTTATCC A TGTTTAAA 1497

1606 UUUGCCUU CUGAUGAG X CGAA IUCCAAAU 1068 ATTTGGAC A AAGGCAAA 1498

1612 AGACGGUU CUGAUGAG X CGAA ICCUUUGU 1069 ACAAAGGC A AACCGTCT 1499

1616 CAUUAGAC CUGAUGAG X CGAA IUUUGCCU 1070 AGGCAAAC C GTCTAATG 1500

1620 AUUACAUU CUGAUGAG X CGAA IACGGUUU 1071 AAACCGTC T AATGTAAT 1501

1633 UUUUCGUU CUGAUGAG X CGAA IUUAAUUA 1072 TAATTAAC C AACGAAAA 1502

1634 UUUUUCGU CUGAUGAG X CGAA IGUUAAUU 1073 AATTAACC A ACGAAAAA 1503

1645 GUCCGGAA CUGAUGAG X CGAA ICUUUUUC 1074 GAAAAAGC T TTCCGGAC 1504

1649 AAAAGUCC CUGAUGAG X CGAA IAAAGCUU 1075 AAGCTTTC C GGACTTTT 1505

1654 CAUUUAAA CUGAUGAG X CGAA IUCCGGAA 1076 TTCCGGAC T TTTAAATG 1506

1664 AAACAGUU CUGAUGAG X CGAA ICAUUUAA 1077 TTAAATGC T AACTGTTT 1507

1668 GGAAAAAC CUGAUGAG X CGAA IUUAGCAU 1078 ATGCTAAC T GTTTTTCC 1508

1676 CAGGAAGG CUGAUGAG X CGAA IAAAAACA 1079 TGTTTTTC c CCTTCCTG 1509

1677 ACAGGAAG CUGAUGAG X CGAA IGAAAAAC 1080 GTTTTTCC c CTTCCTGT 1510

1678 GACAGGAA CUGAUGAG X CGAA IGGAAAAA 1081 TTTTTCCC c TTCCTGTC 1511

1679 AGACAGGA CUGAUGAG X CGAA IGGGAAAA 1082 TTTTCCCC T TCCTGTCT 1512

1682 CCUAGACA CUGAUGAG X CGAA IAAGGGGA 1083 TCCCCTTC c TGTCTAGG 1513

1683 UCCUAGAC CUGAUGAG X CGAA IGAAGGGG 1084 CCCCTTCC T GTCTAGGA 1514

1687 AUUUUCCU CUGAUGAG X CGAA lACAGGAA 1085 TTCCTGTC T AGGAAAAT 1515

1698 AGCUUUAU CUGAUGAG X CGAA ICAUUUUC 1086 GAAAATGC T ATAAAGCT 1516

1706 CUAAUUUG CUGAUGAG X CGAA ICUUUAUA 1087 TATAAAGC T CAAATTAG 1517

1708 AACUAAUU CUGAUGAG X CGAA IAGCUUUA 1088 TAAAGCTC A AATTAGTT 1518

1726 AACGUAUA CUGAUGAG X CGAA IUCAUUCC 1089 GGAATGAC T TATACGTT 1519

1748 AUCUCUUA CUGAUGAG X CGAA IUAUUCAA 1090 TTGAATAC c TAAGAGAT 1520

1749 UAUCUCUU CUGAUGAG X CGAA IGUAUUCA 1091 TGAATACC T AAGAGATA 1521

1759 AUCCAAAA CUGAUGAG X CGAA IUAUCUCU 1092 AGAGATAC T TTTTGGAT 1522

1779 AAGAAUAU CUGAUGAG X CGAA ICAAUAUA 1093 TATATTGC c ATATTCTT 1523

1780 UAAGAAUA CUGAUGAG X CGAA IGCAAUAU 1094 ATATTGCC A TATTCTTA 1524

1786 UUCAAGUA CUGAUGAG X CGAA IAAUAUGG 1095 CCATATTC T TACTTGAA 1525

1790 AGCAUUCA CUGAUGAG X CGAA IUAAGAAU 1096 ATTCTTAC T TGAATGCT 1526

1798 UCAUUCAA CUGAUGAG X CGAA ICAUUCAA 1097 TTGAATGC T TTGAATGA 1527

1808 CUGGAUGU CUGAUGAG X CGAA IUCAUUCA 1098 TGAATGAC T ACATCCAG 1528

1811 GAACUGGA CUGAUGAG X CGAA IUAGUCAU 1099 ATGACTAC A TCCAGTTC 1529

1814 GCAGAACU CUGAUGAG X CGAA IAUGUAGU 1100 ACTACATC C AGTTCTGC 1530

1815 UGCAGAAC CUGAUGAG X CGAA IGAUGUAG 1101 CTACATCC A GTTCTGCA 1531 Table 10

1820 AUAGGUGC CUGAUGAG X CGAA lAACUGGA 1102 TCCAGTTC T GCACCTAT 1532

1823 GGUAUAGG CUGAUGAG X CGAA ICAGAACU 1103 AGTTCTGC A CCTATACC 1533

1825 AGGGUAUA CUGAUGAG X CGAA lUGCAGAA 1104 TTCTGCAC C TATACCCT 1534

1826 GAGGGUAU CUGAUGAG X CGAA IGUGCAGA 1105 TCTGCACC T ATACCCTC 1535

1831 CACCAGAG CUGAUGAG X CGAA IUAUAGGU 1106 ACCTATAC C CTCTGGTG 1536

1832 ACACCAGA CUGAUGAG X CGAA IGUAUAGG 1107 CCTATACC C TCTGGTGT 1537

1833 AACACCAG CUGAUGAG X CGAA IGGUAUAG 1108 CTATACCC T CTGGTGTT 1538

1835 GCAACACC CUGAUGAG X CGAA IAGGGUAU 1109 ATACCCTC T GGTGTTGC 1539

1844 GGUUAAAA CUGAUGAG X CGAA ICAACACC 1110 GGTGTTGC T TTTTAACC 1540

1852 UCCAGGAA CUGAUGAG X CGAA IUUAAAAA llll TTTTTAAC C TTCCTGGA 1541

1853 UUCCAGGA CUGAUGAG X CGAA IGUUAAAA 1112 TTTTAACC T TCCTGGAA 1542

1856 GGAUUCCA CUGAUGAG X CGAA IAAGGUUA 1113 TAACCTTC C TGGAATCC 1543

1857 UGGAUUCC CUGAUGAG X CGAA IGAAGGUU 1114 AACCTTCC T GGAATCCA 1544

1864 UAGAAAAU CUGAUGAG X CGAA IAUUCCAG 1115 CTGGAATC C ATTTTCTA 1545

1865 UUAGAAAA CUGAUGAG X CGAA IGAUUCCA 1116 TGGAATCC A TTTTCTAA 1546

1871 UAUUUUUU CUGAUGAG X CGAA IAAAAUGG 1117 CCATTTTC T AAAAAATA 1547

1885 GAAGAAUG CUGAUGAG X CGAA IUCUUUAU 1118 ATAAAGAC A CATTCTTC 1548

1887 GAGAAGAA CUGAUGAG X CGAA IUGUCUUU 1119 AAAGACAC A TTCTTCTC 1549

1891 UGCUGAGA CUGAUGAG X CGAA IAAUGUGU 1120 ACACATTC T TCTCAGCA 1550

1894 UGGUGCUG CUGAUGAG X CGAA IAAGAAUG 1121 CATTCTTC T CAGCACCA 1551

1896 UGUGGUGC CUGAUGAG X CGAA IAGAAGAA 1122 TTCTTCTC A GCACCACA 1552

1899 UUGUGUGG CUGAUGAG X CGAA ICUGAGAA 1123 TTCTCAGC A CCACACAA 1553

1901 UGUUGUGU CUGAUGAG X CGAA IUGCUGAG 1124 CTCAGCAC C ACACAACA 1554

1902 GUGUUGUG CUGAUGAG X CGAA IGUGCUGA 1125 TCAGCACC A CACAACAC 1555

1904 AGGUGUUG CUGAUGAG X CGAA IUGGUGCU 1126 AGCACCAC A CAACACCT 1556

1906 AUAGGUGU CUGAUGAG X CGAA IUGUGGUG 1127 CACCACAC A ACACCTAT 1557

1909 GGAAUAGG CUGAUGAG X CGAA IUUGUGUG 1128 CACACAAC A CCTATTCC 1558

1911 UUGGAAUA CUGAUGAG X CGAA IUGUUGUG 1129 CACAACAC C TATTCCAA 1559

1912 UUUGGAAU CUGAUGAG X CGAA IGUGUUGU 1130 ACAACACC T ATTCCAAA 1560

1917 UCGAUUUU CUGAUGAG X CGAA IAAUAGGU 1131 ACCTATTC C AAAATCGA 1561

1918 GUCGAUUU CUGAUGAG X CGAA IGAAUAGG 1132 CCTATTCC A AAATCGAC 1562

1927 AAAUAUGU CUGAUGAG X CGAA IUCGAUUU 1133 AAATCGAC C ACATATTT 1563

1928 CAAAUAUG CUGAUGAG X CGAA IGUCGAUU 1134 AATCGACC A CATATTTG 1564

1930 UCCAAAUA CUGAUGAG X CGAA IUGGUCGA 1135 TCGACCAC A TATTTGGA 1565

1947 CUGAGGAG CUGAUGAG X CGAA ICUUUACU 1136 AGTAAAGC T CTCCTCAG 1566

1949 UGCUGAGG CUGAUGAG X CGAA IAGCUUUA 1137 TAAAGCTC T CCTCAGCA 1567

1951 UUUGCUGA CUGAUGAG X CGAA IAGAGCUU 1138 AAGCTCTC C TCAGCAAA 1568

1952 AUUUGCUG CUGAUGAG X CGAA IGAGAGCU 1139 AGCTCTCC T CAGCAAAT 1569

1954 ACAUUUGC CUGAUGAG X CGAA IAGGAGAG 1140 CTCTCCTC A GCAAATGT 1570

1957 UUUACAUU CUGAUGAG X CGAA ICUGAGGA 1141 TCCTCAGC A AATGTAAA 1571

1971 AUAAUUUC CUGAUGAG X CGAA IUUCUUUU 1142 AAAAGAAC A GAAATTAT 1572

1983 AGACAGUU CUGAUGAG X CGAA IUUAUAAU 1143 ATTATAAC A AACTGTCT 1573

1987 UGAGAGAC CUGAUGAG X CGAA IUUUGUUA 1144 TAACAAAC T GTCTCTCA 1574

1991 GGUCUGAG CUGAUGAG X CGAA IACAGUUU 1145 AAACTGTC T CTCAGACC 1575

1993 GUGGUCUG CUGAUGAG X CGAA IAGACAGU 1146 ACTGTCTC T CAGACCAC 1576

1995 CUGUGGUC CUGAUGAG X CGAA IAGAGACA 1147 TGTCTCTC A GACCACAG 1577

1999 UAUACUGU CUGAUGAG X CGAA IUCUGAGA 1148 TCTCAGAC C ACAGTATA 1578 Table 10

2000 UUAUACUG CUGAUGAG X CGAA IGUCUGAG 1149 CTCAGACC A CAGTATAA 1579

2002 GGUUAUAC CUGAUGAG X CGAA IUGGUCUG 1150 CAGACCAC A GTATAACC 1580

2010 UCUAGUUU CUGAUGAG X CGAA lUUAUACU 1151 AGTATAAC C AAACTAGA 1581

2011 UUCUAGUU CUGAUGAG X CGAA IGUUAUAC 1152 GTATAACC A AACTAGAA 1582

2015 UGAGUUCU CUGAUGAG X CGAA lUUUGGUU 1153 AACCAAAC T AGAACTCA 1583

2021 UAAUCCUG CUGAUGAG X CGAA IUUCUAGU 1154 ACTAGAAC T CAGGATTA 1584

2023 CUUAAUCC CUGAUGAG X CGAA IAGUUCUA 1155 TAGAACTC A GGATTAAG 1585

2036 UUUGAGUG CUGAUGAG X CGAA IUUUCUUA 1156 TAAGAAAC T CACTCAAA 1586

2038 GUUUUGAG CUGAUGAG X CGAA IAGUUUCU 1157 AGAAACTC A CTCAAAAC 1587

2040 UGGUUUUG CUGAUGAG X CGAA IUGAGUUU 1158 AAACTCAC T CAAAACCA 1588

2042 UGUGGUUU CUGAUGAG X CGAA IAGUGAGU 1159 ACTCACTC A AAACCACA 1589

2047 AGUUGUGU CUGAUGAG X CGAA IUUUUGAG 1160 CTCAAAAC C ACACAACT 1590

2048 UAGUUGUG CUGAUGAG X CGAA IGUUUUGA 1161 TCAAAACC A CACAACTA 1591

2050 UGUAGUUG CUGAUGAG X CGAA IUGGUUUU 1162 AAAACCAC A CAACTACA 1592

2052 CAUGUAGU CUGAUGAG X CGAA IUGUGGUU 1163 AACCACAC A ACTACATG 1593

2055 UUCCAUGU CUGAUGAG X CGAA IUUGUGUG 1164 CACACAAC T ACATGGAA 1594

2058 AGUUUCCA CUGAUGAG X CGAA lUAGUUGU 1165 ACAACTAC A TGGAAACT 1595

2066 GGUUGUUC CUGAUGAG X CGAA lUUUCCAU 1166 ATGGAAAC T GAACAACC 1596

2071 GAGCAGGU CUGAUGAG X CGAA IUUCAGUU 1167 AACTGAAC A ACCTGCTC 1597

2074 CAGGAGCA CUGAUGAG X CGAA IUUGUUCA 1168 TGAACAAC C TGCTCCTG 1598

2075 UCAGGAGC CUGAUGAG X CGAA IGUUGUUC 1169 GAACAACC T GCTCCTGA 1599

2078 CAUUCAGG CUGAUGAG X CGAA ICAGGUUG 1170 CAACCTGC T CCTGAATG 1600

2080 GUCAUUCA CUGAUGAG X CGAA IAGCAGGU 1171 ACCTGCTC c TGAATGAC 1601

2081 AGUCAUUC CUGAUGAG X CGAA IGAGCAGG 1172 CCTGCTCC T GAATGACT 1602

2089 UAUCCAGU CUGAUGAG X CGAA IUCAUUCA 1173 TGAATGAC T ACTGGATA 1603

2092 AUGUAUCC CUGAUGAG X CGAA IUAGUCAU 1174 ATGACTAC T GGATACAT 1604

2099 UUUUGUUA CUGAUGAG X CGAA IUAUCCAG 1175 CTGGATAC A TAACAAAA 1605

2104 CUUCAUUU CUGAUGAG X CGAA IUUAUGUA 1176 TACATAAC A AAATGAAG 1606

2115 UUUAUUUC CUGAUGAG X CGAA ICCUUCAU 1177 ATGAAGGC A GAAATAAA 1607

2131 GGUUUUAA CUGAUGAG X CGAA IAACAUCU 1178 AGATGTTC T TTAAAACC 1608

2139 UUCUCAUU CUGAUGAG X CGAA IUUUUAAA 1179 TTTAAAAC C AATGAGAA 1609

2140 GUUCUCAU CUGAUGAG X CGAA IGUUUUAA 1180 TTAAAACC A ATGAGAAC 1610

2149 UGUGUCUU CUGAUGAG X CGAA IUUCUCAU 1181 ATGAGAAC A AAGACACA 1611

2155 GUAUGUUG CUGAUGAG X CGAA IUCUUUGU 1182 ACAAAGAC A CAACATAC 1612

2157 UGGUAUGU CUGAUGAG X CGAA IUGUCUUU 1183 AAAGACAC A ACATACCA 1613

2160 UUCUGGUA CUGAUGAG X CGAA IUUGUGUC 1184 GACACAAC A TACCAGAA 1614

2164 GAGAUUCU CUGAUGAG X CGAA IUAUGUUG 1185 CAACATAC C AGAATCTC 1615

2165 AGAGAUUC CUGAUGAG X CGAA IGUAUGUU 1186 AACATACC A GAATCTCT 1616

2171 UGUCCCAG CUGAUGAG X CGAA IAUUCUGG 1187 CCAGAATC T CTGGGACA 1617

2173 UGUGUCCC CUGAUGAG X CGAA IAGAUUCU 1188 AGAATCTC T GGGACACA 1618

2179 UUUGAAUG CUGAUGAG X CGAA IUCCCAGA 1189 TCTGGGAC A CATTCAAA 1619

2181 GCUUUGAA CUGAUGAG X CGAA IUGUCCCA 1190 TGGGACAC A TTCAAAGC 1620

2185 CACUGCUU CUGAUGAG X CGAA IAAUGUGU 1191 ACACATTC A AAGCAGTG 1621

2190 CUACACAC CUGAUGAG X CGAA ICUUUGAA 1192 TTCAAAGC A GTGTGTAG 1622

2214 GCAUUUAG CUGAUGAG X CGAA ICUAUAAA 1193 TTTATAGC A CTAAATGC 1623

2216 GGGCAUUU CUGAUGAG X CGAA IUGCUAUA 1194 TATAGCAC T AAATGCCC 1624

2223 CUCUUGUG CUGAUGAG X CGAA ICAUUUAG 1195 CTAAATGC C CACAAGAG 1625 Table 10

2224 UCUCUUGU CUGAUGAG X CGAA IGCAUUUA 1196 TAAATGCC C ACAAGAGA 1626

2225 UUCUCUUG CUGAUGAG X CGAA IGGCAUUU 1197 AAATGCCC A CAAGAGAA 1627

2227 CUUUCUCU CUGAUGAG X CGAA IUGGGCAU 1198 ATGCCCAC A AGAGAAAG 1628

2237 AUAUUUCC CUGAUGAG X CGAA ICUUUCUC 1199 GAGAAAGC A GGAAATAT 1629

2247 UCAAUUUU CUGAUGAG X CGAA IAUAUUUC 1200 GAAATATC T AAAATTGA 1630

2257 UGUUAGGG CUGAUGAG X CGAA IUCAAUUU 1201 AAATTGAC A CCCTAACA 1631

2259 GAUGUUAG CUGAUGAG X CGAA IUGUCAAU 1202 ATTGACAC C CTAACATC 1632

2260 UGAUGUUA CUGAUGAG X CGAA IGUGUCAA 1203 TTGACACC C TAACATCA 1633

2261 GUGAUGUU CUGAUGAG X CGAA IGGUGUCA 1204 TGACACCC T AACATCAC 1634

2265 AAUUGUGA CUGAUGAG X CGAA IUUAGGGU 1205 ACCCTAAC A TCACAATT 1635

2268 UUUAAUUG CUGAUGAG X CGAA IAUGUUAG 1206 CTAACATC A CAATTAAA 1636

2270 CUUUUAAU CUGAUGAG X CGAA IUGAUGUU 1207 AACATCAC A ATTAAAAG 1637

2282 GCUUCUCU CUGAUGAG X CGAA IUUCUUUU 1208 AAAAGAAC T AGAGAAGC 1638

2291 UUUGCUCU CUGAUGAG X CGAA ICUUCUCU 1209 AGAGAAGC A AGAGCAAA 1639

2297 AAUGUGUU CUGAUGAG X CGAA ICUCUUGC 1210 GCAAGAGC A AACACATT 1640

2301 UUUCAAUG CUGAUGAG X CGAA IUUUGCUC 1211 GAGCAAAC A CATTGAAA 1641

2303 CUUUUCAA CUGAUGAG X CGAA IUGUUUGC 1212 GCAAACAC A TTGAAAAG 1642

2313 CUUCUCUU CUGAUGAG X CGAA ICUUUUCA 1213 TGAAAAGC T AAGAGAAG 1643

2324 UUAUUUCU CUGAUGAG X CGAA ICCUUCUC 1214 GAGAAGGC A AGAAATAA 1644

2334 CUGAUCUU CUGAUGAG X CGAA IUUAUUUC 1215 GAAATAAC T AAGATCAG 1645

2341 UUCUGCUC CUGAUGAG X CGAA IAUCUUAG 1216 CTAAGATC A GAGCAGAA 1646

2346 UUCAGUUC CUGAUGAG X CGAA ICUCUGAU 1217 ATCAGAGC A GAACTGAA 1647

2351 UUUCCUUC CUGAUGAG X CGAA IUUCUGCU 1218 AGCAGAAC T GAAGGAAA 1648

2367 GUUUUUUG CUGAUGAG X CGAA IUCUCUAU 1219 ATAGAGAC A CAAAAAAC 1649

2369 GAGUUUUU CUGAUGAG X CGAA IUGUCUCU 1220 AGAGACAC A AAAAACTC 1650

2376 UUUUGAAG CUGAUGAG X CGAA IUUUUUUG 1221 CAAAAAAC T CTTCAAAA 1651

2378 UUUUUUGA CUGAUGAG X CGAA IAGUUUUU 1222 AAAAACTC T TCAAAAAA 1652

2381 UGAUUUUU CUGAUGAG X CGAA IAAGAGUU 1223 AACTCTTC A AAAAATCA 1653

2389 GGAUUCAU CUGAUGAG X CGAA IAUUUUUU 1224 AAAAAATC A ATGAATCC 1654

2397 CAGCUCCU CUGAUGAG X CGAA IAUUCAUU 1225 AATGAATC C AGGAGCTG 1655

2398 CCAGCUCC CUGAUGAG X CGAA IGAUUCAU 1226 ATGAATCC A GGAGCTGG 1656

2404 AAAAAACC CUGAUGAG X CGAA ICUCCUGG 1227 CCAGGAGC T GGTTTTTT 1657

2422 AAUUUUGU CUGAUGAG X CGAA IAUCGUUU 1228 AAACGATC A ACAAAATT 1658

2425 AUCAAUUU CUGAUGAG X CGAA IUUGAUCG 1229 CGATCAAC A AAATTGAT 1659

2438 CUUGCUAG CUGAUGAG X CGAA IUCUAUCA 1230 TGATAGAC A CTAGCAAG 1660

2440 GUCUUGCU CUGAUGAG X CGAA IUGUCUAU 1231 ATAGACAC T AGCAAGAC 1661

2444 AUUAGUCU CUGAUGAG X CGAA ICUAGUGU 1232 ACACTAGC A AGACTAAT 1662

2449 UCUUUAUU CUGAUGAG X CGAA IUCUUGCU 1233 AGCAAGAC T AATAAAGA 1663

2476 CUUCUAUU CUGAUGAG X CGAA IAUUCUUC 1234 GAAGAATC A AATAGAAG 1664

2486 UUUUUUAU CUGAUGAG X CGAA ICUUCUAU 1235 ATAGAAGC A ATAAAAAA 1665

2511 AUUGGUGG CUGAUGAG X CGAA IAUAUCCC 1236 GGGATATC A CCACCAAT 1666

2513 GGAUUGGU CUGAUGAG X CGAA IUGAUAUC 1237 GATATCAC C ACCAATCC 1667

2514 GGGAUUGG CUGAUGAG X CGAA IGUGAUAU 1238 ATATCACC A CCAATCCC 1668

2516 GUGGGAUU CUGAUGAG X CGAA lUGGUGAU 1239 ATCACCAC C AATCCCAC 1669

2517 UGUGGGAU CUGAUGAG X CGAA IGUGGUGA 1240 TCACCACC A ATCCCACA 1670

2521 UUUCUGUG CUGAUGAG X CGAA IAUUGGUG 1241 CACCAATC C CACAGAAA 1671

2522 AUUUCUGU CUGAUGAG X CGAA IGAUUGGU 1242 ACCAATCC C ACAGAAAT 1672 Table 10

2523 UAUUUCUG CUGAUGAG X CGAA IGGAUUGG 1243 CCAATCCC A CAGAAATA 1S73

2525 UUUAUUUC CUGAUGAG X CGAA IUGGGAUU 1244 AATCCCAC A GAAATAAA 1674

2535 CUGAUGGU CUGAUGAG X CGAA IUUUAUUU 1245 AAATAAAC C ACCATCAG 1675

2536 UCUGAUGG CUGAUGAG X CGAA IGUUUAUU 124S AATAAACC A CCATCAGA 1676

2538 UCUCUGAU CUGAUGAG X CGAA IUGGUUUA 1247 TAAACCAC C ATCAGAGA 1677

2539 UUCUCUGA CUGAUGAG X CGAA IGUGGUUU 1248 AAACCACC A TCAGAGAA 1678

2542 GUAUUCUC CUGAUGAG X CGAA IAUGGUGG 1249 CCACCATC A GAGAATAC 1679

2551 GUGUUUGU CUGAUGAG X CGAA IUAUUCUC 1250 GAGAATAC T ACAAACAC 1680

2554 GAGGUGUU CUGAUGAG X CGAA I AGUAUU 1251 AATACTAC A AACACCTC 1681

2558 CGUAGAGG CUGAUGAG X CGAA IUUUGUAG 1252 CTACAAAC A CCTCTACG 1682

2560 UGCGUAGA CUGAUGAG X CGAA IUGUUUGU 1253 ACAAACAC C TCTACGCA 1683

2561 UUGCGUAG CUGAUGAG X CGAA IGUGUUUG 1254 CAAACACC T CTACGCAA 1684

Input Sequence = HSU29607 Cut Site = CH/

Stem Length = 8 Core Sequence = CUGAUGAG X CGAA (X = GCCGUUAGGC or other stem II)

Seq 1 = HSU2960 (Human methionine aminopeptidase mRNA, complete eds , 2569 bp)

Table 11

Table 11: Human Methionine Aminopeptidase type 2 (MetAP-2) G-cleaver Ribozyme and Target Sequence

Nt. Substrate Sequence Seq. ID Ribozyme Sequence Seq. ID position Nos. Nos.

64 GGAGCCACCU G AAUGG 1685 CCAUU UGAUGGCAUGCACUAUGCGCG AGGUGGCUCC 1834

71 CCUGAAUGGC G ACCUG 1686 CAGGU UGAUGGCAUGCACUAUGCGCG GCCAUUCAGG 1835

86 GGAUCCAGAC G ACAGG 1687 CCUGU UGAUGGCAUGCACUAUGCGCG GUCUGGAUCC 1836

104 AGAAGGAGCU G CCUCU 1688 AGAGG UGAUGGCAUGCACUAUGCGCG AGCUCCUUCU 1837

116 CUCUACGGCU G AGGAA 1689 UUCCU UGAUGGCAUGCACUAUGCGCG AGCCGUAGAG 1838

141 AAAAAAAGAC G AAAGA 1690 UCUUU UGAUGGCAUGCACUAUGCGCG GUCUUUUUUU 1839

170 AGGGCCUUCU G CAGCA 1691 UGCUG UGAUGGCAUGCACUAUGCGCG AGAAGGCCCU 1840

191 ACAGGAACCU G AUAAA 1692 UUUAU UGAUGGCAUGCACUAUGCGCG AGGUUCCUGU 1841

218 CUCAGUGGAU G AAGUA 1693 UACUU UGAUGGCAUGCACUAUGCGCG AUCCACUGAG 1842

269 AGAAAGAGAU G AAGAU 1694 AUCUU UGAUGGCAUGCACUAUGCGCG AUCUCUUUCU 1843

275 AGAUGAAGAU G AUGAA 1695 UUCAU UGAUGGCAUGCACUAUGCGCG AUCUUCAUCU 1844

278 UGAAGAUGAU G AAGAU 1696 AUCUU UGAUGGCAUGCACUAUGCGCG AUCAUCUUCA 1845

293 UGGAGAUGGC G AUGGA 1697 UCCAU UGAUGGCAUGCACUAUGCGCG GCCAUCUCCA 1846

384 GUUCCAAUAU G UGACC 1698 GGUCA UGAUGGCAUGCACUAUGCGCG AUAUUGGAAC 1847

386 UCCAAUAUGU G ACCUG 1699 CAGGU UGAUGGCAUGCACUAUGCGCG ACAUAUUGGA 1848

391 UAUGUGACCU G UAUCC 1700 GGAUA UGAUGGCAUGCACUAUGCGCG AGGUCACAUA . 1849

404 UCCUAAUGGU G UAUUU 1701 AAAUA UGAUGGCAUGCACUAUGCGCG ACCAUUAGGA 1850

426 GGACAAGAAU G CGAAU 1702 AUUCG UGAUGGCAUGCACUAUGCGCG AUUCUUGUCC 1851

428 ACAAGAAUGC G AAUAC 1703 GUAUU UGAUGGCAUGCACUAUGCGCG GCAUUCUUGU 1852

453 CAAGAUGGGC G AACAG 1704 CUGUU UGAUGGCAUGCACUAUGCGCG GCCCAUCUUG 1853

461 GCGAACAGCU G CUUGG 1705 CCAAG UGAUGGCAUGCACUAUGCGCG AGCUGUUCGC 1854

479 AACUACAAGU G AAGAA 1706 UUCUU UGAUGGCAUGCACUAUGCGCG ACUUGUAGUU 1855

509 UCAGGCAAGU G AAGAG 1707 CUCUU UGAUGGCAUGCACUAUGCGCG ACUUGCCUGA 1856

524 GAUUUGGAAU G AUUUU 1708 AAAAU UGAUGGCAUGCACUAUGCGCG AUUCCAAAUC 1857

531 AAUGAUUUUC G AGAAG 1709 CUUCU UGAUGGCAUGCACUAUGCGCG GAAAAUCAUU 1858

539 UCGAGAAGCU G CAGAA 1710 UUCUG UGAUGGCAUGCACUAUGCGCG AGCUUCUCGA 1859

552 GAAGCACAUC G ACAAG 1711 CUUGU UGAUGGCAUGCACUAUGCGCG GAUGUGCUUC 1860

574 AAUACGUAAU G AGCUG 1712 CAGCU UGAUGGCAUGCACUAUGCGCG AUUACGUAUU 1861

Table 11

595 AGCCUGGGAU G ACAAU 1713 AUUGU UGAUGGCAUGCACUAUGCGCG AUCCCAGGCU 1862

601 GGAUGACAAU G AUAGA 1714 UCUAU UGAUGGCAUGCACUAUGCGCG AUUGUCAUCC 1863

612 AUAGAAAUCU G UGAAA 1715 UUUCA UGAUGGCAUGCACUAUGCGCG AGAUUUCUAU 1864

614 AGAAAUCUGU G AAAAG 1716 CUUUU UGAUGGCAUGCACUAUGCGCG ACAGAUUUCU 1865

630 UUGGAAGACU G UUCAC 1717 GUGAA UGAUGGCAUGCACUAUGCGCG AGUCUUCCAA 1866

636 GACUGUUCAC G CAAGU 1718 ACUUG UGAUGGCAUGCACUAUGCGCG GUGAACAGUC 1867

665 UGGAUUAAAU G CAGGC 1719 GCCUG UGAUGGCAUGCACUAUGCGCG AUUUAAUCCA 1868

690 CCUACUGGAU G UUCUC 1720 GAGAA UGAUGGCAUGCACUAUGCGCG AUCCAGUAGG 1869

705 CUCAAUAAUU G UGCUG 1721 CAGCA UGAUGGCAUGCACUAUGCGCG AAUUAUUGAG 1870

707 CAAUAAUUGU G CUGCC 1722 GGCAG UGAUGGCAUGCACUAUGCGCG ACAAUUAUUG 1871

710 UAAUUGUGCU G CCCAU 1723 AUGGG UGAUGGCAUGCACUAUGCGCG AGCACAAUUA 1872

728 UACUCCCAAU G CCGGU 1724 ACCGG UGAUGGCAUGCACUAUGCGCG AUUGGGAGUA 1873

734 CAAUGCCGGU G ACACA 1725 UGUGU UGAUGGCAUGCACUAUGCGCG ACCGGCAUUG 1874

755 AUUACAGUAU G AUGAC 1726 GUCAU UGAUGGCAUGCACUAUGCGCG AUACUGUAAU 1875

758 ACAGUAUGAU G ACAUC 1727 GAUGU UGAUGGCAUGCACUAUGCGCG AUCAUACUGU 1876

765 GAUGACAUCU G UAAAA 1728 UUUUA UGAUGGCAUGCACUAUGCGCG AGAUGUCAUC 1877

806 UAGGAUUAUU G ACUGU 1729 ACAGU UGAUGGCAUGCACUAUGCGCG AAUAAUCCUA 1878

810 AUUAUUGACU G UGCUU 1730 AAGCA UGAUGGCAUGCACUAUGCGCG AGUCAAUAAU 1879

812 UAUUGACUGU G CUUUU 1731 AAAAG UGAUGGCAUGCACUAUGCGCG ACAGUCAAUA 1880

821 UGCUUUUACU G UCACU 1732 AGUGA UGAUGGCAUGCACUAUGCGCG AGUAAAAGCA 1881

842 UCCCAAAUAU G AUACG 1733 CGUAU UGAUGGCAUGCACUAUGCGCG AUAUUUGGGA 1882

860 AUUAAAAGCU G UAAAA 1734 UUUUA UGAUGGCAUGCACUAUGCGCG AGCUUUUAAU 1883

869 UGUAAAAGAU G CUACU 1735 AGUAG UGAUGGCAUGCACUAUGCGCG AUCUUUUACA 1884

891 GGAAUAAAGU G UGCUG 1736 CAGCA UGAUGGCAUGCACUAUGCGCG ACUUUAUUCC 1885

893 AAUAAAGUGU G CUGGA 1737 UCCAG UGAUGGCAUGCACUAUGCGCG ACACUUUAUU 1886

902 UGCUGGAAUU G AUGUU 1738 AACAU UGAUGGCAUGCACUAUGCGCG AAUUCCAGCA 1887

905 UGGAAUUGAU G UUCGU 1739 ACGAA UGAUGGCAUGCACUAUGCGCG AUCAAUUCCA 1888

913 AUGUUCGUCU G UGUGA 1740 UCACA UGAUGGCAUGCACUAUGCGCG AGACGAACAU 1889

915 GUUCGUCUGU G UGAUG 1741 CAUCA UGAUGGCAUGCACUAUGCGCG ACAGACGAAC 1890

917 UCGUCUGUGU G AUGUU 1742 AACAU UGAUGGCAUGCACUAUGCGCG ACACAGACGA 1891

920 UCUGUGUGAU G UUGGU 1743 ACCAA UGAUGGCAUGCACUAUGCGCG AUCACACAGA 1892

Table 11

926 UGAUGUUGGU G AGGCC 1744 GGCCU UGAUGGCAUGCACUAUGCGCG ACCAACAUCA 1893

956 GGAGUCCUAU G AAGUU 1745 AACUU UGAUGGCAUGCACUAUGCGCG AUAGGACUCC 1894

962 CUAUGAAGUU G AAAUA 1746 UAUUU UGAUGGCAUGCACUAUGCGCG AACUUCAUAG 1895

988 CAUAUCAAGU G AAACC 1747 GGUUU UGAUGGCAUGCACUAUGCGCG ACUUGAUAUG 1896

1040 UAGAAUACAU G CUGGA 1748 UCCAG UGAUGGCAUGCACUAUGCGCG AUGUAUUCUA 1897

1054 GAAAAACAGU G CCGAU 1749 AUCGG UGAUGGCAUGCACUAUGCGCG ACUGUUUUUC 1898

1057 AAACAGUGCC G AUUGU 1750 ACAAU UGAUGGCAUGCACUAUGCGCG GGCACUGUUU 1899

1061 AGUGCCGAUU G UGAAA 1751 UUUCA UGAUGGCAUGCACUAUGCGCG AAUCGGCACU 1900

1063 UGCCGAUUGU G AAAGG 1752 CCUUU UGAUGGCAUGCACUAUGCGCG ACAAUCGGCA 1901

1106 AGAAGUAUAU G CAAUU 1753 AAUUG UGAUGGCAUGCACUAUGCGCG AUAUACUUCU 1902

1112 AUAUGCAAUU G AAACC 1754 GGUUU UGAUGGCAUGCACUAUGCGCG AAUUGCAUAU 1903

1139 AGGAAAAGGU G UUGUU 1755 AACAA UGAUGGCAUGCACUAUGCGCG ACCUUUUCCU 1904

1142 AAAAGGUGUU G UUCAU 1756 AUGAA UGAUGGCAUGCACUAUGCGCG AACACCUUUU 1905

1148 UGUUGUUCAU G AUGAU 1757 AUCAU UGAUGGCAUGCACUAUGCGCG AUGAACAACA 1906

1151 UGUUCAUGAU G AUAUG 1758 CAUAU UGAUGGCAUGCACUAUGCGCG AUCAUGAACA 1907

1161 GAUAUGGAAU G UUCAC 1759 GUGAA UGAUGGCAUGCACUAUGCGCG AUUCCAUAUC 1908

1174 CACAUUACAU G AAAAA 1760 UUUUU UGAUGGCAUGCACUAUGCGCG AUGUAAUGUG 1909

1184 GAAAAAUUUU G AUGUU 1761 AACAU UGAUGGCAUGCACUAUGCGCG AAAAUUUUUC 1910

1187 AAAUUUUGAU G UUGGA 1762 UCCAA UGAUGGCAUGCACUAUGCGCG AUCAAAAUUU 1911

1196 UGUUGGACAU G UGCCA 1763 UGGCA UGAUGGCAUGCACUAUGCGCG AUGUCCAACA 1912

1198 UUGGACAUGU G CCAAU 1764 AUUGG UGAUGGCAUGCACUAUGCGCG ACAUGUCCAA 1913

1228 CAAAACACUU G UUAAA 1765 UUUAA UGAUGGCAUGCACUAUGCGCG AAGUGUUUUG 1914

1235 CUUGUUAAAU G UCAUC 1766 GAUGA UGAUGGCAUGCACUAUGCGCG AUUUAACAAG 1915

1244 UGUCAUCAAU G AAAAC 1767 GUUUU UGAUGGCAUGCACUAUGCGCG AUUGAUGACA 1916

1262 UGGAACCCUU σ CCUUC 1768 GAAGG UGAUGGCAUGCACUAUGCGCG AAGGGUUCCA 1917

1269 CUUGCCUUCU G CCGCA 1769 UGCGG UGAUGGCAUGCACUAUGCGCG AGAAGGCAAG 1918

1272 GCCUUCUGCC G CAGAU 1770 AUCUG UGAUGGCAUGCACUAUGCGCG GGCAGAAGGC 1919

1287 UGGCUGGAUC G CUUGG 1771 CCAAG UGAUGGCAUGCACUAUGCGCG GAUCCAGCCA 1920

1309 GUAAAUACUU G AUGGC 1772 GCCAU UGAUGGCAUGCACUAUGCGCG AAGUAUUUAC 1921

1318 UGAUGGCUCU G AAGAA 1773 UUCUU UGAUGGCAUGCACUAUGCGCG AGAGCCAUCA 1922

1327 UGAAGAAUCU G UGUGA 1774 UCACA UGAUGGCAUGCACUAUGCGCG AGAUUCUUCA 1923

Table 11

1329 AAGAAUCUGU G UGACU 1775 AGUCA UGAUGGCAUGCACUAUGCGCG ACAGAUUCUU 1924

1331 GAAUCUGUGU G ACUUG 1776 CAAGU UGAUGGCAUGCACUAUGCGCG ACACAGAUUC 1925

1343 CUUGGGCAUU G UAGAU 1777 AUCUA UGAUGGCAUGCACUAUGCGCG AAUGCCCAAG 1926

1365 CCACCAUUAU G UGACA 1778 UGUCA UGAUGGCAUGCACUAUGCGCG AUAAUGGUGG 1927

1367 ACCAUUAUGU G ACAUU 1779 AAUGU UGAUGGCAUGCACUAUGCGCG ACAUAAUGGU 1928

1390 CAUAUACAGC G CAAUU 1780 AAUUG UGAUGGCAUGCACUAUGCGCG GCUGUAUAUG 1929

1397 AGCGCAAUUU G AACAU 1781 AUGUU UGAUGGCAUGCACUAUGCGCG AAAUUGCGCU 1930

1411 AUACCAUCCU G UUGCG 1782 CGCAA UGAUGGCAUGCACUAUGCGCG AGGAUGGUAU 1931

1414 CCAUCCUGUU G CGUCC 1783 GGACG UGAUGGCAUGCACUAUGCGCG AACAGGAUGG 1932

1425 CGUCCAACAU G UAAAG 1784 CUUUA UGAUGGCAUGCACUAUGCGCG AUGUUGGACG 1933

1436 UAAAGAAGUU G UCAGC 1785 GCUGA UGAUGGCAUGCACUAUGCGCG AACUUCUUUA 1934

1451 CAGAGGAGAU G ACUAU 1786 AUAGU UGAUGGCAUGCACUAUGCGCG AUCUCCUCUG 1935

1496 UUUAUUUUCU G AGCUU 1787 AAGCU UGAUGGCAUGCACUAUGCGCG AGAAAAUAAA 1936

1503 UCUGAGCUUU G UUGGA 1788 UCCAA UGAUGGCAUGCACUAUGCGCG AAAGCUCAGA 1937

1515 UGGAAAACAU G AUACC 1789 GGUAU UGAUGGCAUGCACUAUGCGCG AUGUUUUCCA 1938

1532 GAAUUAAUUU G CCACA 1790 UGUGG UGAUGGCAUGCACUAUGCGCG AAAUUAAUUC 1939

1539 UUUGCCACAU G UUGUC 1791 GACAA UGAUGGCAUGCACUAUGCGCG AUGUGGCAAA 1940

1542 GCCACAUGUU G UCUGU 1792 ACAGA UGAUGGCAUGCACUAUGCGCG AACAUGUGGC 1941

1546 CAUGUUGUCU G UUUUA 1793 UAAAA UGAUGGCAUGCACUAUGCGCG AGACAACAUG 1942

1565 GUGGACCCAU G UAAUA 1794 UAUUA UGAUGGCAUGCACUAUGCGCG AUGGGUCCAC 1943

1582 UUUUAUCCAU G UUUAA 1795 UUAAA UGAUGGCAUGCACUAUGCGCG AUGGAUAAAA 1944

1624 ACCGUCUAAU G UAAUU 1796 AAUUA UGAUGGCAUGCACUAUGCGCG AUUAGACGGU 1945

1637 AUUAACCAAC G AAAAA 1797 UUUUU UGAUGGCAUGCACUAUGCGCG GUUGGUUAAU 1946

1662 ACUUUUAAAU G CUAAC 1798 GUUAG UGAUGGCAUGCACUAUGCGCG AUUUAAAAGU 1947

1669 AAUGCUAACU G UUUUU 1799 AAAAA UGAUGGCAUGCACUAUGCGCG AGUUAGCAUU 1948

1684 UCCCCUUCCU G UCUAG 1800 CUAGA UGAUGGCAUGCACUAUGCGCG AGGAAGGGGA 1949

1696 CUAGGAAAAU G CUAUA 1801 UAUAG UGAUGGCAUGCACUAUGCGCG AUUUUCCUAG 1950

1723 AGUUAGGAAU G ACUUA 1802 UAAGU UGAUGGCAUGCACUAUGCGCG AUUCCUAACU 1951

1737 UAUACGUUUU G UUUUG 1803 CAAAA UGAUGGCAUGCACUAUGCGCG AAAACGUAUA 1952

1742 GUUUUGUUUU G AAUAC 1804 GUAUU UGAUGGCAUGCACUAUGCGCG AAAACAAAAC 1953

1777 UAUUUAUAUU G CCAUA 1805 UAUGG UGAUGGCAUGCACUAUGCGCG AAUAUAAAUA 1954

Table 11

1792 AUUCUUACUU G AAUGC 1806 GCAUU UGAUGGCAUGCACUAUGCGCG AAGUAAGAAU 1955

1796 UUACUUGAAU G CUUUG 1807 CAAAG UGAUGGCAUGCACUAUGCGCG AUUCAAGUAA 1956

1801 UGAAUGCUUU G AAUGA 1808 UCAUU UGAUGGCAUGCACUAUGCGCG AAAGCAUUCA 1957

1805 UGCUUUGAAU G ACUAC 1809 GUAGU UGAUGGCAUGCACUAUGCGCG AUUCAAAGCA 1958

1821 AUCCAGUUCU G CACCU 1810 AGGUG UGAUGGCAUGCACUAUGCGCG AGAACUGGAU 1959

1839 ACCCUCUGGU G UUGCU 1811 AGCAA UGAUGGCAUGCACUAUGCGCG ACCAGAGGGU 1960

1842 CUCUGGUGUU G CUUUU 1812 AAAAG UGAUGGCAUGCACUAUGCGCG AACACCAGAG 1961

1924 UUCCAAAAUC G ACCAC 1813 GUGGU UGAUGGCAUGCACUAUGCGCG GAUUUUGGAA 1962

1961 CUCAGCAAAU G UAAAA 1814 UUUUA UGAUGGCAUGCACUAUGCGCG AUUUGCUGAG 1963

1988 AUAACAAACU G UCUCU 1815 AGAGA UGAUGGCAUGCACUAUGCGCG AGUUUGUUAU 1964

2067 CAUGGAAACU G AACAA 1816 UUGUU UGAUGGCAUGCACUAUGCGCG AGUUUCCAUG 1965

2076 UGAACAACCU G CUCCU 1817 AGGAG UGAUGGCAUGCACUAUGCGCG AGGUUGUUCA 1966

2082 ACCUGCUCCU G AAUGA 1818 UCAUU UGAUGGCAUGCACUAUGCGCG AGGAGCAGGU 1967

2086 GCUCCUGAAU G ACUAC 1819 GUAGU UGAUGGCAUGCACUAUGCGCG AUUCAGGAGC 1968

2109 AUAACAAAAU G AAGGC 1820 GCCUU UGAUGGCAUGCACUAUGCGCG AUUUUGUUAU 1969

2127 AAAUAAAGAU G UUCUU 1821 AAGAA UGAUGGCAUGCACUAUGCGCG AUCUUUAUUU 1970

2143 UAAAACCAAU G AGAAC 1822 GUUCU UGAUGGCAUGCACUAUGCGCG AUUGGUUUUA 1971

2193 UCAAAGCAGU G UGUAG 1823 CUACA UGAUGGCAUGCACUAUGCGCG ACUGCUUUGA 1972

2195 AAAGCAGUGU G UAGAG 1824 CUCUA UGAUGGCAUGCACUAUGCGCG ACACUGCUUU 1973

2221 AGCACUAAAU G CCCAC 1825 GUGGG UGAUGGCAUGCACUAUGCGCG AUUUAGUGCU 1974

2254 AUCUAAAAUU G ACACC 1826 GGUGU UGAUGGCAUGCACUAUGCGCG AAUUUUAGAU 1975

2306 CAAACACAUU G AAAAG 1827 CUUUU UGAUGGCAUGCACUAUGCGCG AAUGUGUUUG 1976

2352 GAGCAGAACU G AAGGA 1828 UCCUU UGAUGGCAUGCACUAUGCGCG AGUUCUGCUC 1977

2392 AAAAAUCAAU G AAUCC 1829 GGAUU UGAUGGCAUGCACUAUGCGCG AUUGAUUUUU 1978

2413 CUGGUUUUUU G AAACG 1830 CGUUU UGAUGGCAUGCACUAUGCGCG AAAAAACCAG 1979

2418 UUUUUGAAAC G AUCAA 1831 UUGAU UGAUGGCAUGCACUAUGCGCG GUUUCAAAAA 1980

2431 CAACAAAAUU G AUAGA 1832 UCUAU UGAUGGCAUGCACUAUGCGCG AAUUUUGUUG 1981

2496 AAUAAAAAAU G AUAAA 1833 UUUAU UGAUGGCAUGCACUAUGCGCG AUUUUUUAUU 1982

Input Sequence = HSU29607. Cut Site = YG/ or UG/U.

Stem Length 5/10. Core Sequence = UGAUG GCAUGCACUAUGC GCG

Table 11

Table 12

Table 12: Anti Human MetAP-2 HH, NCH, and G-Cleaver Ribozymes

Table 13

Table 13: Human telomerase reverse transcriptase (TERT) Hammerhead Ribozyme and Target Sequence nt. Ribozyme Sequence Seq ID Substrate Sequence Seq ID Position Nos. Nos.

13 CGCAGCAG CUGAUGAG X CGAA ACGCAGCG CGCTGCGT C CTGCTGCG

68 GCAGCGGG CUGAUGAG X CGAA AGCGCGCG CGCGCGCT C CCCGCTGC

90 GCAGCAGG CUGAUGAG X CGAA AGCGCACG CGTGCGCT C CCTGCTGC

108 CCUCGCGG CUGAUGAG X CGAA AGUGGCUG CAGCCACT A CCGCGAGG

135 GCCGCACG CUGAUGAG X CGAA ACGUGGCC GGCCACGT T CGTGCGGC

136 CGCCGCAC CUGAUGAG X CGAA AACGUGGC GCCACGTT C GTGCGGCG

194 CGCGCGGA CUGAUGAG X CGAA AGCCGCCG CGGCGGCT T TCCGCGCG

195 GCGCGCGG CUGAUGAG X CGAA AAGCCGCC GGCGGCTT T CCGCGCGC

196 AGCGCGCG CUGAUGAG X CGAA AAAGCCGC GCGGCTTT C CGCGCGCT

264 GGCGGAAG CUGAUGAG X CGAA AGGGGGCG CGCCCCCT C CTTCCGCC

267 CCUGGCGG CUGAUGAG X CGAA AGGAGGGG CCCCTCCT T CCGCCAGG

268 ACCUGGCG CUGAUGAG X CGAA AAGGAGGG CCCTCCTT C CGCCAGGT

279 UCAGGCAG CUGAUGAG X CGAA ACACCUGG CCAGGTGT C CTGCCTGA

351 CGAAGCCG CUGAUGAG X CGAA AGGCCAGC GCTGGCCT T CGGCTTCG

352 GCGAAGCC CUGAUGAG X CGAA AAGGCCAG CTGGCCTT c GGCTTCGC

357 GCAGCGCG CUGAUGAG X CGAA AGCCGAAG CTTCGGCT T CGCGCTGC

358 AGCAGCGC CUGAUGAG X CGAA AAGCCGAA TTCGGCTT c GCGCTGCT

399 UGGUGGUG CUGAUGAG X CGAA AGGCCUCG CGAGGCCT T CACCACCA

400 CUGGUGGU CUGAUGAG X CGAA AAGGCCUC GAGGCCTT c ACCACCAG

420 UGGGCAGG CUGAUGAG X CGAA AGCUGCGC GCGCAGCT A CCTGCCCA .

505 AGCAGGUG CUGAUGAG X CGAA ACCAGCAC GTGCTGGT T CACCTGCT

506 CAGCAGGU CUGAUGAG X CGAA AACCAGCA TGCTGGTT C ACCTGCTG

529 AGCACAAA CUGAUGAG X CGAA AGCGCGCA TGCGCGCT C TTTGTGCT

531 CCAGCACA CUGAUGAG X CGAA AGAGCGCG CGCGCTCT T TGTGCTGG

532 ACCAGCAC CUGAUGAG X CGAA AAGAGCGC GCGCTCTT τ GTGCTGGT

545 GCAGCUGG CUGAUGAG X CGAA AGCCACCA TGGTGGCT c CCAGCTGC

558 ACACCUGG CUGAUGAG X CGAA AGGCGCAG CTGCGCCT A CCAGGTGT

582 CGAGCUGG CUGAUGAG X CGAA ACAGCGGC GCCGCTGT A CCAGCTCG

589 GCAGCGCC CUGAUGAG X CGAA AGCUGGUA TACCAGCT c GGCGCTGC

602 CCGGGCCU CUGAUGAG X CGAA AGUGGCAG CTGCCACT c AGGCCCGG

626 GGGUCCAC CUGAUGAG X CGAA AGCGUGUG CACACGCT A GTGGACCC

644 GCAUCCCA CUGAUGAG X CGAA ACGCCUUC GAAGGCGT c TGGGATGC

671 CCUGACGC CUGAUGAG X CGAA AUGGUUCC . GGAACCAT A GCGTCAGG

676 GCCUCCCU CUGAUGAG X CGAA ACGCUAUG CATAGCGT C AGGGAGGC

691 CCCAGGGG CUGAUGAG X CGAA ACCCCGGC GCCGGGGT C CCCCTGGG

749 CAACGGCA CUGAUGAG X CGAA ACUUCGGC GCCGAAGT c TGCCGTTG

756 UCUUGGGC CUGAUGAG X CGAA ACGGCAGA TCTGCCGT T GCCCAAGA

808 CCCUGCCC CUGAUGAG X CGAA ACGGGCGU ACGCCCGT T GGGCAGGG

819 GGGCCCAG CUGAUGAG X CGAA ACCCCUGC GCAGGGGT c CTGGGCCC

863 CACACAGA CUGAUGAG X CGAA ACCACGGU ACCGTGGT T TCTGTGTG

864 CCACACAG CUGAUGAG X CGAA AACCACGG CCGTGGTT T CTGTGTGG

865 ACCACACA CUGAUGAG X CGAA AAACCACG CGTGGTTT c TGTGTGGT

876 UGGCAGGU CUGAUGAG X CGAA ACACCACA TGTGGTGT c ACCTGCCA Table 13

906 CCUCCAAA CUGAUGAG X CGAA AGGUGGCU AGCCACCT C TTTGGAGG

908 ACCCUCCA CUGAUGAG X CGAA AGAGGUGG CCACCTCT T TGGAGGGT

909 CACCCUCC CUGAUGAG X CGAA AAGAGGUG CACCTCTT T GGAGGGTG

922 GUGCCAGA CUGAUGAG X CGAA AGCGCACC GGTGCGCT C TCTGGCAC

924 GCGUGCCA CUGAUGAG X CGAA AGAGCGCA TGCGCTCT C TGGCACGC

939 AUGGGUGG CUGAUGAG X CGAA AGUGGCGC GCGCCACT C CCACCCAT

948 GGCCCACG CUGAUGAG X CGAA AUGGGUGG CCACCCAT C CGTGGGCC

981 GCGAUGUG CUGAUGAG X CGAA AUGGGGGG CCCCCCAT C CACATCGC

987 GUGGCCGC CUGAUGAG X CGAA AUGUGGAU ATCCACAT C GCGGCCAC

1001 GUCCCAGG CUGAUGAG X CGAA ACGUGGUG CACCACGT C CCTGGGAC

1016 CGGGGGAC CUGAUGAG X CGAA AGGCGUGU ACACGCCT T GTCCCCCG

1019 CACCGGGG CUGAUGAG X CGAA ACAAGGCG CGCCTTGT C CCCCGGTG

1029 UCUCGGCG CUGAUGAG X CGAA ACACCGGG CCCGGTGT A CGCCGAGA

1047 AGUAGAGG CUGAUGAG X CGAA AGUGCUUG CAAGCACT T CCTCTACT

1048 GAGUAGAG CUGAUGAG X CGAA AAGUGCUU AAGCACTT C CTCTACTC

1051 GAGGAGUA CUGAUGAG X CGAA AGGAAGUG CACTTCCT C TACTCCTC

1053 CUGAGGAG CUGAUGAG X CGAA AGAGGAAG CTTCCTCT A CTCCTCAG

1056 CGCCUGAG CUGAUGAG X CGAA AGUAGAGG CCTCTACT C CTCAGGCG

1059 UGUCGCCU CUGAUGAG X CGAA AGGAGUAG CTACTCCT C AGGCGACA

1086 GUAGGAAG CUGAUGAG X CGAA AGGGCCGC GCGGCCCT C CTTCCTAC

1089 UGAGUAGG CUGAUGAG X CGAA AGGAGGGC GCCCTCCT T CCTACTCA

1090 CUGAGUAG CUGAUGAG X CGAA AAGGAGGG CCCTCCTT C CTACTCAG

1093 GAGCUGAG CUGAUGAG X CGAA AGGAAGGA TCCTTCCT A CTCAGCTC

1096 AGAGAGCU CUGAUGAG X CGAA AGUAGGAA TTCCTACT C AGCTCTCT

1101 GCCUCAGA CUGAUGAG X CGAA AGCUGAGU ACTCAGCT C TCTGAGGC

1103 GGGCCUCA CUGAUGAG X CGAA AGAGCUGA TCAGCTCT C TGAGGCCC

1127 GAGCCUCC CUGAUGAG X CGAA AGCGCCAG CTGGCGCT C GGAGGCTC

1135 GUCUCCAC CUGAUGAG X CGAA AGCCUCCG CGGAGGCT C GTGGAGAC

1147 CCCAGAAA CUGAUGAG X CGAA AUGGUCUC GAGACCAT C TTTCTGGG

1149 AACCCAGA CUGAUGAG X CGAA AGAUGGUC GACCATCT T TCTGGGTT

1150 GAACCCAG CUGAUGAG X CGAA AAGAUGGU ACCATCTT T CTGGGTTC

1151 GGAACCCA CUGAUGAG X CGAA AAAGAUGG CCATCTTT c TGGGTTCC

1157 GGGCCUGG CUGAUGAG X CGAA ACCCAGAA TTCTGGGT T CCAGGCCC

1158 AGGGCCUG CUGAUGAG X CGAA AACCCAGA TCTGGGTT c CAGGCCCT

1181 CCUGCGGG CUGAUGAG X CGAA AGUCCCUG CAGGGACT c CCCGCAGG

1191 GGCGGGGC CUGAUGAG X CGAA ACCUGCGG CCGCAGGT T GCCCCGCC

1212 UUUGCCAG CUGAUGAG X CGAA AGCGCUGG CCAGCGCT A CTGGCAAA

1233 GCUCCAGA CUGAUGAG X CGAA ACAGGGGC GCCCCTGT T TCTGGAGC

1234 AGCUCCAG CUGAUGAG X CGAA AACAGGGG CCCCTGTT T CTGGAGCT

1235 CAGCUCCA CUGAUGAG X CGAA AAACAGGG CCCTGTTT C TGGAGCTG

1246 UGGUUCCC CUGAUGAG X CGAA AGCAGCUC GAGCTGCT T GGGAACCA

1269 GCACCCCG CUGAUGAG X CGAA AGGGGCAC GTGCCCCT A CGGGGTGC

1279 GUCUUGAG CUGAUGAG X CGAA AGCACCCC GGGGTGCT C CTCAAGAC

1282 UGCGUCUU CUGAUGAG X CGAA AGGAGCAC GTGCTCCT C AAGACGCA

1312 GCUGGGGU CUGAUGAG X CGAA ACCGCAGC GCTGCGGT C ACCCCAGC

1330 CGGGCACA CUGAUGAG X CGAA ACACCGGC GCCGGTGT C TGTGCCCG

1356 CCGCCACA CUGAUGAG X CGAA AGCCCUGG CCAGGGCT C TGTGGCGG Table 13

1394 CACCAGGC CUGAUGAG X CGAA ACGGGGGU ACCCCCGT c GCCTGGTG

1411 UGCUGGCG CUGAUGAG X CGAA AGCAGCUG CAGCTGCT c CGCCAGCA

1440 CGAAGCCG CUGAUGAG X CGAA ACACCUGC GCAGGTGT A CGGCTTCG

1446 CCCGCACG CUGAUGAG X CGAA AGCCGUAC GTACGGCT T CGTGCGGG

1447 GCCCGCAC CUGAUGAG X CGAA AAGCCGUA TACGGCTT C GTGCGGGC

1486 GAGCCCCA CUGAUGAG X CGAA AGGCCUGG CCAGGCCT C TGGGGCTC

1494 UGUGCCUG CUGAUGAG X CGAA AGCCCCAG CTGGGGCT c CAGGCACA

1515 UCCUGAGG CUGAUGAG X CGAA AGCGGCGU ACGCCGCT T CCTCAGGA

1516 UUCCUGAG CUGAUGAG X CGAA AAGCGGCG CGCCGCTT c CTCAGGAA

1519 GUGUUCCU CUGAUGAG X CGAA AGGAAGCG CGCTTCCT c AGGAACAC

1536 GGGAGAUG CUGAUGAG X CGAA ACUUCUUG CAAGAAGT T CATCTCCC

1537 AGGGAGAU CUGAUGAG X CGAA AACUUCUU AAGAAGTT c ATCTCCCT

1540 CCCAGGGA CUGAUGAG X CGAA AUGAACUU AAGTTCAT c TCCCTGGG

1542 UCCCCAGG CUGAUGAG X CGAA AGAUGAAC GTTCATCT c CCTGGGGA

1564 UGCAGCGA CUGAUGAG X CGAA AGCUUGGC GCCAAGCT c TCGCTGCA

1566 CCUGCAGC CUGAUGAG X CGAA AGAGCUUG CAAGCTCT c GCTGCAGG

1610 GCGCAGCC CUGAUGAG X CGAA AGCGCAGU ACTGCGCT T GGCTGCGC

1633 ACACAGCC CUGAUGAG X CGAA ACCCCUGG CCAGGGGT T GGCTGTGT

1642 GCGGCCGG CUGAUGAG X CGAA ACACAGCC GGCTGTGT T CCGGCCGC

1643 UGCGGCCG CUGAUGAG X CGAA AACACAGC GCTGTGTT c CGGCCGCA

1661 CUCACGCA CUGAUGAG X CGAA ACGGUGCU AGCACCGT c TGCGTGAG

1675 UUGGCCAG CUGAUGAG X CGAA AUCUCCUC GAGGAGAT c CTGGCCAA

1686 AGUGCAGG CUGAUGAG X CGAA ACUUGGCC GGCCAAGT T CCTGCACT

1687 CAGUGCAG CUGAUGAG X CGAA AACUUGGC GCCAAGTT c CTGCACTG

1710 CGACGACG CUGAUGAG X CGAA ACACACUC GAGTGTGT A CGTCGTCG

1714 AGCUCGAC CUGAUGAG X CGAA ACGUACAC GTGTACGT c GTCGAGCT

1717 AGCAGCUC CUGAUGAG X CGAA ACGACGUA TACGTCGT c GAGCTGCT

1726 AAAGACCU CUGAUGAG X CGAA AGCAGCUC GAGCTGCT c AGGTCTTT

1731 AAAAGAAA CUGAUGAG X CGAA ACCUGAGC GCTCAGGT c TTTCTTTT

1733 AUAAAAGA CUGAUGAG X CGAA AGACCUGA TCAGGTCT T TCTTTTAT

1734 CAUAAAAG CUGAUGAG X CGAA AAGACCUG CAGGTCTT T CTTTTATG

1735 ACAUAAAA CUGAUGAG X CGAA AAAGACCU AGGTCTTT c TTTTATGT

1737 UGACAUAA CUGAUGAG X CGAA AGAAAGAC GTCTTTCT T TTATGTCA

1738 GUGACAUA CUGAUGAG X CGAA AAGAAAGA TCTTTCTT T TATGTCAC

1739 CGUGACAU CUGAUGAG X CGAA AAAGAAAG CTTTCTTT T ATGTCACG

1740 CCGUGACA CUGAUGAG X CGAA AAAAGAAA TTTCTTTT A TGTCACGG

1744 GUCUCCGU CUGAUGAG X CGAA ACAUAAAA TTTTATGT c ACGGAGAC

1758 UCUUUUGA CUGAUGAG X CGAA ACGUGGUC GACCACGT T TCAAAAGA

1759 UUCUUUUG CUGAUGAG X CGAA AACGUGGU ACCACGTT T CAAAAGAA

1760 GUUCUUUU CUGAUGAG X CGAA AAACGUGG CCACGTTT c AAAAGAAC

1774 UAGAAAAA CUGAUGAG X CGAA AGCCUGUU AACAGGCT c TTTTTCTA

1776 GGUAGAAA CUGAUGAG X CGAA AGAGCCUG CAGGCTCT T TTTCTACC

1777 CGGUAGAA CUGAUGAG X CGAA AAGAGCCU AGGCTCTT T TTCTACCG

1778 CCGGUAGA CUGAUGAG X CGAA AAAGAGCC GGCTCTTT T TCTACCGG

1779 UCCGGUAG CUGAUGAG X CGAA AAAAGAGC GCTCTTTT T CTACCGGA

1780 UUCCGGUA CUGAUGAG X CGAA AAAAAGAG CTCTTTTT c TACCGGAA

1782 UCUUCCGG CUGAUGAG X CGAA AGAAAAAG CTTTTTCT A CCGGAAGA Table 13

1795 UUGCUCCA CUGAUGAG X CGAA ACACUCUU AAGAGTGT C TGGAGCAA

1806 UGCUUUGC CUGAUGAG X CGAA ACUUGCUC GAGCAAGT T GCAAAGCA

1816 CUGAUUCC CUGAUGAG X CGAA AUGCUUUG CAAAGCAT T GGAATCAG

1822 UGCUGUCU CUGAUGAG X CGAA AUUCCAAU ATTGGAAT c AGACAGCA

1833 CCCUCUUC CUGAUGAG X CGAA AGUGCUGU ACAGCACT T GAAGAGGG

1860 CUGCUUCC CUGAUGAG X CGAA ACAGCUCC GGAGCTGT c GGAAGCAG

1873 UGCUGCCU CUGAUGAG X CGAA ACCUCUGC GCAGAGGT c AGGCAGCA

1883 GGCUUCCC CUGAUGAG X CGAA AUGCUGCC GGCAGCAT c GGGAAGCC

1911 GGAGUCUG CUGAUGAG X CGAA ACGUCAGC GCTGACGT c CAGACTCC

1918 AUGAAGCG CUGAUGAG X CGAA AGUCUGGA TCCAGACT c CGCTTCAT

1923 UGGGGAUG CUGAUGAG X CGAA AGCGGAGU ACTCCGCT T CATCCCCA

1924 UUGGGGAU CUGAUGAG X CGAA AAGCGGAG CTCCGCTT c ATCCCCAA

1927 GGCUUGGG CUGAUGAG X CGAA AUGAAGCG CGCTTCAT c CCCAAGCC

1954 AUGUUCAC CUGAUGAG X CGAA AUCGGCCG CGGCCGAT T GTGAACAT

1968 CCACGACG CUGAUGAG X CGAA AGUCCAUG CATGGACT A CGTCGTGG

1972 GCUCCCAC CUGAUGAG X CGAA ACGUAGUC GACTACGT c GTGGGAGC

1989 CUCUGCGG CUGAUGAG X CGAA ACGUUCUG CAGAACGT T CCGCAGAG

1990 UCUCUGCG CUGAUGAG X CGAA AACGUUCU AGAACGTT c CGCAGAGA

2015 CGAGGUGA CUGAUGAG X CGAA ACGCUCGG CCGAGCGT c TCACCTCG

2017 CUCGAGGU CUGAUGAG X CGAA AGACGCUC GAGCGTCT c ACCTCGAG

2022 UCACCCUC CUGAUGAG X CGAA AGGUGAGA TCTCACCT c GAGGGTGA

2040 GCACGCUG CUGAUGAG X CGAA ACAGUGCC GGCACTGT T CAGCGTGC

2041 AGCACGCU CUGAUGAG X CGAA AACAGUGC GCACTGTT c AGCGTGCT

2050 UCGUAGUU CUGAUGAG X CGAA AGCACGCU AGCGTGCT c AACTACGA

2055 CCCGCUCG CUGAUGAG X CGAA AGUUGAGC GCTCAACT A CGAGCGGG

2080 GCGCCCAG CUGAUGAG X CGAA AGGCCGGG CCCGGCCT c CTGGGCGC

2091 CCAGCACA CUGAUGAG X CGAA AGGCGCCC GGGCGCCT c TGTGCTGG

2111 CCUGUGGA CUGAUGAG X CGAA AUCGUCCA TGGACGAT A TCCACAGG

2113 GCCCUGUG CUGAUGAG X CGAA AUAUCGUC GACGATAT C CACAGGGC

2133 GCAGCACG CUGAUGAG X CGAA AGGUGCGC GCGCACCT T CGTGCTGC

2134 CGCAGCAC CUGAUGAG X CGAA AAGGUGCG CGCACCTT c GTGCTGCG

2175 UGACAAAG CUGAUGAG X CGAA ACAGCUCA TGAGCTGT A CTTTGTCA

2178 CCUUGACA CUGAUGAG X CGAA AGUACAGC GCTGTACT T TGTCAAGG

2179 ACCUUGAC CUGAUGAG X CGAA AAGUACAG CTGTACTT T GTCAAGGT

2182 UCCACCUU CUGAUGAG X CGAA ACAAAGUA TACTTTGT C AAGGTGGA

2205 UGGUGUCG CUGAUGAG X CGAA ACGCGCCC GGGCGCGT A CGACACCA

2215 UCCUGGGG CUGAUGAG X CGAA AUGGUGUC GACACCAT C CCCCAGGA

2230 ACCUCCGU CUGAUGAG X CGAA AGCCUGUC GACAGGCT c ACGGAGGT

2239 CUGGCGAU CUGAUGAG X CGAA ACCUCCGU ACGGAGGT c ATCGCCAG

2242 AUGCUGGC CUGAUGAG X CGAA AUGACCUC GAGGTCAT c GCCAGCAT

2251 GGUUUGAU CUGAUGAG X CGAA AUGCUGGC GCCAGCAT c ATCAAACC

2254 UGGGGUUU CUGAUGAG X CGAA AUGAUGCU AGCATCAT c AAACCCCA

2271 GCACGCAG CUGAUGAG X CGAA ACGUGUUC GAACACGT A CTGCGTGC

2282 GGCAUACC CUGAUGAG X CGAA ACGCACGC GCGTGCGT C GGTATGCC

2286 CCACGGCA CUGAUGAG X CGAA ACCGACGC GCGTCGGT A TGCCGTGG

2296 GCCUUCUG CUGAUGAG X CGAA ACCACGGC GCCGTGGT C CAGAAGGC

2320 GCCUUGCG CUGAUGAG X CGAA ACGUGCCC GGGCACGT C CGCAAGGC Table 13

2331 GGCUCUUG CUGAUGAG X CGAA AGGCCUUG CAAGGCCT T CAAGAGCC

2332 UGGCUCUU CUGAUGAG X CGAA AAGGCCUU AAGGCCTT C AAGAGCCA

2344 AAGGUAGA CUGAUGAG X CGAA ACGUGGCU AGCCACGT C TCTACCTT

2346 UCAAGGUA CUGAUGAG X CGAA AGACGUGG CCACGTCT C TACCTTGA

2348 UGUCAAGG CUGAUGAG X CGAA AGAGACGU ACGTCTCT A CCTTGACA

2352 GGUCUGUC CUGAUGAG X CGAA AGGUAGAG CTCTACCT T GACAGACC

2362 UACGGCUG CUGAUGAG X CGAA AGGUCUGU ACAGACCT C CAGCCGTA

2370 GUCGCAUG CUGAUGAG X CGAA ACGGCUGG CCAGCCGT A CATGCGAC

2382 GAGCCACG CUGAUGAG X CGAA ACUGUCGC GCGACAGT T CGTGGCTC

2383 UGAGCCAC CUGAUGAG X CGAA AACUGUCG CGACAGTT C GTGGCTCA

2390 CUGCAGGU CUGAUGAG X CGAA AGCCACGA TCGTGGCT C ACCTGCAG

2425 UCGAUGAC CUGAUGAG X CGAA ACGGCAUC GATGCCGT C GTCATCGA

2428 UGCUCGAU CUGAUGAG X CGAA ACGACGGC GCCGTCGT C ATCGAGCA

2431 CUCUGCUC CUGAUGAG X CGAA AUGACGAC GTCGTCAT C GAGCAGAG

2442 UCAGGGAG CUGAUGAG X CGAA AGCUCUGC GCAGAGCT C CTCCCTGA

2445 CAUUCAGG CUGAUGAG X CGAA AGGAGCUC GAGCTCCT C CCTGAATG

2470 ACGUCGAA CUGAUGAG X CGAA AGGCCACU AGTGGCCT C TTCGACGT

2472 AGACGUCG CUGAUGAG X CGAA AGAGGCCA TGGCCTCT T CGACGTCT

2473 AAGACGUC CUGAUGAG X CGAA AAGAGGCC GGCCTCTT C GACGTCTT

2479 CGUAGGAA CUGAUGAG X CGAA ACGUCGAA TTCGACGT c TTCCTACG

2481 AGCGUAGG CUGAUGAG X CGAA AGACGUCG CGACGTCT T CCTACGCT

2482 AAGCGUAG CUGAUGAG X CGAA AAGACGUC GACGTCTT c CTACGCTT

2485 AUGAAGCG CUGAUGAG X CGAA AGGAAGAC GTCTTCCT A CGCTTCAT

2490 GGCACAUG CUGAUGAG X CGAA AGCGUAGG CCTACGCT T CATGTGCC

2491 UGGCACAU CUGAUGAG X CGAA AAGCGUAG CTACGCTT C ATGTGCCA

2515 UUGCCCCU CUGAUGAG X CGAA AUGCGCAC GTGCGCAT C AGGGGCAA

2526 GGACGUAG CUGAUGAG X CGAA ACUUGCCC GGGCAAGT C CTACGTCC

2529 ACUGGACG CUGAUGAG X CGAA AGGACUUG CAAGTCCT A CGTCCAGT

2533 UGGCACUG CUGAUGAG X CGAA ACGUAGGA TCCTACGT C CAGTGCCA

2548 CCCUGCGG CUGAUGAG X CGAA AUCCCCUG CAGGGGAT C CCGCAGGG

2559 AGAGGAUG CUGAUGAG X CGAA AGCCCUGC GCAGGGCT C CATCCTCT

2563 GUGGAGAG CUGAUGAG X CGAA AUGGAGCC GGCTCCAT C CTCTCCAC

2566 AGCGUGGA CUGAUGAG X CGAA AGGAUGGA TCCATCCT C TCCACGCT

2568 GCAGCGUG CUGAUGAG X CGAA AGAGGAUG CATCCTCT c CACGCTGC

2578 AGGCUGCA CUGAUGAG X CGAA AGCAGCGU ACGCTGCT c TGCAGCCT

2592 UGUCGCCG CUGAUGAG X CGAA AGCACAGG CCTGTGCT A CGGCGACA

2616 UCCCCGCA CUGAUGAG X CGAA AGAGCUUG CAAGCTGT T TGCGGGGA

2617 AUCCCCGC CUGAUGAG X CGAA AACAGCUU AAGCTGTT T GCGGGGAT

2626 UCCCGCCG CUGAUGAG X CGAA AUCCCCGC GCGGGGAT T CGGCGGGA

2627 GUCCCGCC CUGAUGAG X CGAA AAUCCCCG CGGGGATT C GGCGGGAC

2644 AAACGCAG CUGAUGAG X CGAA AGCAGCCC GGGCTGCT C CTGCGTTT

2651 AUCCACCA CUGAUGAG X CGAA ACGCAGGA TCCTGCGT T TGGTGGAT

2652 CAUCCACC CUGAUGAG X CGAA AACGCAGG CCTGCGTT T GGTGGATG

2663 CAACAAGA CUGAUGAG X CGAA AUCAUCCA TGGATGAT T TCTTGTTG

2664 CCAACAAG CUGAUGAG X CGAA AAUCAUCC GGATGATT T CTTGTTGG

2665 ACCAACAA CUGAUGAG X CGAA AAAUCAUC GATGATTT c TTGTTGGT

2667 UCACCAAC CUGAUGAG X CGAA AGAAAUCA TGATTTCT T GTTGGTGA Table 13

2670 GUGUCACC CUGAUGAG X CGAA ACAAGAAA TTTCTTGT T GGTGACAC

2681 GGUGAGGU CUGAUGAG X CGAA AGGUGUCA TGACACCT C ACCTCACC

2686 GCGUGGGU CUGAUGAG X CGAA AGGUGAGG CCTCACCT C ACCCACGC

2703 UCCUGAGG CUGAUGAG X CGAA AGGUUUUC GAAAACCT T CCTCAGGA

2704 GUCCUGAG CUGAUGAG X CGAA AAGGUUUU AAAACCTT C CTCAGGAC

2707 AGGGUCCU CUGAUGAG X CGAA AGGAAGGU ACCTTCCT C AGGACCCT

2719 ACACCUCG CUGAUGAG X CGAA ACCAGGGU ACCCTGGT C CGAGGTGT

2728 UACUCAGG CUGAUGAG X CGAA ACACCUCG CGAGGTGT c CCTGAGTA

2736 CGCAGCCA CUGAUGAG X CGAA ACUCAGGG CCCTGAGT A TGGCTGCG

2754 UCUUCCGC CUGAUGAG X CGAA AGUUCACC GGTGAACT T GCGGAAGA

2775 CUACAGGG CUGAUGAG X CGAA AGUUCACC GGTGAACT T CCCTGTAG

2776 UCUACAGG CUGAUGAG X CGAA AAGUUCAC GTGAACTT c CCTGTAGA

2782 UCGUCUUC CUGAUGAG X CGAA ACAGGGAA TTCCCTGT A GAAGACGA

2810 CUGAACAA CUGAUGAG X CGAA AGCCGUGC GCACGGCT T TTGTTCAG

2811 UCUGAACA CUGAUGAG X CGAA AAGCCGUG CACGGCTT T TGTTCAGA

2812 AUCUGAAC CUGAUGAG X CGAA AAAGCCGU ACGGCTTT T GTTCAGAT

2815 GGCAUCUG CUGAUGAG X CGAA ACAAAAGC GCTTTTGT T CAGATGCC

2816 CGGCAUCU CUGAUGAG X CGAA AACAAAAG CTTTTGTT c AGATGCCG

2836 CAGGGGAA CUGAUGAG X CGAA AGGCCGUG CACGGCCT A TTCCCCTG

2838 ACCAGGGG CUGAUGAG X CGAA AUAGGCCG CGGCCTAT T CCCCTGGT

2839 CACCAGGG CUGAUGAG X CGAA AAUAGGCC GGCCTATT c CCCTGGTG

2864 GGUCCGGG CUGAUGAG X CGAA AUCCAGCA TGCTGGAT A CCCGGACC

2892 AGCUGGAG CUGAUGAG X CGAA AGUCGCUC GAGCGACT A CTCCAGCT

2895 CAUAGCUG CUGAUGAG X CGAA AGUAGUCG CGACTACT C CAGCTATG

2901 UCCGGGCA CUGAUGAG X CGAA AGCUGGAG CTCCAGCT A TGCCCGGA

2913 CUCUGAUG CUGAUGAG X CGAA AGGUCCGG CCGGACCT C CATCAGAG

2917 CUGGCUCU CUGAUGAG X CGAA AUGGAGGU ACCTCCAT C AGAGCCAG

2927 GAAGGUGA CUGAUGAG X CGAA ACUGGCUC GAGCCAGT C TCACCTTC

2929 UUGAAGGU CUGAUGAG X CGAA AGACUGGC GCCAGTCT C ACCTTCAA

2934 CGCGGUUG CUGAUGAG X CGAA AGGUGAGA TCTCACCT T CAACCGCG

2935 CCGCGGUU CUGAUGAG X CGAA AAGGUGAG CTCACCTT C AACCGCGG

2946 CAGCCUUG CUGAUGAG X CGAA AGCCGCGG CCGCGGCT T CAAGGCTG

2947 CCAGCCUU CUGAUGAG X CGAA AAGCCGCG CGCGGCTT C AAGGCTGG

2969 GAGUUUGC CUGAUGAG X CGAA ACGCAUGU ACATGCGT C GCAAACTC

2977 ACCCCAAA CUGAUGAG X CGAA AGUUUGCG CGCAAACT C TTTGGGGT

2979 AGACCCCA CUGAUGAG X CGAA AGAGUUUG CAAACTCT T TGGGGTCT

2980 AAGACCCC CUGAUGAG X CGAA AAGAGUUU AAACTCTT T GGGGTCTT

2986 AGCCGCAA CUGAUGAG X CGAA ACCCCAAA TTTGGGGT c TTGCGGCT

2988 UCAGCCGC CUGAUGAG X CGAA AGACCCCA TGGGGTCT T GCGGCTGA

3002 CAGGCUGU CUGAUGAG X CGAA ACACUUCA TGAAGTGT c ACAGCCTG

3012 AAUCCAGA CUGAUGAG X CGAA ACAGGCUG CAGCCTGT T TCTGGATT

3013 AAAUCCAG CUGAUGAG X CGAA AACAGGCU AGCCTGTT T CTGGATTT

3014 CAAAUCCA CUGAUGAG X CGAA AAACAGGC GCCTGTTT c TGGATTTG

3020 CACCUGCA CUGAUGAG X CGAA AUCCAGAA TTCTGGAT T TGCAGGTG

3021 UCACCUGC CUGAUGAG X CGAA AAUCCAGA TCTGGATT T GCAGGTGA

3037 ACCGUCUG CUGAUGAG X CGAA AGGCUGUU AACAGCCT c CAGACGGT

3058 AUCUUGUA CUGAUGAG X CGAA AUGUUGGU ACCAACAT c TACAAGAT Table 13

3060 GGAUCUUG CUGAUGAG X CGAA AGAUGUUG CAACATCT A CAAGATCC

3067 AGCAGGAG CUGAUGAG X CGAA AUCUUGUA TACAAGAT C CTCCTGCT

3070 UGCAGCAG CUGAUGAG X CGAA AGGAUCUU AAGATCCT C CTGCTGCA

3084 GAAACCUG CUGAUGAG X CGAA ACGCCUGC GCAGGCGT A CAGGTTTC

3090 AUGCGUGA CUGAUGAG X CGAA ACCUGUAC GTACAGGT T TCACGCAT

3091 CAUGCGUG CUGAUGAG X CGAA AACCUGUA TACAGGTT T CACGCATG

3092 ACAUGCGU CUGAUGAG X CGAA AAACCUGU ACAGGTTT C ACGCATGT

3112 UGAAAUGG CUGAUGAG X CGAA AGCUGCAG CTGCAGCT C CCATTTCA

3117 GCUGAUGA CUGAUGAG X CGAA AUGGGAGC GCTCCCAT T TCATCAGC

3118 UGCUGAUG CUGAUGAG X CGAA AAUGGGAG CTCCCATT T CATCAGCA

3119 UUGCUGAU CUGAUGAG X CGAA AAAUGGGA TCCCATTT C ATCAGCAA

3122 AACUUGCU CUGAUGAG X CGAA AUGAAAUG CATTTCAT C AGCAAGTT

3130 UUCUUCCA CUGAUGAG X CGAA ACUUGCUG CAGCAAGT T TGGAAGAA

3131 GUUCUUCC CUGAUGAG X CGAA AACUUGCU AGCAAGTT T GGAAGAAC

3147 GCAGGAAA CUGAUGAG X CGAA AUGUGOGG CCCCACAT T TTTCCTGC

3148 CGCAGGAA CUGAUGAG X CGAA AAUGUGGG CCCACATT T TTCCTGCG

3149 GCGCAGGA CUGAUGAG X CGAA AAAUGUGG CCACATTT T TCCTGCGC

3150 CGCGCAGG CUGAUGAG X CGAA AAAAUGUG CACATTTT T CCTGCGCG

3151 ACGCGCAG CUGAUGAG X CGAA AAAAAUGU ACATTTTT c CTGCGCGT

3160 UCAGAGAU CUGAUGAG X CGAA ACGCGCAG CTGCGCGT c ATCTCTGA

3163 GUGUCAGA CUGAUGAG X CGAA AUGACGCG CGCGTCAT c TCTGACAC

3165 CCGUGUCA CUGAUGAG X CGAA AGAUGACG CGTCATCT c TGACACGG

3177 AGCAGAGG CUGAUGAG X CGAA AGGCCGUG CACGGCCT c CCTCTGCT

3181 GAGUAGCA CUGAUGAG X CGAA AGGGAGGC GCCTCCCT c TGCTACTC

3186 GGAUGGAG CUGAUGAG X CGAA AGCAGAGG CCTCTGCT A CTCCATCC

3189 UCAGGAUG CUGAUGAG X CGAA AGUAGCAG CTGCTACT c CATCCTGA

3193 GCUUUCAG CUGAUGAG X CGAA AUGGAGUA TACTCCAT c CTGAAAGC

3219 CCCCCAGC CUGAUGAG X CGAA ACAUCCCU AGGGATGT c GCTGGGGG

3248 GGAGGGCA CUGAUGAG X CGAA AGGGCCGG CCGGCCCT c TGCCCTCC

3255 CGGCCUCG CUGAUGAG X CGAA AGGGCAGA TCTGCCCT c CGAGGCCG

3288 UGAGCAGG CUGAUGAG X CGAA AUGCUUGG CCAAGCAT T CCTGCTCA

3289 UUGAGCAG CUGAUGAG X CGAA AAUGCUUG CAAGCATT c CTGCTCAA

3295 GUCAGCUU CUGAUGAG X CGAA AGCAGGAA TTCCTGCT c AAGCTGAC

3305 ACGGUGUC CUGAUGAG X CGAA AGUCAGCU AGCTGACT c GACACCGT

3316 ACGUAGGU CUGAUGAG X CGAA ACACGGUG CACCGTGT c ACCTACGT

3321 GUGGCACG CUGAUGAG X CGAA AGGUGACA TGTCACCT A CGTGCCAC

3331 GACCCCAG CUGAUGAG X CGAA AGUGGCAC GTGCCACT c CTGGGGTC

3339 UCCUGAGU CUGAUGAG X CGAA ACCCCAGG CCTGGGGT c ACTCAGGA

3343 GCUGUCCU CUGAUGAG X CGAA AGUGACCC GGGTCACT c AGGACAGC

3368 GAGCUUCC CUGAUGAG X CGAA ACUCAGCU AGCTGAGT c GGAAGCTC

3376 GUCCCCGG CUGAUGAG X CGAA AGCUUCCG CGGAAGCT c CCGGGGAC

3429 UGAAGUCU CUGAUGAG X CGAA AGGGCAGU ACTGCCCT c AGACTTCA

3435 UGGUCUUG CUGAUGAG X CGAA AGUCUGAG CTCAGACT T CAAGACCA

3436 AUGGUCUU CUGAUGAG X CGAA AAGUCUGA TCAGACTT c AAGACCAT

3445 CAGUCCAG CUGAUGAG X CGAA AUGGUCUU AAGACCAT c CTGGACTG

3503 CCCGGCGU CUGAUGAG X CGAA ACAGGGCU AGCCCTGT c ACGCCGGG

3514 GGGACGUA CUGAUGAG X CGAA AGCCCGGC GCCGGGCT c TACGTCCC Table 13

3516 CUGGGACG CUGAUGAG X CGAA AGAGCCCG CGGGCTCT A CGTCCCAG

3520 CUCCCUGG CUGAUGAG X CGAA ACGUAGAG CTCTACGT C CCAGGGAG

3568 AGGCCUCA CUGAUGAG X CGAA ACUCCCAG CTGGGAGT C TGAGGCCT

3587 CUCGGCCA CUGAUGAG X CGAA ACACUCAC GTGAGTGT T TGGCCGAG

3588 CCUCGGCC CUGAUGAG X CGAA AACACUCA TGAGTGTT T GGCCGAGG

3606 UUCAGCCG CUGAUGAG X CGAA ACAUGCAG CTGCATGT C CGGCTGAA

3625 CUCAGCCG CUGAUGAG X CGAA ACACUCAG CTGAGTGT C CGGCTGAG

3648 CUUGGCUG CUGAUGAG X CGAA ACACUCGC GCGAGTGT C CAGCCAAG

3667 GUGUGCUG CUGAUGAG X CGAA ACACUCAG CTGAGTGT C CAGCACAC

3683 GAACUGAA CUGAUGAG X CGAA ACGGCAGG CCTGCCGT C TTCACTTC

3685 GGGAAGUG CUGAUGAG X CGAA AGACGGCA TGCCGTCT T CACTTCCC

3686 GGGGAAGU CUGAUGAG X CGAA AAGACGGC GCCGTCTT C ACTTCCCC

3690 CUGUGGGG CUGAUGAG X CGAA AGUGAAGA TCTTCACT T CCCCACAG

3691 CCUGUGGG CUGAUGAG X CGAA AAGUGAAG CTTCACTT C CCCACAGG

3708 GUGGAGCC CUGAUGAG X CGAA AGCGCCAG CTGGCGCT C GGCTCCAC

3713 CUGGGGUG CUGAUGAG X CGAA AGCCGAGC GCTCGGCT C CACCCCAG

3730 GUGAGGAA CUGAUGAG X CGAA AGCUGGCC GGCCAGCT T TTCCTCAC

3731 GGUGAGGA CUGAUGAG X CGAA AAGCUGGC GCCAGCTT T TCCTCACC

3732 UGGUGAGG CUGAUGAG X CGAA AAAGCUGG CCAGCTTT T CCTCACCA

3733 CUGGUGAG CUGAUGAG X CGAA AAAAGCUG CAGCTTTT C CTCACCAG

3736 CUCCUGGU CUGAUGAG X CGAA AGGAAAAG CTTTTCCT C ACCAGGAG

3752 GGGAGUGG CUGAUGAG X CGAA AGCCGGOC GCCCGGCT T CCACTCCC

3753 GGGGAGUG CUGAUGAG X CGAA AAGCCGGG CCCGGCTT c CACTCCCC

3758 UAUGUGGG CUGAUGAG X CGAA AGUGGAAG CTTCCACT c CCCACATA

3766 ACUAUUCC CUGAUGAG X CGAA AUGUGGGG CCCCACAT A GGAATAGT

3772 GGAUGGAC CUGAUGAG X CGAA AUUCCUAU ATAGGAAT A GTCCATCC

3775 UGGGGAUG CUGAUGAG X CGAA ACUAUUCC GGAATAGT C CATCCCCA

3779 AAUCUGGG CUGAUGAG X CGAA AUGGACUA TAGTCCAT C CCCAGATT

3787 CAAUGGCG CUGAUGAG X CGAA AUCUGGGG CCCCAGAT T CGCCATTG

3788 ACAAUGGC CUGAUGAG X CGAA AAUCUGGG CCCAGATT C GCCATTGT

3794 GGGUGAAC CUGAUGAG X CGAA AUGGCGAA TTCGCCAT T GTTCACCC

3797 GAGGGGUG CUGAUGAG X CGAA ACAAUGGC GCCATTGT T CACCCCTC

3798 CGAGGGGU CUGAUGAG X CGAA AACAAUGG CCATTGTT c ACCCCTCG

3805 GGCAGGGC CUGAUGAG X CGAA AGGGGUGA TCACCCCT c GCCCTGCC

3816 AGGCAAAG CUGAUGAG X CGAA AGGGCAGG CCTGCCCT c CTTTGCCT

3819 GGAAGGCA CUGAUGAG X CGAA AGGAGGGC GCCCTCCT T TGCCTTCC

3820 UGGAAGGC CUGAUGAG X CGAA AAGGAGGG CCCTCCTT T GCCTTCCA

3825 GGGGGUGG CUGAUGAG X CGAA AGGCAAAG CTTTGCCT T CCACCCCC

3826 UGGGGGUG CUGAUGAG X CGAA AAGGCAAA TTTGCCTT c CACCCCCA

3839 UCCACCUG CUGAUGAG X CGAA AUGGUGGG CCCACCAT c CAGGTGGA

3873 AAUUCCCA CUGAUGAG X CGAA AGCUCCCA TGGGAGCT c TGGGAATT

3881 UCACUCCA CUGAUGAG X CGAA AUUCCCAG CTGGGAAT T TGGAGTGA

3882 GUCACUCC CUGAUGAG X CGAA AAUUCCCA TGGGAATT T GGAGTGAC

3907 CGCCUGUG CUGAUGAG X CGAA ACAGGGCA TGCCCTGT A CACAGGCG

3940 CCCACAGG CUGAUGAG X CGAA ACCCCCAU ATGGGGGT c CCTGTGGG

3950 CCCAAUUU CUGAUGAG X CGAA ACCCACAG CTGTGGGT c AAATTGGG

3955 CUCCCCCC CUGAUGAG X CGAA AUUUGACC GGTCAAAT T GGOGGGAG Table 13

3977 CAGUAUUU CUGAUGAG X CGAA ACUCCCAC GTGGGAGT A AAATACTG

3982 AUAUUCAG CUGAUGAG X CGAA AUUUUACU AGTAAAAT A CTGAATAT

3989 AACUCAUA CUGAUGAG X CGAA AUUCAGUA TACTGAAT A TATGAGTT

3991 AAAACUCA CUGAUGAG X CGAA AUAUUCAG CTGAATAT A TGAGTTTT

3997 AACUGAAA CUGAUGAG X CGAA ACUCAUAU ATATGAGT T TTTCAGTT

3998 AAACUGAA CUGAUGAG X CGAA AACUCAUA TATGAGTT T TTCAGTTT

3999 AAAACUGA CUGAUGAG X CGAA AAACUCAU ATGAGTTT T TCAGTTTT

4000 CAAAACUG CUGAUGAG X CGAA AAAACUCA TGAGTTTT T CAGTTTTG

4001 UCAAAACU CUGAUGAG X CGAA AAAAACUC GAGTTTTT c AGTTTTGA

4005 UUUUUCAA CUGAUGAG X CGAA ACUGAAAA TTTTCAGT T TTGAAAAA

4006 UUUUUUCA CUGAUGAG X CGAA AACUGAAA TTTCAGTT T TGAAAAAA

4007 UUUUUUUC CUGAUGAG X CGAA AAACUGAA TTCAGTTT T GAAAAAAA

Stem Length = 8 . Core Sequence = CUGAUGAG X CGAA (X = GCCGUUAGGC or other stem II sequence and length (greater than or equal to 2 base-pairs))

Seql = TERT (Homo sapiens telomerase reverse transcriptase (TERT) mRNA, 4015 bp); Nakamura et al., Science 277 (5328), 955-959 ( 1997)

Table 14

Table 14: Human telomerase reverse transcriptase (TERT) NCH Ribozyme and Target Sequence

Table 14

155 CCAGCCCU CUGAUGAG X CGAA IGGCCCCA TGGGGCCC C AGGGCTGG

156 GCCAGCCC CUGAUGAG X CGAA IGGGCCCC GGGGCCCC A GGGCTGGC

161 CAGCCGCC CUGAUGAG X CGAA ICCCUGGG CCCAGGGC T GGCGGCTG

168 GCUGCACC CUGAUGAG X CGAA ICCGCCAG CTGGCGGC T GGTGCAGC

174 CCCCGCGC CUGAUGAG X CGAA ICACCAGC GCTGGTGC A GCGCGGGG

185 AGCCGCCG CUGAUGAG X CGAA IUCCCCGC GCGGGGAC C CGGCGGCT

186 AAGCCGCC CUGAUGAG X CGAA IGUCCCCG CGGGGACC C GGCGGCTT

193 GCGCGGAA CUGAUGAG X CGAA ICCGCCGG CCGGCGGC T TTCCGCGC

197 CAGCGCGC CUGAUGAG X CGAA IAAAGCCG CGGCTTTC C GCGCGCTG

204 GGGCCACC CUGAUGAG X CGAA ICGCGCGG CCGCGCGC T GGTGGCCC

211 AGGCACUG CUGAUGAG X CGAA ICCACCAG CTGGTGGC c CAGTGCCT

212 CAGGCACU CUGAUGAG X CGAA IGCCACCA TGGTGGCC c AGTGCCTG

213 CCAGGCAC CUGAUGAG X CGAA IGGCCACC GGTGGCCC A GTGCCTGG

218 GCACACCA CUGAUGAG X CGAA ICACUGGG CCCAGTGC C TGGTGTGC

219 CGCACACC CUGAUGAG X CGAA IGCACUGG CCAGTGCC T GGTGTGCG

231 CGUCCCAG CUGAUGAG X CGAA ICACGCAC GTGCGTGC C CTGGGACG

232 GCGUCCCA CUGAUGAG X CGAA IGCACGCA TGCGTGCC C TGGGACGC

233 UGCGUCCC CUGAUGAG X CGAA IGGCACGC GCGTGCCC T GGGACGCA

241 GGCGGCCG CUGAUGAG X CGAA ICGUCCCA TGGGACGC A CGGCCGCC

246 CGGGGGGC CUGAUGAG X CGAA ICCGUGCG CGCACGGC C GCCCCCCG

249 CGGCGGGG CUGAUGAG X CGAA ICGGCCGU ACGGCCGC C CCCCGCCG

250 GCGGCGGG CUGAUGAG X CGAA IGCGGCCG CGGCCGCC C CCCGCCGC

251 GGCGGCGG CUGAUGAG X CGAA IGGCGGCC GGCCGCCC C CCGCCGCC

252 GGGCGGCG CUGAUGAG X CGAA IGGGCGGC GCCGCCCC C CGCCGCCC

253 GGGGCGGC CUGAUGAG X CGAA IGGGGCGG CCGCCCCC c GCCGCCCC

256 GAGGGGGC CUGAUGAG X CGAA ICGGGGGG CCCCCCGC c GCCCCCTC

259 AAGGAGGG CUGAUGAG X CGAA ICGGCGGG CCCGCCGC c CCCTCCTT

260 GAAGGAGG CUGAUGAG X CGAA IGCGGCGG CCGCCGCC c CCTCCTTC

261 GGAAGGAG CUGAUGAG X CGAA IGGCGGCG CGCCGCCC c CTCCTTCC

262 CGGAAGGA CUGAUGAG X CGAA IGGGCGGC GCCGCCCC c TCCTTCCG

263 GCGGAAGG CUGAUGAG X CGAA IGGGGCGG CCGCCCCC T CCTTCCGC

265 UGGCGGAA CUGAUGAG X CGAA IAGGGGGC GCCCCCTC c TTCCGCCA

266 CUGGCGGA CUGAUGAG X CGAA IGAGGGGG CCCCCTCC T TCCGCCAG

269 CACCUGGC CUGAUGAG X CGAA IAAGGAGG CCTCCTTC c GCCAGGTG

272 GGACACCU CUGAUGAG X CGAA ICGGAAGG CCTTCCGC c AGGTGTCC

273 AGGACACC CUGAUGAG X CGAA IGCGGAAG CTTCCGCC A GGTGTCCT

280 UUCAGGCA CUGAUGAG X CGAA IACACCUG CAGGTGTC c TGCCTGAA

281 CUUCAGGC CUGAUGAG X CGAA IGACACCU AGGTGTCC T GCCTGAAG

284 CUCCUUCA CUGAUGAG X CGAA ICAGGACA TGTCCTGC c TGAAGGAG

285 GCUCCUUC CUGAUGAG X CGAA IGCAGGAC GTCCTGCC T GAAGGAGC

294 GGGCCACC CUGAUGAG X CGAA ICUCCUUC GAAGGAGC T GGTGGCCC

301 AGCACUCG CUGAUGAG X CGAA ICCACCAG CTGGTGGC c CGAGTGCT

302 CAGCACUC CUGAUGAG X CGAA IGCCACCA TGGTGGCC c GAGTGCTG

309 GCCUCUGC CUGAUGAG X CGAA ICACUCGG CCGAGTGC T GCAGAGGC

312 ACAGCCUC CUGAUGAG X CGAA ICAGCACU AGTGCTGC A GAGGCTGT

318 GCUCGCAC CUGAUGAG X CGAA ICCUCUGC GCAGAGGC T GTGCGAGC

345 CGAAGGCC CUGAUGAG X CGAA ICACGUUC GAACGTGC T GGCCTTCG Table 14

349 AAGCCGAA CUGAUGAG X CGAA ICCAGCAC GTGCTGGC C TTCGGCTT

350 GAAGCCGA CUGAUGAG X CGAA IGCCAGCA TGCTGGCC T TCGGCTTC

356 CAGCGCGA CUGAUGAG X CGAA ICCGAAGG CCTTCGGC T TCGCGCTG

363 CGUCCAGC CUGAUGAG X CGAA ICGCGAAG CTTCGCGC T GCTGGACG

366 CCCCGUCC CUGAUGAG X CGAA ICAGCGCG CGCGCTGC T GGACGGGG

376 CCCCCGCG CUGAUGAG X CGAA ICCCCGUC GACGGGGC C CGCGGGGG

377 GCCCCCGC CUGAUGAG X CGAA IGCCCCGU ACGGGGCC c GCGGGGGC

386 CUCGGGGG CUGAUGAG X CGAA ICCCCCGC GCGGGGGC c CCCCCGAG

387 CCUCGGGG CUGAUGAG X CGAA IGCCCCCG CGGGGGCC c CCCCGAGG

388 GCCUCGGG CUGAUGAG X CGAA IGGCCCCC GGGGGCCC c CCCGAGGC

389 GGCCUCGG CUGAUGAG X CGAA IGGGCCCC GGGGCCCC c CCGAGGCC

390 AGGCCUCG CUGAUGAG X CGAA IGGGGCCC GGGCCCCC c CGAGGCCT

391 AAGGCCUC CUGAUGAG X CGAA IGGGGGCC GGCCCCCC c GAGGCCTT

397 GUGGUGAA CUGAUGAG X CGAA ICCUCGGG CCCGAGGC c TTCACCAC

398 GGUGGUGA CUGAUGAG X CGAA IGCCUCGG CCGAGGCC T TCACCACC

401 GCUGGUGG CUGAUGAG X CGAA IAAGGCCU AGGCCTTC A CCACCAGC

403 ACGCUGGU CUGAUGAG X CGAA lUGAAGGC GCCTTCAC c ACCAGCGT

404 CACGCUGG CUGAUGAG X CGAA IGUGAAGG CCTTCACC A CCAGCGTG

406 CGCACGCU CUGAUGAG X CGAA IUGGUGAA TTCACCAC C AGCGTGCG

407 GCGCACGC CUGAUGAG X CGAA IGUGGUGA TCACCACC A GCGTGCGC

416 CAGGUAGC CUGAUGAG X CGAA ICGCACGC GCGTGCGC A GCTACCTG

419 GGGCAGGU CUGAUGAG X CGAA ICUGCGCA TGCGCAGC T ACCTGCCC

422 GUUGGGCA CUGAUGAG X CGAA IUAGCUGC GCAGCTAC C TGCCCAAC

423 UGUUGGGC CUGAUGAG X CGAA IGUAGCUG CAGCTACC T GCCCAACA

426 CCGUGUUG CUGAUGAG X CGAA ICAGGUAG CTACCTGC C CAACACGG

427 ACCGUGUU CUGAUGAG X CGAA IGCAGGUA TACCTGCC C AACACGGT

428 CACCGUGU CUGAUGAG X CGAA IGGCAGGU ACCTGCCC A ACACGGTG

431 GGUCACCG CUGAUGAG X CGAA IUUGGGCA TGCCCAAC A CGGTGACC

439 AGUGCGUC CUGAUGAG X CGAA lUCACCGU ACGGTGAC C GACGCACT

445 CCCCGCAG CUGAUGAG X CGAA ICGUCGGU ACCGACGC A CTGCGGGG

447 UCCCCCGC CUGAUGAG X CGAA IUGCGUCG CGACGCAC T GCGGGGGA

471 GCAGCAGC CUGAUGAG X CGAA ICCCCCAC GTGGGGGC T GCTGCTGC

474 GGCGCAGC CUGAUGAG X CGAA ICAGCCCC GGGGCTGC T GCTGCGCC

477 CGCGGCGC CUGAUGAG X CGAA ICAGCAGC GCTGCTGC T GCGCCGCG

482 GCCCACGC CUGAUGAG X CGAA ICGCAGCA TGCTGCGC C GCGTGGGC

501 GGUGAACC CUGAUGAG X CGAA ICACGUCG CGACGTGC T GGTTCACC

507 CCAGCAGG CUGAUGAG X CGAA IAACCAGC GCTGGTTC A CCTGCTGG

509 UGCCAGCA CUGAUGAG X CGAA IUGAACCA TGGTTCAC C TGCTGGCA

510 GUGCCAGC CUGAUGAG X CGAA IGUGAACC GGTTCACC T GCTGGCAC

513 AGCGUGCC CUGAUGAG X CGAA ICAGGUGA TCACCTGC T GGCACGCT

517 GCGCAGCG CUGAUGAG X CGAA ICCAGCAG CTGCTGGC A CGCTGCGC

521 GAGCGCGC CUGAUGAG X CGAA ICGUGCCA TGGCACGC T GCGCGCTC

528 GCACAAAG CUGAUGAG X CGAA ICGCGCAG CTGCGCGC T CTTTGTGC

530 CAGCACAA CUGAUGAG X CGAA IAGCGCGC GCGCGCTC T TTGTGCTG

537 GAGCCACC CUGAUGAG X CGAA ICACAAAG CTTTGTGC T GGTGGCTC

544 CAGCUGGG CUGAUGAG X CGAA ICCACCAG CTGGTGGC T CCCAGCTG

546 CGCAGCUG CUGAUGAG X CGAA IAGCCACC GGTGGCTC C CAGCTGCG Table 14

547 GCGCAGCU CUGAUGAG X CGAA IGAGCCAC GTGGCTCC C AGCTGCGC

548 GGCGCAGC CUGAUGAG X CGAA IGGAGCCA TGGCTCCC A GCTGCGCC

551 GUAGGCGC CUGAUGAG X CGAA ICUGGGAG CTCCCAGC T GCGCCTAC

556 ACCUGGUA CUGAUGAG X CGAA ICGCAGCU AGCTGCGC c TACCAGGT

557 CACCUGGU CUGAUGAG X CGAA IGCGCAGC GCTGCGCC T ACCAGGTG

560 GCACACCU CUGAUGAG X CGAA IUAGGCGC GCGCCTAC c AGGTGTGC

561 CGCACACC CUGAUGAG X CGAA IGUAGGCG CGCCTACC A GGTGTGCG

573 ACAGCGGC CUGAUGAG X CGAA ICCCGCAC GTGCGGGC C GCCGCTGT

576 GGUACAGC CUGAUGAG X CGAA ICGGCCCG CGGGCCGC C GCTGTACC

579 GCUGGUAC CUGAUGAG X CGAA ICGGCGGC GCCGCCGC T GTACCAGC

584 GCCGAGCU CUGAUGAG X CGAA IUACAGCG CGCTGTAC C AGCTCGGC

585 CGCCGAGC CUGAUGAG X CGAA IGUACAGC GCTGTACC A GCTCGGCG

588 CAGCGCCG CUGAUGAG X CGAA ICUGGUAC GTACCAGC T CGGCGCTG

595 UGAGUGGC CUGAUGAG X CGAA ICGCCGAG CTCGGCGC T GCCACTCA

598 GCCUGAGU CUGAUGAG X CGAA ICAGCGCC GGCGCTGC c ACTCAGGC

599 GGCCUGAG CUGAUGAG X CGAA IGCAGCGC GCGCTGCC A CTCAGGCC

601 CGGGCCUG CUGAUGAG X CGAA IUGGCAGC GCTGCCAC T CAGGCCCG

603 GCCGGGCC CUGAUGAG X CGAA lAGUGGCA TGCCACTC A GGCCCGGC

607 GGGGGCCG CUGAUGAG X CGAA ICCUGAGU ACTCAGGC C CGGCCCCC

608 CGGGGGCC CUGAUGAG X CGAA IGCCUGAG CTCAGGCC C GGCCCCCG

612 GUGGCGGG CUGAUGAG X CGAA ICCGGGCC GGCCCGGC C CCCGCCAC

613 UGUGGCGG CUGAUGAG X CGAA IGCCGGGC GCCCGGCC C CCGCCACA

614 GUGUGGCG CUGAUGAG X CGAA IGGCCGGG CCCGGCCC C CGCCACAC

615 CGUGUGGC CUGAUGAG X CGAA IGGGCCGG CCGGCCCC C GCCACACG

618 UAGCGUGU CUGAUGAG X CGAA ICGGGGGC GCCCCCGC C ACACGCTA

619 CUAGCGUG CUGAUGAG X CGAA IGCGGGGG CCCCCGCC A CACGCTAG

621 CACUAGCG CUGAUGAG X CGAA IUGGCGGG CCCGCCAC A CGCTAGTG

625 GGUCCACU CUGAUGAG X CGAA ICGUGUGG CCACACGC T AGTGGACC

633 GCCUUCGG CUGAUGAG X CGAA IUCCACUA TAGTGGAC C CCGAAGGC

634 CGCCUUCG CUGAUGAG X CGAA IGUCCACU AGTGGACC C CGAAGGCG

635 ACGCCUUC CUGAUGAG X CGAA IGGUCCAC GTGGACCC C GAAGGCGT

645 CGCAUCCC CUGAUGAG X CGAA IACGCCUU AAGGCGTC T GGGATGCG

661 UGGUUCCA CUGAUGAG X CGAA ICCCGUUC GAACGGGC c TGGAACCA

662 AUGGUUCC CUGAUGAG X CGAA IGCCCGUU AACGGGCC T GGAACCAT

668 GACGCUAU CUGAUGAG X CGAA IUUCCAGG CCTGGAAC c ATAGCGTC

669 UGACGCUA CUGAUGAG X CGAA IGUUCCAG CTGGAACC A TAGCGTCA

677 GGCCUCCC CUGAUGAG X CGAA IACGCUAU ATAGCGTC A GGGAGGCC

685 GGGACCCC CUGAUGAG X CGAA ICCUCCCU AGGGAGGC C GGGGTCCC

692 GCCCAGGG CUGAUGAG X CGAA IACCCCGG CCGGGGTC C CCCTGGGC

693 GGCCCAGG CUGAUGAG X CGAA IGACCCCG CGGGGTCC C CCTGGGCC

694 AGGCCCAG CUGAUGAG X CGAA IGGACCCC GGGGTCCC C CTGGGCCT

695 CAGGCCCA CUGAUGAG X CGAA IGGGACCC GGGTCCCC C TGGGCCTG

696 GCAGGCCC CUGAUGAG X CGAA IGGGGACC GGTCCCCC T GGGCCTGC

701 GGCUGGCA CUGAUGAG X CGAA ICCCAGGG CCCTGGGC C TGCCAGCC

702 GGGCUGGC CUGAUGAG X CGAA IGCCCAGG CCTGGGCC T GCCAGCCC

705 CCGGGGCU CUGAUGAG X CGAA ICAGGCCC GGGCCTGC C AGCCCCGG

706 CCCGGGGC CUGAUGAG X CGAA IGCAGGCC GGCCTGCC A GCCCCGGG Table 14

709 GCACCCGG CUGAUGAG X CGAA ICUGGCAG CTGCCAGC C CCGGGTGC

710 CGCACCCG CUGAUGAG X CGAA IGCUGGCA TGCCAGCC C CGGGTGCG

711 UCGCACCC CUGAUGAG X CGAA IGGCUGGC GCCAGCCC C GGGTGCGA

734 GCUGGCAC CUGAUGAG X CGAA ICCCCCGC GCGGGGGC A GTGCCAGC

739 CUUCGGCU CUGAUGAG X CGAA ICACUGCC GGCAGTGC C AGCCGAAG

740 ACUUCGGC CUGAUGAG X CGAA IGCACUGC GCAGTGCC A GCCGAAGT

743 CAGACUUC CUGAUGAG X CGAA ICUGGCAC GTGCCAGC C GAAGTCTG

750 GCAACGGC CUGAUGAG X CGAA IACUUCGG CCGAAGTC T GCCGTTGC

753 UGGGCAAC CUGAUGAG X CGAA ICAGACUU AAGTCTGC C GTTGCCCA

759 GCCUCUUG CUGAUGAG X CGAA ICAACGGC GCCGTTGC C CAAGAGGC

760 GGCCUCUU CUGAUGAG X CGAA IGCAACGG CCGTTGCC C AAGAGGCC

761 GGGCCUCU CUGAUGAG X CGAA IGGCAACG CGTTGCCC A AGAGGCCC

768 CACGCCUG CUGAUGAG X CGAA ICCUCUUG CAAGAGGC C CAGGCGTG

769 CCACGCCU CUGAUGAG X CGAA iσccucuu AAGAGGCC C AGGCGTGG

770 GCCACGCC CUGAUGAG X CGAA IGGCCUCU AGAGGCCC A GGCGTGGC

781 UCAGGGGC CUGAUGAG X CGAA ICGCCACG CGTGGCGC T GCCCCTGA

784 GGCUCAGG CUGAUGAG X CGAA ICAGCGCC GGCGCTGC c CCTGAGCC

785 CGGCUCAG CUGAUGAG X CGAA IGCAGCGC GCGCTGCC c CTGAGCCG

786 CCGGCUCA CUGAUGAG X CGAA IGGCAGCG CGCTGCCC c TGAGCCGG

787 UCCGGCUC CUGAUGAG X CGAA IGGGCAGC GCTGCCCC T GAGCCGGA

792 UCCGCUCC CUGAUGAG X CGAA ICUCAGGG CCCTGAGC c GGAGCGGA

804 GCCCAACG CUGAUGAG X CGAA ICGUCCGC GCGGACGC c CGTTGGGC

805 UGCCCAAC CUGAUGAG X CGAA IGCGUCCG CGGACGCC c GTTGGGCA

813 AGGACCCC CUGAUGAG X CGAA ICCCAACG CGTTGGGC A GGGGTCCT

820 UGGGCCCA CUGAUGAG X CGAA IACCCCUG CAGGGGTC C TGGGCCCA

821 GUGGGCCC CUGAUGAG X CGAA IGACCCCU AGGGGTCC T GGGCCCAC

826 CCCGGGUG CUGAUGAG X CGAA ICCCAGGA TCCTGGGC c CACCCGGG

827 GCCCGGGU CUGAUGAG X CGAA IGCCCAGG CCTGGGCC c ACCCGGGC

828 UGCCCGGG CUGAUGAG X CGAA IGGCCCAG CTGGGCCC A CCCGGGCA

830 CCUGCCCG CUGAUGAG X CGAA IUGGGCCC GGGCCCAC C CGGGCAGG

831 UCCUGCCC CUGAUGAG X CGAA IGUGGGCC GGCCCACC C GGGCAGGA

836 ACGCGUCC CUGAUGAG X CGAA ICCCGGGU ACCCGGGC A GGACGCGT

849 GGUCACUC CUGAUGAG X CGAA IUCCACGC GCGTGGAC C GAGTGACC

857 GAAACCAC CUGAUGAG X CGAA IUCACUCG CGAGTGAC C GTGGTTTC

866 CACCACAC CUGAUGAG X CGAA IAAACCAC GTGGTTTC T GTGTGGTG

877 CUGGCAGG CUGAUGAG X CGAA IACACCAC GTGGTGTC A CCTGCCAG

879 GUCUGGCA CUGAUGAG X CGAA IUGACACC GGTGTCAC C TGCCAGAC

880 GGUCUGGC CUGAUGAG X CGAA IGUGACAC GTGTCACC T GCCAGACC

883 GCGGGUCU CUGAUGAG X CGAA ICAGGUGA TCACCTGC C AGACCCGC

884 GGCGGGUC CUGAUGAG X CGAA IGCAGGUG CACCTGCC A GACCCGCC

888 CUUCGGCG CUGAUGAG X CGAA IUCUGGCA TGCCAGAC C CGCCGAAG

889 UCUUCGGC CUGAUGAG X CGAA IGUCUGGC GCCAGACC C GCCGAAGA

892 GCUUCUUC CUGAUGAG X CGAA ICGGGUCU AGACCCGC C GAAGAAGC

901 AAAGAGGU CUGAUGAG X CGAA ICUUCUUC GAAGAAGC C ACCTCTTT

902 CAAAGAGG CUGAUGAG X CGAA IGCUUCUU AAGAAGCC A CCTCTTTG

904 UCCAAAGA CUGAUGAG X CGAA IUGGCUUC GAAGCCAC C TCTTTGGA

905 CUCCAAAG CUGAUGAG X CGAA IGUGGCUU AAGCCACC T CTTTGGAG Table 14

907 CCCUCCAA CUGAUGAG X CGAA IAGGUGGC GCCACCTC T TTGGAGGG

921 UGCCAGAG CUGAUGAG X CGAA ICGCACCC GGGTGCGC T CTCTGGCA

923 CGUGCCAG CUGAUGAG X CGAA IAGCGCAC GTGCGCTC T CTGGCACG

925 CGCGUGCC CUGAUGAG X CGAA IAGAGCGC GCGCTCTC T GGCACGCG

929 GUGGCGCG CUGAUGAG X CGAA ICCAGAGA TCTCTGGC A CGCGCCAC

935 GUGGGAGU CUGAUGAG X CGAA ICGCGUGC GCACGCGC C ACTCCCAC

936 GGUGGGAG CUGAUGAG X CGAA IGCGCGUG CACGCGCC A CTCCCACC

938 UGGGUGGG CUGAUGAG X CGAA IUGGCGCG CGCGCCAC T CCCACCCA

940 GAUGGGUG CUGAUGAG X CGAA IAGUGGCG CGCCACTC c CACCCATC

941 GGAUGGGU CUGAUGAG X CGAA IGAGUGGC GCCACTCC c ACCCATCC

942 CGGAUGGG CUGAUGAG X CGAA IGGAGUGG CCACTCCC A CCCATCCG

944 CACGGAUG CUGAUGAG X CGAA IUGGGAGU ACTCCCAC C CATCCGTG

945 CCACGGAU CUGAUGAG X CGAA IGUGGGAG CTCCCACC C ATCCGTGG

946 CCCACGGA CUGAUGAG X CGAA IGGUGGGA TCCCACCC A TCCGTGGG

949 CGGCCCAC CUGAUGAG X CGAA IAUGGGUG CACCCATC C GTGGGCCG

956 GUGCUGGC CUGAUGAG X CGAA ICCCACGG CCGTGGGC C GCCAGCAC

959 GUGGUGCU CUGAUGAG X CGAA ICGGCCCA TGGGCCGC C AGCACCAC

960 CGUGGUGC CUGAUGAG X CGAA IGCGGCCC GGGCCGCC A GCACCACG

963 CCGCGUGG CUGAUGAG X CGAA ICUGGCGG CCGCCAGC A CCACGCGG

965 GCCCGCGU CUGAUGAG X CGAA IUGCUGGC GCCAGCAC C ACGCGGGC

966 GGCCCGCG CUGAUGAG X CGAA IGUGCUGG CCAGCACC A CGCGGGCC

974 GGAUGGGG CUGAUGAG X CGAA ICCCGCGU ACGCGGGC C CCCCATCC

975 UGGAUGGG CUGAUGAG X CGAA IGCCCGCG CGCGGGCC C CCCATCCA

976 GUGGAUGG CUGAUGAG X CGAA IGGCCCGC GCGGGCCC C CCATCCAC

977 UGUGGAUG CUGAUGAG X CGAA IGGGCCCG CGGGCCCC C CATCCACA

978 AUGUGGAU CUGAUGAG X CGAA IGGGGCCC GGGCCCCC c ATCCACAT

979 GAUGUGGA CUGAUGAG X CGAA IGGGGGCC GGCCCCCC A TCCACATC

982 CGCGAUGU CUGAUGAG X CGAA IAUGGGGG CCCCCATC C ACATCGCG

983 CCGCGAUG CUGAUGAG X CGAA IGAUGGGG CCCCATCC A CATCGCGG

985 GGCCGCGA CUGAUGAG X CGAA IUGGAUGG CCATCCAC A TCGCGGCC

993 GACGUGGU CUGAUGAG X CGAA ICCGCGAU ATCGCGGC C ACCACGTC

994 GGACGUGG CUGAUGAG X CGAA IGCCGCGA TCGCGGCC A CCACGTCC

996 AGGGACGU CUGAUGAG X CGAA IUGGCCGC GCGGCCAC C ACGTCCCT

997 CAGGGACG CUGAUGAG X CGAA IGUGGCCG CGGCCACC A CGTCCCTG

1002 UGUCCCAG CUGAUGAG X CGAA lACGUGGU ACCACGTC C CTGGGACA

1003 GUGUCCCA CUGAUGAG X CGAA IGACGUGG CCACGTCC C TGGGACAC

1004 CGUGUCCC CUGAUGAG X CGAA IGGACGUG CACGTCCC T GGGACACG

1010 ACAAGGCG CUGAUGAG X CGAA IUCCCAGG CCTGGGAC A CGCCTTGT

1014 GGGGACAA CUGAUGAG X CGAA ICGUGUCC GGACACGC C TTGTCCCC

1015 GGGGGACA CUGAUGAG X CGAA IGCGUGUC GACACGCC T TGTCCCCC

1020 ACACCGGG CUGAUGAG X CGAA IACAAGGC GCCTTGTC C CCCGGTGT

1021 UACACCGG CUGAUGAG X CGAA IGACAAGG CCTTGTCC C CCGGTGTA

1022 GUACACCG CUGAUGAG X CGAA IGGACAAG CTTGTCCC C CGGTGTAC

1023 CGUACACC CUGAUGAG X CGAA IGGGACAA TTGTCCCC C GGTGTACG

1033 UUGGUCUC CUGAUGAG X CGAA ICGUACAC GTGTACGC C GAGACCAA

1039 AAGUGCUU CUGAUGAG X CGAA IUCUCGGC GCCGAGAC C AAGCACTT

1040 GAAGUGCU CUGAUGAG X CGAA IGUCUCGG CCGAGACC A AGCACTTC Table 14

1044 AGAGGAAG CUGAUGAG X CGAA ICUUGGUC GACCAAGC A CTTCCTCT

1046 GUAGAGGA CUGAUGAG X CGAA IUGCUUGG CCAAGCAC T TCCTCTAC

1049 GGAGUAGA CUGAUGAG X CGAA IAAGUGCU AGCACTTC c TCTACTCC

1050 AGGAGUAG CUGAUGAG X CGAA IGAAGUGC GCACTTCC T CTACTCCT

1052 UGAGGAGU CUGAUGAG X CGAA IAGGAAGU ACTTCCTC T ACTCCTCA

1055 GCCUGAGG CUGAUGAG X CGAA lUAGAGGA TCCTCTAC T CCTCAGGC

1057 UCGCCUGA CUGAUGAG X CGAA IAGUAGAG CTCTACTC c TCAGGCGA

1058 GUCGCCUG CUGAUGAG X CGAA IGAGUAGA TCTACTCC T CAGGCGAC

1060 UUGUCGCC CUGAUGAG X CGAA lAGGAGUA TACTCCTC A GGCGACAA

1067 CUGCUCCU CUGAUGAG X CGAA IUCGCCUG CAGGCGAC A AGGAGCAG

1074 GCCGCAGC CUGAUGAG X CGAA ICUCCUUG CAAGGAGC A GCTGCGGC

1077 AGGGCCGC CUGAUGAG X CGAA ICUGCUCC GGAGCAGC T GCGGCCCT

1083 GGAAGGAG CUGAUGAG X CGAA ICCGCAGC GCTGCGGC C CTCCTTCC

1084 AGGAAGGA CUGAUGAG X CGAA IGCCGCAG CTGCGGCC C TCCTTCCT

1085 UAGGAAGG CUGAUGAG X CGAA IGGCCGCA TGCGGCCC T CCTTCCTA

1087 AGUAGGAA CUGAUGAG X CGAA IAGGGCCG CGGCCCTC C TTCCTACT

1088 GAGUAGGA CUGAUGAG X CGAA IGAGGGCC GGCCCTCC T TCCTACTC

1091 GCUGAGUA CUGAUGAG X CGAA IAAGGAGG CCTCCTTC C TACTCAGC

1092 AGCUGAGU CUGAUGAG X CGAA IGAAGGAG CTCCTTCC T ACTCAGCT

1095 GAGAGCUG CUGAUGAG X CGAA IUAGGAAG CTTCCTAC T CAGCTCTC

1097 CAGAGAGC CUGAUGAG X CGAA IAGUAGGA TCCTACTC A GCTCTCTG

1100 CCUCAGAG CUGAUGAG X CGAA ICUGAGUA TACTCAGC T CTCTGAGG

1102 GGCCUCAG CUGAUGAG X CGAA IAGCUGAG CTCAGCTC T CTGAGGCC

1104 UGGGCCUC CUGAUGAG X CGAA IAGAGCUG CAGCTCTC T GAGGCCCA

1110 UCAGGCUG CUGAUGAG X CGAA ICCUCAGA TCTGAGGC c CAGCCTGA llll GUCAGGCU CUGAUGAG X CGAA IGCCUCAG CTGAGGCC c AGCCTGAC

1112 AGUCAGGC CUGAUGAG X CGAA IGGCCUCA TGAGGCCC A GCCTGACT

1115 GCCAGUCA CUGAUGAG X CGAA ICUGGGCC GGCCCAGC C TGACTGGC

1116 CGCCAGUC CUGAUGAG X CGAA IGCUGGGC GCCCAGCC T GACTGGCG

1120 CGAGCGCC CUGAUGAG X CGAA IUCAGGCU AGCCTGAC T GGCGCTCG

1126 AGCCUCCG CUGAUGAG X CGAA ICGCCAGU ACTGGCGC T CGGAGGCT

1134 UCUCCACG CUGAUGAG X CGAA ICCUCCGA TCGGAGGC T CGTGGAGA

1144 AGAAAGAU CUGAUGAG X CGAA IUCUCCAC GTGGAGAC c ATCTTTCT

1145 CAGAAAGA CUGAUGAG X CGAA IGUCUCCA TGGAGACC A TCTTTCTG

1148 ACCCAGAA CUGAUGAG X CGAA IAUGGUCU AGACCATC T TTCTGGGT

1152 UGGAACCC CUGAUGAG X CGAA IAAAGAUG CATCTTTC T GGGTTCCA

1159 CAGGGCCU CUGAUGAG X CGAA IAACCCAG CTGGGTTC c AGGCCCTG

1160 CCAGGGCC CUGAUGAG X CGAA IGAACCCA TGGGTTCC A GGCCCTGG

1164 GCAUCCAG CUGAUGAG X CGAA ICCUGGAA TTCCAGGC C CTGGATGC

1165 GGCAUCCA CUGAUGAG X CGAA IGCCUGGA TCCAGGCC C TGGATGCC

1166 UGGCAUCC CUGAUGAG X CGAA IGGCCUGG CCAGGCCC T GGATGCCA

1173 GAGUCCCU CUGAUGAG X CGAA ICAUCCAG CTGGATGC c AGGGACTC

1174 GGAGUCCC CUGAUGAG X CGAA IGCAUCCA TGGATGCC A GGGACTCC

1180 CUGCGGGG CUGAUGAG X CGAA IUCCCUGG CCAGGGAC T CCCCGCAG

1182 ACCUGCGG CUGAUGAG X CGAA IAGUCCCU AGGGACTC C CCGCAGGT

1183 AACCUGCG CUGAUGAG X CGAA IGAGUCCC GGGACTCC C CGCAGGTT

1184 CAACCUGC CUGAUGAG X CGAA IGGAGUCC GGACTCCC C GCAGGTTG Table 14

1187 GGGCAACC CUGAUGAG X CGAA ICGGGGAG CTCCCCGC A GGTTGCCC

1194 GCAGGCGG CUGAUGAG X CGAA ICAACCUG CAGGTTGC C CCGCCTGC

1195 GGCAGGCG CUGAUGAG X CGAA IGCAACCU AGGTTGCC C CGCCTGCC

1196 GGGCAGGC CUGAUGAG X CGAA IGGCAACC GGTTGCCC C GCCTGCCC

1199 CUGGGGCA CUGAUGAG X CGAA ICGGGGCA TGCCCCGC C TGCCCCAG

1200 GCUGGGGC CUGAUGAG X CGAA IGCGGGGC GCCCCGCC T GCCCCAGC

1203 AGCGCUGG CUGAUGAG X CGAA ICAGGCGG CCGCCTGC C CCAGCGCT

1204 UAGCGCUG CUGAUGAG X CGAA IGCAGGCG CGCCTGCC C CAGCGCTA

1205 GUAGCGCU CUGAUGAG X CGAA IGGCAGGC GCCTGCCC C AGCGCTAC

1206 AGUAGCGC CUGAUGAG X CGAA IGGGCAGG CCTGCCCC A GCGCTACT

1211 UUGCCAGU CUGAUGAG X CGAA ICGCUGGG CCCAGCGC T ACTGGCAA

1214 CAUUUGCC CUGAUGAG X CGAA IUAGCGCU AGCGCTAC T GGCAAATG

1218 GCCGCAUU CUGAUGAG X CGAA ICCAGUAG CTACTGGC A AATGCGGC

1227 GAAACAGG CUGAUGAG X CGAA ICCGCAUU AATGCGGC C CCTGTTTC

1228 AGAAACAG CUGAUGAG X CGAA IGCCGCAU ATGCGGCC C CTGTTTCT

1229 CAGAAACA CUGAUGAG X CGAA IGGCCGCA TGCGGCCC C TGTTTCTG

1230 CCAGAAAC CUGAUGAG X CGAA IGGGCCGC GCGGCCCC T GTTTCTGG

1236 GCAGCUCC CUGAUGAG X CGAA IAAACAGG CCTGTTTC T GGAGCTGC

1242 UCCCAAGC CUGAUGAG X CGAA ICUCCAGA TCTGGAGC T GCTTGGGA

1245 GGUUCCCA CUGAUGAG X CGAA ICAGCUCC GGAGCTGC T TGGGAACC

1253 CUGCGCGU CUGAUGAG X CGAA IUUCCCAA TTGGGAAC c ACGCGCAG

1254 ACUGCGCG CUGAUGAG X CGAA IGUUCCCA TGGGAACC A CGCGCAGT

1260 AGGGGCAC CUGAUGAG X CGAA ICGCGUGG CCACGCGC A GTGCCCCT

1265 CCCGUAGG CUGAUGAG X CGAA ICACUGCG CGCAGTGC C CCTACGGG

1266 CCCCGUAG CUGAUGAG X CGAA IGCACUGC GCAGTGCC C CTACGGGG

1267 ACCCCGUA CUGAUGAG X CGAA IGGCACUG CAGTGCCC C TACGGGGT

1268 CACCCCGU CUGAUGAG X CGAA IGGGCACU AGTGCCCC T ACGGGGTG

1278 UCUUGAGG CUGAUGAG X CGAA ICACCCCG CGGGGTGC T CCTCAAGA

1280 CGUCUUGA CUGAUGAG X CGAA IAGCACCC GGGTGCTC c TCAAGACG

1281 GCGUCUUG CUGAUGAG X CGAA IGAGCACC GGTGCTCC T CAAGACGC

1283 GUGCGUCU CUGAUGAG X CGAA lAGGAGCA TGCTCCTC A AGACGCAC

1290 GCGGGCAG CUGAUGAG X CGAA ICGUCUUG CAAGACGC A CTGCCCGC

1292 CAGCGGGC CUGAUGAG X CGAA IUGCGUCU AGACGCAC T GCCCGCTG

1295 UCGCAGCG CUGAUGAG X CGAA ICAGUGCG CGCACTGC C CGCTGCGA

1296 CUCGCAGC CUGAUGAG X CGAA IGCAGUGC GCACTGCC C GCTGCGAG

1299 CAGCUCGC CUGAUGAG X CGAA ICGGGCAG CTGCCCGC T GCGAGCTG

1306 GUGACCGC CUGAUGAG X CGAA ICUCGCAG CTGCGAGC T GCGGTCAC

1313 UGCUGGGG CUGAUGAG X CGAA IACCGCAG CTGCGGTC A CCCCAGCA

1315 GCUGCUGG CUGAUGAG X CGAA IUGACCGC GCGGTCAC C CCAGCAGC

1316 GGCUGCUG CUGAUGAG X CGAA IGUGACCG CGGTCACC C CAGCAGCC

1317 CGGCUGCU CUGAUGAG X CGAA IGGUGACC GGTCACCC C AGCAGCCG

1318 CCGGCUGC CUGAUGAG X CGAA IGGGUGAC GTCACCCC A GCAGCCGG

1321 ACACCGGC CUGAUGAG X CGAA ICUGGGGU ACCCCAGC A GCCGGTGT

1324 CAGACACC CUGAUGAG X CGAA ICUGCUGG CCAGCAGC C GGTGTCTG

1331 CCGGGCAC CUGAUGAG X CGAA IACACCGG CCGGTGTC T GTGCCCGG

1336 UUCUCCCG CUGAUGAG X CGAA ICACAGAC GTCTGTGC c CGGGAGAA

1337 CUUCUCCC CUGAUGAG X CGAA IGCACAGA TCTGTGCC c GGGAGAAG Table 14

1347 AGCCCUGG CUGAUGAG X CGAA ICUUCUCC GGAGAAGC C CCAGGGCT

1348 GAGCCCUG CUGAUGAG X CGAA IGCUUCUC GAGAAGCC C CAGGGCTC

1349 AGAGCCCU CUGAUGAG X CGAA IGGCUUCU AGAAGCCC C AGGGCTCT

1350 CAGAGCCC CUGAUGAG X CGAA IGGGCUUC GAAGCCCC A GGGCTCTG

1355 CGCCACAG CUGAUGAG X CGAA ICCCUGGG CCCAGGGC T CTGTGGCG

1357 GCCGCCAC CUGAUGAG X CGAA IAGCCCUG CAGGGCTC T GTGGCGGC

1366 UCCUCGGG CUGAUGAG X CGAA ICCGCCAC GTGGCGGC C CCCGAGGA

1367 CUCCUCGG CUGAUGAG X CGAA IGCCGCCA TGGCGGCC C CCGAGGAG

1368 CCUCCUCG CUGAUGAG X CGAA IGGCCGCC GGCGGCCC C CGAGGAGG

1369 UCCUCCUC CUGAUGAG X CGAA IGGGCCGC GCGGCCCC C GAGGAGGA

1382 GGGGUCUG CUGAUGAG X CGAA IUCCUCCU AGGAGGAC A CAGACCCC

1384 CGGGGGUC CUGAUGAG X CGAA IUGUCCUC GAGGACAC A GACCCCCG

1388 GCGACGGG CUGAUGAG X CGAA IUCUGUGU ACACAGAC C CCCGTCGC

1389 GGCGACGG CUGAUGAG X CGAA IGUCUGUG CACAGACC C CCGTCGCC

1390 AGGCGACG CUGAUGAG X CGAA IGGUCUGU ACAGACCC C CGTCGCCT

1391 CAGGCGAC CUGAUGAG X CGAA IGGGUCUG CAGACCCC C GTCGCCTG

1397 CUGCACCA CUGAUGAG X CGAA ICGACGGG CCCGTCGC C TGGTGCAG

1398 GCUGCACC CUGAUGAG X CGAA IGCGACGG CCGTCGCC T GGTGCAGC

1404 GGAGCAGC CUGAUGAG X CGAA ICACCAGG CCTGGTGC A GCTGCTCC

1407 GGCGGAGC CUGAUGAG X CGAA ICUGCACC GGTGCAGC T GCTCCGCC

1410 GCUGGCGG CUGAUGAG X CGAA ICAGCUGC GCAGCTGC T CCGCCAGC

1412 GUGCUGGC CUGAUGAG X CGAA IAGCAGCU AGCTGCTC C GCCAGCAC

1415 GCUGUGCU CUGAUGAG X CGAA ICGGAGCA TGCTCCGC C AGCACAGC

1416 UGCUGUGC CUGAUGAG X CGAA IGCGGAGC GCTCCGCC A GCACAGCA

1419 GGCUGCUG CUGAUGAG X CGAA ICUGGCGG CCGCCAGC A CAGCAGCC

1421 GGGGCUGC CUGAUGAG X CGAA IUGCUGGC GCCAGCAC A GCAGCCCC

1424 CCAGGGGC CUGAUGAG X CGAA ICUGUGCU AGCACAGC A GCCCCTGG

1427 CUGCCAGG CUGAUGAG X CGAA ICUGCUGU ACAGCAGC C CCTGGCAG

1428 CCUGCCAG CUGAUGAG X CGAA IGCUGCUG CAGCAGCC C CTGGCAGG

1429 ACCUGCCA CUGAUGAG X CGAA IGGCUGCU AGCAGCCC C TGGCAGGT

1430 CACCUGCC CUGAUGAG X CGAA IGGGCUGC GCAGCCCC T GGCAGGTG

1434 CGUACACC CUGAUGAG X CGAA ICCAGGGG CCCCTGGC A GGTGTACG

1445 CCGCACGA CUGAUGAG X CGAA ICCGUACA TGTACGGC T TCGTGCGG

1456 CGCAGGCA CUGAUGAG X CGAA ICCCGCAC GTGCGGGC C TGCCTGCG

1457 GCGCAGGC CUGAUGAG X CGAA IGCCCGCA TGCGGGCC T GCCTGCGC

1460 CCGGCGCA CUGAUGAG X CGAA ICAGGCCC GGGCCTGC c TGCGCCGG

1461 GCCGGCGC CUGAUGAG X CGAA IGCAGGCC GGCCTGCC T GCGCCGGC

1466 CACCAGCC CUGAUGAG X CGAA ICGCAGGC GCCTGCGC c GGCTGGTG

1470 GGGGCACC CUGAUGAG X CGAA ICCGGCGC GCGCCGGC T GGTGCCCC

1476 GGCCUGGG CUGAUGAG X CGAA ICACCAGC GCTGGTGC c CCCAGGCC

1477 AGGCCUGG CUGAUGAG X CGAA IGCACCAG CTGGTGCC c CCAGGCCT

1478 GAGGCCUG CUGAUGAG X CGAA IGGCACCA TGGTGCCC c CAGGCCTC

1479 AGAGGCCU CUGAUGAG X CGAA IGGGCACC GGTGCCCC c AGGCCTCT

1480 CAGAGGCC CUGAUGAG X CGAA IGGGGCAC GTGCCCCC A GGCCTCTG

1484 GCCCCAGA CUGAUGAG X CGAA ICCUGGGG CCCCAGGC C TCTGGGGC

1485 AGCCCCAG CUGAUGAG X CGAA IGCCUGGG CCCAGGCC T CTGGGGCT

1487 GGAGCCCC CUGAUGAG X CGAA IAGGCCUG CAGGCCTC T GGGGCTCC Table 14

1493 GUGCCUGG CUGAUGAG X CGAA ICCCCAGA TCTGGGGC T CCAGGCAC

1495 UUGUGCCU CUGAUGAG X CGAA IAGCCCCA TGGGGCTC C AGGCACAA

1496 GUUGUGCC CUGAUGAG X CGAA IGAGCCCC GGGGCTCC A GGCACAAC

1500 GUUCGUUG CUGAUGAG X CGAA ICCUGGAG CTCCAGGC A CAACGAAC

1502 GCGUUCGU CUGAUGAG X CGAA IUGCCUGG CCAGGCAC A ACGAACGC

1511 GAGGAAGC CUGAUGAG X CGAA ICGUUCGU ACGAACGC C GCTTCCTC

1514 CCUGAGGA CUGAUGAG X CGAA ICGGCGUU AACGCCGC T TCCTCAGG

1517 GUUCCUGA CUGAUGAG X CGAA IAAGCGGC GCCGCTTC c TCAGGAAC

1518 UGUUCCUG CUGAUGAG X CGAA IGAAGCGG CCGCTTCC T CAGGAACA

1520 GGUGUUCC CUGAUGAG X CGAA IAGGAAGC GCTTCCTC A GGAACACC

1526 CUUCUUGG CUGAUGAG X CGAA IUUCCUGA TCAGGAAC A CCAAGAAG

1528 AACUUCUU CUGAUGAG X CGAA lUGUUCCU AGGAACAC C AAGAAGTT

1529 GAACUUCU CUGAUGAG X CGAA IGUGUUCC GGAACACC A AGAAGTTC

1538 CAGGGAGA CUGAUGAG X CGAA IAACUUCU AGAAGTTC A TCTCCCTG

1541 CCCCAGGG CUGAUGAG X CGAA IAUGAACU AGTTCATC T CCCTGGGG

1543 UUCCCCAG CUGAUGAG X CGAA IAGAUGAA TTCATCTC C CTGGGGAA

1544 CUUCCCCA CUGAUGAG X CGAA IGAGAUGA TCATCTCC C TGGGGAAG

1545 GCUUCCCC CUGAUGAG X CGAA IGGAGAUG CATCTCCC T GGGGAAGC

1554 GCUUGGCA CUGAUGAG X CGAA ICUUCCCC GGGGAAGC A TGCCAAGC

1558 GAGAGCUU CUGAUGAG X CGAA ICAUGCUU AAGCATGC C AAGCTCTC

1559 CGAGAGCU CUGAUGAG X CGAA IGCAUGCU AGCATGCC A AGCTCTCG

1563 GCAGCGAG CUGAUGAG X CGAA ICUUGGCA TGCCAAGC T CTCGCTGC

1565 CUGCAGCG CUGAUGAG X CGAA IAGCUUGG CCAAGCTC T CGCTGCAG

1569 GCUCCUGC CUGAUGAG X CGAA ICGAGAGC GCTCTCGC T GCAGGAGC

1572 UCAGCUCC CUGAUGAG X CGAA ICAGCGAG CTCGCTGC A GGAGCTGA

1578 UCCACGUC CUGAUGAG X CGAA ICUCCUGC GCAGGAGC T GACGTGGA

1604 CCAAGCGC CUGAUGAG X CGAA IUCCCGCA TGCGGGAC T GCGCTTGG

1609 CGCAGCCA CUGAUGAG X CGAA ICGCAGUC GACTGCGC T TGGCTGCG

1614 UCCUGCGC CUGAUGAG X CGAA ICCAAGCG CGCTTGGC T GCGCAGGA

1619 UGGGCUCC CUGAUGAG X CGAA ICGCAGCC GGCTGCGC A GGAGCCCA

1625 AACCCCUG CUGAUGAG X CGAA ICUCCUGC GCAGGAGC C CAGGGGTT

1626 CAACCCCU CUGAUGAG X CGAA IGCUCCUG CAGGAGCC C AGGGGTTG

1627 CCAACCCC CUGAUGAG X CGAA IGGCUCCU AGGAGCCC A GGGGTTGG

1637 CGGAACAC CUGAUGAG X CGAA ICCAACCC GGGTTGGC T GTGTTCCG

1644 CUGCGGCC CUGAUGAG X CGAA IAACACAG CTGTGTTC c GGCCGCAG

1648 UGCUCUGC CUGAUGAG X CGAA ICCGGAAC GTTCCGGC c GCAGAGCA

1651 CGGUGCUC CUGAUGAG X CGAA ICGGCCGG CCGGCCGC A GAGCACCG

1656 GCAGACGG CUGAUGAG X CGAA ICUCUGCG CGCAGAGC A CCGTCTGC

1658 ACGCAGAC CUGAUGAG X CGAA lUGCUCUG CAGAGCAC C GTCTGCGT

1662 CCUCACGC CUGAUGAG X CGAA IACGGUGC GCACCGTC T GCGTGAGG

1676 CUUGGCCA CUGAUGAG X CGAA IAUCUCCU AGGAGATC C TGGCCAAG

1677 ACUUGGCC CUGAUGAG X CGAA IGAUCUCC GGAGATCC T GGCCAAGT

1681 AGGAACUU CUGAUGAG X CGAA ICCAGGAU ATCCTGGC C AAGTTCCT

1682 CAGGAACU CUGAUGAG X CGAA IGCCAGGA TCCTGGCC A AGTTCCTG

1688 CCAGUGCA CUGAUGAG X CGAA IAACUUGG CCAAGTTC C TGCACTGG

1689 GCCAGUGC CUGAUGAG X CGAA IGAACUUG CAAGTTCC T GCACTGGC

1692 UCAGCCAG CUGAUGAG X CGAA ICAGGAAC GTTCCTGC A CTGGCTGA Table 14

1694 CAUCAGCC CUGAUGAG X CGAA IUGCAGGA TCCTGCAC T GGCTGATG

1698 CACUCAUC CUGAUGAG X CGAA ICCAGUGC GCACTGGC T GATGAGTG

1722 ACCUGAGC CUGAUGAG X CGAA ICUCGACG CGTCGAGC T GCTCAGGT

1725 AAGACCUG CUGAUGAG X CGAA ICAGCUCG CGAGCTGC T CAGGTCTT

1727 GAAAGACC CUGAUGAG X CGAA IAGCAGCU AGCTGCTC A GGTCTTTC

1732 UAAAAGAA CUGAUGAG X CGAA IACCUGAG CTCAGGTC T TTCTTTTA

1736 GACAUAAA CUGAUGAG X CGAA IAAAGACC GGTCTTTC T TTTATGTC

1745 GGUCUCCG CUGAUGAG X CGAA IACAUAAA TTTATGTC A CGGAGACC

1753 UGAAACGU CUGAUGAG X CGAA IUCUCCGU ACGGAGAC C ACGTTTCA

1754 UUGAAACG CUGAUGAG X CGAA IGUCUCCG CGGAGACC A CGTTTCAA

1761 UGUUCUUU CUGAUGAG X CGAA IAAACGUG CACGTTTC A AAAGAACA

1769 AAAGAGCC CUGAUGAG X CGAA IUUCUUUU AAAAGAAC A GGCTCTTT

1773 AGAAAAAG CUGAUGAG X CGAA ICCUGUUC GAACAGGC T CTTTTTCT

1775 GUAGAAAA CUGAUGAG X CGAA IAGCCUGU ACAGGCTC T TTTTCTAC

1781 CUUCCGGU CUGAUGAG X CGAA IAAAAAGA TCTTTTTC T ACCGGAAG

1784 ACUCUUCC CUGAUGAG X CGAA lUAGAAAA TTTTCTAC C GGAAGAGT

1796 CUUGCUCC CUGAUGAG X CGAA IACACUCU AGAGTGTC T GGAGCAAG

1802 UUGCAACU CUGAUGAG X CGAA ICUCCAGA TCTGGAGC A AGTTGCAA

1809 CAAUGCUU CUGAUGAG X CGAA ICAACUUG CAAGTTGC A AAGCATTG

1814 GAUUCCAA CUGAUGAG X CGAA ICUUUGCA TGCAAAGC A TTGGAATC

1823 GUGCUGUC CUGAUGAG X CGAA IAUUCCAA TTGGAATC A GACAGCAC

1827 UCAAGUGC CUGAUGAG X CGAA IUC^'UGAUU AATCAGAC A GCACTTGA

1830 UCUUCAAG CUGAUGAG X CGAA ICUGUCUG CAGACAGC A CTTGAAGA

1832 CCUCUUCA CUGAUGAG X CGAA IUGCUGUC GACAGCAC T TGAAGAGG

1845 CCCGCAGC CUGAUGAG X CGAA ICACCCUC GAGGGTGC A GCTGCGGG

1848 GCUCCCGC CUGAUGAG X CGAA ICUGCACC GGTGCAGC T. GCGGGAGC

1857 CUUCCGAC CUGAUGAG X CGAA ICUCCCGC GCGGGAGC T GTCGGAAG

1867 CUGACCUC CUGAUGAG X CGAA ICUUCCGA TCGGAAGC A GAGGTCAG

1874 AUGCUGCC CUGAUGAG X CGAA IACCUCUG CAGAGGTC A GGCAGCAT

1878 CCCGAUGC CUGAUGAG X CGAA ICCUGACC GGTCAGGC A GCATCGGG

1881 CUUCCCGA CUGAUGAG X CGAA ICUGCCUG CAGGCAGC A TCGGGAAG

1891 GCGGGCCU CUGAUGAG X CGAA ICUUCCCG CGGGAAGC C AGGCCCGC

1892 GGCGGGCC CUGAUGAG X CGAA IGCUUCCC GGGAAGCC A GGCCCGCC

1896 GCAGGGCG CUGAUGAG X CGAA ICCUGGCU AGCCAGGC C CGCCCTGC

1897 AGCAGGGC CUGAUGAG X CGAA IGCCUGGC GCCAGGCC C GCCCTGCT

1900 GUCAGCAG CUGAUGAG X CGAA ICGGGCCU AGGCCCGC C CTGCTGAC

1901 CGUCAGCA CUGAUGAG X CGAA IGCGGGCC GGCCCGCC C TGCTGACG

1902 ACGUCAGC CUGAUGAG X CGAA IGGCGGGC GCCCGCCC T GCTGACGT

1905 UGGACGUC CUGAUGAG X CGAA ICAGGGCG CGCCCTGC T GACGTCCA

1912 CGGAGUCU CUGAUGAG X CGAA IACGUCAG CTGACGTC C AGACTCCG

1913 GCGGAGUC CUGAUGAG X CGAA IGACGUCA TGACGTCC A GACTCCGC

1917 UGAAGCGG CUGAUGAG X CGAA IUCUGGAC GTCCAGAC T CCGCTTCA

1919 GAUGAAGC CUGAUGAG X CGAA IAGUCUGG CCAGACTC C GCTTCATC

1922 GGGGAUGA CUGAUGAG X CGAA ICGGAGUC GACTCCGC T TCATCCCC

1925 CUUGGGGA CUGAUGAG X CGAA IAAGCGGA TCCGCTTC A TCCCCAAG

1928 AGGCUUGG CUGAUGAG X CGAA IAUGAAGC GCTTCATC C CCAAGCCT

1929 CAGGCUUG CUGAUGAG X CGAA IGAUGAAG CTTCATCC C CAAGCCTG Table 14

1930 UCAGGCUU CUGAUGAG X CGAA IGGAUGAA TTCATCCC C AAGCCTGA

1931 GUCAGGCU CUGAUGAG X CGAA IGGGAUGA TCATCCCC A AGCCTGAC

1935 GCCCGUCA CUGAUGAG X CGAA ICUUGGGG CCCCAAGC C TGACGGGC

1936 AGCCCGUC CUGAUGAG X CGAA IGCUUGGG CCCAAGCC T GACGGGCT

1944 UCGGCCGC CUGAUGAG X CGAA ICCCGUCA TGACGGGC T GCGGCCGA

1950 UCACAAUC CUGAUGAG X CGAA ICCGCAGC GCTGCGGC C GATTGTGA

1961 GUAGUCCA CUGAUGAG X CGAA lUUCACAA TTGTGAAC A TGGACTAC

1967 CACGACGU CUGAUGAG X CGAA IUCCAUGU ACATGGAC T ACGTCGTG

1981 AACGUUCU CUGAUGAG X CGAA ICUCCCAC GTGGGAGC C AGAACGTT

1982 GAACGUUC CUGAUGAG X CGAA IGCUCCCA TGGGAGCC A GAACGTTC

1991 UUCUCUGC CUGAUGAG X CGAA IAACGUUC GAACGTTC C GCAGAGAA

1994 CUUUUCUC CUGAUGAG X CGAA ICGGAACG CGTTCCGC A GAGAAAAG

2008 AGACGCUC CUGAUGAG X CGAA ICCCUCUU AAGAGGGC C GAGCGTCT

2016 UCGAGGUG CUGAUGAG X CGAA IACGCUCG CGAGCGTC T CACCTCGA

2018 CCUCGAGG CUGAUGAG X CGAA IAGACGCU AGCGTCTC A CCTCGAGG

2020 ACCCUCGA CUGAUGAG X CGAA IUGAGACG CGTCTCAC C TCGAGGGT

2021 CACCCUCG CUGAUGAG X CGAA IGUGAGAC GTCTCACC T CGAGGGTG

2035 CUGAACAG CUGAUGAG X CGAA ICCUUCAC GTGAAGGC A CTGTTCAG

2037 CGCUGAAC CUGAUGAG X CGAA IUGCCUUC GAAGGCAC T GTTCAGCG

2042 GAGCACGC CUGAUGAG X CGAA IAACAGUG CACTGTTC A GCGTGCTC

2049 CGUAGUUG CUGAUGAG X CGAA ICACGCUG CAGCGTGC T CAACTACG

2051 CUCGUAGU CUGAUGAG X CGAA IAGCACGC GCGTGCTC A ACTACGAG

2054 CCGCUCGU CUGAUGAG X CGAA IUUGAGCA TGCTCAAC T ACGAGCGG

2072 GAGGCCGG CUGAUGAG X CGAA ICGCCGCG CGCGGCGC C CCGGCCTC

2073 GGAGGCCG CUGAUGAG X CGAA IGCGCCGC GCGGCGCC C CGGCCTCC

2074 AGGAGGCC CUGAUGAG X CGAA IGGCGCCG CGGCGCCC C GGCCTCCT

2078 GCCCAGGA CUGAUGAG X CGAA ICCGGGGC GCCCCGGC C TCCTGGGC

2079 CGCCCAGG CUGAUGAG X CGAA IGCCGGGG CCCCGGCC T CCTGGGCG

2081 GGCGCCCA CUGAUGAG X CGAA IAGGCCGG CCGGCCTC C TGGGCGCC

2082 AGGCGCCC CUGAUGAG X CGAA IGAGGCCG CGGCCTCC T GGGCGCCT

2089 AGCACAGA CUGAUGAG X CGAA ICGCCCAG CTGGGCGC C TCTGTGCT

2090 CAGCACAG CUGAUGAG X CGAA IGCGCCCA TGGGCGCC T CTGTGCTG

2092 CCCAGCAC CUGAUGAG X CGAA IAGGCGCC GGCGCCTC T GTGCTGGG

2097 CCAGGCCC CUGAUGAG X CGAA ICACAGAG CTCTGTGC T GGGCCTGG

2102 AUCGUCCA CUGAUGAG X CGAA ICCCAGCA TGCTGGGC c TGGACGAT

2103 UAUCGUCC CUGAUGAG X CGAA IGCCCAGC GCTGGGCC T GGACGATA

2114 GGCCCUGU CUGAUGAG X CGAA IAUAUCGU ACGATATC c ACAGGGCC

2115 AGGCCCUG CUGAUGAG X CGAA IGAUAUCG CGATATCC A CAGGGCCT

2117 CCAGGCCC CUGAUGAG X CGAA IUGGAUAU ATATCCAC A GGGCCTGG

2122 GUGCGCCA CUGAUGAG X CGAA ICCCUGUG CACAGGGC C TGGCGCAC

2123 GGUGCGCC CUGAUGAG X CGAA IGCCCUGU ACAGGGCC T GGCGCACC

2129 CACGAAGG CUGAUGAG X CGAA ICGCCAGG CCTGGCGC A CCTTCGTG

2131 AGCACGAA CUGAUGAG X CGAA lUGCGCCA TGGCGCAC C TTCGTGCT

2132 CAGCACGA CUGAUGAG X CGAA IGUGCGCC GGCGCACC T TCGTGCTG

2139 GCACACGC CUGAUGAG X CGAA ICACGAAG CTTCGTGC T GCGTGTGC

2152 GGGUCCUG CUGAUGAG X CGAA ICCCGCAC GTGCGGGC C CAGGACCC

2153 CGGGUCCU CUGAUGAG X CGAA IGCCCGCA TGCGGGCC C AGGACCCG Table 14

2154 GCGGGUCC CUGAUGAG X CGAA IGGCCCGC GCGGGCCC A GGACCCGC

2159 AGGCGGCG CUGAUGAG X CGAA IUCCUGGG CCCAGGAC C CGCCGCCT

2160 CAGGCGGC CUGAUGAG X CGAA IGUCCUGG CCAGGACC C GCCGCCTG

2163 GCUCAGGC CUGAUGAG X CGAA ICGGGUCC GGACCCGC C GCCTGAGC

2166 ACAGCUCA CUGAUGAG X CGAA ICGGCGGG CCCGCCGC C TGAGCTGT

2167 UACAGCUC CUGAUGAG X CGAA IGCGGCGG CCGCCGCC T GAGCTGTA

2172 CAAAGUAC CUGAUGAG X CGAA ICUCAGGC GCCTGAGC T GTACTTTG

2177 CUUGACAA CUGAUGAG X CGAA IUACAGCU AGCTGTAC T TTGTCAAG

2183 AUCCACCU CUGAUGAG X CGAA lACAAAGU ACTTTGTC A AGGTGGAT

2210 GGGGAUGG CUGAUGAG X CGAA IUCGUACG CGTACGAC A CCATCCCC

2212 UGGGGGAU CUGAUGAG X CGAA lUGUCGUA TACGACAC C ATCCCCCA

2213 CUGGGGGA CUGAUGAG X CGAA IGUGUCGU ACGACACC A TCCCCCAG

2216 GUCCUGGG CUGAUGAG X CGAA IAUGGUGU ACACCATC C CCCAGGAC

2217 UGUCCUGG CUGAUGAG X CGAA IGAUGGUG CACCATCC C CCAGGACA

2218 CUGUCCUG CUGAUGAG X CGAA IGGAUGGU ACCATCCC C CAGGACAG

2219 CCUGUCCU CUGAUGAG X CGAA IGGGAUGG CCATCCCC C AGGACAGG

2220 GCCUGUCC CUGAUGAG X CGAA IGGGGAUG CATCCCCC A GGACAGGC

2225 CGUGAGCC CUGAUGAG X CGAA IUCCUGGG CCCAGGAC A GGCTCACG

2229 CCUCCGUG CUGAUGAG X CGAA ICCUGUCC GGACAGGC T CACGGAGG

2231 GACCUCCG CUGAUGAG X CGAA IAGCCUGU ACAGGCTC A CGGAGGTC

2240 GCUGGCGA CUGAUGAG X CGAA IACCUCCG CGGAGGTC A TCGCCAGC

2245 AUGAUGCU CUGAUGAG X CGAA ICGAUGAC GTCATCGC C AGCATCAT

2246 GAUGAUGC CUGAUGAG X CGAA IGCGAUGA TCATCGCC A GCATCATC

2249 UUUGAUGA CUGAUGAG X CGAA ICUGGCGA TCGCCAGC A TCATCAAA

2252 GGGUUUGA CUGAUGAG X CGAA IAUGCUGG CCAGCATC A TCAAACCC

2255 CUGGGGUU CUGAUGAG X CGAA IAUGAUGC GCATCATC A AACCCCAG

2259 UGUUCUGG CUGAUGAG X CGAA IUUUGAUG CATCAAAC C CCAGAACA

2260 GUGUUCUG CUGAUGAG X CGAA IGUUUGAU ATCAAACC C CAGAACAC

2261 CGUGUUCU CUGAUGAG X CGAA IGGUUUGA TCAAACCC C AGAACACG

2262 ACGUGUUC CUGAUGAG X CGAA IGGGUUUG CAAACCCC A GAACACGT

2267 GCAGUACG CUGAUGAG X CGAA IUUCUGGG CCCAGAAC A CGTACTGC

2273 ACGCACGC CUGAUGAG X CGAA IUACGUGU ACACGTAC T GCGTGCGT

2290 UGGACCAC CUGAUGAG X CGAA ICAUACCG CGGTATGC C GTGGTCCA

2297 GGCCUUCU CUGAUGAG X CGAA IACCACGG CCGTGGTC C AGAAGGCC

2298 CGGCCUUC CUGAUGAG X CGAA IGACCACG CGTGGTCC A GAAGGCCG

2305 CCAUGGGC CUGAUGAG X CGAA ICCUUCUG CAGAAGGC C GCCCATGG

2308 UGCCCAUG CUGAUGAG X CGAA ICGGCCUU AAGGCCGC C CATGGGCA

2309 GUGCCCAU CUGAUGAG X CGAA IGCGGCCU AGGCCGCC C ATGGGCAC

2310 CGUGCCCA CUGAUGAG X CGAA IGGCGGCC GGCCGCCC A TGGGCACG

2316 UGCGGACG CUGAUGAG X CGAA ICCCAUGG CCATGGGC A CGTCCGCA

2321 GGCCUUGC CUGAUGAG X CGAA IACGUGCC GGCACGTC C GCAAGGCC

2324 GAAGGCCU CUGAUGAG X CGAA ICGGACGU ACGTCCGC A AGGCCTTC

2329 CUCUUGAA CUGAUGAG X CGAA ICCUUGCG CGCAAGGC C TTCAAGAG

2330 GCUCUUGA CUGAUGAG X CGAA IGCCUUGC GCAAGGCC T TCAAGAGC

2333 GUGGCUCU CUGAUGAG X CGAA IAAGGCCU AGGCCTTC A AGAGCCAC

2339 AGAGACGU CUGAUGAG X CGAA ICUCUUGA TCAAGAGC C ACGTCTCT

2340 UAGAGACG CUGAUGAG X CGAA IGCUCUUG CAAGAGCC A CGTCTCTA Table 14

2345 CAAGGUAG CUGAUGAG X CGAA IACGUGGC GCCACGTC T CTACCTTG

2347 GUCAAGGU CUGAUGAG X CGAA IAGACGUG CACGTCTC T ACCTTGAC

2350 UCUGUCAA CUGAUGAG X CGAA IUAGAGAC GTCTCTAC C TTGACAGA

2351 GUCUGUCA CUGAUGAG X CGAA IGUAGAGA TCTCTACC T TGACAGAC

2356 UGGAGGUC CUGAUGAG X CGAA IUCAAGGU ACCTTGAC A GACCTCCA

2360 CGGCUGGA CUGAUGAG X CGAA IUCUGUCA TGACAGAC C TCCAGCCG

2361 ACGGCUGG CUGAUGAG X CGAA IGUCUGUC GACAGACC T CCAGCCGT

2363 GUACGGCU CUGAUGAG X CGAA IAGGUCUG CAGACCTC C AGCCGTAC

2364 UGUACGGC CUGAUGAG X CGAA IGAGGUCU AGACCTCC A GCCGTACA

2367 GCAUGUAC CUGAUGAG X CGAA ICUGGAGG CCTCCAGC C GTACATGC

2372 CUGUCGCA CUGAUGAG X CGAA IUACGGCU AGCCGTAC A TGCGACAG

2379 CCACGAAC CUGAUGAG X CGAA IUCGCAUG CATGCGAC A GTTCGTGG

2389 UGCAGGUG CUGAUGAG X CGAA ICCACGAA TTCGTGGC T CACCTGCA

2391 CCUGCAGG CUGAUGAG X CGAA IAGCCACG CGTGGCTC A CCTGCAGG

2393 CUCCUGCA CUGAUGAG X CGAA IUGAGCCA TGGCTCAC C TGCAGGAG

2394 UCUCCUGC CUGAUGAG X CGAA IGUGAGCC GGCTCACC T GCAGGAGA

2397 UGGUCUCC CUGAUGAG X CGAA ICAGGUGA TCACCTGC A GGAGACCA

2404 AGCGGGCU CUGAUGAG X CGAA IUCUCCUG CAGGAGAC C AGCCCGCT

2405 CAGCGGGC CUGAUGAG X CGAA IGUCUCCU AGGAGACC A GCCCGCTG

2408 CCUCAGCG CUGAUGAG X CGAA ICUGGUCU AGACCAGC C CGCTGAGG

2409 CCCUCAGC CUGAUGAG X CGAA IGCUGGUC GACCAGCC C GCTGAGGG

2412 CAUCCCUC CUGAUGAG X CGAA ICGGGCUG CAGCCCGC T GAGGGATG

2422 AUGACGAC CUGAUGAG X CGAA ICAUCCCU AGGGATGC C GTCGTCAT

2429 CUGCUCGA CUGAUGAG X CGAA IACGACGG CCGTCGTC A TCGAGCAG

2436 AGGAGCUC CUGAUGAG X CGAA ICUCGAUG CATCGAGC A GAGCTCCT

2441 CAGGGAGG CUGAUGAG X CGAA ICUCUGCU AGCAGAGC T CCTCCCTG

2443 UUCAGGGA CUGAUGAG X CGAA IAGCUCUG CAGAGCTC c TCCCTGAA

2444 AUUCAGGG CUGAUGAG X CGAA IGAGCUCU AGAGCTCC T CCCTGAAT

2446 UCAUUCAG CUGAUGAG X CGAA IAGGAGCU AGCTCCTC c CTGAATGA

2447 CUCAUUCA CUGAUGAG X CGAA IGAGGAGC GCTCCTCC c TGAATGAG

2448 CCUCAUUC CUGAUGAG X CGAA IGGAGGAG CTCCTCCC T GAATGAGG

2458 CCACUGCU CUGAUGAG X CGAA ICCUCAUU AATGAGGC c AGCAGTGG

2459 GCCACUGC CUGAUGAG X CGAA IGCCUCAU ATGAGGCC A GCAGTGGC

2462 GAGGCCAC CUGAUGAG X CGAA ICUGGCCU AGGCCAGC A GTGGCCTC

2468 GUCGAAGA CUGAUGAG X CGAA ICCACUGC GCAGTGGC C TCTTCGAC

2469 CGUCGAAG CUGAUGAG X CGAA IGCCACUG CAGTGGCC T CTTCGACG

2471 GACGUCGA CUGAUGAG X CGAA IAGGCCAC GTGGCCTC T TCGACGTC

2480 GCGUAGGA CUGAUGAG X CGAA IACGUCGA TCGACGTC T TCCTACGC

2483 GAAGCGUA CUGAUGAG X CGAA IAAGACGU ACGTCTTC C TACGCTTC

2484 UGAAGCGU CUGAUGAG X CGAA IGAAGACG CGTCTTCC T ACGCTTCA

2489 GCACAUGA CUGAUGAG X CGAA ICGUAGGA TCCTACGC T TCATGTGC

2492 GUGGCACA CUGAUGAG X CGAA IAAGCGUA TACGCTTC A TGTGCCAC

2498 GGCGUGGU CUGAUGAG X CGAA ICACAUGA TCATGTGC C ACCACGCC

2499 CGGCGUGG CUGAUGAG X CGAA IGCACAUG CATGTGCC A CCACGCCG

2501 CACGGCGU CUGAUGAG X CGAA IUGGCACA TGTGCCAC C ACGCCGTG

2502 GCACGGCG CUGAUGAG X CGAA IGUGGCAC GTGCCACC A CGCCGTGC

2506 AUGCGCAC CUGAUGAG X CGAA ICGUGGUG CACCACGC C GTGCGCAT Table 14

2513 GCCCCUGA CUGAUGAG X CGAA ICGCACGG CCGTGCGC A TCAGGGGC

2516 CUUGCCCC CUGAUGAG X CGAA IAUGCGCA TGCGCATC A GGGGCAAG

2522 GUAGGACU CUGAUGAG X CGAA ICCCCUGA TCAGGGGC A AGTCCTAC

2527 UGGACGUA CUGAUGAG X CGAA IACUUGCC GGCAAGTC C TACGTCCA

2528 CUGGACGU CUGAUGAG X CGAA IGACUUGC GCAAGTCC T ACGTCCAG

2534 CUGGCACU CUGAUGAG X CGAA IACGUAGG CCTACGTC C AGTGCCAG

2535 CCUGGCAC CUGAUGAG X CGAA IGACGUAG CTACGTCC A GTGCCAGG

2540 GAUCCCCU CUGAUGAG X CGAA ICACUGGA TCCAGTGC C AGGGGATC

2541 GGAUCCCC CUGAUGAG X CGAA IGCACUGG CCAGTGCC A GGGGATCC

2549 GCCCUGCG CUGAUGAG X CGAA IAUCCCCU AGGGGATC C CGCAGGGC

2550 AGCCCUGC CUGAUGAG X CGAA IGAUCCCC GGGGATCC C GCAGGGCT

2553 UGGAGCCC CUGAUGAG X CGAA ICGGGAUC GATCCCGC A GGGCTCCA

2558 GAGGAUGG CUGAUGAG X CGAA ICCCUGCG CGCAGGGC T CCATCCTC

2560 GAGAGGAU CUGAUGAG X CGAA IAGCCCUG CAGGGCTC c ATCCTCTC

2561 GGAGAGGA CUGAUGAG X CGAA IGAGCCCU AGGGCTCC A TCCTCTCC

2564 CGUGGAGA CUGAUGAG X CGAA IAUGGAGC GCTCCATC C TCTCCACG

2565 GCGUGGAG CUGAUGAG X CGAA IGAUGGAG CTCCATCC T CTCCACGC

2567 CAGCGUGG CUGAUGAG X CGAA IAGGAUGG CCATCCTC T CCACGCTG

2569 AGCAGCGU CUGAUGAG X CGAA IAGAGGAU ATCCTCTC c ACGCTGCT

2570 GAGCAGCG CUGAUGAG X CGAA IGAGAGGA TCCTCTCC A CGCTGCTC

2574 UGCAGAGC CUGAUGAG X CGAA ICGUGGAG CTCCACGC T GCTCTGCA

2577 GGCUGCAG CUGAUGAG X CGAA ICAGCGUG CACGCTGC T CTGCAGCC

2579 CAGGCUGC CUGAUGAG X CGAA IAGCAGCG CGCTGCTC T GCAGCCTG

2582 GCACAGGC CUGAUGAG X CGAA ICAGAGCA TGCTCTGC A GCCTGTGC

2585 GUAGCACA CUGAUGAG X CGAA ICUGCAGA TCTGCAGC C TGTGCTAC

2586 CGUAGCAC CUGAUGAG X CGAA IGCUGCAG CTGCAGCC T GTGCTACG

2591 GUCGCCGU CUGAUGAG X CGAA ICACAGGC GCCTGTGC T ACGGCGAC

2600 GUUCUCCA CUGAUGAG X CGAA IUCGCCGU ACGGCGAC A TGGAGAAC

2609 AAACAGCU CUGAUGAG X CGAA lUUCUCCA TGGAGAAC A AGCTGTTT

2613 CCGCAAAC CUGAUGAG X CGAA ICUUGUUC GAACAAGC T GTTTGCGG

2640 GCAGGAGC CUGAUGAG X CGAA ICCCGUCC GGACGGGC T GCTCCTGC

2643 AACGCAGG CUGAUGAG X CGAA ICAGCCCG CGGGCTGC T CCTGCGTT

2645 CAAACGCA CUGAUGAG X CGAA IAGCAGCC GGCTGCTC C TGCGTTTG

2646 CCAAACGC CUGAUGAG X CGAA IGAGCAGC GCTGCTCC T GCGTTTGG

2666 CACCAACA CUGAUGAG X CGAA IAAAUCAU ATGATTTC T TGTTGGTG

2677 AGGUGAGG CUGAUGAG X CGAA IUCACCAA TTGGTGAC A CCTCACCT

2679 UGAGGUGA CUGAUGAG X CGAA IUGUCACC GGTGACAC C TCACCTCA

2680 GUGAGGUG CUGAUGAG X CGAA IGUGUCAC GTGACACC T CACCTCAC

2682 GGGUGAGG CUGAUGAG X CGAA IAGGUGUC GACACCTC A CCTCACCC

2684 GUGGGUGA CUGAUGAG X CGAA IUGAGGUG CACCTCAC C TCACCCAC

2685 CGUGGGUG CUGAUGAG X CGAA IGUGAGGU ACCTCACC T CACCCACG

2687 CGCGUGGG CUGAUGAG X CGAA IAGGUGAG CTCACCTC A CCCACGCG

2689 UUCGCGUG CUGAUGAG X CGAA IUGAGGUG CACCTCAC C CACGCGAA

2690 UUUCGCGU CUGAUGAG X CGAA IGUGAGGU ACCTCACC C ACGCGAAA

2691 UUUUCGCG CUGAUGAG X CGAA IGGUGAGG CCTCACCC A CGCGAAAA

2701 CUGAGGAA CUGAUGAG X CGAA IUUUUCGC GCGAAAAC C TTCCTCAG

2702 CCUGAGGA CUGAUGAG X CGAA IGUUUUCG CGAAAACC T TCCTCAGG Table 14

2705 GGUCCUGA CUGAUGAG X CGAA IAAGGUUU AAACCTTC C TCAGGACC

2706 GGGUCCUG CUGAUGAG X CGAA IGAAGGUU AACCTTCC T CAGGACCC

2708 CAGGGUCC CUGAUGAG X CGAA IAGGAAGG CCTTCCTC A GGACCCTG

2713 CGGACCAG CUGAUGAG X CGAA IUCCUGAG CTCAGGAC C CTGGTCCG

2714 UCGGACCA CUGAUGAG X CGAA IGUCCUGA TCAGGACC C TGGTCCGA

2715 CUCGGACC CUGAUGAG X CGAA IGGUCCUG CAGGACCC T GGTCCGAG

2720 GACACCUC CUGAUGAG X CGAA IACCAGGG CCCTGGTC c GAGGTGTC

2729 AUACUCAG CUGAUGAG X CGAA IACACCUC GAGGTGTC c CTGAGTAT

2730 CAUACUCA CUGAUGAG X CGAA IGACACCU AGGTGTCC c TGAGTATG

2731 CCAUACUC CUGAUGAG X CGAA IGGACACC GGTGTCCC T GAGTATGG

2741 CACCACGC CUGAUGAG X CGAA ICCAUACU AGTATGGC T GCGTGGTG

2753 CUUCCGCA CUGAUGAG X CGAA IUUCACCA TGGTGAAC T TGCGGAAG

2764 UUCACCAC CUGAUGAG X CGAA IUCUUCCG CGGAAGAC A GTGGTGAA

2774 UACAGGGA CUGAUGAG X CGAA IUUCACCA TGGTGAAC T TCCCTGTA

2777 UUCUACAG CUGAUGAG X CGAA lAAGUUCA TGAACTTC C CTGTAGAA

2778 CUUCUACA CUGAUGAG X CGAA IGAAGUUC GAACTTCC C TGTAGAAG

2779 UCUUCUAC CUGAUGAG X CGAA IGGAAGUU AACTTCCC T GTAGAAGA

2794 CCACCCAG CUGAUGAG X CGAA ICCUCGUC GACGAGGC c CTGGGTGG

2795 GCCACCCA CUGAUGAG X CGAA IGCCUCGU ACGAGGCC c TGGGTGGC

2796 UGCCACCC CUGAUGAG X CGAA IGGCCUCG CGAGGCCC T GGGTGGCA

2804 AAAAGCCG CUGAUGAG X CGAA ICCACCCA TGGGTGGC A CGGCTTTT

2809 UGAACAAA CUGAUGAG X CGAA ICCGUGCC GGCACGGC T TTTGTTCA

2817 CCGGCAUC CUGAUGAG X CGAA IAACAAAA TTTTGTTC A GATGCCGG

2823 CGUGGGCC CUGAUGAG X CGAA ICAUCUGA TCAGATGC C GGCCCACG

2827 AGGCCGUG CUGAUGAG X CGAA ICCGGCAU ATGCCGGC C CACGGCCT

2828 UAGGCCGU CUGAUGAG X CGAA IGCCGGCA TGCCGGCC C ACGGCCTA

2829 AUAGGCCG CUGAUGAG X CGAA IGGCCGGC GCCGGCCC A CGGCCTAT

2834 GGGGAAUA CUGAUGAG X CGAA ICCGUGGG CCCACGGC C TATTCCCC

2835 AGGGGAAU CUGAUGAG X CGAA IGCCGUGG CCACGGCC T ATTCCCCT

2840 GCACCAGG CUGAUGAG X CGAA IAAUAGGC GCCTATTC C CCTGGTGC

2841 CGCACCAG CUGAUGAG X CGAA IGAAUAGG CCTATTCC C CTGGTGCG

2842 CCGCACCA CUGAUGAG X CGAA IGGAAUAG CTATTCCC C TGGTGCGG

2843 GCCGCACC CUGAUGAG X CGAA IGGGAAUA TATTCCCC T GGTGCGGC

2852 CAGCAGCA CUGAUGAG X CGAA ICCGCACC GGTGCGGC c TGCTGCTG

2853 CCAGCAGC CUGAUGAG X CGAA IGCCGCAC GTGCGGCC T GCTGCTGG

2856 UAUCCAGC CUGAUGAG X CGAA ICAGGCCG CGGCCTGC T GCTGGATA

2859 GGGUAUCC CUGAUGAG X CGAA ICAGCAGG CCTGCTGC T GGATACCC

2866 AGGGUCCG CUGAUGAG X CGAA IUAUCCAG CTGGATAC c CGGACCCT

2867 CAGGGUCC CUGAUGAG X CGAA IGUAUCCA TGGATACC c GGACCCTG

2872 ACCUCCAG CUGAUGAG X CGAA IUCCGGGU ACCCGGAC c CTGGAGGT

2873 CACCUCCA CUGAUGAG X CGAA IGUCCGGG CCCGGACC c TGGAGGTG

2874 GCACCUCC CUGAUGAG X CGAA IGGUCCGG CCGGACCC T GGAGGTGC

2883 AGUCGCUC CUGAUGAG X CGAA ICACCUCC GGAGGTGC A GAGCGACT

2891 GCUGGAGU CUGAUGAG X CGAA IUCGCUCU AGAGCGAC T ACTCCAGC

2894 AUAGCUGG CUGAUGAG X CGAA IUAGUCGC GCGACTAC T CCAGCTAT

2896 GCAUAGCU CUGAUGAG X CGAA IAGUAGUC GACTACTC c AGCTATGC

2897 GGCAUAGC CUGAUGAG X CGAA IGAGUAGU ACTACTCC A GCTATGCC Table 14

2900 CCGGGCAU CUGAUGAG X CGAA ICUGGAGU ACTCCAGC T ATGCCCGG

2905 GAGGUCCG CUGAUGAG X CGAA ICAUAGCU AGCTATGC C CGGACCTC

2906 GGAGGUCC CUGAUGAG X CGAA IGCAUAGC GCTATGCC C GGACCTCC

2911 CUGAUGGA CUGAUGAG X CGAA IUCCGGGC GCCCGGAC C TCCATCAG

2912 UCUGAUGG CUGAUGAG X CGAA IGUCCGGG CCCGGACC T CCATCAGA

2914 GCUCUGAU CUGAUGAG X CGAA IAGGUCCG CGGACCTC C ATCAGAGC

2915 GGCUCUGA CUGAUGAG X CGAA IGAGGUCC GGACCTCC A TCAGAGCC

2918 ACUGGCUC CUGAUGAG X CGAA lAUGGAGG CCTCCATC A GAGCCAGT

2923 GUGAGACU CUGAUGAG X CGAA ICUCUGAU ATCAGAGC C AGTCTCAC

2924 GGUGAGAC CUGAUGAG X CGAA IGCUCUGA TCAGAGCC A GTCTCACC

2928 UGAAGGUG CUGAUGAG X CGAA IACUGGCU AGCCAGTC T CACCTTCA

2930 GUUGAAGG CUGAUGAG X CGAA IAGACUGG CCAGTCTC A CCTTCAAC

2932 CGGUUGAA CUGAUGAG X CGAA IUGAGACU AGTCTCAC C TTCAACCG

2933 GCGGUUGA CUGAUGAG X CGAA IGUGAGAC GTCTCACC T TCAACCGC

2936 GCCGCGGU CUGAUGAG X CGAA IAAGGUGA TCACCTTC A ACCGCGGC

2939 GAAGCCGC CUGAUGAG X CGAA IUUGAAGG CCTTCAAC C GCGGCTTC

2945 AGCCUUGA CUGAUGAG X CGAA ICCGCGGU ACCGCGGC T TCAAGGCT

2948 CCCAGCCU CUGAUGAG X CGAA IAAGCCGC GCGGCTTC A AGGCTGGG

2953 UUCCUCCC CUGAUGAG X CGAA ICCUUGAA TTCAAGGC T GGGAGGAA

2963 GCGACGCA CUGAUGAG X CGAA IUUCCUCC GGAGGAAC A TGCGTCGC

2972 AAAGAGUU CUGAUGAG X CGAA ICGACGCA TGCGTCGC A AACTCTTT

2976 CCCCAAAG CUGAUGAG X CGAA IUUUGCGA TCGCAAAC T CTTTGGGG

2978 GACCCCAA CUGAUGAG X CGAA IAGUUUGC GCAAACTC T TTGGGGTC

2987 CAGCCGCA CUGAUGAG X CGAA IACCCCAA TTGGGGTC T TGCGGCTG

2994 GACACUUC CUGAUGAG X CGAA ICCGCAAG CTTGCGGC T GAAGTGTC

3003 ACAGGCUG CUGAUGAG X CGAA IACACUUC GAAGTGTC A CAGCCTGT

3005 AAACAGGC CUGAUGAG X CGAA IUGACACU AGTGTCAC A GCCTGTTT

3008 CAGAAACA CUGAUGAG X CGAA ICUGUGAC GTCACAGC C TGTTTCTG

3009 CCAGAAAC CUGAUGAG X CGAA IGCUGUGA TCACAGCC T GTTTCTGG

3015 GCAAAUCC CUGAUGAG X CGAA IAAACAGG CCTGTTTC T GGATTTGC

-3024 UGUUCACC CUGAUGAG X CGAA ICAAAUCC GGATTTGC A GGTGAACA

3032 CUGGAGGC CUGAUGAG X CGAA IUUCACCU AGGTGAAC A GCCTCCAG

3035 CGUCUGGA CUGAUGAG X CGAA ICUGUUCA TGAACAGC C TCCAGACG

3036 CCGUCUGG CUGAUGAG X CGAA IGCUGUUC GAACAGCC T CCAGACGG

3038 CACCGUCU CUGAUGAG X CGAA IAGGCUGU ACAGCCTC C AGACGGTG

3039 ACACCGUC CUGAUGAG X CGAA IGAGGCUG CAGCCTCC A GACGGTGT

3050 GAUGUUGG CUGAUGAG X CGAA ICACACCG CGGTGTGC A CCAACATC

3052 UAGAUGUU CUGAUGAG X CGAA IUGCACAC GTGTGCAC C AACATCTA

3053 GUAGAUGU CUGAUGAG X CGAA IGUGCACA TGTGCACC A ACATCTAC

3056 CUUGUAGA CUGAUGAG X CGAA IUUGGUGC GCACCAAC A TCTACAAG

3059 GAUCUUGU CUGAUGAG X CGAA IAUGUUGG CCAACATC T ACAAGATC

3062 GAGGAUCU CUGAUGAG X CGAA IUAGAUGU ACATCTAC A AGATCCTC

3068 CAGCAGGA CUGAUGAG X CGAA IAUCUUGU ACAAGATC C TCCTGCTG

3069 GCAGCAGG CUGAUGAG X CGAA IGAUCUUG CAAGATCC T CCTGCTGC

3071 CUGCAGCA CUGAUGAG X CGAA IAGGAUCU AGATCCTC C TGCTGCAG

3072 CCUGCAGC CUGAUGAG X CGAA IGAGGAUC GATCCTCC T GCTGCAGG

3075 ACGCCUGC CUGAUGAG X CGAA ICAGGAGG CCTCCTGC T GCAGGCGT Table 14

3078 UGUACGCC CUGAUGAG X CGAA ICAGCAGG CCTGCTGC A GGCGTACA

3086 GUGAAACC CUGAUGAG X CGAA IUACGCCU AGGCGTAC A GGTTTCAC

3093 CACAUGCG CUGAUGAG X CGAA IAAACCUG CAGGTTTC A CGCATGTG

3097 AGCACACA CUGAUGAG X CGAA ICGUGAAA TTTCACGC A TGTGTGCT

3105 GGAGCUGC CUGAUGAG X CGAA ICACACAU ATGTGTGC T GCAGCTCC

3108 AUGGGAGC CUGAUGAG X CGAA ICAGCACA TGTGCTGC A GCTCCCAT

3111 GAAAUGGG CUGAUGAG X CGAA ICUGCAGC GCTGCAGC T CCCATTTC

3113 AUGAAAUG CUGAUGAG X CGAA IAGCUGCA TGCAGCTC C CATTTCAT

3114 GAUGAAAU CUGAUGAG X CGAA IGAGCUGC GCAGCTCC c ATTTCATC

3115 UGAUGAAA CUGAUGAG X CGAA IGGAGCUG CAGCTCCC A TTTCATCA

3120 CUUGCUGA CUGAUGAG X CGAA IAAAUGGG CCCATTTC A TCAGCAAG

3123 AAACUUGC CUGAUGAG X CGAA IAUGAAAU ATTTCATC A GCAAGTTT

3126 UCCAAACU CUGAUGAG X CGAA ICUGAUGA TCATCAGC A AGTTTGGA

3140 AAAUGUGG CUGAUGAG X CGAA IUUCUUCC GGAAGAAC c CCACATTT

3141 AAAAUGUG CUGAUGAG X CGAA IGUUCUUC GAAGAACC c CACATTTT

3142 AAAAAUGU CUGAUGAG X CGAA IGGUUCUU AAGAACCC c ACATTTTT

3143 GAAAAAUG CUGAUGAG X CGAA IGGGUUCU AGAACCCC A CATTTTTC

3145 AGGAAAAA CUGAUGAG X CGAA lUGGGGUU AACCCCAC A TTTTTCCT

3152 GACGCGCA CUGAUGAG X CGAA IAAAAAUG CATTTTTC C TGCGCGTC

3153 UGACGCGC CUGAUGAG X CGAA IGAAAAAU ATTTTTCC T GCGCGTCA

3161 GUCAGAGA CUGAUGAG X CGAA IACGCGCA TGCGCGTC A TCTCTGAC

3164 CGUGUCAG CUGAUGAG X CGAA IAUGACGC GCGTCATC T CTGACACG

3166 GCCGUGUC CUGAUGAG X CGAA IAGAUGAC GTCATCTC T GACACGGC

3170 GGAGGCCG CUGAUGAG X CGAA IUCAGAGA TCTCTGAC A CGGCCTCC

3175 CAGAGGGA CUGAUGAG X CGAA ICCGUGUC GACACGGC C TCCCTCTG

3176 GCAGAGGG CUGAUGAG X CGAA IGCCGUGU ACACGGCC T CCCTCTGC

3178 UAGCAGAG CUGAUGAG X CGAA IAGGCCGU ACGGCCTC C CTCTGCTA

3179 GUAGCAGA CUGAUGAG X CGAA IGAGGCCG CGGCCTCC C TCTGCTAC

3180 AGUAGCAG CUGAUGAG X CGAA IGGAGGCC GGCCTCCC T CTGCTACT

3182 GGAGUAGC CUGAUGAG X CGAA IAGGGAGG CCTCCCTC T GCTACTCC

3185 GAUGGAGU CUGAUGAG X CGAA ICAGAGGG CCCTCTGC T ACTCCATC

3188 CAGGAUGG CUGAUGAG X CGAA IUAGCAGA TCTGCTAC T CCATCCTG

3190 UUCAGGAU CUGAUGAG X CGAA IAGUAGCA TGCTACTC C ATCCTGAA

3191 UUUCAGGA CUGAUGAG X CGAA IGAGUAGC GCTACTCC A TCCTGAAA

3194 GGCUUUCA CUGAUGAG X CGAA lAUGGAGU ACTCCATC C TGAAAGCC

3195 UGGCUUUC CUGAUGAG X CGAA IGAUGGAG CTCCATCC T GAAAGCCA

3202 GCGUUCUU CUGAUGAG X CGAA ICUUUCAG CTGAAAGC C AAGAACGC

3203 UGCGUUCU CUGAUGAG X CGAA IGCUUUCA TGAAAGCC A AGAACGCA

3211 GACAUCCC CUGAUGAG X CGAA ICGUUCUU AAGAACGC A GGGATGTC

3222 UGGCCCCC CUGAUGAG X CGAA ICGACAUC GATGTCGC T GGGGGCCA

3229 σcGcccuu CUGAUGAG X CGAA ICCCCCAG CTGGGGGC C AAGGGCGC

3230 GGCGCCCU CUGAUGAG X CGAA IGCCCCCA TGGGGGCC A AGGGCGCC

3238 GGGCCGGC CUGAUGAG X CGAA ICGCCCUU AAGGGCGC C GCCGGCCC

3241 AGAGGGCC CUGAUGAG X CGAA ICGGCGCC GGCGCCGC C GGCCCTCT

3245 GGGCAGAG CUGAUGAG X CGAA ICCGGCGG CCGCCGGC C CTCTGCCC

3246 AGGGCAGA CUGAUGAG X CGAA IGCCGGCG CGCCGGCC C TCTGCCCT

3247 GAGGGCAG CUGAUGAG X CGAA IGGCCGGC GCCGGCCC T CTGCCCTC Table 14

3249 CGGAGGGC CUGAUGAG X CGAA IAGGGCCG CGGCCCTC T GCCCTCCG

3252 CCUCGGAG CUGAUGAG X CGAA ICAGAGGG CCCTCTGC C CTCCGAGG

3253 GCCUCGGA CUGAUGAG X CGAA IGCAGAGG CCTCTGCC C TCCGAGGC

3254 GGCCUCGG CUGAUGAG X CGAA IGGCAGAG CTCTGCCC T CCGAGGCC

3256 ACGGCCUC CUGAUGAG X CGAA IAGGGCAG CTGCCCTC C GAGGCCGT

3262 CACUGCAC CUGAUGAG X CGAA ICCUCGGA TCCGAGGC C GTGCAGTG

3267 ACAGCCAC CUGAUGAG X CGAA ICACGGCC GGCCGTGC A GTGGCTGT

3273 GGUGGCAC CUGAUGAG X CGAA ICCACUGC GCAGTGGC T GTGCCACC

3278 UGCUUGGU CUGAUGAG X CGAA ICACAGCC GGCTGTGC C ACCAAGCA

3279 AUGCUUGG CUGAUGAG X CGAA IGCACAGC GCTGTGCC A CCAAGCAT

3281 GAAUGCUU CUGAUGAG X CGAA IUGGCACA TGTGCCAC C AAGCATTC

3282 GGAAUGCU CUGAUGAG X CGAA IGUGGCAC GTGCCACC A AGCATTCC

3286 AGCAGGAA CUGAUGAG X CGAA ICUUGGUG CACCAAGC A TTCCTGCT

3290 CUUGAGCA CUGAUGAG X CGAA IAAUGCUU AAGCATTC C TGCTCAAG

3291 GCUUGAGC CUGAUGAG X CGAA IGAAUGCU AGCATTCC T GCTCAAGC

3294 UCAGCUUG CUGAUGAG X CGAA ICAGGAAU ATTCCTGC T CAAGCTGA

3296 AGUCAGCU CUGAUGAG X CGAA IAGCAGGA TCCTGCTC A AGCTGACT

3300 GUCGAGUC CUGAUGAG X CGAA ICUUGAGC GCTCAAGC T GACTCGAC

3304 CGGUGUCG CUGAUGAG X CGAA IUCAGCUU AAGCTGAC T CGACACCG

3309 UGACACGG CUGAUGAG X CGAA IUCGAGUC GACTCGAC A CCGTGTCA

3311 GGUGACAC CUGAUGAG X CGAA IUGUCGAG CTCGACAC C GTGTCACC

3317 CACGUAGG CUGAUGAG X CGAA IACACGGU ACCGTGTC A CCTACGTG

3319 GGCACGUA CUGAUGAG X CGAA IUGACACG CGTGTCAC C TACGTGCC

3320 UGGCACGU CUGAUGAG X CGAA IGUGACAC GTGTCACC T ACGTGCCA

3327 CCAGGAGU CUGAUGAG X CGAA ICACGUAG CTACGTGC C ACTCCTGG

3328 CCCAGGAG CUGAUGAG X CGAA IGCACGUA TACGTGCC A CTCCTGGG

3330 ACCCCAGG CUGAUGAG X CGAA IUGGCACG CGTGCCAC T CCTGGGGT

3332 UGACCCCA CUGAUGAG X CGAA lAGUGGCA TGCCACTC C TGGGGTCA

3333 GUGACCCC CUGAUGAG X CGAA IGAGUGGC GCCACTCC T GGGGTCAC

3340 GUCCUGAG CUGAUGAG X CGAA IACCCCAG CTGGGGTC A CTCAGGAC

3342 CUGUCCUG CUGAUGAG X CGAA IUGACCCC GGGGTCAC T CAGGACAG

3344 GGCUGUCC CUGAUGAG X CGAA IAGUGACC GGTCACTC A GGACAGCC

3349 GUCUGGGC CUGAUGAG X CGAA IUCCUGAG CTCAGGAC A GCCCAGAC

3352 UGCGUCUG CUGAUGAG X CGAA ICUGUCCU AGGACAGC C CAGACGCA

3353 CUGCGUCU CUGAUGAG X CGAA IGCUGUCC GGACAGCC C AGACGCAG

3354 GCUGCGUC CUGAUGAG X CGAA IGGCUGUC GACAGCCC A GACGCAGC

3360 GACUCAGC CUGAUGAG X CGAA ICGUCUGG CCAGACGC A GCTGAGTC

3363 UCCGACUC CUGAUGAG X CGAA ICUGCGUC GACGCAGC T GAGTCGGA

3375 UCCCCGGG CUGAUGAG X CGAA ICUUCCGA TCGGAAGC T CCCGGGGA

3377 CGUCCCCG CUGAUGAG X CGAA IAGCUUCC GGAAGCTC C CGGGGACG

3378 UCGUCCCC CUGAUGAG X CGAA IGAGCUUC GAAGCTCC C GGGGACGA

3390 GGGCAGUC CUGAUGAG X CGAA ICGUCGUC GACGACGC T GACTGCCC

3394 UCCAGGGC CUGAUGAG X CGAA IUCAGCGU ACGCTGAC T GCCCTGGA

3397 GCCUCCAG CUGAUGAG X CGAA ICAGUCAG CTGACTGC c CTGGAGGC

3398 GGCCUCCA CUGAUGAG X CGAA IGCAGUCA TGACTGCC c TGGAGGCC

3399 CGGCCUCC CUGAUGAG X CGAA IGGCAGUC GACTGCCC T GGAGGCCG

3406 UUGGCUGC CUGAUGAG X CGAA ICCUCCAG CTGGAGGC c GCAGCCAA Table 14

3409 GGGUUGGC CUGAUGAG X CGAA ICGGCCUC GAGGCCGC A GCCAACCC

3412 GCCGGGUU CUGAUGAG X CGAA ICUGCGGC GCCGCAGC C AACCCGGC

3413 UGCCGGGU CUGAUGAG X CGAA IGCUGCGG CCGCAGCC A ACCCGGCA

3416 CAGUGCCG CUGAUGAG X CGAA IUUGGCUG CAGCCAAC C CGGCACTG

3417 GCAGUGCC CUGAUGAG X CGAA IGUUGGCU AGCCAACC C GGCACTGC

3421 GAGGGCAG CUGAUGAG X CGAA ICCGGGUU AACCCGGC A CTGCCCTC

3423 CUGAGGGC CUGAUGAG X CGAA IUGCCGGG CCCGGCAC T GCCCTCAG

3426 AGUCUGAG CUGAUGAG X CGAA ICAGUGCC GGCACTGC C CTCAGACT

3427 AAGUCUGA CUGAUGAG X CGAA IGCAGUGC GCACTGCC C TCAGACTT

3428 GAAGUCUG CUGAUGAG X CGAA IGGCAGUG CACTGCCC T CAGACTTC

3430 UUGAAGUC CUGAUGAG X CGAA IAGGGCAG CTGCCCTC A GACTTCAA

3434 GGUCUUGA CUGAUGAG X CGAA IUCUGAGG CCTCAGAC T TCAAGACC

3437 GAUGGUCU CUGAUGAG X CGAA IAAGUCUG CAGACTTC A AGACCATC

3442 UCCAGGAU CUGAUGAG X CGAA IUCUUGAA TTCAAGAC C ATCCTGGA

3443 GUCCAGGA CUGAUGAG X CGAA IGUCUUGA TCAAGACC A TCCTGGAC

3446 UCAGUCCA CUGAUGAG X CGAA IAUGGUCU AGACCATC C TGGACTGA

3447 AUCAGUCC CUGAUGAG X CGAA IGAUGGUC GACCATCC T GGACTGAT

3452 UGGCCAUC CUGAUGAG X CGAA IUCCAGGA TCCTGGAC T GATGGCCA

3459 GGGCGGGU CUGAUGAG X CGAA ICCAUCAG CTGATGGC c ACCCGCCC

3460 UGGGCGGG CUGAUGAG X CGAA IGCCAUCA TGATGGCC A CCCGCCCA

3462 UGUGGGCG CUGAUGAG X CGAA IUGGCCAU ATGGCCAC C CGCCCACA

3463 CUGUGGGC CUGAUGAG X CGAA IGUGGCCA TGGCCACC C GCCCACAG

3466 UGGCUGUG CUGAUGAG X CGAA ICGGGUGG CCACCCGC C CACAGCCA

3467 CUGGCUGU CUGAUGAG X CGAA IGCGGGUG CACCCGCC C ACAGCCAG

3468 CCUGGCUG CUGAUGAG X CGAA IGGCGGGU ACCCGCCC A CAGCCAGG

3470 GGCCUGGC CUGAUGAG X CGAA IUGGGCGG CCGCCCAC A GCCAGGCC

3473 CUCGGCCU CUGAUGAG X CGAA ICUGUGGG CCCACAGC C AGGCCGAG

3474 UCUCGGCC CUGAUGAG X CGAA IGCUGUGG CCACAGCC A GGCCGAGA

3478 CUGCUCUC CUGAUGAG X CGAA ICCUGGCU AGCCAGGC C GAGAGCAG

3485 CUGGUGUC CUGAUGAG X CGAA ICUCUCGG CCGAGAGC A GACACCAG

3489 GCUGCUGG CUGAUGAG X CGAA IUCUGCUC GAGCAGAC A CCAGCAGC

3491 GGGCUGCU CUGAUGAG X CGAA IUGUCUGC GCAGACAC C AGCAGCCC

3492 AGGGCUGC CUGAUGAG X CGAA IGUGUCUG CAGACACC A GCAGCCCT

3495 GACAGGGC CUGAUGAG X CGAA ICUGGUGU ACACCAGC A GCCCTGTC

3498 CGUGACAG CUGAUGAG X CGAA ICUGCUGG CCAGCAGC C CTGTCACG

3499 GCGUGACA CUGAUGAG X CGAA IGCUGCUG CAGCAGCC C TGTCACGC

3500 GGCGUGAC CUGAUGAG X CGAA IGGCUGCU AGCAGCCC T GTCACGCC

3504 GCCCGGCG CUGAUGAG X CGAA IACAGGGC GCCCTGTC A CGCCGGGC

3508 UAGAGCCC CUGAUGAG X CGAA ICGUGACA TGTCACGC C GGGCTCTA

3513 GGACGUAG CUGAUGAG X CGAA ICCCGGCG CGCCGGGC T CTACGTCC

3515 UGGGACGU CUGAUGAG X CGAA IAGCCCGG CCGGGCTC T ACGTCCCA

3521 CCUCCCUG CUGAUGAG X CGAA IACGUAGA TCTACGTC c CAGGGAGG

3522 CCCUCCCU CUGAUGAG X CGAA IGACGUAG CTACGTCC c AGGGAGGG

3523 UCCCUCCC CUGAUGAG X CGAA IGGACGUA TACGTCCC A GGGAGGGA

3540 UGGGUGUG CUGAUGAG X CGAA ICCGCCCC GGGGCGGC C CACACCCA

3541 CUGGGUGU CUGAUGAG X CGAA IGCCGCCC GGGCGGCC C ACACCCAG

3542 CCUGGGUG CUGAUGAG X CGAA IGGCCGCC GGCGGCCC A CACCCAGG Table 14

3544 GGCCUGGG CUGAUGAG X CGAA IUGGGCCG CGGCCCAC A CCCAGGCC

3546 CGGGCCUG CUGAUGAG X CGAA IUGUGGGC GCCCACAC C CAGGCCCG

3547 GCGGGCCU CUGAUGAG X CGAA IGUGUGGG CCCACACC C AGGCCCGC

3548 UGCGGGCC CUGAUGAG X CGAA IGGUGUGG CCACACCC A GGCCCGCA

3552 GCGGUGCG CUGAUGAG X CGAA ICCUGGGU ACCCAGGC C CGCACCGC

3553 AGCGGUGC CUGAUGAG X CGAA IGCCUGGG CCCAGGCC C GCACCGCT

3556 CCCAGCGG CUGAUGAG X CGAA ICGGGCCU AGGCCCGC A CCGCTGGG

3558 CUCCCAGC CUGAUGAG X CGAA IUGCGGGC GCCCGCAC C GCTGGGAG

3561 AGACUCCC CUGAUGAG X CGAA ICGGUGCG CGCACCGC T GGGAGTCT

3569 CAGGCCUC CUGAUGAG X CGAA IACUCCCA TGGGAGTC T GAGGCCTG

3575 CUCACUCA CUGAUGAG X CGAA ICCUCAGA TCTGAGGC C TGAGTGAG

3576 ACUCACUC CUGAUGAG X CGAA IGCCUCAG CTGAGGCC T GAGTGAGT

3592 CAGGCCUC CUGAUGAG X CGAA ICCAAACA TGTTTGGC C GAGGCCTG

3598 GACAUGCA CUGAUGAG X CGAA ICCUCGGC GCCGAGGC C TGCATGTC

3599 GGACAUGC CUGAUGAG X CGAA IGCCUCGG CCGAGGCC T GCATGTCC

3602 GCCGGACA CUGAUGAG X CGAA ICAGGCCU AGGCCTGC A TGTCCGGC

3607 CUUCAGCC CUGAUGAG X CGAA IACAUGCA TGCATGTC C GGCTGAAG

3611 CAGCCUUC CUGAUGAG X CGAA ICCGGACA TGTCCGGC T GAAGGCTG

3618 GGACACUC CUGAUGAG X CGAA ICCUUCAG CTGAAGGC T GAGTGTCC

3626 CCUCAGCC CUGAUGAG X CGAA IACACUCA TGAGTGTC c GGCTGAGG

3630 CAGGCCUC CUGAUGAG X CGAA ICCGGACA TGTCCGGC T GAGGCCTG

3636 CUCGCUCA CUGAUGAG X CGAA ICCUCAGC GCTGAGOC c TGAGCGAG

3637 ACUCGCUC CUGAUGAG X CGAA IGCCUCAG CTGAGGCC T GAGCGAGT

3649 CCUUGGCU CUGAUGAG X CGAA IACACUCG CGAGTGTC c AGCCAAGG

3650 CCCUUGGC CUGAUGAG X CGAA IGACACUC GAGTGTCC A GCCAAGGG

3653 CAGCCCUU CUGAUGAG X CGAA ICUGGACA TGTCCAGC C AAGGGCTG

3654 UCAGCCCU CUGAUGAG X CGAA IGCUGGAC GTCCAGCC A AGGGCTGA

3660 GGACACUC CUGAUGAG X CGAA ICCCUUGG CCAAGGGC T GAGTGTCC

3668 GGUGUGCU CUGAUGAG X CGAA IACACUCA TGAGTGTC C AGCACACC

3669 AGGUGUGC CUGAUGAG X CGAA IGACACUC GAGTGTCC A GCACACCT

3672 GGCAGGUG CUGAUGAG X CGAA ICUGGACA TGTCCAGC A CACCTGCC

3674 ACGGCAGG CUGAUGAG X CGAA IUGCUGGA TCCAGCAC A CCTGCCGT

3676 AGACGGCA CUGAUGAG X CGAA IUGUGCUG CAGCACAC C TGCCGTCT

3677 AAGACGGC CUGAUGAG X CGAA IGUGUGCU AGCACACC T GCCGTCTT

3680 GUGAAGAC CUGAUGAG X CGAA ICAGGUGU ACACCTGC C GTCTTCAC

3684 GGAAGUGA CUGAUGAG X CGAA IACGGCAG CTGCCGTC T TCACTTCC

3687 UGGGGAAG CUGAUGAG X CGAA IAAGACGG CCGTCTTC A CTTCCCCA

3689 UGUGGGGA CUGAUGAG X CGAA IUGAAGAC GTCTTCAC T TCCCCACA

3692 GCCUGUGG CUGAUGAG X CGAA IAAGUGAA TTCACTTC C CCACAGGC

3693 AGCCUGUG CUGAUGAG X CGAA IGAAGUGA TCACTTCC C CACAGGCT

3694 CAGCCUGU CUGAUGAG X CGAA IGGAAGUG CACTTCCC C ACAGGCTG

3695 CCAGCCUG CUGAUGAG X CGAA IGGGAAGU ACTTCCCC A CAGGCTGG

3697 CGCCAGCC CUGAUGAG X CGAA IUGGGGAA TTCCCCAC A GGCTGGCG

3701 CGAGCGCC CUGAUGAG X CGAA ICCUGUGG CCACAGGC T GGCGCTCG

3707 UGGAGCCG CUGAUGAG X CGAA ICGCCAGC GCTGGCGC T CGGCTCCA

3712 UGGGGUGG CUGAUGAG X CGAA ICCGAGCG CGCTCGGC T CCACCCCA

3714 CCUGGGGU CUGAUGAG X CGAA IAGCCGAG CTCGGCTC C ACCCCAGG Table 14

3715 CCCUGGGG CUGAUGAG X CGAA IGAGCCGA TCGGCTCC A CCCCAGGG

3717 GGCCCUGG CUGAUGAG X CGAA IUGGAGCC GGCTCCAC C CCAGGGCC

3718 UGGCCCUG CUGAUGAG X CGAA IGUGGAGC GCTCCACC C CAGGGCCA

3719 CUGGCCCU CUGAUGAG X CGAA IGGUGGAG CTCCACCC C AGGGCCAG

3720 GCUGGCCC CUGAUGAG X CGAA IGGGUGGA TCCACCCC A GGGCCAGC

3725 GAAAAGCU CUGAUGAG X CGAA ICCCUGGG CCCAGGGC C AGCTTTTC

3726 GGAAAAGC CUGAUGAG X CGAA IGCCCUGG CCAGGGCC A GCTTTTCC

3729 UGAGGAAA CUGAUGAG X CGAA ICUGGCCC GGGCCAGC T TTTCCTCA

3734 CCUGGUGA CUGAUGAG X CGAA IAAAAGCU AGCTTTTC C TCACCAGG

3735 UCCUGGUG CUGAUGAG X CGAA IGAAAAGC GCTTTTCC T CACCAGGA

3737 GCUCCUGG CUGAUGAG X CGAA lAGGAAAA TTTTCCTC A CCAGGAGC

3739 GGGCUCCU CUGAUGAG X CGAA IUGAGGAA TTCCTCAC C AGGAGCCC

3740 CGGGCUCC CUGAUGAG X CGAA IGUGAGGA TCCTCACC A GGAGCCCG

3746 GGAAGCCG CUGAUGAG X CGAA ICUCCUGG CCAGGAGC C CGGCTTCC

3747 UGGAAGCC CUGAUGAG X CGAA IGCUCCUG CAGGAGCC C GGCTTCCA

3751 GGAGUGGA CUGAUGAG X CGAA ICCGGGCU AGCCCGGC T TCCACTCC

3754 UGGGGAGU CUGAUGAG X CGAA IAAGCCGG CCGGCTTC C ACTCCCCA

3755 GUGGGGAG CUGAUGAG X CGAA IGAAGCCG CGGCTTCC A CTCCCCAC

3757 AUGUGGGG CUGAUGAG X CGAA IUGGAAGC GCTTCCAC T CCCCACAT

3759 CUAUGUGG CUGAUGAG X CGAA IAGUGGAA TTCCACTC C CCACATAG

3760 CCUAUGUG CUGAUGAG X CGAA IGAGUGGA TCCACTCC C CACATAGG

3761 UCCUAUGU CUGAUGAG X CGAA IGGAGUGG CCACTCCC C ACATAGGA

3762 UUCCUAUG CUGAUGAG X CGAA IGGGAGUG CACTCCCC A CATAGGAA

3764 UAUUCCUA CUGAUGAG X CGAA IUGGGGAG CTCCCCAC A TAGGAATA

3776 CUGGGGAU CUGAUGAG X CGAA IACUAUUC GAATAGTC C ATCCCCAG

3777 UCUGGGGA CUGAUGAG X CGAA IGACUAUU AATAGTCC A TCCCCAGA

3780 GAAUCUGG CUGAUGAG X CGAA IAUGGACU AGTCCATC C CCAGATTC

3781 CGAAUCUG CUGAUGAG X CGAA IGAUGGAC GTCCATCC C CAGATTCG

3782 GCGAAUCU CUGAUGAG X CGAA IGGAUGGA TCCATCCC C AGATTCGC

3783 GGCGAAUC CUGAUGAG X CGAA IGGGAUGG CCATCCCC A GATTCGCC

3791 UGAACAAU CUGAUGAG X CGAA ICGAAUCU AGATTCGC C ATTGTTCA^'

3792 GUGAACAA CUGAUGAG X CGAA IGCGAAUC GATTCGCC A TTGTTCAC

3799 GCGAGGGG^' CUGAUGAG X CGAA IAACAAUG CATTGTTC A CCCCTCGC

3801 GGGCGAGG CUGAUGAG X CGAA IUGAACAA TTGTTCAC C CCTCGCCC

3802 AGGGCGAG CUGAUGAG X CGAA IGUGAACA TGTTCACC C cTcσcccT

3803 CAGGGCGA CUGAUGAG X CGAA IGGUGAAC GTTCACCC C TCGCCCTG

3804 GCAGGGCG CUGAUGAG X CGAA IGGGUGAA TTCACCCC T CGCCCTGC

3808 GAGGGCAG CUGAUGAG X CGAA ICGAGGGG CCCCTCGC C CTGCCCTC

3809 GGAGGGCA CUGAUGAG X CGAA IGCGAGGG CCCTCGCC C TGCCCTCC

3810 AGGAGGGC CUGAUGAG X CGAA IGGCGAGG CCTCGCCC T GCCCTCCT

3813 CAAAGGAG CUGAUGAG X CGAA ICAGGGCG CGCCCTGC C CTCCTTTG

3814 GCAAAGGA CUGAUGAG X CGAA IGCAGGGC GCCCTGCC C TCCTTTGC

3815 GGCAAAGG CUGAUGAG X CGAA IGGCAGGG CCCTGCCC T CCTTTGCC

3817 AAGGCAAA CUGAUGAG X CGAA IAGGGCAG CTGCCCTC c TTTGCCTT

3818 GAAGGCAA CUGAUGAG X CGAA IGAGGGCA TGCCCTCC T TTGCCTTC

3823 GGGUGGAA CUGAUGAG X CGAA ICAAAGGA TCCTTTGC c TTCCACCC

3824 GGGGUGGA CUGAUGAG X CGAA IGCAAAGG CCTTTGCC T TCCACCCC Table 14

3827 GUGGGGGU CUGAUGAG X CGAA IAAGGCAA TTGCCTTC C ACCCCCAC

3828 GGUGGGGG CUGAUGAG X CGAA IGAAGGCA TGCCTTCC A CCCCCACC

3830 AUGGUGGG CUGAUGAG X CGAA IUGGAAGG CCTTCCAC C CCCACCAT

3831 GAUGGUGG CUGAUGAG X CGAA IGUGGAAG CTTCCACC C CCACCATC

3832 GGAUGGUG CUGAUGAG X CGAA IGGUGGAA TTCCACCC C CACCATCC

3833 UGGAUGGU CUGAUGAG X CGAA IGGGUGGA TCCACCCC C ACCATCCA

3834 CUGGAUGG CUGAUGAG X CGAA IGGGGUGG CCACCCCC A CCATCCAG

3836 ACCUGGAU CUGAUGAG X CGAA IUGGGGGU ACCCCCAC C ATCCAGGT

3837 CACCUGGA CUGAUGAG X CGAA IGUGGGGG CCCCCACC A TCCAGGTG

3840 CUCCACCU CUGAUGAG X CGAA IAUGGUGG CCACCATC C AGGTGGAG

3841 UCUCCACC CUGAUGAG X CGAA IGAUGGUG CACCATCC A GGTGGAGA

3851 CUUCUCAG CUGAUGAG X CGAA IUCUCCAC GTGGAGAC C CTGAGAAG

3852 CCUUCUCA CUGAUGAG X CGAA IGUCUCCA TGGAGACC C TGAGAAGG

3853 UCCUUCUC CUGAUGAG X CGAA IGGUCUCC GGAGACCC T GAGAAGGA

3863 GCUCCCAG CUGAUGAG X CGAA IUCCUUCU AGAAGGAC C CTGGGAGC

3864 AGCUCCCA CUGAUGAG X CGAA IGUCCUUC GAAGGACC C TGGGAGCT

3865 GAGCUCCC CUGAUGAG X CGAA IGGUCCUU AAGGACCC T GGGAGCTC

3872 AUUCCCAG CUGAUGAG X CGAA ICUCCCAG CTGGGAGC T CTGGGAAT

3874 AAAUUCCC CUGAUGAG X CGAA IAGCUCCC GGGAGCTC T GGGAATTT

3891 ACACCUUU CUGAUGAG X CGAA IUCACUCC GGAGTGAC c AAAGGTGT

3892 CACACCUU CUGAUGAG X CGAA IGUCACUC GAGTGACC A AAGGTGTG

3902 GUGUACAG CUGAUGAG X CGAA ICACACCU AGGTGTGC C CTGTACAC

3903 UGUGUACA CUGAUGAG X CGAA IGCACACC GGTGTGCC C TGTACACA

3904 CUGUGUAC CUGAUGAG X CGAA IGGCACAC GTGTGCCC T GTACACAG

3909 CUCGCCUG CUGAUGAG X CGAA IUACAGGG CCCTGTAC A CAGGCGAG

3911 UCCUCGCC CUGAUGAG X CGAA IUGUACAG CTGTACAC A GGCGAGGA

3921 AGGUGCAG CUGAUGAG X CGAA IUCCUCGC GCGAGGAC C CTGCACCT

3922 CAGGUGCA CUGAUGAG X CGAA IGUCCUCG CGAGGACC C TGCACCTG

3923 CCAGGUGC CUGAUGAG X CGAA IGGUCCUC GAGGACCC T GCACCTGG

3926 CAUCCAGG CUGAUGAG X CGAA ICAGGGUC GACCCTGC A CCTGGATG

3928 CCCAUCCA CUGAUGAG X CGAA IUGCAGGG CCCTGCAC C TGGATGGG

3929 CCCCAUCC CUGAUGAG X CGAA IGUGCAGG CCTGCACC T GGATGGGG

3941 ACCCACAG CUGAUGAG X CGAA IACCCCCA TGGGGGTC C CTGTGGGT

3942 GACCCACA CUGAUGAG X CGAA IGACCCCC GGGGGTCC C TGTGGGTC

3943 UGACCCAC CUGAUGAG X CGAA IGGACCCC GGGGTCCC T GTGGGTCA

3951 CCCCAAUU CUGAUGAG X CGAA IACCCACA TGTGGGTC A AATTGGGG

3968 ACUCCCAC CUGAUGAG X CGAA ICACCUCC GGAGGTGC T GTGGGAGT

3984 AUAUAUUC CUGAUGAG X CGAA IUAUUUUA TAAAATAC T GAATATAT

4002 UUCAAAAC CUGAUGAG X CGAA IAAAAACU AGTTTTTC A GTTTTGAA

Stem Length = 8 . Core Sequence = CUGAUGAG X CGAA (X = GCCGUUAGGC or other stem II sequence and length (greater than or equal to 2 base-pairs)). I = Inosine nucleotide

Seql = TERT (Homo sapiens telomerase reverse transcriptase (TERT) mRNA, 4015 bp); Nakamura et al.. Science 277 (5328), 955-959 (1997) Table 15

Table 15: Human telomerase reverse transcriptase (TERT) G-Cleaver Ribozyme and Target Sequence

Table 15

202 CUUUCCGCGC G CUGGU ACCAG UGAUGGCAUGCACUAUGCGCG GCGCGGAAAG

216 GUGGCCCAGU G CCUGG CCAGG UGAUGGCAUGCACUAUGCGCG ACUGGGCCAC

223 AGUGCCUGGU G UGCGU ACGCA UGAUGGCAUGCACUAUGCGCG ACCAGGCACU

225 UGCCUGGUGU G CGUGC GCACG UGAUGGCAUGCACUAUGCGCG ACACCAGGCA

229 UGGUGUGCGU G CCCUG CAGGG UGAUGGCAUGCACUAUGCGCG ACGCACACCA

239 GCCCUGGGAC G CACGG CCGUG UGAUGGCAUGCACUAUGCGCG GUCCCAGGGC

247 ACGCACGGCC G CCCCC GGGGG UGAUGGCAUGCACUAUGCGCG GGCCGUGCGU

254 GCCGCCCCCC G CCGCC GGCGG UGAUGGCAUGCACUAUGCGCG GGGGGGCGGC

257 GCCCCCCGCC G CCCCC GGGGG UGAUGGCAUGCACUAUGCGCG GGCGGGGGGC

270 CCCUCCUUCC G CCAGG CCUGG UGAUGGCAUGCACUAUGCGCG GGAAGGAGGG

277 UCCGCCAGGU G UCCUG CAGGA UGAUGGCAUGCACUAUGCGCG ACCUGGCGGA

282 CAGGUGUCCU G CCUGA UCAGG UGAUGGCAUGCACUAUGCGCG AGGACACCUG

286 UGUCCUGCCU G AAGGA UCCUU UGAUGGCAUGCACUAUGCGCG AGGCAGGACA

303 CUGGUGGCCC G AGUGC GCACU UGAUGGCAUGCACUAUGCGCG GGGCCACCAG

307 UGGCCCGAGU G CUGCA UGCAG UGAUGGCAUGCACUAUGCGCG ACUCGGGCCA

310 CCCGAGUGCU G CAGAG CUCUG UGAUGGCAUGCACUAUGCGCG AGCACUCGGG

319 UGCAGAGGCU G UGCGA UCGCA UGAUGGCAUGCACUAUGCGCG AGCCUCUGCA

321 CAGAGGCUGU G CGAGC GCUCG UGAUGGCAUGCACUAUGCGCG ACAGCCUCUG

323 GAGGCUGUGC G AGCGC GCGCU UGAUGGCAUGCACUAUGCGCG GCACAGCCUC

327 CUGUGCGAGC G CGGCG CGCCG UGAUGGCAUGCACUAUGCGCG GCUCGCACAG

332 CGAGCGCGGC G CGAAG CUUCG UGAUGGCAUGCACUAUGCGCG GCCGCGCUCG

334 AGCGCGGCGC G AAGAA UUCUU UGAUGGCAUGCACUAUGCGCG GCGCCGCGCU

343 CGAAGAACGU G CUGGC GCCAG UGAUGGCAUGCACUAUGCGCG ACGUUCUUCG

359 CUUCGGCUUC G CGCUG CAGCG UGAUGGCAUGCACUAUGCGCG GAAGCCGAAG

361 UCGGCUUCGC G CUGCU AGCAG UGAUGGCAUGCACUAUGCGCG GCGAAGCCGA

364 GCUUCGCGCU G CUGGA UCCAG UGAUGGCAUGCACUAUGCGCG AGCGCGAAGC

378 GACGGGGCCC G CGGGG CCCCG UGAUGGCAUGCACUAUGCGCG GGGCCCCGUC

392 GGGCCCCCCC G AGGCC GGCCU UGAUGGCAUGCACUAUGCGCG GGGGGGGCCC

412 CCACCAGCGU G CGCAG CUGCG UGAUGGCAUGCACUAUGCGCG ACGCUGGUGG

414 ACCAGCGUGC G CAGCU AGCUG UGAUGGCAUGCACUAUGCGCG GCACGCUGGU

424 GCAGCUACCU G CCCAA UUGGG UGAUGGCAUGCACUAUGCGCG AGGUAGCUGC

Table 15

436 CCAACACGGU G ACCGA UCGGU UGAUGGCAUGCACUAUGCGCG ACCGUGUUGG

440 CACGGUGACC G ACGCA UGCGU UGAUGGCAUGCACUAUGCGCG GGUCACCGUG

443 GGUGACCGAC G CACUG CAGUG UGAUGGCAUGCACUAUGCGCG GUCGGUCACC

448 CCGACGCACU G CGGGG CCCCG UGAUGGCAUGCACUAUGCGCG AGUGCGUCGG

472 CGUGGGGGCU G CUGCU AGCAG UGAUGGCAUGCACUAUGCGCG AGCCCCCACG

475 GGGGGCUGCU G CUGCG CGCAG UGAUGGCAUGCACUAUGCGCG AGCAGCCCCC

478 GGCUGCUGCU G CGCCG CGGCG UGAUGGCAUGCACUAUGCGCG AGCAGCAGCC

480 CUGCUGCUGC G CCGCG CGCGG UGAUGGCAUGCACUAUGCGCG GCAGCAGCAG

483 CUGCUGCGCC G CGUGG CCACG UGAUGGCAUGCACUAUGCGCG GGCGCAGCAG

491 CCGCGUGGGC G ACGAC GUCGU UGAUGGCAUGCACUAUGCGCG GCCCACGCGG

494 CGUGGGCGAC G ACGUG CACGU UGAUGGCAUGCACUAUGCGCG GUCGCCCACG

499 GCGACGACGU G CUGGU ACCAG UGAUGGCAUGCACUAUGCGCG ACGUCGUCGC

511 UGGUUCACCU G CUGGC GCCAG UGAUGGCAUGCACUAUGCGCG AGGUGAACCA

519 CUGCUGGCAC G CUGCG CGCAG UGAUGGCAUGCACUAUGCGCG GUGCCAGCAG

522 CUGGCACGCU G CGCGC GCGCG UGAUGGCAUGCACUAUGCGCG AGCGUGCCAG

524 GGCACGCUGC G CGCUC GAGCG UGAUGGCAUGCACUAUGCGCG GCAGCGUGCC

526 CACGCUGCGC G CUCUU AAGAG UGAUGGCAUGCACUAUGCGCG GCGCAGCGUG

533 CGCGCUCUUU G UGCUG CAGCA UGAUGGCAUGCACUAUGCGCG AAAGAGCGCG

535 CGCUCUUUGU G CUGGU ACCAG UGAUGGCAUGCACUAUGCGCG ACAAAGAGCG

552 GCUCCCAGCU G CGCCU AGGCG UGAUGGCAUGCACUAUGCGCG AGCUGGGAGC

554 UCCCAGCUGC G CCUAC GUAGG UGAUGGCAUGCACUAUGCGCG GCAGCUGGGA

565 CCUACCAGGU G UGCGG CCGCA UGAUGGCAUGCACUAUGCGCG ACCUGGUAGG

567 UACCAGGUGU G CGGGC GCCCG UGAUGGCAUGCACUAUGCGCG ACACCUGGUA

574 UGUGCGGGCC G CCGCU AGCGG UGAUGGCAUGCACUAUGCGCG GGCCCGCACA

577 GCGGGCCGCC G CUGUA UACAG UGAUGGCAUGCACUAUGCGCG GGCGGCCCGC

580 GGCCGCCGCU G UACCA UGGUA UGAUGGCAUGCACUAUGCGCG AGCGGCGGCC

593 CCAGCUCGGC G CUGCC GGCAG UGAUGGCAUGCACUAUGCGCG GCCGAGCUGG

596 GCUCGGCGCU G CCACU AGUGG UGAUGGCAUGCACUAUGCGCG AGCGCCGAGC

616 CCCGGCCCCC G CCACA UGUGG UGAUGGCAUGCACUAUGCGCG GGGGGCCGGG

623 CCCGCCACAC G CUAGU ACUAG UGAUGGCAUGCACUAUGCGCG GUGUGGCGGG

636 AGUGGACCCC G AAGGC GCCUU UGAUGGCAUGCACUAUGCGCG GGGGUCCACU

1 able 15

651 CGUCUGGGAU G CGAAC GUUCG UGAUGGCAUGCACUAUGCGCG AUCCCAGACG

653 UCUGGGAUGC G AACGG CCGUU UGAUGGCAUGCACUAUGCGCG GCAUCCCAGA

703 CCCUGGGCCU G CCAGC GCUGG UGAUGGCAUGCACUAUGCGCG AGGCCCAGGG

716 AGCCCCGGGU G CGAGG CCUCG UGAUGGCAUGCACUAUGCGCG ACCCGGGGCU

718 CCCCGGGUGC G AGGAG CUCCU UGAUGGCAUGCACUAUGCGCG GCACCCGGGG

726 GCGAGGAGGC G CGGGG CCCCG UGAUGGCAUGCACUAUGCGCG GCCUCCUCGC

737 CGGGGGCAGU G CCAGC GCUGG UGAUGGCAUGCACUAUGCGCG ACUGCCCCCG

744 AGUGCCAGCC G AAGUC GACUU UGAUGGCAUGCACUAUGCGCG GGCUGGCACU

751 GCCGAAGUCU G CCGUU AACGG UGAUGGCAUGCACUAUGCGCG AGACUUCGGC

757 GUCUGCCGUU G CCCAA UUGGG UGAUGGCAUGCACUAUGCGCG AACGGCAGAC

779 CAGGCGUGGC G CUGCC GGCAG UGAUGGCAUGCACUAUGCGCG GCCACGCCUG

782 GCGUGGCGCU G CCCCU AGGGG UGAUGGCAUGCACUAUGCGCG AGCGCCACGC

788 CGCUGCCCCU G AGCCG CGGCU UGAUGGCAUGCACUAUGCGCG AGGGGCAGCG

802 CGGAGCGGAC G CCCGU ACGGG UGAUGGCAUGCACUAUGCGCG GUCCGCUCCG

841 CGGGCAGGAC G CGUGG CCACG UGAUGGCAUGCACUAUGCGCG GUCCUGCCCG

850 CGCGUGGACC G AGUGA UCACU UGAUGGCAUGCACUAUGCGCG GGUCCACGCG

854 UGGACCGAGU G ACCGU ACGGU UGAUGGCAUGCACUAUGCGCG ACUCGGUCCA

867 CGUGGUUUCU G UGUGG CCACA UGAUGGCAUGCACUAUGCGCG AGAAACCACG

869 UGGUUUCUGU G UGGUG CACCA UGAUGGCAUGCACUAUGCGCG ACAGAAACCA

874 UCUGUGUGGU G UCACC GGUGA UGAUGGCAUGCACUAUGCGCG ACCACACAGA

881 GGUGUCACCU G CCAGA UCUGG UGAUGGCAUGCACUAUGCGCG AGGUGACACC

890 UGCCAGACCC G CCGAA UUCGG UGAUGGCAUGCACUAUGCGCG GGGUCUGGCA

893 CAGACCCGCC G AAGAA UUCUU UGAUGGCAUGCACUAUGCGCG GGCGGGUCUG

917 UUUGGAGGGU G CGCUC GAGCG UGAUGGCAUGCACUAUGCGCG ACCCUCCAAA

919 UGGAGGGUGC G CUCUC GAGAG UGAUGGCAUGCACUAUGCGCG GCACCCUCCA

931 UCUCUGGCAC G CGCCA UGGCG UGAUGGCAUGCACUAUGCGCG GUGCCAGAGA

933 UCUGGCACGC G CCACU AGUGG UGAUGGCAUGCACUAUGCGCG GCGUGCCAGA

957 UCCGUGGGCC G CCAGC GCUGG UGAUGGCAUGCACUAUGCGCG GGCCCACGGA

968 CCAGCACCAC G CGGGC GCCCG UGAUGGCAUGCACUAUGCGCG GUGGUGCUGG

988 CAUCCACAUC G CGGCC GGCCG UGAUGGCAUGCACUAUGCGCG GAUGUGGAUG

1012 CCUGGGACAC G CCUUG CAAGG UGAUGGCAUGCACUAUGCGCG GUGUCCCAGG

Table 15

1017 GACACGCCUU G UCCCC GGGGA UGAUGGCAUGCACUAUGCGCG AAGGCGUGUC

1027 GUCCCCCGGU G UACGC GCGUA UGAUGGCAUGCACUAUGCGCG ACCGGGGGAC

1031 CCCGGUGUAC G CCGAG CUCGG UGAUGGCAUGCACUAUGCGCG GUACACCGGG

1034 GGUGUACGCC G AGACC GGUCU UGAUGGCAUGCACUAUGCGCG GGCGUACACC

1064 CUCCUCAGGC G ACAAG CUUGU UGAUGGCAUGCACUAUGCGCG GCCUGAGGAG

1078 AGGAGCAGCU G CGGCC GGCCG UGAUGGCAUGCACUAUGCGCG AGCUGCUCCU

1105 UCAGCUCUCU G AGGCC GGCCU UGAUGGCAUGCACUAUGCGCG AGAGAGCUGA

1117 GGCCCAGCCU G ACUGG CCAGU UGAUGGCAUGCACUAUGCGCG AGGCUGGGCC

1124 CCUGACUGGC G CUCGG CCGAG UGAUGGCAUGCACUAUGCGCG GCCAGUCAGG

1171 GGCCCUGGAU G CCAGG CCUGG UGAUGGCAUGCACUAUGCGCG AUCCAGGGCC

1185 GGGACUCCCC G CAGGU ACCUG UGAUGGCAUGCACUAUGCGCG GGGGAGUCCC

1192 CCCGCAGGUU G CCCCG CGGGG UGAUGGCAUGCACUAUGCGCG AACCUGCGGG

1197 AGGUUGCCCC G CCUGC GCAGG UGAUGGCAUGCACUAUGCGCG GGGGCAACCU

1201 UGCCCCGCCU G CCCCA UGGGG UGAUGGCAUGCACUAUGCGCG AGGCGGGGCA

1209 CUGCCCCAGC G CUACU AGUAG UGAUGGCAUGCACUAUGCGCG GCUGGGGCAG

1222 ACUGGCAAAU G CGGCC GGCCG UGAUGGCAUGCACUAUGCGCG AUUUGCCAGU

1231 UGCGGCCCCU G UUUCU AGAAA UGAUGGCAUGCACUAUGCGCG AGGGGCCGCA

1243 UUCUGGAGCU G CUUGG CCAAG UGAUGGCAUGCACUAUGCGCG AGCUCCAGAA

1256 UGGGAACCAC G CGCAG CUGCG UGAUGGCAUGCACUAUGCGCG GUGGUUCCCA

1258 GGAACCACGC G CAGUG CACUG UGAUGGCAUGCACUAUGCGCG GCGUGGUUCC

1263 CACGCGCAGU G CCCCU AGGGG UGAUGGCAUGCACUAUGCGCG ACUGCGCGUG

1276 CCUACGGGGU G CUCCU AGGAG UGAUGGCAUGCACUAUGCGCG ACCCCGUAGG

1288 UCCUCAAGAC G CACUG CAGUG UGAUGGCAUGCACUAUGCGCG GUCUUGAGGA

1293 AAGACGCACU G CCCGC GCGGG UGAUGGCAUGCACUAUGCGCG AGUGCGUCUU

1297 CGCACUGCCC G CUGCG CGCAG UGAUGGCAUGCACUAUGCGCG GGGCAGUGCG

1300 ACUGCCCGCU G CGAGC GCUCG UGAUGGCAUGCACUAUGCGCG AGCGGGCAGU

1302 UGCCCGCUGC G AGCUG CAGCU UGAUGGCAUGCACUAUGCGCG GCAGCGGGCA

1307 GCUGCGAGCU G CGGUC GACCG UGAUGGCAUGCACUAUGCGCG AGCUCGCAGC

1328 AGCAGCCGGU G UCUGU ACAGA UGAUGGCAUGCACUAUGCGCG ACCGGCUGCU

1332 GCCGGUGUCU G UGCCC GGGCA UGAUGGCAUGCACUAUGCGCG AGACACCGGC

1334 CGGUGUCUGU G CCCGG CCGGG UGAUGGCAUGCACUAUGCGCG ACAGACACCG

Table 15

1358 CCAGGGCUCU G UGGCG CGCCA UGAUGGCAUGCACUAUGCGCG AGAGCCCUGG

1370 GGCGGCCCCC G AGGAG CUCCU UGAUGGCAUGCACUAUGCGCG GGGGGCCGCC

1395 GACCCCCGUC G CCUGG CCAGG UGAUGGCAUGCACUAUGCGCG GACGGGGGUC

1402 GUCGCCUGGU G CAGCU AGCUG UGAUGGCAUGCACUAUGCGCG ACCAGGCGAC

1408 UGGUGCAGCU G CUCCG CGGAG UGAUGGCAUGCACUAUGCGCG AGCUGCACCA

1413 CAGCUGCUCC G CCAGC GCUGG UGAUGGCAUGCACUAUGCGCG GGAGCAGCUG

1438 CCUGGCAGGU G UACGG CCGUA UGAUGGCAUGCACUAUGCGCG ACCUGCCAGG

1450 ACGGCUUCGU G CGGGC GCCCG UGAUGGCAUGCACUAUGCGCG ACGAAGCCGU

1458 GUGCGGGCCU G CCUGC GCAGG UGAUGGCAUGCACUAUGCGCG AGGCCCGCAC

1462 GGGCCUGCCU G CGCCG CGGCG UGAUGGCAUGCACUAUGCGCG AGGCAGGCCC

1464 GCCUGCCUGC G CCGGC GCCGG UGAUGGCAUGCACUAUGCGCG GCAGGCAGGC

1474 GCCGGCUGGU G CCCCC GGGGG UGAUGGCAUGCACUAUGCGCG ACCAGCCGGC

1505 CAGGCACAAC G AACGC GCGUU UGAUGGCAUGCACUAUGCGCG GUUGUGCCUG

1509 CACAACGAAC G CCGCU AGCGG UGAUGGCAUGCACUAUGCGCG GUUCGUUGUG

1512 AACGAACGCC G CUUCC GGAAG UGAUGGCAUGCACUAUGCGCG GGCGUUCGUU

1556 GGGGAAGCAU G CCAAG CUUGG UGAUGGCAUGCACUAUGCGCG AUGCUUCCCC

1567 CCAAGCUCUC G CUGCA UGCAG UGAUGGCAUGCACUAUGCGCG GAGAGCUUGG

1570 AGCUCUCGCU G CAGGA UCCUG UGAUGGCAUGCACUAUGCGCG AGCGAGAGCU

1579 UGCAGGAGCU G ACGUG CACGU UGAUGGCAUGCACUAUGCGCG AGCUCCUGCA

1591 CGUGGAAGAU G AGCGU ACGCU UGAUGGCAUGCACUAUGCGCG AUCUUCCACG

1597 AGAUGAGCGU G CGGGA UCCCG UGAUGGCAUGCACUAUGCGCG ACGCUCAUCU

1605 GUGCGGGACU G CGCUU AAGCG UGAUGGCAUGCACUAUGCGCG AGUCCCGCAC

1607 GCGGGACUGC G CUUGG CCAAG UGAUGGCAUGCACUAUGCGCG GCAGUCCCGC

1615 GCGCUUGGCU G CGCAG CUGCG UGAUGGCAUGCACUAUGCGCG AGCCAAGCGC

1617 GCUUGGCUGC G CAGGA UCCUG UGAUGGCAUGCACUAUGCGCG GCAGCCAAGC

1638 GGGGUUGGCU G UGUUC GAACA UGAUGGCAUGCACUAUGCGCG AGCCAACCCC

1640 GGUUGGCUGU G UUCCG CGGAA UGAUGGCAUGCACUAUGCGCG ACAGCCAACC

1649 UGUUCCGGCC G CAGAG CUCUG UGAUGGCAUGCACUAUGCGCG GGCCGGAACA

1663 AGCACCGUCU G CGUGA UCACG UGAUGGCAUGCACUAUGCGCG AGACGGUGCU

1667 CCGUCUGCGU G AGGAG CUCCU UGAUGGCAUGCACUAUGCGCG ACGCAGACGG

1690 CCAAGUUCCU G CACUG CAGUG UGAUGGCAUGCACUAUGCGCG AGGAACUUGG

Table 15

1699 UGCACUGGCU G AUGAG CUCAU UGAUGGCAUGCACUAUGCGCG AGCCAGUGCA

1702 ACUGGCUGAU G AGUGU ACACU UGAUGGCAUGCACUAUGCGCG AUCAGCCAGU

1706 GCUGAUGAGU G UGUAC GUACA UGAUGGCAUGCACUAUGCGCG ACUCAUCAGC

1708 UGAUGAGUGU G UACGU ACGUA UGAUGGCAUGCACUAUGCGCG ACACUCAUCA

1718 GUACGUCGUC G AGCUG CAGCU UGAUGGCAUGCACUAUGCGCG GACGACGUAC

1723 UCGUCGAGCU G CUCAG CUGAG UGAUGGCAUGCACUAUGCGCG AGCUCGACGA

1742 UUUCUUUUAU G UCACG CGUGA UGAUGGCAUGCACUAUGCGCG AUAAAAGAAA

1793 CCGGAAGAGU G UCUGG CCAGA UGAUGGCAUGCACUAUGCGCG ACUCUUCCGG

1807 GGAGCAAGUU G CAAAG CUUUG UGAUGGCAUGCACUAUGCGCG AACUUGCUCC

1834 GACAGCACUU G AAGAG CUCUU UGAUGGCAUGCACUAUGCGCG AAGUGCUGUC

1843 UGAAGAGGGU G CAGCU AGCUG UGAUGGCAUGCACUAUGCGCG ACCCUCUUCA

1849 GGGUGCAGCU G CGGGA UCCCG UGAUGGCAUGCACUAUGCGCG AGCUGCACCC

1858 UGCGGGAGCU G UCGGA UCCGA UGAUGGCAUGCACUAUGCGCG AGCUCCCGCA

1898 AGCCAGGCCC G CCCUG CAGGG UGAUGGCAUGCACUAUGCGCG GGGCCUGGCU

1903 GGCCCGCCCU G CUGAC GUCAG UGAUGGCAUGCACUAUGCGCG AGGGCGGGCC

1906 CCGCCCUGCU G ACGUC GACGU UGAUGGCAUGCACUAUGCGCG AGCAGGGCGG

1920 UCCAGACUCC G CUUCA UGAAG UGAUGGCAUGCACUAUGCGCG GGAGUCUGGA

1937 CCCCAAGCCU G ACGGG CCCGU UGAUGGCAUGCACUAUGCGCG AGGCUUGGGG

1945 CUGACGGGCU G CGGCC GGCCG UGAUGGCAUGCACUAUGCGCG AGCCCGUCAG

1951 GGCUGCGGCC G AUUGU ACAAU UGAUGGCAUGCACUAUGCGCG GGCCGCAGCC

1955 GCGGCCGAUU G UGAAC GUUCA UGAUGGCAUGCACUAUGCGCG AAUCGGCCGC

1957 GGCCGAUUGU G AACAU AUGUU UGAUGGCAUGCACUAUGCGCG ACAAUCGGCC

1992 AGAACGUUCC G CAGAG CUCUG UGAUGGCAUGCACUAUGCGCG GGAACGUUCU

2009 AAAGAGGGCC G AGCGU ACGCU UGAUGGCAUGCACUAUGCGCG GGCCCUCUUU

2023 GUCUCACCUC G AGGGU ACCCU UGAUGGCAUGCACUAUGCGCG GAGGUGAGAC

2029 CCUCGAGGGU G AAGGC GCCUU UGAUGGCAUGCACUAUGCGCG ACCCUCGAGG

2038 UGAAGGCACU G UUCAG CUGAA UGAUGGCAUGCACUAUGCGCG AGUGCCUUCA

2047 UGUUCAGCGU G CUCAA UUGAG UGAUGGCAUGCACUAUGCGCG ACGCUGAACA

2057 GCUCAACUAC G AGCGG CCGCU UGAUGGCAUGCACUAUGCGCG GUAGUUGAGC

2065 ACGAGCGGGC G CGGCG CGCCG UGAUGGCAUGCACUAUGCGCG GCCCGCUCGU

2070 CGGGCGCGGC G CCCCG CGGGG UGAUGGCAUGCACUAUGCGCG GCCGCGCCCG

Table 15

2087 CCUCCUGGGC G CCUCU AGAGG UGAUGGCAUGCACUAUGCGCG GCCCAGGAGG

2093 GGGCGCCUCU G UGCUG CAGCA UGAUGGCAUGCACUAUGCGCG AGAGGCGCCC

2095 GCGCCUCUGU G CUGGG CCCAG UGAUGGCAUGCACUAUGCGCG ACAGAGGCGC

2108 GGGCCUGGAC G AUAUC GAUAU UGAUGGCAUGCACUAUGCGCG GUCCAGGCCC

2127 AGGGCCUGGC G CACCU AGGUG UGAUGGCAUGCACUAUGCGCG GCCAGGCCCU

2137 GCACCUUCGU G CUGCG CGCAG UGAUGGCAUGCACUAUGCGCG ACGAAGGUGC

2140 CCUUCGUGCU G CGUGU ACACG UGAUGGCAUGCACUAUGCGCG AGCACGAAGG

2144 CGUGCUGCGU G UGCGG CCGCA UGAUGGCAUGCACUAUGCGCG ACGCAGCACG

2146 UGCUGCGUGU G CGGGC GCCCG UGAUGGCAUGCACUAUGCGCG ACACGCAGCA

2161 CCCAGGACCC G CCGCC GGCGG UGAUGGCAUGCACUAUGCGCG GGGUCCUGGG

2164 AGGACCCGCC G CCUGA UCAGG UGAUGGCAUGCACUAUGCGCG GGCGGGUCCU

2168 CCCGCCGCCU G AGCUG CAGCU UGAUGGCAUGCACUAUGCGCG AGGCGGCGGG

2173 CGCCUGAGCU G UACUU AAGUA UGAUGGCAUGCACUAUGCGCG AGCUCAGGCG

2180 GCUGUACUUU G UCAAG CUUGA UGAUGGCAUGCACUAUGCGCG AAAGUACAGC

2192 CAAGGUGGAU G UGACG CGUCA UGAUGGCAUGCACUAUGCGCG AUCCACCUUG

2194 AGGUGGAUGU G ACGGG CCCGU UGAUGGCAUGCACUAUGCGCG ACAUCCACCU

2201 UGUGACGGGC G CGUAC GUACG UGAUGGCAUGCACUAUGCGCG GCCCGUCACA

2207 GGGCGCGUAC G ACACC GGUGU UGAUGGCAUGCACUAUGCGCG GUACGCGCCC

2243 GGAGGUCAUC G CCAGC GCUGG UGAUGGCAUGCACUAUGCGCG GAUGACCUCC

2274 AACACGUACU G CGUGC GCACG UGAUGGCAUGCACUAUGCGCG AGUACGUGUU

2278 CGUACUGCGU G CGUCG CGACG UGAUGGCAUGCACUAUGCGCG ACGCAGUACG

2288 GCGUCGGUAU G CCGUG CACGG UGAUGGCAUGCACUAUGCGCG AUACCGACGC

2306 CCAGAAGGCC G CCCAU AUGGG UGAUGGCAUGCACUAUGCGCG GGCCUUCUGG

2322 GGGCACGUCC G CAAGG CCUUG UGAUGGCAUGCACUAUGCGCG GGACGUGCCC

2353 UCUCUACCUU G ACAGA UCUGU UGAUGGCAUGCACUAUGCGCG AAGGUAGAGA

2374 AGCCGUACAU G CGACA UGUCG UGAUGGCAUGCACUAUGCGCG AUGUACGGCU

2376 CCGUACAUGC G ACAGU ACUGU UGAUGGCAUGCACUAUGCGCG GCAUGUACGG

2395 UGGCUCACCU G CAGGA UCCUG UGAUGGCAUGCACUAUGCGCG AGGUGAGCCA

2410 AGACCAGCCC G CUGAG CUCAG UGAUGGCAUGCACUAUGCGCG GGGCUGGUCU

2413 CCAGCCCGCU G AGGGA UCCCU UGAUGGCAUGCACUAUGCGCG AGCGGGCUGG

2420 GCUGAGGGAU G CCGUC GACGG UGAUGGCAUGCACUAUGCGCG AUCCCUCAGC

Table 15

2432 CGUCGUCAUC G AGCAG CUGCU UGAUGGCAUGCACUAUGCGCG GAUGACGACG

2449 GCUCCUCCCU G AAUGA UCAUU UGAUGGCAUGCACUAUGCGCG AGGGAGGAGC

2453 CUCCCUGAAU G AGGCC GGCCU UGAUGGCAUGCACUAUGCGCG AUUCAGGGAG

2474 UGGCCUCUUC G ACGUC GACGU UGAUGGCAUGCACUAUGCGCG GAAGAGGCCA

2487 GUCUUCCUAC G CUUCA UGAAG UGAUGGCAUGCACUAUGCGCG GUAGGAAGAC

2494 UACGCUUCAU G UGCCA UGGCA UGAUGGCAUGCACUAUGCGCG AUGAAGGGUA

2496 CGCUUCAUGU G CCACC GGUGG UGAUGGCAUGCACUAUGCGCG ACAUGAAGCG

2504 GUGCCACCAC G CCGUG CACGG UGAUGGCAUGCACUAUGCGCG GUGGUGGCAC

2509 ACCACGCCGU G CGCAU AUGCG UGAUGGCAUGCACUAUGCGCG ACGGCGUGGU

2511 CACGCCGUGC G CAUCA UGAUG UGAUGGCAUGCACUAUGCGCG GCACGGCGUG

2538 UACGUCCAGU G CCAGG CCUGG UGAUGGCAUGCACUAUGCGCG ACUGGACGUA

2551 AGGGGAUCCC G CAGGG CCCUG UGAUGGCAUGCACUAUGCGCG GGGAUCCCCU

2572 UCCUCUCCAC G CUGCU AGCAG UGAUGGCAUGCACUAUGCGCG GUGGAGAGGA

2575 UCUCCACGCU G CUCUG CAGAG UGAUGGCAUGCACUAUGCGCG AGCGUGGAGA

2580 ACGCUGCUCU G CAGCC GGCUG UGAUGGCAUGCACUAUGCGCG AGAGCAGCGU

2587 UCUGCAGCCU G UGCUA UAGCA UGAUGGCAUGCACUAUGCGCG AGGCUGCAGA

2589 UGCAGCCUGU G CUACG CGUAG UGAUGGCAUGCACUAUGCGCG ACAGGCUGCA

2597 GUGCUACGGC G ACAUG CAUGU UGAUGGCAUGCACUAUGCGCG GCCGUAGCAC

2614 AGAACAAGCU G UUUGC GCAAA UGAUGGCAUGCACUAUGCGCG AGCUUGUUCU

2618 CAAGCUGUUU G CGGGG CCCCG UGAUGGCAUGCACUAUGCGCG AAACAGCUUG

2641 GGGACGGGCU G CUCCU AGGAG UGAUGGCAUGCACUAUGCGCG AGCCCGUCCC

2647 GGCUGCUCCU G CGUUU AAACG UGAUGGCAUGCACUAUGCGCG AGGAGCAGCC

2660 UUUGGUGGAU G AUUUC GAAAU UGAUGGCAUGCACUAUGCGCG AUCCACCAAA

2668 AUGAUUUCUU G UUGGU ACCAA UGAUGGCAUGCACUAUGCGCG AAGAAAUCAU

2674 UCUUGUUGGU G ACACC GGUGU UGAUGGCAUGCACUAUGCGCG ACCAACAAGA

2693 CCUCACCCAC G CGAAA UUUCG UGAUGGCAUGCACUAUGCGCG GUGGGUGAGG

2695 UCACCCACGC G AAAAC GUUUU UGAUGGCAUGCACUAUGCGCG GCGUGGGUGA

2721 ACCCUGGUCC G AGGUG CACCU UGAUGGCAUGCACUAUGCGCG GGACCAGGGU

2726 GGUCCGAGGU G UCCCU AGGGA UGAUGGCAUGCACUAUGCGCG ACCUCGGACC

2732 AGGUGUCCCU G AGUAU AUACU UGAUGGCAUGCACUAUGCGCG AGGGACACCU

2742 GAGUAUGGCU G CGUGG CCACG UGAUGGCAUGCACUAUGCGCG AGCCAUACUC

Table 15

2749 GCUGCGUGGU G AACUU AAGUU UGAUGGCAUGCACUAUGCGCG ACCACGCAGC

2755 UGGUGAACUU G CGGAA UUCCG UGAUGGCAUGCACUAUGCGCG AAGUUCACCA

2770 AGACAGUGGU G AACUU AAGUU UGAUGGCAUGCACUAUGCGCG ACCACUGUCU

2780 GAACUUCCCU G UAGAA UUCUA UGAUGGCAUGCACUAUGCGCG AGGGAAGUUC

2789 UGUAGAAGAC G AGGCC GGCCU UGAUGGCAUGCACUAUGCGCG GUCUUCUACA

2813 CACGGCUUUU G UUCAG CUGAA UGAUGGCAUGCACUAUGCGCG AAAAGCCGUG

2821 UUGUUCAGAU G CCGGC GCCGG UGAUGGCAUGCACUAUGCGCG AUCUGAACAA

2847 UUCCCCUGGU G CGGCC GGCCG UGAUGGCAUGCACUAUGCGCG ACCAGGGGAA

2854 GGUGCGGCCU G CUGCU AGCAG UGAUGGCAUGCACUAUGCGCG AGGCCGCACC

2857 GCGGCCUGCU G CUGGA UCCAG UGAUGGCAUGCACUAUGCGCG AGCAGGCCGC

2881 CCCUGGAGGU G CAGAG CUCUG UGAUGGCAUGCACUAUGCGCG ACCUCCAGGG

2888 GGUGCAGAGC G ACUAC GUAGU UGAUGGCAUGCACUAUGCGCG GCUCUGCACC

2903 CUCCAGCUAU G CCCGG CCGGG UGAUGGCAUGCACUAUGCGCG AUAGCUGGAG

2940 ACCUUCAACC G CGGCU AGCCG UGAUGGCAUGCACUAUGCGCG GGUUGAAGGU

2965 GGAGGAACAU G CGUCG CGACG UGAUGGCAUGCACUAUGCGCG AUGUUCCUCC

2970 AACAUGCGUC G CAAAC GUUUG UGAUGGCAUGCACUAUGCGCG GACGCAUGUU

2989 UUGGGGUCUU G CGGCU AGCCG UGAUGGCAUGCACUAUGCGCG AAGACCCCAA

2995 UCUUGCGGCU G AAGUG CACUU UGAUGGCAUGCACUAUGCGCG AGCCGCAAGA

3000 CGGCUGAAGU G UCACA UGUGA UGAUGGCAUGCACUAUGCGCG ACUUCAGCCG

3010 GUCACAGCCU G UUUCU AGAAA UGAUGGCAUGCACUAUGCGCG AGGCUGUGAC

3022 UUCUGGAUUU G CAGGU ACCUG UGAUGGCAUGCACUAUGCGCG AAAUCCAGAA

3028 AUUUGCAGGU G AACAG CUGUU UGAUGGCAUGCACUAUGCGCG ACCUGCAAAU

3046 UCCAGACGGU G UGCAC GUGCA UGAUGGCAUGCACUAUGCGCG ACCGUCUGGA

3048 CAGACGGUGU G CACCA UGGUG UGAUGGCAUGCACUAUGCGCG ACACCGUCUG

3073 AGAUCCUCCU G CUGCA UGCAG UGAUGGCAUGCACUAUGCGCG AGGAGGAUCU

3076 UCCUCCUGCU G CAGGC GCCUG UGAUGGCAUGCACUAUGCGCG AGCAGGAGGA

3095 CAGGUUUCAC G CAUGU ACAUG UGAUGGCAUGCACUAUGCGCG GUGAAACCUG

3099 UUUCACGCAU G UGUGC GCACA UGAUGGCAUGCACUAUGCGCG AUGCGUGAAA

3101 UCACGCAUGU G UGCUG CAGCA UGAUGGCAUGCACUAUGCGCG ACAUGCGUGA

3103 ACGCAUGUGU G CUGCA UGCAG UGAUGGCAUGCACUAUGCGCG ACACAUGCGU

3106 CAUGUGUGCU G CAGCU AGCUG UGAUGGCAUGCACUAUGCGCG AGCACACAUG

Table 15

3154 CAUUUUUCCU G CGCGU ACGCG UGAUGGCAUGCACUAUGCGCG AGGAAAAAUG

3156 UUUUUCCUGC G CGUCA UGACG UGAUGGCAUGCACUAUGCGCG GCAGGAAAAA

3167 CGUCAUCUCU G ACACG CGUGU UGAUGGCAUGCACUAUGCGCG AGAGAUGACG

3183 GCCUCCCUCU G CUACU AGUAG UGAUGGCAUGCACUAUGCGCG AGAGGGAGGC

3196 ACUCCAUCCU G AAAGC GCUUU UGAUGGCAUGCACUAUGCGCG AGGAUGGAGU

3209 AGCCAAGAAC G CAGGG CCCUG UGAUGGCAUGCACUAUGCGCG GUUCUUGGCU

3217 ACGCAGGGAU G UCGCU AGCGA UGAUGGCAUGCACUAUGCGCG AUCCCUGCGU

3220 CAGGGAUGUC G CUGGG CCCAG UGAUGGCAUGCACUAUGCGCG GACAUCCCUG

3236 GGCCAAGGGC G CCGCC GGCGG UGAUGGCAUGCACUAUGCGCG GCCCUUGGCC

3239 CAAGGGCGCC G CCGGC GCCGG UGAUGGCAUGCACUAUGCGCG GGCGCCCUUG

3250 CCGGCCCUCU G CCCUC GAGGG UGAUGGCAUGCACUAUGCGCG AGAGGGCCGG

3257 UCUGCCCUCC G AGGCC GGCCU UGAUGGCAUGCACUAUGCGCG GGAGGGCAGA

3265 CCGAGGCCGU G CAGUG CACUG UGAUGGCAUGCACUAUGCGCG ACGGCCUCGG

3274 UGCAGUGGCU G UGCCA UGGCA UGAUGGCAUGCACUAUGCGCG AGCCACUGCA

3276 CAGUGGCUGU G CCACC GGUGG UGAUGGCAUGCACUAUGCGCG ACAGCCACUG

3292 AAGCAUUCCU G CUCAA UUGAG UGAUGGCAUGCACUAUGCGCG AGGAAUGCUU

3301 UGCUCAAGCU G ACUCG CGAGU UGAUGGCAUGCACUAUGCGCG AGCUUGAGCA

3306 AAGCUGACUC G ACACC GGUGU UGAUGGCAUGCACUAUGCGCG GAGUCAGCUU

3314 UCGACACCGU G UCACC GGUGA UGAUGGCAUGCACUAUGCGCG ACGGUGUCGA

3325 UCACCUACGU G CCACU AGUGG UGAUGGCAUGCACUAUGCGCG ACGUAGGUGA

3358 CAGCCCAGAC G CAGCU AGCUG UGAUGGCAUGCACUAUGCGCG GUCUGGGCUG

3364 AGACGCAGCU G AGUCG CGACU UGAUGGCAUGCACUAUGCGCG AGCUGCGUCU

3385 UCCCGGGGAC G ACGCU AGCGU UGAUGGCAUGCACUAUGCGCG GUCCCCGGGA

3388 CGGGGACGAC G CUGAC GUCAG UGAUGGCAUGCACUAUGCGCG GUCGUCCCCG

3391 GGACGACGCU G ACUGC GCAGU UGAUGGCAUGCACUAUGCGCG AGCGUCGUCC

3395 GACGCUGACU G CCCUG CAGGG UGAUGGCAUGCACUAUGCGCG AGUCAGCGUC

3407 CCUGGAGGCC G CAGCC GGCUG UGAUGGCAUGCACUAUGCGCG GGCCUCCAGG

3424 ACCCGGCACU G CCCUC GAGGG UGAUGGCAUGCACUAUGCGCG AGUGCCGGGU

3453 AUCCUGGACU G AUGGC GCCAU UGAUGGCAUGCACUAUGCGCG AGUCCAGGAU

3464 AUGGCCACCC G CCCAC GUGGG UGAUGGCAUGCACUAUGCGCG GGGUGGCCAU

3479 CAGCCAGGCC G AGAGC GCUCU UGAUGGCAUGCACUAUGCGCG GGCCUGGCUG

Table 15

3501 CAGCAGCCCU G UCACG CGUGA UGAUGGCAUGCACUAUGCGCG AGGGCUGCUG

3506 GCCCUGUCAC G CCGGG CCCGG UGAUGGCAUGCACUAUGCGCG GUGACAGGGC

3554 ACCCAGGCCC G CACCG CGGUG UGAUGGCAUGCACUAUGCGCG GGGCCUGGGU

3559 GGCCCGCACC G CUGGG CCCAG UGAUGGCAUGCACUAUGCGCG GGUGCGGGCC

3570 CUGGGAGUCU G AGGCC GGCCU UGAUGGCAUGCACUAUGCGCG AGACUCCCAG

3577 UCUGAGGCCU G AGUGA UCACU UGAUGGCAUGCACUAUGCGCG AGGCCUCAGA

3581 AGGCCUGAGU G AGUGU ACACU UGAUGGCAUGCACUAUGCGCG ACUCAGGCCU

3585 CUGAGUGAGU G UUUGG CCAAA UGAUGGCAUGCACUAUGCGCG ACUCACUCAG

3593 GUGUUUGGCC G AGGCC GGCCU UGAUGGCAUGCACUAUGCGCG GGCCAAACAC

3600 GCCGAGGCCU G CAUGU ACAUG UGAUGGCAUGCACUAUGCGCG AGGCCUCGGC

3604 AGGCCUGCAU G UCCGG CCGGA UGAUGGCAUGCACUAUGCGCG AUGCAGGCCU

3612 AUGUCCGGCU G AAGGC GCCUU UGAUGGCAUGCACUAUGCGCG AGCCGGACAU

3619 GCUGAAGGCU G AGUGU ACACU UGAUGGCAUGCACUAUGCGCG AGCCUUCAGC

3623 AAGGCUGAGU G UCCGG CCGGA UGAUGGCAUGCACUAUGCGCG ACUCAGCCUU

3631 GUGUCCGGCU G AGGCC GGCCU UGAUGGCAUGCACUAUGCGCG AGCCGGACAC

3638 GCUGAGGCCU G AGCGA UCGCU UGAUGGCAUGCACUAUGCGCG AGGCCUCAGC

3642 AGGCCUGAGC G AGUGU ACACU UGAUGGCAUGCACUAUGCGCG GCUCAGGCCU

3646 CUGAGCGAGU G UCCAG CUGGA UGAUGGCAUGCACUAUGCGCG ACUCGCUCAG

3661 GCCAAGGGCU G AGUGU ACACU UGAUGGCAUGCACUAUGCGCG AGCCCUUGGC

3665 AGGGCUGAGU G UCCAG CUGGA UGAUGGCAUGCACUAUGCGCG ACUCAGCCCU

3678 CAGCACACCU G CCGUC GACGG UGAUGGCAUGCACUAUGCGCG AGGUGUGCUG

3705 ACAGGCUGGC G CUCGG CCGAG UGAUGGCAUGCACUAUGCGCG GCCAGCCUGU

3789 CCCCAGAUUC G CCAUU AAUGG UGAUGGCAUGCACUAUGCGCG GAAUCUGGGG

3795 AUUCGCCAUU G UUCAC GUGAA UGAUGGCAUGCACUAUGCGCG AAUGGCGAAU

3806 UUCACCCCUC G CCCUG CAGGG UGAUGGCAUGCACUAUGCGCG GAGGGGUGAA

3811 CCCUCGCCCU G CCCUC GAGGG UGAUGGCAUGCACUAUGCGCG AGGGCGAGGG

3821 GCCCUCCUUU G CCUUC GAAGG UGAUGGCAUGCACUAUGCGCG AAAGGAGGGC

3854 UGGAGACCCU G AGAAG CUUCU UGAUGGCAUGCACUAUGCGCG AGGGUCUCCA

3888 AAUUUGGAGU G ACCAA UUGGU UGAUGGCAUGCACUAUGCGCG ACUCCAAAUU

3898 GACCAAAGGU G UGCCC GGGCA UGAUGGCAUGCACUAUGCGCG ACCUUUGGUC

3900 CCAAAGGUGU G CCCUG CAGGG UGAUGGCAUGCACUAUGCGCG ACACCUUUGG

Table 15

3905 GGUGUGCCCU G UACAC GUGUA UGAUGGCAUGCACUAUGCGCG AGGGCACACC

3915 GUACACAGGC G AGGAC GUCCU UGAUGGCAUGCACUAUGCGCG GCCUGUGUAC

3924 CGAGGACCCU G CACCU AGGUG UGAUGGCAUGCACUAUGCGCG AGGGUCCUCG

3944 GGGGGUCCCU G UGGGU ACCCA UGAUGGCAUGCACUAUGCGCG AGGGACCCCC

3966 GGGGGGAGGU G CUGUG CACAG UGAUGGCAUGCACUAUGCGCG ACCUCCCCCC

3969 GGGAGGUGCU G UGGGA UCCCA UGAUGGCAUGCACUAUGCGCG AGCACCUCCC

3985 GUAAAAUACU G AAUAU AUAUU UGAUGGCAUGCACUAUGCGCG AGUAUUUUAC

3993 CUGAAUAUAU G AGUUU AAACU UGAUGGCAUGCACUAUGCGCG AUAUAUUCAG

4008 UUUCAGUUUU G AAAAA UUUUU UGAUGGCAUGCACUAUGCGCG AAAACUGAAA

Seq l = TERT (Homo sapiens telomerase reverse transcriptase (TERT) mRNA, 4015 bp); Nakamura et al., Science 277 (5328), 955-959 (1997)

Input Sequence = TERT. Cut Site = YG/M or UG/U.

Stem Length = 5/10. Core Sequence = UGAUG GCAUGCACUAUGC GCG

Table 16

Table 16: Human telomerase reverse transcriptase (TERT) DNAzyme and Target Sequence

Table 16

105 GCGGTAGT GGCTAGCTACAACGA GGCTGCGC GCGCAGCC A ACTACCGC

108 CTCGCGGT GGCTAGCTACAACGA AGTGGCTG CAGCCACT A ACCGCGAG

111 CACCTCGC GGCTAGCTACAACGA GGTAGTGG CCACTACC G GCGAGGTG

116 GGCAGCAC GGCTAGCTACAACGA CTCGCGGT ACCGCGAG G GTGCTGCC

118 GCGGCAGC GGCTAGCTACAACGA ACCTCGCG CGCGAGGT G GCTGCCGC

121 CCAGCGGC GGCTAGCTACAACGA AGCACCTC GAGGTGCT G GCCGCTGG

124 TGGCCAGC GGCTAGCTACAACGA GGCAGCAC GTGCTGCC G GCTGGCCA

128 AACGTGGC GGCTAGCTACAACGA CAGCGGCA TGCCGCTG G GCCACGTT

131 ACGAACGT GGCTAGCTACAACGA GGCCAGCG CGCTGGCC A ACGTTCGT

133 GCACGAAC GGCTAGCTACAACGA GTGGCCAG CTGGCCAC G GTTCGTGC

137 CGCCGCAC GGCTAGCTACAACGA GAACGTGG CCACGTTC G GTGCGGCG

139 GGCGCCGC GGCTAGCTACAACGA ACGAACGT ACGTTCGT G GCGGCGCC

142 CCAGGCGC GGCTAGCTACAACGA CGCACGAA TTCGTGCG G GCGCCTGG

144 CCCCAGGC GGCTAGCTACAACGA GCCGCACG CGTGCGGC G GCCTGGGG

151 CCTGGGGC GGCTAGCTACAACGA CCCAGGCG CGCCTGGG G GCCCCAGG

159 CCGCCAGC GGCTAGCTACAACGA CCTGGGGC GCCCCAGG G GCTGGCGG

163 CCAGCCGC GGCTAGCTACAACGA CAGCCCTG CAGGGCTG G GCGGCTGG

166 GCACCAGC GGCTAGCTACAACGA CGCCAGCC GGCTGGCG G GCTGGTGC

170 CGCTGCAC GGCTAGCTACAACGA CAGCCGCC GGCGGCTG G GTGCAGCG

172 CGCGCTGC GGCTAGCTACAACGA ACCAGCCG CGGCTGGT G GCAGCGCG

175 CCCCGCGC GGCTAGCTACAACGA TGCACCAG CTGGTGCA G GCGCGGGG

177 GTCCCCGC GGCTAGCTACAACGA GCTGCACC GGTGCAGC G GCGGGGAC

183 CGCCGGGT GGCTAGCTACAACGA CCCCGCGC GCGCGGGG A ACCCGGCG

188 AAAGCCGC GGCTAGCTACAACGA CGGGTCCC GGGACCCG G GCGGCTTT

191 CGGAAAGC GGCTAGCTACAACGA CGCCGGGT ACCCGGCG G GCTTTCCG

198 CAGCGCGC GGCTAGCTACAACGA GGAAAGCC GGCTTTCC G GCGCGCTG

200 ACCAGCGC GGCTAGCTACAACGA GCGGAAAG CTTTCCGC G GCGCTGGT

202 CCACCAGC GGCTAGCTACAACGA GCGCGGAA TTCCGCGC G GCTGGTGG

206 TGGGCCAC GGCTAGCTACAACGA CAGCGCGC GCGCGCTG G GTGGCCCA

209 CACTGGGC GGCTAGCTACAACGA CACCAGCG CGCTGGTG G GCCCAGTG

214 CCAGGCAC GGCTAGCTACAACGA TGGGCCAC GTGGCCCA G GTGCCTGG

Table 16

Table 16

341 GCCAGCAC GGCTAGCTACAACGA GTTCTTCG CGAAGAAC G GTGCTGGC

343 AGGCCAGC GGCTAGCTACAACGA ACGTTCTT AAGAACGT G GCTGGCCT

347 CCGAAGGC GGCTAGCTACAACGA CAGCACGT ACGTGCTG G GCCTTCGG

354 CGCGAAGC GGCTAGCTACAACGA CGAAGGCC GGCCTTCG G GCTTCGCG

359 AGCAGCGC GGCTAGCTACAACGA GAAGCCGA TCGGCTTC G GCGCTGCT

361 CCAGCAGC GGCTAGCTACAACGA GCGAAGCC GGCTTCGC G GCTGCTGG

364 CGTCCAGC GGCTAGCTACAACGA AGCGCGAA TTCGCGCT G GCTGGACG

369 GGCCCCGT GGCTAGCTACAACGA CCAGCAGC GCTGCTGG A ACGGGGCC

374 CCGCGGGC GGCTAGCTACAACGA CCCGTCCA TGGACGGG G GCCCGCGG

378 GCCCCCGC GGCTAGCTACAACGA GGGCCCCG CGGGGCCC G GCGGGGGC

384 GGGGGGGC GGCTAGCTACAACGA CCCCGCGG CCGCGGGG G GCCCCCCC

395 GTGAAGGC GGCTAGCTACAACGA CTCGGGGG CCCCCGAG G GCCTTCAC

401 CTGGTGGT GGCTAGCTACAACGA GAAGGCCT AGGCCTTC A ACCACCAG

404 ACGCTGGT GGCTAGCTACAACGA GGTGAAGG CCTTCACC A ACCAGCGT

408 GCGCACGC GGCTAGCTACAACGA TGGTGGTG CACCACCA G GCGTGCGC

410 CTGCGCAC GGCTAGCTACAACGA GCTGGTGG CCACCAGC G GTGCGCAG

412 AGCTGCGC GGCTAGCTACAACGA ACGCTGGT ACCAGCGT G GCGCAGCT

414 GTAGCTGC GGCTAGCTACAACGA GCACGCTG CAGCGTGC G GCAGCTAC

417 CAGGTAGC GGCTAGCTACAACGA TGCGCACG CGTGCGCA G GCTACCTG

420 GGGCAGGT GGCTAGCTACAACGA AGCTGCGC GCGCAGCT A ACCTGCCC

424 TGTTGGGC GGCTAGCTACAACGA AGGTAGCT AGCTACCT G GCCCAACA

429 CACCGTGT GGCTAGCTACAACGA TGGGCAGG CCTGCCCA A ACACGGTG

431 GTCACCGT GGCTAGCTACAACGA GTTGGGCA TGCCCAAC A ACGGTGAC

434 TCGGTCAC GGCTAGCTACAACGA CGTGTTGG CCAACACG G GTGACCGA

437 GCGTCGGT GGCTAGCTACAACGA CACCGTGT ACACGGTG A ACCGACGC

441 CAGTGCGT GGCTAGCTACAACGA CGGTCACC GGTGACCG A ACGCACTG

443 CGCAGTGC GGCTAGCTACAACGA GTCGGTCA TGACCGAC G GCACTGCG

445 CCCGCAGT GGCTAGCTACAACGA GCGTCGGT ACCGACGC A ACTGCGGG

448 TCCCCCGC GGCTAGCTACAACGA AGTGCGTC GACGCACT G GCGGGGGA

456 CGCCCCGC GGCTAGCTACAACGA TCCCCCGC GCGGGGGA G GCGGGGCG

461 CCCCACGC GGCTAGCTACAACGA CCCGCTCC GGAGCGGG G GCGTGGGG

Table 16

Table 16

Table 16

689 AGGGGGAC GGCTAGCTACAACGA CCCGGCCT AGGCCGGG G GTCCCCCT

699 TGGCAGGC GGCTAGCTACAACGA CCAGGGGG CCCCCTGG G GCCTGCCA

703 GGGCTGGC GGCTAGCTACAACGA AGGCCCAG CTGGGCCT G GCCAGCCC

707 CCCGGGGC GGCTAGCTACAACGA TGGCAGGC GCCTGCCA G GCCCCGGG

714 CCTCGCAC GGCTAGCTACAACGA CCGGGGCT AGCCCCGG G GTGCGAGG

716 CTCCTCGC GGCTAGCTACAACGA ACCCGGGG CCCCGGGT G GCGAGGAG

724 CCCCGCGC GGCTAGCTACAACGA CTCCTCGC GCGAGGAG G GCGCGGGG

726 GCCCCCGC GGCTAGCTACAACGA GCCTCCTC GAGGAGGC G GCGGGGGC

732 GGCACTGC GGCTAGCTACAACGA CCCCGCGC GCGCGGGG G GCAGTGCC

735 GCTGGCAC GGCTAGCTACAACGA TGCCCCCG CGGGGGCA G GTGCCAGC

737 CGGCTGGC GGCTAGCTACAACGA ACTGCCCC GGGGCAGT G GCCAGCCG

741 ACTTCGGC GGCTAGCTACAACGA TGGCACTG CAGTGCCA G GCCGAAGT

747 CGGCAGAC GGCTAGCTACAACGA TTCGGCTG CAGCCGAA G GTCTGCCG

751 GCAACGGC GGCTAGCTACAACGA AGACTTCG CGAAGTCT G GCCGTTGC

754 TGGGCAAC GGCTAGCTACAACGA GGCAGACT AGTCTGCC G GTTGCCCA

757 TCTTGGGC GGCTAGCTACAACGA AACGGCAG CTGCCGTT G GCCCAAGA

766 GCCTGGGC GGCTAGCTACAACGA CTCTTGGG CCCAAGAG G GCCCAGGC

772 CGCCACGC GGCTAGCTACAACGA CTGGGCCT AGGCCCAG G GCGTGGCG

774 AGCGCCAC GGCTAGCTACAACGA GCCTGGGC GCCCAGGC G GTGGCGCT

777 GGCAGCGC GGCTAGCTACAACGA CACGCCTG CAGGCGTG G GCGCTGCC

779 GGGGCAGC GGCTAGCTACAACGA GCCACGCC GGCGTGGC G GCTGCCCC

782 TCAGGGGC GGCTAGCTACAACGA AGCGCCAC GTGGCGCT G GCCCCTGA

790 GCTCCGGC GGCTAGCTACAACGA TCAGGGGC GCCCCTGA G GCCGGAGC

796 GCGTCCGC GGCTAGCTACAACGA TCCGGCTC GAGCCGGA G GCGGACGC

800 ACGGGCGT GGCTAGCTACAACGA CCGCTCCG CGGAGCGG A ACGCCCGT

802 CAACGGGC GGCTAGCTACAACGA GTCCGCTC GAGCGGAC G GCCCGTTG

806 TGCCCAAC GGCTAGCTACAACGA GGGCGTCC GGACGCCC G GTTGGGCA

811 ACCCCTGC GGCTAGCTACAACGA CCAACGGG CCCGTTGG G GCAGGGGT

817 CCCAGGAC GGCTAGCTACAACGA CCCTGCCC GGGCAGGG G GTCCTGGG

824 GGGTGGGC GGCTAGCTACAACGA CCAGGACC GGTCCTGG G GCCCACCC

828 GCCCGGGT GGCTAGCTACAACGA GGGCCCAG CTGGGCCC A ACCCGGGC

Table 16

834 CGTCCTGC GGCTAGCTACAACGA CCGGGTGG CCACCCGG G GCAGGACG

839 CCACGCGT GGCTAGCTACAACGA CCTGCCCG CGGGCAGG A ACGCGTGG

841 GTCCACGC GGCTAGCTACAACGA GTCCTGCC GGCAGGAC G GCGTGGAC

843 CGGTCCAC GGCTAGCTACAACGA GCGTCCTG CAGGACGC G GTGGACCG

847 CACTCGGT GGCTAGCTACAACGA CCACGCGT ACGCGTGG A ACCGAGTG

852 .ACGGTCAC GGCTAGCTACAACGA TCGGTCCA TGGACCGA G GTGACCGT

855 ACCACGGT GGCTAGCTACAACGA CACTCGGT ACCGAGTG A ACCGTGGT

858 GAAACCAC GGCTAGCTACAACGA GGTCACTC GAGTGACC G GTGGTTTC

861 ACAGAAAC GGCTAGCTACAACGA CACGGTCA TGACCGTG G GTTTCTGT

867 CACCACAC GGCTAGCTACAACGA AGAAACCA TGGTTTCT G GTGTGGTG

869 GACACCAC GGCTAGCTACAACGA ACAGAAAC GTTTCTGT G GTGGTGTC

872 GGTGACAC GGCTAGCTACAACGA CACACAGA TCTGTGTG G GTGTCACC

874 CAGGTGAC GGCTAGCTACAACGA ACCACACA TGTGTGGT G GTCACCTG

877 TGGCAGGT GGCTAGCTACAACGA GACACCAC GTGGTGTC A ACCTGCCA

881 GGTCTGGC GGCTAGCTACAACGA AGGTGACA TGTCACCT G GCCAGACC

886 CGGCGGGT GGCTAGCTACAACGA CTGGCAGG CCTGCCAG A ACCCGCCG

890 TCTTCGGC GGCTAGCTACAACGA GGGTCTGG CCAGACCC G GCCGAAGA

899 GAGGTGGC GGCTAGCTACAACGA TTCTTCGG CCGAAGAA G GCCACCTC

902 AAAGAGGT GGCTAGCTACAACGA GGCTTCTT AAGAAGCC A ACCTCTTT

915 GAGCGCAC GGCTAGCTACAACGA CCTCCAAA TTTGGAGG G GTGCGCTC

917 GAGAGCGC GGCTAGCTACAACGA ACCCTCCA TGGAGGGT G GCGCTCTC

919 CAGAGAGC GGCTAGCTACAACGA GCACCCTC GAGGGTGC G GCTCTCTG

927 GCGCGTGC GGCTAGCTACAACGA CAGAGAGC GCTCTCTG G GCACGCGC

929 TGGCGCGT GGCTAGCTACAACGA GCCAGAGA TCTCTGGC A ACGCGCCA

931 AGTGGCGC GGCTAGCTACAACGA GTGCCAGA TCTGGCAC G GCGCCACT

933 GGAGTGGC GGCTAGCTACAACGA GCGTGCCA TGGCACGC G GCCACTCC

936 GTGGGAGT GGCTAGCTACAACGA GGCGCGTG CACGCGCC A ACTCCCAC

942 GGATGGGT GGCTAGCTACAACGA GGGAGTGG CCACTCCC A ACCCATCC

946 CCACGGAT GGCTAGCTACAACGA GGGTGGGA TCCCACCC A ATCCGTGG

950 CGGCCCAC GGCTAGCTACAACGA GGATGGGT ACCCATCC G GTGGGCCG

954 CTGGCGGC GGCTAGCTACAACGA CCACGGAT ATCCGTGG G GCCGCCAG

Table 16

957 GTGCTGGC GGCTAGCTACAACGA GGCCCACG CGTGGGCC G GCCAGCAC

961 CGTGGTGC GGCTAGCTACAACGA TGGCGGCC GGCCGCCA G GCACCACG

963 CGCGTGGT GGCTAGCTACAACGA GCTGGCGG CCGCCAGC A ACCACGCG

966 GCCCGCGT GGCTAGCTACAACGA GGTGCTGG CCAGCACC A ACGCGGGC

968 GGGCCCGC GGCTAGCTACAACGA GTGGTGCT AGCACCAC G GCGGGCCC

972 TGGGGGGC GGCTAGCTACAACGA CCGCGTGG CCACGCGG G GCCCCCCA

979 ATGTGGAT GGCTAGCTACAACGA GGGGGGCC GGCCCCCC A ATCCACAT

983 CGCGATGT GGCTAGCTACAACGA GGATGGGG CCCCATCC A ACATCGCG

985 GCCGCGAT GGCTAGCTACAACGA GTGGATGG CCATCCAC A ATCGCGGC

988 GTGGCCGC GGCTAGCTACAACGA GATGTGGA TCCACATC G GCGGCCAC

991 GTGGTGGC GGCTAGCTACAACGA CGCGATGT ACATCGCG G GCCACCAC

994 GACGTGGT GGCTAGCTACAACGA GGCCGCGA TCGCGGCC A ACCACGTC

997 AGGGACGT GGCTAGCTACAACGA GGTGGCCG CGGCCACC A ACGTCCCT

999 CCAGGGAC GGCTAGCTACAACGA GTGGTGGC GCCACCAC G GTCCCTGG

1008 AGGCGTGT GGCTAGCTACAACGA CCCAGGGA TCCCTGGG A ACACGCCT

1010 CAAGGCGT GGCTAGCTACAACGA GTCCCAGG CCTGGGAC A ACGCCTTG

1012 GACAAGGC GGCTAGCTACAACGA GTGTCCCA TGGGACAC G GCCTTGTC

1017 CGGGGGAC GGCTAGCTACAACGA AAGGCGTG CACGCCTT G GTCCCCCG

1025 GCGTACAC GGCTAGCTACAACGA CGGGGGAC GTCCCCCG G GTGTACGC

1027 CGGCGTAC GGCTAGCTACAACGA ACCGGGGG CCCCCGGT G GTACGCCG

1029 CTCGGCGT GGCTAGCTACAACGA ACACCGGG CCCGGTGT A ACGCCGAG

1031 GTCTCGGC GGCTAGCTACAACGA GTACACCG CGGTGTAC G GCCGAGAC

1037 TGCTTGGT GGCTAGCTACAACGA CTCGGCGT ACGCCGAG A ACCAAGCA

1042 GGAAGTGC GGCTAGCTACAACGA TTGGTCTC GAGACCAA G GCACTTCC

1044 GAGGAAGT GGCTAGCTACAACGA GCTTGGTC GACCAAGC A ACTTCCTC

1053 TGAGGAGT GGCTAGCTACAACGA AGAGGAAG CTTCCTCT A ACTCCTCA

1062 CTTGTCGC GGCTAGCTACAACGA CTGAGGAG CTCCTCAG G GCGACAAG

1065 CTCCTTGT GGCTAGCTACAACGA CGCCTGAG CTCAGGCG A ACAAGGAG

1072 GCAGCTGC GGCTAGCTACAACGA TCCTTGTC GACAAGGA G GCAGCTGC

1075 GCCGCAGC GGCTAGCTACAACGA TGCTCCTT AAGGAGCA G GCTGCGGC

1078 AGGGCCGC GGCTAGCTACAACGA AGCTGCTC GAGCAGCT G GCGGCCCT

Table 16

1081 AGGAGGGC GGCTAGCTACAACGA CGCAGCTG CAGCTGCG G GCCCTCCT

1093 AGCTGAGT GGCTAGCTACAACGA AGGAAGGA TCCTTCCT A ACTCAGCT

1098 CAGAGAGC GGCTAGCTACAACGA TGAGTAGG CCTACTCA G GCTCTCTG

1108 GGCTGGGC GGCTAGCTACAACGA CTCAGAGA TCTCTGAG G GCCCAGCC

1113 AGTCAGGC GGCTAGCTACAACGA TGGGCCTC GAGGCCCA G GCCTGACT

1118 GCGCCAGT GGCTAGCTACAACGA CAGGCTGG CCAGCCTG A ACTGGCGC

1122 CCGAGCGC GGCTAGCTACAACGA CAGTCAGG CCTGACTG G GCGCTCGG

1124 CTCCGAGC GGCTAGCTACAACGA GCCAGTCA TGACTGGC G GCTCGGAG

1132 CCACGAGC GGCTAGCTACAACGA CTCCGAGC GCTCGGAG G GCTCGTGG

1136 GTCTCCAC GGCTAGCTACAACGA GAGCCTCC GGAGGCTC G GTGGAGAC

1142 AAGATGGT GGCTAGCTACAACGA CTCCACGA TCGTGGAG A ACCATCTT

1145 AGAAAGAT GGCTAGCTACAACGA GGTCTCCA TGGAGACC A ATCTTTCT

1155 CCTGGAAC GGCTAGCTACAACGA CCAGAAAG CTTTCTGG G GTTCCAGG

1162 TCCAGGGC GGCTAGCTACAACGA CTGGAACC GGTTCCAG G GCCCTGGA

1169 CCTGGCAT GGCTAGCTACAACGA CCAGGGCC GGCCCTGG A ATGCCAGG

1171 TCCCTGGC GGCTAGCTACAACGA ATCCAGGG CCCTGGAT G GCCAGGGA

1178 CGGGGAGT GGCTAGCTACAACGA CCCTGGCA TGCCAGGG A ACTCCCCG

1185 CAACCTGC GGCTAGCTACAACGA GGGGAGTC GACTCCCC G GCAGGTTG

1189 GGGGCAAC GGCTAGCTACAACGA CTGCGGGG CCCCGCAG G GTTGCCCC

1192 GGCGGGGC GGCTAGCTACAACGA AACCTGCG CGCAGGTT G GCCCCGCC

1197 GGGCAGGC GGCTAGCTACAACGA GGGGCAAC GTTGCCCC G GCCTGCCC

1201 GCTGGGGC GGCTAGCTACAACGA AGGCGGGG CCCCGCCT G GCCCCAGC

1207 AGTAGCGC GGCTAGCTACAACGA TGGGGCAG CTGCCCCA G GCGCTACT

1209 CCAGTAGC GGCTAGCTACAACGA GCTGGGGC GCCCCAGC G GCTACTGG

1212 TTGCCAGT GGCTAGCTACAACGA AGCGCTGG CCAGCGCT A ACTGGCAA

1216 GCATTTGC GGCTAGCTACAACGA CAGTAGCG CGCTACTG G GCAAATGC

1220 GGCCGCAT GGCTAGCTACAACGA TTGCCAGT ACTGGCAA A ATGCGGCC

1222 GGGGCCGC GGCTAGCTACAACGA ATTTGCCA TGGCAAAT G GCGGCCCC

1225 ACAGGGGC GGCTAGCTACAACGA CGCATTTG CAAATGCG G GCCCCTGT

1231 CCAGAAAC GGCTAGCTACAACGA AGGGGCCG CGGCCCCT G GTTTCTGG

1240 CAAGCAGC GGCTAGCTACAACGA TCCAGAAA TTTCTGGA G GCTGCTTG

Table 16

1243 TCCCAAGC GGCTAGCTACAACGA AGCTCCAG CTGGAGCT G GCTTGGGA

1251 CGCGTGGT GGCTAGCTACAACGA TCCCAAGC GCTTGGGA A ACCACGCG

1254 CTGCGCGT GGCTAGCTACAACGA GGTTCCCA TGGGAACC A ACGCGCAG

1256 CACTGCGC GGCTAGCTACAACGA GTGGTTCC GGAACCAC G GCGCAGTG

1258 GGCACTGC GGCTAGCTACAACGA GCGTGGTT AACCACGC G GCAGTGCC

1261 AGGGGCAC GGCTAGCTACAACGA TGCGCGTG CACGCGCA G GTGCCCCT

1263 GTAGGGGC GGCTAGCTACAACGA ACTGCGCG CGCGCAGT G GCCCCTAC

1269 CACCCCGT GGCTAGCTACAACGA AGGGGCAC GTGCCCCT A ACGGGGTG

1274 AGGAGCAC GGCTAGCTACAACGA CCCGTAGG CCTACGGG G GTGCTCCT

1276 TGAGGAGC GGCTAGCTACAACGA ACCCCGTA TACGGGGT G GCTCCTCA

1286 CAGTGCGT GGCTAGCTACAACGA CTTGAGGA TCCTCAAG A ACGCACTG

1288 GGCAGTGC GGCTAGCTACAACGA GTCTTGAG CTCAAGAC G GCACTGCC

1290 CGGGCAGT GGCTAGCTACAACGA GCGTCTTG CAAGACGC A ACTGCCCG

1293 CAGCGGGC GGCTAGCTACAACGA AGTGCGTC GACGCACT G GCCCGCTG

1297 CTCGCAGC GGCTAGCTACAACGA GGGCAGTG CACTGCCC G GCTGCGAG

1300 CAGCTCGC GGCTAGCTACAACGA AGCGGGCA TGCCCGCT G GCGAGCTG

1304 ACCGCAGC GGCTAGCTACAACGA TCGCAGCG CGCTGCGA G GCTGCGGT

1307 GTGACCGC GGCTAGCTACAACGA AGCTCGCA TGCGAGCT G GCGGTCAC

1310 GGGGTGAC GGCTAGCTACAACGA CGCAGCTC GAGCTGCG G GTCACCCC

1313 GCTGGGGT GGCTAGCTACAACGA GACCGCAG CTGCGGTC A ACCCCAGC

1319 CCGGCTGC GGCTAGCTACAACGA TGGGGTGA TCACCCCA G GCAGCCGG

1322 ACACCGGC GGCTAGCTACAACGA TGCTGGGG CCCCAGCA G GCCGGTGT

1326 ACAGACAC GGCTAGCTACAACGA CGGCTGCT AGCAGCCG G GTGTCTGT

1328 GCACAGAC GGCTAGCTACAACGA ACCGGCTG CAGCCGGT G GTCTGTGC

1332 CCGGGCAC GGCTAGCTACAACGA AGACACCG CGGTGTCT G GTGCCCGG

1334 TCCCGGGC GGCTAGCTACAACGA ACAGACAC GTGTCTGT G GCCCGGGA

1345 CCTGGGGC GGCTAGCTACAACGA TTCTCCCG CGGGAGAA G GCCCCAGG

1353 CACAGAGC GGCTAGCTACAACGA CCTGGGGC GCCCCAGG G GCTCTGTG

1358 GCCGCCAC GGCTAGCTACAACGA AGAGCCCT AGGGCTCT G GTGGCGGC

1361 GGGGCCGC GGCTAGCTACAACGA CACAGAGC GCTCTGTG G GCGGCCCC

1364 TCGGGGGC GGCTAGCTACAACGA CGCCACAG CTGTGGCG G GCCCCCGA

Table 16

1380 GTCTGTGT GGCTAGCTACAACGA CCTCCTCC GGAGGAGG A ACACAGAC

1382 GGGTCTGT GGCTAGCTACAACGA GTCCTCCT AGGAGGAC A ACAGACCC

1386 ACGGGGGT GGCTAGCTACAACGA CTGTGTCC GGACACAG A ACCCCCGT

1392 CAGGCGAC GGCTAGCTACAACGA GGGGGTCT AGACCCCC G GTCGCCTG

1395 CACCAGGC GGCTAGCTACAACGA GACGGGGG CCCCCGTC G GCCTGGTG

1400 AGCTGCAC GGCTAGCTACAACGA CAGGCGAC GTCGCCTG G GTGCAGCT

1402 GCAGCTGC GGCTAGCTACAACGA ACCAGGCG CGCCTGGT G GCAGCTGC

1405 GGAGCAGC GGCTAGCTACAACGA TGCACCAG CTGGTGCA G GCTGCTCC

1408 GGCGGAGC GGCTAGCTACAACGA AGCTGCAC GTGCAGCT G GCTCCGCC

1413 GTGCTGGC GGCTAGCTACAACGA GGAGCAGC GCTGCTCC G GCCAGCAC

1417 TGCTGTGC GGCTAGCTACAACGA TGGCGGAG CTCCGCCA G GCACAGCA

1419 GCTGCTGT GGCTAGCTACAACGA GCTGGCGG CCGCCAGC A ACAGCAGC

1422 GGGGCTGC GGCTAGCTACAACGA TGTGCTGG CCAGCACA G GCAGCCCC

1425 CCAGGGGC GGCTAGCTACAACGA TGCTGTGC GCACAGCA G GCCCCTGG

1432 ACACCTGC GGCTAGCTACAACGA CAGGGGCT AGCCCCTG G GCAGGTGT

1436 CCGTACAC GGCTAGCTACAACGA CTGCCAGG CCTGGCAG G GTGTACGG

1438 AGCCGTAC GGCTAGCTACAACGA ACCTGCCA TGGCAGGT G GTACGGCT

1440 GAAGCCGT GGCTAGCTACAACGA ACACCTGC GCAGGTGT A ACGGCTTC

1443 CACGAAGC GGCTAGCTACAACGA CGTACACC GGTGTACG G GCTTCGTG

1448 GCCCGCAC GGCTAGCTACAACGA GAAGCCGT ACGGCTTC G GTGCGGGC

1450 AGGCCCGC GGCTAGCTACAACGA ACGAAGCC GGCTTCGT G GCGGGCCT

1454 AGGCAGGC GGCTAGCTACAACGA CCGCACGA TCGTGCGG G GCCTGCCT

1458 GCGCAGGC GGCTAGCTACAACGA AGGCCCGC GCGGGCCT G GCCTGCGC

1462 GCCGGCGC GGCTAGCTACAACGA AGGCAGGC GCCTGCCT G GCGCCGGC

1464 CAGCCGGC GGCTAGCTACAACGA GCAGGCAG CTGCCTGC G GCCGGCTG

1468 GCACCAGC GGCTAGCTACAACGA CGGCGCAG CTGCGCCG G GCTGGTGC

1472 GGGGGCAC GGCTAGCTACAACGA CAGCCGGC GCCGGCTG G GTGCCCCC

1474 CTGGGGGC GGCTAGCTACAACGA ACCAGCCG CGGCTGGT G GCCCCCAG

1482 CCAGAGGC GGCTAGCTACAACGA CTGGGGGC GCCCCCAG G GCCTCTGG

1491 CCTGGAGC GGCTAGCTACAACGA CCCAGAGG CCTCTGGG G GCTCCAGG

1498 CGTTGTGC GGCTAGCTACAACGA CTGGAGCC GGCTCCAG G GCACAACG

Table 16

Table 16

1638 CGGAACAC GGCTAGCTACAACGA AGCCAACC GGTTGGCT G GTGTTCCG

1640 GCCGGAAC GGCTAGCTACAACGA ACAGCCAA TTGGCTGT G GTTCCGGC

1646 TCTGCGGC GGCTAGCTACAACGA CGGAACAC GTGTTCCG G GCCGCAGA

1649 TGCTCTGC GGCTAGCTACAACGA GGCCGGAA TTCCGGCC G GCAGAGCA

1654 GACGGTGC GGCTAGCTACAACGA TCTGCGGC GCCGCAGA G GCACCGTC

1656 CAGACGGT GGCTAGCTACAACGA GCTCTGCG CGCAGAGC A ACCGTCTG

1659 ACGCAGAC GGCTAGCTACAACGA GGTGCTCT AGAGCACC G GTCTGCGT

1663 CCTCACGC GGCTAGCTACAACGA AGACGGTG CACCGTCT G GCGTGAGG

1665 CTCCTCAC GGCTAGCTACAACGA GCAGACGG CCGTCTGC G GTGAGGAG

1673 GCCAGGAT GGCTAGCTACAACGA CTCCTCAC GTGAGGAG A ATCCTGGC

1679 AACTTGGC GGCTAGCTACAACGA CAGGATCT AGATCCTG G GCCAAGTT

1684 GCAGGAAC GGCTAGCTACAACGA TTGGCCAG CTGGCCAA G GTTCCTGC

1690 GCCAGTGC GGCTAGCTACAACGA AGGAACTT AAGTTCCT G GCACTGGC

1692 CAGCCAGT GGCTAGCTACAACGA GCAGGAAC GTTCCTGC A ACTGGCTG

1696 TCATCAGC GGCTAGCTACAACGA CAGTGCAG CTGCACTG G GCTGATGA

1700 ACACTCAT GGCTAGCTACAACGA CAGCCAGT ACTGGCTG A ATGAGTGT

1704 GTACACAC GGCTAGCTACAACGA TCATCAGC GCTGATGA G GTGTGTAC

1706 ACGTACAC GGCTAGCTACAACGA ACTCATCA TGATGAGT G GTGTACGT

1708 CGACGTAC GGCTAGCTACAACGA ACACTCAT ATGAGTGT G GTACGTCG

1710 GACGACGT GGCTAGCTACAACGA ACACACTC GAGTGTGT A ACGTCGTC

1712 TCGACGAC GGCTAGCTACAACGA GTACACAC GTGTGTAC G GTCGTCGA

1715 AGCTCGAC GGCTAGCTACAACGA GACGTACA TGTACGTC G GTCGAGCT

1720 TGAGCAGC GGCTAGCTACAACGA TCGACGAC GTCGTCGA G GCTGCTCA

1723 ACCTGAGC GGCTAGCTACAACGA AGCTCGAC GTCGAGCT G GCTCAGGT

1729 AGAAAGAC GGCTAGCTACAACGA CTGAGCAG CTGCTCAG G GTCTTTCT

1740 CGTGACAT GGCTAGCTACAACGA AAAAGAAA TTTCTTTT A ATGTCACG

1742 TCCGTGAC GGCTAGCTACAACGA ATAAAAGA TCTTTTAT G GTCACGGA

1745 GTCTCCGT GGCTAGCTACAACGA GACATAAA TTTATGTC A ACGGAGAC

1751 AACGTGGT GGCTAGCTACAACGA CTCCGTGA TCACGGAG A ACCACGTT

1754 TGAAACGT GGCTAGCTACAACGA GGTCTCCG CGGAGACC A ACGTTTCA

1756 TTTGAAAC GGCTAGCTACAACGA GTGGTCTC GAGACCAC G GTTTCAAA

Table 16

1767 GAGCCTGT GGCTAGCTACAACGA TCTTTTGA TCAAAAGA A ACAGGCTC

1771 AAAAGAGC GGCTAGCTACAACGA CTGTTCTT AAGAACAG G GCTCTTTT

1782 CTTCCGGT GGCTAGCTACAACGA AGAAAAAG CTTTTTCT A ACCGGAAG

1791 CCAGACAC GGCTAGCTACAACGA TCTTCCGG CCGGAAGA G GTGTCTGG

1793 CTCCAGAC GGCTAGCTACAACGA ACTCTTCC GGAAGAGT G GTCTGGAG

1800 CAACTTGC GGCTAGCTACAACGA TCCAGACA TGTCTGGA G GCAAGTTG

1804 TTTGCAAC GGCTAGCTACAACGA TTGCTCCA TGGAGCAA G GTTGCAAA

1807 TGCTTTGC GGCTAGCTACAACGA AACTTGCT AGCAAGTT G GCAAAGCA

1812 TCCAATGC GGCTAGCTACAACGA TTTGCAAC GTTGCAAA G GCATTGGA

1814 ATTCCAAT GGCTAGCTACAACGA GCTTTGCA TGCAAAGC A ATTGGAAT

1820 TGTCTGAT GGCTAGCTACAACGA TCCAATGC GCATTGGA A ATCAGACA

1825 AGTGCTGT GGCTAGCTACAACGA CTGATTCC GGAATCAG A ACAGCACT

1828 TCAAGTGC GGCTAGCTACAACGA TGTCTGAT ATCAGACA G GCACTTGA

1830 CTTCAAGT GGCTAGCTACAACGA GCTGTCTG CAGACAGC A ACTTGAAG ¹

1841 AGCTGCAC GGCTAGCTACAACGA CCTCTTCA TGAAGAGG G GTGCAGCT

1843 GCAGCTGC GGCTAGCTACAACGA ACCCTCTT AAGAGGGT G GCAGCTGC

1846 CCCGCAGC GGCTAGCTACAACGA TGCACCCT AGGGTGCA G GCTGCGGG

1849 GCTCCCGC GGCTAGCTACAACGA AGCTGCAC GTGCAGCT G GCGGGAGC

1855 CCGACAGC GGCTAGCTACAACGA TCCCGCAG CTGCGGGA G GCTGTCGG

1858 CTTCCGAC GGCTAGCTACAACGA AGCTCCCG CGGGAGCT G GTCGGAAG

1865 ACCTCTGC GGCTAGCTACAACGA TTCCGACA TGTCGGAA G GCAGAGGT

1871 TGCCTGAC GGCTAGCTACAACGA CTCTGCTT AAGCAGAG G GTCAGGCA

1876 GATGCTGC GGCTAGCTACAACGA CTGACCTC GAGGTCAG G GCAGCATC

1879 CCCGATGC GGCTAGCTACAACGA TGCCTGAC GTCAGGCA G GCATCGGG

1881 TTCCCGAT GGCTAGCTACAACGA GCTGCCTG CAGGCAGC A ATCGGGAA

1889 GGCCTGGC GGCTAGCTACAACGA TTCCCGAT ATCGGGAA G GCCAGGCC

1894 GGGCGGGC GGCTAGCTACAACGA CTGGCTTC GAAGCCAG G GCCCGCCC

1898 AGCAGGGC GGCTAGCTACAACGA GGGCCTGG CCAGGCCC G GCCCTGCT

1903 ACGTCAGC GGCTAGCTACAACGA AGGGCGGG CCCGCCCT G GCTGACGT

1907 CTGGACGT GGCTAGCTACAACGA CAGCAGGG CCCTGCTG A ACGTCCAG

1909 GTCTGGAC GGCTAGCTACAACGA GTCAGCAG CTGCTGAC G GTCCAGAC

Table 16

1915 AGCGGAGT GGCTAGCTACAACGA CTGGACGT ACGTCCAG A ACTCCGCT

1920 GATGAAGC GGCTAGCTACAACGA GGAGTCTG CAGACTCC G GCTTCATC

1925 TTGGGGAT GGCTAGCTACAACGA GAAGCGGA TCCGCTTC A ATCCCCAA

1933 CGTCAGGC GGCTAGCTACAACGA TTGGGGAT ATCCCCAA G GCCTGACG

1938 CAGCCCGT GGCTAGCTACAACGA CAGGCTTG CAAGCCTG A ACGGGCTG

1942 GCCGCAGC GGCTAGCTACAACGA CCGTCAGG CCTGACGG G GCTGCGGC

1945 TCGGCCGC GGCTAGCTACAACGA AGCCCGTC GACGGGCT G GCGGCCGA

1948 CAATCGGC GGCTAGCTACAACGA CGCAGCCC GGGCTGCG G GCCGATTG

1952 TTCACAAT GGCTAGCTACAACGA CGGCCGCA TGCGGCCG A ATTGTGAA

1955 ATGTTCAC GGCTAGCTACAACGA AATCGGCC GGCCGATT G GTGAACAT

1959 GTCCATGT GGCTAGCTACAACGA TCACAATC GATTGTGA A ACATGGAC

1961 TAGTCCAT GGCTAGCTACAACGA GTTCACAA TTGTGAAC A ATGGACTA

1965 GACGTAGT GGCTAGCTACAACGA CCATGTTC GAACATGG A ACTACGTC

1968 CACGACGT GGCTAGCTACAACGA AGTCCATG CATGGACT A ACGTCGTG

1970 CCCACGAC GGCTAGCTACAACGA GTAGTCCA TGGACTAC G GTCGTGGG

1973 GCTCCCAC GGCTAGCTACAACGA GACGTAGT ACTACGTC G GTGGGAGC

1979 GTTCTGGC GGCTAGCTACAACGA TCCCACGA TCGTGGGA G GCCAGAAC

1985 CGGAACGT GGCTAGCTACAACGA TCTGGCTC GAGCCAGA A ACGTTCCG

1987 TGCGGAAC GGCTAGCTACAACGA GTTCTGGC GCCAGAAC G GTTCCGCA

1992 TTCTCTGC GGCTAGCTACAACGA GGAACGTT AACGTTCC G GCAGAGAA

2006 CGCTCGGC GGCTAGCTACAACGA CCTCTTTT AAAAGAGG G GCCGAGCG

2011 TGAGACGC GGCTAGCTACAACGA TCGGCCCT AGGGCCGA G GCGTCTCA

2013 GGTGAGAC GGCTAGCTACAACGA GCTCGGCC GGCCGAGC G GTCTCACC

2018 CTCGAGGT GGCTAGCTACAACGA GAGACGCT AGCGTCTC A ACCTCGAG

2027 GCCTTCAC GGCTAGCTACAACGA CCTCGAGG CCTCGAGG G GTGAAGGC

2033 AACAGTGC GGCTAGCTACAACGA CTTCACCC GGGTGAAG G GCACTGTT

2035 TGAACAGT GGCTAGCTACAACGA GCCTTCAC GTGAAGGC A ACTGTTCA

2038 CGCTGAAC GGCTAGCTACAACGA AGTGCCTT AAGGCACT G GTTCAGCG

2043 GAGCACGC GGCTAGCTACAACGA TGAACAGT ACTGTTCA G GCGTGCTC

2045 TTGAGCAC GGCTAGCTACAACGA GCTGAACA TGTTCAGC G GTGCTCAA

2047 AGTTGAGC GGCTAGCTACAACGA ACGCTGAA TTCAGCGT G GCTCAACT

Table 16

2052 CTCGTAGT GGCTAGCTACAACGA TGAGCACG CGTGCTCA A ACTACGAG

2055 CCGCTCGT GGCTAGCTACAACGA AGTTGAGC GCTCAACT A ACGAGCGG

2059 GCGCCCGC GGCTAGCTACAACGA TCGTAGTT AACTACGA G GCGGGCGC

2063 CGCCGCGC GGCTAGCTACAACGA CCGCTCGT ACGAGCGG G GCGCGGCG

2065 GGCGCCGC GGCTAGCTACAACGA GCCCGCTC GAGCGGGC G GCGGCGCC

2068 CGGGGCGC GGCTAGCTACAACGA CGCGCCCG CGGGCGCG G GCGCCCCG

2070 GCCGGGGC GGCTAGCTACAACGA GCCGCGCC GGCGCGGC G GCCCCGGC

2076 CAGGAGGC GGCTAGCTACAACGA CGGGGCGC GCGCCCCG G GCCTCCTG

2085 AGAGGCGC GGCTAGCTACAACGA CCAGGAGG CCTCCTGG G GCGCCTCT

2087 ACAGAGGC GGCTAGCTACAACGA GCCCAGGA TCCTGGGC G GCCTCTGT

2093 CCCAGCAC GGCTAGCTACAACGA AGAGGCGC GCGCCTCT G GTGCTGGG

2095 GGCCCAGC GGCTAGCTACAACGA ACAGAGGC GCCTCTGT G GCTGGGCC

2100 GTCCAGGC GGCTAGCTACAACGA CCAGCACA TGTGCTGG G GCCTGGAC

2106 GATATCGT GGCTAGCTACAACGA CCAGGCCC GGGCCTGG A ACGATATC

2109 GTGGATAT GGCTAGCTACAACGA CGTCCAGG CCTGGACG A ATATCCAC

2111 CTGTGGAT GGCTAGCTACAACGA ATCGTCCA TGGACGAT A ATCCACAG

2115 GGCCCTGT GGCTAGCTACAACGA GGATATCG ' CGATATCC A ACAGGGCC

2120 CGCCAGGC GGCTAGCTACAACGA CCTGTGGA TCCACAGG G GCCTGGCG

2125 AGGTGCGC GGCTAGCTACAACGA CAGGCCCT AGGGCCTG G GCGCACCT

2127 GAAGGTGC GGCTAGCTACAACGA GCCAGGCC GGCCTGGC G GCACCTTC

2129 ACGAAGGT GGCTAGCTACAACGA GCGCCAGG CCTGGCGC A ACCTTCGT

2135 CGCAGCAC GGCTAGCTACAACGA GAAGGTGC GCACCTTC G GTGCTGCG

2137 CACGCAGC GGCTAGCTACAACGA ACGAAGGT ACCTTCGT G GCTGCGTG

2140 GCACACGC GGCTAGCTACAACGA AGCACGAA TTCGTGCT G GCGTGTGC

2142 CCGCACAC GGCTAGCTACAACGA GCAGCACG CGTGCTGC G GTGTGCGG

2144 GCCCGCAC GGCTAGCTACAACGA ACGCAGCA TGCTGCGT G GTGCGGGC

2146 GGGCCCGC GGCTAGCTACAACGA ACACGCAG CTGCGTGT G GCGGGCCC

2150 TCCTGGGC GGCTAGCTACAACGA CCGCACAC GTGTGCGG G GCCCAGGA

2157 CGGCGGGT GGCTAGCTACAACGA CCTGGGCC GGCCCAGG A ACCCGCCG

2161 CAGGCGGC GGCTAGCTACAACGA GGGTCCTG CAGGACCC G GCCGCCTG

2164 GCTCAGGC GGCTAGCTACAACGA GGCGGGTC GACCCGCC G GCCTGAGC

Table 16

Table 16

2278 ACCGACGC GGCTAGCTACAACGA ACGCAGTA TACTGCGT G GCGTCGGT

2280 ATACCGAC GGCTAGCTACAACGA GCACGCAG CTGCGTGC G GTCGGTAT

2284 CGGCATAC GGCTAGCTACAACGA CGACGCAC GTGCGTCG G GTATGCCG

2286 CACGGCAT GGCTAGCTACAACGA ACCGACGC GCGTCGGT A ATGCCGTG

2288 ACCACGGC GGCTAGCTACAACGA ATACCGAC GTCGGTAT G GCCGTGGT

2291 TGGACCAC GGCTAGCTACAACGA GGCATACC GGTATGCC G GTGGTCCA

2294 TTCTGGAC GGCTAGCTACAACGA CACGGCAT ATGCCGTG G GTCCAGAA

2303 TGGGCGGC GGCTAGCTACAACGA CTTCTGGA TCCAGAAG G GCCGCCCA

2306 CCATGGGC GGCTAGCTACAACGA GGCCTTCT AGAAGGCC G GCCCATGG

2310 GTGCCCAT GGCTAGCTACAACGA GGGCGGCC GGCCGCCC A ATGGGCAC

2314 GGACGTGC GGCTAGCTACAACGA CCATGGGC GCCCATGG G GCACGTCC

2316 GCGGACGT GGCTAGCTACAACGA GCCCATGG CCATGGGC A ACGTCCGC

2318 TTGCGGAC GGCTAGCTACAACGA GTGCCCAT ATGGGCAC G GTCCGCAA

2322 GGCCTTGC GGCTAGCTACAACGA GGACGTGC GCACGTCC G GCAAGGCC

2327 TTGAAGGC GGCTAGCTACAACGA CTTGCGGA TCCGCAAG G GCCTTCAA

2337 GACGTGGC GGCTAGCTACAACGA TCTTGAAG CTTCAAGA G GCCACGTC

2340 AGAGACGT GGCTAGCTACAACGA GGCTCTTG CAAGAGCC A ACGTCTCT

2342 GTAGAGAC GGCTAGCTACAACGA GTGGCTCT AGAGCCAC G GTCTCTAC

2348 GTCAAGGT GGCTAGCTACAACGA AGAGACGT ACGTCTCT A ACCTTGAC

2354 AGGTCTGT GGCTAGCTACAACGA CAAGGTAG CTACCTTG A ACAGACCT

2358 CTGGAGGT GGCTAGCTACAACGA CTGTCAAG CTTGACAG A ACCTCCAG

2365 TGTACGGC GGCTAGCTACAACGA TGGAGGTC GACCTCCA G GCCGTACA

2368 GCATGTAC GGCTAGCTACAACGA GGCTGGAG CTCCAGCC G GTACATGC

2370 TCGCATGT GGCTAGCTACAACGA ACGGCTGG CCAGCCGT A ACATGCGA

2372 TGTCGCAT GGCTAGCTACAACGA GTACGGCT AGCCGTAC A ATGCGACA

2374 ACTGTCGC GGCTAGCTACAACGA ATGTACGG CCGTACAT G GCGACAGT

2377 CGAACTGT GGCTAGCTACAACGA CGCATGTA TACATGCG A ACAGTTCG

2380 CCACGAAC GGCTAGCTACAACGA TGTCGCAT ATGCGACA G GTTCGTGG

2384 TGAGCCAC GGCTAGCTACAACGA GAACTGTC GACAGTTC G GTGGCTCA

2387 AGGTGAGC GGCTAGCTACAACGA CACGAACT AGTTCGTG G GCTCACCT

2391 CTGCAGGT GGCTAGCTACAACGA GAGCCACG CGTGGCTC A ACCTGCAG

Table 16

2395 TCTCCTGC GGCTAGCTACAACGA AGGTGAGC GCTCACCT G GCAGGAGA

2402 GGGCTGGT GGCTAGCTACAACGA CTCCTGCA TGCAGGAG A ACCAGCCC

2406 CAGCGGGC GGCTAGCTACAACGA TGGTCTCC GGAGACCA G GCCCGCTG

2410 CCCTCAGC GGCTAGCTACAACGA GGGCTGGT ACCAGCCC G GCTGAGGG

2418 GACGGCAT GGCTAGCTACAACGA CCCTCAGC GCTGAGGG A ATGCCGTC

2420 ACGACGGC GGCTAGCTACAACGA ATCCCTCA TGAGGGAT G GCCGTCGT

2423 ATGACGAC GGCTAGCTACAACGA GGCATCCC GGGATGCC G GTCGTCAT

2426 TCGATGAC GGCTAGCTACAACGA GACGGCAT ATGCCGTC G GTCATCGA

2429 TGCTCGAT GGCTAGCTACAACGA GACGACGG CCGTCGTC A ATCGAGCA

2434 AGCTCTGC GGCTAGCTACAACGA TCGATGAC GTCATCGA G GCAGAGCT

2439 GGAGGAGC GGCTAGCTACAACGA TCTGCTCG CGAGCAGA G GCTCCTCC

2451 GGCCTCAT GGCTAGCTACAACGA TCAGGGAG CTCCCTGA A ATGAGGCC

2456 CTGCTGGC GGCTAGCTACAACGA CTCATTCA TGAATGAG G GCCAGCAG

2460 GCCACTGC GGCTAGCTACAACGA TGGCCTCA TGAGGCCA G GCAGTGGC

2463 GAGGCCAC GGCTAGCTACAACGA TGCTGGCC GGCCAGCA G GTGGCCTC

2466 GAAGAGGC GGCTAGCTACAACGA CACTGCTG CAGCAGTG G GCCTCTTC

2475 GAAGACGT GGCTAGCTACAACGA CGAAGAGG CCTCTTCG A ACGTCTTC

2477 AGGAAGAC GGCTAGCTACAACGA GTCGAAGA TCTTCGAC G GTCTTCCT

2485 TGAAGCGT GGCTAGCTACAACGA AGGAAGAC GTCTTCCT A ACGCTTCA

2487 CATGAAGC GGCTAGCTACAACGA GTAGGAAG CTTCCTAC G GCTTCATG

2492 TGGCACAT GGCTAGCTACAACGA GAAGCGTA TACGCTTC A ATGTGCCA

2494 GGTGGCAC GGCTAGCTACAACGA ATGAAGCG CGCTTCAT G GTGCCACC

2496 GTGGTGGC GGCTAGCTACAACGA ACATGAAG CTTCATGT G GCCACCAC

2499 GGCGTGGT GGCTAGCTACAACGA GGCACATG CATGTGCC A ACCACGCC

2502 CACGGCGT GGCTAGCTACAACGA GGTGGCAC GTGCCACC A ACGCCGTG

2504 CGCACGGC GGCTAGCTACAACGA GTGGTGGC GCCACCAC G GCCGTGCG

2507 ATGCGCAC GGCTAGCTACAACGA GGCGTGGT ACCACGCC G GTGCGCAT

2509 TGATGCGC GGCTAGCTACAACGA ACGGCGTG CACGCCGT G GCGCATCA

2511 CCTGATGC GGCTAGCTACAACGA GCACGGCG CGCCGTGC G GCATCAGG

2513 CCCCTGAT GGCTAGCTACAACGA GCGCACGG CCGTGCGC A ATCAGGGG

2520 GGACTTGC GGCTAGCTACAACGA CCCTGATG CATCAGGG G GCAAGTCC

Table 16

2524 CGTAGGAC GGCTAGCTACAACGA TTGCCCCT AGGGGCAA G GTCCTACG

2529 CTGGACGT GGCTAGCTACAACGA AGGACTTG CAAGTCCT A ACGTCCAG

2531 CACTGGAC GGCTAGCTACAACGA GTAGGACT AGTCCTAC G GTCCAGTG

2536 CCTGGCAC GGCTAGCTACAACGA TGGACGTA TACGTCCA G GTGCCAGG

2538 CCCCTGGC GGCTAGCTACAACGA ACTGGACG CGTCCAGT G GCCAGGGG

2546 TGCGGGAT GGCTAGCTACAACGA CCCCTGGC GCCAGGGG A ATCCCGCA

2551 AGCCCTGC GGCTAGCTACAACGA GGGATCCC GGGATCCC G GCAGGGCT

2556 GATGGAGC GGCTAGCTACAACGA CCTGCGGG CCCGCAGG G GCTCCATC

2561 GAGAGGAT GGCTAGCTACAACGA GGAGCCCT AGGGCTCC A ATCCTCTC

2570 AGCAGCGT GGCTAGCTACAACGA GGAGAGGA TCCTCTCC A ACGCTGCT

2572 AGAGCAGC GGCTAGCTACAACGA GTGGAGAG CTCTCCAC G GCTGCTCT

2575 TGCAGAGC GGCTAGCTACAACGA AGCGTGGA TCCACGCT G GCTCTGCA

2580 CAGGCTGC GGCTAGCTACAACGA AGAGCAGC GCTGCTCT G GCAGCCTG

2583 GCACAGGC GGCTAGCTACAACGA TGCAGAGC GCTCTGCA G GCCTGTGC

2587 CGTAGCAC GGCTAGCTACAACGA AGGCTGCA TGCAGCCT G GTGCTACG

2589 GCCGTAGC GGCTAGCTACAACGA ACAGGCTG CAGCCTGT G GCTACGGC

2592 GTCGCCGT GGCTAGCTACAACGA AGCACAGG CCTGTGCT A ACGGCGAC

2595 CATGTCGC GGCTAGCTACAACGA CGTAGCAC GTGCTACG G GCGACATG

2598 CTCCATGT GGCTAGCTACAACGA CGCCGTAG CTACGGCG A ACATGGAG

2600 TTCTCCAT GGCTAGCTACAACGA GTCGCCGT ACGGCGAC A ATGGAGAA

2607 CAGCTTGT GGCTAGCTACAACGA TCTCCATG CATGGAGA A ACAAGCTG

2611 CAAACAGC GGCTAGCTACAACGA TTGTTCTC GAGAACAA G GCTGTTTG

2614 CCGCAAAC GGCTAGCTACAACGA AGCTTGTT AACAAGCT G GTTTGCGG

2618 ATCCCCGC GGCTAGCTACAACGA AAACAGCT AGCTGTTT G GCGGGGAT

2624 CGCCGAAT GGCTAGCTACAACGA CCCCGCAA TTGCGGGG A ATTCGGCG

2629 CGTCCCGC GGCTAGCTACAACGA CGAATCCC GGGATTCG G GCGGGACG

2634 CAGCCCGT GGCTAGCTACAACGA CCCGCCGA TCGGCGGG A ACGGGCTG

2638 GGAGCAGC GGCTAGCTACAACGA CCGTCCCG CGGGACGG G GCTGCTCC

2641 GCAGGAGC GGCTAGCTACAACGA AGCCCGTC GACGGGCT G GCTCCTGC

2647 CCAAACGC GGCTAGCTACAACGA AGGAGCAG CTGCTCCT G GCGTTTGG

2649 CACCAAAC GGCTAGCTACAACGA GCAGGAGC GCTCCTGC G GTTTGGTG

Table 16

2654 TCATCCAC GGCTAGCTACAACGA CAAACGCA TGCGTTTG G GTGGATGA

2658 GAAATCAT GGCTAGCTACAACGA CCACCAAA TTTGGTGG A ATGATTTC

2661 CAAGAAAT GGCTAGCTACAACGA CATCCACC GGTGGATG A ATTTCTTG

2668 TCACCAAC GGCTAGCTACAACGA AAGAAATC GATTTCTT G GTTGGTGA

2672 GGTGTCAC GGCTAGCTACAACGA CAACAAGA TCTTGTTG G GTGACACC

2675 TGAGGTGT GGCTAGCTACAACGA CACCAACA TGTTGGTG A ACACCTCA

2677 GGTGAGGT GGCTAGCTACAACGA GTCACCAA TTGGTGAC A ACCTCACC

2682 GGTGAGGT GGCTAGCTACAACGA GAGGTGTC GACACCTC A ACCTCACC

2687 GCGTGGGT GGCTAGCTACAACGA GAGGTGAG CTCACCTC A ACCCACGC

2691 TTTCGCGT GGCTAGCTACAACGA GGGTGAGG CCTCACCC A ACGCGAAA

2693 GTTTTCGC GGCTAGCTACAACGA GTGGGTGA TCACCCAC G GCGAAAAC

2699 AGGAAGGT GGCTAGCTACAACGA TTTCGCGT ACGCGAAA A ACCTTCCT

2711 ACCAGGGT GGCTAGCTACAACGA CCTGAGGA TCCTCAGG A ACCCTGGT

2717 CCTCGGAC GGCTAGCTACAACGA CAGGGTCC GGACCCTG G GTCCGAGG

2724 AGGGACAC GGCTAGCTACAACGA CTCGGACC GGTCCGAG G GTGTCCCT

2726 TCAGGGAC GGCTAGCTACAACGA ACCTCGGA TCCGAGGT G GTCCCTGA

2734 AGCCATAC GGCTAGCTACAACGA TCAGGGAC GTCCCTGA G GTATGGCT

2736 GCAGCCAT GGCTAGCTACAACGA ACTCAGGG CCCTGAGT A ATGGCTGC

2739 CACGCAGC GGCTAGCTACAACGA CATACTCA TGAGTATG G GCTGCGTG

2742 CACCACGC GGCTAGCTACAACGA AGCCATAC GTATGGCT G GCGTGGTG

2744 TTCACCAC GGCTAGCTACAACGA GCAGCCAT ATGGCTGC G GTGGTGAA

2747 AAGTTCAC GGCTAGCTACAACGA CACGCAGC GCTGCGTG G GTGAACTT

2751 CCGCAAGT GGCTAGCTACAACGA TCACCACG CGTGGTGA A ACTTGCGG

2755 TCTTCCGC GGCTAGCTACAACGA AAGTTCAC GTGAACTT G GCGGAAGA

2762 ACCACTGT GGCTAGCTACAACGA CTTCCGCA TGCGGAAG A ACAGTGGT

2765 TTCACCAC GGCTAGCTACAACGA TGTCTTCC GGAAGACA G GTGGTGAA

2768 AAGTTCAC GGCTAGCTACAACGA CACTGTCT AGACAGTG G GTGAACTT

2772 AGGGAAGT GGCTAGCTACAACGA TCACCACT AGTGGTGA A ACTTCCCT

2780 TCTTCTAC GGCTAGCTACAACGA AGGGAAGT ACTTCCCT G GTAGAAGA

2787 GGCCTCGT GGCTAGCTACAACGA CTTCTACA TGTAGAAG A ACGAGGCC

2792 CCCAGGGC GGCTAGCTACAACGA CTCGTCTT AAGACGAG G GCCCTGGG

Table 16

2799 CGTGCCAC GGCTAGCTACAACGA CCAGGGCC GGCCCTGG G GTGGCACG

2802 AGCCGTGC GGCTAGCTACAACGA CACCCAGG CCTGGGTG G GCACGGCT

2804 AAAGCCGT GGCTAGCTACAACGA GCCACCCA TGGGTGGC A ACGGCTTT

2807 ACAAAAGC GGCTAGCTACAACGA CGTGCCAC GTGGCACG G GCTTTTGT

2813 ATCTGAAC GGCTAGCTACAACGA AAAAGCCG CGGCTTTT G GTTCAGAT

2819 GCCGGCAT GGCTAGCTACAACGA CTGAACAA TTGTTCAG A ATGCCGGC

2821 GGGCCGGC GGCTAGCTACAACGA ATCTGAAC GTTCAGAT G GCCGGCCC

2825 CCGTGGGC GGCTAGCTACAACGA CGGCATCT AGATGCCG G GCCCACGG

2829 TAGGCCGT GGCTAGCTACAACGA GGGCCGGC GCCGGCCC A ACGGCCTA

2832 GAATAGGC GGCTAGCTACAACGA CGTGGGCC GGCCCACG G GCCTATTC

2836 AGGGGAAT GGCTAGCTACAACGA AGGCCGTG CACGGCCT A ATTCCCCT

2845 GGCCGCAC GGCTAGCTACAACGA CAGGGGAA TTCCCCTG G GTGCGGCC

2847 CAGGCCGC GGCTAGCTACAACGA ACCAGGGG CCCCTGGT G GCGGCCTG

2850 CAGCAGGC GGCTAGCTACAACGA CGCACCAG CTGGTGCG G GCCTGCTG

2854 CCAGCAGC GGCTAGCTACAACGA AGGCCGCA TGCGGCCT G GCTGCTGG

2857 TATCCAGC GGCTAGCTACAACGA AGCAGGCC GGCCTGCT G GCTGGATA

2862 CCGGGTAT GGCTAGCTACAACGA CCAGCAGC GCTGCTGG A ATACCCGG

2864 GTCCGGGT GGCTAGCTACAACGA ATCCAGCA TGCTGGAT A ACCCGGAC

2870 TCCAGGGT GGCTAGCTACAACGA CCGGGTAT ATACCCGG A ACCCTGGA

2879 CTCTGCAC GGCTAGCTACAACGA CTCCAGGG CCCTGGAG G GTGCAGAG

2881 CGCTCTGC GGCTAGCTACAACGA ACCTCCAG CTGGAGGT G GCAGAGCG

2886 GTAGTCGC GGCTAGCTACAACGA TCTGCACC GGTGCAGA G GCGACTAC

2889 GGAGTAGT GGCTAGCTACAACGA CGCTCTGC GCAGAGCG A ACTACTCC

2892 GCTGGAGT GGCTAGCTACAACGA AGTCGCTC GAGCGACT A ACTCCAGC

2898 GGCATAGC GGCTAGCTACAACGA TGGAGTAG CTACTCCA G GCTATGCC

2901 CCGGGCAT GGCTAGCTACAACGA AGCTGGAG CTCCAGCT A ATGCCCGG

2903 GTCCGGGC GGCTAGCTACAACGA ATAGCTGG CCAGCTAT G GCCCGGAC

2909 ATGGAGGT GGCTAGCTACAACGA CCGGGCAT ATGCCCGG A ACCTCCAT

2915 GCTCTGAT GGCTAGCTACAACGA GGAGGTCC GGACCTCC A ATCAGAGC

2921 AGACTGGC GGCTAGCTACAACGA TCTGATGG CCATCAGA G GCCAGTCT

2925 GGTGAGAC GGCTAGCTACAACGA TGGCTCTG CAGAGCCA G GTCTCACC

Table 16

2930 TTGAAGGT GGCTAGCTACAACGA GAGACTGG CCAGTCTC A ACCTTCAA

2937 GCCGCGGT GGCTAGCTACAACGA TGAAGGTG CACCTTCA A ACCGCGGC

2940 GAAGCCGC GGCTAGCTACAACGA GGTTGAAG CTTCAACC G GCGGCTTC

2943 CTTGAAGC GGCTAGCTACAACGA CGCGGTTG CAACCGCG G GCTTCAAG

2951 CTCCCAGC GGCTAGCTACAACGA CTTGAAGC GCTTCAAG G GCTGGGAG

2961 ACGCATGT GGCTAGCTACAACGA TCCTCCCA TGGGAGGA A ACATGCGT

2963 CGACGCAT GGCTAGCTACAACGA GTTCCTCC GGAGGAAC A ATGCGTCG

2965 TGCGACGC GGCTAGCTACAACGA ATGTTCCT AGGAACAT G GCGTCGCA

2967 TTTGCGAC GGCTAGCTACAACGA GCATGTTC ^' GAACATGC G GTCGCAAA

2970 GAGTTTGC GGCTAGCTACAACGA GACGCATG CATGCGTC G GCAAACTC

2974 CAAAGAGT GGCTAGCTACAACGA TTGCGACG CGTCGCAA A ACTCTTTG

2984 CGCAAGAC GGCTAGCTACAACGA CCCAAAGA TCTTTGGG G GTCTTGCG

2989 TCAGCCGC GGCTAGCTACAACGA AAGACCCC GGGGTCTT G GCGGCTGA

2992 ACTTCAGC GGCTAGCTACAACGA CGCAAGAC GTCTTGCG G GCTGAAGT

2998 TGTGACAC GGCTAGCTACAACGA TTCAGCCG CGGCTGAA G GTGTCACA

3000 GCTGTGAC GGCTAGCTACAACGA ACTTCAGC GCTGAAGT G GTCACAGC

3003 CAGGCTGT GGCTAGCTACAACGA GACACTTC GAAGTGTC A ACAGCCTG

3006 AAACAGGC GGCTAGCTACAACGA TGTGACAC GTGTCACA G GCCTGTTT

3010 CCAGAAAC GGCTAGCTACAACGA AGGCTGTG CACAGCCT G GTTTCTGG

3018 CTGCAAAT GGCTAGCTACAACGA CCAGAAAC GTTTCTGG A ATTTGCAG

3022 TCACCTGC GGCTAGCTACAACGA AAATCCAG CTGGATTT G GCAGGTGA

3026 CTGTTCAC GGCTAGCTACAACGA CTGCAAAT ATTTGCAG G GTGAACAG

3030 GAGGCTGT GGCTAGCTACAACGA TCACCTGC GCAGGTGA A ACAGCCTC

3033 CTGGAGGC GGCTAGCTACAACGA TGTTCACC GGTGAACA G GCCTCCAG

3041 CACACCGT GGCTAGCTACAACGA CTGGAGGC GCCTCCAG A ACGGTGTG

3044 GTGCACAC GGCTAGCTACAACGA CGTCTGGA TCCAGACG G GTGTGCAC

3046 TGGTGCAC GGCTAGCTACAACGA ACCGTCTG CAGACGGT G GTGCACCA

3048 GTTGGTGC GGCTAGCTACAACGA ACACCGTC GACGGTGT G GCACCAAC

3050 ATGTTGGT GGCTAGCTACAACGA GCACACCG CGGTGTGC A ACCAACAT

3054 GTAGATGT GGCTAGCTACAACGA TGGTGCAC GTGCACCA A ACATCTAC

3056 TTGTAGAT GGCTAGCTACAACGA GTTGGTGC GCACCAAC A ATCTACAA

Table 16

3060 GATCTTGT GGCTAGCTACAACGA AGATGTTG CAACATCT A ACAAGATC

3065 AGGAGGAT GGCTAGCTACAACGA CTTGTAGA TCTACAAG A ATCCTCCT

3073 CCTGCAGC GGCTAGCTACAACGA AGGAGGAT ATCCTCCT G GCTGCAGG

3076 ACGCCTGC GGCTAGCTACAACGA AGCAGGAG CTCCTGCT G GCAGGCGT

3080 CTGTACGC GGCTAGCTACAACGA CTGCAGCA TGCTGCAG G GCGTACAG

3082 ACCTGTAC GGCTAGCTACAACGA GCCTGCAG CTGCAGGC G GTACAGGT

3084 AAACCTGT GGCTAGCTACAACGA ACGCCTGC GCAGGCGT A ACAGGTTT

3088 CGTGAAAC GGCTAGCTACAACGA CTGTACGC GCGTACAG G GTTTCACG

3093 ACATGCGT GGCTAGCTACAACGA GAAACCTG CAGGTTTC A ACGCATGT

3095 ACACATGC GGCTAGCTACAACGA GTGAAACC GGTTTCAC G GCATGTGT

3097 GCACACAT GGCTAGCTACAACGA GCGTGAAA TTTCACGC A ATGTGTGC

3099 CAGCACAC GGCTAGCTACAACGA ATGCGTGA TCACGCAT G GTGTGCTG

3101 TGCAGCAC GGCTAGCTACAACGA ACATGCGT ACGCATGT G GTGCTGCA

3103 GCTGCAGC GGCTAGCTACAACGA ACACATGC GCATGTGT G GCTGCAGC

3106 GGAGCTGC GGCTAGCTACAACGA AGCACACA TGTGTGCT G GCAGCTCC

3109 ATGGGAGC GGCTAGCTACAACGA TGCAGCAC GTGCTGCA G GCTCCCAT

3115 GATGAAAT GGCTAGCTACAACGA GGGAGCTG CAGCTCCC A ATTTCATC

3120 TTGCTGAT GGCTAGCTACAACGA GAAATGGG CCCATTTC A ATCAGCAA

3124 AAACTTGC GGCTAGCTACAACGA TGATGAAA TTTCATCA G GCAAGTTT

3128 TTCCAAAC GGCTAGCTACAACGA TTGCTGAT ATCAGCAA G GTTTGGAA

3138 TGTGGGGT GGCTAGCTACAACGA TCTTCCAA TTGGAAGA A ACCCCACA

3143 AAAAATGT GGCTAGCTACAACGA GGGGTTCT AGAACCCC A ACATTTTT

3145 GGAAAAAT GGCTAGCTACAACGA GTGGGGTT AACCCCAC A ATTTTTCC

3154 TGACGCGC GGCTAGCTACAACGA AGGAAAAA TTTTTCCT G GCGCGTCA

3156 GATGACGC GGCTAGCTACAACGA GCAGGAAA TTTCCTGC G GCGTCATC

3158 GAGATGAC GGCTAGCTACAACGA GCGCAGGA TCCTGCGC G GTCATCTC

3161 TCAGAGAT GGCTAGCTACAACGA GACGCGCA TGCGCGTC A ATCTCTGA

3168 GGCCGTGT GGCTAGCTACAACGA CAGAGATG CATCTCTG A ACACGGCC

3170 GAGGCCGT GGCTAGCTACAACGA GTCAGAGA TCTCTGAC A ACGGCCTC

3173 AGGGAGGC GGCTAGCTACAACGA CGTGTCAG CTGACACG G GCCTCCCT

3183 GGAGTAGC GGCTAGCTACAACGA AGAGGGAG CTCCCTCT G GCTACTCC

Table 16

Table 16

3317 ACGTAGGT GGCTAGCTACAACGA GACACGGT ACCGTGTC A ACCTACGT

3321 TGGCACGT GGCTAGCTACAACGA AGGTGACA TGTCACCT A ACGTGCCA

3323 AGTGGCAC GGCTAGCTACAACGA GTAGGTGA TCACCTAC G GTGCCACT

3325 GGAGTGGC GGCTAGCTACAACGA ACGTAGGT ACCTACGT G GCCACTCC

3328 CCAGGAGT GGCTAGCTACAACGA GGCACGTA TACGTGCC A ACTCCTGG

3337 TGAGTGAC GGCTAGCTACAACGA CCCAGGAG CTCCTGGG G GTCACTCA

3340 TCCTGAGT GGCTAGCTACAACGA GACCCCAG CTGGGGTC A ACTCAGGA

3347 TGGGCTGT GGCTAGCTACAACGA CCTGAGTG CACTCAGG A ACAGCCCA

3350 GTCTGGGC GGCTAGCTACAACGA TGTCCTGA TCAGGACA G GCCCAGAC

3356 AGCTGCGT GGCTAGCTACAACGA CTGGGCTG CAGCCCAG A ACGCAGCT

3358 TCAGCTGC GGCTAGCTACAACGA GTCTGGGC GCCCAGAC G GCAGCTGA

3361 GACTCAGC GGCTAGCTACAACGA TGCGTCTG CAGACGCA G GCTGAGTC

3366 CTTCCGAC GGCTAGCTACAACGA TCAGCTGC GCAGCTGA G GTCGGAAG

3373 CCGGGAGC GGCTAGCTACAACGA TTCCGACT AGTCGGAA G GCTCCCGG

3383 AGCGTCGT GGCTAGCTACAACGA CCCCGGGA TCCCGGGG A ACGACGCT

3386 GTCAGCGT GGCTAGCTACAACGA CGTCCCCG CGGGGACG A ACGCTGAC

3388 CAGTCAGC GGCTAGCTACAACGA GTCGTCCC GGGACGAC G GCTGACTG

3392 AGGGCAGT GGCTAGCTACAACGA CAGCGTCG CGACGCTG A ACTGCCCT

3395 TCCAGGGC GGCTAGCTACAACGA AGTCAGCG CGCTGACT G GCCCTGGA

3404 GCTGCGGC GGCTAGCTACAACGA CTCCAGGG CCCTGGAG G GCCGCAGC

3407 TTGGCTGC GGCTAGCTACAACGA GGCCTCCA TGGAGGCC G GCAGCCAA

3410 GGGTTGGC GGCTAGCTACAACGA TGCGGCCT AGGCCGCA G GCCAACCC

3414 TGCCGGGT GGCTAGCTACAACGA TGGCTGCG CGCAGCCA A ACCCGGCA

3419 GGCAGTGC GGCTAGCTACAACGA CGGGTTGG CCAACCCG G GCACTGCC

3421 AGGGCAGT GGCTAGCTACAACGA GCCGGGTT AACCCGGC A ACTGCCCT

3424 CTGAGGGC GGCTAGCTACAACGA AGTGCCGG CCGGCACT G GCCCTCAG

3432 CTTGAAGT GGCTAGCTACAACGA CTGAGGGC GCCCTCAG A ACTTCAAG

3440 AGGATGGT GGCTAGCTACAACGA CTTGAAGT ACTTCAAG A ACCATCCT

3443 TCCAGGAT GGCTAGCTACAACGA GGTCTTGA TCAAGACC A ATCCTGGA

3450 CCATCAGT GGCTAGCTACAACGA CCAGGATG CATCCTGG A ACTGATGG

3454 GTGGCCAT GGCTAGCTACAACGA CAGTCCAG CTGGACTG A ATGGCCAC

Table 16

3457 CGGGTGGC GGCTAGCTACAACGA CATCAGTC GACTGATG G GCCACCCG

3460 GGGCGGGT GGCTAGCTACAACGA GGCCATCA TGATGGCC A ACCCGCCC

3464 CTGTGGGC GGCTAGCTACAACGA GGGTGGCC GGCCACCC G GCCCACAG

3468 CTGGCTGT GGCTAGCTACAACGA GGGCGGGT ACCCGCCC A ACAGCCAG

3471 GGCCTGGC GGCTAGCTACAACGA TGTGGGCG CGCCCACA G GCCAGGCC

3476 CTCTCGGC GGCTAGCTACAACGA CTGGCTGT ACAGCCAG G GCCGAGAG

3483 GTGTCTGC GGCTAGCTACAACGA TCTCGGCC GGCCGAGA G GCAGACAC

3487 GCTGGTGT GGCTAGCTACAACGA CTGCTCTC GAGAGCAG A ACACCAGC

3489 CTGCTGGT GGCTAGCTACAACGA GTCTGCTC GAGCAGAC A ACCAGCAG

3493 AGGGCTGC GGCTAGCTACAACGA TGGTGTCT AGACACCA G GCAGCCCT

3496 GACAGGGC GGCTAGCTACAACGA TGCTGGTG CACCAGCA G GCCCTGTC

3501 GGCGTGAC GGCTAGCTACAACGA AGGGCTGC GCAGCCCT G GTCACGCC

3504 CCCGGCGT GGCTAGCTACAACGA GACAGGGC GCCCTGTC A ACGCCGGG

3506 AGCCCGGC GGCTAGCTACAACGA GTGACAGG CCTGTCAC G GCCGGGCT

3511 CGTAGAGC GGCTAGCTACAACGA CCGGCGTG CACGCCGG G GCTCTACG

3516 TGGGACGT GGCTAGCTACAACGA AGAGCCCG CGGGCTCT A ACGTCCCA

3518 CCTGGGAC GGCTAGCTACAACGA GTAGAGCC GGCTCTAC G GTCCCAGG

3535 TGGGCCGC GGCTAGCTACAACGA CCCTCCCT AGGGAGGG G GCGGCCCA

3538 GTGTGGGC GGCTAGCTACAACGA CGCCCCTC GAGGGGCG G GCCCACAC

3542 CTGGGTGT GGCTAGCTACAACGA GGGCCGCC GGCGGCCC A ACACCCAG

3544 GCCTGGGT GGCTAGCTACAACGA GTGGGCCG CGGCCCAC A ACCCAGGC

3550 GTGCGGGC GGCTAGCTACAACGA CTGGGTGT ACACCCAG G GCCCGCAC

3554 AGCGGTGC GGCTAGCTACAACGA GGGCCTGG CCAGGCCC G GCACCGCT

3556 CCAGCGGT GGCTAGCTACAACGA GCGGGCCT AGGCCCGC A ACCGCTGG

3559 CTCCCAGC GGCTAGCTACAACGA GGTGCGGG CCCGCACC G GCTGGGAG

3566 CCTCAGAC GGCTAGCTACAACGA TCCCAGCG CGCTGGGA G GTCTGAGG

3573 ACTCAGGC GGCTAGCTACAACGA CTCAGACT AGTCTGAG G GCCTGAGT

3579 ACACTCAC GGCTAGCTACAACGA TCAGGCCT AGGCCTGA G GTGAGTGT

3583 CCAAACAC GGCTAGCTACAACGA TCACTCAG CTGAGTGA G GTGTTTGG

3585 GGCCAAAC GGCTAGCTACAACGA ACTCACTC GAGTGAGT G GTTTGGCC

3590 GCCTCGGC GGCTAGCTACAACGA CAAACACT AGTGTTTG G GCCGAGGC

Table 16

3596 ATGCAGGC GGCTAGCTACAACGA CTCGGCCA TGGCCGAG G GCCTGCAT

3600 GGACATGC GGCTAGCTACAACGA AGGCCTCG ,CGAGGCCT G GCATGTCC

3602 CCGGACAT GGCTAGCTACAACGA GCAGGCCT AGGCCTGC A ATGTCCGG

3604 AGCCGGAC GGCTAGCTACAACGA ATGCAGGC GCCTGCAT G GTCCGGCT

3609 CCTTCAGC GGCTAGCTACAACGA CGGACATG CATGTCCG G GCTGAAGG

3616 CACTCAGC GGCTAGCTACAACGA CTTCAGCC GGCTGAAG G GCTGAGTG

3621 CCGGACAC GGCTAGCTACAACGA TCAGCCTT AAGGCTGA G GTGTCCGG

3623 AGCCGGAC GGCTAGCTACAACGA ACTCAGCC GGCTGAGT G GTCCGGCT

3628 GCCTCAGC GGCTAGCTACAACGA CGGACACT AGTGTCCG G GCTGAGGC

3634 GCTCAGGC GGCTAGCTACAACGA CTCAGCCG CGGCTGAG G GCCTGAGC

3640 ACACTCGC GGCTAGCTACAACGA TCAGGCCT AGGCCTGA G GCGAGTGT

3644 CTGGACAC GGCTAGCTACAACGA TCGCTCAG CTGAGCGA G GTGTCCAG

3646 GGCTGGAC GGCTAGCTACAACGA ACTCGCTC GAGCGAGT G GTCCAGCC

3651 CCCTTGGC GGCTAGCTACAACGA TGGACACT AGTGTCCA G GCCAAGGG

3658 CACTCAGC GGCTAGCTACAACGA CCTTGGCT AGCCAAGG G GCTGAGTG

3663 CTGGACAC GGCTAGCTACAACGA TCAGCCCT AGGGCTGA G GTGTCCAG

3665 TGCTGGAC GGCTAGCTACAACGA ACTCAGCC GGCTGAGT G GTCCAGCA

3670 AGGTGTGC GGCTAGCTACAACGA TGGACACT AGTGTCCA G GCACACCT

3672 GCAGGTGT GGCTAGCTACAACGA GCTGGACA TGTCCAGC A ACACCTGC

3674 CGGCAGGT GGCTAGCTACAACGA GTGCTGGA TCCAGCAC A ACCTGCCG

3678 AAGACGGC GGCTAGCTACAACGA AGGTGTGC GCACACCT G GCCGTCTT

3681 GTGAAGAC GGCTAGCTACAACGA GGCAGGTG CACCTGCC G GTCTTCAC

3687 GGGGAAGT GGCTAGCTACAACGA GAAGACGG CCGTCTTC A ACTTCCCC

3695 CAGCCTGT GGCTAGCTACAACGA GGGGAAGT ACTTCCCC A ACAGGCTG

3699 GCGCCAGC GGCTAGCTACAACGA CTGTGGGG CCCCACAG G GCTGGCGC

3703 CCGAGCGC GGCTAGCTACAACGA CAGCCTGT ACAGGCTG G GCGCTCGG

3705 AGCCGAGC GGCTAGCTACAACGA GCCAGCCT AGGCTGGC G GCTCGGCT

3710 GGTGGAGC GGCTAGCTACAACGA CGAGCGCC GGCGCTCG G GCTCCACC

3715 CCTGGGGT GGCTAGCTACAACGA GGAGCCGA TCGGCTCC A ACCCCAGG

3723 AAGCTGGC GGCTAGCTACAACGA CCTGGGGT ACCCCAGG G GCCAGCTT

3727 GGAAAAGC GGCTAGCTACAACGA TGGCCCTG CAGGGCCA G GCTTTTCC

Table 16

3737 CTCCTGGT GGCTAGCTACAACGA GAGGAAAA TTTTCCTC A ACCAGGAG

3744 AGCCGGGC GGCTAGCTACAACGA TCCTGGTG CACCAGGA G GCCCGGCT

3749 GTGGAAGC GGCTAGCTACAACGA CGGGCTCC GGAGCCCG G GCTTCCAC

3755 TGGGGAGT GGCTAGCTACAACGA GGAAGCCG CGGCTTCC A ACTCCCCA

3762 TCCTATGT GGCTAGCTACAACGA GGGGAGTG CACTCCCC A ACATAGGA

3764 ATTCCTAT GGCTAGCTACAACGA GTGGGGAG CTCCCCAC A ATAGGAAT

3770 TGGACTAT GGCTAGCTACAACGA TCCTATGT ACATAGGA A ATAGTCCA

3773 GGATGGAC GGCTAGCTACAACGA TATTCCTA TAGGAATA G GTCCATCC

3777 CTGGGGAT GGCTAGCTACAACGA GGACTATT AATAGTCC A ATCCCCAG

3785 TGGCGAAT GGCTAGCTACAACGA CTGGGGAT ATCCCCAG A ATTCGCCA

3789 ACAATGGC GGCTAGCTACAACGA GAATCTGG CCAGATTC G GCCATTGT

3792 TGAACAAT GGCTAGCTACAACGA GGCGAATC GATTCGCC A ATTGTTCA

3795 GGGTGAAC GGCTAGCTACAACGA AATGGCGA TCGCCATT G GTTCACCC

3799 CGAGGGGT GGCTAGCTACAACGA GAACAATG CATTGTTC A ACCCCTCG

3806 GGCAGGGC GGCTAGCTACAACGA GAGGGGTG CACCCCTC G GCCCTGCC

3811 AGGAGGGC GGCTAGCTACAACGA AGGGCGAG CTCGCCCT G GCCCTCCT

3821 TGGAAGGC GGCTAGCTACAACGA AAAGGAGG CCTCCTTT G GCCTTCCA

3828 GTGGGGGT GGCTAGCTACAACGA GGAAGGCA TGCCTTCC A ACCCCCAC

3834 TGGATGGT GGCTAGCTACAACGA GGGGGTGG CCACCCCC A ACCATCCA

3837 ACCTGGAT GGCTAGCTACAACGA GGTGGGGG CCCCCACC A ATCCAGGT

3843 GTCTCCAC GGCTAGCTACAACGA CTGGATGG CCATCCAG G GTGGAGAC

3849 CTCAGGGT GGCTAGCTACAACGA CTCCACCT AGGTGGAG A ACCCTGAG

3861 CCCAGGGT GGCTAGCTACAACGA CCTTCTCA TGAGAAGG A ACCCTGGG

3870 CCCAGAGC GGCTAGCTACAACGA TCCCAGGG CCCTGGGA G GCTCTGGG

3879 CTCCAAAT GGCTAGCTACAACGA TCCCAGAG CTCTGGGA A ATTTGGAG

3886 TTGGTCAC GGCTAGCTACAACGA TCCAAATT AATTTGGA G GTGACCAA

3889 CCTTTGGT GGCTAGCTACAACGA CACTCCAA TTGGAGTG A ACCAAAGG

3896 GGGCACAC GGCTAGCTACAACGA CTTTGGTC GACCAAAG G GTGTGCCC

3898 CAGGGCAC GGCTAGCTACAACGA ACCTTTGG CCAAAGGT G GTGCCCTG

3900 TACAGGGC GGCTAGCTACAACGA ACACCTTT AAAGGTGT G GCCCTGTA

3905 CTGTGTAC GGCTAGCTACAACGA AGGGCACA TGTGCCCT G GTACACAG

Table 16

3907 GCCTGTGT GGCTAGCTACAACGA ACAGGGCA TGCCCTGT A ACACAGGC

3909 TCGCCTGT GGCTAGCTACAACGA GTACAGGG CCCTGTAC A ACAGGCGA

3913 GTCCTCGC GGCTAGCTACAACGA CTGTGTAC GTACACAG G GCGAGGAC

3919 TGCAGGGT GGCTAGCTACAACGA CCTCGCCT AGGCGAGG A ACCCTGCA

3924 CCAGGTGC GGCTAGCTACAACGA AGGGTCCT AGGACCCT G GCACCTGG

3926 ATCCAGGT GGCTAGCTACAACGA GCAGGGTC GACCCTGC A ACCTGGAT

3932 ACCCCCAT GGCTAGCTACAACGA CCAGGTGC GCACCTGG A ATGGGGGT

3938 ACAGGGAC GGCTAGCTACAACGA CCCCATCC GGATGGGG G GTCCCTGT

3944 TGACCCAC GGCTAGCTACAACGA AGGGACCC GGGTCCCT G GTGGGTCA

3948 AATTTGAC GGCTAGCTACAACGA CCACAGGG CCCTGTGG G GTCAAATT

3953 CCCCCAAT GGCTAGCTACAACGA TTGACCCA TGGGTCAA A ATTGGGGG

3964 CACAGCAC GGCTAGCTACAACGA CTCCCCCC GGGGGGAG G GTGCTGTG

3966 CCCACAGC GGCTAGCTACAACGA ACCTCCCC GGGGAGGT G GCTGTGGG

3969 ACTCCCAC GGCTAGCTACAACGA AGCACCTC GAGGTGCT G GTGGGAGT

3975 TATTTTAC GGCTAGCTACAACGA TCCCACAG CTGTGGGA G GTAAAATA

3980 TTCAGTAT GGCTAGCTACAACGA TTTACTCC GGAGTAAA A ATACTGAA

3982 TATTCAGT GGCTAGCTACAACGA ATTTTACT AGTAAAAT A ACTGAATA

3987 TCATATAT GGCTAGCTACAACGA TCAGTATT AATACTGA A ATATATGA

3989 ACTCATAT GGCTAGCTACAACGA ATTCAGTA TACTGAAT A ATATGAGT

3991 AAACTCAT GGCTAGCTACAACGA ATATTCAG CTGAATAT A ATGAGTTT

3995 TGAAAAAC GGCTAGCTACAACGA TCATATAT ATATATGA G GTTTTTCA

4003 TTCAAAAC GGCTAGCTACAACGA TGAAAAAC GTTTTTCA G GTTTTGAA

Seql = TERT (Homo sapiens telomerase reverse transcriptase (TERT) mRNA, 4015 bp); Nakamura et al, Science 277 (5328), 955-959 (1997) Cut Site = R/Y (Purine/Pyrimidine)

Stem Length = 8 . Core Sequence = GGCTAGCTACAACGA

Table 17

Table 17: Anti-TERT HH and G-Cleaver Ribozymes

Table 18 Table 18: Human BACE Hammerhead Ribozyme and Target Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

9 CCACGCGU C CGCAGCCC 1 GGGCUGCG CUGAUGAG X CGAA ACGCGUGG 1776

47 AGCUGGAU U AUGGUGGC 2 GCCACCAU CUGAUGAG X CGAA AUCCAGCU 1777

48 GCUGGAUU A UGGUGGCC 3 GGCCACCA CUGAUGAG X CGAA AAUCCAGC 1778

93 GGAGCCCU U GCCCCUGC 4 GCAGGGGC CUGAUGAG X CGAA AGGGCUCC 1779

163 CCGCCCCU C CCAGCCCC 5 GGGGCUGG CUGAUGAG X CGAA AGGGGCGG 1780

221 GCCGAUGU A GCGGGCUC 6 GAGCCCGC CUGAUGAG X CGAA ACAUCGGC 1781

229 AGCGGGCU C CGGAUCCC 7 GGGAUCCG CUGAUGAG X CGAA AGCCCGCU 1782

235 CUCCGGAU C CCAGCCUC 8 GAGGCUGG CUGAUGAG X CGAA AUCCGGAG 1783

243 CCCAGCCU C UCCCCUGC 9 GCAGGGGA CUGAUGAG X CGAA AGGCUGGG 1784

245 CAGCCUCU C CCCUGCUC 10 GAGCAGGG CUGAUGAG X CGAA AGAGGCUG 1785

253 CCCCUGCU C CCGUGCUC 11 GAGCACGG CUGAUGAG X CGAA AGCAGGGG 1786

261 CCCGUGCU C UGCGGAUC 12 GAUCCGCA CUGAUGAG X CGAA AGCACGGG 1787

269 CUGCGGAU C UCCCCUGA 13 UCAGGGGA CUGAUGAG X CGAA AUCCGCAG 1788

271 GCGGAUCU C CCCUGACC 14 GGUCAGGG CUGAUGAG X CGAA AGAUCCGC 1789

283 UGACCGCU C UCCACAGC 15 GCUGUGGA CUGAUGAG X CGAA AGCGGUCA 1790

285 ACCGCUCU c CACAGCCC 16 GGGCUGUG CUGAUGAG X CGAA AGAGCGGU 1791

334 CCUGGCGU c CUGAUGCC 17 GGCAUCAG CUGAUGAG X CGAA ACGCCAGG 1792

351 CCCAAGCU c CCUCUCCU 18 AGGAGAGG CUGAUGAG X CGAA AGCUUGGG 1793

355 AGCUCCCU c UCCUGAGA 19 UCUCAGGA CUGAUGAG X CGAA AGGGAGCU 1794

357 CUCCCUCU c CUGAGAAG 20 CUUCUCAG CUGAUGAG X CGAA AGAGGGAG 1795

386 CCCAGACU U GGGGGCAG 21 CUGCCCCC CUGAUGAG X CGAA AGUCUGGG 1796

477 CCCUGGCU c CUGCUGUG 22 CACAGCAG CUGAUGAG X CGAA AGCCAGGG 1797

531 CACGGCAU c CGGCUGCC 23 GGCAGCCG CUGAUGAG X CGAA AUGCCGUG 1798

632 GGGCAGCU u UGUGGAGA 24 UCUCCACA CUGAUGAG X CGAA AGCUGCCC 1799

633 GGCAGCUU u GUGGAGAU 25 AUCUCCAC CUGAUGAG X CGAA AAGCUGCC 1800

665 GGGCAAGU c GGGGCAGG 26 CCUGCCCC CUGAUGAG X CGAA ACUUGCCC 1801

677 GCAGGGCU A CUACGUGG 27 CCACGUAG CUGAUGAG X CGAA AGCCCUGC 1802

680 GGGCUACU A CGUGGAGA 28 UCUCCACG CUGAUGAG X CGAA AGUAGCCC 1803

717 CAGACGCU C AACAUCCU 29 AGGAUGUU CUGAUGAG X CGAA AGCGUCUG 1804

723 CUCAACAU C CUGGUGGA 30 UCCACCAG CUGAUGAG X CGAA AUGUUGAG 1805

733 UGGUGGAU A CAGGCAGC 31 GCUGCCUG CUGAUGAG X CGAA AUCCACCA 1806

745 GCAGCAGU A ACUUUGCA 32 UGCAAAGU CUGAUGAG X CGAA ACUGCUGC 1807

749 CAGUAACU U UGCAGUGG 33 CCACUGCA CUGAUGAG X CGAA AGUUACUG 1808

750 AGUAACUU U GCAGUGGG 34 CCCACUGC CUGAUGAG X CGAA AAGUUACU 1809

776 CCACCCCU U CCUGCAUC 35 GAUGCAGG CUGAUGAG X CGAA AGGGGUGG 1810

777 CACCCCUU C CUGCAUCG 36 CGAUGCAG CUGAUGAG X CGAA AAGGGGUG 1811

784 UCCUGCAU C GCUACUAC 37 GUAGUAGC CUGAUGAG X CGAA AUGCAGGA 1812

788 GCAUCGCU A CUACCAGA 38 UCUGGUAG CUGAUGAG X CGAA AGCGAUGC 1813

791 UCGCUACU A CCAGAGGC 39 GCCUCUGG CUGAUGAG X CGAA AGUAGCGA 1814

806 GCAGCUGU C CAGCACAU 40 AUGUGCUG CUGAUGAG X CGAA ACAGCUGC 1815

815 CAGCACAU A CCGGGACC 41 GGUCCCGG CUGAUGAG X CGAA AUGUGCUG 1816

825 CGGGACCU C CGGAAGGG 42 CCCUUCCG CUGAUGAG X CGAA AGGUCCCG 1817

839 GGGUGUGU A UGUGCCCU 43 AGGGCACA CUGAUGAG X CGAA ACACACCC 1818

848 UGUGCCCU A CACCCAGG 44 CCUGGGUG CUGAUGAG X CGAA AGGGCACA 1819

891 GACCUGGU A AGCAUCCC 45 GGGAUGCU CUGAUGAG X CGAA ACCAGGUC 1820

897 GUAAGCAU C CCCCAUGG 46 CCAUGGGG CUGAUGAG X CGAA AUGCUUAC 1821

915 CCCAACGU C ACUGUGCG 47 CGCACAGU CUGAUGAG X CGAA ACGUUGGG 1822 Table 18

933 GCCAACAU U GCUGCCAU 48 AUGGCAGC CUGAUGAG X CGAA AUGUUGGC 1823

942 GCUGCCAU C ACUGAAUC 49 GAUUCAGU CUGAUGAG X CGAA AUGGCAGC 1824

950 CACUGAAU C AGACAAGU 50 ACUUGUCU CUGAUGAG X CGAA AUUCAGUG 1825

959 AGACAAGU U CUUCAUCA 51 UGAUGAAG CUGAUGAG X CGAA ACUUGUCU 1826

960 GACAAGUU C UUCAUCAA 52 UUGAUGAA CUGAUGAG X CGAA AACUUGUC 1827

962 CAAGUUCU U CAUCAACG 53 CGUUGAUG CUGAUGAG X CGAA AGAACUUG 1828

963 AAGUUCUU C AUCAACGG 54 CCGUUGAU CUGAUGAG X CGAA AAGAACUU 1829

966 UUCUUCAU C AACGGCUC 55 GAGCCGUU CUGAUGAG X CGAA AUGAAGAA 1830

974 CAACGGCU C CAACUGGG 56 CCCAGUUG CUGAUGAG X CGAA AGCCGUUG 1831

990 GAAGGCAU C CUGGGGCU 57 AGCCCCAG CUGAUGAG X CGAA AUGCCUUC 1832

1004 GCUGGCCU A UGCUGAGA 58 UCUCAGCA CUGAUGAG X CGAA AGGCCAGC 1833

1014 GCUGAGAU U GCCAGGCC 59 GGCCUGGC CUGAUGAG X CGAA AUCUCAGC 1834

1031 UGACGACU C CCUGGAGC 60 GCUCCAGG CUGAUGAG X CGAA AGUCGUCA 1835

1042 UGGAGCCU U UCUUUGAC 61 GUCAAAGA CUGAUGAG X CGAA AGGCUCCA 1836

1043 GGAGCCUU U CUUUGACU 62 AGUCAAAG CUGAUGAG X CGAA AAGGCUCC 1837

1044 GAGCCUUU C UUUGACUC 63 GAGUCAAA CUGAUGAG X CGAA AAAGGCUC 1838

1046 GCCUUUCU U UGACUCUC 64 GAGAGUCA CUGAUGAG X CGAA AGAAAGGC 1839

1047 CCUUUCUU U GACUCUCU 65 AGAGAGUC CUGAUGAG X CGAA AAGAAAGG 1840

1052 CUUUGACU C UCUGGUAA 66 UUACCAGA CUGAUGAG X CGAA AGUCAAAG 1841

1054 UUGACUCU C UGGUAAAG 67 CUUUACCA CUGAUGAG X CGAA AGAGUCAA 1842

1059 UCUCUGGU A AAGCAGAC 68 GUCUGCUU CUGAUGAG X CGAA ACCAGAGA 1843

1074 ACCCACGU U CCCAACCU 69 AGGUUGGG CUGAUGAG X CGAA ACGUGGGU 1844

1075 CCCACGUU C CCAACCUC 70 GAGGUUGG CUGAUGAG X CGAA AACGUGGG 1845

1083 CCCAACCU C UUCUCCCU 71 AGGGAGAA CUGAUGAG X CGAA AGGUUGGG 1846

1085 CAACCUCU U CUCCCUGC 72 GCAGGGAG CUGAUGAG X CGAA AGAGGUUG 1847

1086 AACCUCUU C UCCCUGCA 73 UGCAGGGA CUGAUGAG X CGAA AAGAGGUU 1848

1088 CCUCUUCU C CCUGCAGC 74 GCUGCAGG CUGAUGAG X CGAA AGAAGAGG 1849

1098 CUGCAGCU U UGUGGUGC 75 GCACCACA CUGAUGAG X CGAA AGCUGCAG 1850

1099 UGCAGCUU U GUGGUGCU 76 AGCACCAC CUGAUGAG X CGAA AAGCUGCA 1851

1112 UGCUGGCU U CCCCCUCA 77 UGAGGGGG CUGAUGAG X CGAA AGCCAGCA 1852

1113 GCUGGCUU C CCCCUCAA 78 UUGAGGGG CUGAUGAG X CGAA AAGCCAGC 1853

1119 UUCCCCCU C AACCAGUC 79 GACUGGUU CUGAUGAG X CGAA AGGGGGAA 1854

1127 CAACCAGU c UGAAGUGC 80 GCACUUCA CUGAUGAG X CGAA ACUGGUUG 1855

1142 GCUGGCCU c UGUCGGAG 81 CUCCGACA CUGAUGAG X CGAA AGGCCAGC 1856

1146 GCCUCUGU c GGAGGGAG 82 CUCCCUCC CUGAUGAG X CGAA ACAGAGGC 1857

1161 AGCAUGAU c AUUGGAGG 83 CCUCCAAU CUGAUGAG X CGAA AUCAUGCU 1858

1164 AUGAUCAU u GGAGGUAU 84 AUACCUCC CUGAUGAG X CGAA AUGAUCAU 1859

1171 UUGGAGGU A UCGACCAC 85 GUGGUCGA CUGAUGAG X CGAA ACCUCCAA 1860

1173 GGAGGUAU C GACCACUC 86 GAGUGGUC CUGAUGAG X CGAA AUACCUCC 1861

1181 CGACCACU C GCUGUACA 87 UGUACAGC CUGAUGAG X CGAA AGUGGUCG 1862

1187 CUCGCUGU A CACAGGCA 88 UGCCUGUG CUGAUGAG X CGAA ACAGCGAG 1863

1198 CAGGCAGU C UCUGGUAU 89 AUACCAGA CUGAUGAG X CGAA ACUGCCUG 1864

1200 GGCAGUCU C UGGUAUAC 90 GUAUACCA CUGAUGAG X CGAA AGACUGCC 1865

1205 UCUCUGGU A UACACCCA 91 UGGGUGUA CUGAUGAG X CGAA ACCAGAGA 1866

1207 UCUGGUAU A CACCCAUC 92 GAUGGGUG CUGAUGAG X CGAA AUACCAGA 1867

1215 ACACCCAU C CGGCGGGA 93 UCCCGCCG CUGAUGAG X CGAA AUGGGUGU 1868

1229 GGAGUGGU A UUAUGAGG 94 CCUCAUAA CUGAUGAG X CGAA ACCACUCC 1869

1231 AGUGGUAU U AUGAGGUG 95 CACCUCAU CUGAUGAG X CGAA AUACCACU 1870

1232 GUGGUAUU A UGAGGUGA 96 UCACCUCA CUGAUGAG X CGAA AAUACCAC 1871

1242 GAGGUGAU C AUUGUGCG 97 CGCACAAU CUGAUGAG X CGAA AUCACCUC 1872

1245 GUGAUCAU U GUGCGGGU 98 ACCCGCAC CUGAUGAG X CGAA AUGAUCAC 1873 Table 18

1260 GUGGAGAU C AAUGGACA 99 UGUCCAUU CUGAUGAG X CGAA AUCUCCAC 1874

1273 GACAGGAU C UGAAAAUG 100 CAUUUUCA CUGAUGAG X CGAA AUCCUGUC 1875

1295 CAAGGAGU A CAACUAUG 101 CAUAGUUG CUGAUGAG X CGAA ACUCCUUG 1876

1301 GUACAACU A UGACAAGA 102 UCUUGUCA CUGAUGAG X CGAA AGUUGUAC 1877

1314 AAGAGCAU U GUGGACAG 103 CUGUCCAC CUGAUGAG X CGAA AUGCUCUU 1878

1338 ACCAACCU U CGUUUGCC 104 GGCAAACG CUGAUGAG X CGAA AGGUUGGU 1879

1339 CCAACCUU C GUUUGCCC 105 GGGCAAAC CUGAUGAG X CGAA AAGGUUGG 1880

1342 ACCUUCGU u UGCCCAAG 106 CUUGGGCA CUGAUGAG X CGAA ACGAAGGU 1881

1343 CCUUCGUU u GCCCAAGA 107 UCUUGGGC CUGAUGAG X CGAA AACGAAGG 1882

1358 GAAAGUGU u UGAAGCUG 108 CAGCUUCA CUGAUGAG X CGAA ACACUUUC 1883

1359 AAAGUGUU u GAAGCUGC 109 GCAGCUUC CUGAUGAG X CGAA AACACUUU 1884

1371 GCUGCAGU c AAAUCCAU 110 AUGGAUUU CUGAUGAG X CGAA ACUGCAGC 1885

1376 AGUCAAAU c CAUCAAGG 111 CCUUGAUG CUGAUGAG X CGAA AUUUGACU 1886

1380 AAAUCCAU c AAGGCAGC 112 GCUGCCUU CUGAUGAG X CGAA AUGGAUUU 1887

1391 GGCAGCCU c CUCCACGG 113 CCGUGGAG CUGAUGAG X CGAA AGGCUGCC 1888

1394 AGCCUCCU c CACGGAGA 114 UCUCCGUG CUGAUGAG X CGAA AGGAGGCU 1889

1406 GGAGAAGU u CCCUGAUG 115 CAUCAGGG CUGAUGAG X CGAA ACUUCUCC 1890

1407 GAGAAGUU c CCUGAUGG 116 CCAUCAGG CUGAUGAG X CGAA AACUUCUC 1891

1417 CUGAUGGU u UCUGGCUA 117 UAGCCAGA CUGAUGAG X CGAA ACCAUCAG 1892

1418 UGAUGGUU u CUGGCUAG 118 CUAGCCAG CUGAUGAG X CGAA AACCAUCA 1893

1419 GAUGGUUU c UGGCUAGG 119 CCUAGCCA CUGAUGAG X CGAA AAACCAUC 1894

1425 UUCUGGCU A GGAGAGCA 120 UGCUCUCC CUGAUGAG X CGAA AGCCAGAA 1895

1465 CCACCCCU u GGAACAUU 121 AAUGUUCC CUGAUGAG X CGAA AGGGGUGG 1896

1473 UGGAACAU u UUCCCAGU 122 ACUGGGAA CUGAUGAG X CGAA AUGUUCCA 1897

1474 GGAACAUU u UCCCAGUC 123 GACUGGGA CUGAUGAG X CGAA AAUGUUCC 1898

1475 GAACAUUU u CCCAGUCA 124 UGACUGGG CUGAUGAG X CGAA AAAUGUUC 1899

1476 AACAUUUU c CCAGUCAU 125 AUGACUGG CUGAUGAG X CGAA AAAAUGUU 1900

1482 UUCCCAGU c AUCUCACU 126 AGUGAGAU CUGAUGAG X CGAA ACUGGGAA 1901

1485 CCAGUCAU c UCACUCUA 127 UAGAGUGA CUGAUGAG X CGAA AUGACUGG 1902

1487 AGUCAUCU c ACUCUACC 128 GGUAGAGU CUGAUGAG X CGAA AGAUGACU 1903

1491 AUCUCACU c UACCUAAU 129 AUUAGGUA CUGAUGAG X CGAA AGUGAGAU 1904

1493 CUCACUCU A CCUAAUGG 130 CCAUUAGG CUGAUGAG X CGAA AGAGUGAG 1905

1497 CUCUACCU A AUGGGUGA 131 UCACCCAU CUGAUGAG X CGAA AGGUAGAG 1906

1509 GGUGAGGU U ACCAACCA 132 UGGUUGGU CUGAUGAG X CGAA ACCUCACC 1907

1510 GUGAGGUU A CCAACCAG 133 CUGGUUGG CUGAUGAG X CGAA AACCUCAC 1908

1520 CAACCAGU C CUUCCGCA 134 UGCGGAAG CUGAUGAG X CGAA ACUGGUUG 1909

1523 CCAGUCCU U CCGCAUCA 135 UGAUGCGG CUGAUGAG X CGAA AGGACUGG 1910

1524 CAGUCCUU C CGCAUCAC 136 GUGAUGCG CUGAUGAG X CGAA AAGGACUG 1911

1530 UUCCGCAU C ACCAUCCU 137 AGGAUGGU CUGAUGAG X CGAA AUGCGGAA 1912

1536 AUCACCAU C CUUCCGCA 138 UGCGGAAG CUGAUGAG X CGAA AUGGUGAU 1913

1539 ACCAUCCU U CCGCAGCA 139 UGCUGCGG CUGAUGAG X CGAA AGGAUGGU 1914

1540 CCAUCCUU C CGCAGCAA 140 UUGCUGCG CUGAUGAG X CGAA AAGGAUGG 1915

1550 GCAGCAAU A CCUGCGGC 141 GCCGCAGG CUGAUGAG X CGAA AUUGCUGC 1916

1580 GGCCACGU C CCAAGACG 142 CGUCUUGG CUGAUGAG X CGAA ACGUGGCC 1917

1594 ACGACUGU U ACAAGUUU 143 AAACUUGU CUGAUGAG X CGAA ACAGUCGU 1918

1595 CGACUGUU A CAAGUUUG 144 CAAACUUG CUGAUGAG X CGAA AACAGUCG 1919

1601 UUACAAGU U UGCCAUCU 145 AGAUGGCA CUGAUGAG X CGAA ACUUGUAA 1920

1602 UACAAGUU U GCCAUCUC 146 GAGAUGGC CUGAUGAG X CGAA AACUUGUA 1921

1608 UUUGCCAU C UCACAGUC 147 GACUGUGA CUGAUGAG X CGAA AUGGCAAA 1922

1610 UGCCAUCU C ACAGUCAU 148 AUGACUGU CUGAUGAG X CGAA AGAUGGCA 1923

1616 CUCACAGU C AUCCACGG 149 CCGUGGAU CUGAUGAG X CGAA ACUGUGAG 1924 Table 18

1619 ACAGUCAU C CACGGGCA 150 UGCCCGUG CUGAUGAG X CGAA AUGACUGU 1925

1632 GGCACUGU U AUGGGAGC 151 GCUCCCAU CUGAUGAG X CGAA ACAGUGCC 1926

1633 GCACUGUU A UGGGAGCU 152 AGCUCCCA CUGAUGAG X CGAA AACAGUGC 1927

1644 GGAGCUGU U AUCAUGGA 153 UCCAUGAU CUGAUGAG X CGAA ACAGCUCC 1928

1645 GAGCUGUU A UCAUGGAG 154 CUCCAUGA CUGAUGAG X CGAA AACAGCUC 1929

1647 GCUGUUAU C AUGGAGGG 155 CCCUCCAU CUGAUGAG X CGAA AUAACAGC 1930

1658 GGAGGGCU U CUACGUUG 156 CAACGUAG CUGAUGAG X CGAA AGCCCUCC 1931

1659 GAGGGCUU C UACGUUGU 157 ACAACGUA CUGAUGAG X CGAA AAGCCCUC 1932

1661 GGGCUUCU A CGUUGUCU 158 AGACAACG CUGAUGAG X CGAA AGAAGCCC 1933

1665 UUCUACGU U GUCUUUGA 159 UCAAAGAC CUGAUGAG X CGAA ACGUAGAA 1934

1668 UACGUUGU C UUUGAUCG 160 CGAUCAAA CUGAUGAG X CGAA ACAACGUA 1935

1670 CGUUGUCU U UGAUCGGG 161 CCCGAUCA CUGAUGAG X CGAA AGACAACG 1936

1671 GUUGUCUU U GAUCGGGC 162 GCCCGAUC CUGAUGAG X CGAA AAGACAAC 1937

1675 UCUUUGAU C GGGCCCGA 163 UCGGGCCC CUGAUGAG X CGAA AUCAAAGA 1938

1692 AAACGAAU U GGCUUUGC 164 GCAAAGCC CUGAUGAG X CGAA AUUCGUUU 1939

1697 AAUUGGCU U UGCUGUCA 165 UGACAGCA CUGAUGAG X CGAA AGCCAAUU 1940

1698 AUUGGCUU U GCUGUCAG 166 CUGACAGC CUGAUGAG X CGAA AAGCCAAU 1941

1704 UUUGCUGU C AGCGCUUG 167 CAAGCGCU CUGAUGAG X CGAA ACAGCAAA 1942

1711 UCAGCGCU U GCCAUGUG 168 CACAUGGC CUGAUGAG X CGAA AGCGCUGA 1943

1730 CGAUGAGU U CAGGACGG 169 CCGUCCUG CUGAUGAG X CGAA ACUCAUCG 1944

1731 GAUGAGUU C AGGACGGC 170 GCCGUCCU CUGAUGAG X CGAA AACUCAUC 1945

1756 AAGGCCCU U UUGUCACC 171 GGUGACAA CUGAUGAG X CGAA AGGGCCUU 1946

1757 AGGCCCUU U UGUCACCU 172 AGGUGACA CUGAUGAG X CGAA AAGGGCCU 1947

1758 GGCCCUUU U GUCACCUU 173 AAGGUGAC CUGAUGAG X CGAA AAAGGGCC 1948

1761 CCUUUUGU C ACCUUGGA 174 UCCAAGGU CUGAUGAG X CGAA ACAAAAGG 1949

1766 UGUCACCU U GGACAUGG 175 CCAUGUCC CUGAUGAG X CGAA AGGUGACA 1950

1787 CUGUGGCU A CAACAUUC 176 GAAUGUUG CUGAUGAG X CGAA AGCCACAG 1951

1794 UACAACAU U CCACAGAC 177 GUCUGUGG CUGAUGAG X CGAA AUGUUGUA 1952

1795 ACAACAUU C CACAGACA 178 UGUCUGUG CUGAUGAG X CGAA AAUGUUGU 1953

1811 AGAUGAGU C AACCCUCA , 179 UGAGGGUU CUGAUGAG X CGAA ACUCAUCU 1954

1818 UCAACCCU C AUGACCAU 180 AUGGUCAU CUGAUGAG X CGAA AGGGUUGA 1955

1827 AUGACCAU A GCCUAUGU 181 ACAUAGGC CUGAUGAG X CGAA AUGGUCAU 1956

1832 CAUAGCCU A UGUCAUGG 182 CCAUGACA CUGAUGAG X CGAA AGGCUAUG 1957

1836 GCCUAUGU C AUGGCUGC 183 GCAGCCAU CUGAUGAG X CGAA ACAUAGGC 1958

1848 GCUGCCAU C UGCGCCCU 184 AGGGCGCA CUGAUGAG X CGAA AUGGCAGC 1959

1857 UGCGCCCU C UUCAUGCU 185 AGCAUGAA CUGAUGAG X CGAA AGGGCGCA 1960

1859 CGCCCUCU U CAUGCUGC 186 GCAGCAUG CUGAUGAG X CGAA AGAGGGCG 1961

1860 GCCCUCUU C AUGCUGCC 187 GGCAGCAU CUGAUGAG X CGAA AAGAGGGC 1962

1872 CUGCCACU C UGCCUCAU 188 AUGAGGCA CUGAUGAG X CGAA AGUGGCAG 1963

1878 CUCUGCCU C AUGGUGUG 189 CACACCAU CUGAUGAG X CGAA AGGCAGAG 1964

1888 UGGUGUGU C AGUGGCGC 190 GCGCCACU CUGAUGAG X CGAA ACACACCA 1965

1902 CGCUGCCU C CGCUGCCU 191 AGGCAGCG CUGAUGAG X CGAA AGGCAGCG 1966

1931 UGAUGACU U UGCUGAUG 192 CAUCAGCA CUGAUGAG X CGAA AGUCAUCA 1967

1932 GAUGACUU U GCUGAUGA 193 UCAUCAGC CUGAUGAG X CGAA AAGUCAUC 1968

1944 GAUGACAU C UCCCUGCU 194 AGCAGGGA CUGAUGAG X CGAA AUGUCAUC 1969

1946 UGACAUCU C CCUGCUGA 195 UCAGCAGG CUGAUGAG X CGAA AGAUGUCA 1970

1981 CAGAAGAU A GAGAUUCC 196 GGAAUCUC CUGAUGAG X CGAA AUCUUCUG 1971

1987 AUAGAGAU U CCCCUGGA 197 UCCAGGGG CUGAUGAG X CGAA AUCUCUAU 1972

1988 UAGAGAUU C CCCUGGAC 198 GUCCAGGG CUGAUGAG X CGAA AAUCUCUA 1973

2004 CCACACCU C CGUGGUUC 199 GAACCACG CUGAUGAG X CGAA AGGUGUGG 1974

2011 UCCGUGGU U CACUUUGG 200 CCAAAGUG CUGAUGAG X CGAA ACCACGGA 1975 Table 18

2012 CCGUGGUU c ACUUUGGU 201 ACCAAAGU CUGAUGAG X CGAA AACCACGG 1976

2016 GGUUCACU u UGGUCACA 202 UGUGACCA CUGAUGAG X CGAA AGUGAACC 1977

2017 GUUCACUU u GGUCACAA 203 UUGUGACC CUGAUGAG X CGAA AAGUGAAC 1978

2021 ACUUUGGU c ACAAGUAG 204 CUACUUGU CUGAUGAG X CGAA ACCAAAGU 1979

2028 UCACAAGU A GGAGACAC 205 GUGUCUCC CUGAUGAG X CGAA ACUUGUGA 1980

2063 GAGCACCU c AGGACCCU 206 AGGGUCCU CUGAUGAG X CGAA AGGUGCUC 1981

2072 AGGACCCU c CCCACCCA 207 UGGGUGGG CUGAUGAG X CGAA AGGGUCCU 1982

2091 AAAUGCCU c UGCCUUGA 208 UCAAGGCA CUGAUGAG X CGAA AGGCAUUU 1983

2097 CUCUGCCU u GAUGGAGA 209 UCUCCAUC CUGAUGAG X CGAA AGGCAGAG 1984

2129 AGGUGGGU u CCAGGGAC 210 GUCCCUGG CUGAUGAG X CGAA ACCCACCU 1985

2130 GGUGGGUU c CAGGGACU 211 AGUCCCUG CUGAUGAG X CGAA AACCCACC 1986

2141 GGGACUGU A CCUGUAGG 212 CCUACAGG CUGAUGAG X CGAA ACAGUCCC 1987

2147 GUACCUGU A GGAAACAG 213 CUGUUUCC CUGAUGAG X CGAA ACAGGUAC 1988

2177 GAAGCACU C UGCUGGCG 214 CGCCAGCA CUGAUGAG X CGAA AGUGCUUC 1989

2191 GCGGGAAU A CUCUUGGU 215 ACCAAGAG CUGAUGAG X CGAA AUUCCCGC 1990

2194 GGAAUACU C UUGGUCAC 216 GUGACCAA CUGAUGAG X CGAA AGUAUUCC 1991

2196 AAUACUCU u GGUCACCU 217 AGGUGACC CUGAUGAG X CGAA AGAGUAUU 1992

2200 CUCUUGGU C ACCUCAAA 218 UUUGAGGU CUGAUGAG X CGAA ACCAAGAG 1993

2205 GGUCACCU c AAAUUUAA 219 UUAAAUUU CUGAUGAG X CGAA AGGUGACC 1994

2210 CCUCAAAU u UAAGUCGG 220 CCGACUUA CUGAUGAG X CGAA AUUUGAGG 1995

2211 CUCAAAUU u AAGUCGGG 221 CCCGACUU CUGAUGAG X CGAA AAUUUGAG 1996

2212 UCAAAUUU A AGUCGGGA 222 UCCCGACU CUGAUGAG X CGAA AAAUUUGA 1997

2216 AUUUAAGU C GGGAAAUU 223 AAUUUCCC CUGAUGAG X CGAA ACUUAAAU 1998

2224 CGGGAAAU U CUGCUGCU 224 AGCAGCAG CUGAUGAG X CGAA AUUUCCCG 1999

2225 GGGAAAUU C UGCUGCUU 225 AAGCAGCA CUGAUGAG X CGAA AAUUUCCC 2000

2233 CUGCUGCU U GAAACUUC 226 GAAGUUUC CUGAUGAG X CGAA AGCAGCAG 2001

2240 UUGAAACU u CAGCCCUG 227 CAGGGCUG CUGAUGAG X CGAA AGUUUCAA 2002

2241 UGAAACUU c AGCCCUGA 228 UCAGGGCU CUGAUGAG X CGAA AAGUUUCA 2003

2254 CUGAACCU u UGUCCACC 229 GGUGGACA CUGAUGAG X CGAA AGGUUCAG 2004

2255 UGAACCUU u GUCCACCA 230 UGGUGGAC CUGAUGAG X CGAA AAGGUUCA 2005

2258 ACCUUUGU c CACCAUUC 231 GAAUGGUG CUGAUGAG X CGAA ACAAAGGU 2006

2265 UCCACCAU u CCUUUAAA 232 UUUAAAGG CUGAUGAG X CGAA AUGGUGGA 2007

2266 CCACCAUU c CUUUAAAU 233 AUUUAAAG CUGAUGAG X CGAA AAUGGUGG 2008

2269 CCAUUCCU u UAAAUUCU 234 AGAAUUUA CUGAUGAG X CGAA AGGAAUGG 2009

2270 CAUUCCUU u AAAUUCUC 235 GAGAAUUU CUGAUGAG X CGAA AAGGAAUG 2010

2271 AUUCCUUU A AAUUCUCC 236 GGAGAAUU CUGAUGAG X CGAA AAAGGAAU 2011

2275 CUUUAAAU U CUCCAACC 237 GGUUGGAG CUGAUGAG X CGAA AUUUAAAG 2012

2276 UUUAAAUU C UCCAACCC 238 GGGUUGGA CUGAUGAG X CGAA AAUUUAAA 2013

2278 UAAAUUCU c CAACCCAA 239 UUGGGUUG CUGAUGAG X CGAA AGAAUUUA 2014

2290 CCCAAAGU A UUCUUCUU 240 AAGAAGAA CUGAUGAG X CGAA ACUUUGGG 2015

2292 CAAAGUAU U CUUCUUUU 241 AAAAGAAG CUGAUGAG X CGAA AUACUUUG 2016

2293 AAAGUAUU C UUCUUUUC 242 GAAAAGAA CUGAUGAG X CGAA AAUACUUU 2017

2295 AGUAUUCU U CUUUUCUU 243 AAGAAAAG CUGAUGAG X CGAA AGAAUACU 2018

2296 GUAUUCUU C UUUUCUUA 244 UAAGAAAA CUGAUGAG X CGAA AAGAAUAC 2019

2298 AUUCUUCU U UUCUUAGU 245 ACUAAGAA CUGAUGAG X CGAA AGAAGAAU 2020

2299 UUCUUCUU U UCUUAGUU 246 AACUAAGA CUGAUGAG X CGAA AAGAAGAA 2021

2300 UCUUCUUU U CUUAGUUU 247 AAACUAAG CUGAUGAG X CGAA AAAGAAGA 2022

2301 cuucuuuu c UUAGUUUC 248 GAAACUAA CUGAUGAG X CGAA AAAAGAAG 2023

2303 ucuuuucu u AGUUUCAG 249 CUGAAACU CUGAUGAG X CGAA AGAAAAGA 2024

2304 cuuuucuu A GUUUCAGA 250 UCUGAAAC CUGAUGAG X CGAA AAGAAAAG 2025

2307 UUCUUAGU U UCAGAAGU 251 ACUUCUGA CUGAUGAG X CGAA ACUAAGAA 2026 Table 18

2308 UCUUAGUU U CAGAAGUA 252 UACUUCUG CUGAUGAG X CGAA AACUAAGA 2027

2309 CUUAGUUU C AGAAGUAC 253 GUACUUCU CUGAUGAG X CGAA AAACUAAG 2028

2316 UCAGAAGU A CUGGCAUC 254 GAUGCCAG CUGAUGAG X CGAA ACUUCUGA 2029

2324 ACUGGCAU C ACACGCAG 255 CUGCGUGU CUGAUGAG X CGAA AUGCCAGU 2030

2335 ACGCAGGU U ACCUUGGC 256 GCCAAGGU CUGAUGAG X CGAA ACCUGCGU 2031

2336 CGCAGGUU A CCUUGGCG 257 CGCCAAGG CUGAUGAG X CGAA AACCUGCG 2032

2340 GGUUACCU U GGCGUGUG 258 CACACGCC CUGAUGAG X CGAA AGGUAACC 2033

2350 GCGUGUGU C CCUGUGGU 259 ACCACAGG CUGAUGAG X CGAA ACACACGC 2034

2359 CCUGUGGU A CCCUGGCA 260 UGCCAGGG CUGAUGAG X CGAA ACCACAGG 2035

2384 ACCAAGCU U GUUUCCCU 261 AGGGAAAC CUGAUGAG X CGAA AGCUUGGU 2036

2387 AAGCUUGU U UCCCUGCU 262 AGCAGGGA CUGAUGAG X CGAA ACAAGCUU 2037

2388 AGCUUGUU U CCCUGCUG 263 CAGCAGGG CUGAUGAG X CGAA AACAAGCU 2038

2389 GCUUGUUU C CCUGCUGG 264 CCAGCAGG CUGAUGAG X CGAA AAACAAGC 2039

2405 GCCAAAGU C AGUAGGAG 265 CUCCUACU CUGAUGAG X CGAA ACUUUGGC 2040

2409 AAGUCAGU A GGAGAGGA 266 UCCUCUCC CUGAUGAG X CGAA ACUGACUU 2041

2426 UGCACAGU U UGCUAUUU 267 AAAUAGCA CUGAUGAG X CGAA ACUGUGCA 2042

2427 GCACAGUU u GCUAUUUG 268 CAAAUAGC CUGAUGAG X CGAA AACUGUGC 2043

2431 AGUUUGCU A UUUGCUUU 269 AAAGCAAA CUGAUGAG X CGAA AGCAAACU 2044

2433 UUUGCUAU U UGCUUUAG 270 CUAAAGCA CUGAUGAG X CGAA AUAGCAAA 2045

2434 UUGCUAUU U GCUUUAGA 271 UCUAAAGC CUGAUGAG X CGAA AAUAGCAA 2046

2438 UAUUUGCU U UAGAGACA 272 UGUCUCUA CUGAUGAG X CGAA AGCAAAUA 2047

2439 AUUUGCUU U AGAGACAG 273 CUGUCUCU CUGAUGAG X CGAA AAGCAAAU 2048

2440 UUUGCUUU A GAGACAGG 274 ccuσucuc CUGAUGAG X CGAA AAAGCAAA 2049

2455 GGGACUGU A UAAACAAG 275 CUUGUUUA CUGAUGAG X CGAA ACAGUCCC 2050

2457 GACUGUAU A AACAAGCC 276 GGCUUGUU CUGAUGAG X CGAA AUACAGUC 2051

2467 ACAAGCCU A ACAUUGGU , 277 ACCAAUGU CUGAUGAG X CGAA AGGCUUGU 2052

2472 CCUAACAU U GGUGCAAA 278 UUUGCACC CUGAUGAG X CGAA AUGUUAGG 2053

2484 GCAAAGAU U GCCUCUUG 279 CAAGAGGC CUGAUGAG X CGAA AUCUUUGC 2054

2489 GAUUGCCU C UUGAAUUA 280 UAAUUCAA CUGAUGAG X CGAA AGGCAAUC 2055

2491 UUGCCUCU U GAAUUAAA 281 UUUAAUUC CUGAUGAG X CGAA AGAGGCAA 2056

2496 UCUUGAAU U AAAAAAAA 282 UUUUUUUU CUGAUGAG X CGAA AUUCAAGA 2057

2497 CUUGAAUU A AAAAAAAA 283 UUUUUUUU CUGAUGAG X CGAA AAUUCAAG 2058

2510 AAAAAACU A GAAAAAAA 284 uuuuuuuc CUGAUGAG X CGAA AGUUUUUU 2059

Input Sequence = AF190725. Cut Site = G/ .

Stem Length = 8 . Core Sequence = CUGAUGAG X CGAA (X = GCCGUUAGGC or other stem II)

AF190725 (Homo sapiens beta- site APP cleaving enzyme (BACE) mRNA; 2526 bp)

Table 19 Table 19: Human BACE NCH Ribozyme and Target Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

10 CACGCGUC C GCAGCCCG 285 CGGGCUGC CUGAUGAG X CGAA IACGCGUG 2060

13 GCGUCCGC A GCCCGCCC 286 J GGGCGGGC CUGAUGAG X CGAA ICGGACGC 2061

16 UCCGCAGC C CGCCCGGG 287 CCCGGGCG CUGAUGAG X CGAA ICUGCGGA 2062

17 CCGCAGCC C GCCCGGGA 288 UCCCGGGC CUGAUGAG X CGAA IGCUGCGG 2063

20 CAGCCCGC C CGGGAGCU 289 AGCUCCCG CUGAUGAG X CGAA ICGGGCUG 2064

21 AGCCCGCC C GGGAGCUG 290 CAGCUCCC CUGAUGAG X CGAA IGCGGGCU 2065

28 CCGGGAGC U GCGAGCCG 291 CGGCUCGC CUGAUGAG X CGAA ICUCCCGG 2066

35 CUGCGAGC C GCGAGCUG 292 CAGCUCGC CUGAUGAG X CGAA ICUCGCAG 2067

42 CCGCGAGC U GGAUUAUG 293 CAUAAUCC CUGAUGAG X CGAA ICUCGCGG 2068

56 AUGGUGGC C UGAGCAGC 294 GCUGCUCA CUGAUGAG X CGAA ICCACCAU 2069

57 UGGUGGCC U GAGCAGCC 295 GGCUGCUC CUGAUGAG X CGAA IGCCACCA 2070

62 GCCUGAGC A GCCAACGC 296 GCGUUGGC CUGAUGAG X CGAA ICUCAGGC 2071

65 UGAGCAGC C AACGCAGC 297 GCUGCGUU CUGAUGAG X CGAA ICUGCUCA 2072

66 GAGCAGCC A ACGCAGCC 298 GGCUGCGU CUGAUGAG X CGAA IGCUGCUC 2073

71 GCCAACGC A GCCGCAGG 299 CCUGCGGC CUGAUGAG X CGAA ICGUUGGC 2074

74 AACGCAGC C GCAGGAGC 300 GCUCCUGC CUGAUGAG X CGAA ICUGCGUU 2075

77 GCAGCCGC A GGAGCCCG 301 CGGGCUCC CUGAUGAG X CGAA ICGGCUGC 2076

83 GCAGGAGC C CGGAGCCC 302 GGGCUCCG CUGAUGAG X CGAA ICUCCUGC 2077

84 CAGGAGCC C GGAGCCCU 303 AGGGCUCC CUGAUGAG X CGAA IGCUCCUG 2078

90 CCCGGAGC C CUUGCCCC 304 GGGGCAAG CUGAUGAG X CGAA ICUCCGGG 2079

91 CCGGAGCC C UUGCCCCU 305 AGGGGCAA CUGAUGAG X CGAA IGCUCCGG 2080

92 CGGAGCCC U UGCCCCUG 306 CAGGGGCA CUGAUGAG X CGAA IGGCUCCG 2081

96 GCCCUUGC C CCUGCCCG 307 CGGGCAGG CUGAUGAG X CGAA ICAAGGGC 2082

97 CCCUUGCC C CUGCCCGC 308 GCGGGCAG CUGAUGAG X CGAA IGCAAGGG 2083

98 CCUUGCCC C UGCCCGCG 309 CGCGGGCA CUGAUGAG X CGAA IGGCAAGG 2084

99 CUUGCCCC U GCCCGCGC 310 GCGCGGGC CUGAUGAG X CGAA IGGGCAAG 2085

102 GCCCCUGC C CGCGCCGC 311 GCGGCGCG CUGAUGAG X CGAA ICAGGGGC 2086

103 CCCCUGCC C GCGCCGCC 312 GGCGGCGC CUGAUGAG X CGAA IGCAGGGG 2087

108 GCCCGCGC C GCCGCCCG 313 CGGGCGGC CUGAUGAG X CGAA ICGCGGGC 2088

111 CGCGCCGC C GCCCGCCG 314 CGGCGGGC CUGAUGAG X CGAA ICGGCGCG 2089

114 GCCGCCGC C CGCCGGGG 315 CCCCGGCG CUGAUGAG X CGAA ICGGCGGC 2090

115 CCGCCGCC C GCCGGGGG 316 CCCCCGGC CUGAUGAG X CGAA IGCGGCGG 2091

118 CCGCCCGC C GGGGGGAC 317 GUCCCCCC CUGAUGAG X CGAA ICGGGCGG 2092

127 GGGGGGAC C AGGGAAGC 318 GCUUCCCU CUGAUGAG X CGAA IUCCCCCC 2093

128 GGGGGACC A GGGAAGCC 319 GGCUUCCC CUGAUGAG X CGAA IGUCCCCC 2094

136 AGGGAAGC C GCCACCGG 320 CCGGUGGC CUGAUGAG X CGAA ICUUCCCU 2095

139 GAAGCCGC C ACCGGCCC 321 GGGCCGGU CUGAUGAG X CGAA ICGGCUUC 2096

140 AAGCCGCC A CCGGCCCG 322 CGGGCCGG CUGAUGAG X CGAA IGCGGCUU 2097

142 GCCGCCAC C GGCCCGCC 323 GGCGGGCC CUGAUGAG X CGAA IUGGCGGC 2098

146 CCACCGGC C CGCCAUGC 324 GCAUGGCG CUGAUGAG X CGAA ICCGGUGG 2099

147 CACCGGCC C GCCAUGCC 325 GGCAUGGC CUGAUGAG X CGAA IGCCGGUG 2100

150 CGGCCCGC C AUGCCCGC 326 GCGGGCAU CUGAUGAG X CGAA ICGGGCCG 2101

151 GGCCCGCC A UGCCCGCC 327 GGCGGGCA CUGAUGAG X CGAA IGCGGGCC 2102

155 CGCCAUGC C CGCCCCUC 328 GAGGGGCG CUGAUGAG X CGAA ICAUGGCG 2103

156 GCCAUGCC C GCCCCUCC 329 GGAGGGGC CUGAUGAG X CGAA IGCAUGGC 2104

159 AUGCCCGC C CCUCCCAG 330 CUGGGAGG CUGAUGAG X CGAA ICGGGCAU 2105

160 UGCCCGCC C CUCCCAGC 331 GCUGGGAG CUGAUGAG X CGAA IGCGGGCA 2106 Table 19

161 GCCCGCCC C UCCCAGCC 332 GGCUGGGA CUGAUGAG X CGAA IGGCGGGC 2107

162 CCCGCCCC U CCCAGCCC 333 GGGCUGGG CUGAUGAG X CGAA IGGGCGGG 2108

164 CGCCCCUC C CAGCCCCG 334 CGGGGCUG CUGAUGAG X CGAA IAGGGGCG 2109

165 GCCCCUCC C AGCCCCGC 335 GCGGGGCU CUGAUGAG X CGAA IGAGGGGC 2110

166 CCCCUCCC A GCCCCGCC 336 GGCGGGGC CUGAUGAG X CGAA IGGAGGGG 2111

169 CUCCCAGC C CCGCCGGG 337 CCCGGCGG CUGAUGAG X CGAA ICUGGGAG 2112

170 UCCCAGCC C CGCCGGGA 338 UCCCGGCG CUGAUGAG X CGAA IGCUGGGA 2113

171 CCCAGCCC C GCCGGGAG 339 CUCCCGGC CUGAUGAG X CGAA IGGCUGGG 2114

174 AGCCCCGC C GGGAGCCC 340 GGGCUCCC CUGAUGAG X CGAA ICGGGGCU 2115

181 CCGGGAGC C CGCGCCCG 341 CGGGCGCG CUGAUGAG X CGAA ICUCCCGG 2116

182 CGGGAGCC C GCGCCCGC 342 GCGGGCGC CUGAUGAG X CGAA IGCUCCCG 2117

187 GCCCGCGC C CGCUGCCC 343 GGGCAGCG CUGAUGAG X CGAA ICGCGGGC 2118

188 CCCGCGCC C GCUGCCCA 344 UGGGCAGC CUGAUGAG X CGAA IGCGCGGG 2119

191 GCGCCCGC U GCCCAGGC 345 GCCUGGGC CUGAUGAG X CGAA ICGGGCGC 2120

194 CCCGCUGC C CAGGCUGG 346 CCAGCCUG CUGAUGAG X CGAA ICAGCGGG 2121

195 CCGCUGCC C AGGCUGGC 347 GCCAGCCU CUGAUGAG X CGAA IGCAGCGG 2122

196 CGCUGCCC A GGCUGGCC 348 GGCCAGCC CUGAUGAG X CGAA IGGCAGCG 2123

200 GCCCAGGC U GGCCGCCG 349 CGGCGGCC CUGAUGAG X CGAA ICCUGGGC 2124

204 AGGCUGGC C GCCGCCGU 350 ACGGCGGC CUGAUGAG X CGAA ICCAGCCU 2125

207 CUGGCCGC C GCCGUGCC 351 GGCACGGC CUGAUGAG X CGAA ICGGCCAG 2126

210 GCCGCCGC C GUGCCGAU 352 AUCGGCAC CUGAUGAG X CGAA ICGGCGGC 2127

215 CGCCGUGC C GAUGUAGC 353 GCUACAUC CUGAUGAG X CGAA ICACGGCG 2128

228 UAGCGGGC U CCGGAUCC 354 GGAUCCGG CUGAUGAG X CGAA ICCCGCUA 2129

230 GCGGGCUC C GGAUCCCA 355 UGGGAUCC CUGAUGAG X CGAA IAGCCCGC 2130

236 UCCGGAUC C CAGCCUCU 356 AGAGGCUG CUGAUGAG X CGAA IAUCCGGA 2131

237 CCGGAUCC C AGCCUCUC 357 GAGAGGCU CUGAUGAG X CGAA IGAUCCGG 2132

238 CGGAUCCC A GCCUCUCC 358 GGAGAGGC CUGAUGAG X CGAA IGGAUCCG 2133

241 AUCCCAGC C UCUCCCCU 359 AGGGGAGA CUGAUGAG X CGAA ICUGGGAU 2134

242 UCCCAGCC U CUCCCCUG 360 CAGGGGAG CUGAUGAG X CGAA IGCUGGGA 2135

244 CCAGCCUC U CCCCUGCU 361 AGCAGGGG CUGAUGAG X CGAA lAGGCUGG 2136

246 AGCCUCUC C CCUGCUCC 362 GGAGCAGG CUGAUGAG X CGAA IAGAGGCU 2137

247 GCCUCUCC C CUGCUCCC 363 GGGAGCAG CUGAUGAG X CGAA IGAGAGGC 2138

248 CCUCUCCC C UGCUCCCG 364 CGGGAGCA CUGAUGAG X CGAA IGGAGAGG 2139

249 CUCUCCCC U GCUCCCGU 365 ACGGGAGC CUGAUGAG X CGAA IGGGAGAG 2140

252 UCCCCUGC u CCCGUGCU 366 AGCACGGG CUGAUGAG X CGAA ICAGGGGA 2141

254 CCCUGCUC c CGUGCUCU 367 AGAGCACG CUGAUGAG X CGAA IAGCAGGG 2142

255 CCUGCUCC c GUGCUCUG 368 CAGAGCAC CUGAUGAG X CGAA IGAGCAGG 2143

260 UCCCGUGC u CUGCGGAU 369 AUCCGCAG CUGAUGAG X' CGAA ICACGGGA 2144

262 CCGUGCUC u GCGGAUCU 370 AGAUCCGC CUGAUGAG X CGAA IAGCACGG 2145

270 UGCGGAUC u CCCCUGAC 371 GUCAGGGG CUGAUGAG X CGAA IAUCCGCA 2146

272 CGGAUCUC c CCUGACCG 372 CGGUCAGG CUGAUGAG X CGAA IAGAUCCG 2147

273 GGAUCUCC c CUGACCGC 373 GCGGUCAG CUGAUGAG X CGAA IGAGAUCC 2148

274 GAUCUCCC c UGACCGCU 374 AGCGGUCA CUGAUGAG X CGAA IGGAGAUC 2149

275 AUCUCCCC u GACCGCUC 375 GAGCGGUC CUGAUGAG X CGAA IGGGAGAU 2150

279 CCCCUGAC c GCUCUCCA 376 UGGAGAGC CUGAUGAG X CGAA IUCAGGGG 2151

282 CUGACCGC u CUCCACAG 377 CUGUGGAG CUGAUGAG X CGAA ICGGUCAG 2152

284 GACCGCUC u CCACAGCC 378 GGCUGUGG CUGAUGAG X CGAA IAGCGGUC 2153

286 CCGCUCUC c ACAGCCCG 379 CGGGCUGU CUGAUGAG X CGAA IAGAGCGG 2154

287 CGCUCUCC A CAGCCCGG 380 CCGGGCUG CUGAUGAG X CGAA IGAGAGCG 2155

289 CUCUCCAC A GCCCGGAC 381 GUCCGGGC CUGAUGAG X CGAA IUGGAGAG 2156

292 UCCACAGC C CGGACCCG 382 CGGGUCCG CUGAUGAG X CGAA ICUGUGGA 2157 Table 19

293 CCACAGCC C GGACCCGG 383 CCGGGUCC CUGAUGAG X CGAA IGCUGUGG 2158

298 GCCCGGAC C CGGGGGCU 384 AGCCCCCG CUGAUGAG X CGAA IUCCGGGC 2159

299 CCCGGACC C GGGGGCUG 385 CAGCCCCC CUGAUGAG X CGAA IGUCCGGG 2160

306 CCGGGGGC U GGCCCAGG 386 CCUGGGCC CUGAUGAG X CGAA ICCCCCGG 2161

310 GGGCUGGC C CAGGGCCC 387 GGGCCCUG CUGAUGAG X CGAA ICCAGCCC 2162

311 GGCUGGCC C AGGGCCCU 388 AGGGCCCU CUGAUGAG X CGAA IGCCAGCC 2163

312 GCUGGCCC A GGGCCCUG 389 CAGGGCCC CUGAUGAG X CGAA IGGCCAGC 2164

317 CCCAGGGC C CUGCAGGC 390 GCCUGCAG CUGAUGAG X CGAA ICCCUGGG 2165

318 CCAGGGCC C UGCAGGCC 391 GGCCUGCA CUGAUGAG X CGAA IGCCCUGG 2166

319 CAGGGCCC U GCAGGCCC 392 GGGCCUGC CUGAUGAG X CGAA IGGCCCUG 2167

322 GGCCCUGC A GGCCCUGG 393 CCAGGGCC CUGAUGAG X CGAA ICAGGGCC 2168

326 CUGCAGGC C CUGGCGUC 394 GACGCCAG CUGAUGAG X CGAA ICCUGCAG 2169

327 UGCAGGCC C UGGCGUCC 395 GGACGCCA CUGAUGAG X CGAA IGCCUGCA 2170

328 GCAGGCCC U GGCGUCCU 396 AGGACGCC CUGAUGAG X CGAA IGGCCUGC 2171

335 CUGGCGUC C UGAUGCCC 397 GGGCAUCA CUGAUGAG X CGAA IACGCCAG 2172

336 UGGCGUCC u GAUGCCCC 398 GGGGCAUC CUGAUGAG X CGAA IGACGCCA 2173

342 CCUGAUGC c CCCAAGCU 399 AGCUUGGG CUGAUGAG X CGAA ICAUCAGG 2174

343 CUGAUGCC c CCAAGCUC 400 GAGCUUGG CUGAUGAG X CGAA IGCAUCAG 2175

344 UGAUGCCC c CAAGCUCC 401 GGAGCUUG CUGAUGAG X CGAA IGGCAUCA 2176

345 GAUGCCCC c AAGCUCCC 402 GGGAGCUU CUGAUGAG X CGAA IGGGCAUC 2177

346 AUGCCCCC A AGCUCCCU 403 AGGGAGCU CUGAUGAG X CGAA IGGGGCAU 2178

350 CCCCAAGC U CCCUCUCC 404 GGAGAGGG CUGAUGAG X CGAA ICUUGGGG 2179

352 CCAAGCUC C CUCUCCUG 405 CAGGAGAG CUGAUGAG X CGAA IAGCUUGG 2180

353 CAAGCUCC C UCUCCUGA 406 UCAGGAGA CUGAUGAG X CGAA IGAGCUUG 2181

354 AAGCUCCC u CUCCUGAG 407 CUCAGGAG CUGAUGAG X CGAA IGGAGCUU 2182

356 GCUCCCUC u CCUGAGAA 408 UUCUCAGG CUGAUGAG X CGAA IAGGGAGC 2183

358 UCCCUCUC c UGAGAAGC 409 GCUUCUCA CUGAUGAG X CGAA IAGAGGGA 2184

359 CCCUCUCC u GAGAAGCC 410 GGCUUCUC CUGAUGAG X CGAA IGAGAGGG 2185

367 UGAGAAGC c ACCAGCAC 411 GUGCUGGU CUGAUGAG X CGAA ICUUCUCA 2186

368 GAGAAGCC A CCAGCACC 412 GGUGCUGG CUGAUGAG X CGAA IGCUUCUC 2187

370 GAAGCCAC C AGCACCAC 413 GUGGUGCU CUGAUGAG X CGAA IUGGCUUC 2188

371 AAGCCACC A GCACCACC 414 GGUGGUGC CUGAUGAG X CGAA IGUGGCUU 2189

374 CCACCAGC A CCACCCAG 415 CUGGGUGG CUGAUGAG X CGAA ICUGGUGG 2190

376 ACCAGCAC C ACCCAGAC 416 GUCUGGGU CUGAUGAG X CGAA IUGCUGGU 2191

377 CCAGCACC A CCCAGACU 417 AGUCUGGG CUGAUGAG X CGAA IGUGCUGG 2192

379 AGCACCAC C CAGACUUG 418 CAAGUCUG CUGAUGAG X CGAA IUGGUGCU 2193

380 GCACCACC C AGACUUGG 419 CCAAGUCU CUGAUGAG X CGAA IGUGGUGC 2194

381 CACCACCC A GACUUGGG 420 CCCAAGUC CUGAUGAG X CGAA IGGUGGUG 2195

385 ACCCAGAC u UGGGGGCA 421 UGCCCCCA CUGAUGAG X CGAA lUCUGGGU 2196

393 UUGGGGGC A GGCGCCAG 422 CUGGCGCC CUGAUGAG X CGAA ICCCCCAA 2197

399 GCAGGCGC C AGGGACGG 423 CCGUCCCU CUGAUGAG X CGAA ICGCCUGC 2198

400 CAGGCGCC A GGGACGGA 424 UCCGUCCC CUGAUGAG X CGAA IGCGCCUG 2199

416 ACGUGGGC C AGUGCGAG 425 CUCGCACU CUGAUGAG X CGAA ICCCACGU 2200

417 CGUGGGCC A GUGCGAGC 426 GCUCGCAC CUGAUGAG X CGAA IGCCCACG 2201

426 GUGCGAGC C CAGAGGGC 427 GCCCUCUG CUGAUGAG X CGAA ICUCGCAC 2202

427 UGCGAGCC C AGAGGGCC 428 GGCCCUCU CUGAUGAG X CGAA IGCUCGCA 2203

428 GCGAGCCC A GAGGGCCC 429 GGGCCCUC CUGAUGAG X CGAA IGGCUCGC 2204

435 CAGAGGGC C CGAAGGCC 430 GGCCUUCG CUGAUGAG X CGAA ICCCUCUG 2205

436 AGAGGGCC C GAAGGCCG 431 CGGCCUUC CUGAUGAG X CGAA IGCCCUCU 2206

443 CCGAAGGC C GGGGCCCA 432 UGGGCCCC CUGAUGAG X CGAA ICCUUCGG 2207

449 GCCGGGGC C CACCAUGG 433 CCAUGGUG CUGAUGAG X CGAA ICCCCGGC 2208 Table 19

450 CCGGGGCC C ACCAUGGC 434 GCCAUGGU CUGAUGAG X CGAA IGCCCCGG 2209

451 CGGGGCCC A CCAUGGCC 435 GGCCAUGG CUGAUGAG X CGAA IGGCCCCG 2210

453 GGGCCCAC C AUGGCCCA 436 UGGGCCAU CUGAUGAG X CGAA IUGGGCCC 2211

454 GGCCCACC A UGGCCCAA 437 UUGGGCCA CUGAUGAG X CGAA IGUGGGCC 2212

459 ACCAUGGC C CAAGCCCU 438 AGGGCUUG CUGAUGAG X CGAA ICCAUGGU 2213

460 CCAUGGCC C AAGCCCUG 439 CAGGGCUU CUGAUGAG X CGAA IGCCAUGG 2214

461 CAUGGCCC A AGCCCUGC 440 GCAGGGCU CUGAUGAG X CGAA IGGCCAUG 2215

465 GCCCAAGC C CUGCCCUG 441 CAGGGCAG CUGAUGAG X CGAA ICUUGGGC 2216

466 CCCAAGCC C UGCCCUGG 442 CCAGGGCA CUGAUGAG X CGAA IGCUUGGG 2217

467 CCAAGCCC U GCCCUGGC 443 GCCAGGGC CUGAUGAG X CGAA IGGCUUGG 2218

470 AGCCCUGC c CUGGCUCC 444 GGAGCCAG CUGAUGAG X CGAA ICAGGGCU 2219

471 GCCCUGCC c UGGCUCCU 445 AGGAGCCA CUGAUGAG X CGAA IGCAGGGC 2220

472 CCCUGCCC u GGCUCCUG 446 CAGGAGCC CUGAUGAG X CGAA IGGCAGGG 2221

476 GCCCUGGC u CCUGCUGU 447 ACAGCAGG CUGAUGAG X CGAA ICCAGGGC 2222

478 CCUGGCUC c UGCUGUGG 448 CCACAGCA CUGAUGAG X CGAA IAGCCAGG 2223

479 CUGGCUCC u GCUGUGGA 449 UCCACAGC CUGAUGAG X CGAA IGAGCCAG 2224

482 GCUCCUGC u GUGGAUGG 450 CCAUCCAC CUGAUGAG X CGAA ICAGGAGC 2225

503 GGGAGUGC u GCCUGCCC 451 GGGCAGGC CUGAUGAG X CGAA ICACUCCC 2226

506 AGUGCUGC c UGCCCACG 452 CGUGGGCA CUGAUGAG X CGAA ICAGCACU 2227

507 GUGCUGCC u GCCCACGG 453 CCGUGGGC CUGAUGAG X CGAA IGCAGCAC 2228

510 CUGCCUGC c CACGGCAC 454 GUGCCGUG CUGAUGAG X CGAA ICAGGCAG 2229

511 UGCCUGCC c ACGGCACC 455 GGUGCCGU CUGAUGAG X CGAA IGCAGGCA 2230

512 GCCUGCCC A CGGCACCC 456 GGGUGCCG CUGAUGAG X CGAA IGGCAGGC 2231

517 CCCACGGC A CCCAGCAC 457 GUGCUGGG CUGAUGAG X CGAA ICCGUGGG 2232

519 CACGGCAC C CAGCACGG 458 CCGUGCUG CUGAUGAG X CGAA IUGCCGUG 2233

520 ACGGCACC C AGCACGGC 459 GCCGUGCU CUGAUGAG X CGAA IGUGCCGU 2234

521 CGGCACCC A GCACGGCA 460 UGCCGUGC CUGAUGAG X CGAA IGGUGCCG 2235

524 CACCCAGC A CGGCAUCC 461 GGAUGCCG CUGAUGAG X CGAA ICUGGGUG 2236

529 AGCACGGC A UCCGGCUG 462 CAGCCGGA CUGAUGAG X CGAA ICCGUGCU 2237

532 ACGGCAUC C GGCUGCCC 463 GGGCAGCC CUGAUGAG X CGAA IAUGCCGU 2238

536 CAUCCGGC U GCCCCUGC 464 GCAGGGGC CUGAUGAG X CGAA ICCGGAUG 2239

539 CCGGCUGC C CCUGCGCA 465 UGCGCAGG CUGAUGAG X CGAA ICAGCCGG 2240

540 CGGCUGCC C CUGCGCAG 466 CUGCGCAG CUGAUGAG X CGAA IGCAGCCG 2241

541 GGCUGCCC C UGCGCAGC 467 GCUGCGCA CUGAUGAG X CGAA IGGCAGCC 2242

542 GCUGCCCC U GCGCAGCG 468 CGCUGCGC CUGAUGAG X CGAA IGGGCAGC 2243

547 CCCUGCGC A GCGGCCUG 469 CAGGCCGC CUGAUGAG X CGAA ICGCAGGG 2244

553 GCAGCGGC C UGGGGGGC 470 GCCCCCCA CUGAUGAG X CGAA ICCGCUGC 2245

554 CAGCGGCC u GGGGGGCG 471 CGCCCCCC CUGAUGAG X CGAA IGCCGCUG 2246

564 GGGGGCGC c CCCCUGGG 472 CCCAGGGG CUGAUGAG X CGAA ICGCCCCC 2247

565 GGGGCGCC c CCCUGGGG 473 CCCCAGGG CUGAUGAG X CGAA IGCGCCCC 2248

566 GGGCGCCC c CCUGGGGC 474 GCCCCAGG CUGAUGAG X CGAA IGGCGCCC 2249

567 GGCGCCCC c CUGGGGCU 475 AGCCCCAG CUGAUGAG X CGAA IGGGCGCC 2250

568 GCGCCCCC c UGGGGCUG 476 CAGCCCCA CUGAUGAG X CGAA IGGGGCGC ~ 2251

569 CGCCCCCC u GGGGCUGC 477 GCAGCCCC CUGAUGAG X CGAA IGGGGGCG 2252

575 CCUGGGGC u GCGGCUGC 478 GCAGCCGC CUGAUGAG X CGAA ICCCCAGG 2253

581 GCUGCGGC u GCCCCGGG 479 CCCGGGGC CUGAUGAG X CGAA ICCGCAGC 2254

584 GCGGCUGC c CCGGGAGA 480 UCUCCCGG CUGAUGAG X CGAA ICAGCCGC 2255

585 CGGCUGCC c CGGGAGAC 481 GUCUCCCG CUGAUGAG X CGAA IGCAGCCG 2256

586 GGCUGCCC c GGGAGACC 482 GGUCUCCC CUGAUGAG X CGAA IGGCAGCC 2257

594 CGGGAGAC c GACGAAGA 483 UCUUCGUC CUGAUGAG X CGAA IUCUCCCG 2258

605 CGAAGAGC c CGAGGAGC 484 σcuccucG CUGAUGAG X CGAA ICUCUUCG 2259 Table 19

606 GAAGAGCC C GAGGAGCC 485 GGCUCCUC CUGAUGAG X CGAA IGCUCUUC 2260

614 CGAGGAGC C CGGCCGGA 486 UCCGGCCG CUGAUGAG X CGAA ICUCCUCG 2261

615 GAGGAGCC C GGCCGGAG 487 CUCCGGCC CUGAUGAG X CGAA IGCUCCUC 2262

619 AGCCCGGC C GGAGGGGC 488 GCCCCUCC CUGAUGAG X CGAA ICCGGGCU 2263

628 GGAGGGGC A GCUUUGUG 489 CACAAAGC CUGAUGAG X CGAA ICCCCUCC 2264

631 GGGGCAGC U UUGUGGAG 490 CUCCACAA CUGAUGAG X CGAA ICUGCCCC 2265

649 UGGUGGAC A ACCUGAGG 491 CCUCAGGU CUGAUGAG X CGAA IUCCACCA 2266

652 UGGACAAC C UGAGGGGC 492 GCCCCUCA CUGAUGAG X CGAA IUUGUCCA 2267

653 GGACAACC U GAGGGGCA 493 UGCCCCUC CUGAUGAG X CGAA IGUUGUCC 2268

661 UGAGGGGC A AGUCGGGG 494 CCCCGACU CUGAUGAG X CGAA ICCCCUCA 2269

671 GUCGGGGC A GGGCUACU 495 AGUAGCCC CUGAUGAG X CGAA ICCCCGAC 2270

676 GGCAGGGC U ACUACGUG 496 CACGUAGU CUGAUGAG X CGAA ICCCUGCC 2271

679 AGGGCUAC U ACGUGGAG 497 CUCCACGU CUGAUGAG X CGAA IUAGCCCU 2272

693 GAGAUGAC C GUGGGCAG 498 CUGCCCAC CUGAUGAG X CGAA IUCAUCUC 2273

700 CCGUGGGC A GCCCCCCG 499 CGGGGGGC CUGAUGAG X CGAA ICCCACGG 2274

703 UGGGCAGC C CCCCGCAG 500 CUGCGGGG CUGAUGAG X CGAA ICUGCCCA 2275

704 GGGCAGCC C CCCGCAGA 501 UCUGCGGG CUGAUGAG X CGAA IGCUGCCC 2276

705 GGCAGCCC C CCGCAGAC 502 GUCUGCGG CUGAUGAG X CGAA IGGCUGCC 2277

706 GCAGCCCC C CGCAGACG 503 CGUCUGCG CUGAUGAG X CGAA IGGGCUGC 2278

707 CAGCCCCC C GCAGACGC 504 GCGUCUGC CUGAUGAG X CGAA IGGGGCUG 2279

710 CCCCCCGC A GACGCUCA 505 UGAGCGUC CUGAUGAG X CGAA ICGGGGGG 2280

716 GCAGACGC U CAACAUCC 506 GGAUGUUG CUGAUGAG X CGAA ICGUCUGC 2281

718 AGACGCUC A ACAUCCUG 507 CAGGAUGU CUGAUGAG X CGAA IAGCGUCU 2282

721 CGCUCAAC A UCCUGGUG 508 CACCAGGA CUGAUGAG X CGAA IUUGAGCG 2283

724 UCAACAUC C UGGUGGAU 509 AUCCACCA CUGAUGAG X CGAA IAUGUUGA 2284

725 CAACAUCC U GGUGGAUA 510 UAUCCACC CUGAUGAG X CGAA IGAUGUUG 2285

735 GUGGAUAC A GGCAGCAG 511 CUGCUGCC CUGAUGAG X CGAA IUAUCCAC 2286

739 AUACAGGC A GCAGUAAC 512 GUUACUGC CUGAUGAG X CGAA ICCUGUAU 2287

742 CAGGCAGC A GUAACUUU 513 AAAGUUAC CUGAUGAG X CGAA ICUGCCUG 2288

748 GCAGUAAC U UUGCAGUG 514 CACUGCAA CUGAUGAG X CGAA IUUACUGC 2289

753 AACUUUGC A GUGGGUGC 515 GCACCCAC CUGAUGAG X CGAA ICAAAGUU 2290

762 GUGGGUGC U GCCCCCCA 516 UGGGGGGC CUGAUGAG X CGAA ICACCCAC 2291

765 GGUGCUGC C CCCCACCC 517 GGGUGGGG CUGAUGAG X CGAA ICAGCACC 2292

766 GUGCUGCC C CCCACCCC 518 GGGGUGGG CUGAUGAG X CGAA IGCAGCAC 2293

767 UGCUGCCC C CCACCCCU 519 AGGGGUGG CUGAUGAG X CGAA IGGCAGCA 2294

768 GCUGCCCC C CACCCCUU 520 AAGGGGUG CUGAUGAG X CGAA IGGGCAGC 2295

769 CUGCCCCC C ACCCCUUC 521 GAAGGGGU CUGAUGAG X CGAA IGGGGCAG 2296

770 UGCCCCCC A CCCCUUCC 522 GGAAGGGG CUGAUGAG X CGAA IGGGGGCA 2297

772 CCCCCCAC C CCUUCCUG 523 CAGGAAGG CUGAUGAG X CGAA IUGGGGGG 2298

773 CCCCCACC C CUUCCUGC 524 GCAGGAAG CUGAUGAG X CGAA IGUGGGGG 2299

774 CCCCACCC C UUCCUGCA 525 UGCAGGAA CUGAUGAG X CGAA IGGUGGGG 2300

775 CCCACCCC U UCCUGCAU 526 AUGCAGGA CUGAUGAG X CGAA IGGGUGGG 2301

778 ACCCCUUC C UGCAUCGC 527 GCGAUGCA CUGAUGAG X CGAA IAAGGGGU 2302

779 CCCCUUCC U GCAUCGCU 528 AGCGAUGC CUGAUGAG X CGAA IGAAGGGG 2303

782 CUUCCUGC A UCGCUACU 529 AGUAGCGA CUGAUGAG X CGAA ICAGGAAG 2304

787 UGCAUCGC U ACUACCAG 530 CUGGUAGU CUGAUGAG X CGAA ICGAUGCA 2305

790 AUCGCUAC U ACCAGAGG 531 CCUCUGGU CUGAUGAG X CGAA IUAGCGAU 2306

793 GCUACUAC C AGAGGCAG 532 CUGCCUCU CUGAUGAG X CGAA IUAGUAGC 2307

794 CUACUACC A GAGGCAGC 533 GCUGCCUC CUGAUGAG X CGAA IGUAGUAG 2308

800 CCAGAGGC A GCUGUCCA 534 UGGACAGC CUGAUGAG X CGAA ICCUCUGG 2309

803 GAGGCAGC U GUCCAGCA 535 UGCUGGAC CUGAUGAG X CGAA ICUGCCUC 2310 Table 19

807 CAGCUGUC C AGCACAUA 536 UAUGUGCU CUGAUGAG X CGAA I CAGCUG 2311

808 AGCUGUCC A GCACAUAC 537 GUAUGUGC CUGAUGAG X CGAA IGACAGCU 2312

811 UGUCCAGC A CAUACCGG 538 CCGGUAUG CUGAUGAG X CGAA ICUGGACA 2313

813 UCCAGCAC A UACCGGGA 539 UCCCGGUA CUGAUGAG X CGAA IUGCUGGA 2314

817 GCACAUAC C GGGACCUC 540 GAGGUCCC CUGAUGAG X CGAA IUAUGUGC 2315

823 ACCGGGAC C UCCGGAAG 541 CUUCCGGA CUGAUGAG X CGAA IUCCCGGU 2316

824 CCGGGACC U CCGGAAGG 542 CCUUCCGG CUGAUGAG X CGAA IGUCCCGG 2317

826 GGGACCUC C GGAAGGGU 543 ACCCUUCC CUGAUGAG X CGAA IAGGUCCC 2318

845 GUAUGUGC C CUACACCC 544 GGGUGUAG CUGAUGAG X CGAA ICACAUAC 2319

846 UAUGUGCC C UACACCCA 545 UGGGUGUA CUGAUGAG X CGAA IGCACAUA 2320

847 AUGUGCCC U ACACCCAG 546 CUGGGUGU CUGAUGAG X CGAA IGGCACAU 2321

850 UGCCCUAC A CCCAGGGC 547 GCCCUGGG CUGAUGAG X CGAA IUAGGGCA 2322

852 CCCUACAC C CAGGGCAA 548 UUGCCCUG CUGAUGAG X CGAA IUGUAGGG 2323

853 CCUACACC C AGGGCAAG 549 CUUGCCCU CUGAUGAG X CGAA IGUGUAGG 2324

854 CUACACCC A GGGCAAGU 550 ACUUGCCC CUGAUGAG X CGAA IGGUGUAG 2325

859 CCCAGGGC A AGUGGGAA 551 UUCCCACU CUGAUGAG X CGAA ICCCUGGG 2326

875 AGGGGAGC U GGGCACCG 552 CGGUGCCC CUGAUGAG X CGAA ICUCCCCU 2327

880 AGCUGGGC A CCGACCUG 553 CAGGUCGG CUGAUGAG X CGAA ICCCAGCU 2328

882 CUGGGCAC C GACCUGGU 554 ACCAGGUC CUGAUGAG X CGAA IUGCCCAG 2329

886 GCACCGAC C UGGUAAGC 555 GCUUACCA CUGAUGAG X CGAA IUCGGUGC 2330

887 CACCGACC U GGUAAGCA 556 UGCUUACC CUGAUGAG X CGAA IGUCGGUG 2331

895 UGGUAAGC A UCCCCCAU 557 AUGGGGGA CUGAUGAG X CGAA ICUUACCA 2332

898 UAAGCAUC C CCCAUGGC 558 GCCAUGGG CUGAUGAG X CGAA IAUGCUUA 2333

899 AAGCAUCC C CCAUGGCC 559 GGCCAUGG CUGAUGAG X CGAA IGAUGCUU 2334

900 AGCAUCCC C CAUGGCCC 560 GGGCCAUG CUGAUGAG X CGAA IGGAUGCU 2335

901 GCAUCCCC C AUGGCCCC 561 GGGGCCAU CUGAUGAG X CGAA IGGGAUGC 2336

902 CAUCCCCC A UGGCCCCA 562 UGGGGCCA CUGAUGAG X CGAA IGGGGAUG 2337

907 CCCAUGGC C CCAACGUC 563 GACGUUGG CUGAUGAG X CGAA ICCAUGGG 2338

908 CCAUGGCC C CAACGUCA 564 UGACGUUG CUGAUGAG X CGAA IGCCAUGG 2339

909 CAUGGCCC C AACGUCAC 565 GUGACGUU CUGAUGAG X CGAA IGGCCAUG 2340

910 AUGGCCCC A ACGUCACU 566 AGUGACGU CUGAUGAG X CGAA IGGGCCAU 2341

916 CCAACGUC A CUGUGCGU 567 ACGCACAG CUGAUGAG X CGAA IACGUUGG 2342

918 AACGUCAC U GUGCGUGC 568 GCACGCAC CUGAUGAG X CGAA IUGACGUU 2343

927 GUGCGUGC c AACAUUGC 569 GCAAUGUU CUGAUGAG X CGAA ICACGCAC 2344

928 UGCGUGCC A ACAUUGCU 570 AGCAAUGU CUGAUGAG X CGAA IGCACGCA 2345

931 GUGCCAAC A UUGCUGCC 571 GGCAGCAA CUGAUGAG X CGAA IUUGGCAC 2346

936 AACAUUGC U GCCAUCAC 572 GUGAUGGC CUGAUGAG X CGAA ICAAUGUU 2347

939 AUUGCUGC C AUCACUGA 573 UCAGUGAU CUGAUGAG X CGAA ICAGCAAU 2348

940 UUGCUGCC A UCACUGAA 574 UUCAGUGA CUGAUGAG X CGAA IGCAGCAA 2349

943 CUGCCAUC A CUGAAUCA 575 UGAUUCAG CUGAUGAG X CGAA IAUGGCAG 2350

945 GCCAUCAC U GAAUCAGA 576 UCUGAUUC CUGAUGAG X CGAA IUGAUGGC 2351

951 ACUGAAUC A GACAAGUU 577 AACUUGUC CUGAUGAG X CGAA IAUUCAGU 2352

955 AAUCAGAC A AGUUCUUC 578 GAAGAACU CUGAUGAG X CGAA IUCUGAUU 2353

961 ACAAGUUC U UCAUCAAC 579 GUUGAUGA CUGAUGAG X CGAA IAACUUGU 2354

964 AGUUCUUC A UCAACGGC 580 GCCGUUGA CUGAUGAG X CGAA IAAGAACU 2355

967 UCUUCAUC A ACGGCUCC 581 GGAGCCGU CUGAUGAG X CGAA IAUGAAGA 2356

973 UCAACGGC U CCAACUGG 582 CCAGUUGG CUGAUGAG X CGAA ICCGUUGA 2357

975 AACGGCUC C AACUGGGA 583 UCCCAGUU CUGAUGAG X CGAA lAGCCGUU 2358

976 ACGGCUCC A ACUGGGAA 584 UUCCCAGU CUGAUGAG X CGAA IGAGCCGU 2359

979 GCUCCAAC U GGGAAGGC 585 GCCUUCCC CUGAUGAG X CGAA IUUGGAGC 2360

988 GGGAAGGC A UCCUGGGG 586 CCCCAGGA CUGAUGAG X CGAA ICCUUCCC 2361 Table 19

991 AAGGCAUC C UGGGGCUG 587 CAGCCCCA CUGAUGAG X CGAA IAUGCCUU 2362

992 AGGCAUCC U GGGGCUGG 588 CCAGCCCC CUGAUGAG X CGAA IGAUGCCU 2363

998 CCUGGGGC U GGCCUAUG 589 CAUAGGCC CUGAUGAG X CGAA ICCCCAGG 2364

1002 GGGCUGGC C UAUGCUGA 590 UCAGCAUA CUGAUGAG X CGAA ICCAGCCC 2365

1003 GGCUGGCC U AUGCUGAG 591 CUCAGCAU CUGAUGAG X CGAA IGCCAGCC 2366

1008 GCCUAUGC U GAGAUUGC 592 GCAAUCUC CUGAUGAG X CGAA ICAUAGGC 2367

1017 GAGAUUGC C AGGCCUGA 593 UCAGGCCU CUGAUGAG X CGAA ICAAUCUC 2368

1018 AGAUUGCC A GGCCUGAC 594 GUCAGGCC CUGAUGAG X CGAA IGCAAUCU 2369

1022 UGCCAGGC C UGACGACU 595 AGUCGUCA CUGAUGAG X CGAA ^■ICCUGGCA 2370

1023 GCCAGGCC U GACGACUC 596 GAGUCGUC CUGAUGAG X CGAA IGCCUGGC 2371

1030 CUGACGAC U CCCUGGAG 597 CUCCAGGG CUGAUGAG X CGAA IUCGUCAG 2372

1032 GACGACUC c CUGGAGCC 598 GGCUCCAG CUGAUGAG X CGAA IAGUCGUC 2373

1033 ACGACUCC c UGGAGCCU 599 AGGCUCCA CUGAUGAG X CGAA IGAGUCGU 2374

1034 CGACUCCC u GGAGCCUU 600 AAGGCUCC CUGAUGAG X CGAA IGGAGUCG 2375

1040 CCUGGAGC c UUUCUUUG 601 CAAAGAAA CUGAUGAG X CGAA ICUCCAGG 2376

1041 CUGGAGCC u UUCUUUGA 602 UCAAAGAA CUGAUGAG X CGAA IGCUCCAG 2377

1045 AGCCUUUC u UUGACUCU 603 AGAGUCAA CUGAUGAG X CGAA IAAAGGCU 2378

1051 UCUUUGAC u CUCUGGUA 604 UACCAGAG CUGAUGAG X CGAA IUCAAAGA 2379

1053 UUUGACUC u CUGGUAAA 605 UUUACCAG CUGAUGAG X CGAA IAGUCAAA 2380

1055 UGACUCUC u GGUAAAGC 606 GCUUUACC CUGAUGAG X CGAA IAGAGUCA 2381

1064 GGUAAAGC A GACCCACG 607 CGUGGGUC CUGAUGAG X CGAA ICUUUACC 2382

1068 AAGCAGAC C CACGUUCC 608 GGAACGUG CUGAUGAG X CGAA IUCUGCUU 2383

1069 AGCAGACC c ACGUUCCC 609 GGGAACGU CUGAUGAG X CGAA IGUCUGCU 2384

1070 GCAGACCC A CGUUCCCA 610 UGGGAACG CUGAUGAG X CGAA IGGUCUGC 2385

1076 CCACGUUC C CAACCUCU 611 AGAGGUUG CUGAUGAG X CGAA IAACGUGG 2386

1077 CACGUUCC C AACCUCUU 612 AAGAGGUU CUGAUGAG X CGAA IGAACGUG 2387

1078 ACGUUCCC A ACCUCUUC 613 GAAGAGGU CUGAUGAG X CGAA IGGAACGU 2388

1081 UUCCCAAC C UCUUCUCC 614 GGAGAAGA CUGAUGAG X CGAA IUUGGGAA 2389

1082 UCCCAACC U CUUCUCCC 615 GGGAGAAG CUGAUGAG X CGAA IGUUGGGA 2390

1084 CCAACCUC U UCUCCCUG 616 CAGGGAGA CUGAUGAG X CGAA IAGGUUGG 2391

1087 ACCUCUUC U CCCUGCAG 617 CUGCAGGG CUGAUGAG X CGAA IAAGAGGU 2392

1089 CUCUUCUC C CUGCAGCU 618 AGCUGCAG CUGAUGAG X CGAA IAGAAGAG 2393

1090 UCUUCUCC C UGCAGCUU 619 AAGCUGCA CUGAUGAG X CGAA IGAGAAGA 2394

1091 cuucuccc u GCAGCUUU 620 AAAGCUGC CUGAUGAG X CGAA IGGAGAAG 2395

1094 CUCCCUGC A GCUUUGUG 621 CACAAAGC CUGAUGAG X CGAA ICAGGGAG 2396

1097 CCUGCAGC U UUGUGGUG 622 CACCACAA CUGAUGAG X CGAA ICUGCAGG 2397

1107 UGUGGUGC U GGCUUCCC 623 GGGAAGCC CUGAUGAG X CGAA ICACCACA 2398 llll GUGCUGGC U UCCCCCUC 624 GAGGGGGA CUGAUGAG X CGAA ICCAGCAC 2399

1114 CUGGCUUC C CCCUCAAC 625 GUUGAGGG CUGAUGAG X CGAA IAAGCCAG 2400

1115 UGGCUUCC C CCUCAACC 626 GGUUGAGG CUGAUGAG X CGAA IGAAGCCA 2401

1116 GGCUUCCC C CUCAACCA 627 UGGUUGAG CUGAUGAG X CGAA IGGAAGCC 2402

1117 GCUUCCCC C UCAACCAG 628 CUGGUUGA CUGAUGAG X CGAA IGGGAAGC 2403

1118 CUUCCCCC U CAACCAGU 629 ACUGGUUG CUGAUGAG X CGAA IGGGGAAG 2404

1120 UCCCCCUC A ACCAGUCU 630 AGACUGGU CUGAUGAG X CGAA lAGGGGGA 2405

1123 CCCUCAAC C AGUCUGAA 631 UUCAGACU CUGAUGAG X CGAA IUUGAGGG 2406

1124 CCUCAACC A GUCUGAAG 632 CUUCAGAC CUGAUGAG X CGAA IGUUGAGG 2407

1128 AACCAGUC U GAAGUGCU 633 AGCACUUC CUGAUGAG X CGAA lACUGGUU 2408

1136 UGAAGUGC U GGCCUCUG 634 CAGAGGCC CUGAUGAG X CGAA ICACUUCA 2409

1140 GUGCUGGC C UCUGUCGG 635 CCGACAGA CUGAUGAG X CGAA ICCAGCAC 2410

1141 UGCUGGCC U CUGUCGGA 636 UCCGACAG CUGAUGAG X CGAA IGCCAGCA 2411 •

1143 CUGGCCUC U GUCGGAGG 637 CCUCCGAC CUGAUGAG X CGAA IAGGCCAG 2412 Table 19

1156 GAGGGAGC A UGAUCAUU 638 AAUGAUCA CUGAUGAG X CGAA ICUCCCUC 2413

1162 GCAUGAUC A UUGGAGGU 639 ACCUCCAA CUGAUGAG X CGAA IAUCAUGC 2414

1177 GUAUCGAC C ACUCGCUG 640 CAGCGAGU CUGAUGAG X CGAA IUCGAUAC 2415

1178 UAUCGACC A CUCGCUGU 641 ACAGCGAG CUGAUGAG X CGAA IGUCGAUA 2416

1180 UCGACCAC U CGCUGUAC 642 GUACAGCG CUGAUGAG X CGAA IUGGUCGA 2417

1184 CCACUCGC U GUACACAG 643 CUGUGUAC CUGAUGAG X CGAA ICGAGUGG 2418

1189 CGCUGUAC A CAGGCAGU 644 ACUGCCUG CUGAUGAG X CGAA IUACAGCG 2419

1191 CUGUACAC A GGCAGUCU 645 AGACUGCC CUGAUGAG X CGAA IUGUACAG 2420

1195 ACACAGGC A GUCUCUGG 646 CCAGAGAC CUGAUGAG X CGAA ICCUGUGU 2421

1199 AGGCAGUC U CUGGUAUA 647 UAUACCAG CUGAUGAG X CGAA IACUGCCU 2422

1201 GCAGUCUC U GGUAUACA 648 UGUAUACC CUGAUGAG X CGAA IAGACUGC 2423

1209 UGGUAUAC A CCCAUCCG 649 CGGAUGGG CUGAUGAG X CGAA IUAUACCA 2424

1211 GUAUACAC C CAUCCGGC 650 GCCGGAUG CUGAUGAG X CGAA IUGUAUAC 2425

1212 UAUACACC C AUCCGGCG 651 CGCCGGAU CUGAUGAG X CGAA IGUGUAUA 2426

1213 AUACACCC A UCCGGCGG 652 CCGCCGGA CUGAUGAG X CGAA IGGUGUAU 2427

1216 CACCCAUC C GGCGGGAG 653 CUCCCGCC CUGAUGAG X CGAA IAUGGGUG 2428

1243 AGGUGAUC A UUGUGCGG 654 CCGCACAA CUGAUGAG X CGAA IAUCACCU 2429

1261 UGGAGAUC A AUGGACAG 655 CUGUCCAU CUGAUGAG X CGAA IAUCUCCA 2430

1268 CAAUGGAC A GGAUCUGA 656 UCAGAUCC CUGAUGAG X CGAA IUCCAUUG 2431

1274 ACAGGAUC U GAAAAUGG 657 CCAUUUUC CUGAUGAG X CGAA IAUCCUGU 2432

1285 AAAUGGAC U GCAAGGAG 658 CUCCUUGC CUGAUGAG X CGAA IUCCAUUU 2433

1288 UGGACUGC A AGGAGUAC 659 GUACUCCU CUGAUGAG X CGAA ICAGUCCA 2434

1297 AGGAGUAC A ACUAUGAC 660 GUCAUAGU CUGAUGAG X CGAA IUACUCCU 2435

1300 AGUACAAC U AUGACAAG 661 CUUGUCAU CUGAUGAG X CGAA IUUGUACU 2436

1306 ACUAUGAC A AGAGCAUU 662 AAUGCUCU CUGAUGAG X CGAA IUCAUAGU 2437

1312 ACAAGAGC A UUGUGGAC 663 GUCCACAA CUGAUGAG X CGAA ICUCUUGU 2438

1321 UUGUGGAC A GUGGCACC 664 GGUGCCAC CUGAUGAG X CGAA IUCCACAA 2439

1327 ACAGUGGC A CCACCAAC 665 GUUGGUGG CUGAUGAG X CGAA ICCACUGU 2440

1329 AGUGGCAC C ACCAACCU 666 AGGUUGGU CUGAUGAG X CGAA IUGCCACU 2441

1330 GUGGCACC A CCAACCUU 667 AAGGUUGG CUGAUGAG X CGAA IGUGCCAC 2442

1332 GGCACCAC C AACCUUCG 668 CGAAGGUU CUGAUGAG X CGAA IUGGUGCC 2443

1333 GCACCACC A ACCUUCGU 669 ACGAAGGU CUGAUGAG X CGAA IGUGGUGC 2444

1336 CCACCAAC C UUCGUUUG 670 CAAACGAA CUGAUGAG X CGAA IUUGGUGG 2445

1337 CACCAACC U UCGUUUGC 671 GCAAACGA CUGAUGAG X CGAA IGUUGGUG 2446

1346 UCGUUUGC C CAAGAAAG 672 CUUUCUUG CUGAUGAG X CGAA ICAAACGA 2447

1347 CGUUUGCC C AAGAAAGU 673 ACUUUCUU CUGAUGAG X CGAA IGCAAACG 2448

1348 GUUUGCCC A AGAAAGUG 674 CACUUUCU CUGAUGAG X CGAA IGGCAAAC 2449

1365 UUUGAAGC U GCAGUCAA 675 UUGACUGC CUGAUGAG X CGAA ICUUCAAA 2450

1368 GAAGCUGC A GUCAAAUC 676 GAUUUGAC CUGAUGAG X CGAA ICAGCUUC 2451

1372 CUGCAGUC A AAUCCAUC 677 GAUGGAUU CUGAUGAG X CGAA IACUGCAG 2452

1377 GUCAAAUC C AUCAAGGC 678 GCCUUGAU CUGAUGAG X CGAA IAUUUGAC 2453

1378 UCAAAUCC A UCAAGGCA 679 UGCCUUGA CUGAUGAG X CGAA IGAUUUGA 2454

1381 AAUCCAUC A AGGCAGCC 680 GGCUGCCU CUGAUGAG X CGAA IAUGGAUU 2455

1386 AUCAAGGC A GCCUCCUC 681 GAGGAGGC CUGAUGAG X CGAA ICCUUGAU 2456

1389 AAGGCAGC C UCCUCCAC 682 GUGGAGGA CUGAUGAG X CGAA ICUGCCUU 2457

1390 AGGCAGCC U CCUCCACG 683 CGUGGAGG CUGAUGAG X CGAA IGCUGCCU 2458

1392 GCAGCCUC C UCCACGGA 684 UCCGUGGA CUGAUGAG X CGAA IAGGCUGC 2459

1393 CAGCCUCC U CCACGGAG 685 CUCCGUGG CUGAUGAG X CGAA IGAGGCUG 2460

1395 GCCUCCUC C ACGGAGAA 686 UUCUCCGU CUGAUGAG X CGAA IAGGAGGC 2461

1396 CCUCCUCC A CGGAGAAG 687 CUUCUCCG CUGAUGAG X CGAA IGAGGAGG 2462

1408 AGAAGUUC C CUGAUGGU 688 ACCAUCAG CUGAUGAG X CGAA lAACUUCU 2463 Table 19

1409 GAAGUUCC C UGAUGGUU 689 AACCAUCA CUGAUGAG X CGAA IGAACUUC 2464

1410 AAGUUCCC U GAUGGUUU 690 AAACCAUC CUGAUGAG X CGAA IGGAACUU 2465

1420 AUGGUUUC U GGCUAGGA 691 UCCUAGCC CUGAUGAG X CGAA IAAACCAU 2466

1424 UUUCUGGC U AGGAGAGC 692 GCUCUCCU CUGAUGAG X CGAA ICCAGAAA 2467

1433 AGGAGAGC A GCUGGUGU 693 ACACCAGC CUGAUGAG X CGAA ICUCUCCU 2468

1436 AGAGCAGC U GGUGUGCU 694 AGCACACC CUGAUGAG X CGAA ICUGCUCU 2469

1444 UGGUGUGC U GGCAAGCA 695 UGCUUGCC CUGAUGAG X CGAA ICACACCA 2470

1448 GUGCUGGC A AGCAGGCA 696 UGCCUGCU CUGAUGAG X CGAA ICCAGCAC 2471

1452 UGGCAAGC A GGCACCAC 697 GUGGUGCC CUGAUGAG X CGAA ICUUGCCA 2472

1456 AAGCAGGC A CCACCCCU 698 AGGGGUGG CUGAUGAG X CGAA ICCUGCUU 2473

1458 GCAGGCAC C ACCCCUUG 699 CAAGGGGU CUGAUGAG X CGAA IUGCCUGC 2474

1459 CAGGCACC A CCCCUUGG 700 CCAAGGGG CUGAUGAG X CGAA IGUGCCUG 2475

1461 GGCACCAC C CCUUGGAA 701 UUCCAAGG CUGAUGAG X CGAA IUGGUGCC 2476

1462 GCACCACC C CUUGGAAC 702 GUUCCAAG CUGAUGAG X CGAA IGUGGUGC 2477

1463 CACCACCC C UUGGAACA 703 UGUUCCAA CUGAUGAG X CGAA IGGUGGUG 2478

1464 ACCACCCC U UGGAACAU 704 AUGUUCCA CUGAUGAG X CGAA IGGGUGGU 2479

1471 CUUGGAAC A UUUUCCCA 705 UGGGAAAA CUGAUGAG X CGAA IUUCCAAG 2480

1477 ACAUUUUC C CAGUCAUC 706 GAUGACUG CUGAUGAG X CGAA IAAAAUGU 2481

1478 CAUUUUCC C AGUCAUCU 707 AGAUGACU CUGAUGAG X CGAA IGAAAAUG 2482

1479 AUUUUCCC A GUCAUCUC 708 GAGAUGAC CUGAUGAG X CGAA IGGAAAAU 2483

1483 UCCCAGUC A UCUCACUC 709 GAGUGAGA CUGAUGAG X CGAA IACUGGGA 2484

1486 CAGUCAUC U CACUCUAC 710 GUAGAGUG CUGAUGAG X CGAA IAUGACUG 2485

1488 GUCAUCUC A CUCUACCU 711 AGGUAGAG CUGAUGAG X CGAA IAGAUGAC 2486

1490 CAUCUCAC U CUACCUAA 712 UUAGGUAG CUGAUGAG X CGAA IUGAGAUG 2487

1492 UCUCACUC U ACCUAAUG 713 CAUUAGGU CUGAUGAG X CGAA IAGUGAGA 2488

1495 CACUCUAC C UAAUGGGU 714 ACCCAUUA CUGAUGAG X CGAA IUAGAGUG 2489

1496 ACUCUACC U AAUGGGUG 715 CACCCAUU CUGAUGAG X CGAA IGUAGAGU 2490

1512 GAGGUUAC C AACCAGUC 716 GACUGGUU CUGAUGAG X CGAA IUAACCUC 2491

1513 AGGUUACC A ACCAGUCC 717 GGACUGGU CUGAUGAG X CGAA IGUAACCU 2492

1516 UUACCAAC C AGUCCUUC 718 GAAGGACU CUGAUGAG X CGAA IUUGGUAA 2493

1517 UACCAACC A GUCCUUCC 719 GGAAGGAC CUGAUGAG X CGAA IGUUGGUA 2494

1521 AACCAGUC C UUCCGCAU 720 AUGCGGAA CUGAUGAG X CGAA lACUGGUU 2495

1522 ACCAGUCC U UCCGCAUC 721 GAUGCGGA CUGAUGAG X CGAA IGACUGGU 2496

1525 AGUCCUUC C GCAUCACC 722 GGUGAUGC CUGAUGAG X CGAA IAAGGACU 2497

1528 CCUUCCGC A UCACCAUC 723 GAUGGUGA CUGAUGAG X CGAA ICGGAAGG 2498

1531 UCCGCAUC A CCAUCCUU 724 AAGGAUGG CUGAUGAG X CGAA lAUGCGGA 2499

1533 CGCAUCAC C AUCCUUCC 725 GGAAGGAU CUGAUGAG X CGAA IUGAUGCG 2500

1534 GCAUCACC A UCCUUCCG 726 CGGAAGGA CUGAUGAG X CGAA IGUGAUGC 2501

1537 UCACCAUC C UUCCGCAG 727 CUGCGGAA CUGAUGAG X CGAA IAUGGUGA 2502

1538 CACCAUCC U UCCGCAGC 728 GCUGCGGA CUGAUGAG X CGAA IGAUGGUG 2503

1541 CAUCCUUC C GCAGCAAU 729 AUUGCUGC CUGAUGAG X CGAA IAAGGAUG 2504

1544 CCUUCCGC A GCAAUACC 730 GGUAUUGC CUGAUGAG X CGAA ICGGAAGG 2505

1547 UCCGCAGC A AUACCUGC 731 GCAGGUAU CUGAUGAG X CGAA ICUGCGGA 2506

1552 AGCAAUAC C UGCGGCCA 732 UGGCCGCA CUGAUGAG X CGAA IUAUUGCU 2507

1553 GCAAUACC U GCGGCCAG 733 CUGGCCGC CUGAUGAG X CGAA IGUAUUGC 2508

1559 CCUGCGGC C AGUGGAAG 734 CUUCCACU CUGAUGAG X CGAA ICCGCAGG 2509

1560 CUGCGGCC A GUGGAAGA 735 UCUUCCAC CUGAUGAG X CGAA IGCCGCAG 2510

1575 GAUGUGGC C ACGUCCCA 736 UGGGACGU CUGAUGAG X CGAA ICCACAUC 2511

1576 AUGUGGCC A CGUCCCAA 737 UUGGGACG CUGAUGAG X CGAA IGCCACAU 2512

1581 GCCACGUC C CAAGACGA 738 UCGUCUUG CUGAUGAG X CGAA IACGUGGC 2513

1582 CCACGUCC C AAGACGAC 739 GUCGUCUU CUGAUGAG X CGAA IGACGUGG 2514 Table 19

1583 CACGUCCC A AGACGACU 740 AGUCGUCU CUGAUGAG X CGAA IGGACGUG 2515

1591 AAGACGAC U GUUACAAG 741 CUUGUAAC CUGAUGAG X CGAA IUCGUCUU 2516

1597 ACUGUUAC A AGUUUGCC 742 GGCAAACU CUGAUGAG X CGAA IUAACAGU 2517

1605 AAGUUUGC C AUCUCACA 743 UGUGAGAU CUGAUGAG X CGAA ICAAACUU 2518

1606 AGUUUGCC A UCUCACAG 744 CUGUGAGA CUGAUGAG X CGAA IGCAAACU 2519

1609 UUGCCAUC U CACAGUCA 745 UGACUGUG CUGAUGAG X CGAA IAUGGCAA 2520

1611 GCCAUCUC A CAGUCAUC 746 GAUGACUG CUGAUGAG X CGAA IAGAUGGC 2521

1613 CAUCUCAC A GUCAUCCA 747 UGGAUGAC CUGAUGAG X CGAA IUGAGAUG 2522

1617 UCACAGUC A UCCACGGG 748 CCCGUGGA CUGAUGAG X CGAA IACUGUGA 2523

1620 CAGUCAUC C ACGGGCAC 749 GUGCCCGU CUGAUGAG X CGAA IAUGACUG 2524

1621 AGUCAUCC A CGGGCACU 750 AGUGCCCG CUGAUGAG X CGAA IGAUGACU 2525

1627 CCACGGGC A CUGUUAUG 751 CAUAACAG CUGAUGAG X CGAA ICCCGUGG 2526

1629 ACGGGCAC U GUUAUGGG 752 CCCAUAAC CUGAUGAG X CGAA IUGCCCGU 2527

1641 AUGGGAGC U GUUAUCAU 753 AUGAUAAC CUGAUGAG X CGAA ICUCCCAU 2528

1648 CUGUUAUC A UGGAGGGC 754 GCCCUCCA CUGAUGAG X CGAA IAUAACAG 2529

1657 UGGAGGGC U UCUACGUU 755 AACGUAGA CUGAUGAG X CGAA ICCCUCCA 2530

1660 AGGGCUUC U ACGUUGUC 756 GACAACGU CUGAUGAG X CGAA IAAGCCCU 2531

1669 ACGUUGUC U UUGAUCGG 757 CCGAUCAA CUGAUGAG X CGAA IACAACGU 2532

1680 GAUCGGGC C CGAAAACG 758 CGUUUUCG CUGAUGAG X CGAA ICCCGAUC 2533

1681 AUCGGGCC C GAAAACGA 759 UCGUUUUC CUGAUGAG X CGAA IGCCCGAU 2534

1696 GAAUUGGC U UUGCUGUC 760 GACAGCAA CUGAUGAG X CGAA ICCAAUUC 2535

1701 GGCUUUGC U GUCAGCGC 761 GCGCUGAC CUGAUGAG X CGAA ICAAAGCC 2536

1705 UUGCUGUC A GCGCUUGC 762 GCAAGCGC CUGAUGAG X CGAA lACAGCAA 2537

1710 GUCAGCGC U UGCCAUGU 763 ACAUGGCA CUGAUGAG X CGAA ICGCUGAC 2538

1714 GCGCUUGC C AUGUGCAC 764 GUGCACAU CUGAUGAG X CGAA ICAAGCGC 2539

1715 CGCUUGCC A UGUGCACG 765 CGUGCACA CUGAUGAG X CGAA IGCAAGCG 2540

1721 CCAUGUGC A CGAUGAGU 766 ACUCAUCG CUGAUGAG X CGAA ICACAUGG 2541

1732 AUGAGUUC A GGACGGCA 767 UGCCGUCC CUGAUGAG X CGAA IAACUCAU 2542

1740 AGGACGGC A GCGGUGGA 768 UCCACCGC CUGAUGAG X CGAA ICCGUCCU 2543

1753 UGGAAGGC C CUUUUGUC 769 GACAAAAG CUGAUGAG X CGAA ICCUUCCA 2544

1754 GGAAGGCC C UUUUGUCA 770 UGACAAAA CUGAUGAG X CGAA IGCCUUCC 2545

1755 GAAGGCCC U UUUGUCAC 771 GUGACAAA CUGAUGAG X CGAA IGGCCUUC 2546

1762 CUUUUGUC A CCUUGGAC 772 GUCCAAGG CUGAUGAG X CGAA IACAAAAG 2547

1764 UUUGUCAC C UUGGACAU 773 AUGUCCAA CUGAUGAG X CGAA lUGACAAA 2548

1765 UUGUCACC U UGGACAUG 774 CAUGUCCA CUGAUGAG X CGAA IGUGACAA 2549

1771 CCUUGGAC A UGGAAGAC 775 GUCUUCCA CUGAUGAG X CGAA IUCCAAGG 2550

1780 UGGAAGAC U GUGGCUAC 776 GUAGCCAC CUGAUGAG X CGAA IUCUUCCA 2551

1786 ACUGUGGC U ACAACAUU 777 AAUGUUGU CUGAUGAG X CGAA ICCACAGU 2552

1789 GUGGCUAC A ACAUUCCA 778 UGGAAUGU CUGAUGAG X CGAA IUAGCCAC 2553

1792 GCUACAAC A UUCCACAG 779 CUGUGGAA CUGAUGAG X CGAA IUUGUAGC 2554

1796 CAACAUUC C ACAGACAG 780 CUGUCUGU CUGAUGAG X CGAA IAAUGUUG 2555

1797 AACAUUCC A CAGACAGA 781 UCUGUCUG CUGAUGAG X CGAA IGAAUGUU 2556

1799 CAUUCCAC A GACAGAUG 782 CAUCUGUC CUGAUGAG X CGAA IUGGAAUG 2557

1803 CCACAGAC A GAUGAGUC 783 GACUCAUC CUGAUGAG X CGAA IUCUGUGG 2558

1812 GAUGAGUC A ACCCUCAU 784 AUGAGGGU CUGAUGAG X CGAA IACUCAUC 2559

1815 GAGUCAAC C CUCAUGAC 785 GUCAUGAG CUGAUGAG X CGAA IUUGACUC 2560

1816 AGUCAACC C UCAUGACC 786 GGUCAUGA CUGAUGAG X CGAA IGUUGACU 2561

1817 GUCAACCC U CAUGACCA 787 UGGUCAUG CUGAUGAG X CGAA IGGUUGAC 2562

1819 CAACCCUC A UGACCAUA 788 ^' UAUGGUCA CUGAUGAG X CGAA IAGGGUUG 2563

1824 CUCAUGAC C AUAGCCUA 789 UAGGCUAU CUGAUGAG X CGAA IUCAUGAG 2564

1825 UCAUGACC -A UAGCCUAU 790 AUAGGCUA CUGAUGAG X CGAA IGUCAUGA 2565 Table 19

1830 ACCAUAGC C UAUGUCAU 791 AUGACAUA CUGAUGAG X CGAA ICUAUGGU 2566

1831 CCAUAGCC U AUGUCAUG 792 CAUGACAU CUGAUGAG X CGAA IGCUAUGG 2567

1837 CCUAUGUC A UGGCUGCC 793 GGCAGCCA CUGAUGAG X CGAA IACAUAGG 2568

1842 GUCAUGGC U GCCAUCUG 794 CAGAUGGC CUGAUGAG X CGAA ICCAUGAC 2569

1845 AUGGCUGC C AUCUGCGC 795 GCGCAGAU CUGAUGAG X CGAA ICAGCCAU 2570

1846 UGGCUGCC A UCUGCGCC 796 GGCGCAGA CUGAUGAG X CGAA IGCAGCCA 2571

1849 CUGCCAUC U GCGCCCUC 797 GAGGGCGC CUGAUGAG X CGAA IAUGGCAG 2572

1854 AUCUGCGC C CUCUUCAU 798 AUGAAGAG CUGAUGAG X CGAA ICGCAGAU 2573

1855 UCUGCGCC C UCUUCAUG 799 CAUGAAGA CUGAUGAG X CGAA IGCGCAGA 2574

1856 CUGCGCCC U CUUCAUGC 800 GCAUGAAG CUGAUGAG X CGAA IGGCGCAG 2575

1858 GCGCCCUC U UCAUGCUG 801 CAGCAUGA CUGAUGAG X CGAA IAGGGCGC 2576

1861 CCCUCUUC A UGCUGCCA 802 UGGCAGCA CUGAUGAG X CGAA IAAGAGGG 2577

1865 CUUCAUGC U GCCACUCU 803 AGAGUGGC CUGAUGAG X CGAA ICAUGAAG 2578

1868 CAUGCUGC C ACUCUGCC 804 GGCAGAGU CUGAUGAG X CGAA ICAGCAUG 2579

1869 AUGCUGCC A CUCUGCCU 805 AGGCAGAG CUGAUGAG X CGAA IGCAGCAU 2580

1871 GCUGCCAC U CUGCCUCA 806 UGAGGCAG CUGAUGAG X CGAA IUGGCAGC 2581

1873 UGCCACUC U GCCUCAUG 807 CAUGAGGC CUGAUGAG X CGAA lAGUGGCA 2582

1876 CACUCUGC C UCAUGGUG 808 CACCAUGA CUGAUGAG X CGAA ICAGAGUG 2583

1877 ACUCUGCC U CAUGGUGU 809 ACACCAUG CUGAUGAG X CGAA IGCAGAGU 2584

1879 UCUGCCUC A UGGUGUGU 810 ACACACCA CUGAUGAG X CGAA IAGGCAGA 2585

1889 GGUGUGUC A GUGGQGCU 811 AGCGCCAC CUGAUGAG X CGAA IACACACC 2586

1897 AGUGGCGC U GCCUCCGC 812 GCGGAGGC CUGAUGAG X CGAA ICGCCACU 2587

1900 GGCGCUGC C UCCGCUGC 813 GCAGCGGA CUGAUGAG X CGAA ICAGCGCC 2588

1901 GCGCUGCC U CCGCUGCC 814 GGCAGCGG CUGAUGAG X CGAA IGCAGCGC 2589

1903 GCUGCCUC C GCUGCCUG 815 CAGGCAGC CUGAUGAG X CGAA IAGGCAGC 2590

1906 GCCUCCGC u GCCUGCGC 816 GCGCAGGC CUGAUGAG X CGAA ICGGAGGC 2591

1909 UCCGCUGC c UGCGCCAG 817 CUGGCGCA CUGAUGAG X CGAA ICAGCGGA 2592

1910 CCGCUGCC u GCGCCAGC 818 GCUGGCGC CUGAUGAG X CGAA IGCAGCGG 2593

1915 GCCUGCGC c AGCAGCAU 819 AUGCUGCU CUGAUGAG X CGAA ICGCAGGC 2594

1916 CCUGCGCC A GCAGCAUG 820 CAUGCUGC CUGAUGAG X CGAA IGCGCAGG 2595

1919 GCGCCAGC A GCAUGAUG 821 CAUCAUGC CUGAUGAG X CGAA ICUGGCGC 2596

1922 CCAGCAGC A UGAUGACU 822 AGUCAUCA CUGAUGAG X CGAA ICUGCUGG 2597

1930 AUGAUGAC u UUGCUGAU 823 AUCAGCAA CUGAUGAG X CGAA lUCAUCAU 2598

1935 GACUUUGC U GAUGACAU 824 AUGUCAUC CUGAUGAG X CGAA ICAAAGUC 2599

1942 CUGAUGAC A UCUCCCUG ^'825 CAGGGAGA CUGAUGAG X CGAA IUCAUCAG 2600

1945 AUGACAUC U CCCUGCUG 826 CAGCAGGG CUGAUGAG X CGAA IAUGUCAU 2601

1947 GACAUCUC C CUGCUGAA 827 UUCAGCAG CUGAUGAG X CGAA IAGAUGUC 2602

1948 ACAUCUCC C UGCUGAAG 828 CUUCAGCA CUGAUGAG X CGAA IGAGAUGU 2603

1949 CAUCUCCC U GCUGAAGU 829 ACUUCAGC CUGAUGAG X CGAA IGGAGAUG 2604

1952 CUCCCUGC U GAAGUGAG 830 CUCACUUC CUGAUGAG X CGAA ICAGGGAG 2605

1966 GAGGAGGC C CAUGGGCA 831 UGCCCAUG CUGAUGAG X CGAA ICCUCCUC 2606

1967 AGGAGGCC C AUGGGCAG 832 CUGCCCAU CUGAUGAG X CGAA IGCCUCCU 2607

1968 GGAGGCCC A UGGGCAGA 833 UCUGCCCA CUGAUGAG X CGAA IGGCCUCC 2608

1974 CCAUGGGC A GAAGAUAG 834 CUAUCUUC CUGAUGAG X CGAA ICCCAUGG 2609

1989 AGAGAUUC C CCUGGACC 835 GGUCCAGG CUGAUGAG X CGAA IAAUCUCU 2610

1990 GAGAUUCC C CUGGACCA 836 UGGUCCAG CUGAUGAG X CGAA IGAAUCUC 2611

1991 AGAUUCCC C UGGACCAC 837 GUGGUCCA CUGAUGAG X CGAA IGGAAUCU 2612

1992 GAUUCCCC u GGACCACA 838 UGUGGUCC CUGAUGAG X CGAA IGGGAAUC 2613

1997 CCCUGGAC c ACACCUCC 839 GGAGGUGU CUGAUGAG X CGAA IUCCAGGG 2614

1998 CCUGGACC A CACCUCCG 840 CGGAGGUG CUGAUGAG X CGAA IGUCCAGG 2615

2000 UGGACCAC A CCUCCGUG 841 CACGGAGG CUGAUGAG X CGAA IUGGUCCA 2616 Table 19

2002 GACCACAC C UCCGUGGU 842 ACCACGGA CUGAUGAG X CGAA IUGUGGUC 2617

2003 ACCACACC U CCGUGGUU 843 AACCACGG CUGAUGAG X CGAA IGUGUGGU 2618

2005 CACACCUC C GUGGUUCA 844 UGAACCAC CUGAUGAG X CGAA IAGGUGUG 2619

2013 CGUGGUUC A CUUUGGUC 845 GACCAAAG CUGAUGAG X CGAA IAACCACG 2620

2015 UGGUUCAC U UUGGUCAC 846 GUGACCAA CUGAUGAG X CGAA IUGAACCA 2621

2022 CUUUGGUC A CAAGUAGG 847 CCUACUUG CUGAUGAG X CGAA IACCAAAG 2622

2024 UUGGUCAC A AGUAGGAG 848 CUCCUACU CUGAUGAG X CGAA lUGACCAA 2623

2035 UAGGAGAC A CAGAUGGC 849 GCCAUCUG CUGAUGAG X CGAA IUCUCCUA 2624

2037 GGAGACAC A GAUGGCAC 850 GUGCCAUC CUGAUGAG X CGAA IUGUCUCC 2625

2044 CAGAUGGC A CCUGUGGC 851 GCCACAGG CUGAUGAG X CGAA ICCAUCUG 2626

2046 GAUGGCAC C UGUGGCCA 852 UGGCCACA CUGAUGAG X CGAA IUGCCAUC 2627

2047 AUGGCACC U GUGGCCAG 853 CUGGCCAC CUGAUGAG X CGAA IGUGCCAU 2628

2053 CCUGUGGC C AGAGCACC 854 GGUGCUCU CUGAUGAG X CGAA ICCACAGG 2629

2054 CUGUGGCC A GAGCACCU 855 AGGUGCUC CUGAUGAG X CGAA IGCCACAG 2630

2059 GCCAGAGC A CCUCAGGA 856 UCCUGAGG CUGAUGAG X CGAA ICUCUGGC 2631

2061 CAGAGCAC C UCAGGACC 857 GGUCCUGA CUGAUGAG X CGAA lUGCUCUG 2632

2062 AGAGCACC U CAGGACCC 858 GGGUCCUG CUGAUGAG X CGAA IGUGCUCU 2633

2064 AGCACCUC A GGACCCUC 859 GAGGGUCC CUGAUGAG X CGAA IAGGUGCU 2634

2069 CUCAGGAC C CUCCCCAC 860 GUGGGGAG CUGAUGAG X CGAA IUCCUGAG 2635

2070 UCAGGACC C UCCCCACC 861 GGUGGGGA CUGAUGAG X CGAA IGUCCUGA 2636

2071 CAGGACCC U CCCCACCC 862 GGGUGGGG CUGAUGAG X CGAA IGGUCCUG 2637

2073 GGACCCUC c CCACCCAC 863 GUGGGUGG CUGAUGAG X CGAA IAGGGUCC 2638

2074 GACCCUCC c CACCCACC 864 GGUGGGUG CUGAUGAG X CGAA IGAGGGUC 2639

2075 ACCCUCCC c ACCCACCA 865 UGGUGGGU CUGAUGAG X CGAA IGGAGGGU 2640

2076 CCCUCCCC A CCCACCAA 866 UUGGUGGG CUGAUGAG X CGAA IGGGAGGG 2641

2078 CUCCCCAC C CACCAAAU 867 AUUUGGUG CUGAUGAG X CGAA IUGGGGAG 2642

2079 UCCCCACC C ACCAAAUG 868 CAUUUGGU CUGAUGAG X CGAA IGUGGGGA 2643

2080 CCCCACCC A CCAAAUGC 869 GCAUUUGG CUGAUGAG X CGAA IGGUGGGG 2644

2082 CCACCCAC C AAAUGCCU 870 AGGCAUUU CUGAUGAG X CGAA IUGGGUGG 2645

2083 CACCCACC A AAUGCCUC 871 GAGGCAUU CUGAUGAG X CGAA IGUGGGUG 2646

2089 CCAAAUGC C UCUGCCUU 872 AAGGCAGA CUGAUGAG X CGAA ICAUUUGG 2647

2090 CAAAUGCC U CUGCCUUG 873 CAAGGCAG CUGAUGAG X CGAA IGCAUUUG 2648

2092 AAUGCCUC U GCCUUGAU 874 AUCAAGGC CUGAUGAG X CGAA IAGGCAUU 2649

2095 GCCUCUGC C UUGAUGGA 875 UCCAUCAA CUGAUGAG X CGAA ICAGAGGC 2650

2096 CCUCUGCC U UGAUGGAG 876 CUCCAUCA CUGAUGAG X CGAA IGCAGAGG 2651

2116 GAAAAGGC U GGCAAGGU 877 ACCUUGCC CUGAUGAG X CGAA ICCUUUUC 2652

2120 AGGCUGGC A AGGUGGGU 878 ACCCACCU CUGAUGAG X CGAA ICCAGCCU 2653

2131 GUGGGUUC C AGGGACUG 879 CAGUCCCU CUGAUGAG X CGAA IAACCCAC 2654

2132 UGGGUUCC A GGGACUGU 880 ACAGUCCC CUGAUGAG X CGAA IGAACCCA 2655

2138 CCAGGGAC U GUACCUGU 881 ACAGGUAC CUGAUGAG X CGAA lUCCCUGG 2656

2143 GACUGUAC C UGUAGGAA 882 UUCCUACA CUGAUGAG X CGAA IUACAGUC 2657

2144 ACUGUACC U GUAGGAAA 883 UUUCCUAC CUGAUGAG X CGAA IGUACAGU 2658

2154 UAGGAAAC A GAAAAGAG 884 CUCUUUUC CUGAUGAG X CGAA IUUUCCUA 2659

2174 AAAGAAGC A CUCUGCUG 885 CAGCAGAG CUGAUGAG X CGAA ICUUCUUU 2660

2176 AGAAGCAC U CUGCUGGC 886 GCCAGCAG CUGAUGAG X CGAA IUGCUUCU 2661

2178 AAGCACUC u GCUGGCGG 887 CCGCCAGC CUGAUGAG X CGAA IAGUGCUU 2662

2181 CACUCUGC u GGCGGGAA 888 UUCCCGCC CUGAUGAG X CGAA ICAGAGUG 2663

2193 GGGAAUAC u CUUGGUCA 889 UGACCAAG CUGAUGAG X CGAA IUAUUCCC 2664

2195 GAAUACUC u UGGUCACC 890 GGUGACCA CUGAUGAG X CGAA IAGUAUUC 2665

2201 UCUUGGUC A CCUCAAAU 891 AUUUGAGG CUGAUGAG X CGAA lACCAAGA 2666

2203 UUGGUCAC C UCAAAUUU 892 AAAUUUGA CUGAUGAG X CGAA lUGACCAA 2667 Table 19

2204 UGGUCACC U CAAAUUUA 893 UAAAUUUG CUGAUGAG X CGAA IGUGACCA 2668

2206 GUCACCUC A AAUUUAAG 894 CUUAAAUU CUGAUGAG X CGAA IAGGUGAC 2669

2226 GGAAAUUC U GCUGCUUG 895 CAAGCAGC CUGAUGAG X CGAA IAAUUUCC 2670

2229 AAUUCUGC U GCUUGAAA 896 UUUCAAGC CUGAUGAG X CGAA ICAGAAUU 2671

2232 UCUGCUGC u UGAAACUU 897 AAGUUUCA CUGAUGAG X CGAA ICAGCAGA 2672

2239 CUUGAAAC u UCAGCCCU 898 AGGGCUGA CUGAUGAG X CGAA IUUUCAAG 2673

2242 GAAACUUC A GCCCUGAA 899 UUCAGGGC CUGAUGAG X CGAA IAAGUUUC 2674

2245 ACUUCAGC C CUGAACCU 900 AGGUUCAG CUGAUGAG X CGAA ICUGAAGU 2675

2246 CUUCAGCC C UGAACCUU 901 AAGGUUCA CUGAUGAG X CGAA IGCUGAAG 2676

2247 UUCAGCCC u GAACCUUU 902 AAAGGUUC CUGAUGAG X CGAA IGGCUGAA 2677

2252 CCCUGAAC C UUUGUCCA 903 UGGACAAA CUGAUGAG X CGAA IUUCAGGG 2678

2253 CCUGAACC u UUGUCCAC 904 GUGGACAA CUGAUGAG X CGAA IGUUCAGG 2679

2259 CCUUUGUC c ACCAUUCC 905 GGAAUGGU CUGAUGAG X CGAA IACAAAGG 2680

2260 CUUUGUCC A CCAUUCCU 906 AGGAAUGG CUGAUGAG X CGAA IGACAAAG 2681

2262 UUGUCCAC C AUUCCUUU 907 AAAGGAAU CUGAUGAG X CGAA IUGGACAA 2682

2263 UGUCCACC A UUCCUUUA 908 UAAAGGAA CUGAUGAG X CGAA IGUGGACA 2683

2267 CACCAUUC C UUUAAAUU 909 AAUUUAAA CUGAUGAG X CGAA IAAUGGUG 2684

2268 ACCAUUCC u UUAAAUUC 910 GAAUUUAA CUGAUGAG X CGAA IGAAUGGU 2685

2277 UUAAAUUC u CCAACCCA 911 UGGGUUGG CUGAUGAG X CGAA IAAUUUAA 2686

2279 AAAUUCUC c AACCCAAA 912 UUUGGGUU CUGAUGAG X CGAA IAGAAUUU 2687

2280 AAUUCUCC A ACCCAAAG 913 CUUUGGGU CUGAUGAG X CGAA IGAGAAUU 2688

2283 UCUCCAAC C CAAAGUAU 914 AUACUUUG CUGAUGAG X CGAA IUUGGAGA 2689

2284 CUCCAACC C AAAGUAUU 915 AAUACUUU CUGAUGAG X CGAA IGUUGGAG 2690

2285 UCCAACCC A AAGUAUUC 916 GAAUACUU CUGAUGAG X CGAA IGGUUGGA 2691

2294 AAGUAUUC U UCUUUUCU 917 AGAAAAGA CUGAUGAG X CGAA IAAUACUU 2692

2297 UAUUCUUC U UUUCUUAG 918 CUAAGAAA CUGAUGAG X CGAA IAAGAAUA 2693

2302 UUCUUUUC U UAGUUUCA 919 UGAAACUA CUGAUGAG X CGAA IAAAAGAA 2694

2310 UUAGUUUC A GAAGUACU 920 AGUACUUC CUGAUGAG X CGAA IAAACUAA 2695

2318 AGAAGUAC U GGCAUCAC 921 GUGAUGCC CUGAUGAG X CGAA IUACUUCU 2696

2322 GUACUGGC A UCACACGC 922 GCGUGUGA CUGAUGAG X CGAA ICCAGUAC 2697

2325 CUGGCAUC A CACGCAGG 923 CCUGCGUG CUGAUGAG X CGAA IAUGCCAG 2698

2327 GGCAUCAC A CGCAGGUU 924 AACCUGCG CUGAUGAG X CGAA IUGAUGCC 2699

2331 UCACACGC A GGUUACCU 925 AGGUAACC CUGAUGAG X CGAA ICGUGUGA 2700

2338 CAGGUUAC C UUGGCGUG 926 CACGCCAA CUGAUGAG X CGAA IUAACCUG 2701

2339 AGGUUACC U UGGCGUGU 927 ACACGCCA CUGAUGAG X CGAA IGUAACCU 2702

2351 CGUGUGUC c CUGUGGUA 928 UACCACAG CUGAUGAG X CGAA IACACACG 2703

2352 GUGUGUCC c UGUGGUAC 929 GUACCACA CUGAUGAG X CGAA IGACACAC 2704

2353 UGUGUCCC u GUGGUACC 930 GGUACCAC CUGAUGAG X CGAA IGGACACA 2705

2361 UGUGGUAC c CUGGCAGA 931 UCUGCCAG CUGAUGAG X CGAA IUACCACA 2706

2362 GUGGUACC c UGGCAGAG 932 CUCUGCCA CUGAUGAG X CGAA IGUACCAC 2707

2363 UGGUACCC u GGCAGAGA 933 UCUCUGCC CUGAUGAG X CGAA IGGUACCA 2708

2367 ACCCUGGC A GAGAAGAG 934 CUCUUCUC CUGAUGAG X CGAA ICCAGGGU 2709

2378 GAAGAGAC C AAGCUUGU 935 ACAAGCUU CUGAUGAG X CGAA IUCUCUUC 2710

2379 AAGAGACC A AGCUUGUU 936 AACAAGCU CUGAUGAG X CGAA IGUCUCUU 2711

2383 GACCAAGC U UGUUUCCC 937 GGGAAACA CUGAUGAG X CGAA ICUUGGUC 2712

2390 CUUGUUUC C CUGCUGGC 938 GCCAGCAG CUGAUGAG X CGAA IAAACAAG 2713

2391 UUGUUUCC C UGCUGGCC 939 GGCCAGCA CUGAUGAG X CGAA IGAAACAA 2714

2392 UGUUUCCC u GCUGGCCA 940 UGGCCAGC CUGAUGAG X CGAA IGGAAACA 2715

2395 UUCCCUGC u GGCCAAAG 941 CUUUGGCC CUGAUGAG X CGAA ICAGGGAA 2716

2399 CUGCUGGC c AAAGUCAG 942 CUGACUUU CUGAUGAG X CGAA ICCAGCAG 2717

2400 UGCUGGCC A AAGUCAGU 943 ACUGACUU CUGAUGAG X CGAA IGCCAGCA 2718 Table 19

2406 CCAAAGUC A GUAGGAGA 944 UCUCCUAC CUGAUGAG X CGAA IACUUUGG 2719

2421 GAGGAUGC A CAGUUUGC 945 GCAAACUG CUGAUGAG X CGAA ICAUCCUC 2720

2423 GGAUGCAC A GUUUGCUA 946 UAGCAAAC CUGAUGAG X CGAA IUGCAUCC 2721

2430 CAGUUUGC U AUUUGCUU 947 AAGCAAAU CUGAUGAG X CGAA ICAAACUG 2722

2437 CUAUUUGC U UUAGAGAC 948 GUCUCUAA CUGAUGAG X CGAA ICAAAUAG 2723

2446 UUAGAGAC A GGGACUGU 949 ACAGUCCC CUGAUGAG X CGAA IUCUCUAA 2724

2452 ACAGGGAC U GUAUAAAC 950 GUUUAUAC CUGAUGAG X CGAA IUCCCUGU 2725

2461 GUAUAAAC A AGCCUAAC 951 GUUAGGCU CUGAUGAG X CGAA IUUUAUAC 2726

2465 AAACAAGC C UAACAUUG 952 CAAUGUUA CUGAUGAG X CGAA ICUUGUUU 2727

2466 AACAAGCC U AACAUUGG 953 CCAAUGUU CUGAUGAG X CGAA IGCUUGUU 2728

2470 AGCCUAAC A UUGGUGCA 954 UGCACCAA CUGAUGAG X CGAA lUUAGGCU 2729

2478 AUUGGUGC A AAGAUUGC 955 GCAAUCUU CUGAUGAG X CGAA ICACCAAU 2730

2487 AAGAUUGC C UCUUGAAU 956 AUUCAAGA CUGAUGAG X CGAA ICAAUCUU 2731

2488 AGAUUGCC U CUUGAAUU 957 AAUUCAAG CUGAUGAG X CGAA IGCAAUCU 2732

2490 AUUGCCUC u UGAAUUAA 958 UUAAUUCA CUGAUGAG X CGAA IAGGCAAU 2733

2509 AAAAAAAC u AGAAAAAA 959 UUUUUUCU CUGAUGAG X CGAA IUUUUUUU 2734

Input Sequence = AF190725. Cut Site = G/ .

Stem Length = 8 . Core Sequence = CUGAUGAG X CGAA (X = GCCGUUAGGC or other stem II)

AF190725 (Homo sapiens beta-site APP cleaving enzyme (BACE) mRNA; 2526 bp)

Table 20

Table 20: Human BACE G-cleaver Ribozyme and Target Sequence

Pos Substrate Seq ID Ribozyme Rz Seq

ID

11 ACGCGUCC G CAGCCCGC 960 GCGGGCUG UGAUG GCAUGCACUAUGC GCG GGACGCGU 2735

18 CGCAGCCC G CCCGGGAG 961 CUCCCGGG UGAUG GCAUGCACUAUGC GCG GGGCUGCG 2736

29 CGGGAGCU G CGAGCCGC 962 GCGGCUCG UGAUG GCAUGCACUAUGC GCG AGCUCCCG 2737

31 GGAGCUGC G AGCCGCGA 963 UCGCGGCU UGAUG GCAUGCACUAUGC GCG GCAGCUCC 2738

36 UGCGAGCC G CGAGCUGG 964 CCAGCUCG UGAUG GCAUGCACUAUGC GCG GGCUCGCA 2739

38 CGAGCCGC G AGCUGGAU 965 AUCCAGCU UGAUG GCAUGCACUAUGC GCG GCGGCUCG 2740

58 GGUGGCCU G AGCAGCCA 966 UGGCUGCU UGAUG GCAUGCACUAUGC GCG AGGCCACC 2741

69 CAGCCAAC G CAGCCGCA 967 UGCGGCUG UGAUG GCAUGCACUAUGC GCG GUUGGCUG 2742

75 ACGCAGCC G CAGGAGCC 968 GGCUCCUG UGAUG GCAUGCACUAUGC GCG GGCUGCGU 2743

94 GAGCCCUU G CCCCUGCC 969 GGCAGGGG UGAUG GCAUGCACUAUGC GCG AAGGGCUC 2744

100 UUGCCCCU G CCCGCGCC 970 GGCGCGGG UGAUG GCAUGCACUAUGC GCG AGGGGCAA 2745

104 CCCUGCCC G CGCCGCCG 971 CGGCGGCG UGAUG GCAUGCACUAUGC GCG GGGCAGGG 2746

106 CUGCCCGC G CCGCCGCC 972 GGCGGCGG UGAUG GCAUGCACUAUGC GCG GCGGGCAG 2747

109 CCCGCGCC G CCGCCCGC 973 GCGGGCGG UGAUG GCAUGCACUAUGC GCG GGCGCGGG 2748

112 GCGCCGCC G CCCGCCGG 974 CCGGCGGG UGAUG GCAUGCACUAUGC GCG GGCGGCGC 2749

116 CGCCGCCC G CCGGGGGG 975 CCCCCCGG UGAUG GCAUGCACUAUGC GCG GGGCGGCG 2750

137 GGGAAGCC G CCACCGGC 976 GCCGGUGG UGAUG GCAUGCACUAUGC GCG GGCUUCCC 2751

148 ACCGGCCC G CCAUGCCC 977 GGGCAUGG UGAUG GCAUGCACUAUGC GCG GGGCCGGU 2752

153 CCCGCCAU G CCCGCCCC 978 GGGGCGGG UGAUG GCAUGCACUAUGC GCG AUGGCGGG 2753

157 CCAUGCCC G CCCCUCCC 979 GGGAGGGG UGAUG GCAUGCACUAUGC GCG GGGCAUGG 2754

172 CCAGCCCC G CCGGGAGC 980 GCUCCCGG UGAUG GCAUGCACUAUGC GCG GGGGCUGG 2755

183 GGGAGCCC G CGCCCGCU 981 AGCGGGCG UGAUG GCAUGCACUAUGC GCG GGGCUCCC 2756

185 GAGCCCGC G CCCGCUGC 982 GCAGCGGG UGAUG GCAUGCACUAUGC GCG GCGGGCUC 2757

189 CCGCGCCC G CUGCCCAG 983 CUGGGCAG UGAUG GCAUGCACUAUGC GCG GGGCGCGG 2758

192 CGCCCGCU G CCCAGGCU 984 AGCCUGGG UGAUG GCAUGCACUAUGC GCG AGCGGGCG 2759

205 GGCUGGCC G CCGCCGUG 985 CACGGCGG UGAUG GCAUGCACUAUGC GCG GGCCAGCC 2760

208 UGGCCGCC G CCGUGCCG 986 CGGCACGG UGAUG GCAUGCACUAUGC GCG GGCGGCCA 2761

213 GCCGCCGU G CCGAUGUA 987 UACAUCGG UGAUG GCAUGCACUAUGC GCG ACGGCGGC 2762

216 GCCGUGCC G AUGUAGCG 988 CGCUACAU UGAUG GCAUGCACUAUGC GCG GGCACGGC 2763

250 UCUCCCCU G CUCCCGUG 989 CACGGGAG UGAUG GCAUGCACUAUGC GCG AGGGGAGA 2764

Table 20

258 GCUCCCGU G CUCUGCGG 990 CCGCAGAG UGAUG GCAUGCACUAUGC GCG ACGGGAGC 2765

263 CGUGCUCU G CGGAUCUC 991 GAGAUCCG UGAUG GCAUGCACUAUGC GCG AGAGCACG 2766

276 UCUCCCCU G ACCGCUCU 992 AGAGCGGU UGAUG GCAUGCACUAUGC GςG AGGGGAGA 2767

280 CCCUGACC G CUCUCCAC 993 GUGGAGAG UGAUG GCAUGCACUAUGC GCG GGUCAGGG 2768

320 AGGGCCCU G CAGGCCCU 994 AGGGCCUG UGAUG GCAUGCACUAUGC GCG AGGGCCCU 2769

337 GGCGUCCU G AUGCCCCC 995 GGGGGCAU UGAUG GCAUGCACUAUGC GCG AGGACGCC 2770

340 GUCCUGAU G CCCCCAAG 996 CUUGGGGG UGAUG GCAUGCACUAUGC GCG AUCAGGAC 2771

360 CCUCUCCU G AGAAGCCA 997 UGGCUUCU UGAUG GCAUGCACUAUGC GCG AGGAGAGG 2772

397 GGGCAGGC G CCAGGGAC 998 GUCCCUGG UGAUG GCAUGCACUAUGC GCG GCCUGCCC 2773

420 GGGCCAGU G CGAGCCCA 999 UGGGCUCG UGAUG GCAUGCACUAUGC GCG ACUGGCCC 2774

422 GCCAGUGC G AGCCCAGA 1000 UCUGGGCU UGAUG GCAUGCACUAUGC GCG GCACUGGC 2775

437 GAGGGCCC G AAGGCCGG 1001 CCGGCCUU UGAUG GCAUGCACUAUGC GCG GGGCCCUC 2776

468 CAAGCCCU G CCCUGGCU 1002 AGCCAGGG UGAUG GCAUGCACUAUGC GCG AGGGCUUG 2777

480 UGGCUCCU G CUGUGGAU 1003 AUCCACAG UGAUG GCAUGCACUAUGC GCG AGGAGCCA 2778

493 GGAUGGGC G CGGGAGUG 1004 CACUCCCG UGAUG GCAUGCACUAUGC GCG GCCCAUCC 2779

501 GCGGGAGU G CUGCCUGC 1005 GCAGGCAG UGAUG GCAUGCACUAUGC GCG ACUCCCGC 2780

504 GGAGUGCU G CCUGCCCA 1006 UGGGCAGG UGAUG GCAUGCACUAUGC GCG AGCACUCC 2781

508 UGCUGCCU G CCCACGGC 1007 GCCGUGGG UGAUG GCAUGCACUAUGC GCG AGGCAGCA 2782

537 AUCCGGCU G CCCCUGCG 1008 CGCAGGGG UGAUG GCAUGCACUAUGC GCG AGCCGGAU 2783

543 CUGCCCCU G CGCAGCGG 1009 CCGCUGCG UGAUG GCAUGCACUAUGC GCG AGGGGCAG 2784

545 GCCCCUGC G CAGCGGCC 1010 GGCCGCUG UGAUG GCAUGCACUAUGC GCG GCAGGGGC 2785

562 UGGGGGGC G CCCCCCUG 1011 CAGGGGGG UGAUG GCAUGCACUAUGC GCG GCCCCCCA 2786

576 CUGGGGCU G CGGCUGCC 1012 GGCAGCCG UGAUG GCAUGCACUAUGC GCG AGCCCCAG 2787

582 CUGCGGCU G CCCCGGGA 1013 UCCCGGGG UGAUG GCAUGCACUAUGC GCG AGCCGCAG 2788

595 GGGAGACC G ACGAAGAG 1014 CUCUUCGU UGAUG GCAUGCACUAUGC GCG GGUCUCCC 2789

598 AGACCGAC G AAGAGCCC 1015 GGGCUCUU UGAUG GCAUGCACUAUGC GCG GUCGGUCU 2790

607 AAGAGCCC G AGGAGCCC 1016 GGGCUCCU UGAUG GCAUGCACUAUGC GCG GGGCUCUU 2791

654 GACAACCU G AGGGGCAA 1017 UUGCCCCU UGAUG GCAUGCACUAUGC GCG AGGUUGUC 2792

690 GUGGAGAU G ACCGUGGG 1018 CCCACGGU UGAUG GCAUGCACUAUGC GCG AUCUCCAC 2793

708 AGCCCCCC G CAGACGCU 1019 AGCGUCUG UGAUG GCAUGCACUAUGC GCG GGGGGGCU 2794

714 CCGCAGAC G CUCAACAU 1020 AUGUUGAG UGAUG GCAUGCACUAUGC GCG GUCUGCGG 2795

751 GUAACUUU G CAGUGGGU 1021 ACCCACUG UGAUG GCAUGCACUAUGC GCG AAAGUUAC 2796

760 CAGUGGGU G CUGCCCCC 1022 GGGGGCAG UGAUG GCAUGCACUAUGC GCG ACCCACUG 2797

763 UGGGUGCU G CCCCCCAC 1023 GUGGGGGG UGAUG GCAUGCACUAUGC GCG AGCACCCA 2798

Table 20

780 CCCUUCCU G CAUCGCUA 1024 UAGCGAUG UGAUG GCAUGCACUAUGC GCG AGGAAGGG 2799

785 CCUGCAUC G CUACUACC 1025 GGUAGUAG UGAUG GCAUGCACUAUGC GCG GAUGCAGG 2800

843 GUGUAUGU G CCCUACAC 1026 GUGUAGGG UGAUG GCAUGCACUAUGC GCG ACAUACAC 2801

883 UGGGCACC G ACCUGGUA 1027 UACCAGGU UGAUG GCAUGCACUAUGC GCG GGUGCCCA 2802

921 GUCACUGU G CGUGCCAA 1028 UUGGCACG UGAUG GCAUGCACUAUGC GCG ACAGUGAC 2803

925 CUGUGCGU G CCAACAUU 1029 AAUGUUGG UGAUG GCAUGCACUAUGC GCG ACGCACAG 2804

934 CCAACAUU G CUGCCAUC 1030 GAUGGCAG UGAUG GCAUGCACUAUGC GCG AAUGUUGG 2805

937 ACAUUGCU G CCAUCACU 1031 AGUGAUGG UGAUG GCAUGCACUAUGC GCG AGCAAUGU 2806

946 CCAUCACU G AAUCAGAC 1032 GUCUGAUU UGAUG GCAUGCACUAUGC GCG AGUGAUGG 2807

1006 UGGCCUAU G CUGAGAUU 1033 AAUCUCAG UGAUG GCAUGCACUAUGC GCG AUAGGCCA 2808

1009 CCUAUGCU G AGAUUGCC 1034 GGCAAUCU UGAUG GCAUGCACUAUGC GCG AGCAUAGG 2809

1015 CUGAGAUU G CCAGGCCU 1035 AGGCCUGG UGAUG GCAUGCACUAUGC GCG AAUCUCAG 2810

1024 CCAGGCCU G ACGACUCC 1036 GGAGUCGU UGAUG GCAUGCACUAUGC GCG AGGCCUGG 2811

1027 GGCCUGAC G ACUCCCUG 1037 CAGGGAGU UGAUG GCAUGCACUAUGC GCG GUCAGGCC 2812

1048 CUUUCUUU G ACUCUCUG 1038 CAGAGAGU UGAUG GCAUGCACUAUGC GCG AAAGAAAG 2813

1092 UUCUCCCU G CAGCUUUG 1039 CAAAGCUG UGAUG GCAUGCACUAUGC GCG AGGGAGAA 2814

1105 UUUGUGGU G CUGGCUUC 1040 GAAGCCAG UGAUG GCAUGCACUAUGC GCG ACCACAAA 2815

1129 ACCAGUCU G AAGUGCUG 1041 CAGCACUU UGAUG GCAUGCACUAUGC GCG AGACUGGU 2816

1134 UCUGAAGU G CUGGCCUC 1042 GAGGCCAG UGAUG GCAUGCACUAUGC GCG ACUUCAGA 2817

1158 GGGAGCAU G AUCAUUGG 1043 CCAAUGAU UGAUG GCAUGCACUAUGC GCG AUGCUCCC 2818

1174 GAGGUAUC G ACCACUCG 1044 CGAGUGGU UGAUG GCAUGCACUAUGC GCG GAUACCUC 2819

1182 GACCACUC G CUGUACAC 1045 GUGUACAG UGAUG GCAUGCACUAUGC GCG GAGUGGUC 2820

1234 GGUAUUAU G AGGUGAUC 1046 GAUCACCU UGAUG GCAUGCACUAUGC GCG AUAAUACC 2821

1239 UAUGAGGU G AUCAUUGU 1047 ACAAUGAU UGAUG GCAUGCACUAUGC GCG ACCUCAUA 2822

1248 AUCAUUGU G CGGGUGGA 1048 UCCACCCG UGAUG GCAUGCACUAUGC GCG ACAAUGAU 2823

1275 CAGGAUCU G AAAAUGGA 1049 UCCAUUUU UGAUG GCAUGCACUAUGC GCG AGAUCCUG 2824

1286 AAUGGACU G CAAGGAGU 1050 ACUCCUUG UGAUG GCAUGCACUAUGC GCG AGUCCAUU 2825

1303 ACAACUAU G ACAAGAGC 1051 GCUCUUGU UGAUG GCAUGCACUAUGC GCG AUAGUUGU 2826

1344 CUUCGUUU G CCCAAGAA 1052 UUCUUGGG UGAUG GCAUGCACUAUGC GCG AAACGAAG 2827

1360 AAGUGUUU G AAGCUGCA 1053 UGCAGCUU UGAUG GCAUGCACUAUGC GCG AAACACUU 2828

1366 UUGAAGCU G CAGUCAAA 1054 UUUGACUG UGAUG GCAUGCACUAUGC GCG AGCUUCAA 2829

1411 AGUUCCCU G AUGGUUUC 1055 GAAACCAU UGAUG GCAUGCACUAUGC GCG AGGGAACU 2830

1442 GCUGGUGU G CUGGCAAG 1056 CUUGCCAG UGAUG GCAUGCACUAUGC GCG ACACCAGC 2831

1504 UAAUGGGU G AGGUUACC 1057 GGUAACCU UGAUG GCAUGCACUAUGC GCG ACCCAUUA 2832

Table 20

1526 GUCCUUCC G CAUCACCA 1058 UGGUGAUG UGAUG GCAUGCACUAUGC GCG GGAAGGAC 2833

1542 AUCCUUCC G CAGCAAUA 1059 UAUUGCUG UGAUG GCAUGCACUAUGC GCG GGAAGGAU 2834

1554 CAAUACCU G CGGCCAGU 1060 ACUGGCCG UGAUG GCAUGCACUAUGC GCG AGGUAUUG 2835

1588 CCCAAGAC G ACUGUUAC 1061 GUAACAGU UGAUG GCAUGCACUAUGC GCG GUCUUGGG 2836

1603 ACAAGUUU G CCAUCUCA 1062 UGAGAUGG UGAUG GCAUGCACUAUGC GCG AAACUUGU 2837

1672 UUGUCUUU G AUCGGGCC 1063 GGCCCGAU UGAUG GCAUGCACUAUGC GCG AAAGACAA 2838

1682 UCGGGCCC G AAAACGAA 1064 UUCGUUUU UGAUG GCAUGCACUAUGC GCG GGGCCCGA 2839

1688 CCGAAAAC G AAUUGGCU 1065 AGCCAAUU UGAUG GCAUGCACUAUGC GCG GUUUUCGG 2840

1699 UUGGCUUU G CUGUCAGC 1066 GCUGACAG UGAUG GCAUGCACUAUGC GCG AAAGCCAA 2841

1708 CUGUCAGC G CUUGCCAU 1067 AUGGCAAG UGAUG GCAUGCACUAUGC GCG GCUGACAG 2842

1712 CAGCGCUU G CCAUGUGC 1068 GCACAUGG UGAUG GCAUGCACUAUGC GCG AAGCGCUG 2843

1719 UGCCAUGU G CACGAUGA 1069 UCAUCGUG UGAUG GCAUGCACUAUGC GCG ACAUGGCA 2844

1723 AUGUGCAC G AUGAGUUC 1070 GAACUCAU UGAUG GCAUGCACUAUGC GCG GUGCACAU 2845

1726 UGCACGAU G AGUUCAGG 1071 CCUGAACU UGAUG GCAUGCACUAUGC GCG AUCGUGCA 2846

1807 AGACAGAU G AGUCAACC 1072 GGUUGACU UGAUG GCAUGCACUAUGC GCG AUCUGUCU 2847

1821 ACCCUCAU G ACCAUAGC 1073 GCUAUGGU UGAUG GCAUGCACUAUGC GCG AUGAGGGU 2848

1843 UCAUGGCU G CCAUCUGC 1074 GCAGAUGG UGAUG GCAUGCACUAUGC GCG AGCCAUGA 2849

1850 UGCCAUCU G CGCCCUCU 1075 AGAGGGCG UGAUG GCAUGCACUAUGC GCG AGAUGGCA 2850

1852 CCAUCUGC G CCCUCUUC 1076 GAAGAGGG UGAUG GCAUGCACUAUGC GCG GCAGAUGG 2851

1863 CUCUUCAU G CUGCCACU 1077 AGUGGCAG UGAUG GCAUGCACUAUGC GCG AUGAAGAG 2852

1866 UUCAUGCU G CCACUCUG 1078 CAGAGUGG UGAUG GCAUGCACUAUGC GCG AGCAUGAA 2853

1874 GCCACUCU G CCUCAUGG 1079 CCAUGAGG UGAUG GCAUGCACUAUGC GCG AGAGUGGC 2854

1895 UCAGUGGC G CUGCCUCC 1080 GGAGGCAG UGAUG GCAUGCACUAUGC GCG GCCACUGA 2855

1898 GUGGCGCU G CCUCCGCU 1081 AGCGGAGG UGAUG GCAUGCACUAUGC GCG AGCGCCAC 2856

1904 CUGCCUCC G CUGCCUGC 1082 GCAGGCAG UGAUG GCAUGCACUAUGC GCG GGAGGCAG 2857

1907 CCUCCGCU G CCUGCGCC 1083 GGCGCAGG UGAUG GCAUGCACUAUGC GCG AGCGGAGG 2858

1911 CGCUGCCU G CGCCAGCA 1084 UGCUGGCG UGAUG GCAUGCACUAUGC GCG AGGCAGCG 2859

1913 CUGCCUGC G CCAGCAGC 1085 GCUGCUGG UGAUG GCAUGCACUAUGC GCG GCAGGCAG 2860

1924 AGCAGCAU G AUGACUUU 1086 AAAGUCAU UGAUG GCAUGCACUAUGC GCG AUGCUGCU 2861

1927 AGCAUGAU G ACUUUGCU 1087 AGCAAAGU UGAUG GCAUGCACUAUGC GCG AUCAUGCU 2862

1933 AUGACUUU G CUGAUGAC 1088 GUCAUCAG UGAUG GCAUGCACUAUGC GCG AAAGUCAU 2863

1936 ACUUUGCU G AUGACAUC 1089 GAUGUCAU UGAUG GCAUGCACUAUGC GCG AGCAAAGU 2864

1939 UUGCUGAU G ACAUCUCC 1090 GGAGAUGU UGAUG GCAUGCACUAUGC GCG AUCAGCAA 2865

1950 AUCUCCCU G CUGAAGUG 1091 CACUUCAG UGAUG GCAUGCACUAUGC GCG AGGGAGAU 2866

Table 20

1953 UCCCUGCU G AAGUGAGG 1092 CCUCACUU UGAUG GCAUGCACUAUGC GCG AGCAGGGA 2867

1958 GCUGAAGU G AGGAGGCC 1093 GGCCUCCU UGAUG GCAUGCACUAUGC GCG ACUUCAGC 2868

2087 CACCAAAU G CCUCUGCC 1094 GGCAGAGG UGAUG GCAUGCACUAUGC GCG AUUUGGUG 2869

2093 AUGCCUCU G CCUUGAUG 1095 CAUCAAGG UGAUG GCAUGCACUAUGC GCG AGAGGCAU 2870

2098 UCUGCCUU G AUGGAGAA 1096 UUCUCCAU UGAUG GCAUGCACUAUGC GCG AAGGCAGA 2871

2179 AGCACUCU G CUGGCGGG 1097 CCCGCCAG UGAUG GCAUGCACUAUGC GCG AGAGUGCU 2872

2227 GAAAUUCU G CUGCUUGA 1098 UCAAGCAG UGAUG GCAUGCACUAUGC GCG AGAAUUUC 2873

2230 AUUCUGCU G CUUGAAAC 1099 GUUUCAAG UGAUG GCAUGCACUAUGC GCG AGCAGAAU 2874

2234 UGCUGCUU G AAACUUCA 1100 UGAAGUUU UGAUG GCAUGCACUAUGC GCG AAGCAGCA 2875

2248 UCAGCCCU G AACCUUUG 1101 CAAAGGUU UGAUG GCAUGCACUAUGC GCG AGGGCUGA 2876

2329 CAUCACAC G CAGGUUAC 1102 GUAACCUG UGAUG GCAUGCACUAUGC GCG GUGUGAUG 2877

2393 GUUUCCCU G CUGGCCAA 1103 UUGGCCAG UGAUG GCAUGCACUAUGC GCG AGGGAAAC 2878

2419 GAGAGGAU G CACAGUUU 1104 AAACUGUG UGAUG GCAUGCACUAUGC GCG AUCCUCUC 2879

2428 CACAGUUU G CUAUUUGC 1105 GCAAAUAG UGAUG GCAUGCACUAUGC GCG AAACUGUG 2880

2435 UGCUAUUU G CUUUAGAG 1106 CUCUAAAG UGAUG GCAUGCACUAUGC GCG AAAUAGCA 2881

2476 ACAUUGGU G CAAAGAUU 1107 AAUCUUUG UGAUG GCAUGCACUAUGC GCG ACCAAUGU 2882

2485 CAAAGAUU G CCUCUUGA 1108 UCAAGAGG UGAUG GCAUGCACUAUGC GCG AAUCUUUG 2883

2492 UGCCUCUU G AAUUAAAA 1109 UUUUAAUU UGAUG GCAUGCACUAUGC GCG AAGAGGCA 2884

219 GUGCCGAU G UAGCGGGC 1110 GCCCGCUA UGAUG GCAUGCACUAUGC GCG AUCGGCAC 2885

483 CUCCUGCU G UGGAUGGG llll CCCAUCCA UGAUG GCAUGCACUAUGC GCG AGCAGGAG 2886

634 GCAGCUUU G UGGAGAUG 1112 CAUCUCCA UGAUG GCAUGCACUAUGC GCG AAAGCUGC 2887

804 AGGCAGCU G UCCAGCAC 1113 GUGCUGGA UGAUG GCAUGCACUAUGC GCG AGCUGCCU 2888

835 GGAAGGGU G UGUAUGUG 1114 CACAUACA UGAUG GCAUGCACUAUGC GCG ACCCUUCC 2889

837 AAGGGUGU G UAUGUGCC 1115 GGCACAUA UGAUG GCAUGCACUAUGC GCG ACACCCUU 2890

841 GUGUGUAU G UGCCCUAC 1116 GUAGGGCA UGAUG GCAUGCACUAUGC GCG AUACACAC 2891

919 ACGUCACU G UGCGUGCC 1117 GGCACGCA UGAUG GCAUGCACUAUGC GCG AGUGACGU 2892

1100 GCAGCUUU G UGGUGCUG 1118 CAGCACCA UGAUG GCAUGCACUAUGC GCG AAAGCUGC 2893

1144 UGGCCUCU G UCGGAGGG 1119 CCCUCCGA UGAUG GCAUGCACUAUGC GCG AGAGGCCA 2894

1185 CACUCGCU G UACACAGG 1120 CCUGUGUA UGAUG GCAUGCACUAUGC GCG AGCGAGUG 2895

1246 UGAUCAUU G UGCGGGUG 1121 CACCCGCA UGAUG GCAUGCACUAUGC GCG AAUGAUCA 2896

1315 AGAGCAUU G UGGACAGU 1122 ACUGUCCA UGAUG GCAUGCACUAUGC GCG AAUGCUCU 2897

1356 AAGAAAGU G UUUGAAGC 1123 GCUUCAAA UGAUG GCAUGCACUAUGC GCG ACUUUCUU 2898

1440 CAGCUGGU G UGCUGGCA 1124 UGCCAGCA UGAUG GCAUGCACUAUGC GCG ACCAGCUG 2899

1570 UGGAAGAU G UGGCCACG 1125 CGUGGCCA UGAUG GCAUGCACUAUGC GCG AUCUUCCA 2900

Table 20

1592 AGACGACU G UUACAAGU 1126 ACUUGUAA UGAUG GCAUGCACUAUGC GCG AGUCGUCU 2901

1630 CGGGCACU G UUAUGGGA 1127 UCCCAUAA UGAUG GCAUGCACUAUGC GCG AGUGCCCG 2902

1642 UGGGAGCU G UUAUCAUG 1128 CAUGAUAA UGAUG GCAUGCACUAUGC GCG AGCUCCCA 2903

1666 UCUACGUU G UCUUUGAU 1129 AUCAAAGA UGAUG GCAUGCACUAUGC GCG AACGUAGA 2904

1702 GCUUUGCU G UCAGCGCU 1130 AGCGCUGA UGAUG GCAUGCACUAUGC GCG AGCAAAGC 2905

1717 CUUGCCAU G UGCACGAU 1131 AUCGUGCA UGAUG GCAUGCACUAUGC GCG AUGGCAAG 2906

1759 GCCCUUUU G UCACCUUG 1132 CAAGGUGA UGAUG GCAUGCACUAUGC GCG AAAAGGGC 2907

1781 GGAAGACU G UGGCUACA 1133 UGUAGCCA UGAUG GCAUGCACUAUGC GCG AGUCUUCC 2908

1834 UAGCCUAU G UCAUGGCU 1134 AGCCAUGA UGAUG GCAUGCACUAUGC GCG AUAGGCUA 2909

1884 CUCAUGGU G UGUCAGUG 1135 CACUGACA UGAUG GCAUGCACUAUGC GCG ACCAUGAG 2910

1886 CAUGGUGU G UCAGUGGC 1136 GCCACUGA UGAUG GCAUGCACUAUGC GCG ACACCAUG 2911

2048 UGGCACCU G UGGCCAGA 1137 UCUGGCCA UGAUG GCAUGCACUAUGC GCG AGGUGCCA 2912

2139 CAGGGACU G UACCUGUA 1138 UACAGGUA UGAUG GCAUGCACUAUGC GCG AGUCCCUG 2913

2145 CUGUACCU G UAGGAAAC 1139 GUUUCCUA UGAUG GCAUGCACUAUGC GCG AGGUACAG 2914

2256 GAACCUUU G UCCACCAU 1140 AUGGUGGA UGAUG GCAUGCACUAUGC GCG AAAGGUUC 2915

2346 CUUGGCGU G UGUCCCUG 1141 CAGGGACA UGAUG GCAUGCACUAUGC GCG ACGCCAAG 2916

2348 UGGCGUGU G UCCCUGUG 1142 CACAGGGA UGAUG GCAUGCACUAUGC GCG ACACGCCA 2917

2354 GUGUCCCU G UGGUACCC 1143 GGGUACCA UGAUG GCAUGCACUAUGC GCG AGGGACAC 2918

2385 CCAAGCUU G UUUCCCUG 1144 CAGGGAAA UGAUG GCAUGCACUAUGC GCG AAGCUUGG 2919

2453 CAGGGACU G UAUAAACA 1145 UGUUUAUA UGAUG GCAUGCACUAUGC GCG AGUCCCUG 2920

Input Sequence = AF190725. Cut Site = G/ .

Stem Length = 8. Core Sequence = UGAUG GCAUGCACUAUGC GCG

AF190725 (Homo sapiens beta-site APP cleaving enzyme (BACE) mRNA; 2526 bp)

Table 21 Table 21: Human BACE Zinzyme Ribozyme and Target Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

11 ACGCGUCC G CAGCCCGC 960 GCGGGCUG GCCGAAAGGCGAGUCAAGGUCU GGACGCGU 2921

18 CGCAGCCC G CCCGGGAG 961 , CUCCCGGG GCCGAAAGGCGAGUCAAGGUCU GGGCUGCG 2922

29 CGGGAGCU G CGAGCCGC 962 GCGGCUCG GCCGAAAGGCGAGUCAAGGUCU AGCUCCCG 2923

36 UGCGAGCC G CGAGCUGG 964 CCAGCUCG GCCGAAAGGCGAGUCAAGGUCU GGCUCGCA 2924

69 CAGCCAAC G CAGCCGCA 967 UGCGGCUG GCCGAAAGGCGAGUCAAGGUCU GUUGGCUG 2925

75 ACGCAGCC G CAGGAGCC 968 GGCUCCUG GCCGAAAGGCGAGUCAAGGUCU GGCUGCGU 2926

94 GAGCCCUU G CCCCUGCC 969 ^■ GGCAGGGG GCCGAAAGGCGAGUCAAGGUCU AAGGGCUC 2927

100 UUGCCCCU G CCCGCGCC 970 GGCGCGGG GCCGAAAGGCGAGUCAAGGUCU AGGGGCAA 2928

104 CCCUGCCC G CGCCGCCG 971 CGGCGGCG GCCGAAAGGCGAGUCAAGGUCU GGGCAGGG 2929

106 CUGCCCGC G CCGCCGCC 972 GGCGGCGG GCCGAAAGGCGAGUCAAGGUCU GCGGGCAG 2930

109 CCCGCGCC G CCGCCCGC 973 GCGGGCGG GCCGAAAGGCGAGUCAAGGUCU GGCGCGGG 2931

112 GCGCCGCC G CCCGCCGG 974 CCGGCGGG GCCGAAAGGCGAGUCAAGGUCU GGCGGCGC 2932

116 CGCCGCCC G CCGGGGGG 975 CCCCCCGG GCCGAAAGGCGAGUCAAGGUCU GGGCGGCG 2933

137 GGGAAGCC G CCACCGGC 976 GCCGGUGG GCCGAAAGGCGAGUCAAGGUCU GGCUUCCC 2934

148 ACCGGCCC G CCAUGCCC 977 GGGCAUGG GCCGAAAGGCGAGUCAAGGUCU GGGCCGGU 2935

153 CCCGCCAU G CCCGCCCC 978 GGGGCGGG GCCGAAAGGCGAGUCAAGGUCU AUGGCGGG 2936

157 CCAUGCCC G CCCCUCCC 979 GGGAGGGG GCCGAAAGGCGAGUCAAGGUCU GGGCAUGG 2937

172 CCAGCCCC G CCGGGAGC 980 GCUCCCGG GCCGAAAGGCGAGUCAAGGUCU GGGGCUGG 2938

183 GGGAGCCC G CGCCCGCU 981 AGCGGGCG GCCGAAAGGCGAGUCAAGGUCU GGGCUCCC 2939

185 GAGCCCGC G CCCGCUGC 982 GCAGCGGG GCCGAAAGGCGAGUCAAGGUCU GCGGGCUC 2940

189 CCGCGCCC G CUGCCCAG 983 CUGGGCAG GCCGAAAGGCGAGUCAAGGUCU GGGCGCGG 2941

192 CGCCCGCU G CCCAGGCU 984 AGCCUGGG GCCGAAAGGCGAGUCAAGGUCU AGCGGGCG 2942

205 GGCUGGCC G CCGCCGUG 985 CACGGCGG GCCGAAAGGCGAGUCAAGGUCU GGCCAGCC 2943

208 UGGCCGCC G CCGUGCCG 986 CGGCACGG GCCGAAAGGCGAGUCAAGGUCU GGCGGCCA 2944

213 GCCGCCGU G CCGAUGUA 987 UACAUCGG GCCGAAAGGCGAGUCAAGGUCU ACGGCGGC 2945

250 UCUCCCCU G CUCCCGUG 989 CACGGGAG GCCGAAAGGCGAGUCAAGGUCU AGGGGAGA 2946

258 GCUCCCGU G CUCUGCGG 990 CCGCAGAG GCCGAAAGGCGAGUCAAGGUCU ACGGGAGC 2947

263 CGUGCUCU G CGGAUCUC 991 GAGAUCCG GCCGAAAGGCGAGUCAAGGUCU AGAGCACG 2948

280 CCCUGACC G CUCUCCAC 993 GUGGAGAG GCCGAAAGGCGAGUCAAGGUCU GGUCAGGG 2949

320 AGGGCCCU G CAGGCCCU 994 AGGGCCUG GCCGAAAGGCGAGUCAAGGUCU AGGGCCCU 2950

340 GUCCUGAU G CCCCCAAG 996 CUUGGGGG GCCGAAAGGCGAGUCAAGGUCU AUCAGGAC 2951

397 GGGCAGGC G CCAGGGAC 998 GUCCCUGG GCCGAAAGGCGAGUCAAGGUCU GCCUGCCC 2952

420 GGGCCAGU G CGAGCCCA 999 UGGGCUCG GCCGAAAGGCGAGUCAAGGUCU ACUGGCCC 2953

468 CAAGCCCU G CCCUGGCU 1002 AGCCAGGG GCCGAAAGGCGAGUCAAGGUCU AGGGCUUG 2954

480 UGGCUCCU G CUGUGGAU 1003 AUCCACAG GCCGAAAGGCGAGUCAAGGUCU AGGAGCCA 2955

493 GGAUGGGC G CGGGAGUG 1004 CACUCCCG GCCGAAAGGCGAGUCAAGGUCU GCCCAUCC ^* 2956

501 GCGGGAGU G CUGCCUGC 1005 GCAGGCAG GCCGAAAGGCGAGUCAAGGUCU ACUCCCGC 2957

504 GGAGUGCU G CCUGCCCA 1006 UGGGCAGG GCCGAAAGGCGAGUCAAGGUCU AGCACUCC 2958

508 UGCUGCCU G CCCACGGC 1007 GCCGUGGG GCCGAAAGGCGAGUCAAGGUCU AGGCAGCA 2959

537 AUCCGGCU G CCCCUGCG 1008 CGCAGGGG GCCGAAAGGCGAGUCAAGGUCU AGCCGGAU 2960

543 CUGCCCCU G CGCAGCGG 1009 CCGCUGCG GCCGAAAGGCGAGUCAAGGUCU AGGGGCAG 2961

545 GCCCCUGC G CAGCGGCC 1010 GGCCGCUG GCCGAAAGGCGAGUCAAGGUCU GCAGGGGC 2962

562 UGGGGGGC G CCCCCCUG 1011 CAGGGGGG GCCGAAAGGCGAGUCAAGGUCU GCCCCCCA 2963

576 CUGGGGCU G CGGCUGCC 1012 GGCAGCCG GCCGAAAGGCGAGUCAAGGUCU AGCCCCAG 2964

582 CUGCGGCU G CCCCGGGA 1013 UCCCGGGG GCCGAAAGGCGAGUCAAGGUCU AGCCGCAG 2965

708 AGCCCCCC G CAGACGCU 1019 AGCGUCUG GCCGAAAGGCGAGUCAAGGUCU GGGGGGCU 2966

714 CCGCAGAC G CUCAACAU 1020 AUGUUGAG GCCGAAAGGCGAGUCAAGGUCU GUCUGCGG 2967 Table 21

751 GUAACUUU G CAGUGGGU 1021 ACCCACUG GCCGAAAGGCGAGUCAAGGUCU AAAGUUAC 2968

760 CAGUGGGU G CUGCCCCC 1022 GGGGGCAG GCCGAAAGGCGAGUCAAGGUCU ACCCACUG 2969

763 UGGGUGCU G CCCCCCAC 1023 GUGGGGGG GCCGAAAGGCGAGUCAAGGUCU AGCACCCA 2970

780 CCCUUCCU G CAUCGCUA 1024 UAGCGAUG GCCGAAAGGCGAGUCAAGGUCU AGGAAGGG 2971

785 CCUGCAUC G CUACUACC 1025 GGUAGUAG GCCGAAAGGCGAGUCAAGGUCU GAUGCAGG 2972

843 GUGUAUGU G CCCUACAC 1026 GUGUAGGG GCCGAAAGGCGAGUCAAGGUCU ACAUACAC 2973

921 GUCACUGU G CGUGCCAA 1028 UUGGCACG GCCGAAAGGCGAGUCAAGGUCU ACAGUGAC 2974

925 CUGUGCGU G CCAACAUU 1029 AAUGUUGG GCCGAAAGGCGAGUCAAGGUCU ACGCACAG 2975

934 CCAACAUU G CUGCCAUC 1030 GAUGGCAG GCCGAAAGGCGAGUCAAGGUCU AAUGUUGG 2976

937 ACAUUGCU G CCAUCACU 1031 AGUGAUGG GCCGAAAGGCGAGUCAAGGUCU AGCAAUGU 2977

1006 UGGCCUAU G CUGAGAUU 1033 AAUCUCAG GCCGAAAGGCGAGUCAAGGUCU AUAGGCCA 2978

1015 CUGAGAUU G CCAGGCCU 1035 AGGCCUGG GCCGAAAGGCGAGUCAAGGUCU AAUCUCAG 2979

1092 UUCUCCCU G CAGCUUUG 1039 CAAAGCUG GCCGAAAGGCGAGUCAAGGUCU AGGGAGAA 2980

1105 UUUGUGGU G CUGGCUUC 1040 GAAGCCAG GCCGAAAGGCGAGUCAAGGUCU ACCACAAA 2981

1134 UCUGAAGU G CUGGCCUC 1042 GAGGCCAG GCCGAAAGGCGAGUCAAGGUCU ACUUCAGA 2982

1182 GACCACUC G CUGUACAC 1045 GUGUACAG GCCGAAAGGCGAGUCAAGGUCU GAGUGGUC 2983

1248 AUCAUUGU G CGGGUGGA 1048 UCCACCCG GCCGAAAGGCGAGUCAAGGUCU ACAAUGAU 2984

1286 AAUGGACU G CAAGGAGU 1050 ACUCCUUG GCCGAAAGGCGAGUCAAGGUCU AGUCCAUU 2985

1344 CUUCGUUU G CCCAAGAA 1052 UUCUUGGG GCCGAAAGGCGAGUCAAGGUCU AAACGAAG 2986

1366 UUGAAGCU G CAGUCAAA 1054 UUUGACUG GCCGAAAGGCGAGUCAAGGUCU AGCUUCAA 2987

1442 GCUGGUGU G CUGGCAAG 1056 ^" CUUGCCAG GCCGAAAGGCGAGUCAAGGUCU ACACCAGC 2988

1526 GUCCUUCC G CAUCACCA 1058 UGGUGAUG GCCGAAAGGCGAGUCAAGGUCU GGAAGGAC 2989

1542 AUCCUUCC G CAGCAAUA 1059 UAUUGCUG GCCGAAAGGCGAGUCAAGGUCU GGAAGGAU 2990

1554 CAAUACCU G CGGCCAGU 1060 ACUGGCCG GCCGAAAGGCGAGUCAAGGUCU AGGUAUUG 2991

1603 ACAAGUUU G CCAUCUCA 1062 UGAGAUGG GCCGAAAGGCGAGUCAAGGUCU AAACUUGU 2992

1699 UUGGCUUU G CUGUCAGC 1066 GCUGACAG GCCGAAAGGCGAGUCAAGGUCU AAAGCCAA 2993

1708 CUGUCAGC G CUUGCCAU 1067 AUGGCAAG GCCGAAAGGCGAGUCAAGGUCU GCUGACAG 2994

1712 CAGCGCUU G CCAUGUGC 1068 GCACAUGG GCCGAAAGGCGAGUCAAGGUCU AAGCGCUG 2995

1719 UGCCAUGU G CACGAUGA 1069 UCAUCGUG GCCGAAAGGCGAGUCAAGGUCU ACAUGGCA 2996

1843 UCAUGGCU G CCAUCUGC 1074 GCAGAUGG GCCGAAAGGCGAGUCAAGGUCU AGCCAUGA 2997

1850 UGCCAUCU G CGCCCUCU 1075 AGAGGGCG GCCGAAAGGCGAGUCAAGGUCU AGAUGGCA 2998

1852 CCAUCUGC G CCCUCUUC 1076 GAAGAGGG GCCGAAAGGCGAGUCAAGGUCU GCAGAUGG 2999

1863 CUCUUCAU G CUGCCACU 1077 AGUGGCAG GCCGAAAGGCGAGUCAAGGUCU AUGAAGAG 3000

1866 UUCAUGCU G CCACUCUG 1078 CAGAGUGG GCCGAAAGGCGAGUCAAGGUCU AGCAUGAA 3001

1874 GCCACUCU G CCUCAUGG 1079 CCAUGAGG GCCGAAAGGCGAGUCAAGGUCU AGAGUGGC 3002

1895 UCAGUGGC G CUGCCUCC 1080 GGAGGCAG GCCGAAAGGCGAGUCAAGGUCU GCCACUGA 3003

1898 GUGGCGCU G CCUCCGCU 1081 AGCGGAGG GCCGAAAGGCGAGUCAAGGUCU AGCGCCAC 3004

1904 CUGCCUCC G CUGCCUGC 1082 GCAGGCAG GCCGAAAGGCGAGUCAAGGUCU GGAGGCAG 3005

1907 CCUCCGCU G CCUGCGCC 1083 GGCGCAGG GCCGAAAGGCGAGUCAAGGUCU AGCGGAGG 3006

1911 CGCUGCCU G CGCCAGCA 1084 UGCUGGCG GCCGAAAGGCGAGUCAAGGUCU AGGCAGCG 3007

1913 CUGCCUGC G CCAGCAGC 1085 GCUGCUGG GCCGAAAGGCGAGUCAAGGUCU GCAGGCAG 3008

1933 AUGACUUU G CUGAUGAC 1088 GUCAUCAG GCCGAAAGGCGAGUCAAGGUCU AAAGUCAU 3009

1950 AUCUCCCU G CUGAAGUG 1091 CACUUCAG GCCGAAAGGCGAGUCAAGGUCU AGGGAGAU 3010

2087 CACCAAAU G CCUCUGCC 1094 GGCAGAGG GCCGAAAGGCGAGUCAAGGUCU AUUUGGUG 3011

2093 AUGCCUCU G CCUUGAUG 1095 CAUCAAGG GCCGAAAGGCGAGUCAAGGUCU AGAGGCAU 3012

2179 AGCACUCU G CUGGCGGG 1097 CCCGCCAG GCCGAAAGGCGAGUCAAGGUCU AGAGUGCU 3013

2227 GAAAUUCU G CUGCUUGA 1098 UCAAGCAG GCCGAAAGGCGAGUCAAGGUCU AGAAUUUC 3014

2230 AUUCUGCU G CUUGAAAC 1099 GUUUCAAG GCCGAAAGGCGAGUCAAGGUCU AGCAGAAU 3015

2329 CAUCACAC G CAGGUUAC 1102 GUAACCUG GCCGAAAGGCGAGUCAAGGUCU GUGUGAUG 3016

2393 GUUUCCCU G CUGGCCAA 1103 UUGGCCAG GCCGAAAGGCGAGUCAAGGUCU AGGGAAAC 3017

2419 GAGAGGAU G CACAGUUU 1104 AAACUGUG GCCGAAAGGCGAGUCAAGGUCU AUCCUCUC 3018 Table 21

2428 CACAGUUU G CUAUUUGC 1105 GCAAAUAG GCCGAAAGGCGAGUCAAGGUCU AAACUGUG 3019

2435 UGCUAUUU G CUUUAGAG 1106 CUCUAAAG GCCGAAAGGCGAGUCAAGGUCU AAAUAGCA 3020

2476 ACAUUGGU G CAAAGAUU 1107 AAUCUUUG GCCGAAAGGCGAGUCAAGGUCU ACCAAUGU 3021

2485 CAAAGAUU G CCUCUUGA 1108 UCAAGAGG GCCGAAAGGCGAGUCAAGGUCU AAUCUUUG 3022

219 GUGCCGAU G UAGCGGGC 1110 GCCCGCUA GCCGAAAGGCGAGUCAAGGUCU AUCGGCAC 3023

483 CUCCUGCU G UGGAUGGG llll CCCAUCCA GCCGAAAGGCGAGUCAAGGUCU AGCAGGAG 3024

634 GCAGCUUU G UGGAGAUG 1112 CAUCUCCA GCCGAAAGGCGAGUCAAGGUCU AAAGCUGC 3025

804 AGGCAGCU G UCCAGCAC 1113 GUGCUGGA GCCGAAAGGCGAGUCAAGGUCU AGCUGCCU 3026

835 GGAAGGGU G UGUAUGUG 1114 CACAUACA GCCGAAAGGCGAGUCAAGGUCU ACCCUUCC 3027

837 AAGGGUGU G UAUGUGCC 1115 GGCACAUA GCCGAAAGGCGAGUCAAGGUCU ACACCCUU 3028

841 GUGUGUAU G UGCCCUAC 1116 GUAGGGCA GCCGAAAGGCGAGUCAAGGUCU AUACACAC 3029

919 ACGUCACU G UGCGUGCC 1117 GGCACGCA GCCGAAAGGCGAGUCAAGGUCU AGUGACGU 3030

1100 GCAGCUUU G UGGUGCUG 1118 CAGCACCA GCCGAAAGGCGAGUCAAGGUCU AAAGCUGC 3031

1144 UGGCCUCU G UCGGAGGG 1119 CCCUCCGA GCCGAAAGGCGAGUCAAGGUCU AGAGGCCA 3032

1185 CACUCGCU G UACACAGG 1120 CCUGUGUA GCCGAAAGGCGAGUCAAGGUCU AGCGAGUG 3033

1246 UGAUCAUU G UGCGGGUG 1121 CACCCGCA GCCGAAAGGCGAGUCAAGGUCU AAUGAUCA 3034

1315 AGAGCAUU G UGGACAGU 1122 ACUGUCCA GCCGAAAGGCGAGUCAAGGUCU AAUGCUCU 3035

1356 AAGAAAGU G UUUGAAGC 1123 GCUUCAAA GCCGAAAGGCGAGUCAAGGUCU ACUUUCUU 3036

1440 CAGCUGGU G UGCUGGCA 1124 UGCCAGCA GCCGAAAGGCGAGUCAAGGUCU ACCAGCUG 3037

1570 UGGAAGAU G UGGCCACG 1125 CGUGGCCA GCCGAAAGGCGAGUCAAGGUCU AUCUUCCA 3038

1592 AGACGACU G UUACAAGU 1126 ACUUGUAA GCCGAAAGGCGAGUCAAGGUCU AGUCGUCU 3039

1630 CGGGCACU G UUAUGGGA 1127 UCCCAUAA GCCGAAAGGCGAGUCAAGGUCU AGUGCCCG 3040

1642 UGGGAGCU G UUAUCAUG 1128 CAUGAUAA GCCGAAAGGCGAGUCAAGGUCU AGCUCCCA 3041

1666 UCUACGUU G UCUUUGAU 1129 AUCAAAGA GCCGAAAGGCGAGUCAAGGUCU AACGUAGA 3042

1702 GCUUUGCU G UCAGCGCU 1130 AGCGCUGA GCCGAAAGGCGAGUCAAGGUCU AGCAAAGC 3043

1717 CUUGCCAU G UGCACGAU 1131 AUCGUGCA GCCGAAAGGCGAGUCAAGGUCU AUGGCAAG 3044

1759 GCCCUUUU G UCACCUUG 1132 CAAGGUGA GCCGAAAGGCGAGUCAAGGUCU AAAAGGGC 3045

1781 GGAAGACU G UGGCUACA 1133 UGUAGCCA GCCGAAAGGCGAGUCAAGGUCU AGUCUUCC 3046

1834 UAGCCUAU G UCAUGGCU 1134 AGCCAUGA GCCGAAAGGCGAGUCAAGGUCU AUAGGCUA 3047

1884 CUCAUGGU G UGUCAGUG 1135 CACUGACA GCCGAAAGGCGAGUCAAGGUCU ACCAUGAG 3048

1886 CAUGGUGU G UCAGUGGC 1136 GCCACUGA GCCGAAAGGCGAGUCAAGGUCU ACACCAUG 3049

2048 UGGCACCU G UGGCCAGA 1137 UCUGGCCA GCCGAAAGGCGAGUCAAGGUCU AGGUGCCA 3050

2139 CAGGGACU G UACCUGUA 1138 UACAGGUA GCCGAAAGGCGAGUCAAGGUCU AGUCCCUG 3051

2145 CUGUACCU G UAGGAAAC 1139 GUUUCCUA GCCGAAAGGCGAGUCAAGGUCU AGGUACAG 3052

2256 GAACCUUU G UCCACCAU 1140 AUGGUGGA GCCGAAAGGCGAGUCAAGGUCU AAAGGUUC 3053

2346 CUUGGCGU G UGUCCCUG 1141 CAGGGACA GCCGAAAGGCGAGUCAAGGUCU ACGCCAAG 3054

2348 UGGCGUGU G UCCCUGUG 1142 CACAGGGA GCCGAAAGGCGAGUCAAGGUCU ACACGCCA 3055

2354 GUGUCCCU G UGGUACCC 1143 GGGUACCA GCCGAAAGGCGAGUCAAGGUCU AGGGACAC 3056

2385 CCAAGCUU G UUUCCCUG 1144 CAGGGAAA GCCGAAAGGCGAGUCAAGGUCU AAGCUUGG 3057

2453 CAGGGACU G UAUAAACA 1145 UGUUUAUA GCCGAAAGGCGAGUCAAGGUCU AGUCCCUG 3058

14 CGUCCGCA G CCCGCCCG 1146 CGGGCGGG GCCGAAAGGCGAGUCAAGGUCU UGCGGACG 3059

26 GCCCGGGA G CUGCGAGC 1147 GCUCGCAG GCCGAAAGGCGAGUCAAGGUCU UCCCGGGC 3060

33 AGCUGCGA G CCGCGAGC 1148 GCUCGCGG GCCGAAAGGCGAGUCAAGGUCU UCGCAGCU 3061

40 AGCCGCGA G CUGGAUUA 1149 UAAUCCAG GCCGAAAGGCGAGUCAAGGUCU UCGCGGCU 3062

51 GGAUUAUG G UGGCCUGA 1150 UCAGGCCA GCCGAAAGGCGAGUCAAGGUCU CAUAAUCC 3063

54 UUAUGGUG G CCUGAGCA 1151 UGCUCAGG GCCGAAAGGCGAGUCAAGGUCU CACCAUAA 3064

60 UGGCCUGA G CAGCCAAC 1152 GUUGGCUG GCCGAAAGGCGAGUCAAGGUCU UCAGGCCA 3065

63 CCUGAGCA G CCAACGCA 1153 UGCGUUGG GCCGAAAGGCGAGUCAAGGUCU UGCUCAGG 3066

72 CCAACGCA G CCGCAGGA 1154 UCCUGCGG GCCGAAAGGCGAGUCAAGGUCU UGCGUUGG 3067

81 CCGCAGGA G CCCGGAGC 1155 GCUCCGGG GCCGAAAGGCGAGUCAAGGUCU UCCUGCGG 3068

88 AGCCCGGA G CCCUUGCC 1156 GGCAAGGG GCCGAAAGGCGAGUCAAGGUCU UCCGGGCU 3069 Table 21

134 CCAGGGAA G CCGCCACC 1157 GGUGGCGG GCCGAAAGGCGAGUCAAGGUCU UUCCCUGG 3070

144 CGCCACCG G CCCGCCAU 1158 AUGGCGGG GCCGAAAGGCGAGUCAAGGUCU CGGUGGCG 3071

167 CCCUCCCA G CCCCGCCG 1159 CGGCGGGG GCCGAAAGGCGAGUCAAGGUCU UGGGAGGG 3072

179 CGCCGGGA G CCCGCGCC 1160 GGCGCGGG GCCGAAAGGCGAGUCAAGGUCU UCCCGGCG 3073

198 CUGCCCAG G CUGGCCGC 1161 GCGGCCAG GCCGAAAGGCGAGUCAAGGUCU CUGGGCAG 3074

202 CCAGGCUG G CCGCCGCC 1162 GGCGGCGG GCCGAAAGGCGAGUCAAGGUCU CAGCCUGG 3075

211 CCGCCGCC G UGCCGAUG 1163 CAUCGGCA GCCGAAAGGCGAGUCAAGGUCU GGCGGCGG 3076

222 CCGAUGUA G CGGGCUCC 1164 GGAGCCCG GCCGAAAGGCGAGUCAAGGUCU UACAUCGG 3077

226 UGUAGCGG G CUCCGGAU 1165 AUCCGGAG GCCGAAAGGCGAGUCAAGGUCU CCGCUACA 3078

239 GGAUCCCA G CCUCUCCC 1166 GGGAGAGG GCCGAAAGGCGAGUCAAGGUCU UGGGAUCC 3079

256 CUGCUCCC G UGCUCUGC 1167 GCAGAGCA GCCGAAAGGCGAGUCAAGGUCU GGGAGCAG 3080

290 UCUCCACA G CCCGGACC 1168 GGUCCGGG GCCGAAAGGCGAGUCAAGGUCU UGUGGAGA 3081

304 ACCCGGGG G CUGGCCCA 1169 UGGGCCAG GCCGAAAGGCGAGUCAAGGUCU CCCCGGGU 3082

308 GGGGGCUG G CCCAGGGC 1170 GCCCUGGG GCCGAAAGGCGAGUCAAGGUCU CAGCCCCC 3083

315 GGCCCAGG G CCCUGCAG 1171 CUGCAGGG GCCGAAAGGCGAGUCAAGGUCU CCUGGGCC 3084

324 CCCUGCAG G CCCUGGCG 1172 CGCCAGGG GCCGAAAGGCGAGUCAAGGUCU CUGCAGGG 3085

330 AGGCCCUG G CGUCCUGA 1173 UCAGGACG GCCGAAAGGCGAGUCAAGGUCU CAGGGCCU 3086

332 GCCCUGGC G UCCUGAUG 1174 CAUCAGGA GCCGAAAGGCGAGUCAAGGUCU GCCAGGGC 3087

348 GCCCCCAA G CUCCCUCU 1175 AGAGGGAG GCCGAAAGGCGAGUCAAGGUCU UUGGGGGC 3088

365 CCUGAGAA G CCACCAGC 1176 GCUGGUGG GCCGAAAGGCGAGUCAAGGUCU UUCUCAGG 3089

372 AGCCACCA G CACCACCC 1177 GGGUGGUG GCCGAAAGGCGAGUCAAGGUCU UGGUGGCU 3090

391 ACUUGGGG G CAGGCGCC 1178 GGCGCCUG GCCGAAAGGCGAGUCAAGGUCU CCCCAAGU 3091

395 GGGGGCAG G CGCCAGGG 1179 CCCUGGCG GCCGAAAGGCGAGUCAAGGUCU CUGCCCCC 3092

410 GGACGGAC G UGGGCCAG 1180 CUGGCCCA GCCGAAAGGCGAGUCAAGGUCU GUCCGUCC 3093

414 GGACGUGG G CCAGUGCG 1181 CGCACUGG GCCGAAAGGCGAGUCAAGGUCU CCACGUCC 3094

418 GUGGGCCA G UGCGAGCC 1182 GGCUCGCA GCCGAAAGGCGAGUCAAGGUCU UGGCCCAC 3095

424 CAGUGCGA G CCCAGAGG 1183 CCUCUGGG GCCGAAAGGCGAGUCAAGGUCU UCGCACUG 3096

433 CCCAGAGG G CCCGAAGG 1184 CCUUCGGG GCCGAAAGGCGAGUCAAGGUCU CCUCUGGG 3097

441 GCCCGAAG G CCGGGGCC 1185 GGCCCCGG GCCGAAAGGCGAGUCAAGGUCU CUUCGGGC 3098

447 AGGCCGGG G CCCACCAU 1186 AUGGUGGG GCCGAAAGGCGAGUCAAGGUCU CCCGGCCU 3099

457 CCACCAUG G CCCAAGCC 1187 GGCUUGGG GCCGAAAGGCGAGUCAAGGUCU CAUGGUGG 3100

463 UGGCCCAA G CCCUGCCC 1188 GGGCAGGG GCCGAAAGGCGAGUCAAGGUCU UUGGGCCA 3101

474 CUGCCCUG G CUCCUGCU 1189 AGCAGGAG GCCGAAAGGCGAGUCAAGGUCU CAGGGCAG 3102

491 GUGGAUGG G CGCGGGAG 1190 CUCCCGCG GCCGAAAGGCGAGUCAAGGUCU CCAUCCAC 3103

499 GCGCGGGA G UGCUGCCU 1191 AGGCAGCA GCCGAAAGGCGAGUCAAGGUCU UCCCGCGC 3104

515 UGCCCACG G CACCCAGC 1192 GCUGGGUG GCCGAAAGGCGAGUCAAGGUCU CGUGGGCA 3105

522 GGCACCCA G CACGGCAU 1193 AUGCCGUG GCCGAAAGGCGAGUCAAGGUCU UGGGUGCC 3106

527 CCAGCACG G CAUCCGGC 1194 GCCGGAUG GCCGAAAGGCGAGUCAAGGUCU CGUGCUGG 3107

534 GGCAUCCG G CUGCCCCU 1195 AGGGGCAG GCCGAAAGGCGAGUCAAGGUCU CGGAUGCC 3108

548 CCUGCGCA G CGGCCUGG 1196 CCAGGCCG GCCGAAAGGCGAGUCAAGGUCU UGCGCAGG 3109

551 GCGCAGCG G CCUGGGGG 1197 CCCCCAGG GCCGAAAGGCGAGUCAAGGUCU CGCUGCGC 3110

560 CCUGGGGG G CGCCCCCC 1198 GGGGGGCG GCCGAAAGGCGAGUCAAGGUCU CCCCCAGG 3111

573 CCCCUGGG G CUGCGGCU 1199 AGCCGCAG GCCGAAAGGCGAGUCAAGGUCU CCCAGGGG 3112

579 GGGCUGCG G CUGCCCCG 1200 CGGGGCAG GCCGAAAGGCGAGUCAAGGUCU CGCAGCCC 3113

603 GACGAAGA G CCCGAGGA 1201 UCCUCGGG GCCGAAAGGCGAGUCAAGGUCU UCUUCGUC 3114

612 CCCGAGGA G CCCGGCCG 1202 CGGCCGGG GCCGAAAGGCGAGUCAAGGUCU UCCUCGGG 3115

617 GGAGCCCG G CCGGAGGG 1203 CCCUCCGG GCCGAAAGGCGAGUCAAGGUCU CGGGCUCC 3116

626 CCGGAGGG G CAGCUUUG 1204 CAAAGCUG GCCGAAAGGCGAGUCAAGGUCU CCCUCCGG 3117

629 GAGGGGCA G CUUUGUGG 1205 CCACAAAG GCCGAAAGGCGAGUCAAGGUCU UGCCCCUC 3118

643 UGGAGAUG G UGGACAAC 1206 GUUGUCCA GCCGAAAGGCGAGUCAAGGUCU CAUCUCCA 3119

659 CCUGAGGG G CAAGUCGG 1207 CCGACUUG GCCGAAAGGCGAGUCAAGGUCU CCCUCAGG 3120 Table 21

663 AGGGGCAA G UCGGGGCA 1208- UGCCCCGA GCCGAAAGGCGAGUCAAGGUCU UUGCCCCU 3121

669 AAGUCGGG G CAGGGCUA 1209 UAGCCCUG GCCGAAAGGCGAGUCAAGGUCU CCCGACUU 3122

674 GGGGCAGG G CUACUACG 1210 CGUAGUAG GCCGAAAGGCGAGUCAAGGUCU CCUGCCCC 3123

682 GCUACUAC G UGGAGAUG 1211 CAUCUCCA GCCGAAAGGCGAGUCAAGGUCU GUAGUAGC 3124

694 AGAUGACC G UGGGCAGC 1212 GCUGCCCA GCCGAAAGGCGAGUCAAGGUCU GGUCAUCU 3125

698 GACCGUGG G CAGCCCCC 1213 GGGGGCUG GCCGAAAGGCGAGUCAAGGUCU CCACGGUC 3126

701 CGUGGGCA G CCCCCCGC 1214 GCGGGGGG GCCGAAAGGCGAGUCAAGGUCU UGCCCACG 3127

727 ACAUCCUG G UGGAUACA 1215 UGUAUCCA GCCGAAAGGCGAGUCAAGGUCU CAGGAUGU 3128

737 GGAUACAG G CAGCAGUA 1216 UACUGCUG GCCGAAAGGCGAGUCAAGGUCU CUGUAUCC 3129

740 UACAGGCA G CAGUAACU 1217 AGUUACUG GCCGAAAGGCGAGUCAAGGUCU UGCCUGUA 3130

743 AGGCAGCA G UAACUUUG 1218 CAAAGUUA GCCGAAAGGCGAGUCAAGGUCU UGCUGCCU 3131

754 ACUUUGCA G UGGGUGCU 1219 AGCACCCA GCCGAAAGGCGAGUCAAGGUCU UGCAAAGU 3132

758 UGCAGUGG G UGCUGCCC 1220 GGGCAGCA GCCGAAAGGCGAGUCAAGGUCU CCACUGCA 3133

798 UACCAGAG G CAGCUGUC 1221 GACAGCUG GCCGAAAGGCGAGUCAAGGUCU CUCUGGUA 3134

801 CAGAGGCA G CUGUCCAG 1222 CUGGACAG GCCGAAAGGCGAGUCAAGGUCU UGCCUCUG 3135

809 GCUGUCCA G CACAUACC 1223 GGUAUGUG GCCGAAAGGCGAGUCAAGGUCU UGGACAGC 3136

833 CCGGAAGG G UGUGUAUG 1224 CAUACACA GCCGAAAGGCGAGUCAAGGUCU CCUUCCGG 3137

857 CACCCAGG G CAAGUGGG 1225 CCCACUUG GCCGAAAGGCGAGUCAAGGUCU CCUGGGUG 3138

861 CAGGGCAA G UGGGAAGG 1226 CCUUCCCA GCCGAAAGGCGAGUCAAGGUCU UUGCCCUG 3139

873 GAAGGGGA G CUGGGCAC 1227 GUGCCCAG GCCGAAAGGCGAGUCAAGGUCU UCCCCUUC 3140

878 GGAGCUGG G CACCGACC 1228 GGUCGGUG GCCGAAAGGCGAGUCAAGGUCU CCAGCUCC 3141

889 CCGACCUG G UAAGCAUC 1229 GAUGCUUA GCCGAAAGGCGAGUCAAGGUCU CAGGUCGG 3142

893 CCUGGUAA G CAUCCCCC 1230 GGGGGAUG GCCGAAAGGCGAGUCAAGGUCU UUACCAGG 3143

905 CCCCCAUG G CCCCAACG 1231 CGUUGGGG GCCGAAAGGCGAGUCAAGGUCU CAUGGGGG 3144

913 GCCCCAAC G UCACUGUG 1232 CACAGUGA GCCGAAAGGCGAGUCAAGGUCU GUUGGGGC 3145

923 CACUGUGC G UGCCAACA 1233 UGUUGGCA GCCGAAAGGCGAGUCAAGGUCU GCACAGUG 3146

957 UCAGACAA G UUCUUCAU 1234 AUGAAGAA GCCGAAAGGCGAGUCAAGGUCU UUGUCUGA 3147

971 CAUCAACG G CUCCAACU 1235 AGUUGGAG GCCGAAAGGCGAGUCAAGGUCU CGUUGAUG 3148

986 CUGGGAAG G CAUCCUGG 1236 CCAGGAUG GCCGAAAGGCGAGUCAAGGUCU CUUCCCAG 3149

996 AUCCUGGG G CUGGCCUA 1237 UAGGCCAG GCCGAAAGGCGAGUCAAGGUCU CCCAGGAU 3150

1000 UGGGGCUG G CCUAUGCU 1238 AGCAUAGG GCCGAAAGGCGAGUCAAGGUCU CAGCCCCA 3151

1020 AUUGCCAG G CCUGACGA 1239 UCGUCAGG GCCGAAAGGCGAGUCAAGGUCU CUGGCAAU 3152

1038 UCCCUGGA G CCUUUCUU 1240 AAGAAAGG GCCGAAAGGCGAGUCAAGGUCU UCCAGGGA 3153

1057 ACUCUCUG G UAAAGCAG 1241 CUGCUUUA GCCGAAAGGCGAGUCAAGGUCU CAGAGAGU 3154

1062 CUGGUAAA G CAGACCCA 1242 UGGGUCUG GCCGAAAGGCGAGUCAAGGUCU UUUACCAG 3155

1072 AGACCCAC G UUCCCAAC 1243 GUUGGGAA GCCGAAAGGCGAGUCAAGGUCU GUGGGUCU 3156

1095 UCCCUGCA G CUUUGUGG 1244 CCACAAAG GCCGAAAGGCGAGUCAAGGUCU UGCAGGGA 3157

1103 GCUUUGUG G UGCUGGCU 1245 AGCCAGCA GCCGAAAGGCGAGUCAAGGUCU CACAAAGC 3158

1109 UGGUGCUG G CUUCCCCC 1246 GGGGGAAG GCCGAAAGGCGAGUCAAGGUCU CAGCACCA 3159

1125 CUCAACCA G UCUGAAGU 1247 ACUUCAGA GCCGAAAGGCGAGUCAAGGUCU UGGUUGAG 3160

1132 AGUCUGAA G UGCUGGCC 1248 GGCCAGCA GCCGAAAGGCGAGUCAAGGUCU UUCAGACU 3161

1138 AAGUGCUG G CCUCUGUC 1249 GACAGAGG GCCGAAAGGCGAGUCAAGGUCU CAGCACUU 3162

1154 CGGAGGGA G CAUGAUCA 1250 UGAUCAUG GCCGAAAGGCGAGUCAAGGUCU UCCCUCCG 3163

1169 CAUUGGAG G UAUCGACC 1251 GGUCGAUA GCCGAAAGGCGAGUCAAGGUCU CUCCAAUG 3164

1193 GUACACAG G CAGUCUCU 1252 AGAGACUG GCCGAAAGGCGAGUCAAGGUCU CUGUGUAC 3165

1196 CACAGGCA G UCUCUGGU 1253 ACCAGAGA GCCGAAAGGCGAGUCAAGGUCU UGCCUGUG 3166

1203 AGUCUCUG G UAUACACC 1254 GGUGUAUA GCCGAAAGGCGAGUCAAGGUCU CAGAGACU 3167

1218 CCCAUCCG G CGGGAGUG 1255 CACUCCCG GCCGAAAGGCGAGUCAAGGUCU CGGAUGGG 3168

1224 CGGCGGGA G UGGUAUUA 1256 UAAUACCA GCCGAAAGGCGAGUCAAGGUCU UCCCGCCG 3169

1227 CGGGAGUG G UAUUAUGA 1257 UCAUAAUA GCCGAAAGGCGAGUCAAGGUCU CACUCCCG 3170

1237 AUUAUGAG G UGAUCAUU 1258 AAUGAUCA GCCGAAAGGCGAGUCAAGGUCU CUCAUAAU 3171 Table 21

1252 UUGUGCGG G UGGAGAUC 1259 GAUCUCCA GCCGAAAGGCGAGUCAAGGUCU CCGCACAA 3172

1293 UGCAAGGA G UACAACUA 1260 UAGUUGUA GCCGAAAGGCGAGUCAAGGUCU UCCUUGCA 3173

1310 UGACAAGA G CAUUGUGG 1261 CCACAAUG GCCGAAAGGCGAGUCAAGGUCU UCUUGUCA 3174

1322 UGUGGACA G UGGCACCA 1262 UGGUGCCA GCCGAAAGGCGAGUCAAGGUCU UGUCCACA 3175

1325 GGACAGUG G CACCACCA 1263 UGGUGGUG GCCGAAAGGCGAGUCAAGGUCU CACUGUCC 3176

1340 CAACCUUC G UUUGCCCA 1264 UGGGCAAA GCCGAAAGGCGAGUCAAGGUCU GAAGGUUG 3177

1354 CCAAGAAA G UGUUUGAA 1265 UUCAAACA GCCGAAAGGCGAGUCAAGGUCU UUUCUUGG 3178

1363 UGUUUGAA G CUGCAGUC 1266 GACUGCAG GCCGAAAGGCGAGUCAAGGUCU UUCAAACA 3179

1369 AAGCUGCA G UCAAAUCC 1267 GGAUUUGA GCCGAAAGGCGAGUCAAGGUCU UGCAGCUU 3180

1384 CCAUCAAG G CAGCCUCC 1268 GGAGGCUG GCCGAAAGGCGAGUCAAGGUCU CUUGAUGG 3181

1387 UCAAGGCA G CCUCCUCC 1269 GGAGGAGG GCCGAAAGGCGAGUCAAGGUCU UGCCUUGA 3182

1404 ACGGAGAA G UUCCCUGA 1270 UCAGGGAA GCCGAAAGGCGAGUCAAGGUCU UUCUCCGU 3183

1415 CCCUGAUG G UUUCUGGC 1271 GCCAGAAA GCCGAAAGGCGAGUCAAGGUCU CAUCAGGG 3184

1422 GGUUUCUG G CUAGGAGA 1272 UCUCCUAG GCCGAAAGGCGAGUCAAGGUCU CAGAAACC 3185

1431 CUAGGAGA G CAGCUGGU 1273 ACCAGCUG GCCGAAAGGCGAGUCAAGGUCU UCUCCUAG 3186

1434 GGAGAGCA G CUGGUGUG 1274 CACACCAG GCCGAAAGGCGAGUCAAGGUCU UGCUCUCC 3187

1438 AGCAGCUG G UGUGCUGG 1275 CCAGCACA GCCGAAAGGCGAGUCAAGGUCU CAGCUGCU 3188

1446 GUGUGCUG G CAAGCAGG 1276 CCUGCUUG GCCGAAAGGCGAGUCAAGGUCU CAGCACAC 3189

1450 GCUGGCAA G CAGGCACC 1277 GGUGCCUG GCCGAAAGGCGAGUCAAGGUCU UUGCCAGC 3190

1454 GCAAGCAG G CACCACCC 1278 GGGUGGUG GCCGAAAGGCGAGUCAAGGUCU CUGCUUGC 3191

1480 UUUUCCCA G UCAUCUCA 1279 UGAGAUGA GCCGAAAGGCGAGUCAAGGUCU UGGGAAAA 3192

1502 CCUAAUGG G UGAGGUUA 1280 UAACCUCA GCCGAAAGGCGAGUCAAGGUCU CCAUUAGG 3193

1507 UGGGUGAG G UUACCAAC 1281 GUUGGUAA GCCGAAAGGCGAGUCAAGGUCU CUCACCCA 3194

1518 ACCAACCA G UCCUUCCG 1282 CGGAAGGA GCCGAAAGGCGAGUCAAGGUCU UGGUUGGU 3195

1545 CUUCCGCA G CAAUACCU 1283 AGGUAUUG GCCGAAAGGCGAGUCAAGGUCU UGCGGAAG 3196

1557 UACCUGCG G CCAGUGGA 1284 UCCACUGG GCCGAAAGGCGAGUCAAGGUCU CGCAGGUA 3197

1561 UGCGGCCA G UGGAAGAU 1285 AUCUUCCA GCCGAAAGGCGAGUCAAGGUCU UGGCCGCA 3198

1573 AAGAUGUG G CCACGUCC 1286 GGACGUGG GCCGAAAGGCGAGUCAAGGUCU CACAUCUU 3199

1578 GUGGCCAC G UCCCAAGA 1287 UCUUGGGA GCCGAAAGGCGAGUCAAGGUCU GUGGCCAC 3200

1599 UGUUACAA G UUUGCCAU 1288 AUGGCAAA GCCGAAAGGCGAGUCAAGGUCU UUGUAACA 3201

1614 AUCUCACA G UCAUCCAC 1289 GUGGAUGA GCCGAAAGGCGAGUCAAGGUCU UGUGAGAU 3202

1625 AUCCACGG G CACUGUUA 1290 UAACAGUG GCCGAAAGGCGAGUCAAGGUCU CCGUGGAU 3203

1639 UUAUGGGA G CUGUUAUC 1291 GAUAACAG GCCGAAAGGCGAGUCAAGGUCU UCCCAUAA 3204

1655 CAUGGAGG G CUUCUACG 1292 CGUAGAAG GCCGAAAGGCGAGUCAAGGUCU CCUCCAUG 3205

1663 GCUUCUAC G uuσucuuu 1293 AAAGACAA GCCGAAAGGCGAGUCAAGGUCU GUAGAAGC 3206

1678 UUGAUCGG G CCCGAAAA 1294 UUUUCGGG GCCGAAAGGCGAGUCAAGGUCU CCGAUCAA 3207

1694 ACGAAUUG G CUUUGCUG 1295 CAGCAAAG GCCGAAAGGCGAGUCAAGGUCU CAAUUCGU 3208

1706 UGCUGUCA G CGCUUGCC 1296 GGCAAGCG GCCGAAAGGCGAGUCAAGGUCU UGACAGCA 3209

1728 CACGAUGA G UUCAGGAC 1297 GUCCUGAA GCCGAAAGGCGAGUCAAGGUCU UCAUCGUG 3210

1738 UCAGGACG G CAGCGGUG 1298 CACCGCUG GCCGAAAGGCGAGUCAAGGUCU CGUCCUGA 3211

1741 GGACGGCA G CGGUGGAA 1299 UUCCACCG GCCGAAAGGCGAGUCAAGGUCU UGCCGUCC 3212

1744 CGGCAGCG G UGGAAGGC 1300 GCCUUCCA GCCGAAAGGCGAGUCAAGGUCU CGCUGCCG 3213

1751 GGUGGAAG G CCCUUUUG 1301 CAAAAGGG GCCGAAAGGCGAGUCAAGGUCU CUUCCACC 3214

1784 AGACUGUG G CUACAACA 1302 UGUUGUAG GCCGAAAGGCGAGUCAAGGUCU CACAGUCU 3215

1809 ACAGAUGA G UCAACCCU 1303 AGGGUUGA GCCGAAAGGCGAGUCAAGGUCU UCAUCUGU 3216

1828 UGACCAUA G CCUAUGUC 1304 GACAUAGG GCCGAAAGGCGAGUCAAGGUCU UAUGGUCA 3217

1840 AUGUCAUG G CUGCCAUC 1305 GAUGGCAG GCCGAAAGGCGAGUCAAGGUCU CAUGACAU 3218

1882 GCCUCAUG G UGUGUCAG 1306 CUGACACA GCCGAAAGGCGAGUCAAGGUCU CAUGAGGC 3219

1890 GUGUGUCA G UGGCGCUG 1307 CAGCGCCA GCCGAAAGGCGAGUCAAGGUCU UGACACAC 3220

1893 UGUCAGUG G CGCUGCCU 1308 AGGCAGCG GCCGAAAGGCGAGUCAAGGUCU CACUGACA 3221

1917 CUGCGCCA G CAGCAUGA 1309 UCAUGCUG GCCGAAAGGCGAGUCAAGGUCU UGGCGCAG 3222 Table 21

1920 CGCCAGCA G CAUGAUGA 1310 UCAUCAUG GCCGAAAGGCGAGUCAAGGUCU UGCUGGCG 3223

1956 CUGCUGAA G UGAGGAGG 1311 CCUCCUCA GCCGAAAGGCGAGUCAAGGUCU UUCAGCAG 3224

1964 GUGAGGAG G CCCAUGGG 1312 CCCAUGGG GCCGAAAGGCGAGUCAAGGUCU CUCCUCAC 3225

1972 GCCCAUGG G CAGAAGAU 1313 AUCUUCUG GCCGAAAGGCGAGUCAAGGUCU CCAUGGGC 3226

2006 ACACCUCC G UGGUUCAC 1314 GUGAACCA GCCGAAAGGCGAGUCAAGGUCU GGAGGUGU 3227

2009 CCUCCGUG G UUCACUUU 1315 AAAGUGAA GCCGAAAGGCGAGUCAAGGUCU CACGGAGG 3228

2019 UCACUUUG G UCACAAGU 1316 ACUUGUGA GCCGAAAGGCGAGUCAAGGUCU CAAAGUGA 3229

2026 GGUCACAA G UAGGAGAC 1317 GUCUCCUA GCCGAAAGGCGAGUCAAGGUCU UUGUGACC 3230

2042 CACAGAUG G CACCUGUG 1318 CACAGGUG GCCGAAAGGCGAGUCAAGGUCU CAUCUGUG 3231

2051 CACCUGUG G CCAGAGCA 1319 UGCUCUGG GCCGAAAGGCGAGUCAAGGUCU CACAGGUG 3232

2057 UGGCCAGA G CACCUCAG 1320 CUGAGGUG GCCGAAAGGCGAGUCAAGGUCU UCUGGCCA 3233

2114 AGGAAAAG G CUGGCAAG 1321 CUUGCCAG GCCGAAAGGCGAGUCAAGGUCU CUUUUCCU 3234

2118 AAAGGCUG G CAAGGUGG 1322 CCACCUUG GCCGAAAGGCGAGUCAAGGUCU CAGCCUUU 3235

2123 CUGGCAAG G UGGGUUCC 1323 GGAACCCA GCCGAAAGGCGAGUCAAGGUCU CUUGCCAG 3236

2127 CAAGGUGG G UUCCAGGG 1324 CCCUGGAA GCCGAAAGGCGAGUCAAGGUCU CCACCUUG 3237

2172 AGAAAGAA G CACUCUGC 1325 GCAGAGUG GCCGAAAGGCGAGUCAAGGUCU UUCUUUCU 3238

2183 CUCUGCUG G CGGGAAUA 1326 UAUUCCCG GCCGAAAGGCGAGUCAAGGUCU CAGCAGAG 3239

2198 UACUCUUG G UCACCUCA 1327 UGAGGUGA GCCGAAAGGCGAGUCAAGGUCU CAAGAGUA 3240

2214 AAAUUUAA G UCGGGAAA 1328 UUUCCCGA GCCGAAAGGCGAGUCAAGGUCU UUAAAUUU 3241

2243 AAACUUCA G CCCUGAAC 1329 GUUCAGGG GCCGAAAGGCGAGUCAAGGUCU UGAAGUUU 3242

2288 AACCCAAA G UAUUCUUC 1330 GAAGAAUA GCCGAAAGGCGAGUCAAGGUCU UUUGGGUU 3243

2305 UUUUCUUA G UUUCAGAA 1331 UUCUGAAA GCCGAAAGGCGAGUCAAGGUCU UAAGAAAA 3244

2314 UUUCAGAA G UACUGGCA 1332 UGCCAGUA GCCGAAAGGCGAGUCAAGGUCU UUCUGAAA 3245

2320 AAGUACUG G CAUCACAC 1333 GUGUGAUG GCCGAAAGGCGAGUCAAGGUCU CAGUACUU 3246

2333 ACACGCAG G UUACCUUG 1334 CAAGGUAA GCCGAAAGGCGAGUCAAGGUCU CUGCGUGU 3247

2342 UUACCUUG G CGUGUGUC 1335 GACACACG GCCGAAAGGCGAGUCAAGGUCU CAAGGUAA 3248

2344 ACCUUGGC G UGUGUCCC 1336 GGGACACA GCCGAAAGGCGAGUCAAGGUCU GCCAAGGU 3249

2357 UCCCUGUG G UACCCUGG 1337 CCAGGGUA GCCGAAAGGCGAGUCAAGGUCU CACAGGGA 3250

2365 GUACCCUG G CAGAGAAG 1338 CUUCUCUG GCCGAAAGGCGAGUCAAGGUCU CAGGGUAC 3251

2381 GAGACCAA G CUUGUUUC 1339 GAAACAAG GCCGAAAGGCGAGUCAAGGUCU UUGGUCUC 3252

2397 CCCUGCUG G CCAAAGUC 1340 GACUUUGG GCCGAAAGGCGAGUCAAGGUCU CAGCAGGG 3253

2403 UGGCCAAA G UCAGUAGG 1341 CCUACUGA GCCGAAAGGCGAGUCAAGGUCU UUUGGCCA 3254

2407 CAAAGUCA G UAGGAGAG 1342 CUCUCCUA GCCGAAAGGCGAGUCAAGGUCU UGACUUUG 3255

2424 GAUGCACA G UUUGCUAU 1343 AUAGCAAA GCCGAAAGGCGAGUCAAGGUCU UGUGCAUC 3256

2463 AUAAACAA G CCUAACAU 1344 AUGUUAGG GCCGAAAGGCGAGUCAAGGUCU UUGUUUAU 3257

2474 UAACAUUG G UGCAAAGA 1345 UCUUUGCA GCCGAAAGGCGAGUCAAGGUCU CAAUGUUA 3258

Input Sequence = AF190725. Cut Site = G/ .

Stem Length = 8 . Core Sequence = GCcgaaagGCGaGuCaaGGuCu

AF190725 (Homo sapiens beta-site APP cleaving enzyme (BACE) mRNA; 2526 bp)

Table 22 Table 22: Human BACE DNAzyme and Target Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

48 GCUGGAUU A UGGUGGCC 3 GGCCACCA GGCTAGCTACAACGA AATCCAGC 3259

677 GCAGGGCU A CUACGUGG 27 CCACGTAG GGCTAGCTACAACGA AGCCCTGC 3260

680 GGGCUACU A CGUGGAGA 28 TCTCCACG GGCTAGCTACAACGA AGTAGCCC 3261

733 UGGUGGAU A CAGGCAGC 31 GCTGCCTG GGCTAGCTACAACGA ATCCACCA 3262

788 GCAUCGCU A CUACCAGA 38 TCTGGTAG GGCTAGCTACAACGA AGCGATGC 3263

791 UCGCUACU A CCAGAGGC 39 GCCTCTGG GGCTAGCTACAACGA AGTAGCGA 3264

815 CAGCACAU A CCGGGACC 41 GGTCCCGG GGCTAGCTACAACGA ATGTGCTG 3265

839 GGGUGUGU A UGUGCCCU 43 AGGGCACA GGCTAGCTACAACGA ACACACCC 3266

848 UGUGCCCU A CACCCAGG 44 CCTGGGTG GGCTAGCTACAACGA AGGGCACA 3267

1004 GCUGGCCU A UGCUGAGA 58 TCTCAGCA GGCTAGCTACAACGA AGGCCAGC 3268

1171 UUGGAGGU A UCGACCAC 85 GTGGTCGA GGCTAGCTACAACGA ACCTCCAA 3269

1187 CUCGCUGU A CACAGGCA 88 TGCCTGTG GGCTAGCTACAACGA ACAGCGAG 3270

1205 UCUCUGGU A UACACCCA 91 TGGGTGTA GGCTAGCTACAACGA ACCAGAGA 3271

1207 UCUGGUAU A CACCCAUC 92 GATGGGTG GGCTAGCTACAACGA ATACCAGA 3272

1229 GGAGUGGU A UUAUGAGG 94 CCTCATAA GGCTAGCTACAACGA ACCACTCC 3273

1232 GUGGUAUU A UGAGGUGA 96 TCACCTCA GGCTAGCTACAACGA AATACCAC 3274

1295 CAAGGAGU A CAACUAUG 101 CATAGTTG GGCTAGCTACAACGA ACTCCTTG 3275

1301 GUACAACU A UGACAAGA 102 TCTTGTCA GGCTAGCTACAACGA AGTTGTAC 3276

1493 CUCACUCU A CCUAAUGG 130 CCATTAGG GGCTAGCTACAACGA AGAGTGAG 3277

1510 GUGAGGUU A CCAACCAG 133 CTGGTTGG GGCTAGCTACAACGA AACCTCAC 3278

1550 GCAGCAAU A CCUGCGGC 141 GCCGCAGG GGCTAGCTACAACGA ATTGCTGC 3279

1595 CGACUGUU A CAAGUUUG 144 CAAACTTG GGCTAGCTACAACGA AACAGTCG 3280

1633 GCACUGUU A UGGGAGCU 152 AGCTCCCA GGCTAGCTACAACGA AACAGTGC 3281

1645 GAGCUGUU A UCAUGGAG 154 CTCCATGA GGCTAGCTACAACGA AACAGCTC 3282

1661 GGGCUUCU A CGUUGUCU 158 AGACAACG GGCTAGCTACAACGA AGAAGCCC 3283

1787 CUGUGGCU A CAACAUUC 176 GAATGTTG GGCTAGCTACAACGA AGCCACAG 3284

1832 CAUAGCCU A UGUCAUGG 182 CCATGACA GGCTAGCTACAACGA AGGCTATG 3285

2141 GGGACUGU A CCUGUAGG 212 CCTACAGG GGCTAGCTACAACGA ACAGTCCC 3286

2191 GCGGGAAU A CUCUUGGU 215 ACCAAGAG GGCTAGCTACAACGA ATTCCCGC 3287

2290 CCCAAAGU A UUCUUCUU 240 AAGAAGAA GGCTAGCTACAACGA ACTTTGGG 3288

2316 UCAGAAGU A CUGGCAUC 254 GATGCCAG GGCTAGCTACAACGA ACTTCTGA 3289

2336 CGCAGGUU A CCUUGGCG 257 CGCCAAGG GGCTAGCTACAACGA AACCTGCG 3290

2359 CCUGUGGU A CCCUGGCA 260 TGCCAGGG GGCTAGCTACAACGA ACCACAGG 3291

2431 AGUUUGCU A UUUGCUUU 269 AAAGCAAA GGCTAGCTACAACGA AGCAAACT 3292

2455 GGGACUGU A UAAACAAG 275 CTTGTTTA GGCTAGCTACAACGA ACAGTCCC 3293

140 AAGCCGCC A CCGGCCCG 322 CGGGCCGG GGCTAGCTACAACGA GGCGGCTT 3294

151 GGCCCGCC A UGCCCGCC 327 GGCGGGCA GGCTAGCTACAACGA GGCGGGCC 3295

287 CGCUCUCC A CAGCCCGG 380 CCGGGCTG GGCTAGCTACAACGA GGAGAGCG 3296

368 GAGAAGCC A CCAGCACC 412 GGTGCTGG GGCTAGCTACAACGA GGCTTCTC 3297

374 CCACCAGC A CCACCCAG 415 CTGGGTGG GGCTAGCTACAACGA GCTGGTGG 3298

377 CCAGCACC A CCCAGACU 417 AGTCTGGG GGCTAGCTACAACGA GGTGCTGG 3299

451 CGGGGCCC A CCAUGGCC 435 GGCCATGG GGCTAGCTACAACGA GGGCCCCG 3300

454 GGCCCACC A UGGCCCAA 437 TTGGGCCA GGCTAGCTACAACGA GGTGGGCC 3301

512 GCCUGCCC A CGGCACCC 456 GGGTGCCG GGCTAGCTACAACGA GGGCAGGC 3302

517 CCCACGGC A CCCAGCAC 457 GTGCTGGG GGCTAGCTACAACGA GCCGTGGG 3303

524 CACCCAGC A CGGCAUCC 461 GGATGCCG GGCTAGCTACAACGA GCTGGGTG 3304

529 AGCACGGC A UCCGGCUG 462 CAGCCGGA GGCTAGCTACAACGA GCCGTGCT 3305 Table 22

721 CGCUCAAC A UCCUGGUG 508 CACCAGGA GGCTAGCTACAACGA GTTGAGCG 3306

770 UGCCCCCC A CCCCUUCC 522 GGAAGGGG GGCTAGCTACAACGA GGGGGGCA , 3307

782 CUUCCUGC A UCGCUACU 529 AGTAGCGA GGCTAGCTACAACGA GCAGGAAG 3308

811 UGUCCAGC A CAUACCGG 538 CCGGTATG GGCTAGCTACAACGA GCTGGACA 3309

813 UCCAGCAC A UACCGGGA 539 TCCCGGTA GGCTAGCTACAACGA GTGCTGGA 3310

850 UGCCCUAC A CCCAGGGC 547 GCCCTGGG GGCTAGCTACAACGA GTAGGGCA 3311

880 AGCUGGGC A CCGACCUG 553 CAGGTCGG GGCTAGCTACAACGA GCCCAGCT 3312

895 UGGUAAGC A UCCCCCAU 557 ATGGGGGA GGCTAGCTACAACGA GCTTACCA 3313

902 CAUCCCCC A UGGCCCCA 562 TGGGGCCA GGCTAGCTACAACGA GGGGGATG 3314

916 CCAACGUC A CUGUGCGU 567 ACGCACAG GGCTAGCTACAACGA GACGTTGG 3315

931 GUGCCAAC A UUGCUGCC 571 GGCAGCAA GGCTAGCTACAACGA GTTGGCAC 3316

940 UUGCUGCC A UCACUGAA 574 TTCAGTGA GGCTAGCTACAACGA GGCAGCAA 3317

943 CUGCCAUC A CUGAAUCA 575 TGATTCAG GGCTAGCTACAACGA GATGGCAG 3318

964 AGUUCUUC A UCAACGGC 580 GCCGTTGA GGCTAGCTACAACGA GAAGAACT 3319

988 GGGAAGGC A UCCUGGGG 586 CCCCAGGA GGCTAGCTACAACGA GCCTTCCC 3320

1070 GCAGACCC A CGUUCCCA 610 TGGGAACG GGCTAGCTACAACGA GGGTCTGC 3321

1156 GAGGGAGC A UGAUCAUU 638 AATGATCA GGCTAGCTACAACGA GCTCCCTC 3322

1162 GCAUGAUC A UUGGAGGU 639 ACCTCCAA GGCTAGCTACAACGA GATCATGC 3323

1178 UAUCGACC A CUCGCUGU 641 ACAGCGAG GGCTAGCTACAACGA GGTCGATA 3324

1189 CGCUGUAC A CAGGCAGU 644 ACTGCCTG GGCTAGCTACAACGA GTACAGCG 3325

1209 UGGUAUAC A CCCAUCCG 649 CGGATGGG GGCTAGCTACAACGA GTATACCA 3326

1213 AUACACCC A UCCGGCGG 652 CCGCCGGA GGCTAGCTACAACGA GGGTGTAT 3327

1243 AGGUGAUC A UUGUGCGG 654 CCGCACAA GGCTAGCTACAACGA GATCACCT 3328

1312 ACAAGAGC A UUGUGGAC 663 GTCCACAA GGCTAGCTACAACGA GCTCTTGT 3329

1327 ACAGUGGC A CCACCAAC 665 GTTGGTGG GGCTAGCTACAACGA GCCACTGT 3330

1330 GUGGCACC A CCAACCUU 667 AAGGTTGG GGCTAGCTACAACGA GGTGCCAC 3331

1378 UCAAAUCC A UCAAGGCA 679 TGCCTTGA GGCTAGCTACAACGA GGATTTGA 3332

1396 CCUCCUCC A CGGAGAAG 687 CTTCTCCG GGCTAGCTACAACGA GGAGGAGG 3333

1456 AAGCAGGC A CCACCCCU 698 AGGGGTGG GGCTAGCTACAACGA GCCTGCTT 3334

1459 CAGGCACC A CCCCUUGG 700 CCAAGGGG GGCTAGCTACAACGA GGTGCCTG 3335

1471 CUUGGAAC A UUUUCCCA 705 TGGGAAAA GGCTAGCTACAACGA GTTCCAAG 3336

1483 UCCCAGUC A UCUCACUC 709 GAGTGAGA GGCTAGCTACAACGA GACTGGGA 3337

1488 GUCAUCUC A CUCUACCU 711 AGGTAGAG GGCTAGCTACAACGA GAGATGAC 3338

1528 CCUUCCGC A UCACCAUC 723 GATGGTGA GGCTAGCTACAACGA GCGGAAGG 3339

1531 UCCGCAUC A CCAUCCUU 724 AAGGATGG GGCTAGCTACAACGA GATGCGGA 3340

1534 GCAUCACC A UCCUUCCG 726 CGGAAGGA GGCTAGCTACAACGA GGTGATGC 3341

1576 AUGUGGCC A CGUCCCAA 737 TTGGGACG GGCTAGCTACAACGA GGCCACAT 3342

1606 AGUUUGCC A UCUCACAG 744 CTGTGAGA GGCTAGCTACAACGA GGCAAACT 3343

1611 GCCAUCUC A CAGUCAUC 746 GATGACTG GGCTAGCTACAACGA GAGATGGC 3344

1617 UCACAGUC A UCCACGGG 748 CCCGTGGA GGCTAGCTACAACGA GACTGTGA 3345

1621 AGUCAUCC A CGGGCACU 750 AGTGCCCG GGCTAGCTACAACGA GGATGACT 3346

1627 CCACGGGC A CUGUUAUG 751 CATAACAG GGCTAGCTACAACGA GCCCGTGG 3347

1648 CUGUUAUC A UGGAGGGC 754 GCCCTCCA GGCTAGCTACAACGA GATAACAG 3348

1715 CGCUUGCC A UGUGCACG 765 CGTGCACA GGCTAGCTACAACGA GGCAAGCG 3349

1721 CCAUGUGC A CGAUGAGU 766 ACTCATCG GGCTAGCTACAACGA GCACATGG 3350

1762 CUUUUGUC A CCUUGGAC 772 GTCCAAGG GGCTAGCTACAACGA GACAAAAG 3351

1771 CCUUGGAC A UGGAAGAC 775 GTCTTCCA GGCTAGCTACAACGA GTCCAAGG 3352

1792 GCUACAAC A UUCCACAG 779 CTGTGGAA GGCTAGCTACAACGA GTTGTAGC 3353

1797 AACAUUCC A CAGACAGA 781 TCTGTCTG GGCTAGCTACAACGA GGAATGTT 3354

1819 CAACCCUC A UGACCAUA 788 TATGGTCA GGCTAGCTACAACGA GAGGGTTG 3355

1825 UCAUGACC A UAGCCUAU 790 ATAGGCTA GGCTAGCTACAACGA GGTCATGA 3356 Table 22

1837 CCUAUGUC A UGGCUGCC 793 GGCAGCCA GGCTAGCTACAACGA GACATAGG 3357

1846 UGGCUGCC A UCUGCGCC 796 GGCGCAGA GGCTAGCTACAACGA GGCAGCCA 3358

1861 CCCUCUUC A UGCUGCCA 802 TGGCAGCA GGCTAGCTACAACGA GAAGAGGG 3359

1869 AUGCUGCC A CUCUGCCU 805 AGGCAGAG GGCTAGCTACAACGA GGCAGCAT 3360

1879 UCUGCCUC A UGGUGUGU 810 ACACACCA GGCTAGCTACAACGA GAGGCAGA 3361

1922 CCAGCAGC A UGAUGACU 822 AGTCATCA GGCTAGCTACAACGA GCTGCTGG 3362

1942 CUGAUGAC A UCUCCCUG 825 CAGGGAGA GGCTAGCTACAACGA GTCATCAG 3363

1968 GGAGGCCC A UGGGCAGA 833 TCTGCCCA GGCTAGCTACAACGA GGGCCTCC 3364

1998 CCUGGACC A CACCUCCG 840 CGGAGGTG GGCTAGCTACAACGA GGTCCAGG 3365

2000 UGGACCAC A CCUCCGUG 841 CACGGAGG GGCTAGCTACAACGA GTGGTCCA 3366

2013 CGUGGUUC A CUUUGGUC 845 GACCAAAG GGCTAGCTACAACGA GAACCACG 3367

2022 CUUUGGUC A CAAGUAGG 847 CCTACTTG GGCTAGCTACAACGA GACCAAAG 3368

2035 UAGGAGAC A CAGAUGGC 849 GCCATCTG GGCTAGCTACAACGA GTCTCCTA 3369

2044 CAGAUGGC A CCUGUGGC 851 GCCACAGG GGCTAGCTACAACGA GCCATCTG 3370

2059 GCCAGAGC A CCUCAGGA 856 TCCTGAGG GGCTAGCTACAACGA GCTCTGGC 3371

2076 CCCUCCCC A CCCACCAA 866 TTGGTGGG GGCTAGCTACAACGA GGGGAGGG 3372

2080 CCCCACCC A CCAAAUGC 869 GCATTTGG GGCTAGCTACAACGA GGGTGGGG 3373

2174 AAAGAAGC A CUCUGCUG 885 CAGCAGAG GGCTAGCTACAACGA GCTTCTTT 3374

2201 UCUUGGUC A CCUCAAAU 891 ATTTGAGG GGCTAGCTACAACGA GACCAAGA 3375

2260 CUUUGUCC A CCAUUCCU 906 AGGAATGG GGCTAGCTACAACGA GGACAAAG 3376

2263 UGUCCACC A UUCCUUUA 908 TAAAGGAA GGCTAGCTACAACGA GGTGGACA 3377

2322 GUACUGGC A UCACACGC 922 GCGTGTGA GGCTAGCTACAACGA GCCAGTAC 3378

2325 CUGGCAUC A CACGCAGG 923 CCTGCGTG GGCTAGCTACAACGA GATGCCAG 3379

2327 GGCAUCAC A CGCAGGUU 924 AACCTGCG GGCTAGCTACAACGA GTGATGCC 3380

2421 GAGGAUGC A CAGUUUGC 945 GCAAACTG GGCTAGCTACAACGA GCATCCTC 3381

2470 AGCCUAAC A UUGGUGCA 954 TGCACCAA GGCTAGCTACAACGA GTTAGGCT 3382

11 ACGCGUCC G CAGCCCGC 960 GCGGGCTG GGCTAGCTACAACGA GGACGCGT 3383

18 CGCAGCCC G CCCGGGAG 961 CTCCCGGG GGCTAGCTACAACGA GGGCTGCG 3384

29 CGGGAGCU G CGAGCCGC 962 GCGGCTCG GGCTAGCTACAACGA AGCTCCCG 3385

36 UGCGAGCC G CGAGCUGG 964 CCAGCTCG GGCTAGCTACAACGA GGCTCGCA 3386

69 CAGCCAAC G CAGCCGCA 967 TGCGGCTG GGCTAGCTACAACGA GTTGGCTG 3387

75 ACGCAGCC G CAGGAGCC 968 GGCTCCTG GGCTAGCTACAACGA GGCTGCGT 3388

94 GAGCCCUU G CCCCUGCC 969 GGCAGGGG GGCTAGCTACAACGA AAGGGCTC 3389

100 UUGCCCCU G CCCGCGCC 970 GGCGCGGG GGCTAGCTACAACGA AGGGGCAA 3390

104 CCCUGCCC G CGCCGCCG 971 CGGCGGCG GGCTAGCTACAACGA GGGCAGGG 3391

106 CUGCCCGC G CCGCCGCC 972 GGCGGCGG GGCTAGCTACAACGA GCGGGCAG 3392

109 CCCGCGCC G CCGCCCGC 973 GCGGGCGG GGCTAGCTACAACGA GGCGCGGG 3393

112 GCGCCGCC G CCCGCCGG 974 CCGGCGGG GGCTAGCTACAACGA GGCGGCGC 3394

116 CGCCGCCC G CCGGGGGG 975 CCCCCCGG GGCTAGCTACAACGA GGGCGGCG 3395

137 GGGAAGCC G CCACCGGC 976 GCCGGTGG GGCTAGCTACAACGA GGCTTCCC 3396

148 ACCGGCCC G CCAUGCCC 977 GGGCATGG GGCTAGCTACAACGA GGGCCGGT 3397

153 CCCGCCAU G CCCGCCCC 978 GGGGCGGG GGCTAGCTACAACGA ATGGCGGG 3398

157 CCAUGCCC G CCCCUCCC 979 GGGAGGGG GGCTAGCTACAACGA GGGCATGG 3399

172 CCAGCCCC G CCGGGAGC 980 GCTCCCGG GGCTAGCTACAACGA GGGGCTGG 3400

183 GGGAGCCC G CGCCCGCU 981 AGCGGGCG GGCTAGCTACAACGA GGGCTCCC 3401

185 GAGCCCGC G CCCGCUGC 982 GCAGCGGG GGCTAGCTACAACGA GCGGGCTC 3402

189 CCGCGCCC G CUGCCCAG 983 CTGGGCAG GGCTAGCTACAACGA GGGCGCGG 3403

192 CGCCCGCU G CCCAGGCU 984 AGCCTGGG GGCTAGCTACAACGA AGCGGGCG 3404

205 GGCUGGCC G CCGCCGUG 985 CACGGCGG GGCTAGCTACAACGA GGCCAGCC 3405

208 UGGCCGCC G CCGUGCCG 986 CGGCACGG GGCTAGCTACAACGA GGCGGCCA 3406

213 GCCGCCGU G CCGAUGUA 987 TACATCGG GGCTAGCTACAACGA ACGGCGGC 3407 Table 22

250 UCUCCCCU G CUCCCGUG 989 CACGGGAG GGCTAGCTACAACGA AGGGGAGA 3408

258 GCUCCCGU G CUCUGCGG 990 CCGCAGAG GGCTAGCTACAACGA ACGGGAGC 3409

263 CGUGCUCU G CGGAUCUC 991 GAGATCCG GGCTAGCTACAACGA AGAGCACG 3410

280 CCCUGACC G CUCUCCAC 993 GTGGAGAG GGCTAGCTACAACGA GGTCAGGG 3411

320 AGGGCCCU G CAGGCCCU 994 AGGGCCTG GGCTAGCTACAACGA AGGGCCCT 3412

340 GUCCUGAU G CCCCCAAG 996 CTTGGGGG GGCTAGCTACAACGA ATCAGGAC 3413

397 GGGCAGGC G CCAGGGAC 998 GTCCCTGG GGCTAGCTACAACGA GCCTGCCC 3414

420 GGGCCAGU G CGAGCCCA 999 TGGGCTCG GGCTAGCTACAACGA ACTGGCCC 3415

468 CAAGCCCU G CCCUGGCU 1002 AGCCAGGG GGCTAGCTACAACGA AGGGCTTG 3416

480 UGGCUCCU G CUGUGGAU 1003 ATCCACAG GGCTAGCTACAACGA AGGAGCCA 3417

493 GGAUGGGC G CGGGAGUG 1004 CACTCCCG GGCTAGCTACAACGA GCCCATCC 3418

501 GCGGGAGU G CUGCCUGC 1005 GCAGGCAG GGCTAGCTACAACGA ACTCCCGC 3419

504 GGAGUGCU G CCUGCCCA 1006 TGGGCAGG GGCTAGCTACAACGA AGCACTCC 3420

508 UGCUGCCU G CCCACGGC 1007 GCCGTGGG GGCTAGCTACAACGA AGGCAGCA 3421

537 AUCCGGCU G CCCCUGCG 1008 CGCAGGGG GGCTAGCTACAACGA AGCCGGAT 3422

543 CUGCCCCU G CGCAGCGG 1009 CCGCTGCG GGCTAGCTACAACGA AGGGGCAG 3423

545 GCCCCUGC G CAGCGGCC 1010 GGCCGCTG GGCTAGCTACAACGA GCAGGGGC 3424

562 UGGGGGGC G CCCCCCUG 1011 CAGGGGGG GGCTAGCTACAACGA GCCCCCCA 3425

576 CUGGGGCU G CGGCUGCC 1012 GGCAGCCG GGCTAGCTACAACGA AGCCCCAG 3426

582 CUGCGGCU G CCCCGGGA 1013 TCCCGGGG GGCTAGCTACAACGA AGCCGCAG 3427

708 AGCCCCCC G CAGACGCU 1019 AGCGTCTG GGCTAGCTACAACGA GGGGGGCT 3428

714 CCGCAGAC G CUCAACAU 1020 ATGTTGAG GGCTAGCTACAACGA GTCTGCGG 3429

751 GUAACUUU G CAGUGGGU 1021 ACCCACTG GGCTAGCTACAACGA AAAGTTAC 3430

760 CAGUGGGU G CUGCCCCC 1022 GGGGGCAG GGCTAGCTACAACGA ACCCACTG 3431

763 UGGGUGCU G CCCCCCAC 1023 GTGGGGGG GGCTAGCTACAACGA AGCACCCA 3432

780 CCCUUCCU G CAUCGCUA 1024 TAGCGATG GGCTAGCTACAACGA AGGAAGGG 3433

785 CCUGCAUC G CUACUACC 1025 GGTAGTAG GGCTAGCTACAACGA GATGCAGG 3434

843 GUGUAUGU G CCCUACAC 1026 GTGTAGGG GGCTAGCTACAACGA ACATACAC 3435

921 GUCACUGU G CGUGCCAA 1028 TTGGCACG GGCTAGCTACAACGA ACAGTGAC 3436

925 CUGUGCGU G CCAACAUU 1029 AATGTTGG GGCTAGCTACAACGA ACGCACAG 3437

934 CCAACAUU G CUGCCAUC 1030 GATGGCAG GGCTAGCTACAACGA AATGTTGG 3438

937 ACAUUGCU G CCAUCACU 1031 AGTGATGG GGCTAGCTACAACGA AGCAATGT 3439

1006 UGGCCUAU G CUGAGAUU 1033 AATCTCAG GGCTAGCTACAACGA ATAGGCCA 3440

1015 CUGAGAUU G CCAGGCCU 1035 AGGCCTGG GGCTAGCTACAACGA AATCTCAG 3441

1092 UUCUCCCU G CAGCUUUG 1039 CAAAGCTG GGCTAGCTACAACGA AGGGAGAA 3442

1105 UUUGUGGU G CUGGCUUC 1040 GAAGCCAG GGCTAGCTACAACGA ACCACAAA 3443

1134 UCUGAAGU G CUGGCCUC 1042 GAGGCCAG GGCTAGCTACAACGA ACTTCAGA 3444

1182 GACCACUC G CUGUACAC 1045 GTGTACAG GGCTAGCTACAACGA GAGTGGTC 3445

1248 AUCAUUGU G CGGGUGGA 1048 TCCACCCG GGCTAGCTACAACGA ACAATGAT 3446

1286 AAUGGACU G CAAGGAGU 1050 ACTCCTTG GGCTAGCTACAACGA AGTCCATT 3447

1344 CUUCGUUU G CCCAAGAA 1052 TTCTTGGG GGCTAGCTACAACGA AAACGAAG 3448

1366 UUGAAGCU G CAGUCAAA 1054 TTTGACTG GGCTAGCTACAACGA AGCTTCAA 3449

1442 GCUGGUGU G CUGGCAAG 1056 CTTGCCAG GGCTAGCTACAACGA ACACCAGC 3450

1526 GUCCUUCC G CAUCACCA 1058 TGGTGATG GGCTAGCTACAACGA GGAAGGAC 3451

1542 AUCCUUCC G CAGCAAUA 1059 TATTGCTG GGCTAGCTACAACGA GGAAGGAT 3452

1554 CAAUACCU G CGGCCAGU 1060 ACTGGCCG GGCTAGCTACAACGA AGGTATTG 3453

1603 ACAAGUUU G CCAUCUCA 1062 TGAGATGG GGCTAGCTACAACGA AAACTTGT 3454

1699 UUGGCUUU G CUGUCAGC 1066 GCTGACAG GGCTAGCTACAACGA AAAGCCAA 3455

1708 CUGUCAGC G CUUGCCAU 1067 ATGGCAAG GGCTAGCTACAACGA GCTGACAG 3456

1712 CAGCGCUU G CCAUGUGC 1068 GCACATGG GGCTAGCTACAACGA AAGCGCTG 3457

1719 UGCCAUGU G CACGAUGA 1069 TCATCGTG GGCTAGCTACAACGA ACATGGCA 3458 Table 22

1843 UCAUGGCU G CCAUCUGC 1074 GCAGATGG GGCTAGCTACAACGA AGCCATGA 3459

1850 UGCCAUCU G CGCCCUCU 1075 AGAGGGCG GGCTAGCTACAACGA AGATGGCA 3460

1852 CCAUCUGC G CCCUCUUC 1076 GAAGAGGG GGCTAGCTACAACGA GCAGATGG 3461

1863 CUCUUCAU G CUGCCACU 1077 AGTGGCAG GGCTAGCTACAACGA ATGAAGAG 3462

1866 UUCAUGCU G CCACUCUG 1078 CAGAGTGG GGCTAGCTACAACGA AGCATGAA 3463

1874 GCCACUCU G CCUCAUGG 1079 CCATGAGG GGCTAGCTACAACGA AGAGTGGC 3464

1895 UCAGUGGC G CUGCCUCC 1080 GGAGGCAG GGCTAGCTACAACGA GCCACTGA 3465

1898 GUGGCGCU G CCUCCGCU 1081 AGCGGAGG GGCTAGCTACAACGA AGCGCCAC 3466

1904 CUGCCUCC G CUGCCUGC 1082 GCAGGCAG GGCTAGCTACAACGA GGAGGCAG 3467

1907 CCUCCGCU G CCUGCGCC 1083 GGCGCAGG GGCTAGCTACAACGA AGCGGAGG 3468

1911 CGCUGCCU G CGCCAGCA 1084 TGCTGGCG GGCTAGCTACAACGA AGGCAGCG 3469

1913 CUGCCUGC G CCAGCAGC 1085 GCTGCTGG GGCTAGCTACAACGA GCAGGCAG 3470

1933 AUGACUUU G CUGAUGAC 1088 GTCATCAG GGCTAGCTACAACGA AAAGTCAT 3471

1950 AUCUCCCU G CUGAAGUG 1091 CACTTCAG GGCTAGCTACAACGA AGGGAGAT 3472

2087 CACCAAAU G CCUCUGCC 1094 GGCAGAGG GGCTAGCTACAACGA ATTTGGTG 3473

2093 AUGCCUCU G CCUUGAUG 1095 CATCAAGG GGCTAGCTACAACGA AGAGGCAT 3474

2179 AGCACUCU G CUGGCGGG 1097 CCCGCCAG GGCTAGCTACAACGA AGAGTGCT 3475

2227 GAAAUUCU G CUGCUUGA 1098 TCAAGCAG GGCTAGCTACAACGA AGAATTTC 3476

2230 AUUCUGCU σ CUUGAAAC 1099 GTTTCAAG GGCTAGCTACAACGA AGCAGAAT 3477

2329 CAUCACAC G CAGGUUAC 1102 GTAACCTG GGCTAGCTACAACGA GTGTGATG 3478

2393 GUUUCCCU G CUGGCCAA 1103 TTGGCCAG GGCTAGCTACAACGA AGGGAAAC 3479

2419 GAGAGGAU G CACAGUUU 1104 AAACTGTG GGCTAGCTACAACGA ATCCTCTC 3480

2428 CACAGUUU G CUAUUUGC 1105 GCAAATAG GGCTAGCTACAACGA AAACTGTG 3481

2435 UGCUAUUU G CUUUAGAG 1106 CTCTAAAG GGCTAGCTACAACGA AAATAGCA 3482

2476 ACAUUGGU G CAAAGAUU 1107 AATCTTTG GGCTAGCTACAACGA ACCAATGT 3483

2485 CAAAGAUU G CCUCUUGA 1108 TCAAGAGG GGCTAGCTACAACGA AATCTTTG 3484

219 GUGCCGAU G UAGCGGGC 1110 GCCCGCTA GGCTAGCTACAACGA ATCGGCAC 3485

483 CUCCUGCU G UGGAUGGG llll CCCATCCA GGCTAGCTACAACGA AGCAGGAG 3486

634 GCAGCUUU G UGGAGAUG 1112 CATCTCCA GGCTAGCTACAACGA AAAGCTGC 3487

804 AGGCAGCU G UCCAGCAC 1113 GTGCTGGA GGCTAGCTACAACGA AGCTGCCT 3488

835 GGAAGGGU G UGUAUGUG 1114 CACATACA GGCTAGCTACAACGA ACCCTTCC 3489

837 AAGGGUGU G UAUGUGCC 1115 GGCACATA GGCTAGCTACAACGA ACACCCTT 3490

841 GUGUGUAU G UGCCCUAC 1116 GTAGGGCA GGCTAGCTACAACGA ATACACAC 3491

919 ACGUCACU G UGCGUGCC 1117 GGCACGCA GGCTAGCTACAACGA AGTGACGT 3492

1100 GCAGCUUU G UGGUGCUG 1118 CAGCACCA GGCTAGCTACAACGA AAAGCTGC 3493

1144 UGGCCUCU G UCGGAGGG 1119 CCCTCCGA GGCTAGCTACAACGA AGAGGCCA 3494

1185 CACUCGCU G UACACAGG 1120 CCTGTGTA GGCTAGCTACAACGA AGCGAGTG 3495

1246 UGAUCAUU G UGCGGGUG 1121 CACCCGCA GGCTAGCTACAACGA AATGATCA 3496

1315 AGAGCAUU G UGGACAGU 1122 ACTGTCCA GGCTAGCTACAACGA AATGCTCT 3497

1356 AAGAAAGU G UUUGAAGC 1123 GCTTCAAA GGCTAGCTACAACGA ACTTTCTT 3498

1440 CAGCUGGU G UGCUGGCA 1124 TGCCAGCA GGCTAGCTACAACGA ACCAGCTG 3499

1570 UGGAAGAU G UGGCCACG 1125 CGTGGCCA GGCTAGCTACAACGA ATCTTCCA 3500

1592 AGACGACU G UUACAAGU 1126 ACTTGTAA GGCTAGCTACAACGA AGTCGTCT 3501

1630 CGGGCACU G UUAUGGGA 1127 TCCCATAA GGCTAGCTACAACGA AGTGCCCG 3502

1642 UGGGAGCU G UUAUCAUG 1128 CATGATAA GGCTAGCTACAACGA AGCTCCCA 3503

1666 UCUACGUU G UCUUUGAU 1129 ATCAAAGA GGCTAGCTACAACGA AACGTAGA 3504

1702 GCUUUGCU G UCAGCGCU 1130 AGCGCTGA GGCTAGCTACAACGA AGCAAAGC 3505

1717 CUUGCCAU G UGCACGAU 1131 ATCGTGCA GGCTAGCTACAACGA ATGGCAAG 3506

1759 GCCCUUUU G UCACCUUG 1132 CAAGGTGA GGCTAGCTACAACGA AAAAGGGC 3507

1781 GGAAGACU G UGGCUACA 1133 TGTAGCCA GGCTAGCTACAACGA AGTCTTCC 3508

1834 UAGCCUAU G UCAUGGCU 1134 AGCCATGA GGCTAGCTACAACGA ATAGGCTA 3509 Table 22

1884 CUCAUGGU G UGUCAGUG 1135 CACTGACA GGCTAGCTACAACGA ACCATGAG 3510

1886 CAUGGUGU G UCAGUGGC 1136 GCCACTGA GGCTAGCTACAACGA ACACCATG 3511

2048 UGGCACCU G UGGCCAGA 1137 TCTGGCCA GGCTAGCTACAACGA AGGTGCCA 3512

2139 CAGGGACU G UACCUGUA 1138 TACAGGTA GGCTAGCTACAACGA AGTCCCTG 3513

2145 CUGUACCU G UAGGAAAC 1139 GTTTCCTA GGCTAGCTACAACGA AGGTACAG 3514

2256 GAACCUUU G UCCACCAU 1140 ATGGTGGA GGCTAGCTACAACGA AAAGGTTC 3515

2346 CUUGGCGU G UGUCCCUG 1141 CAGGGACA GGCTAGCTACAACGA ACGCCAAG 3516

2348 UGGCGUGU G UCCCUGUG 1142 CACAGGGA GGCTAGCTACAACGA ACACGCCA 3517

2354 GUGUCCCU G UGGUACCC 1143 GGGTACCA GGCTAGCTACAACGA AGGGACAC 3518

2385 CCAAGCUU G UUUCCCUG 1144 CAGGGAAA GGCTAGCTACAACGA AAGCTTGG 3519

2453 CAGGGACU G UAUAAACA 1145 TGTTTATA GGCTAGCTACAACGA AGTCCCTG 3520

14 CGUCCGCA G CCCGCCCG 1146 CGGGCGGG GGCTAGCTACAACGA TGCGGACG 3521

26 GCCCGGGA G CUGCGAGC 1147 GCTCGCAG GGCTAGCTACAACGA TCCCGGGC 3522

33 AGCUGCGA G CCGCGAGC 1148 GCTCGCGG GGCTAGCTACAACGA TCGCAGCT 3523

40 AGCCGCGA G CUGGAUUA 1149 TAATCCAG GGCTAGCTACAACGA TCGCGGCT 3524

51 GGAUUAUG G UGGCCUGA 1150 TCAGGCCA GGCTAGCTACAACGA CATAATCC 3525

54 UUAUGGUG G CCUGAGCA 1151 TGCTCAGG GGCTAGCTACAACGA CACCATAA 3526

60 UGGCCUGA G CAGCCAAC 1152 GTTGGCTG GGCTAGCTACAACGA TCAGGCCA 3527

63 CCUGAGCA G CCAACGCA 1153 TGCGTTGG GGCTAGCTACAACGA TGCTCAGG 3528

72 CCAACGCA G CCGCAGGA 1154 TCCTGCGG GGCTAGCTACAACGA TGCGTTGG 3529

81 CCGCAGGA G CCCGGAGC 1155 GCTCCGGG GGCTAGCTACAACGA TCCTGCGG 3530

88 AGCCCGGA G CCCUUGCC 1156 GGCAAGGG GGCTAGCTACAACGA TCCGGGCT 3531

134 CCAGGGAA G CCGCCACC 1157 GGTGGCGG GGCTAGCTACAACGA TTCCCTGG 3532

144 CGCCACCG G CCCGCCAU 1158 ATGGCGGG GGCTAGCTACAACGA CGGTGGCG 3533

167 CCCUCCCA G CCCCGCCG 1159 CGGCGGGG GGCTAGCTACAACGA TGGGAGGG 3534

179 CGCCGGGA G CCCGCGCC 1160 GGCGCGGG GGCTAGCTACAACGA TCCCGGCG 3535

198 CUGCCCAG G CUGGCCGC 1161 GCGGCCAG GGCTAGCTACAACGA CTGGGCAG 3536

202 CCAGGCUG G CCGCCGCC 1162 GGCGGCGG GGCTAGCTACAACGA CAGCCTGG 3537

211 CCGCCGCC G UGCCGAUG 1163 CATCGGCA GGCTAGCTACAACGA GGCGGCGG 3538

222 CCGAUGUA G CGGGCUCC 1164 GGAGCCCG GGCTAGCTACAACGA TACATCGG 3539

226 UGUAGCGG G CUCCGGAU 1165 ATCCGGAG GGCTAGCTACAACGA CCGCTACA 3540

239 GGAUCCCA G CCUCUCCC 1166 GGGAGAGG GGCTAGCTACAACGA TGGGATCC 3541

256 CUGCUCCC G UGCUCUGC 1167 GCAGAGCA GGCTAGCTACAACGA GGGAGCAG 3542

290 UCUCCACA G CCCGGACC 1168 GGTCCGGG GGCTAGCTACAACGA TGTGGAGA 3543

304 ACCCGGGG G CUGGCCCA 1169 TGGGCCAG GGCTAGCTACAACGA CCCCGGGT 3544

308 GGGGGCUG G CCCAGGGC 1170 GCCCTGGG GGCTAGCTACAACGA CAGCCCCC 3545

315 GGCCCAGG G CCCUGCAG 1171 CTGCAGGG GGCTAGCTACAACGA CCTGGGCC 3546

324 CCCUGCAG G CCCUGGCG 1172 CGCCAGGG GGCTAGCTACAACGA CTGCAGGG 3547

330 AGGCCCUG G CGUCCUGA 1173 TCAGGACG GGCTAGCTACAACGA CAGGGCCT 3548

332 GCCCUGGC G UCCUGAUG 1174 CATCAGGA GGCTAGCTACAACGA GCCAGGGC 3549

348 GCCCCCAA G CUCCCUCU 1175 AGAGGGAG GGCTAGCTACAACGA TTGGGGGC 3550

365 CCUGAGAA G CCACCAGC 1176 GCTGGTGG GGCTAGCTACAACGA TTCTCAGG 3551

372 AGCCACCA G CACCACCC 1177 GGGTGGTG GGCTAGCTACAACGA TGGTGGCT 3552

391 ACUUGGGG G CAGGCGCC 1178 GGCGCCTG GGCTAGCTACAACGA CCCCAAGT 3553

395 GGGGGCAG G CGCCAGGG 1179 CCCTGGCG GGCTAGCTACAACGA CTGCCCCC 3554

410 GGACGGAC G UGGGCCAG 1180 CTGGCCCA GGCTAGCTACAACGA GTCCGTCC 3555

414 GGACGUGG G CCAGUGCG 1181 CGCACTGG GGCTAGCTACAACGA CCACGTCC 3556

418 GUGGGCCA G UGCGAGCC 1182 GGCTCGCA GGCTAGCTACAACGA TGGCCCAC 3557

424 CAGUGCGA G CCCAGAGG 1183 CCTCTGGG GGCTAGCTACAACGA TCGCACTG 3558

433 CCCAGAGG G CCCGAAGG 1184 CCTTCGGG GGCTAGCTACAACGA CCTCTGGG 3559

441 GCCCGAAG G CCGGGGCC 1185 GGCCCCGG GGCTAGCTACAACGA CTTCGGGC 3560 Table 22

447 AGGCCGGG G CCCACCAU 1186 ATGGTGGG GGCTAGCTACAACGA CCCGGCCT 3561

457 CCACCAUG G CCCAAGCC 1187 GGCTTGGG GGCTAGCTACAACGA CATGGTGG 3562

463 UGGCCCAA G CCCUGCCC 1188 GGGCAGGG GGCTAGCTACAACGA TTGGGCCA 3563

474 CUGCCCUG G CUCCUGCU 1189 AGCAGGAG GGCTAGCTACAACGA CAGGGCAG 3564

491 GUGGAUGG G CGCGGGAG 1190 CTCCCGCG GGCTAGCTACAACGA CCATCCAC 3565

499 GCGCGGGA G UGCUGCCU 1191 AGGCAGCA GGCTAGCTACAACGA TCCCGCGC 3566

515 UGCCCACG G CACCCAGC 1192 GCTGGGTG GGCTAGCTACAACGA CGTGGGCA 3567

522 GGCACCCA G CACGGCAU 1193 ATGCCGTG GGCTAGCTACAACGA TGGGTGCC 3568

527 CCAGCACG G CAUCCGGC 1194 GCCGGATG GGCTAGCTACAACGA CGTGCTGG 3569

534 GGCAUCCG G CUGCCCCU 1195 AGGGGCAG GGCTAGCTACAACGA CGGATGCC 3570

548 CCUGCGCA G CGGCCUGG 1196 CCAGGCCG GGCTAGCTACAACGA TGCGCAGG 3571

551 GCGCAGCG G CCUGGGGG 1197 CCCCCAGG GGCTAGCTACAACGA CGCTGCGC 3572

560 CCUGGGGG G CGCCCCCC 1198 GGGGGGCG GGCTAGCTACAACGA CCCCCAGG 3573

573 CCCCUGGG G CUGCGGCU 1199 AGCCGCAG GGCTAGCTACAACGA CCCAGGGG 3574

579 GGGCUGCG G CUGCCCCG 1200 CGGGGCAG GGCTAGCTACAACGA CGCAGCCC 3575

603 GACGAAGA G CCCGAGGA 1201 TCCTCGGG GGCTAGCTACAACGA TCTTCGTC 3576

612 CCCGAGGA G CCCGGCCG 1202 CGGCCGGG GGCTAGCTACAACGA TCCTCGGG 3577

617 GGAGCCCG G CCGGAGGG 1203 CCCTCCGG GGCTAGCTACAACGA CGGGCTCC 3578

626 CCGGAGGG G CAGCUUUG 1204 CAAAGCTG GGCTAGCTACAACGA CCCTCCGG 3579

629 GAGGGGCA G CUUUGUGG 1205 CCACAAAG GGCTAGCTACAACGA TGCCCCTC 3580

643 UGGAGAUG G UGGACAAC 1206 GTTGTCCA GGCTAGCTACAACGA CATCTCCA 3581

659 CCUGAGGG G CAAGUCGG 1207 CCGACTTG GGCTAGCTACAACGA CCCTCAGG 3582

663 AGGGGCAA G UCGGGGCA 1208 TGCCCCGA GGCTAGCTACAACGA TTGCCCCT 3583

669 AAGUCGGG G CAGGGCUA 1209 TAGCCCTG GGCTAGCTACAACGA CCCGACTT 3584

674 GGGGCAGG G CUACUACG 1210 CGTAGTAG GGCTAGCTACAACGA CCTGCCCC 3585

682 GCUACUAC G UGGAGAUG 1211 CATCTCCA GGCTAGCTACAACGA GTAGTAGC 3586

694 AGAUGACC G UGGGCAGC 1212 GCTGCCCA GGCTAGCTACAACGA GGTCATCT 3587

698 GACCGUGG G CAGCCCCC 1213 GGGGGCTG GGCTAGCTACAACGA CCACGGTC 3588

701 CGUGGGCA G CCCCCCGC 1214 GCGGGGGG GGCTAGCTACAACGA TGCCCACG 3589

727 ACAUCCUG G UGGAUACA 1215 TGTATCCA GGCTAGCTACAACGA CAGGATGT 3590

737 GGAUACAG G CAGCAGUA 1216 TACTGCTG GGCTAGCTACAACGA CTGTATCC 3591

740 UACAGGCA G CAGUAACU 1217 AGTTACTG GGCTAGCTACAACGA TGCCTGTA 3592

743 AGGCAGCA G UAACUUUG 1218 CAAAGTTA GGCTAGCTACAACGA TGCTGCCT 3593

754 ACUUUGCA G UGGGUGCU 1219 AGCACCCA GGCTAGCTACAACGA TGCAAAGT 3594

758 UGCAGUGG G UGCUGCCC 1220 GGGCAGCA GGCTAGCTACAACGA CCACTGCA 3595

798 UACCAGAG G CAGCUGUC 1221 GACAGCTG GGCTAGCTACAACGA CTCTGGTA ^' 3596

801 CAGAGGCA G CUGUCCAG 1222 CTGGACAG GGCTAGCTACAACGA TGCCTCTG 3597

809 GCUGUCCA G CACAUACC 1223 GGTATGTG GGCTAGCTACAACGA TGGACAGC 3598

833 CCGGAAGG G UGUGUAUG 1224 CATACACA GGCTAGCTACAACGA CCTTCCGG 3599

857 CACCCAGG G CAAGUGGG 1225 CCCACTTG GGCTAGCTACAACGA CCTGGGTG 3600

861 CAGGGCAA G UGGGAAGG 1226 CCTTCCCA GGCTAGCTACAACGA TTGCCCTG 3601

873 GAAGGGGA G CUGGGCAC 1227 GTGCCCAG GGCTAGCTACAACGA TCCCCTTC 3602

878 GGAGCUGG G CACCGACC 1228 GGTCGGTG GGCTAGCTACAACGA CCAGCTCC 3603

889 CCGACCUG G UAAGCAUC 1229 GATGCTTA GGCTAGCTACAACGA CAGGTCGG 3604

893 CCUGGUAA G CAUCCCCC 1230 GGGGGATG GGCTAGCTACAACGA TTACCAGG 3605

905 CCCCCAUG G CCCCAACG 1231 CGTTGGGG GGCTAGCTACAACGA CATGGGGG 3606

913 GCCCCAAC G UCACUGUG 1232 CACAGTGA GGCTAGCTACAACGA GTTGGGGC 3607

923 CACUGUGC G UGCCAACA 1233 TGTTGGCA GGCTAGCTACAACGA GCACAGTG 3608

957 UCAGACAA G UUCUUCAU 1234 ATGAAGAA GGCTAGCTACAACGA TTGTCTGA 3609

971 CAUCAACG G CUCCAACU 1235 AGTTGGAG GGCTAGCTACAACGA CGTTGATG 3610

986 CUGGGAAG G CAUCCUGG 1236 CCAGGATG GGCTAGCTACAACGA CTTCCCAG 3611 Table 22

996 AUCCUGGG G CUGGCCUA 1237 TAGGCCAG GGCTAGCTACAACGA CCCAGGAT 3612

1000 UGGGGCUG G CCUAUGCU 1238 AGCATAGG GGCTAGCTACAACGA CAGCCCCA 3613

1020 AUUGCCAG G CCUGACGA 1239 TCGTCAGG GGCTAGCTACAACGA CTGGCAAT 3614

1038 UCCCUGGA G CCUUUCUU 1240 AAGAAAGG GGCTAGCTACAACGA TCCAGGGA 3615

1057 ACUCUCUG G UAAAGCAG 1241 CTGCTTTA GGCTAGCTACAACGA CAGAGAGT 3616

1062 CUGGUAAA G CAGACCCA 1242 TGGGTCTG GGCTAGCTACAACGA TTTACCAG 3617

1072 AGACCCAC G UUCCCAAC 1243 GTTGGGAA GGCTAGCTACAACGA GTGGGTCT 3618

1095 UCCCUGCA G CUUUGUGG 1244 CCACAAAG GGCTAGCTACAACGA TGCAGGGA 3619

1103 GCUUUGUG G UGCUGGCU 1245 AGCCAGCA GGCTAGCTACAACGA CACAAAGC 3620

1109 UGGUGCUG G CUUCCCCC 1246 GGGGGAAG GGCTAGCTACAACGA CAGCACCA 3621

1125 CUCAACCA G UCUGAAGU 1247 ACTTCAGA GGCTAGCTACAACGA TGGTTGAG 3622

1132 AGUCUGAA G UGCUGGCC 1248 GGCCAGCA GGCTAGCTACAACGA TTCAGACT 3623

1138 AAGUGCUG G CCUCUGUC 1249 GACAGAGG GGCTAGCTACAACGA CAGCACTT 3624

1154 CGGAGGGA G CAUGAUCA 1250 TGATCATG GGCTAGCTACAACGA TCCCTCCG 3625

1169 CAUUGGAG G UAUCGACC 1251 GGTCGATA GGCTAGCTACAACGA CTCCAATG .3626

1193 GUACACAG G CAGUCUCU 1252 AGAGACTG GGCTAGCTACAACGA CTGTGTAC 3627

1196 CACAGGCA G UCUCUGGU 1253 ACCAGAGA GGCTAGCTACAACGA TGCCTGTG 3628

1203 AGUCUCUG G UAUACACC 1254 GGTGTATA GGCTAGCTACAACGA CAGAGACT 3629

1218 CCCAUCCG G CGGGAGUG 1255 CACTCCCG GGCTAGCTACAACGA CGGATGGG 3630

1224 CGGCGGGA G UGGUAUUA 1256 TAATACCA GGCTAGCTACAACGA TCCCGCCG 3631

1227 CGGGAGUG G UAUUAUGA 1257 TCATAATA GGCTAGCTACAACGA CACTCCCG 3632

1237 AUUAUGAG G UGAUCAUU 1258 AATGATCA GGCTAGCTACAACGA CTCATAAT 3633

1252 UUGUGCGG G UGGAGAUC 1259 GATCTCCA GGCTAGCTACAACGA CCGCACAA 3634

1293 UGCAAGGA G UACAACUA 1260 TAGTTGTA GGCTAGCTACAACGA TCCTTGCA 3635

1310 UGACAAGA G CAUUGUGG 1261 CCACAATG GGCTAGCTACAACGA TCTTGTCA 3636

1322 UGUGGACA G UGGCACCA 1262 TGGTGCCA GGCTAGCTACAACGA TGTCCACA 3637

1325 GGACAGUG G CACCACCA 1263 TGGTGGTG GGCTAGCTACAACGA CACTGTCC 3638

1340 CAACCUUC G UUUGCCCA 1264 TGGGCAAA GGCTAGCTACAACGA GAAGGTTG 3639

1354 CCAAGAAA G UGUUUGAA 1265 TTCAAACA GGCTAGCTACAACGA TTTCTTGG 3640

1363 UGUUUGAA G CUGCAGUC 1266 GACTGCAG GGCTAGCTACAACGA TTCAAACA 3641

1369 AAGCUGCA G UCAAAUCC 1267 GGATTTGA GGCTAGCTACAACGA TGCAGCTT 3642

1384 CCAUCAAG G CAGCCUCC 1268 GGAGGCTG GGCTAGCTACAACGA CTTGATGG 3643

1387 UCAAGGCA G CCUCCUCC 1269 GGAGGAGG GGCTAGCTACAACGA TGCCTTGA 3644

1404 ACGGAGAA G UUCCCUGA 1270 TCAGGGAA GGCTAGCTACAACGA TTCTCCGT 3645

1415 CCCUGAUG G UUUCUGGC 1271 GCCAGAAA GGCTAGCTACAACGA CATCAGGG 3646

1422 GGUUUCUG G CUAGGAGA 1272 TCTCCTAG GGCTAGCTACAACGA CAGAAACC 3647

1431 CUAGGAGA G CAGCUGGU 1273 ACCAGCTG GGCTAGCTACAACGA TCTCCTAG 3648

1434 GGAGAGCA G CUGGUGUG 1274 CACACCAG GGCTAGCTACAACGA TGCTCTCC 3649

1438 AGCAGCUG G UGUGCUGG 1275 CCAGCACA GGCTAGCTACAACGA CAGCTGCT 3650

1446 GUGUGCUG G CAAGCAGG 1276 CCTGCTTG GGCTAGCTACAACGA CAGCACAC 3651

1450 GCUGGCAA G CAGGCACC 1277 GGTGCCTG GGCTAGCTACAACGA TTGCCAGC 3652

1454 GCAAGCAG G CACCACCC 1278 GGGTGGTG GGCTAGCTACAACGA CTGCTTGC 3653

1480 UUUUCCCA G UCAUCUCA 1279 TGAGATGA GGCTAGCTACAACGA TGGGAAAA 3654

1502 CCUAAUGG G UGAGGUUA 1280 TAACCTCA GGCTAGCTACAACGA CCATTAGG 3655

1507 UGGGUGAG G UUACCAAC 1281 GTTGGTAA GGCTAGCTACAACGA CTCACCCA 3656

1518 ACCAACCA G UCCUUCCG 1282 CGGAAGGA GGCTAGCTACAACGA TGGTTGGT 3657

1545 CUUCCGCA G CAAUACCU 1283 AGGTATTG GGCTAGCTACAACGA TGCGGAAG 3658

1557 UACCUGCG G CCAGUGGA 1284 TCCACTGG GGCTAGCTACAACGA CGCAGGTA 3659

1561 UGCGGCCA G UGGAAGAU 1285 ATCTTCCA GGCTAGCTACAACGA TGGCCGCA 3660

1573 AAGAUGUG G CCACGUCC 1286 GGACGTGG GGCTAGCTACAACGA CACATCTT 3661

1578 GUGGCCAC G UCCCAAGA 1287 TCTTGGGA GGCTAGCTACAACGA GTGGCCAC 3662 Table 22

1599 UGUUACAA G UUUGCCAU 1288 ATGGCAAA GGCTAGCTACAACGA TTGTAACA 3663

1614 AUCUCACA G UCAUCCAC 1289 GTGGATGA GGCTAGCTACAACGA TGTGAGAT 3664

1625 AUCCACGG G CACUGUUA 1290 TAACAGTG GGCTAGCTACAACGA CCGTGGAT 3665

1639 UUAUGGGA G CUGUUAUC 1291 GATAACAG GGCTAGCTACAACGA TCCCATAA 3666

1655 CAUGGAGG G CUUCUACG 1292 CGTAGAAG GGCTAGCTACAACGA CCTCCATG 3667

1663 GCUUCUAC G UUGUCUUU 1293 AAAGACAA GGCTAGCTACAACGA GTAGAAGC 3668

1678 UUGAUCGG G CCCGAAAA 1294 TTTTCGGG GGCTAGCTACAACGA CCGATCAA 3669

1694 ACGAAUUG G CUUUGCUG 1295 CAGCAAAG GGCTAGCTACAACGA CAATTCGT 3670

1706 UGCUGUCA G CGCUUGCC 1296 GGCAAGCG GGCTAGCTACAACGA TGACAGCA 3671

1728 CACGAUGA G UUCAGGAC ^' 1297 GTCCTGAA GGCTAGCTACAACGA TCATCGTG 3672

1738 UCAGGACG G CAGCGGUG 1298 CACCGCTG GGCTAGCTACAACGA CGTCCTGA 3673

1741 GGACGGCA G CGGUGGAA 1299 TTCCACCG GGCTAGCTACAACGA TGCCGTCC 3674

1744 CGGCAGCG G UGGAAGGC 1300 GCCTTCCA GGCTAGCTACAACGA CGCTGCCG. 3675

1751 GGUGGAAG G CCCUUUUG 1301 CAAAAGGG GGCTAGCTACAACGA CTTCCACC 3676

1784 AGACUGUG G CUACAACA 1302 TGTTGTAG GGCTAGCTACAACGA CACAGTCT 3677

1809 ACAGAUGA G UCAACCCU 1303 AGGGTTGA GGCTAGCTACAACGA TCATCTGT 3678

1828 UGACCAUA G CCUAUGUC 1304 GACATAGG GGCTAGCTACAACGA TATGGTCA 3679

1840 AUGUCAUG G CUGCCAUC 1305 GATGGCAG GGCTAGCTACAACGA CATGACAT 3680

1882 GCCUCAUG G UGUGUCAG 1306 CTGACACA GGCTAGCTACAACGA CATGAGGC 3681

1890 GUGUGUCA G UGGCGCUG 1307 CAGCGCCA GGCTAGCTACAACGA TGACACAC 3682

1893 UGUCAGUG G CGCUGCCU 1308 AGGCAGCG GGCTAGCTACAACGA CACTGACA 3683

1917 CUGCGCCA G CAGCAUGA 1309 TCATGCTG GGCTAGCTACAACGA TGGCGCAG 3684

1920 CGCCAGCA G CAUGAUGA 1310 TCATCATG GGCTAGCTACAACGA TGCTGGCG 3685

1956 CUGCUGAA G UGAGGAGG 1311 CCTCCTCA GGCTAGCTACAACGA TTCAGCAG 3686

1964 GUGAGGAG G CCCAUGGG 1312 CCCATGGG GGCTAGCTACAACGA CTCCTCAC 3687

1972 GCCCAUGG G CAGAAGAU 1313 ATCTTCTG GGCTAGCTACAACGA CCATGGGC 3688

2006 ACACCUCC G UGGUUCAC 1314 GTGAACCA GGCTAGCTACAACGA GGAGGTGT 3689

2009 CCUCCGUG G UUCACUUU 1315 AAAGTGAA GGCTAGCTACAACGA CACGGAGG 3690

2019 UCACUUUG G UCACAAGU 1316 ACTTGTGA GGCTAGCTACAACGA CAAAGTGA 3691

2026 GGUCACAA G UAGGAGAC 1317 GTCTCCTA GGCTAGCTACAACGA TTGTGACC 3692

2042 CACAGAUG G CACCUGUG 1318 CACAGGTG GGCTAGCTACAACGA CATCTGTG 3693

2051 CACCUGUG G CCAGAGCA 1319 TGCTCTGG GGCTAGCTACAACGA CACAGGTG 3694

2057 UGGCCAGA G CACCUCAG 1320 CTGAGGTG GGCTAGCTACAACGA TCTGGCCA 3695

2114 AGGAAAAG G CUGGCAAG 1321 CTTGCCAG GGCTAGCTACAACGA CTTTTCCT 3696

2118 AAAGGCUG G CAAGGUGG 1322 CCACCTTG GGCTAGCTACAACGA CAGCCTTT 3697

2123 CUGGCAAG G UGGGUUCC 1323 GGAACCCA GGCTAGCTACAACGA CTTGCCAG 3698

2127 CAAGGUGG G UUCCAGGG 1324 ^■ CCCTGGAA GGCTAGCTACAACGA CCACCTTG 3699

2172 AGAAAGAA G CACUCUGC 1325 GCAGAGTG GGCTAGCTACAACGA TTCTTTCT 3700

2183 CUCUGCUG G CGGGAAUA 1326 TATTCCCG GGCTAGCTACAACGA CAGCAGAG 3701

2198 UACUCUUG G UCACCUCA 1327 TGAGGTGA GGCTAGCTACAACGA CAAGAGTA 3702

2214 AAAUUUAA G UCGGGAAA 1328 TTTCCCGA GGCTAGCTACAACGA TTAAATTT 3703

2243 AAACUUCA G CCCUGAAC 1329 GTTCAGGG GGCTAGCTACAACGA TGAAGTTT 3704

2288 AACCCAAA G UAUUCUUC 1330 GAAGAATA GGCTAGCTACAACGA TTTGGGTT 3705

2305 UUUUCUUA G UUUCAGAA 1331 TTCTGAAA GGCTAGCTACAACGA TAAGAAAA 3706

2314 UUUCAGAA G UACUGGCA 1332 TGCCAGTA GGCTAGCTACAACGA TTCTGAAA 3707

2320 AAGUACUG G CAUCACAC 1333 GTGTGATG GGCTAGCTACAACGA CAGTACTT 3708

2333 ACACGCAG G UUACCUUG 1334 CAAGGTAA GGCTAGCTACAACGA CTGCGTGT 3709

2342 UUACCUUG G CGUGUGUC 1335 GACACACG GGCTAGCTACAACGA CAAGGTAA 3710

2344 ACCUUGGC G UGUGUCCC 1336 GGGACACA GGCTAGCTACAACGA GCCAAGGT 3711

2357 UCCCUGUG G UACCCUGG 1337 CCAGGGTA GGCTAGCTACAACGA CACAGGGA 3712

2365 GUACCCUG G CAGAGAAG 1338 CTTCTCTG GGCTAGCTACAACGA CAGGGTAC 3713 Table 22

2381 GAGACCAA G CUUGUUUC 1339 GAAACAAG GGCTAGCTACAACGA TTGGTCTC 3714

2397 CCCUGCUG G CCAAAGUC 1340 GACTTTGG GGCTAGCTACAACGA CAGCAGGG 3715

2403 UGGCCAAA G UCAGUAGG 1341 CCTACTGA GGCTAGCTACAACGA TTTGGCCA 3716

2407 CAAAGUCA G UAGGAGAG 1342 CTCTCCTA GGCTAGCTACAACGA TGACTTTG 3717

2424 GAUGCACA G UUUGCUAU 1343 ATAGCAAA GGCTAGCTACAACGA TGTGCATC 3718

2463 AUAAACAA G CCUAACAU 1344 ATGTTAGG GGCTAGCTACAACGA TTGTTTAT 3719

2474 UAACAUUG G UGCAAAGA 1345 TCTTTGCA GGCTAGCTACAACGA CAATGTTA 3720

45 CGAGCUGG A UUAUGGUG 1346 CACCATAA GGCTAGCTACAACGA CCAGCTCG 3721

67 AGCAGCCA A CGCAGCCG 1347 CGGCTGCG GGCTAGCTACAACGA TGGCTGCT 3722

125 CCGGGGGG A CCAGGGAA 1348 TTCCCTGG GGCTAGCTACAACGA CCCCCCGG 3723

217 CCGUGCCG A UGUAGCGG 1349 CCGCTACA GGCTAGCTACAACGA CGGCACGG 3724

233 GGCUCCGG A UCCCAGCC 1350 GGCTGGGA GGCTAGCTACAACGA CCGGAGCC 3725

267 CUCUGCGG A UCUCCCCU 1351 AGGGGAGA GGCTAGCTACAACGA CCGCAGAG 3726

277 CUCCCCUG A CCGCUCUC 1352 GAGAGCGG GGCTAGCTACAACGA CAGGGGAG 3727

296 CAGCCCGG A CCCGGGGG 1353 CCCCCGGG GGCTAGCTACAACGA CCGGGCTG 3728

338 GCGUCCUG A UGCCCCCA 1354 TGGGGGCA GGCTAGCTACAACGA CAGGACGC 3729

383 CCACCCAG A CUUGGGGG 1355 CCCCCAAG GGCTAGCTACAACGA CTGGGTGG 3730

404 CGCCAGGG A CGGACGUG 1356 CACGTCCG GGCTAGCTACAACGA CCCTGGCG 3731

408 AGGGACGG A CGUGGGCC 1357 GGCCCACG GGCTAGCTACAACGA CCGTCCCT 3732

487 UGCUGUGG A UGGGCGCG 1358 CGCGCCCA GGCTAGCTACAACGA CCACAGCA 3733

592 CCCGGGAG A CCGACGAA 1359 TTCGTCGG GGCTAGCTACAACGA CTCCCGGG 3734

596 GGAGACCG A CGAAGAGC 1360 GCTCTTCG GGCTAGCTACAACGA CGGTCTCC 3735

640 UUGUGGAG A UGGUGGAC 1361 GTCCACCA GGCTAGCTACAACGA CTCCACAA 3736

647 GAUGGUGG A CAACCUGA 1362 TCAGGTTG GGCTAGCTACAACGA CCACCATC 3737

650 GGUGGACA A CCUGAGGG 1363 CCCTCAGG GGCTAGCTACAACGA TGTCCACC 3738

688 ACGUGGAG A UGACCGUG 1364 CACGGTCA GGCTAGCTACAACGA CTCCACGT 3739

691 UGGAGAUG A CCGUGGGC 1365 GCCCACGG GGCTAGCTACAACGA CATCTCCA 3740

712 CCCCGCAG A CGCUCAAC 1366 GTTGAGCG GGCTAGCTACAACGA CTGCGGGG 3741

719 GACGCUCA A CAUCCUGG 1367 CCAGGATG GGCTAGCTACAACGA TGAGCGTC 3742

731 CCUGGUGG A UACAGGCA 1368 TGCCTGTA GGCTAGCTACAACGA CCACCAGG 3743

746 CAGCAGUA A CUUUGCAG 1369 CTGCAAAG GGCTAGCTACAACGA TACTGCTG 3744

821 AUACCGGG A CCUCCGGA 1370 TCCGGAGG GGCTAGCTACAACGA CCCGGTAT 3745

884 GGGCACCG A CCUGGUAA 1371 TTACCAGG GGCTAGCTACAACGA CGGTGCCC 3746

911 UGGCCCCA A CGUCACUG 1372 CAGTGACG GGCTAGCTACAACGA TGGGGCCA 3747

929 GCGUGCCA A CAUUGCUG 1373 CAGCAATG GGCTAGCTACAACGA TGGCACGC 3748

948 AUCACUGA A UCAGACAA 1374 TTGTCTGA GGCTAGCTACAACGA TCAGTGAT 3749

953 UGAAUCAG A CAAGUUCU 1375 AGAACTTG GGCTAGCTACAACGA CTGATTCA 3750

968 CUUCAUCA A CGGCUCCA 1376 TGGAGCCG GGCTAGCTACAACGA TGATGAAG 3751

977 CGGCUCCA A CUGGGAAG 1377 CTTCCCAG GGCTAGCTACAACGA TGGAGCCG 3752

1012 AUGCUGAG A UUGCCAGG 1378 CCTGGCAA GGCTAGCTACAACGA CTCAGCAT 3753

1025 CAGGCCUG A CGACUCCC 1379 GGGAGTCG GGCTAGCTACAACGA CAGGCCTG 3754

1028 GCCUGACG A CUCCCUGG 1380 CCAGGGAG GGCTAGCTACAACGA CGTCAGGC 3755

1049 UUUCUUUG A CUCUCUGG 1381 CCAGAGAG GGCTAGCTACAACGA CAAAGAAA 3756

1066 UAAAGCAG A CCCACGUU 1382 AACGTGGG GGCTAGCTACAACGA CTGCTTTA 3757

1079 CGUUCCCA A CCUCUUCU 1383 AGAAGAGG GGCTAGCTACAACGA TGGGAACG 3758

1121 CCCCCUCA A CCAGUCUG 1384 CAGACTGG GGCTAGCTACAACGA TGAGGGGG 3759

1159 GGAGCAUG A UCAUUGGA 1385 TCCAATGA GGCTAGCTACAACGA CATGCTCC 3760

1175 AGGUAUCG A CCACUCGC 1386 GCGAGTGG GGCTAGCTACAACGA CGATACCT 3761

1240 AUGAGGUG A UCAUUGUG 1387 CACAATGA GGCTAGCTACAACGA CACCTCAT 3762

1258 GGGUGGAG A UCAAUGGA 1388 TCCATTGA GGCTAGCTACAACGA CTCCACCC 3763

1262 GGAGAUCA A UGGACAGG 1389 CCTGTCCA GGCTAGCTACAACGA TGATCTCC 3764 Table 22

1266 AUCAAUGG A CAGGAUCU 1390 AGATCCTG GGCTAGCTACAACGA CCATTGAT 3765

1271 UGGACAGG A UCUGAAAA 1391 TTTTCAGA GGCTAGCTACAACGA CCTGTCCA 3766

1279 AUCUGAAA A UGGACUGC 1392 GCAGTCCA GGCTAGCTACAACGA TTTCAGAT 3767

1283 GAAAAUGG A CUGCAAGG 1393 CCTTGCAG GGCTAGCTACAACGA CCATTTTC 3768

1298 GGAGUACA A CUAUGACA 1394 TGTCATAG GGCTAGCTACAACGA TGTACTCC 3769

1304 CAACUAUG A CAAGAGCA 1395 TGCTCTTG GGCTAGCTACAACGA CATAGTTG 3770

1319 CAUUGUGG A CAGUGGCA 1396 TGCCACTG GGCTAGCTACAACGA CCACAATG 3771

1334 CACCACCA A CCUUCGUU 1397 AACGAAGG GGCTAGCTACAACGA TGGTGGTG 3772

1374 GCAGUCAA A UCCAUCAA 1398 TTGATGGA GGCTAGCTACAACGA TTGACTGC 3773

1412 GUUCCCUG A UGGUUUCU 1399 AGAAACCA GGCTAGCTACAACGA CAGGGAAC 3774

1469 CCCUUGGA A CAUUUUCC 1400 GGAAAATG GGCTAGCTACAACGA TCCAAGGG 3775

1498 UCUACCUA A UGGGUGAG 1401 CTCACCCA GGCTAGCTACAACGA TAGGTAGA 3776

1514 GGUUACCA A CCAGUCCU 1402 AGGACTGG GGCTAGCTACAACGA TGGTAACC 3777

1548 CCGCAGCA A UACCUGCG 1403 CGCAGGTA GGCTAGCTACAACGA TGCTGCGG 3778

1568 AGUGGAAG A UGUGGCCA 1404 TGGCCACA GGCTAGCTACAACGA CTTCCACT 3779

1586 GUCCCAAG A CGACUGUU 1405 AACAGTCG GGCTAGCTACAACGA CTTGGGAC 3780

1589 CCAAGACG A CUGUUACA 1406 TGTAACAG GGCTAGCTACAACGA CGTCTTGG 3781

1673 UGUCUUUG A UCGGGCCC 1407 GGGCCCGA GGCTAGCTACAACGA CAAAGACA 3782

1686 GCCCGAAA A CGAAUUGG 1408 CCAATTCG GGCTAGCTACAACGA TTTCGGGC 3783

1690 GAAAACGA A UUGGCUUU 1409 AAAGCCAA GGCTAGCTACAACGA TCGTTTTC 3784

1724 UGUGCACG A UGAGUUCA 1410 TGAACTCA GGCTAGCTACAACGA CGTGCACA 3785

1735 AGUUCAGG A CGGCAGCG 1411 CGCTGCCG GGCTAGCTACAACGA CCTGAACT 3786

1769 CACCUUGG A CAUGGAAG 1412 CTTCCATG GGCTAGCTACAACGA CCAAGGTG 3787

1778 CAUGGAAG A CUGUGGCU 1413 AGCCACAG GGCTAGCTACAACGA CTTCCATG 3788

1790 UGGCUACA A CAUUCCAC 1414 GTGGAATG GGCTAGCTACAACGA TGTAGCCA 3789

1801 UUCCACAG A CAGAUGAG 1415 CTCATCTG GGCTAGCTACAACGA CTGTGGAA 3790

1805 ACAGACAG A UGAGUCAA 1416 TTGACTCA GGCTAGCTACAACGA CTGTCTGT 3791

1813 AUGAGUCA A CCCUCAUG 1417 CATGAGGG GGCTAGCTACAACGA TGACTCAT 3792

1822 CCCUCAUG A CCAUAGCC 1418 GGCTATGG GGCTAGCTACAACGA CATGAGGG 3793

1925 GCAGCAUG A UGACUUUG 1419 CAAAGTCA GGCTAGCTACAACGA CATGCTGC 3794

1928 GCAUGAUG A CUUUGCUG 1420 CAGCAAAG GGCTAGCTACAACGA CATCATGC 3795

1937 CUUUGCUG A UGACAUCU 1421 AGATGTCA GGCTAGCTACAACGA CAGCAAAG 3796

1940 UGCUGAUG A CAUCUCCC 1422 GGGAGATG GGCTAGCTACAACGA CATCAGCA 3797

1979 GGCAGAAG A UAGAGAUU 1423 AATCTCTA GGCTAGCTACAACGA CTTCTGCC 3798

1985 AGAUAGAG A UUCCCCUG 1424 CAGGGGAA GGCTAGCTACAACGA CTCTATCT 3799

1995 UCCCCUGG A CCACACCU 1425 AGGTGTGG GGCTAGCTACAACGA CCAGGGGA 3800

2033 AGUAGGAG A CACAGAUG 1426 CATCTGTG GGCTAGCTACAACGA CTCCTACT 3801

2039 AGACACAG A UGGCACCU 1427 AGGTGCCA GGCTAGCTACAACGA CTGTGTCT 3802

2067 ACCUCAGG A CCCUCCCC 1428 GGGGAGGG GGCTAGCTACAACGA CCTGAGGT 3803

2085 CCCACCAA A UGCCUCUG 1429 CAGAGGCA GGCTAGCTACAACGA TTGGTGGG 3804

2099 CUGCCUUG A UGGAGAAG 1430 CTTCTCCA GGCTAGCTACAACGA CAAGGCAG 3805

2136 UUCCAGGG A CUGUACCU 1431 AGGTACAG GGCTAGCTACAACGA CCCTGGAA 3806

2152 UGUAGGAA A CAGAAAAG 1432 CTTTTCTG GGCTAGCTACAACGA TTCCTACA 3807

2189 UGGCGGGA A UACUCUUG 1433 CAAGAGTA GGCTAGCTACAACGA TCCCGCCA 3808

2208 CACCUCAA A UUUAAGUC 1434 GACTTAAA GGCTAGCTACAACGA TTGAGGTG 3809

2222 GUCGGGAA A UUCUGCUG 1435 CAGCAGAA GGCTAGCTACAACGA TTCCCGAC 3810

2237 UGCUUGAA A CUUCAGCC ^" 1436 GGCTGAAG GGCTAGCTACAACGA TTCAAGCA 3811

2250 AGCCCUGA A CCUUUGUC 1437 GACAAAGG GGCTAGCTACAACGA TCAGGGCT 3812

2273 UCCUUUAA A UUCUCCAA 1438 TTGGAGAA GGCTAGCTACAACGA TTAAAGGA 3813

2281 AUUCUCCA A CCCAAAGU 1439 ACTTTGGG GGCTAGCTACAACGA TGGAGAAT 3814

2376 GAGAAGAG A CCAAGCUU 1440 AAGCTTGG GGCTAGCTACAACGA CTCTTCTC 3815 Table 22

2417 AGGAGAGG A UGCACAGU 1441 ACTGTGCA GGCTAGCTACAACGA CCTCTCCT 3816

2444 CUUUAGAG A CAGGGACU 1442 AGTCCCTG GGCTAGCTACAACGA CTCTAAAG 3817

2450 AGACAGGG A CUGUAUAA 1443 TTATACAG GGCTAGCTACAACGA CCCTGTCT 3818

2459 CUGUAUAA A CAAGCCUA 1444 TAGGCTTG GGCTAGCTACAACGA TTATACAG 3819

2468 CAAGCCUA A CAUUGGUG 1445 CACCAATG GGCTAGCTACAACGA TAGGCTTG 3820

2482 GUGCAAAG A UUGCCUCU 1446 AGAGGCAA GGCTAGCTACAACGA CTTTGCAC 3821

2494 CCUCUUGA A UUAAAAAA 1447 TTTTTTAA GGCTAGCTACAACGA TCAAGAGG 3822

2507 AAAAAAAA A CUAGAAAA 1448 TTTTCTAG GGCTAGCTACAACGA TTTTTTTT 3823

Input Sequence = AF190725. Cut Site = G/ .

Stem Length = 8 . Core Sequence = GGCTAGCTACAACGA

AF190725 (Homo sapiens beta-site APP cleaving enzyme (BACE) mRNA; 2526 bp)

Table 23

Table 23: Human BACE Amberzyme Ribozyme and Target Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

11 ACGCGUCC G CAGCCCGC 960 GCGGGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGACGCGU 3260

18 CGCAGCCC G CCCGGGAG 961 CUCCCGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGCUGCG 3261

29 CGGGAGCU G CGAGCCGC 962 GCGGCUCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUCCCG 3262

31 GGAGCUGC G AGCCGCGA 963 UCGCGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAGCUCC 3263

36 UGCGAGCC G CGAGCUGG 964 CCAGCUCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCUCGCA 3264

38 CGAGCCGC G AGCUGGAU 965 AUCCAGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGGCUCG 3265

58 GGUGGCCU G AGCAGCCA 966 UGGCUGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGCCACC 3266

69 CAGCCAAC G CAGCCGCA 967 UGCGGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUGGCUG 3267

75 ACGCAGCC G CAGGAGCC 968 GGCUCCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCUGCGU 3268

94 GAGCCCUU G CCCCUGCC 969 GGCAGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGGCUC 3269

100 UUGCCCCU G CCCGCGCC 970 GGCGCGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGGCAA 3270

104 CCCUGCCC G CGCCGCCG 971 CGGCGGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGCAGGG 3271

106 CUGCCCGC G CCGCCGCC 972 GGCGGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGGGCAG 3272

109 CCCGCGCC G CCGCCCGC 973 GCGGGCGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGCGCGGG 3273

112 GCGCCGCC G CCCGCCGG 974 CCGGCGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGCGGCGC 3274

116 CGCCGCCC G CCGGGGGG 975 CCCCCCGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGCGGCG 3275

137 GGGAAGCC G CCACCGGC 976 GCCGGUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGCUUCCC 3276

148 ACCGGCCC G CCAUGCCC 977 GGGCAUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGCCGGU 3277

153 CCCGCCAU G CCCGCCCC 978 GGGGCGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGGCGGG 3278

157 CCAUGCCC G CCCCUCCC 979 GGGAGGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGCAUGG 3279

172 CCAGCCCC G CCGGGAGC 980 GCUCCCGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGGCUGG 3280

183 GGGAGCCC G CGCCCGCU 981 AGCGGGCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGCUCCC 3281

185 GAGCCCGC G CCCGCUGC 982 GCAGCGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCGGGCUC 3282

189 CCGCGCCC G CUGCCCAG 983 CUGGGCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGCGCGG 3283

192 CGCCCGCU G CCCAGGCU 984 AGCCUGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCGGGCG 3284

205 GGCUGGCC G CCGCCGUG 985 CACGGCGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGCCAGCC 3285

208 UGGCCGCC G CCGUGCCG 986 CGGCACGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGCGGCCA 3286

213 GCCGCCGU G CCGAUGUA 987 UACAUCGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACGGCGGC 3287

216 GCCGUGCC G AUGUAGCG 988 CGCUACAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGCACGGC 3288

250 UCUCCCCU G CUCCCGUG 989 CACGGGAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGGGAGA 3289

Table 23

258 GCUCCCGU G CUCUGCGG 990 CCGCAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGGGAGC 3290

263 CGUGCUCU G CGGAUCUC 991 GAGAUCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGCACG 3291

276 UCUCCCCU G ACCGCUCU 992 AGAGCGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGGAGA 3292

280 CCCUGACC G CUCUCCAC 993 GUGGAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUCAGGG 3293

320 AGGGCCCU G CAGGCCCU 994 AGGGCCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGCCCU 3294

337 GGCGUCCU G AUGCCCCC 995 GGGGGCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGACGCC 3295

340 GUCCUGAU G CCCCCAAG 996 CUUGGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCAGGAC 3296

360 CCUCUCCU G AGAAGCCA 997 UGGCUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAGAGG 3297

397 GGGCAGGC G CCAGGGAC 998 GUCCCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCUGCCC 3298

420 GGGCCAGU G CGAGCCCA 999 UGGGCUCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGGCCC 3299

422 GCCAGUGC G AGCCCAGA 1000 UCUGGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCACUGGC 3300

437 GAGGGCCC G AAGGCCGG 1001 CCGGCCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGCCCUC 3301

468 CAAGCCCU G CCCUGGCU 1002 AGCCAGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGGCUUG 3302

480 UGGCUCCU G CUGUGGAU 1003 AUCCACAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGAGCCA 3303

493 GGAUGGGC G CGGGAGUG 1004 CACUCCCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCCCAUCC 3304

501 GCGGGAGU G CUGCCUGC 1005 GCAGGCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACUCCCGC 3305

504 GGAGUGCU G CCUGCCCA 1006 UGGGCAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCACUCC 3306

508 UGCUGCCU G CCCACGGC 1007 GCCGUGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGCAGCA 3307

537 AUCCGGCU G CCCCUGCG 1008 CGCAGGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCCGGAU 3308

543 CUGCCCCU G CGCAGCGG 1009 CCGCUGCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGGGCAG 3309

545 GCCCCUGC G CAGCGGCC 1010 GGCCGCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCAGGGGC 3310

562 UGGGGGGC G CCCCCCUG 1011 CAGGGGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCCCCCCA 3311

576 CUGGGGCU G CGGCUGCC 1012 GGCAGCCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCCCCAG 3312

582 CUGCGGCU G CCCCGGGA 1013 UCCCGGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCCGCAG 3313

595 GGGAGACC G ACGAAGAG 1014 CUCUUCGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGUCUCCC 3314

598 AGACCGAC G AAGAGCCC 1015 GGGCUCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUCGGUCU 3315

607 AAGAGCCC G AGGAGCCC 1016 GGGCUCCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGCUCUU 3316

654 GACAACCU G AGGGGCAA 1017 UUGCCCCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGUUGUC 3317

690 GUGGAGAU G ACCGUGGG 1018 CCCACGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCUCCAC 3318

708 AGCCCCCC G CAGACGCU 1019 AGCGUCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGGGGCU 3319

714 CCGCAGAC G CUCAACAU 1020 AUGUUGAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUCUGCGG 3320

751 GUAACUUU G CAGUGGGU 1021 ACCCACUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAGUUAC 3321

760 CAGUGGGU G CUGCCCCC 1022 GGGGGCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCCACUG 3322

763 UGGGUGCU G CCCCCCAC 1023 GUGGGGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCACCCA 3323

Table 23

780 CCCUUCCU G CAUCGCUA 1024 UAGCGAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAAGGG 3324

785 CCUGCAUC G CUACUACC 1025 GGUAGUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUGCAGG 3325

843 GUGUAUGU G CCCUACAC 1026 GUGUAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUACAC 3326

883 UGGGCACC G ACCUGGUA 1027 UACCAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUGCCCA 3327

921 GUCACUGU G CGUGCCAA 1028 UUGGCACG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGUGAC 3328

925 CUGUGCGU G CCAACAUU 1029 AAUGUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGCACAG 3329

934 CCAACAUU G CUGCCAUC 1030 GAUGGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUGUUGG 3330

937 ACAUUGCU G CCAUCACU 1031 AGUGAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAAUGU 3331

946 CCAUCACU G AAUCAGAC 1032 GUCUGAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUGAUGG 3332

1006 UGGCCUAU G CUGAGAUU 1033 AAUCUCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAGGCCA 3333

1009 CCUAUGCU G AGAUUGCC 1034 GGCAAUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAUAGG 3334

1015 CUGAGAUU G CCAGGCCU 1035 AGGCCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUCUCAG 3335

1024 CCAGGCCU G ACGACUCC 1036 GGAGUCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGCCUGG 3336

1027 GGCCUGAC G ACUCCCUG 1037 CAGGGAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCAGGCC 3337

1048 CUUUCUUU G ACUCUCUG 1038 CAGAGAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGAAAG 3338

1092 UUCUCCCU G CAGCUUUG 1039 CAAAGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGAGAA 3339

1105 UUUGUGGU G CUGGCUUC 1040 GAAGCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCACAAA 3340

1129 ACCAGUCU G AAGUGCUG 1041 CAGCACUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGACUGGU 3341

1134 UCUGAAGU G CUGGCCUC 1042 GAGGCCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACUUCAGA 3342

1158 GGGAGCAU G AUCAUUGG 1043 CCAAUGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGCUCCC 3343

1174 GAGGUAUC G ACCACUCG 1044 CGAGUGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAUACCUC 3344

1182 GACCACUC G CUGUACAC 1045 GUGUACAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAGUGGUC 3345

1234 GGUAUUAU G AGGUGAUC 1046 GAUCACCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAAUACC 3346

1239 UAUGAGGU G AUCAUUGU 1047 ACAAUGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCUCAUA 3347

1248 AUCAUUGU G CGGGUGGA 1048 UCCACCCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAAUGAU 3348

1275 CAGGAUCU G AAAAUGGA 1049 UCCAUUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAUCCUG 3349

1286 AAUGGACU G CAAGGAGU 1050 ACUCCUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUCCAUU 3350

1303 ACAACUAU G ACAAGAGC 1051 GCUCUUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAGUUGU 3351

1344 CUUCGUUU G CCCAAGAA 1052 UUCUUGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAACGAAG 3352

1360 AAGUGUUU G AAGCUGCA 1053 UGCAGCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAACACUU 3353

1366 UUGAAGCU G CAGUCAAA 1054 UUUGACUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCUUCAA 3354

1411 AGUUCCCU G AUGGUUUC 1055 GAAACCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGGAACU 3355

1442 GCUGGUGU G CUGGCAAG 1056 CUUGCCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACACCAGC 3356

1504 UAAUGGGU G AGGUUACC 1057 GGUAACCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCCAUUA 3357

Table 23

1526 GUCCUUCC G CAUCACCA 1058 UGGUGAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAAGGAC 3358

1542 AUCCUUCC G CAGCAAUA 1059 UAUUGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAAGGAU 3359

1554 CAAUACCU G CGGCCAGU 1060 ACUGGCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUAUUG 3360

1588 CCCAAGAC G ACUGUUAC 1061 GUAACAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCUUGGG 3361

1603 ACAAGUUU G CCAUCUCA 1062 UGAGAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAACUUGU 3362

1672 UUGUCUUU G AUCGGGCC 1063 GGCCCGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGACAA 3363

1682 UCGGGCCC G AAAACGAA 1064 UUCGUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGCCCGA 3364

1688 CCGAAAAC G AAUUGGCU 1065 AGCCAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUUUCGG 3365

1699 UUGGCUUU G CUGUCAGC 1066 GCUGACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGCCAA 3366

1708 CUGUCAGC G CUUGCCAU 1067 AUGGCAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUGACAG 3367

1712 CAGCGCUU G CCAUGUGC 1068 GCACAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGCGCUG 3368

1719 UGCCAUGU G CACGAUGA 1069 UCAUCGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUGGCA 3369

1723 AUGUGCAC G AUGAGUUC 1070 GAACUCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUGCACAU 3370

1726 UGCACGAU G AGUUCAGG 1071 CCUGAACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCGUGCA 3371

1807 AGACAGAU G AGUCAACC 1072 GGUUGACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCUGUCU 3372

1821 ACCCUCAU G ACCAUAGC 1073 GCUAUGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGAGGGU 3373

1843 UCAUGGCU G CCAUCUGC 1074 GCAGAUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCCAUGA 3374

1850 UGCCAUCU G CGCCCUCU 1075 AGAGGGCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAUGGCA 3375

1852 CCAUCUGC G CCCUCUUC 1076 GAAGAGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCAGAUGG 3376

1863 CUCUUCAU G CUGCCACU 1077 AGUGGCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGAAGAG 3377

1866 UUCAUGCU G CCACUCUG 1078 CAGAGUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCAUGAA 3378

1874 GCCACUCU G CCUCAUGG 1079 CCAUGAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAGUGGC 3379

1895 UCAGUGGC G CUGCCUCC 1080 GGAGGCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCCACUGA 3380

1898 GUGGCGCU G CCUCCGCU 1081 AGCGGAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCGCCAC 3381

1904 CUGCCUCC G CUGCCUGC 1082 GCAGGCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGAGGCAG 3382

1907 CCUCCGCU G CCUGCGCC 1083 GGCGCAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCGGAGG 3383

1911 CGCUGCCU G CGCCAGCA 1084 UGCUGGCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGCAGCG 3384

1913 CUGCCUGC G CCAGCAGC 1085 GCUGCUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCAGGCAG 3385

1924 AGCAGCAU G AUGACUUU 1086 AAAGUCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGCUGCU 3386

1927 AGCAUGAU G ACUUUGCU 1087 AGCAAAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCAUGCU 3387

1933 AUGACUUU G CUGAUGAC 1088 GUCAUCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAGUCAU 3388

1936 ACUUUGCU G AUGACAUC 1089 GAUGUCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCAAAGU 3389

1939 UUGCUGAU G ACAUCUCC 1090 GGAGAUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCAGCAA 3390

1950 AUCUCCCU G CUGAAGUG 1091 CACUUCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGGAGAU 3391

Table 23

1953 UCCCUGCU G AAGUGAGG 1092 CCUCACUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAGGGA 3392

1958 GCUGAAGU G AGGAGGCC 1093 GGCCUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUUCAGC 3393

2087 CACCAAAU G CCUCUGCC 1094 GGCAGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUGGUG 3394

2093 AUGCCUCU G CCUUGAUG 1095 CAUCAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG 'AGAGGCAU 3395

2098 UCUGCCUU G AUGGAGAA 1096 UUCUCCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGCAGA 3396

2179 AGCACUCU G CUGGCGGG 1097 CCCGCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGUGCU 3397

2227 GAAAUUCU G CUGCUUGA 1098 UCAAGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAUUUC 3398

2230 AUUCUGCU G CUUGAAAC 1099 GUUUCAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAGAAU 3399

2234 UGCUGCUU G AAACUUCA 1100 UGAAGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGCAGCA 3400

2248 UCAGCCCU G AACCUUUG 1101 CAAAGGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGCUGA 3401

2329 CAUCACAC G CAGGUUAC 1102 GUAACCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUGUGAUG 3402

2393 GUUUCCCU G CUGGCCAA 1103 UUGGCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGAAAC 3403

2419 GAGAGGAU G CACAGUUU 1104 AAACUGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCCUCUC 3404

2428 CACAGUUU G CUAUUUGC 1105 GCAAAUAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAACUGUG 3405

2435 UGCUAUUU G CUUUAGAG 1106 CUCUAAAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAUAGCA 3406

2476 ACAUUGGU G CAAAGAUU 1107 AAUCUUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCAAUGU 3407

2485 CAAAGAUU G CCUCUUGA 1108 UCAAGAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUCUUUG 3408

2492 UGCCUCUU G AAUUAAAA 1109 UUUUAAUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGAGGCA 3409

219 GUGCCGAU G UAGCGGGC 1110 GCCCGCUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCGGCAC 3410

483 CUCCUGCU G UGGAUGGG llll CCCAUCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCAGGAG 3411

634 GCAGCUUU G UGGAGAUG 1112 CAUCUCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAGCUGC 3412

804 AGGCAGCU G UCCAGCAC 1113 GUGCUGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCUGCCU 3413

835 GGAAGGGU G UGUAUGUG 1114 CACAUACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCCUUCC 3414

837 AAGGGUGU G UAUGUGCC 1115 GGCACAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACACCCUU 3415

841 GUGUGUAU G UGCCCUAC 1116 GUAGGGCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUACACAC 3416

919 ACGUCACU G UGCGUGCC 1117 GGCACGCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUGACGU 3417

1100 GCAGCUUU G UGGUGCUG 1118 CAGCACCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAGCUGC 3418

1144 UGGCCUCU G UCGGAGGG 1119 CCCUCCGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAGGCCA 3419

1185 CACUCGCU G UACACAGG 1120 CCUGUGUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCGAGUG 3420

1246 UGAUCAUU G UGCGGGUG 1121 CACCCGCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUGAUCA 3421

1315 AGAGCAUU G UGGACAGU 1122 ACUGUCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUGCUCU 3422

1356 AAGAAAGU G UUUGAAGC 1123 GCUUCAAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACUUUCUU 3423

1440 CAGCUGGU G UGCUGGCA 1124 UGCCAGCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCAGCUG 3424

1570 UGGAAGAU G UGGCCACG 1125 CGUGGCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCUUCCA 3425

Table 23

1592 AGACGACU G UUACAAGU 1126 ACUUGUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUCGUCU 3426

1630 CGGGCACU G UUAUGGGA 1127 UCCCAUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUGCCCG 3427

1642 UGGGAGCU G UUAUCAUG 1128 CAUGAUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUCCCA 3428

1666 UCUACGUU G UCUUUGAU 1129 AUCAAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACGUAGA 3429

1702 GCUUUGCU G UCAGCGCU 1130 AGCGCUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAAAGC 3430

1717 CUUGCCAU G UGCACGAU 1131 AUCGUGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGGCAAG 3431

1759 GCCCUUUU G UCACCUUG 1132 CAAGGUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAGGGC 3432

1781 GGAAGACU G UGGCUACA 1133 UGUAGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUCUUCC 3433

1834 UAGCCUAU G UCAUGGCU 1134 AGCCAUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAGGCUA 3434

1884 CUCAUGGU G UGUCAGUG 1135 CACUGACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCAUGAG 3435

1886 CAUGGUGU G UCAGUGGC 1136 GCCACUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACCAUG 3436

2048 UGGCACCU G UGGCCAGA 1137 UCUGGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUGCCA 3437

2139 CAGGGACU G UACCUGUA 1138 UACAGGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUCCCUG 3438

2145 CUGUACCU G UAGGAAAC 1139 GUUUCCUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGUACAG 3439

2256 GAACCUUU G UCCACCAU 1140 AUGGUGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAGGUUC 3440

2346 CUUGGCGU G UGUCCCUG 1141 CAGGGACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACGCCAAG 3441

2348 UGGCGUGU G UCCCUGUG 1142 CACAGGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACACGCCA 3442

2354 GUGUCCCU G UGGUACCC 1143 GGGUACCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGGACAC 3443

2385 CCAAGCUU G UUUCCCUG 1144 CAGGGAAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGCUUGG 3444

2453 CAGGGACU G UAUAAACA 1145 UGUUUAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUCCCUG 3445

14 CGUCCGCA G CCCGCCCG 1146 CGGGCGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCGGACG 3446

26 GCCCGGGA G CUGCGAGC 1147 GCUCGCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCCGGGC 3447

33 AGCUGCGA G CCGCGAGC 1148 GCUCGCGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCGCAGCU 3448

40 AGCCGCGA G CUGGAUUA 1149 UAAUCCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCGCGGCU 3449

51 GGAUUAUG G UGGCCUGA 1150 UCAGGCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUAAUCC 3450

54 UUAUGGUG G CCUGAGCA 1151 UGCUCAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACCAUAA 3451

60 UGGCCUGA G CAGCCAAC 1152 GUUGGCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCAGGCCA 3452

63 CCUGAGCA G CCAACGCA 1153 UGCGUUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCUCAGG 3453

72 CCAACGCA G CCGCAGGA 1154 UCCUGCGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCGUUGG 3454

81 CCGCAGGA G CCCGGAGC 1155 GCUCCGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCUGCGG 3455

88 AGCCCGGA G CCCUUGCC 1156 GGCAAGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCGGGCU 3456

134 CCAGGGAA G CCGCCACC 1157 GGUGGCGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCCCUGG 3457

144 CGCCACCG G CCCGCCAU 1158 AUGGCGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGGUGGCG 3458

167 CCCUCCCA G CCCCGCCG 1159 CGGCGGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGGAGGG 3459

Table 23

179 CGCCGGGA G CCCGCGCC 1160 GGCGCGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCGGCG 3460

198 CUGCCCAG G CUGGCCGC 1161 GCGGCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGGCAG 3461

202 CCAGGCUG G CCGCCGCC 1162 GGCGGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCCUGG 3462

211 CCGCCGCC G UGCCGAUG 1163 CAUCGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCGGCGG 3463

222 CCGAUGUA G CGGGCUCC 1164 GGAGCCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACAUCGG 3464

226 UGUAGCGG G CUCCGGAU 1165 AUCCGGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGCUACA 3465

239 GGAUCCCA G CCUCUCCC 1166 GGGAGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGAUCC 3466

256 CUGCUCCC G UGCUCUGC 1167 GCAGAGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGAGCAG 3467

290 UCUCCACA G CCCGGACC 1168 GGUCCGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUGGAGA 3468

304 ACCCGGGG G CUGGCCCA 1169 UGGGCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCGGGU 3469

308 GGGGGCUG G CCCAGGGC 1170 GCCCUGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGCCCCC 3470

315 GGCCCAGG G CCCUGCAG 1171 CUGCAGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUGGGCC 3471

324 CCCUGCAG G CCCUGGCG 1172 CGCCAGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGCAGGG 3472

330 AGGCCCUG G CGUCCUGA 1173 UCAGGACG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGGGCCU 3473

332 GCCCUGGC G UCCUGAUG 1174 CAUCAGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCCAGGGC 3474

348 GCCCCCAA G CUCCCUCU 1175 AGAGGGAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGGGGGC 3475

365 CCUGAGAA G CCACCAGC 1176 GCUGGUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCUCAGG 3476

372 AGCCACCA G CACCACCC 1177 GGGUGGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGUGGCU 3477

391 ACUUGGGG G CAGGCGCC 1178 GGCGCCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCCAAGU 3478

395 GGGGGCAG G CGCCAGGG 1179 CCCUGGCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGCCCCC 3479

410 GGACGGAC G UGGGCCAG 1180 CUGGCCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUCCGUCC 3480

414 GGACGUGG G CCAGUGCG 1181 CGCACUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCACGUCC 3481

418 GUGGGCCA G UGCGAGCC 1182 GGCUCGCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGCCCAC 3482

424 CAGUGCGA G CCCAGAGG 1183 CCUCUGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCGCACUG 3483

433 CCCAGAGG G CCCGAAGG 1184 CCUUCGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUCUGGG 3484

441 GCCCGAAG G CCGGGGCC 1185 GGCCCCGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUCGGGC 3485

447 AGGCCGGG G CCCACCAU 1186 AUGGUGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCGGCCU 3486

457 CCACCAUG G CCCAAGCC 1187 GGCUUGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUGGUGG 3487

463 UGGCCCAA G CCCUGCCC 1188 GGGCAGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGGGCCA 3488

474 CUGCCCUG G CUCCUGCU 1189 AGCAGGAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGGGCAG 3489

491 GUGGAUGG G CGCGGGAG 1190 CUCCCGCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAUCCAC 3490

499 GCGCGGGA G UGCUGCCU 1191 AGGCAGCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCCGCGC 3491

515 UGCCCACG G CACCCAGC 1192 GCUGGGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGUGGGCA 3492

522 GGCACCCA G CACGGCAU 1193 AUGCCGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGGUGCC 3493

Table 23

527 CCAGCACG G CAUCCGGC 1194 GCCGGAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUGCUGG 3494

534 GGCAUCCG G CUGCCCCU 1195 AGGGGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGAUGCC 3495

548 CCUGCGCA G CGGCCUGG 1196 CCAGGCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCGCAGG 3496

551 GCGCAGCG G CCUGGGGG 1197 CCCCCAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCUGCGC 3497

560 CCUGGGGG G CGCCCCCC 1198 GGGGGGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCCAGG 3498

573 CCCCUGGG G CUGCGGCU 1199 AGCCGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAGGGG 3499

579 GGGCUGCG G CUGCCCCG 1200 CGGGGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCAGCCC 3500

603 GACGAAGA G CCCGAGGA 1201 UCCUCGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUCGUC 3501

612 CCCGAGGA G CCCGGCCG 1202 CGGCCGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCGGG 3502

617 GGAGCCCG G CCGGAGGG 1203 CCCUCCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGGCUCC 3503

626 CCGGAGGG G CAGCUUUG 1204 CAAAGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCUCCGG 3504

629 GAGGGGCA G CUUUGUGG 1205 CCACAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCCCUC 3505

643 UGGAGAUG G UGGACAAC 1206 GUUGUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUCUCCA 3506

659 CCUGAGGG G CAAGUCGG 1207 CCGACUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCUCAGG 3507

663 AGGGGCAA G UCGGGGCA 1208 UGCCCCGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGCCCCU 3508

669 AAGUCGGG G CAGGGCUA 1209 UAGCCCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCGACUU 3509

674 GGGGCAGG G CUACUACG 1210 CGUAGUAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUGCCCC 3510

682 GCUACUAC G UGGAGAUG 1211 CAUCUCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUAGUAGC 3511

694 AGAUGACC G UGGGCAGC 1212 GCUGCCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGUCAUCU 3512

698 GACCGUGG G CAGCCCCC 1213 GGGGGCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCACGGUC 3513

701 CGUGGGCA G CCCCCCGC 1214 GCGGGGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCCCACG 3514

727 ACAUCCUG G UGGAUACA 1215 UGUAUCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGGAUGU 3515

737 GGAUACAG G CAGCAGUA 1216 UACUGCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGUAUCC 3516

740 UACAGGCA G CAGUAACU 1217 AGUUACUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCCUGUA 3517

743 AGGCAGCA G UAACUUUG 1218 CAAAGUUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCUGCCU 3518

754 ACUUUGCA G UGGGUGCU 1219 AGCACCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCAAAGU 3519

758 UGCAGUGG G UGCUGCCC 1220 GGGCAGCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCACUGCA 3520

798 UACCAGAG G CAGCUGUC 1221 GACAGCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCUGGUA 3521

801 CAGAGGCA G CUGUCCAG 1222 CUGGACAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCCUCUG 3522

809 GCUGUCCA G CACAUACC 1223 GGUAUGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGACAGC 3523

833 CCGGAAGG G UGUGUAUG 1224 CAUACACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUUCCGG 3524

857 CACCCAGG G CAAGUGGG 1225 CCCACUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUGGGUG 3525

861 CAGGGCAA G UGGGAAGG 1226 CCUUCCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGCCCUG 3526

873 GAAGGGGA G CUGGGCAC 1227 GUGCCCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCCCUUC 3527

Table 23

878 GGAGCUGG G CACCGACC 1228 GGUCGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGCUCC 3528

889 CCGACCUG G UAAGCAUC 1229 GAUGCUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGUCGG 3529

893 CCUGGUAA G CAUCCCCC 1230 GGGGGAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUACCAGG 3530

905 CCCCCAUG G CCCCAACG 1231 CGUUGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGGGGG 3531

913 GCCCCAAC G UCACUGUG 1232 CACAGUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUGGGGC 3532

923 CACUGUGC G UGCCAACA 1233 UGUUGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCACAGUG 3533

957 UCAGACAA G UUCUUCAU 1234 AUGAAGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUCUGA 3534

971 CAUCAACG G CUCCAACU 1235 AGUUGGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUUGAUG 3535

986 CUGGGAAG G CAUCCUGG 1236 CCAGGAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCCCAG 3536

996 AUCCUGGG G CUGGCCUA 1237 UAGGCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAGGAU 3537

1000 UGGGGCUG G CCUAUGCU 1238 AGCAUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCCCCA 3538

1020 AUUGCCAG G CCUGACGA 1239 UCGUCAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGCAAU 3539

1038 UCCCUGGA G CCUUUCUU 1240 AAGAAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAGGGA 3540

1057 ACUCUCUG G UAAAGCAG 1241 CUGCUUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGAGAGU 3541

1062 CUGGUAAA G CAGACCCA 1242 UGGGUCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUACCAG 3542

1072 AGACCCAC G UUCCCAAC 1243 GUUGGGAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUGGGUCU 3543

1095 UCCCUGCA G CUUUGUGG 1244 CCACAAAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCAGGGA 3544

1103 GCUUUGUG G UGCUGGCU 1245 AGCCAGCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACAAAGC 3545

1109 UGGUGCUG G CUUCCCCC 1246 GGGGGAAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGCACCA 3546

1125 CUCAACCA G UCUGAAGU 1247 ACUUCAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGUUGAG 3547

1132 AGUCUGAA G UGCUGGCC 1248 GGCCAGCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCAGACU 3548

1138 AAGUGCUG G CCUCUGUC 1249 GACAGAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGCACUU 3549

1154 CGGAGGGA G CAUGAUCA 1250 UGAUCAUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCCUCCG 3550

1169 CAUUGGAG G UAUCGACC 1251 GGUCGAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCCAAUG 3551

1193 GUACACAG G CAGUCUCU 1252 AGAGACUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGUGUAC 3552

1196 CACAGGCA G UCUCUGGU 1253 ACCAGAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCCUGUG 3553

1203 AGUCUCUG G UAUACACC 1254 GGUGUAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGAGACU 3554

1218 CCCAUCCG G CGGGAGUG 1255 CACUCCCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGGAUGGG 3555

1224 CGGCGGGA G UGGUAUUA 1256 UAAUACCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCCGCCG 3556

1227 CGGGAGUG G UAUUAUGA 1257 UCAUAAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACUCCCG 3557

1237 AUUAUGAG G UGAUCAUU 1258 AAUGAUCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCAUAAU 3558

1252 UUGUGCGG G UGGAGAUC 1259 GAUCUCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGCACAA 3559

1293 UGCAAGGA G UACAACUA 1260 UAGUUGUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCUUGCA 3560

1310 UGACAAGA G CAUUGUGG 1261 CCACAAUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCUUGUCA 3561

Table 23

1322 UGUGGACA G UGGCACCA 1262 UGGUGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUCCACA 3562

1325 GGACAGUG G CACCACCA 1263 UGGUGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUGUCC 3563

1340 CAACCUUC G UUUGCCCA 1264 UGGGCAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAGGUUG 3564

1354 CCAAGAAA G UGUUUGAA 1265 UUCAAACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUCUUGG 3565

1363 UGUUUGAA G CUGCAGUC 1266 GACUGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCAAACA 3566

1369 AAGCUGCA G UCAAAUCC 1267 GGAUUUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAGCUU 3567

1384 CCAUCAAG G CAGCCUCC 1268 GGAGGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGAUGG 3568

1387 UCAAGGCA G CCUCCUCC 1269 GGAGGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCUUGA 3569

1404 ACGGAGAA G UUCCCUGA 1270 UCAGGGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUCCGU 3570

1415 CCCUGAUG G UUUCUGGC 1271 GCCAGAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUCAGGG 3571

1422 GGUUUCUG G CUAGGAGA 1272 UCUCCUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGAAACC 3572

1431 CUAGGAGA G CAGCUGGU 1273 ACCAGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUCCUAG 3573

1434 GGAGAGCA G CUGGUGUG 1274 CACACCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUCUCC 3574

1438 AGCAGCUG G UGUGCUGG 1275 CCAGCACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGCUGCU 3575

1446 GUGUGCUG G CAAGCAGG 1276 CCUGCUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGCACAC 3576

1450 GCUGGCAA G CAGGCACC 1277 GGUGCCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGCCAGC 3577

1454 GCAAGCAG G CACCACCC 1278 GGGUGGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGCUUGC 3578

1480 UUUUCCCA G UCAUCUCA 1279 UGAGAUGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGGAAAA 3579

1502 CCUAAUGG G UGAGGUUA 1280 UAACCUCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAUUAGG 3580

1507 UGGGUGAG G UUACCAAC 1281 GUUGGUAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCACCCA 3581

1518 ACCAACCA G UCCUUCCG 1282 CGGAAGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGUUGGU 3582

1545 CUUCCGCA G CAAUACCU 1283 AGGUAUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCGGAAG 3583

1557 UACCUGCG G CCAGUGGA 1284 UCCACUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGCAGGUA 3584

1561 UGCGGCCA G UGGAAGAU 1285 AUCUUCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGCCGCA 3585

1573 AAGAUGUG G CCACGUCC 1286 GGACGUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACAUCUU 3586

1578 GUGGCCAC G UCCCAAGA 1287 UCUUGGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUGGCCAC 3587

1599 UGUUACAA G UUUGCCAU 1288 AUGGCAAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGUAACA 3588

1614 AUCUCACA G UCAUCCAC 1289 GUGGAUGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUGAGAU 3589

1625 AUCCACGG G CACUGUUA 1290 UAACAGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGUGGAU 3590

1639 UUAUGGGA G CUGUUAUC 1291 GAUAACAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCCAUAA 3591

1655 CAUGGAGG G CUUCUACG 1292 CGUAGAAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUCCAUG 3592

1663 GCUUCUAC G UUGUCUUU 1293 AAAGACAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUAGAAGC 3593

1678 UUGAUCGG G CCCGAAAA 1294 UUUUCGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGAUCAA 3594

1694j ACGAAUUG G CUUUGCUG 1295 CAGCAAAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAUUCGU 3595

Table 23

1706 UGCUGUCA G CGCUUGCC 1296 GGCAAGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGACAGCA 3596

1728 CACGAUGA G UUCAGGAC 1297 GUCCUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAUCGUG 3597

1738 UCAGGACG G CAGCGGUG 1298 CACCGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUCCUGA 3598

1741 GGACGGCA G CGGUGGAA 1299 UUCCACCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCGUCC 3599

1744 CGGCAGCG G UGGAAGGC 1300 GCCUUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCUGCCG 3600

1751 GGUGGAAG G CCCUUUUG 1301 CAAAAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCCACC 3601

1784 AGACUGUG G CUACAACA 1302 UGUUGUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAGUCU 3602

1809 ACAGAUGA G UCAACCCU 1303 AGGGUUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAUCUGU 3603

1828 UGACCAUA G CCUAUGUC 1304 GACAUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUGGUCA 3604

1840 AUGUCAUG G CUGCCAUC 1305 GAUGGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGACAU 3605

1882 GCCUCAUG G UGUGUCAG 1306 CUGACACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGAGGC 3606

1890 GUGUGUCA G UGGCGCUG 1307 CAGCGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGACACAC 3607

1893 UGUCAGUG G CGCUGCCU 1308 AGGCAGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUGACA 3608

1917 CUGCGCCA G CAGCAUGA 1309 UCAUGCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGCGCAG 3609

1920 CGCCAGCA G CAUGAUGA 1310 UCAUCAUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCUGGCG 3610

1956 CUGCUGAA G UGAGGAGG 1311 CCUCCUCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCAGCAG 3611

1964 GUGAGGAG G CCCAUGGG 1312 CCCAUGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCCUCAC 3612

1972 GCCCAUGG G CAGAAGAU 1313 AUCUUCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAUGGGC 3613

2006 ACACCUCC G UGGUUCAC 1314 GUGAACCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGAGGUGU 3614

2009 CCUCCGUG G UUCACUUU 1315 AAAGUGAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACGGAGG 3615

2019 UCACUUUG G UCACAAGU 1316 ACUUGUGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAAGUGA 3616

2026 GGUCACAA G UAGGAGAC 1317 GUCUCCUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGUGACC 3617

2042 CACAGAUG G CACCUGUG 1318 CACAGGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUCUGUG 3618

2051 CACCUGUG G CCAGAGCA 1319 UGCUCUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACAGGUG 3619

2057 UGGCCAGA G CACCUCAG 1320 CUGAGGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCUGGCCA 3620

2114 AGGAAAAG G CUGGCAAG 1321 CUUGCCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUUUCCU 3621

2118 AAAGGCUG G CAAGGUGG 1322 CCACCUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGCCUUU 3622

2123 CUGGCAAG G UGGGUUCC 1323 GGAACCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUGCCAG 3623

2127 CAAGGUGG G UUCCAGGG 1324 CCCUGGAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCACCUUG 3624

2172 AGAAAGAA G CACUCUGC 1325 GCAGAGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCUUUCU 3625

2183 CUCUGCUG G CGGGAAUA 1326 UAUUCCCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGCAGAG 3626

2198 UACUCUUG G UCACCUCA 1327 UGAGGUGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAGAGUA 3627

2214 AAAUUUAA G UCGGGAAA 1328 UUUCCCGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUAAAUUU 3628

2243 AAACUUCA G CCCUGAAC 1329 GUUCAGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGAAGUUU 3629

Table 23

2288 AACCCAAA G UAUUCUUC 1330 GAAGAAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGGGUU 3630

2305 UUUUCUUA G UUUCAGAA 1331 UUCUGAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAGAAAA 3631

2314 UUUCAGAA G UACUGGCA 1332 UGCCAGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUGAAA 3632

2320 AAGUACUG G CAUCACAC 1333 GUGUGAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGUACUU 3633

2333 ACACGCAG G UUACCUUG 1334 CAAGGUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCGUGU 3634

2342 UUACCUUG G CGUGUGUC 1335 GACACACG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGGUAA 3635

2344 ACCUUGGC G UGUGUCCC 1336 GGGACACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCAAGGU 3636

2357 UCCCUGUG G UACCCUGG 1337 CCAGGGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAGGGA 3637

2365 GUACCCUG G CAGAGAAG 1338 CUUCUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGGUAC 3638

2381 GAGACCAA G CUUGUUUC 1339 GAAACAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGUCUC 3639

2397 CCCUGCUG G CCAAAGUC 1340 GACUUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCAGGG 3640

2403 UGGCCAAA G UCAGUAGG 1341 CCUACUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGGCCA 3641

2407 CAAAGUCA G UAGGAGAG 1342 CUCUCCUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGACUUUG 3642

2424 GAUGCACA G UUUGCUAU 1343 AUAGCAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUGCAUC 3643

2463 AUAAACAA G CCUAACAU 1344 AUGUUAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGUUUAU 3644

2474 UAACAUUG G UGCAAAGA 1345 UCUUUGCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAUGUUA 3645

22 GCCCGCCC G GGAGCUGC 1449 GCAGCUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGCGGGC 3646

23 CCCGCCCG G GAGCUGCG 1450 CGCAGCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGGGCGGG 3647

24 CCGCCCGG G AGCUGCGA 1451 UCGCAGCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGGGCGG 3648

43 CGCGAGCU G GAUUAUGG 1452 CCAUAAUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCUCGCG 3649

44 GCGAGCUG G AUUAUGGU 1453 ACCAUAAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGCUCGC 3650

50 UGGAUUAU G GUGGCCUG 1454 CAGGCCAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAAUCCA 3651

53 AUUAUGGU G GCCUGAGC 1455 GCUCAGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCAUAAU 3652

78 CAGCCGCA G GAGCCCGG 1456 CCGGGCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCGGCUG 3653

79 AGCCGCAG G AGCCCGGA 1457 UCCGGGCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGCGGCU 3654

85 AGGAGCCC G GAGCCCUU 1458 AAGGGCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGCUCCU 3655

86 GGAGCCCG G AGCCCUUG 1459 CAAGGGCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGGGCUCC 3656

119 CGCCCGCC G GGGGGACC 1460 GGUCCCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGCGGGCG 3657

120 GCCCGCCG G GGGGACCA 1461 UGGUCCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGGCGGGC 3658

121 CCCGCCGG G GGGACCAG 1462 CUGGUCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGGCGGG 3659

122 CCGCCGGG G GGACCAGG 1463 CCUGGUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCGGCGG 3660

123 CGCCGGGG G GACCAGGG 1464 CCCUGGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCCGGCG 3661

124 GCCGGGGG G ACCAGGGA 1465 UCCCUGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCCCGGC 3662

129 GGGGACCA G GGAAGCCG 1466 CGGCUUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGUCCCC 3663

Table 23

130 GGGACCAG G GAAGCCGC 1467 GCGGCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGUCCC 3664

131 GGACCAGG G AAGCCGCC 1468 GGCGGCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGGUCC 3665

143 CCGCCACC G GCCCGCCA 1469 UGGCGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUGGCGG 3666

175 GCCCCGCC G GGAGCCCG 1470 CGGGCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCGGGGC 3667

176 CCCCGCCG G GAGCCCGC 1471 GCGGGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGCGGGG 3668

177 CCCGCCGG G AGCCCGCG 1472 CGCGGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGGCGGG 3669

197 GCUGCCCA G GCUGGCCG 1473 CGGCCAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGCAGC 3670

201 CCCAGGCU G GCCGCCGC 1474 GCGGCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCUGGG 3671

224 GAUGUAGC G GGCUCCGG 1475 CCGGAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUACAUC 3672

225 AUGUAGCG G GCUCCGGA 1476 UCCGGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCUACAU 3673

231 CGGGCUCC G GAUCCCAG 1477 CUGGGAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAGCCCG 3674

232 GGGCUCCG G AUCCCAGC 1478 GCUGGGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGAGCCC 3675

265 UGCUCUGC G GAUCUCCC 1479 GGGAGAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAGAGCA 3676

266 GCUCUGCG G AUCUCCCC 1480 GGGGAGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGCAGAGC 3677

294 CACAGCCC G GACCCGGG 1481 CCCGGGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGCUGUG 3678

295 ACAGCCCG G ACCCGGGG 1482 CCCCGGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGGGCUGU 3679

300 CCGGACCC G GGGGCUGG 1483 CCAGCCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGUCCGG 3680

301 CGGACCCG G GGGCUGGC 1484 GCCAGCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGGGUCCG 3681

302 GGACCCGG G GGCUGGCC 1485 GGCCAGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGGGUCC 3682

303 GACCCGGG G GCUGGCCC 1486 GGGCCAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCGGGUC 3683

307 CGGGGGCU G GCCCAGGG 1487 CCCUGGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCCCCCG 3684

313 CUGGCCCA G GGCCCUGC 1488 GCAGGGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGGCCAG 3685

314 UGGCCCAG G GCCCUGCA 1489 UGCAGGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGGGCCA 3686

323 GCCCUGCA G GCCCUGGC 1490 GCCAGGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCAGGGC 3687

329 CAGGCCCU G GCGUCCUG 1491 CAGGACGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGGCCUG 3688

362 UCUCCUGA G AAGCCACC 1492 GGUGGCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCAGGAGA 3689

382 ACCACCCA G ACUUGGGG 1493 CCCCAAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGGUGGU 3690

387 CCAGACUU G GGGGCAGG 1494 CCUGCCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGUCUGG 3691

388 CAGACUUG G GGGCAGGC 1495 GCCUGCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAGUCUG 3692

389 AGACUUGG G GGCAGGCG 1496 CGCCUGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAAGUCU 3693

390 GACUUGGG G GCAGGCGC 1497 GCGCCUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCAAGUC 3694

394 UGGGGGCA G GCGCCAGG 1498 CCUGGCGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCCCCCA 3695

401 AGGCGCCA G GGACGGAC 1499 GUCCGUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGCGCCU 3696

402 GGCGCCAG G GACGGACG 1500 CGUCCGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGGCGCC 3697

Table 23

403 GCGCCAGG G ACGGACGU 1501 ACGUCCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGGCGC 3698

406 CCAGGGAC G GACGUGGG 1502 CCCACGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCCCUGG 3699

407 CAGGGACG G ACGUGGGC 1503 GCCCACGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUCCCUG 3700

412 ACGGACGU G GGCCAGUG 1504 CACUGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGUCCGU 3701

413 CGGACGUG G GCCAGUGC 1505 GCACUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACGUCCG 3702

429 CGAGCCCA G AGGGCCCG 1506 CGGGCCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGCUCG 3703

431 AGCCCAGA G GGCCCGAA 1507 UUCGGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGGGCU 3704

432 GCCCAGAG G GCCCGAAG 1508 CUUCGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCUGGGC 3705

440 GGCCCGAA G GCCGGGGC 1509 GCCCCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCGGGCC 3706

444 CGAAGGCC G GGGCCCAC 1510 GUGGGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCCUUCG 3707

445 GAAGGCCG G GGCCCACC 1511 GGUGGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGCCUUC 3708

446 AAGGCCGG G GCCCACCA 1512 UGGUGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGGCCUU 3709

456 CCCACCAU G GCCCAAGC 1513 GCUUGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGGUGGG 3710

473 CCUGCCCU G GCUCCUGC 1514 GCAGGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGCAGG 3711

485 CCUGCUGU G GAUGGGCG 1515 CGCCCAUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAGCAGG 3712

486 CUGCUGUG G AUGGGCGC 1516 GCGCCCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACAGCAG 3713

489 CUGUGGAU G GGCGCGGG 1517 CCCGCGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCCACAG 3714

490 UGUGGAUG G GCGCGGGA 1518 UCCCGCGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUCCACA 3715

495 AUGGGCGC G GGAGUGCU 1519 AGCACUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCGCCCAU 3716

496 UGGGCGCG G GAGUGCUG 1520 CAGCACUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGCGCCCA 3717

497 GGGCGCGG G AGUGCUGC 1521 GCAGCACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGCGCCC 3718

514 CUGCCCAC G GCACCCAG 1522 CUGGGUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUGGGCAG 3719

526 CCCAGCAC G GCAUCCGG 1523 CCGGAUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUGCUGGG 3720

533 CGGCAUCC G GCUGCCCC 1524 GGGGCAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGAUGCCG 3721

550 UGCGCAGC G GCCUGGGG 1525 CCCCAGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCUGCGCA 3722

555 AGCGGCCU G GGGGGCGC 1526 GCGCCCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGCCGCU 3723

556 GCGGCCUG G GGGGCGCC 1527 GGCGCCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGGCCGC 3724

557 CGGCCUGG G GGGCGCCC 1528 GGGCGCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAGGCCG 3725

558 GGCCUGGG G GGCGCCCC 1529 GGGGCGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCAGGCC 3726

559 GCCUGGGG G GCGCCCCC 1530 GGGGGCGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCCAGGC 3727

570 GCCCCCCU G GGGCUGCG 1531 CGCAGCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGGGGGC 3728

571 CCCCCCUG G GGCUGCGG 1532 CCGCAGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGGGGGG 3729

572 CCCCCUGG G GCUGCGGC 1533 GCCGCAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAGGGGG 3730

578 GGGGCUGC G GCUGCCCC 1534 GGGGCAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCAGCCCC 3731

Table 23

587 GCUGCCCC G GGAGACCG 1535 CGGUCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGGCAGC 3732

588 CUGCCCCG G GAGACCGA 1536 UCGGUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGGGCAG 3733

589 UGCCCCGG G AGACCGAC 1537 GUCGGUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGGGGCA 3734

591 CCCCGGGA G ACCGACGA 1538 UCGUCGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCGGGG 3735

601 CCGACGAA G AGCCCGAG 1539 CUCGGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCGUCGG 3736

609 GAGCCCGA G GAGCCCGG 1540 CCGGGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGGGCUC 3737

610 AGCCCGAG G AGCCCGGC 1541 GCCGGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCGGGCU 3738

616 AGGAGCCC G GCCGGAGG 1542 CCUCCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGCUCCU 3739

620 GCCCGGCC G GAGGGGCA 1543 UGCCCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCCGGGC 3740

621 CCCGGCCG G AGGGGCAG 1544 CUGCCCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGCCGGG 3741

623 CGGCCGGA G GGGCAGCU 1545 AGCUGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCGGCCG 3742

624 GGCCGGAG G GGCAGCUU 1546 AAGCUGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCGGCC 3743

625 GCCGGAGG G GCAGCUUU 1547 AAAGCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUCCGGC 3744

636 AGCUUUGU G GAGAUGGU 1548 ACCAUCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAAAGCU 3745

637 GCUUUGUG G AGAUGGUG 1549 CACCAUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACAAAGC 3746

639 UUUGUGGA G AUGGUGGA 1550 UCCACCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCACAAA 3747

642 GUGGAGAU G GUGGACAA 1551 UUGUCCAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCUCCAC 3748

645 GAGAUGGU G GACAACCU 1552 AGGUUGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCAUCUC 3749

646 AGAUGGUG G ACAACCUG 1553 CAGGUUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACCAUCU 3750

656 CAACCUGA G GGGCAAGU 1554 ACUUGCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCAGGUUG 3751

657 AACCUGAG G GGCAAGUC 1555 GACUUGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCAGGUU 3752

658 ACCUGAGG G GCAAGUCG 1556 CGACUUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUCAGGU 3753

666 GGCAAGUC G GGGCAGGG 1557 CCCUGCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GACUUGCC 3754

667 GCAAGUCG G GGCAGGGC 1558 GCCCUGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGACUUGC 3755

668 CAAGUCGG G GCAGGGCU 1559 AGCCCUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGACUUG 3756

672 UCGGGGCA G GGCUACUA 1560 UAGUAGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCCCCGA 3757

673 CGGGGCAG G GCUACUAC 1561 GUAGUAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGCCCCG 3758

684 UACUACGU G GAGAUGAC 1562 GUCAUCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACGUAGUA 3759

685 ACUACGUG G AGAUGACC 1563 GGUCAUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACGUAGU 3760

687 UACGUGGA G AUGACCGU 1564 ACGGUCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCACGUA 3761

696 AUGACCGU G GGCAGCCC 1565 GGGCUGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACGGUCAU 3762

697 UGACCGUG G GCAGCCCC 1566 GGGGCUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACGGUCA 3763

711 CCCCCGCA G ACGCUCAA 1567 UUGAGCGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCGGGGG 3764

726 AACAUCCU G GUGGAUAC 1568 GUAUCCAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGAUGUU 3765

Table 23

729 AUCCUGGU G GAUACAGG 1569 CCUGUAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCAGGAU 3766

730 UCCUGGUG G AUACAGGC 1570. GCCUGUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCAGGA 3767

736 UGGAUACA G GCAGCAGU 1571 ACUGCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUAUCCA 3768

756 UUUGCAGU G GGUGCUGC 1572 GCAGCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGCAAA 3769

757 UUGCAGUG G GUGCUGCC 1573 GGCAGCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUGCAA 3770

795 UACUACCA G AGGCAGCU 1574 AGCUGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUAGUA 3771

797 CUACCAGA G GCAGCUGU 1575 ACAGCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGGUAG 3772

818 CACAUACC G GGACCUCC 1576 GGAGGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUAUGUG 3773

819 ^' ACAUACCG G GACCUCCG 1577 CGGAGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGUAUGU 3774

820 CAUACCGG G ACCUCCGG 1578 CCGGAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGGUAUG 3775

827 GGACCUCC G GAAGGGUG 1579 CACCCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAGGUCC 3776

828 GACCUCCG G AAGGGUGU 1580 ACACCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGAGGUC 3777

831 CUCCGGAA G GGUGUGUA 1581 UACACACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCGGAG 3778

832 UCCGGAAG G GUGUGUAU 1582 AUACACAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUCCGGA 3779

855 UACACCCA G GGCAAGUG 1583 CACUUGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGGUGUA 3780

856 ACACCCAG G GCAAGUGG 1584 CCACUUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGGGUGU 3781

863 GGGCAAGU G GGAAGGGG 1585 CCCCUUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACUUGCCC 3782

864 GGCAAGUG G GAAGGGGA 1586 UCCCCUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACUUGCC 3783

865 GCAAGUGG G AAGGGGAG 1587 cuccccuu GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCACUUGC 3784

868 AGUGGGAA G GGGAGCUG 1588 CAGCUCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCCCACU 3785

869 GUGGGAAG G GGAGCUGG 1589 CCAGCUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUCCCAC 3786

870 UGGGAAGG G GAGCUGGG 1590 CCCAGCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUUCCCA 3787

871 GGGAAGGG G AGCUGGGC 1591 GCCCAGCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCUUCCC 3788

876 GGGGAGCU G GGCACCGA 1592 UCGGUGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCUCCCC 3789

877 GGGAGCUG G GCACCGAC 1593 GUCGGUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGCUCCC 3790

888 ACCGACCU G GUAAGCAU 1594 AUGCUUAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGUCGGU 3791

904 UCCCCCAU G GCCCCAAC 1595 GUUGGGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGGGGGA 3792

952 CUGAAUCA G ACAAGUUC 1596 GAACUUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGAUUCAG 3793

970 UCAUCAAC G GCUCCAAC 1597 GUUGGAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUUGAUGA 3794

980 CUCCAACU G GGAAGGCA 1598 UGCCUUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUUGGAG 3795

981 UCCAACUG G GAAGGCAU 1599 AUGCCUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGUUGGA 3796

982 CCAACUGG G AAGGCAUC 1600 GAUGCCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAGUUGG 3797

985 ACUGGGAA G GCAUCCUG 1601 CAGGAUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCCCAGU 3798

993 GGCAUCCU G GGGCUGGC 1602 GCCAGCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGAUGCC 3799

Table 23

994 GCAUCCUG G GGCUGGCC 1603 GGCCAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGAUGC 3800

995 CAUCCUGG G GCUGGCCU 1604 AGGCCAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGGAUG 3801

999 CUGGGGCU G GCCUAUGC 1605 GCAUAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCCCAG 3802

1011 UAUGCUGA G AUUGCCAG 1606 CUGGCAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAGCAUA 3803

1019 GAUUGCCA G GCCUGACG 1607 CGUCAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCAAUC 3804

1035 GACUCCCU G GAGCCUUU 1608 AAAGGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGAGUC 3805

1036 ACUCCCUG G AGCCUUUC 1609 GAAAGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGGAGU 3806

1056 GACUCUCU G GUAAAGCA 1610 UGCUUUAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGAGUC 3807

1065 GUAAAGCA G ACCCACGU 1611 ACGUGGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUUUAC 3808

1102 AGCUUUGU G GUGCUGGC 1612 GCCAGCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAAAGCU 3809

1108 GUGGUGCU G GCUUCCCC 1613 GGGGAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCACCAC 3810

1137 GAAGUGCU G GCCUCUGU 1614 ACAGAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCACUUC 3811

1147 CCUCUGUC G GAGGGAGC 1615 GCUCCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACAGAGG 3812

1148 CUCUGUCG G AGGGAGCA 1616 UGCUCCCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGACAGAG 3813

1150 CUGUCGGA G GGAGCAUG 1617 CAUGCUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCGACAG 3814

1151 UGUCGGAG G GAGCAUGA 1618 UCAUGCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCCGACA 3815

1152 GUCGGAGG G AGCAUGAU 1619 AUCAUGCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUCCGAC 3816

1165 UGAUCAUU G GAGGUAUC 1620 GAUACCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUGAUCA 3817

1166 GAUCAUUG G AGGUAUCG 1621 CGAUACCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAUGAUC 3818

1168 UCAUUGGA G GUAUCGAC 1622 GUCGAUAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCAAUGA 3819

1192 UGUACACA G GCAGUCUC 1623 GAGACUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUGUACA 3820

1202 CAGUCUCU G GUAUACAC 1624 GUGUAUAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAGACUG 3821

1217 ACCCAUCC G GCGGGAGU 1625 ACUCCCGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGAUGGGU 3822

1220 CAUCCGGC G GGAGUGGU 1626 ACCACUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCCGGAUG 3823

1221 AUCCGGCG G GAGUGGUA 1627 UACCACUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGCCGGAU 3824

1222 UCCGGCGG G AGUGGUAU 1628 AUACCACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGCCGGA 3825

1226 GCGGGAGU G GUAUUAUG 1629 CAUAAUAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACUCCCGC 3826

1236 UAUUAUGA G GUGAUCAU 1630 AUGAUCAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCAUAAUA 3827

1250 CAUUGUGC G GGUGGAGA 1631 UCUCCACC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCACAAUG 3828

1251 AUUGUGCG G GUGGAGAU 1632 AUCUCCAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGCACAAU 3829

1254 GUGCGGGU G GAGAUCAA 1633 UUGAUCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCCGCAC 3830

1255 UGCGGGUG G AGAUCAAU 1634 AUUGAUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACCCGCA 3831

1257 CGGGUGGA G AUCAAUGG 1635 CCAUUGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCACCCG 3832

1264 AGAUCAAU G GACAGGAU 1636 AUCCUGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUUGAUCU 3833

Table 23

1265 GAUCAAUG G ACAGGAUC 1637 GAUCCUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUUGAUC 3834

1269 AAUGGACA G GAUCUGAA 1638 UUCAGAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUCCAUU 3835

1270 AUGGACAG G AUCUGAAA 1639 UUUCAGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUCCAU 3836

1281 CUGAAAAU G GACUGCAA 1640 UUGCAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUUCAG 3837

1282 UGAAAAUG G ACUGCAAG 1641 CUUGCAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUUUUCA 3838

1290 GACUGCAA G GAGUACAA 1642 UUGUACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGCAGUC 3839

1291 ACUGCAAG G AGUACAAC 1643 GUUGUACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGCAGU 3840

1308 UAUGACAA G AGCAUUGU 1644 ACAAUGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUCAUA 3841

1317 AGCAUUGU G GACAGUGG 1645 CCACUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAAUGCU 3842

1318 GCAUUGUG G ACAGUGGC 1646 GCCACUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAAUGC 3843

1324 UGGACAGU G GCACCACC 1647 GGUGGUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGUCCA 3844

1350 UUGCCCAA G AAAGUGUU 1648 AACACUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGGCAA 3845

1383 UCCAUCAA G GCAGCCUC 1649 GAGGCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAUGGA 3846

1398 UCCUCCAC G GAGAAGUU 1650 AACUUCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUGGAGGA 3847

1399 CCUCCACG G AGAAGUUC 1651 GAACUUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGUGGAGG 3848

1401 UCCACGGA G AAGUUCCC 1652 GGGAACUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCGUGGA 3849

1414 UCCCUGAU G GUUUCUGG 1653 CCAGAAAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCAGGGA 3850

1421 UGGUUUCU G GCUAGGAG 1654 CUCCUAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAAACCA 3851

1426 UCUGGCUA G GAGAGCAG 1655 CUGCUCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAGCCAGA 3852

1427 CUGGCUAG G AGAGCAGC 1656 GCUGCUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUAGCCAG 3853

1429 GGCUAGGA G AGCAGCUG 1657 CAGCUGCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCUAGCC 3854

1437 GAGCAGCU G GUGUGCUG 1658 CAGCACAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCUGCUC 3855

1445 GGUGUGCU G GCAAGCAG 1659 CUGCUUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCACACC 3856

1453 GGCAAGCA G GCACCACC 1660 GGUGGUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCUUGCC 3857

1466 CACCCCUU G GAACAUUU 1661 AAAUGUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGGGGUG 3858

1467 ACCCCUUG G AACAUUUU 1662 AAAAUGUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAGGGGU 3859

1500 UACCUAAU G GGUGAGGU 1663 ACCUCACC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUUAGGUA 3860

1501 ACCUAAUG G GUGAGGUU 1664 AACCUCAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUUAGGU 3861

1506 AUGGGUGA G GUUACCAA 1665 UUGGUAAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCACCCAU 3862

1556 AUACCUGC G GCCAGUGG 1666 CCACUGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCAGGUAU 3863

1563 CGGCCAGU G GAAGAUGU 1667 ACAUCUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACUGGCCG 3864

1564 GGCCAGUG G AAGAUGUG 1668 CACAUCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACUGGCC 3865

1567 CAGUGGAA G AUGUGGCC 1669 GGCCACAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCCACUG 3866

1572 GAAGAUGU G GCCACGUC 1670 GACGUGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAUCUUC 3867

Table 23

1585 CGUCCCAA G ACGACUGU 1671 ACAGUCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGGACG 3868

1623 UCAUCCAC G GGCACUGU 1672 ACAGUGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUGGAUGA 3869

1624 CAUCCACG G GCACUGUU 1673 AACAGUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUGGAUG 3870

1635 ACUGUUAU G GGAGCUGU 1674 ACAGCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAACAGU 3871

1636 CUGUUAUG G GAGCUGUU 1675 AACAGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUAACAG 3872

1637 UGUUAUGG G AGCUGUUA 1676 UAACAGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAUAACA 3873

1650 GUUAUCAU G GAGGGCUU 1677 AAGCCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGAUAAC 3874

1651 UUAUCAUG G AGGGCUUC 1678 GAAGCCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGAUAA 3875

1653 AUCAUGGA G GGCUUCUA 1679 UAGAAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAUGAU 3876

1654 UCAUGGAG G GCUUCUAC 1680 GUAGAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCAUGA 3877

1676 CUUUGAUC G GGCCCGAA 1681 UUCGGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUCAAAG 3878

1677 UUUGAUCG G GCCCGAAA 1682 UUUCGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGAUCAAA 3879

1693 AACGAAUU G GCUUUGCU 1683 AGCAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUUCGUU 3880

1733 UGAGUUCA G GACGGCAG 1684 CUGCCGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGAACUCA 3881

1734 GAGUUCAG G ACGGCAGC 1685 GCUGCCGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGAACUC 3882

1737 UUCAGGAC G GCAGCGGU 1686 ACCGCUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUCCUGAA 3883

1743 ACGGCAGC G GUGGAAGG 1687 CCUUCCAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCUGCCGU 3884

1746 GCAGCGGU G GAAGGCCC 1688 GGGCCUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCGCUGC 3885

1747 CAGCGGUG G AAGGCCCU 1689 AGGGCCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACCGCUG 3886

1750 CGGUGGAA G GCCCUUUU 1690 AAAAGGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCCACCG 3887

1767 GUCACCUU G GACAUGGA 1691 UCCAUGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGGUGAC 3888

1768 UCACCUUG G ACAUGGAA 1692 UUCCAUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAGGUGA 3889

1773 UUGGACAU G GAAGACUG 1693 CAGUCUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGUCCAA 3890

1774 UGGACAUG G AAGACUGU 1694 ACAGUCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUGUCCA 3891

1777 ACAUGGAA G ACUGUGGC 1695 GCCACAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCCAUGU 3892

1783 AAGACUGU G GCUACAAC 1696 GUUGUAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAGUCUU 3893

1800 AUUCCACA G ACAGAUGA 1697 UCAUCUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUGGAAU 3894

1804 CACAGACA G AUGAGUCA 1698 UGACUCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUCUGUG 3895

1839 UAUGUCAU G GCUGCCAU 1699 AUGGCAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGACAUA 3896 ^'

1881 UGCCUCAU G GUGUGUCA 1700 UGACACAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGAGGCA 3897

1892 GUGUCAGU G GCGCUGCC 1701 GGCAGCGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACUGACAC 3898

1960 UGAAGUGA G GAGGCCCA 1702 UGGGCCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCACUUCA 3899

1961 GAAGUGAG G AGGCCCAU 1703 AUGGGCCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCACUUC 3900

1963 AGUGAGGA G GCCCAUGG 1704 CCAUGGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCUCACU 3901

Table 23

1970 AGGCCCAU G GGCAGAAG 1705 CUUCUGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGGGCCU 3902

1971 GGCCCAUG G GCAGAAGA 1706 UCUUCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGGGCC 3903

1975 CAUGGGCA G AAGAUAGA 1707 UCUAUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCCAUG 3904

1978 GGGCAGAA G AUAGAGAU 1708 AUCUCUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUGCCC 3905

1982 AGAAGAUA G AGAUUCCC 1709 GGGAAUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUCUUCU 3906

1984 AAGAUAGA G AUUCCCCU 1710 AGGGGAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUAUCUU 3907

1993 AUUCCCCU G GACCACAC 1711 GUGUGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGGAAU 3908

1994 UUCCCCUG G ACCACACC 1712 GGUGUGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGGGAA 3909

2008 ACCUCCGU G GUUCACUU 1713 AAGUGAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGGAGGU 3910

2018 UUCACUUU G GUCACAAG 1714 CUUGUGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGUGAA 3911

2029 CACAAGUA G GAGACACA 1715 UGUGUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACUUGUG 3912

2030 ACAAGUAG G AGACACAG 1716 CUGUGUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUACUUGU 3913

2032 AAGUAGGA G ACACAGAU 1717 AUCUGUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCUACUU 3914

2038 GAGACACA G AUGGCACC 1718 GGUGCCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUGUCUC 3915

2041 ACACAGAU G GCACCUGU 1719 ACAGGUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCUGUGU 3916

2050 GCACCUGU G GCCAGAGC 1720 GCUCUGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAGGUGC 3917

2055 UGUGGCCA G AGCACCUC 1721 GAGGUGCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGCCACA 3918

2065 GCACCUCA G GACCCUCC 1722 GGAGGGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGAGGUGC 3919

2066 CACCUCAG G ACCCUCCC 1723 GGGAGGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGAGGUG 3920

2101 GCCUUGAU G GAGAAGGA 1724 UCCUUCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCAAGGC 3921

2102 CCUUGAUG G AGAAGGAA 1725 UUCCUUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUCAAGG 3922

2104 UUGAUGGA G AAGGAAAA 1726 UUUUCCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCAUCAA 3923

2107 AUGGAGAA G GAAAAGGC 1727 . GCCUUUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCUCCAU 3924

2108 UGGAGAAG G AAAAGGCU 1728 AGCCUUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUCUCCA 3925

2113 AAGGAAAA G GCUGGCAA 1729 UUGCCAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUUCCUU 3926

2117 AAAAGGCU G GCAAGGUG 1730 CACCUUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCCUUUU 3927

2122 GCUGGCAA G GUGGGUUC 1731 GAACCCAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGCCAGC 3928

2125 GGCAAGGU G GGUUCCAG 1732 CUGGAACC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCUUGCC 3929

2126 GCAAGGUG G GUUCCAGG 1733 CCUGGAAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACCUUGC 3930

2133 GGGUUCCA G GGACUGUA 1734 UACAGUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGAACCC 3931

2134 GGUUCCAG G GACUGUAC 1735 GUACAGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGGAACC 3932

2135 GUUCCAGG G ACUGUACC 1736 GGUACAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUGGAAC 3933

2148 UACCUGUA G GAAACAGA 1737 UCUGUUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UACAGGUA 3934

2149 ACCUGUAG G AAACAGAA 1738 UUCUGUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUACAGGU 3935

Laϋi zό

2155 AGGAAACA G AAAAGAGA 1739 UCUCUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUCCU 3936

2160 ACAGAAAA G AGAAGAAA 1740 UUUCUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUCUGU 3937

2162 AGAAAAGA G AAGAAAGA 1741 UCUUUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUUUCU 3938

2165 AAAGAGAA G AAAGAAGC 1742 GCUUCUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUCUUU 3939

2169 AGAAGAAA G AAGCACUC 1743 GAGUGCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUCUUCU 3940

2182 ACUCUGCU G GCGGGAAU 1744 AUUCCCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAGAGU 3941

2185 CUGCUGGC G GGAAUACU 1745 AGUAUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCAGCAG 3942

2186 UGCUGGCG G GAAUACUC 1746 GAGUAUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCCAGCA 3943

2187 GCUGGCGG G AAUACUCU 1747 AGAGUAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGCCAGC 3944

2197 AUACUCUU G GUCACCUC 1748 GAGGUGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAGUAU 3945

2217 UUUAAGUC G GGAAAUUC 1749 GAAUUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACUUAAA 3946

2218 UUAAGUCG G GAAAUUCU 1750 AGAAUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGACUUAA 3947

2219 UAAGUCGG G AAAUUCUG 1751 CAGAAUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGACUUA 3948

2311 UAGUUUCA G AAGUACUG 1752 CAGUACUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGAAACUA 3949

2319 GAAGUACU G GCAUCACA 1753 UGUGAUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUACUUC 3950

2332 CACACGCA G GUUACCUU 1754 AAGGUAAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCGUGUG 3951

2341 GUUACCUU G GCGUGUGU 1755 ACACACGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGGUAAC 3952

2356 GUCCCUGU G GUACCCUG 1756 CAGGGUAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAGGGAC 3953

2364 GGUACCCU G GCAGAGAA 1757 UUCUCUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGGUACC 3954

2368 CCCUGGCA G AGAAGAGA 1758 UCUCUUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCCAGGG 3955

2370 CUGGCAGA G AAGAGACC 1759 GGUCUCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCUGCCAG 3956

2373 GCAGAGAA G AGACCAAG 1760 CUUGGUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCUCUGC 3957

2375 AGAGAAGA G ACCAAGCU 1761 AGCUUGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCUUCUCU 3958

2396 UCCCUGCU G GCCAAAGU 1762 ACUUUGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCAGGGA 3959

2410 AGUCAGUA G GAGAGGAU 1763 AUCCUCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UACUGACU 3960

2411 GUCAGUAG G AGAGGAUG 1764 CAUCCUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUACUGAC 3961

2413 CAGUAGGA G AGGAUGCA 1765 UGCAUCCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCUACUG 3962

2415 GUAGGAGA G GAUGCACA 1766 UGUGCAUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCUCCUAC 3963

2416 UAGGAGAG G AUGCACAG 1767 CUGUGCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCUCCUA 3964

2441 UUGCUUUA G AGACAGGG 1768 CCCUGUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAAAGCAA 3965

2443 GCUUUAGA G ACAGGGAC 1769 GUCCCUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCUAAAGC 3966

2447 UAGAGACA G GGACUGUA 1770 UACAGUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUCUCUA 3967

2448 AGAGACAG G GACUGUAU 1771 AUACAGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGUCUCU 3968

2449 GAGACAGG G ACUGUAUA 1772 UAUACAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUGUCUC 3969

Table 23

Input Sequence = AF190725. Cut Site = G/ .

Stem Length = 8. Core Sequence = GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG

AF190725 (Homo sapiens beta-site APP cleaving enzyme (BACE) mRNA; 2526 bp)

Table 24

Table 24: Human Phospholamban (PLN) Hammerhead Ribozyme and Target Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

16 AGAAAACU C CCCAGCUA 1 UAGCUGGG CUGAUGAG X CGAA AGUUUUCU 1137

24 CCCCAGCU A AACACCCG 2 CGGGUGUU CUGAUGAG X CGAA AGCUGGGG 1138

34 ACACCCGU A AGACUUCA 3 UGAAGUCU CUGAUGAG X CGAA ACGGGUGU 1139

40 GUAAGACU U CAUACAAC 4 GUUGUAUG CUGAUGAG X CGAA AGUCUUAC 1140

41 UAAGACUU c AUACAACA 5 UGUUGUAU CUGAUGAG X CGAA AAGUCUUA 1141

44 GACUUCAU A CAACACAA 6 UUGUGUUG CUGAUGAG X CGAA AUGAAGUC 1142

54 AACACAAU A CUCUAUAC 7 GUAUAGAG CUGAUGAG X CGAA AUUGUGUU 1143

57 ACAAUACU C UAUACUGU 8 ACAGUAUA CUGAUGAG X CGAA AGUAUUGU 1144

59 AAUACUCU A UACUGUGA 9 UCACAGUA CUGAUGAG X CGAA AGAGUAUU 1145

61 UACUCUAU A CUGUGAUG 10 CAUCACAG CUGAUGAG X CGAA AUAGAGUA 1146

72 GUGAUGAU C ACAGCUGC 11 GCAGCUGU CUGAUGAG X CGAA AUCAUCAC 1147

88 CCAAGGCU A CCUAAAAG 12 CUUUUAGG CUGAUGAG X CGAA AGCCUUGG 1148

92 GGCUACCU A AAAGAAGA 13 UCUUCUUU CUGAUGAG X CGAA AGGUAGCC 1149

105 AAGACAGU U AUCUCAUA 14 UAUGAGAU CUGAUGAG X CGAA ACUGUCUU 1150

106 AGACAGUU A UCUCAUAU 15 AUAUGAGA CUGAUGAG X CGAA AACUGUCU 1151

108 ACAGUUAU C UCAUAUUU 16 AAAUAUGA CUGAUGAG X CGAA AUAACUGU 1152

110 AGUUAUCU C AUAUUUGG 17 CCAAAUAU CUGAUGAG X CGAA AGAUAACU 1153

113 UAUCUCAU A UUUGGCUG 18 CAGCCAAA CUGAUGAG X CGAA AUGAGAUA 1154

115 UCUCAUAU U UGGCUGCC 19 GGCAGCCA CUGAUGAG X CGAA AUAUGAGA 1155

116 CUCAUAUU U GGCUGCCA 20 UGGCAGCC CUGAUGAG X CGAA AAUAUGAG 1156

128 UGCCAGCU U UUUAUCUU 21 AAGAUAAA CUGAUGAG X CGAA AGCUGGCA 1157

129 GCCAGCUU U UUAUCUUU 22 AAAGAUAA CUGAUGAG X CGAA AAGCUGGC 1158

130 CCAGCUUU U UAUCUUUC 23 GAAAGAUA CUGAUGAG X CGAA AAAGCUGG 1159

131 CAGCUUUU U AUCUUUCU 24 AGAAAGAU CUGAUGAG X CGAA AAAAGCUG 1160

132 AGCUUUUU A UCUUUCUC 25 GAGAAAGA CUGAUGAG X CGAA AAAAAGCU 1161

134 CUUUUUAU C UUUCUCUC 26 GAGAGAAA CUGAUGAG X CGAA AUAAAAAG 1162

136 UUUUAUCU U UCUCUCGA 27 UCGAGAGA CUGAUGAG X CGAA AGAUAAAA 1163

137 UUUAUCUU U CUCUCGAC 28 GUCGAGAG CUGAUGAG X CGAA AAGAUAAA 1164

138 UUAUCUUU C UCUCGACC 29 GGUCGAGA CUGAUGAG X CGAA AAAGAUAA 1165

140 AUCUUUCU C UCGACCAC 30 GUGGUCGA CUGAUGAG X CGAA AGAAAGAU 1166

142 cuuucucu C GACCACUU 31 AAGUGGUC CUGAUGAG X CGAA AGAGAAAG 1167

150 CGACCACU U AAAACUUC 32 GAAGUUUU CUGAUGAG X CGAA AGUGGUCG 1168

151 GACCACUU A AAACUUCA 33 UGAAGUUU CUGAUGAG X CGAA AAGUGGUC 1169

157 UUAAAACU U CAGACUUC 34 GAAGUCUG CUGAUGAG X CGAA AGUUUUAA 1170

158 UAAAACUU C AGACUUCC 35 GGAAGUCU CUGAUGAG X CGAA AAGUUUUA 1171

164 UUCAGACU U CCUGUCCU 36 AGGACAGG CUGAUGAG X CGAA AGUCUGAA 1172

165 UCAGACUU C CUGUCCUG 37 CAGGACAG CUGAUGAG X CGAA AAGUCUGA 1173

170 CUUCCUGU C CUGCUGGU 38 ACCAGCAG CUGAUGAG X CGAA ACAGGAAG 1174

179 CUGCUGGU A UCAUGGAG 39 CUCCAUGA CUGAUGAG X CGAA ACCAGCAG 1175

181 GCUGGUAU C AUGGAGAA 40 UUCUCCAU CUGAUGAG X CGAA AUACCAGC 1176

193 GAGAAAGU C CAAUACCU 41 AGGUAUUG CUGAUGAG X CGAA ACUUUCUC 1177

198 AGUCCAAU A CCUCACUC 42 GAGUGAGG CUGAUGAG X CGAA AUUGGACU 1178 Table 24

202 CAAUACCU C ACUCGCUC 43 GAGCGAGU CUGAUGAG X CGAA AGGUAUUG 1179

206 ACCUCACU C GCUCAGCU 44 AGCUGAGC CUGAUGAG X CGAA AGUGAGGU 1180

210 CACUCGCU C AGCUAUAA 45 UUAUAGCU CUGAUGAG X CGAA AGCGAGUG 1181

215 GCUCAGCU A UAAGAAGA 46 UCUUCUUA CUGAUGAG X CGAA AGCUGAGC 1182

217 UCAGCUAU A AGAAGAGC 47 GCUCUUCU CUGAUGAG X CGAA AUAGCUGA 1183

228 AAGAGCCU C AACCAUUG 48 CAAUGGUU CUGAUGAG X CGAA AGGCUCUU 1184

235 UCAACCAU U GAAAUGCC 49 GGCAUUUC CUGAUGAG X CGAA AUGGUUGA 1185

245 AAAUGCCU C AACAAGCA 50 UGCUUGUU CUGAUGAG X CGAA AGGCAUUU 1186

257 AAGCACGU C AAAAGCUA 51 UAGCUUUU CUGAUGAG X CGAA ACGUGCUU 1187

265 CAAAAGCU A CAGAAUCU 52 AGAUUCUG CUGAUGAG X CGAA AGCUUUUG 1188

272 UACAGAAU C UAUUUAUC 53 GAUAAAUA CUGAUGAG X CGAA AUUCUGUA 1189

274 CAGAAUCU A UUUAUCAA 54 UUGAUAAA CUGAUGAG X CGAA AGAUUCUG 1190

276 GAAUCUAU U UAUCAAUU 55 AAUUGAUA CUGAUGAG X CGAA AUAGAUUC 1191

277 AAUCUAUU U AUCAAUUU 56 AAAUUGAU CUGAUGAG X CGAA AAUAGAUU 1192

278 AUCUAUUU A UCAAUUUC 57 GAAAUUGA CUGAUGAG X CGAA AAAUAGAU 1193

280 CUAUUUAU C AAUUUCUG 58 CAGAAAUU CUGAUGAG X CGAA AUAAAUAG 1194

284 UUAUCAAU U UCUGUCUC 59 GAGACAGA CUGAUGAG X CGAA AUUGAUAA 1195

285 UAUCAAUU U CUGUCUCA 60 UGAGACAG CUGAUGAG X CGAA AAUUGAUA 1196

286 AUCAAUUU C UGUCUCAU 61 AUGAGACA CUGAUGAG X CGAA AAAUUGAU 1197

290 AUUUCUGU C UCAUCUUA 62 UAAGAUGA CUGAUGAG X CGAA ACAGAAAU 1198

292 UUCUGUCU C AUCUUAAU 63 AUUAAGAU CUGAUGAG X CGAA AGACAGAA 1199

295 UGUCUCAU C UUAAUAUG 64 CAUAUUAA CUGAUGAG X CGAA AUGAGACA 1200

297 UCUCAUCU U AAUAUGUC 65 GACAUAUU CUGAUGAG X CGAA AGAUGAGA 1201

298 CUCAUCUU A AUAUGUCU 66 AGACAUAU CUGAUGAG X CGAA AAGAUGAG 1202

301 AUCUUAAU A UGUCUCUU 67 AAGAGACA CUGAUGAG X CGAA AUUAAGAU 1203

305 UAAUAUGU C UCUUGCUG 68 CAGCAAGA CUGAUGAG X CGAA ACAUAUUA 1204

307 AUAUGUCU C UUGCUGAU 69 AUCAGCAA CUGAUGAG X CGAA AGACAUAU 1205

309 AUGUCUCU U GCUGAUCU 70 AGAUCAGC CUGAUGAG X CGAA AGAGACAU 1206

316 UUGCUGAU C UGUAUCAU 71 AUGAUACA CUGAUGAG X CGAA AUCAGCAA 1207

320 UGAUCUGU A UCAUCGUG 72 CACGAUGA CUGAUGAG X CGAA ACAGAUCA 1208

322 AUCUGUAU C AUCGUGAU 73 AUCACGAU CUGAUGAG X CGAA AUACAGAU 1209

325 UGUAUCAU C GUGAUGCU 74 AGCAUCAC CUGAUGAG X CGAA AUGAUACA 1210

334 GUGAUGCU U CUCUGAAG 75 CUUCAGAG CUGAUGAG X CGAA AGCAUCAC 1211

335 UGAUGCUU C UCUGAAGU 76 ACUUCAGA CUGAUGAG X CGAA AAGCAUCA 1212

337 AUGCUUCU C UGAAGUUC 77 GAACUUCA CUGAUGAG X CGAA AGAAGCAU 1213

344 UCUGAAGU U CUGCUACA 78 UGUAGCAG CUGAUGAG X CGAA ACUUCAGA 1214

345 CUGAAGUU C UGCUACAA 79 UUGUAGCA CUGAUGAG X CGAA AACUUCAG 1215

350 GUUCUGCU A CAACCUCU 80 AGAGGUUG CUGAUGAG X CGAA AGCAGAAC 1216

357 UACAACCU C UAGAUCUG 81 CAGAUCUA CUGAUGAG X CGAA AGGUUGUA 1217

359 CAACCUCU A GAUCUGCA 82 UGCAGAUC CUGAUGAG X CGAA AGAGGUUG 1218

363 CUCUAGAU C UGCAGCUU 83 AAGCUGCA CUGAUGAG X CGAA AUCUAGAG 1219

371 CUGCAGCU U GCCACAUC 84 GAUGUGGC CUGAUGAG X CGAA AGCUGCAG 1220

379 UGCCACAU C AGCUUAAA 85 UUUAAGCU CUGAUGAG X CGAA AUGUGGCA 1221

384 CAUCAGCU U AAAAUCUG 86 CAGAUUUU CUGAUGAG X CGAA AGCUGAUG 1222

385 AUCAGCUU A AAAUCUGU 87 ACAGAUUU CUGAUGAG X CGAA AAGCUGAU 1223

390 CUUAAAAU C UGUCAUCC 88 GGAUGACA CUGAUGAG X CGAA AUUUUAAG 1224

394 AAAUCUGU C AUCCCAUG 89 CAUGGGAU CUGAUGAG X CGAA ACAGAUUU 1225 Table 24

397 UCUGUCAU C CCAUGCAG 90 CUGCAUGG CUGAUGAG X CGAA AUGACAGA 1226

419 AAAACAAU A UUGUAUAA 91 UUAUACAA CUGAUGAG X CGAA AUUGUUUU 1227

421 AACAAUAU U GUAUAACA 92 UGUUAUAC CUGAUGAG X CGAA AUAUUGUU 1228

424 AAUAUUGU A UAACAGAC 93 GUCUGUUA CUGAUGAG X CGAA ACAAUAUU 1229

426 UAUUGUAU A ACAGACCA 94 UGGUCUGU CUGAUGAG X CGAA AUACAAUA 1230

437 AGACCACU U CCUGAGUA 95 UACUCAGG CUGAUGAG X CGAA AGUGGUCU 1231

438 GACCACUU C CUGAGUAG 96 CUACUCAG CUGAUGAG X CGAA AAGUGGUC 1232

445 UCCUGAGU A GAAGAGUU 97 AACUCUUC CUGAUGAG X CGAA ACUCAGGA 1233

453 AGAAGAGU U UCUUUGUG 98 CACAAAGA CUGAUGAG X CGAA ACUCUUCU 1234

454 GAAGAGUU U CUUUGUGA 99 UCACAAAG CUGAUGAG X CGAA AACUCUUC 1235

455 AAGAGUUU C UUUGUGAA 100 UUCACAAA CUGAUGAG X CGAA AAACUCUU 1236

457 GAGUUUCU U UGUGAAAA 101 UUUUCACA CUGAUGAG X CGAA AGAAACUC 1237

458 AGUUUCUU U GUGAAAAG 102 CUUUUCAC CUGAUGAG X CGAA AAGAAACU 1238

469 GAAAAGGU C AAGAUUAA 103 UUAAUCUU CUGAUGAG X CGAA ACCUUUUC 1239

475 GUCAAGAU U AAGACUAA 104 UUAGUCUU CUGAUGAG X CGAA AUCUUGAC 1240

476 UCAAGAUU A AGACUAAA 105 UUUAGUCU CUGAUGAG X CGAA AAUCUUGA 1241

482 UUAAGACU A AAACUUAU 106 AUAAGUUU CUGAUGAG X CGAA AGUCUUAA 1242

488 CUAAAACU U AUUGUUAC 107 GUAACAAU CUGAUGAG X CGAA AGUUUUAG 1243

489 UAAAACUU A UUGUUACC 108 GGUAACAA CUGAUGAG X CGAA AAGUUUUA 1244

491 AAACUUAU U GUUACCAU 109 AUGGUAAC CUGAUGAG X CGAA AUAAGUUU 1245

494 CUUAUUGU U ACCAUAUG 110 CAUAUGGU CUGAUGAG X CGAA ACAAUAAG 1246

495 UUAUUGUU A CCAUAUGU 111 ACAUAUGG CUGAUGAG X CGAA AACAAUAA 1247

500 GUUACCAU A UGUAUUCA 112 UGAAUACA CUGAUGAG X CGAA AUGGUAAC 1248

504 CCAUAUGU A UUCAUCUG 113 CAGAUGAA CUGAUGAG X CGAA ACAUAUGG 1249

506 AUAUGUAU U CAUCUGUU 114 AACAGAUG CUGAUGAG X CGAA AUACAUAU 1250

507 UAUGUAUU C AUCUGUUG 115 CAACAGAU CUGAUGAG X CGAA AAUACAUA 1251

510 GUAUUCAU C UGUUGGAU 116 AUCCAACA CUGAUGAG X CGAA AUGAAUAC 1252

514 UCAUCUGU U GGAUCUUG 117 CAAGAUCC CUGAUGAG X CGAA ACAGAUGA 1253

519 UGUUGGAU C UUGUAAAC 118 GUUUACAA CUGAUGAG X CGAA AUCCAACA 1254

521 UUGGAUCU U GUAAACAU 119 AUGUUUAC CUGAUGAG X CGAA AGAUCCAA 1255

524 GAUCUUGU A AACAUGAA 120 UUCAUGUU CUGAUGAG X CGAA ACAAGAUC 1256

540 AAAGGGCU U UAUUUUCA 121 UGAAAAUA CUGAUGAG X CGAA AGCCCUUU 1257

541 AAGGGCUU U AUUUUCAA 122 UUGAAAAU CUGAUGAG X CGAA AAGCCCUU 1258

542 AGGGCUUU A UUUUCAAA 123 UUUGAAAA CUGAUGAG X CGAA AAAGCCCU 1259

544 GGCUUUAU U UUCAAAAA 124 UUUUUGAA CUGAUGAG X CGAA AUAAAGCC 1260

545 GCUUUAUU U UCAAAAAU 125 AUUUUUGA CUGAUGAG X CGAA AAUAAAGC 1261

546 CUUUAUUU U CAAAAAUU 126 AAUUUUUG CUGAUGAG X CGAA AAAUAAAG 1262

547 UUUAUUUU C AAAAAUUA 127 UAAUUUUU CUGAUGAG X CGAA AAAAUAAA 1263

554 UCAAAAAU U AACUUCAA 128 UUGAAGUU CUGAUGAG X CGAA AUUUUUGA 1264

555 CAAAAAUU A ACUUCAAA 129 UUUGAAGU CUGAUGAG X CGAA AAUUUUUG 1265

559 AAUUAACU U CAAAAUAA 130 UUAUUUUG CUGAUGAG X CGAA AGUUAAUU 1266

560 AUUAACUU C AAAAUAAG 131 CUUAUUUU CUGAUGAG X CGAA AAGUUAAU 1267

566 UUCAAAAU A AGUGUAUA 132 UAUACACU CUGAUGAG X CGAA AUUUUGAA 1268

572 AUAAGUGU A UAAAAUGC 133 GCAUUUUA CUGAUGAG X CGAA ACACUUAU 1269

574 AAGUGUAU A AAAUGCAA 134 UUGCAUUU CUGAUGAG X CGAA AUACACUU 1270

587 GCAACUGU U GAUUUCCU 135 AGGAAAUC CUGAUGAG X CGAA ACAGUUGC 1271

591 CUGUUGAU U UCCUCAAC 136 GUUGAGGA CUGAUGAG X CGAA AUCAACAG 1272 Table 24

592 UGUUGAUU U CCUCAACA 137 UGUUGAGG CUGAUGAG X CGAA AAUCAACA 1273

593 GUUGAUUU C CUCAACAU 138 AUGUUGAG CUGAUGAG X CGAA AAAUCAAC 1274

596 GAUUUCCU C AACAUGGC 139 GCCAUGUU CUGAUGAG X CGAA AGGAAAUC 1275

606 ACAUGGCU C ACAAAUUU 140 AAAUUUGU CUGAUGAG X CGAA AGCCAUGU 1276

613 UCACAAAU U UCUAUCCC 141 GGGAUAGA CUGAUGAG X CGAA AUUUGUGA 1277

614 CACAAAUU U CUAUCCCA 142 UGGGAUAG CUGAUGAG X CGAA AAUUUGUG 1278

615 ACAAAUUU C UAUCCCAA 143 UUGGGAUA CUGAUGAG X CGAA AAAUUUGU 1279

617 AAAUUUCU A UCCCAAAU 144 AUUUGGGA CUGAUGAG X CGAA AGAAAUUU 1280

619 AUUUCUAU C CCAAAUCU 145 AGAUUUGG CUGAUGAG X CGAA AUAGAAAU 1281

626 UCCCAAAU C UUUUCUGA 146 UCAGAAAA CUGAUGAG X CGAA AUUUGGGA 1282

628 CCAAAUCU U UUCUGAAG 147 CUUCAGAA CUGAUGAG X CGAA AGAUUUGG 1283

629 CAAAUCUU u UCUGAAGA 148 UCUUCAGA CUGAUGAG X CGAA AAGAUUUG 1284

630 AAAUCUUU u CUGAAGAU 149 AUCUUCAG CUGAUGAG X CGAA AAAGAUUU 1285

631 AAUCUUUU c UGAAGAUG 150 CAUCUUCA CUGAUGAG X CGAA AAAAGAUU 1286

646 UGAAGAGU u UAGUUUUA 151 UAAAACUA CUGAUGAG X CGAA ACUCUUCA 1287

647 GAAGAGUU u AGUUUUAA 152 UUAAAACU CUGAUGAG X CGAA AACUCUUC 1288

648 AAGAGUUU A GUUUUAAA 153 UUUAAAAC CUGAUGAG X CGAA AAACUCUU 1289

651 AGUUUAGU U UUAAAACU 154 AGUUUUAA CUGAUGAG X CGAA ACUAAACU 1290

652 GUUUAGUU U UAAAACUG 155 CAGUUUUA CUGAUGAG X CGAA AACUAAAC 1291

653 UUUAGUUU U AAAACUGC 156 GCAGUUUU CUGAUGAG X CGAA AAACUAAA 1292

654 UUAGUUUU A AAACUGCA 157 UGCAGUUU CUGAUGAG X CGAA AAAACUAA 1293

675 CAACAAGU U CACUUCAU 158 AUGAAGUG CUGAUGAG X CGAA ACUUGUUG 1294

676 AACAAGUU C ACUUCAUA 159 UAUGAAGU CUGAUGAG X CGAA AACUUGUU 1295

680 AGUUCACU U CAUAUAUA 160 UAUAUAUG CUGAUGAG X CGAA AGUGAACU 1296

681 GUUCACUU C AUAUAUAA 161 UUAUAUAU CUGAUGAG X CGAA AAGUGAAC 1297

684 CACUUCAU A UAUAAAGC 162 GCUUUAUA CUGAUGAG X CGAA AUGAAGUG 1298

686 CUUCAUAU A UAAAGCAU 163 AUGCUUUA CUGAUGAG X CGAA AUAUGAAG 1299

688 UCAUAUAU A AAGCAUUA 164 UAAUGCUU CUGAUGAG X CGAA AUAUAUGA 1300

695 UAAAGCAU U AUUUUUAC 165 GUAAAAAU CUGAUGAG X CGAA AUGCUUUA 1301

696 AAAGCAUU A UUUUUACU 166 AGUAAAAA CUGAUGAG X CGAA AAUGCUUU 1302

698 AGCAUUAU U UUUACUCU 167 AGAGUAAA CUGAUGAG X CGAA AUAAUGCU 1303

699 GCAUUAUU U UUACUCUU 168 AAGAGUAA CUGAUGAG X CGAA AAUAAUGC 1304

700 CAUUAUUU U UACUCUUU 169 AAAGAGUA CUGAUGAG X CGAA AAAUAAUG 1305

701 AUUAUUUU U ACUCUUUU 170 AAAAGAGU CUGAUGAG X CGAA AAAAUAAU 1306

702 UUAUUUUU A CUCUUUUG 171 CAAAAGAG CUGAUGAG X CGAA AAAAAUAA 1307

705 UUUUUACU C UUUUGAGG 172 CCUCAAAA CUGAUGAG X CGAA AGUAAAAA 1308

707 UUUACUCU U UUGAGGUG 173 CACCUCAA CUGAUGAG X CGAA AGAGUAAA 1309

708 UUACUCUU U UGAGGUGA 174 UCACCUCA CUGAUGAG X CGAA AAGAGUAA 1310

709 UACUCUUU U GAGGUGAA 175 UUCACCUC CUGAUGAG X CGAA AAAGAGUA 1311

719 AGGUGAAU A UAAUUUAU 176 AUAAAUUA CUGAUGAG X CGAA AUUCACCU 1312

721 GUGAAUAU A AUUUAUAU 177 AUAUAAAU CUGAUGAG X CGAA AUAUUCAC 1313

724 AAUAUAAU U UAUAUUAC 178 GUAAUAUA CUGAUGAG X CGAA AUUAUAUU 1314

725 AUAUAAUU U AUAUUACA 179 UGUAAUAU CUGAUGAG X CGAA AAUUAUAU 1315

726 UAUAAUUU A UAUUACAA 180 UUGUAAUA CUGAUGAG X CGAA AAAUUAUA 1316

728 UAAUUUAU A UUACAAUG 181 CAUUGUAA CUGAUGAG X CGAA AUAAAUUA 1317

730 AUUUAUAU U ACAAUGUA 182 UACAUUGU CUGAUGAG X CGAA AUAUAAAU 1318

731 UUUAUAUU A CAAUGUAA 183 UUACAUUG CUGAUGAG X CGAA AAUAUAAA 1319 Table 24

738 UACAAUGU A AAAGCUUC 184 GAAGCUUU CUGAUGAG X CGAA ACAUUGUA 1320

745 UAAAAGCU U CUUUAAUA 185 UAUUAAAG CUGAUGAG X CGAA AGCUUUUA 1321

746 AAAAGCUU C UUUAAUAC 186 GUAUUAAA CUGAUGAG X CGAA AAGCUUUU 1322

748 AAGCUUCU U UAAUACUA 187 UAGUAUUA CUGAUGAG X CGAA AGAAGCUU 1323

749 AGCUUCUU U AAUACUAA 188 UUAGUAUU CUGAUGAG X CGAA AAGAAGCU 1324

750 GCUUCUUU A AUACUAAG 189 CUUAGUAU CUGAUGAG X CGAA AAAGAAGC 1325

753 UCUUUAAU A CUAAGUAU 190 AUACUUAG CUGAUGAG X CGAA AUUAAAGA 1326

756 UUAAUACU A AGUAUUUU 191 AAAAUACU CUGAUGAG X CGAA AGUAUUAA 1327

760 UACUAAGU A UUUUUCAG 192 CUGAAAAA CUGAUGAG X CGAA ACUUAGUA 1328

762 CUAAGUAU U UUUCAGGU 193 ACCUGAAA CUGAUGAG X CGAA AUACUUAG 1329

763 UAAGUAUU U UUCAGGUC 194 GACCUGAA CUGAUGAG X CGAA AAUACUUA 1330

764 AAGUAUUU U UCAGGUCU 195 AGACCUGA CUGAUGAG X CGAA AAAUACUU 1331

765 AGUAUUUU U CAGGUCUU 196 AAGACCUG CUGAUGAG X CGAA AAAAUACU 1332

766 GUAUUUUU C AGGUCUUC 197 GAAGACCU CUGAUGAG X CGAA AAAAAUAC 1333

771 UUUCAGGU C UUCACCAA 198 UUGGUGAA CUGAUGAG X CGAA ACCUGAAA 1334

773 UCAGGUCU U CACCAAGU 199 ACUUGGUG CUGAUGAG X CGAA AGACCUGA 1335

774 CAGGUCUU C ACCAAGUA 200 UACUUGGU CUGAUGAG X CGAA AAGACCUG 1336

782 CACCAAGU A UCAAAGUA 201 UACUUUGA CUGAUGAG X CGAA ACUUGGUG 1337

784 CCAAGUAU C AAAGUAAU 202 AUUACUUU CUGAUGAG X CGAA AUACUUGG 1338

790 AUCAAAGU A AUAACACA 203 UGUGUUAU CUGAUGAG X CGAA ACUUUGAU 1339

793 AAAGUAAU A ACACAAAU 204 AUUUGUGU CUGAUGAG X CGAA AUUACUUU 1340

809 UGAAGUGU C AUUAUUGA 205 UGAAUAAU CUGAUGAG X CGAA ACACUUCA 1341

812 AGUGUCAU U AUUCAAAA 206 UUUUGAAU CUGAUGAG X CGAA AUGACACU 1342

813 GUGUCAUU A UUCAAAAU 207 AUUUUGAA CUGAUGAG X CGAA AAUGACAC 1343

815 GUCAUUAU U CAAAAUAG 208 CUAUUUUG CUGAUGAG X CGAA AUAAUGAC 1344

816 UCAUUAUU C AAAAUAGU 209 ACUAUUUU CUGAUGAG X CGAA AAUAAUGA 1345

822 UUCAAAAU A GUCCACUG 210 CAGUGGAC CUGAUGAG X CGAA AUUUUGAA 1346

825 AAAAUAGU C CACUGACU 211 AGUCAGUG CUGAUGAG X CGAA ACUAUUUU 1347

834 CACUGACU C CUCACAUC 212 GAUGUGAG CUGAUGAG X CGAA AGUCAGUG 1348

837 UGACUCCU C ACAUCUGU 213 ACAGAUGU CUGAUGAG X CGAA AGGAGUCA 1349

842 CCUCACAU C UGUUAUCU 214 AGAUAACA CUGAUGAG X CGAA AUGUGAGG 1350

846 ACAUCUGU U AUCUUAUU 215 AAUAAGAU CUGAUGAG X CGAA ACAGAUGU 1351

847 CAUCUGUU A UCUUAUUA 216 UAAUAAGA CUGAUGAG X CGAA AACAGAUG 1352

849 UCUGUUAU C UUAUUAUA 217 UAUAAUAA CUGAUGAG X CGAA AUAACAGA 1353

851 UGUUAUCU U AUUAUAAA 218 UUUAUAAU CUGAUGAG X CGAA AGAUAACA 1354

852 GUUAUCUU A UUAUAAAG 219 CUUUAUAA CUGAUGAG X CGAA AAGAUAAC 1355

854 UAUCUUAU U AUAAAGAA 220 UUCUUUAU CUGAUGAG X CGAA AUAAGAUA 1356

855 AUCUUAUU A UAAAGAAC 221 GUUCUUUA CUGAUGAG X CGAA AAUAAGAU 1357

857 CUUAUUAU A AAGAACUA 222 UAGUUCUU CUGAUGAG X CGAA AUAAUAAG 1358

865 AAAGAACU A UUUGUAGU 223 ACUACAAA CUGAUGAG X CGAA AGUUCUUU 1359

867 AGAACUAU U UGUAGUAA 224 UUACUACA CUGAUGAG X CGAA AUAGUUCU 1360

868 GAACUAUU U GUAGUAAC 225 GUUACUAC CUGAUGAG X CGAA AAUAGUUC 1361

871 CUAUUUGU A GUAACUAU 226 AUAGUUAC CUGAUGAG X CGAA ACAAAUAG 1362

874 UUUGUAGU A ACUAUCAG 227 CUGAUAGU CUGAUGAG X CGAA ACUACAAA 1363

878 UAGUAACU A UCAGAAUC 228 GAUUCUGA CUGAUGAG X CGAA AGUUACUA 1364

880 GUAACUAU C AGAAUCUA 229 UAGAUUCU CUGAUGAG X CGAA AUAGUUAC 1365

886 AUCAGAAU C UACAUUCU 230 AGAAUGUA CUGAUGAG X CGAA AUUCUGAU 1366 Table 24

888 CAGAAUCU A CAUUCUAA 231 UUAGAAUG CUGAUGAG X CGAA AGAUUCUG 1367

892 AUCUACAU U CUAAAACA 232 UGUUUUAG CUGAUGAG X CGAA AUGUAGAU 1368

893 UCUACAUU C UAAAACAG 233 CUGUUUUA CUGAUGAG X CGAA AAUGUAGA 1369

895 UACAUUCU A AAACAGAA 234 UUCUGUUU CUGAUGAG X CGAA AGAAUGUA 1370

906 ACAGAAAU U GUAUUUUU 235 AAAAAUAC CUGAUGAG X CGAA AUUUCUGU 1371

909 GAAAUUGU A UUUUUUCU 236 AGAAAAAA CUGAUGAG X CGAA ACAAUUUC 1372

911 AAUUGUAU U UUUUCUAU 237 AUAGAAAA CUGAUGAG X CGAA AUACAAUU 1373

912 AUUGUAUU U UUUCUAUG 238 CAUAGAAA CUGAUGAG X CGAA AAUACAAU 1374

913 UUGUAUUU U UUCUAUGC 239 GCAUAGAA CUGAUGAG X CGAA AAAUACAA 1375

914 UGUAUUUU U UCUAUGCC 240 GGCAUAGA CUGAUGAG X CGAA AAAAUACA 1376

915 GUAUUUUU U CUAUGCCA 241 UGGCAUAG CUGAUGAG X CGAA AAAAAUAC 1377

916 UAUUUUUU C UAUGCCAC 242 GUGGCAUA CUGAUGAG X CGAA AAAAAAUA 1378

918 UUUUUUCU A UGCCACAU 243 AUGUGGCA CUGAUGAG X CGAA AGAAAAAA 1379

927 UGCCACAU U AACAUCUU 244 AAGAUGUU CUGAUGAG X CGAA AUGUGGCA 1380

928 GCCACAUU A ACAUCUUU 245 AAAGAUGU CUGAUGAG X CGAA AAUGUGGC 1381

933 AUUAACAU C UUUUAAAG 246 CUUUAAAA CUGAUGAG X CGAA AUGUUAAU 1382

935 UAACAUCU U UUAAAGUU 247 AACUUUAA CUGAUGAG X CGAA AGAUGUUA 1383

936 AACAUCUU U UAAAGUUG 248 CAACUUUA CUGAUGAG X CGAA AAGAUGUU 1384

937 ACAUCUUU U AAAGUUGA 249 UCAACUUU CUGAUGAG X CGAA AAAGAUGU 1385

938 CAUCUUUU A AAGUUGAU 250 AUCAACUU CUGAUGAG X CGAA AAAAGAUG 1386

943 UUUAAAGU U GAUGAGAA 251 UUCUCAUC CUGAUGAG X CGAA ACUUUAAA 1387

953 AUGAGAAU C AAGUAUGG 252 CCAUACUU CUGAUGAG X CGAA AUUCUCAU 1388

958 AAUCAAGU A UGGAAAAG 253 CUUUUCCA CUGAUGAG X CGAA ACUUGAUU 1389

968 GGAAAAGU A AGGCCAUA 254 UAUGGCCU CUGAUGAG X CGAA ACUUUUCC 1390

976 AAGGCCAU A CUCUUACA 255 UGUAAGAG CUGAUGAG X CGAA AUGGCCUU 1391

979 GCCAUACU C UUACAUAA 256 UUAUGUAA CUGAUGAG X CGAA AGUAUGGC 1392

981 CAUACUCU U ACAUAAUA 257 UAUUAUGU CUGAUGAG X CGAA AGAGUAUG 1393

982 AUACUCUU A CAUAAUAA 258 UUAUUAUG CUGAUGAG X CGAA AAGAGUAU 1394

986 UCUUACAU A AUAAAAUU 259 AAUUUUAU CUGAUGAG X CGAA AUGUAAGA 1395

989 UACAUAAU A AAAUUCCU 260 AGGAAUUU CUGAUGAG X CGAA AUUAUGUA 1396

994 AAUAAAAU U CCUUUUAA 261 UUAAAAGG CUGAUGAG X CGAA AUUUUAUU 1397

995 AUAAAAUU C CUUUUAAG 262 CUUAAAAG CUGAUGAG X CGAA AAUUUUAU 1398

998 AAAUUCCU U UUAAGUAA 263 UUACUUAA CUGAUGAG X CGAA AGGAAUUU 1399

999 AAUUCCUU U UAAGUAAU 264 AUUACUUA CUGAUGAG X CGAA AAGGAAUU 1400

1000 AUUCCUUU U AAGUAAUU 265 AAUUACUU CUGAUGAG X CGAA AAAGGAAU 1401

1001 UUCCUUUU A AGUAAUUU 266 AAAUUACU CUGAUGAG X CGAA AAAAGGAA 1402

1005 UUUUAAGU A AUUUUUUC 267 GAAAAAAU CUGAUGAG X CGAA ACUUAAAA 1403

1008 UAAGUAAU U UUUUCAAA 268 UUUGAAAA CUGAUGAG X CGAA AUUACUUA 1404

1009 AAGUAAUU U UUUCAAAG 269 CUUUGAAA CUGAUGAG X CGAA AAUUACUU 1405

1010 AGUAAUUU U UUCAAAGA 270 UCUUUGAA CUGAUGAG X CGAA AAAUUACU 1406

1011 GUAAUUUU U UCAAAGAA 271 UUCUUUGA CUGAUGAG X CGAA AAAAUUAC 1407

1012 UAAUUUUU U CAAAGAAU 272 AUUCUUUG CUGAUGAG X CGAA AAAAAUUA 1408

1013 AAUUUUUU C AAAGAAUC 273 GAUUCUUU CUGAUGAG X CGAA AAAAAAUU 1409

1021 CAAAGAAU C ACAGAAUU 274 AAUUCUGU CUGAUGAG X CGAA AUUCUUUG 1410

1029 CACAGAAU U CUAGUACA 275 UGUACUAG CUGAUGAG X CGAA AUUCUGUG 1411

1030 ACAGAAUU C UAGUACAU 276 AUGUACUA CUGAUGAG X CGAA AAUUCUGU 1412

1032 AGAAUUCU A GUACAUGU 277 ACAUGUAC CUGAUGAG X CGAA AGAAUUCU 1413 Table 24

1035 AUUCUAGU A CAUGUAGG 278 CCUACAUG CUGAUGAG X CGAA ACUAGAAU 1414

1041 GUACAUGU A GGUAAAUC 279 GAUUUACC CUGAUGAG X CGAA ACAUGUAC 1415

1045 AUGUAGGU A AAUCAUAA 280 UUAUGAUU CUGAUGAG X CGAA ACCUACAU 1416

1049 AGGUAAAU C AUAAAUCU 281 AGAUUUAU CUGAUGAG X CGAA AUUUACCU 1417

1052 UAAAUCAU A AAUCUGUU 282 AACAGAUU CUGAUGAG X CGAA AUGAUUUA 1418

1056 UCAUAAAU C UGUUCUAA 283 UUAGAACA CUGAUGAG X CGAA AUUUAUGA 1419

1060 AAAUCUGU U CUAAGACA 284 UGUCUUAG CUGAUGAG X CGAA ACAGAUUU 1420

1061 AAUCUGUU C UAAGACAU 285 AUGUCUUA CUGAUGAG X CGAA AACAGAUU 1421

1063 UCUGUUCU A AGACAUAU 286 AUAUGUCU CUGAUGAG X CGAA AGAACAGA 1422

1070 UAAGACAU A UGAUCAAC 287 GUUGAUCA CUGAUGAG X CGAA AUGUCUUA 1423

1075 CAUAUGAU C AACAGAUG 288 CAUCUGUU CUGAUGAG X CGAA AUCAUAUG 1424

1096 CUGGUGGU U AAUAUGUG 289 CACAUAUU CUGAUGAG X CGAA ACCACCAG 1425

1097 UGGUGGUU A AUAUGUGA 290 UCACAUAU CUGAUGAG X CGAA AACCACCA 1426

1100 UGGUUAAU A UGUGACAG 291 CUGUCACA CUGAUGAG X CGAA AUUAACCA 1427

1115 AGUGAGAU U AGUCAUAU 292 AUAUGACU CUGAUGAG X CGAA AUCUCACU 1428

1116 GUGAGAUU A GUCAUAUC 293 GAUAUGAC CUGAUGAG X CGAA AAUCUCAC 1429

1119 AGAUUAGU C AUAUCACU 294 AGUGAUAU CUGAUGAG X CGAA ACUAAUCU 1430

1122 UUAGUCAU A UCACUAAU 295 AUUAGUGA CUGAUGAG X CGAA AUGACUAA 1431

1124 AGUCAUAU C ACUAAUAU 296 AUAUUAGU CUGAUGAG X CGAA AUAUGACU 1432

1128 AUAUCACU A AUAUACUA 297 UAGUAUAU CUGAUGAG X CGAA AGUGAUAU 1433

1131 UCACUAAU A UACUAACA 298 UGUUAGUA CUGAUGAG X CGAA AUUAGUGA 1434

1133 ACUAAUAU A CUAACAAC 299 GUUGUUAG CUGAUGAG X CGAA AUAUUAGU 1435

1136 AAUAUACU A ACAACAGA 300 UCUGUUGU CUGAUGAG X CGAA AGUAUAUU 1436

1147 AACAGAAU C UAAUCUUC 301 GAAGAUUA CUGAUGAG X CGAA AUUCUGUU 1437

1149 CAGAAUCU A AUCUUCAU 302 AUGAAGAU CUGAUGAG X CGAA AGAUUCUG 1438

1152 AAUCUAAU C UUCAUUUA 303 UAAAUGAA CUGAUGAG X CGAA AUUAGAUU 1439

1154 UCUAAUCU U CAUUUAAG 304 CUUAAAUG CUGAUGAG X CGAA AGAUUAGA 1440

1155 CUAAUCUU C AUUUAAGG 305 CCUUAAAU CUGAUGAG X CGAA AAGAUUAG 1441

1158 AUCUUCAU U UAAGGCAC 306 GUGCCUUA CUGAUGAG X CGAA AUGAAGAU 1442

1159 UCUUCAUU U AAGGCACU 307 AGUGCCUU CUGAUGAG X CGAA AAUGAAGA 1443

1160 CUUCAUUU A AGGCACUG 308 CAGUGCCU CUGAUGAG X CGAA AAAUGAAG 1444

1170 GGCACUGU A GUGAAUUA 309 UAAUUCAC CUGAUGAG X CGAA ACAGUGCC 1445

1177 UAGUGAAU U AUCUGAGC 310 GCUCAGAU CUGAUGAG X CGAA AUUCACUA 1446

1178 AGUGAAUU A UCUGAGCU 311 AGCUCAGA CUGAUGAG X CGAA AAUUCACU 1447

1180 UGAAUUAU C UGAGCUAG 312 CUAGCUCA CUGAUGAG X CGAA AUAAUUCA 1448

1187 UCUGAGCU A GAGUUACC 313 GGUAACUC CUGAUGAG X CGAA AGCUCAGA 1449

1192 GCUAGAGU U ACCUAGCU 314 AGCUAGGU CUGAUGAG X CGAA ACUCUAGC 1450

1193 CUAGAGUU A CCUAGCUU 315 AAGCUAGG CUGAUGAG X CGAA AACUCUAG 1451

1197 AGUUACCU A GCUUACCA 316 UGGUAAGC CUGAUGAG X CGAA AGGUAACU 1452

1201 ACCUAGCU U ACCAUACU 317 AGUAUGGU CUGAUGAG X CGAA AGCUAGGU 1453

1202 CCUAGCUU A CCAUACUA 318 UAGUAUGG CUGAUGAG X CGAA AAGCUAGG 1454

1207 CUUACCAU A CUAUAUCU 319 AGAUAUAG CUGAUGAG X CGAA AUGGUAAG 1455

1210 ACCAUACU A UAUCUUUG 320 CAAAGAUA CUGAUGAG X CGAA AGUAUGGU 1456

1212 CAUACUAU A UCUUUGGA 321 UCCAAAGA CUGAUGAG X CGAA AUAGUAUG 1457

1214 UACUAUAU C UUUGGAAU 322 AUUCCAAA CUGAUGAG X CGAA AUAUAGUA 1458

1216 CUAUAUCU U UGGAAUCA 323 UGAUUCCA CUGAUGAG X CGAA AGAUAUAG 1459

1217 UAUAUCUU U GGAAUCAU 324 AUGAUUCC CUGAUGAG X CGAA AAGAUAUA 1460 Table 24

1223 UUUGGAAU C AUGAAACC 325 GGUUUCAU CUGAUGAG X CGAA AUUCCAAA 1461

1233 UGAAACCU U AAGACUUC 326 GAAGUCUU CUGAUGAG X CGAA AGGUUUCA 1462

1234 GAAACCUU A AGACUUCA 327 UGAAGUCU CUGAUGAG X CGAA AAGGUUUC 1463

1240 UUAAGACU U CAGAAUGA 328 UCAUUCUG CUGAUGAG X CGAA AGUCUUAA 1464

1241 UAAGACUU C AGAAUGAU 329 AUCAUUCU CUGAUGAG X CGAA AAGUCUUA 1465

1250 AGAAUGAU U UUGCAGGU 330 ACCUGCAA CUGAUGAG X CGAA AUCAUUCU 1466

1251 GAAUGAUU U UGCAGGUU 331 AACCUGCA CUGAUGAG X CGAA AAUCAUUC 1467

1252 AAUGAUUU U GCAGGUUG 332 CAACCUGC CUGAUGAG X CGAA AAAUCAUU 1468

1259 UUGGAGGU U GUCUUCCA 333 UGGAAGAC CUGAUGAG X CGAA ACCUGCAA 1469

1262 CAGGUUGU C UUCCAUUC 334 GAAUGGAA CUGAUGAG X CGAA ACAACCUG 1470

1264 GGUUGUCU U CCAUUCCA 335 UGGAAUGG CUGAUGAG X CGAA AGACAACC 1471

1265 GUUGUCUU C CAUUCCAG 336 CUGGAAUG CUGAUGAG X CGAA AAGACAAC 1472

1269 UCUUCCAU U CCAGCCUA 337 UAGGCUGG CUGAUGAG X CGAA AUGGAAGA 1473

1270 CUUCCAUU C CAGCCUAA 338 UUAGGCUG CUGAUGAG X CGAA AAUGGAAG 1474

1277 UCCAGCCU A ACAUCCAA 339 UUGGAUGU CUGAUGAG X CGAA AGGCUGGA 1475

1282 CCUAACAU C CAAUGCAG 340 CUGCAUUG CUGAUGAG X CGAA AUGUUAGG 1476

1302 AGGAAAAU A AAAGAUUU 341 AAAUCUUU CUGAUGAG X CGAA AUUUUCCU 1477

1309 UAAAAGAU U UCCAGUGA 342 UCACUGGA CUGAUGAG X CGAA AUCUUUUA 1478

1310 AAAAGAUU U CCAGUGAC 343 GUCACUGG CUGAUGAG X CGAA AAUCUUUU 1479

1311 AAAGAUUU C CAGUGACA 344 UGUCACUG CUGAUGAG X CGAA AAAUCUUU 1480

1327 AGAAAAAU A UAUUAUCU 345 AGAUAAUA CUGAUGAG X CGAA AUUUUUCU 1481

1329 AAAAAUAU A UUAUCUCA 346 UGAGAUAA CUGAUGAG X CGAA AUAUUUUU 1482

1331 AAAUAUAU U AUCUCAAG 347 CUUGAGAU CUGAUGAG X CGAA AUAUAUUU 1483

1332 AAUAUAUU A UCUCAAGU 348 ACUUGAGA CUGAUGAG X CGAA AAUAUAUU 1484

1334 UAUAUUAU C UCAAGUAU 349 AUACUUGA CUGAUGAG X CGAA AUAAUAUA 1485

1336 UAUUAUCU C AAGUAUUU 350 AAAUACUU CUGAUGAG X CGAA AGAUAAUA 1486

1341 UCUCAAGU A UUUUUUAA 351 UUAAAAAA CUGAUGAG X CGAA ACUUGAGA 1487

1343 UCAAGUAU U UUUUAAAA 352 UUUUAAAA CUGAUGAG X CGAA AUACUUGA 1488

1344 CAAGUAUU U UUUAAAAA 353 UUUUUAAA CUGAUGAG X CGAA AAUACUUG 1489

1345 AAGUAUUU U UUAAAAAU 354 AUUUUUAA CUGAUGAG X CGAA AAAUACUU 1490

1346 AGUAUUUU U UAAAAAUA 355 UAUUUUUA CUGAUGAG X CGAA AAAAUACU 1491

1347 GUAUUUUU U AAAAAUAU 356 AUAUUUUU CUGAUGAG X CGAA AAAAAUAC 1492

1348 UAUUUUUU A AAAAUAUA 357 UAUAUUUU CUGAUGAG X CGAA AAAAAAUA 1493

1354 UUAAAAAU A UAUGAAUU 358 AAUUCAUA CUGAUGAG X CGAA AUUUUUAA 1494

1356 AAAAAUAU A UGAAUUCU 359 AGAAUUCA CUGAUGAG X CGAA AUAUUUUU 1495

1362 AUAUGAAU U CUCUCUCC 360 GGAGAGAG CUGAUGAG X CGAA AUUCAUAU 1496

1363 UAUGAAUU C UCUCUCCA 361 UGGAGAGA CUGAUGAG X CGAA AAUUCAUA 1497

1365 UGAAUUCU C UCUCCAAA 362 UUUGGAGA CUGAUGAG X CGAA AGAAUUCA 1498

1367 AAUUCUCU C UCCAAAUA 363 UAUUUGGA CUGAUGAG X CGAA AGAGAAUU 1499

1369 UUCUCUCU C CAAAUAUU 364 AAUAUUUG CUGAUGAG X CGAA AGAGAGAA 1500

1375 CUCCAAAU A UUAACUAA 365 UUAGUUAA CUGAUGAG X CGAA AUUUGGAG 1501

1377 CCAAAUAU U AACUAAUU 366 AAUUAGUU CUGAUGAG X CGAA AUAUUUGG 1502

1378 CAAAUAUU A ACUAAUUA 367 UAAUUAGU CUGAUGAG X CGAA AAUAUUUG 1503

1382 UAUUAACU A AUUAUUAG 368 CUAAUAAU CUGAUGAG X CGAA AGUUAAUA 1504

1385 UAACUAAU U AUUAGAUU 369 AAUCUAAU CUGAUGAG X CGAA AUUAGUUA 1505

1386 AACUAAUU A UUAGAUUA 370 UAAUCUAA CUGAUGAG X CGAA AAUUAGUU 1506

1388 CUAAUUAU U AGAUUAUA 371 UAUAAUCU CUGAUGAG X CGAA AUAAUUAG 1507 Table 24

1389 UAAUUAUU A GAUUAUAU 372 AUAUAAUC CUGAUGAG X CGAA AAUAAUUA 1508

1393 UAUUAGAU U AUAUUUUG 373 CAAAAUAU CUGAUGAG X CGAA AUCUAAUA 1509

1394 AUUAGAUU A UAUUUUGA 374 UCAAAAUA CUGAUGAG X CGAA AAUCUAAU 1510

1396 UAGAUUAU A UUUUGAAA 375 UUUCAAAA CUGAUGAG X CGAA AUAAUCUA 1511

1398 GAUUAUAU U UUGAAAUG 376 CAUUUCAA CUGAUGAG X CGAA AUAUAAUC 1512

1399 AUUAUAUU U UGAAAUGA 377 UCAUUUCA CUGAUGAG X CGAA AAUAUAAU 1513

1400 UUAUAUUU U GAAAUGAA 378 UUCAUUUC CUGAUGAG X CGAA AAAUAUAA 1514

1411 AAUGAACU U GUUGGCCC 379 GGGCCAAC CUGAUGAG X CGAA AGUUCAUU 1515

1414 GAACUUGU U GGCCCAUC 380 GAUGGGCC CUGAUGAG X CGAA ACAAGUUC 1516

1422 UGGCCCAU C UAUUACAU 381 AUGUAAUA CUGAUGAG X CGAA AUGGGCCA 1517

1424 GCCCAUCU A UUACAUCU 382 AGAUGUAA CUGAUGAG X CGAA AGAUGGGC 1518

1426 CCAUCUAU U ACAUCUAC 383 GUAGAUGU CUGAUGAG X CGAA AUAGAUGG 1519

1427 CAUCUAUU A CAUCUACA 384 UGUAGAUG CUGAUGAG X CGAA AAUAGAUG 1520

1431 UAUUACAU C UACAGCUG 385 CAGCUGUA CUGAUGAG X CGAA AUGUAAUA 1521

1433 UUACAUCU A CAGCUGAC 386 GUCAGCUG CUGAUGAG X CGAA AGAUGUAA 1522

1445 CUGACCCU U GAACAUGG 387 CCAUGUUC CUGAUGAG X CGAA AGGGUCAG 1523

1458 AUGGGGGU U AGGGGAGC 388 GCUCCCCU CUGAUGAG X CGAA ACCCCCAU 1524

1459 UGGGGGUU A GGGGAGCU 389 AGCUCCCC CUGAUGAG X CGAA AACCCCCA 1525

1474 CUGACAAU U CGUGGGUC 390 GACCCACG CUGAUGAG X CGAA AUUGUCAG 1526

1475 UGACAAUU C GUGGGUCC 391 GGACCCAC CUGAUGAG X CGAA AAUUGUCA 1527

1482 UCGUGGGU C CGCAAAAU 392 AUUUUGCG CUGAUGAG X CGAA ACCCACGA 1528

1491 CGCAAAAU C UUAACUAC 393 GUAGUUAA CUGAUGAG X CGAA AUUUUGCG 1529

1493 CAAAAUCU U AACUACCU 394 AGGUAGUU CUGAUGAG X CGAA AGAUUUUG 1530

1494 AAAAUCUU A ACUACCUA 395 UAGGUAGU CUGAUGAG X CGAA AAGAUUUU 1531

1498 UCUUAACU A CCUAAUAG 396 CUAUUAGG CUGAUGAG X CGAA AGUUAAGA 1532

1502 AACUACCU A AUAGCCUA 397 UAGGCUAU CUGAUGAG X CGAA AGGUAGUU 1533

1505 UACCUAAU A GCCUACUA 398 UAGUAGGC CUGAUGAG X CGAA AUUAGGUA 1534

1510 AAUAGCCU A CUAUUGAC 399 GUCAAUAG CUGAUGAG X CGAA AGGCUAUU 1535

1513 AGCCUACU A UUGACCAU 400 AUGGUCAA CUGAUGAG X CGAA AGUAGGCU 1536

1515 CCUACUAU U GACCAUAA 401 UUAUGGUC CUGAUGAG X CGAA AUAGUAGG 1537

1522 UUGACCAU A AACCUUAC 402 GUAAGGUU CUGAUGAG X CGAA AUGGUCAA 1538

1528 AUAAACCU U ACUGAUAA 403 UUAUCAGU CUGAUGAG X CGAA AGGUUUAU 1539

1529 UAAACCUU A CUGAUAAC 404 GUUAUCAG CUGAUGAG X CGAA AAGGUUUA 1540

1535 UUACUGAU A ACAUAAAC 405 GUUUAUGU CUGAUGAG X CGAA AUCAGUAA 1541

1540 GAUAACAU A AACAGUAA 406 UUACUGUU CUGAUGAG X CGAA AUGUUAUC 1542

1547 UAAACAGU A AAUUAACA 407 UGUUAAUU CUGAUGAG X CGAA ACUGUUUA 1543

1551 CAGUAAAU U AACACAUA 408 UAUGUGUU CUGAUGAG X CGAA AUUUACUG 1544

1552 AGUAAAUU A ACACAUAU 409 AUAUGUGU CUGAUGAG X CGAA AAUUUACU 1545

1559 UAACACAU A UUUUGCGU 410 ACGCAAAA CUGAUGAG X CGAA AUGUGUUA 1546

1561 ACACAUAU U UUGCGUGU 411 ACACGCAA CUGAUGAG X CGAA AUAUGUGU 1547

1562 CACAUAUU U UGCGUGUU 412 AACACGCA CUGAUGAG X CGAA AAUAUGUG 1548

1563 ACAUAUUU U GCGUGUUA 413 UAACACGC CUGAUGAG X CGAA AAAUAUGU 1549

1570 UUGCGUGU U AUAUGUAU 414 AUACAUAU CUGAUGAG X CGAA ACACGCAA 1550

1571 UGCGUGUU A UAUGUAUU 415 AAUACAUA CUGAUGAG X CGAA AACACGCA 1551

1573 CGUGUUAU A UGUAUUAU 416 AUAAUACA CUGAUGAG X CGAA AUAACACG 1552

1577 UUAUAUGU A UUAUACAC 417 GUGUAUAA CUGAUGAG X CGAA ACAUAUAA 1553

1579 AUAUGUAU U AUACACUA 418 UAGUGUAU CUGAUGAG X CGAA AUACAUAU 1554 Table 24

1580 UAUGUAUU A UACACUAU 419 AUAGUGUA CUGAUGAG X CGAA AAUACAUA 1555

1582 UGUAUUAU A CACUAUAU 420 AUAUAGUG CUGAUGAG X CGAA AUAAUACA 1556

1587 UAUACACU A UAUUCCUA 421 UAGGAAUA CUGAUGAG X CGAA AGUGUAUA 1557

1589 UACACUAU A UUCCUACA 422 UGUAGGAA CUGAUGAG X CGAA AUAGUGUA 1558

1591 CACUAUAU U CCUACAAU 423 AUUGUAGG CUGAUGAG X CGAA AUAUAGUG 1559

1592 ACUAUAUU C CUACAAUA 424 UAUUGUAG CUGAUGAG X CGAA AAUAUAGU 1560

1595 AUAUUCCU A CAAUAAAG 425 CUUUAUUG CUGAUGAG X CGAA AGGAAUAU 1561

1600 CCUACAAU A AAGUAAGC 426 GCUUACUU CUGAUGAG X CGAA AUUGUAGG 1562

1605 AAUAAAGU A AGCUAGAG 427 CUCUAGCU CUGAUGAG X CGAA ACUUUAUU 1563

1610 AGUAAGCU A GAGAAAAU 428 AUUUUCUC CUGAUGAG X CGAA AGCUUACU 1564

1621 GAAAAUGU U AUUUAGAA 429 UUCUAAAU CUGAUGAG X CGAA ACAUUUUC 1565

1622 AAAAUGUU A UUUAGAAA 430 UUUCUAAA CUGAUGAG X CGAA AACAUUUU 1566

1624 AAUGUUAU U UAGAAAAU 431 AUUUUCUA CUGAUGAG X CGAA AUAACAUU 1567

1625 AUGUUAUU U AGAAAAUC 432 GAUUUUCU CUGAUGAG X CGAA AAUAACAU 1568

1626 UGUUAUUU A GAAAAUCA 433 UGAUUUUC CUGAUGAG X CGAA AAAUAACA 1569

Input Sequence = PLN. Cut Site = UH/.

Stem Length = 8 . Core Sequence = CUGAUGAG X CGAA (X = GCCGUUAGGC or other stem II)

PLN (Homo sapiens phospholamban (PLN) mRNA.; 1635 bp)

Table 25 Table 25: Human Phospholamban (PLN) NCH Ribozyme and Target Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

15 CAGAAAAC U AGCUAAAC 434 GUUUAGCU CUGAUGAG X CGAA IUUUUCUG 1570

17 GAAAACUC C CUAAACAC 435 GUGUUUAG CUGAUGAG X CGAA IAGUUUUC 1571

18 AAAACUCC C UAAACACC 436 GGUGUUUA CUGAUGAG X CGAA IGAGUUUU 1572

19 AAACUCCC C AAACACCC 437 GGGUGUUU CUGAUGAG X CGAA IGGAGUUU 1573

20 AACUCCCC A AACACCCG 438 CGGGUGUU CUGAUGAG X CGAA IGGGAGUU 1574

23 UCCCCAGC U ACCCGUAA 439 UUACGGGU CUGAUGAG X CGAA ICUGGGGA 1575

28 AGCUAAAC A UAAGACUU 440 AAGUCUUA CUGAUGAG X CGAA IUUUAGCU 1576

^' 30 CUAAACAC C AGACUUCA 441 UGAAGUCU CUGAUGAG X CGAA IUGUUUAG 1577

31 UAAACACC C GACUUCAU 442 AUGAAGUC CUGAUGAG X CGAA IGUGUUUA 1578

39 CGUAAGAC U ACAACACA 443 UGUGUUGU CUGAUGAG X CGAA IUCUUACG 1579

42 AAGACUUC A ACACAAUA 444 UAUUGUGU CUGAUGAG X CGAA IAAGUCUU 1580

46 CUUCAUAC A AAUACUCU 445 AGAGUAUU CUGAUGAG X CGAA IUAUGAAG 1581

49 CAUACAAC A ACUCUAUA 446 UAUAGAGU CUGAUGAG X CGAA IUUGUAUG 1582

51 UACAACAC A UCUAUACU 447 AGUAUAGA CUGAUGAG X CGAA IUGUUGUA 1583

56 CACAAUAC U ACUGUGAU 448 AUCACAGU CUGAUGAG X CGAA IUAUUGUG 1584

58 CAAUACUC U UGUGAUGA 449 UCAUCACA CUGAUGAG X CGAA IAGUAUUG 1585

63 CUCUAUAC U UGAUCACA 450 UGUGAUCA CUGAUGAG X CGAA IUAUAGAG 1586

73 UGAUGAUC A UGCCAAGG 451 CCUUGGCA CUGAUGAG X CGAA IAUCAUCA 1587

75 AUGAUCAC A CCAAGGCU 452 AGCCUUGG CUGAUGAG X CGAA IUGAUCAU 1588

78 AUCACAGC U AGGCUACC 453 GGUAGCCU CUGAUGAG X CGAA ICUGUGAU 1589

81 ACAGCUGC C CUACCUAA 454 UUAGGUAG CUGAUGAG X CGAA ICAGCUGU 1590

82 CAGCUGCC A UACCUAAA 455 UUUAGGUA CUGAUGAG X CGAA IGCAGCUG 1591

87 GCCAAGGC U AAAAGAAG 456 CUUCUUUU CUGAUGAG X CGAA ICCUUGGC 1592

90 AAGGCUAC C AGAAGACA 457 UGUCUUCU CUGAUGAG X CGAA IUAGCCUU 1593

91 AGGCUACC U GAAGACAG 458 CUGUCUUC CUGAUGAG X CGAA IGUAGCCU 1594

102 AAGAAGAC A UCUCAUAU 459 AUAUGAGA CUGAUGAG X CGAA IUCUUCUU 1595

109 CAGUUAUC U UUUGGCUG 460 CAGCCAAA CUGAUGAG X CGAA IAUAACUG 1596

111 GUUAUCUC A UGGCUGCC 461 GGCAGCCA CUGAUGAG X CGAA IAGAUAAC 1597

120 UAUUUGGC U GCUUUUUA 462 UAAAAAGC CUGAUGAG X CGAA ICCAAAUA 1598

123 UUGGCUGC C UUUUAUCU 463 AGAUAAAA CUGAUGAG X CGAA ICAGCCAA 1599

124 UGGCUGCC A UUUAUCUU 464 AAGAUAAA CUGAUGAG X CGAA IGCAGCCA 1600

127 CUGCCAGC U AUCUUUCU 465 AGAAAGAU CUGAUGAG X CGAA ICUGGCAG 1601

135 UUUUUAUC U CUCGACCA 466 UGGUCGAG CUGAUGAG X CGAA IAUAAAAA 1602

139 UAUCUUUC U ACCACUUA 467 UAAGUGGU CUGAUGAG X CGAA IAAAGAUA 1603

141 UCUUUCUC U CACUUAAA 468 UUUAAGUG CUGAUGAG X CGAA IAGAAAGA 1604

146 CUCUCGAC C AAAACUUC 469 GAAGUUUU CUGAUGAG X CGAA IUCGAGAG 1605

147 UCUCGACC A AAACUUCA 470 UGAAGUUU CUGAUGAG X CGAA IGUCGAGA 1606

149 UCGACCAC U ACUUCAGA 471 UCUGAAGU CUGAUGAG X CGAA IUGGUCGA 1607

156 CUUAAAAC U ACUUCCUG 472 CAGGAAGU CUGAUGAG X CGAA IUUUUAAG 1608

159 AAAACUUC A UCCUGUCC 473 GGACAGGA CUGAUGAG X CGAA IAAGUUUU 1609

163 CUUCAGAC U GUCCUGCU 474 AGCAGGAC CUGAUGAG X CGAA IUCUGAAG 1610

166 CAGACUUC C CUGCUGGU 475 ACCAGCAG CUGAUGAG X CGAA IAAGUCUG 1611

167 AGACUUCC U UGCUGGUA 476 UACCAGCA CUGAUGAG X CGAA IGAAGUCU 1612

171 UUCCUGUC C GGUAUCAU 477 AUGAUACC CUGAUGAG X CGAA lACAGGAA 1613 Table 25

172 UCCUGUCC U GUAUCAUG 478 CAUGAUAC CUGAUGAG X CGAA IGACAGGA 1614

175 UGUCCUGC U UCAUGGAG 479 CUCCAUGA CUGAUGAG X CGAA ICAGGACA 1615

182 CUGGUAUC A GAAAGUCC 480 GGACUUUC CUGAUGAG X CGAA IAUACCAG 1616

194 AGAAAGUC C CCUCACUC 481 GAGUGAGG CUGAUGAG X CGAA IACUUUCU 1617

195 GAAAGUCC A CUCACUCG 482 CGAGUGAG CUGAUGAG X CGAA IGACUUUC 1618

200 UCCAAUAC C UCGCUCAG 483 CUGAGCGA CUGAUGAG X CGAA IUAUUGGA 1619

201 CCAAUACC U CGCUCAGC 484 GCUGAGCG CUGAUGAG X CGAA IGUAUUGG 1620

203 AAUACCUC A CUCAGCUA 485 UAGCUGAG CUGAUGAG X CGAA IAGGUAUU 1621

205 UACCUCAC U CAGCUAUA 486 UAUAGCUG CUGAUGAG X CGAA IUGAGGUA 1622

209 UCACUCGC U UAUAAGAA 487 UUCUUAUA CUGAUGAG X CGAA ICGAGUGA 1623

211 ACUCGCUC A UAAGAAGA 488 UCUUCUUA CUGAUGAG X CGAA IAGCGAGU 1624

214 CGCUCAGC U GAAGAGCC 489 GGCUCUUC CUGAUGAG X CGAA ICUGAGCG 1625

226 AGAAGAGC C CCAUUGAA 490 UUCAAUGG CUGAUGAG X CGAA ICUCUUCU 1626

227 GAAGAGCC U CAUUGAAA 491 UUUCAAUG CUGAUGAG X CGAA IGCUCUUC 1627

229 AGAGCCUC A UUGAAAUG 492 CAUUUCAA CUGAUGAG X CGAA IAGGCUCU 1628

232 GCCUCAAC C AAAUGCCU 493 AGGCAUUU CUGAUGAG X CGAA IUUGAGGC 1629

233 CCUCAACC A AAUGCCUC 494 GAGGCAUU CUGAUGAG X CGAA IGUUGAGG 1630

243 UGAAAUGC C CAAGCACG 495 CGUGCUUG CUGAUGAG X CGAA ICAUUUCA 1631

244 GAAAUGCC U AAGCACGU 496 ACGUGCUU CUGAUGAG X CGAA IGCAUUUC 1632

246 AAUGCCUC A GCACGUCA 497 UGACGUGC CUGAUGAG X CGAA IAGGCAUU 1633

249 GCCUCAAC A CGUCAAAA 498 UUUUGACG CUGAUGAG X CGAA IUUGAGGC 1634

253 CAACAAGC A AAAAGCUA 499 UAGCUUUU CUGAUGAG X CGAA ICUUGUUG 1635

258 AGCACGUC A CUACAGAA 500 UUCUGUAG CUGAUGAG X CGAA IACGUGCU 1636

264 UCAAAAGC U AAUCUAUU 501 AAUAGAUU CUGAUGAG X CGAA ICUUUUGA 1637

267 AAAGCUAC A CUAUUUAU 502 AUAAAUAG CUGAUGAG X CGAA lUAGCUUU 1638

273 ACAGAAUC U AUCAAUUU 503 AAAUUGAU CUGAUGAG X CGAA IAUUCUGU 1639

281 UAUUUAUC A CUGUCUCA 504 UGAGACAG CUGAUGAG X CGAA IAUAAAUA 1640

287 UCAAUUUC U CAUCUUAA 505 UUAAGAUG CUGAUGAG X CGAA IAAAUUGA 1641

291 uuucuσuc U UUAAUAUG 506 CAUAUUAA CUGAUGAG X CGAA IACAGAAA 1642

293 UCUGUCUC A AAUAUGUC 507 GACAUAUU CUGAUGAG X CGAA IAGACAGA 1643

296 GUCUCAUC U AUGUCUCU 508 AGAGACAU CUGAUGAG X CGAA IAUGAGAC 1644

306 AAUAUGUC U CUGAUCUG 509 CAGAUCAG CUGAUGAG X CGAA IACAUAUU 1645

308 UAUGUCUC U GAUCUGUA 510 UACAGAUC CUGAUGAG X CGAA IAGACAUA 1646

312 UCUCUUGC U UGUAUCAU 511 AUGAUACA CUGAUGAG X CGAA ICAAGAGA 1647

317 UGCUGAUC U CAUCGUGA 512 - UCACGAUG CUGAUGAG X CGAA IAUCAGCA 1648

323 UCUGUAUC A GAUGCUUC 513 GAAGCAUC CUGAUGAG X CGAA IAUACAGA 1649

333 CGUGAUGC U UGAAGUUC 514 GAACUUCA CUGAUGAG X CGAA ICAUCACG 1650

336 GAUGCUUC U AGUUCUGC 515 GCAGAACU CUGAUGAG X CGAA IAAGCAUC 1651

338 UGCUUCUC U UUCUGCUA 516 UAGCAGAA CUGAUGAG X CGAA lAGAAGCA 1652

346 UGAAGUUC U CAACCUCU 517 AGAGGUUG CUGAUGAG X CGAA lAACUUCA 1653

349 AGUUCUGC U CCUCUAGA 518 UCUAGAGG CUGAUGAG X CGAA ICAGAACU 1654

352 UCUGCUAC A CUAGAUCU 519 AGAUCUAG CUGAUGAG X CGAA lUAGCAGA 1655

355 GCUACAAC C GAUCUGCA 520 UGCAGAUC CUGAUGAG X CGAA IUUGUAGC 1656

356 CUACAACC U AUCUGCAG 521 CUGCAGAU CUGAUGAG X CGAA IGUUGUAG 1657

358 ACAACCUC U CUGCAGCU 522 AGCUGCAG CUGAUGAG X CGAA IAGGUUGU 1658

364 UCUAGAUC U CUUGCCAC 523 GUGGCAAG CUGAUGAG X CGAA IAUCUAGA 1659

367 AGAUCUGC A GCCACAUC 524 GAUGUGGC CUGAUGAG X CGAA ICAGAUCU 1660 Table 25

370 UCUGCAGC U ACAUCAGC 525 GCUGAUGU CUGAUGAG X CGAA ICUGCAGA 1661

374 CAGCUUGC C CAGCUUAA 526 UUAAGCUG CUGAUGAG X CGAA ICAAGCUG 1662

375 AGCUUGCC A AGCUUAAA 527 UUUAAGCU CUGAUGAG X CGAA IGCAAGCU 1663

377 CUUGCCAC A CUUAAAAU 528 AUUUUAAG CUGAUGAG X CGAA IUGGCAAG 1664

380 GCCACAUC A AAAAUCUG 529 CAGAUUUU CUGAUGAG X CGAA IAUGUGGC 1665

383 ACAUCAGC U AUCUGUCA 530 UGACAGAU CUGAUGAG X CGAA ICUGAUGU 1666

391 UUAAAAUC U UCCCAUGC 531 GCAUGGGA CUGAUGAG X CGAA IAUUUUAA 1667

395 AAUCUGUC A AUGCAGAC 532 GUCUGCAU CUGAUGAG X CGAA IACAGAUU 1668

398 CUGUCAUC C CAGACAGG 533 CCUGUCUG CUGAUGAG X CGAA IAUGACAG 1669

399 UGUCAUCC C AGACAGGA 534 UCCUGUCU CUGAUGAG X CGAA IGAUGACA 1670

400 GUCAUCCC A GACAGGAA 535 UUCCUGUC CUGAUGAG X CGAA IGGAUGAC 1671

404 UCCCAUGC A GGAAAACA 536 UGUUUUCC CUGAUGAG X CGAA ICAUGGGA 1672

408 AUGCAGAC A AACAAUAU 537 AUAUUGUU CUGAUGAG X CGAA IUCUGCAU 1673

416 AGGAAAAC A UGUAUAAC 538 GUUAUACA CUGAUGAG X CGAA IUUUUCCU 1674

429 UGUAUAAC A ACUUCCUG 539 CAGGAAGU CUGAUGAG X CGAA IUUAUACA 1675

433 UAACAGAC C CCUGAGUA 540 UACUCAGG CUGAUGAG X CGAA IUCUGUUA 1676

434 AACAGACC A CUGAGUAG 541 CUACUCAG CUGAUGAG X CGAA IGUCUGUU 1677

436 CAGACCAC U GAGUAGAA 542 UUCUACUC CUGAUGAG X CGAA IUGGUCUG 1678

439 ACCACUUC C UAGAAGAG 543 CUCUUCUA CUGAUGAG X CGAA IAAGUGGU 1679

440 CCACUUCC U AGAAGAGU 544 ACUCUUCU CUGAUGAG X CGAA IGAAGUGG 1680

456 AGAGUUUC U GAAAAGGU 545 ACCUUUUC CUGAUGAG X CGAA IAAACUCU 1681

470 AAAAGGUC A UAAGACUA 546 UAGUCUUA CUGAUGAG X CGAA IACCUUUU 1682

481 AUUAAGAC U CUUAUUGU 547 ACAAUAAG CUGAUGAG X CGAA IUCUUAAU 1683

487 ACUAAAAC U GUUACCAU 548 AUGGUAAC CUGAUGAG X CGAA IUUUUAGU 1684

497 AUUGUUAC C GUAUUCAU 549 AUGAAUAC CUGAUGAG X CGAA IUAACAAU 1685

498 UUGUUACC A UAUUCAUC 550 GAUGAAUA CUGAUGAG X CGAA IGUAACAA 1686

508 AUGUAUUC A UUGGAUCU 551 AGAUCCAA CUGAUGAG X CGAA IAAUACAU 1687

511 UAUUCAUC U GAUCUUGU 552 ACAAGAUC CUGAUGAG X CGAA lAUGAAUA 1688

520 GUUGGAUC U AACAUGAA 553 UUCAUGUU CUGAUGAG X CGAA IAUCCAAC 1689

528 UUGUAAAC A AAGGGCUU 554 AAGCCCUU CUGAUGAG X CGAA IUUUACAA 1690

539 AAAAGGGC U UUUCAAAA 555 UUUUGAAA CUGAUGAG X CGAA ICCCUUUU 1691

548 UUAUUUUC A UUAACUUC 556 GAAGUUAA CUGAUGAG X CGAA IAAAAUAA 1692

558 AAAUUAAC U AAUAAGUG 557 CACUUAUU CUGAUGAG X CGAA IUUAAUUU 1693

561 UUAACUUC A AAGUGUAU 558 AUACACUU CUGAUGAG X CGAA IAAGUUAA 1694

581 UAAAAUGC A UUGAUUUC 559 GAAAUCAA CUGAUGAG X CGAA ICAUUUUA 1695

584 AAUGCAAC U AUUUCCUC 560 GAGGAAAU CUGAUGAG X CGAA IUUGCAUU 1696

594 UUGAUUUC C CAUGGCUC 561 GAGCCAUG CUGAUGAG X CGAA IAAAUCAA 1697

595 UGAUUUCC U AUGGCUCA 562 UGAGCCAU CUGAUGAG X CGAA IGAAAUCA 1698

597 AUUUCCUC A GGCUCACA 563 UGUGAGCC CUGAUGAG X CGAA IAGGAAAU 1699

600 UCCUCAAC A UCACAAAU 564 AUUUGUGA CUGAUGAG X CGAA IUUGAGGA 1700

605 AACAUGGC U AAUUUCUA 565 UAGAAAUU CUGAUGAG X CGAA ICCAUGUU 1701

607 CAUGGCUC A UUUCUAUC 566 GAUAGAAA CUGAUGAG X CGAA IAGCCAUG 1702

609 UGGCUCAC A UCUAUCCC 567 GGGAUAGA CUGAUGAG X CGAA IUGAGCCA 1703

616 CAAAUUUC U CAAAUCUU 568 AAGAUUUG CUGAUGAG X CGAA IAAAUUUG 1704

620 UUUCUAUC C UCUUUUCU 569 AGAAAAGA CUGAUGAG X CGAA lAUAGAAA 1705

621 UUCUAUCC C CUUUUCUG 570 CAGAAAAG CUGAUGAG X CGAA IGAUAGAA 1706

622 UCUAUCCC A UUUUCUGA 571 UCAGAAAA CUGAUGAG X CGAA IGGAUAGA 1707 Table 25

627 CCCAAAUC U UGAAGAUG 572 CAUCUUCA CUGAUGAG X CGAA IAUUUGGG 1708

632 AUCUUUUC U AUGAAGAG 573 CUCUUCAU CUGAUGAG X CGAA IAAAAGAU 1709

659 UUUAAAAC U UGCCAACA 574 UGUUGGCA CUGAUGAG X CGAA IUUUUAAA 1710

662 AAAACUGC A CAACAAGU 575 ACUUGUUG CUGAUGAG X CGAA ICAGUUUU 1711

664 AACUGCAC U ACAAGUUC 576 GAACUUGU CUGAUGAG X CGAA IUGCAGUU 1712

667 UGCACUGC C AGUUCACU 577 AGUGAACU CUGAUGAG X CGAA ICAGUGCA 1713

668 GCACUGCC A GUUCACUU 578 AAGUGAAC CUGAUGAG X CGAA IGCAGUGC 1714

671 CUGCCAAC A CACUUCAU 579 AUGAAGUG CUGAUGAG X CGAA IUUGGCAG 1715

677 ACAAGUUC A AUAUAUAA 580 UUAUAUAU CUGAUGAG X CGAA IAACUUGU 1716

679 AAGUUCAC U AUAUAAAG 581 CUUUAUAU CUGAUGAG X CGAA IUGAACUU 1717

682 UUCACUUC A UAAAGCAU 582 AUGCUUUA CUGAUGAG X CGAA IAAGUGAA 1718

693 UAUAAAGC A UUUUACUC 583 GAGUAAAA CUGAUGAG X CGAA ICUUUAUA 1719

704 AUUUUUAC U UGAGGUGA 584 UCACCUCA CUGAUGAG X CGAA IUAAAAAU 1720

706 UUUUACUC U AGGUGAAU 585 AUUCACCU CUGAUGAG X CGAA IAGUAAAA 1721

733 UAUAUUAC A AAAAGCUU 586 AAGCUUUU CUGAUGAG X CGAA IUAAUAUA 1722

744 GUAAAAGC U UAAUACUA 587 UAGUAUUA CUGAUGAG X CGAA ICUUUUAC 1723

747 AAAGCUUC U UACUAAGU 588 ACUUAGUA CUGAUGAG X CGAA IAAGCUUU 1724

755 UUUAAUAC U AUUUUUCA 589 UGAAAAAU CUGAUGAG X CGAA IUAUUAAA 1725

767 UAUUUUUC A UUCACCAA 590 UUGGUGAA CUGAUGAG X CGAA IAAAAAUA 1726

772 UUCAGGUC U CAAGUAUC 591 GAUACUUG CUGAUGAG X CGAA IACCUGAA 1727

775 AGGUCUUC A GUAUCAAA 592 UUUGAUAC CUGAUGAG X CGAA IAAGACCU 1728

777 GUCUUCAC C AUCAAAGU 593 ACUUUGAU CUGAUGAG X CGAA IUGAAGAC 1729

778 UCUUCACC A UCAAAGUA 594 UACUUUGA CUGAUGAG X CGAA IGUGAAGA 1730

785 CAAGUAUC A AAUAACAC 595 GUGUUAUU CUGAUGAG X CGAA IAUACUUG 1731

796 GUAAUAAC A UGAAGUGU 596 ACACUUCA CUGAUGAG X CGAA IUUAUUAC 1732

798 AAUAACAC A AAGUGUCA 597 UGACACUU CUGAUGAG X CGAA IUGUUAUU 1733

810 GAAGUGUC A UCAAAAUA 598 UAUUUUGA CUGAUGAG X CGAA IACACUUC 1734

817 CAUUAUUC A AGUCCACU 599 AGUGGACU CUGAUGAG X CGAA IAAUAAUG 1735

826 AAAUAGUC C ACUCCUCA 600 UGAGGAGU CUGAUGAG X CGAA IACUAUUU 1736

827 AAUAGUCC A CUCCUCAC 601 GUGAGGAG CUGAUGAG X CGAA IGACUAUU 1737

829 UAGUCCAC U CCUCACAU 602 AUGUGAGG CUGAUGAG X CGAA lUGGACUA 1738

833 CCACUGAC U ACAUCUGU 603 ACAGAUGU CUGAUGAG X CGAA IUCAGUGG 1739

835 ACUGACUC C AUCUGUUA 604 UAACAGAU CUGAUGAG X CGAA IAGUCAGU 1740

836 CUGACUCC U UCUGUUAU 605 AUAACAGA CUGAUGAG X CGAA IGAGUCAG 1741

838 GACUCCUC A UGUUAUCU 606 AGAUAACA CUGAUGAG X CGAA IAGGAGUC 1742

840 CUCCUCAC A UUAUCUUA 607 UAAGAUAA CUGAUGAG X CGAA IUGAGGAG 1743

843 CUCACAUC U UCUUAUUA 608 UAAUAAGA CUGAUGAG X CGAA IAUGUGAG 1744

850 CUGUUAUC U AUAAAGAA 609 UUCUUUAU CUGAUGAG X CGAA IAUAACAG 1745

864 UAAAGAAC U GUAGUAAC 610 GUUACUAC CUGAUGAG X CGAA IUUCUUUA 1746

877 GUAGUAAC U GAAUCUAC 611 GUAGAUUC CUGAUGAG X CGAA IUUACUAC 1747

881 UAACUAUC A CUACAUUC 612 GAAUGUAG CUGAUGAG X CGAA IAUAGUUA 1748

887 UCAGAAUC U UCUAAAAC 613 GUUUUAGA CUGAUGAG X CGAA lAUUCUGA 1749

890 GAAUCUAC A AAAACAGA 614 UCUGUUUU CUGAUGAG X CGAA IUAGAUUC 1750

894 CUACAUUC U CAGAAAUU 615 AAUUUCUG CUGAUGAG X CGAA IAAUGUAG 1751

900 UCUAAAAC A UUGUAUUU 616 AAAUACAA CUGAUGAG X CGAA IUUUUAGA 1752

917 AUUUUUUC U CACAUUAA 617 UUAAUGUG CUGAUGAG X CGAA IAAAAAAU 1753

922 UUCUAUGC C UAACAUCU 618 AGAUGUUA CUGAUGAG X CGAA ICAUAGAA 1754 Table 25

923 UCUAUGCC A AACAUCUU 619 AAGAUGUU CUGAUGAG X CGAA IGCAUAGA 1755

925 UAUGCCAC A CAUCUUUU 620 AAAAGAUG CUGAUGAG X CGAA IUGGCAUA 1756

931 ACAUUAAC A UUAAAGUU 621 AACUUUAA CUGAUGAG X CGAA IUUAAUGU 1757

934 UUAACAUC U AAGUUGAU 622 AUCAACUU CUGAUGAG X CGAA IAUGUUAA 1758

954 UGAGAAUC A UGGAAAAG 623 CUUUUCCA CUGAUGAG X CGAA IAUUCUCA 1759

973 AGUAAGGC C UCUUACAU 624 AUGUAAGA CUGAUGAG X CGAA ICCUUACU 1760

974 GUAAGGCC A CUUACAUA 625 UAUGUAAG CUGAUGAG X CGAA IGCCUUAC 1761

978 GGCCAUAC U CAUAAUAA 626 UUAUUAUG CUGAUGAG X CGAA IUAUGGCC 1762

980 CCAUACUC U UAAUAAAA 627 UUUUAUUA CUGAUGAG X CGAA IAGUAUGG 1763

984 ACUCUUAC A AAAAUUCC 628 GGAAUUUU CUGAUGAG X CGAA IUAAGAGU 1764

996 UAAAAUUC C AAGUAAUU 629 AAUUACUU CUGAUGAG X CGAA IAAUUUUA 1765

997 AAAAUUCC U AGUAAUUU 630 AAAUUACU CUGAUGAG X CGAA IGAAUUUU 1766

1014 AUUUUUUC A AUCACAGA 631 UCUGUGAU CUGAUGAG X CGAA IAAAAAAU 1767

1022 AAAGAAUC A AUUCUAGU 632 ACUAGAAU CUGAUGAG X CGAA IAUUCUUU 1768

1024 AGAAUCAC A UCUAGUAC 633 GUACUAGA CUGAUGAG X CGAA IUGAUUCU 1769

1031 CAGAAUUC U CAUGUAGG 634 CCUACAUG CUGAUGAG X CGAA IAAUUCUG 1770

1037 UCUAGUAC A GGUAAAUC 635 GAUUUACC CUGAUGAG X CGAA IUACUAGA 1771

1050 GGUAAAUC A UCUGUUCU 636 AGAACAGA CUGAUGAG X CGAA IAUUUACC 1772

1057 CAUAAAUC U UAAGACAU 637 AUGUCUUA CUGAUGAG X CGAA IAUUUAUG 1773

1062 AUCUGUUC U CAUAUGAU 638 AUCAUAUG CUGAUGAG X CGAA IAACAGAU 1774

1068 UCUAAGAC A AUCAACAG 639 CUGUUGAU CUGAUGAG X CGAA IUCUUAGA 1775

1076 AUAUGAUC A AUGAGAAC 640 GUUCUCAU CUGAUGAG X CGAA IAUCAUAU 1776

1079 UGAUCAAC A AGAACUGG 641 CCAGUUCU CUGAUGAG X CGAA IUUGAUCA 1777

1089 AUGAGAAC U GUUAAUAU 642 AUAUUAAC CUGAUGAG X CGAA IUUCUCAU 1778

1107 UAUGUGAC A GAUUAGUC 643 GACUAAUC CUGAUGAG X CGAA lUCACAUA 1779

1120 GAUUAGUC A ACUAAUAU 644 AUAUUAGU CUGAUGAG X CGAA IACUAAUC 1780

1125 GUCAUAUC A UAUACUAA 645 UUAGUAUA CUGAUGAG X CGAA IAUAUGAC 1781

1127 CAUAUCAC U UACUAACA 646 UGUUAGUA CUGAUGAG X CGAA IUGAUAUG 1782

1135 UAAUAUAC U ACAGAAUC 647 GAUUCUGU CUGAUGAG X CGAA IUAUAUUA 1783

1139 AUACUAAC A AAUCUAAU 648 AUUAGAUU CUGAUGAG X CGAA IUUAGUAU 1784

1142 CUAACAAC A CUAAUCUU 649 AAGAUUAG CUGAUGAG X CGAA IUUGUUAG 1785

1148 ACAGAAUC U UUCAUUUA 650 UAAAUGAA CUGAUGAG X CGAA IAUUCUGU 1786

1153 AUCUAAUC U UUAAGGCA 651 UGCCUUAA CUGAUGAG X CGAA IAUUAGAU 1787

1156 UAAUCUUC A AGGCACUG 652 CAGUGCCU CUGAUGAG X CGAA IAAGAUUA 1788

1165 UUUAAGGC A AGUGAAUU 653 AAUUCACU CUGAUGAG X CGAA ICCUUAAA 1789

1167 UAAGGCAC U UGAAUUAU 654 AUAAUUCA CUGAUGAG X CGAA IUGCCUUA 1790

1181 GAAUUAUC U UAGAGUUA 655 UAACUCUA CUGAUGAG X CGAA IAUAAUUC 1791

1186 AUCUGAGC U UUACCUAG 656 CUAGGUAA CUGAUGAG X CGAA ICUCAGAU 1792

1195 AGAGUUAC C UUACCAUA 657 UAUGGUAA CUGAUGAG X CGAA IUAACUCU 1793

1196 GAGUUACC U UACCAUAC 658 GUAUGGUA CUGAUGAG X CGAA IGUAACUC 1794

1200 UACCUAGC U AUACUAUA 659 UAUAGUAU CUGAUGAG X CGAA ICUAGGUA 1795

1204 UAGCUUAC C UAUAUCUU 660 AAGAUAUA CUGAUGAG X CGAA lUAAGCUA 1796

1205 AGCUUACC A AUAUCUUU 661 AAAGAUAU CUGAUGAG X CGAA IGUAAGCU 1797

1209 UACCAUAC U CUUUGGAA 662 UUCCAAAG CUGAUGAG X CGAA IUAUGGUA 1798

1215 ACUAUAUC U AAUCAUGA 663 UCAUGAUU CUGAUGAG X CGAA IAUAUAGU 1799

1224 UUGGAAUC A ACCUUAAG 664 CUUAAGGU CUGAUGAG X CGAA IAUUCCAA 1800

1231 CAUGAAAC C GACUUCAG 665 CUGAAGUC CUGAUGAG X CGAA IUUUCAUG 1801 Table 25

1232 AUGAAACC U ACUUCAGA 666 UCUGAAGU CUGAUGAG X CGAA IGUUUCAU 1802

1239 CUUAAGAC U AAUGAUUU 667 AAAUCAUU CUGAUGAG X CGAA IUCUUAAG 1803

1242 AAGACUUC A GAUUUUGC 668 GCAAAAUC CUGAUGAG X CGAA IAAGUCUU 1804

1255 GAUUUUGC A GUCUUCCA 669 UGGAAGAC CUGAUGAG X CGAA ICAAAAUC 1805 ^■

1263 AGGUUGUC U UUCCAGCC 670 GGCUGGAA CUGAUGAG X CGAA IACAACCU 1806

1266 UUGUCUUC C CAGCCUAA 671 UUAGGCUG CUGAUGAG X CGAA IAAGACAA 1807

1267 UGUCUUCC A AGCCUAAC 672 GUUAGGCU CUGAUGAG X CGAA IGAAGACA 1808

1271 UUCCAUUC C UAACAUCC 673 GGAUGUUA CUGAUGAG X CGAA IAAUGGAA 1809

1272 UCCAUUCC A AACAUCCA 674 UGGAUGUU CUGAUGAG X CGAA IGAAUGGA 1810

1275 AUUCCAGC C AUCCAAUG 675 CAUUGGAU CUGAUGAG X CGAA ICUGGAAU 1811

1276 UUCCAGCC U UCCAAUGC 676 GCAUUGGA CUGAUGAG X CGAA IGCUGGAA 1812

1280 AGCCUAAC A AUGCAGGC 677 GCCUGCAU CUGAUGAG X CGAA lUUAGGCU 1813

1283 CUAACAUC C CAGGCAAG 678 CUUGCCUG CUGAUGAG X CGAA IAUGUUAG 1814

1284 UAACAUCC A AGGCAAGG 679 CCUUGCCU CUGAUGAG X CGAA IGAUGUUA 1815

1289 UCCAAUGC A AGGAAAAU 680 AUUUUCCU CUGAUGAG X CGAA ICAUUGGA 1816

1293 AUGCAGGC A AAAUAAAA 681 UUUUAUUU CUGAUGAG X CGAA ICCUGCAU 1817

1312 AAGAUUUC C ACAGAAAA 682 uuuucuσu CUGAUGAG X CGAA IAAAUCUU 1818

1313 AGAUUUCC A CAGAAAAA 683 UUUUUCUG CUGAUGAG X CGAA IGAAAUCU 1819

1319 CCAGUGAC A AAUAUAUU 684 AAUAUAUU CUGAUGAG X CGAA IUCACUGG 1820

1335 AUAUUAUC U UAUUUUUU 685 AAAAAAUA CUGAUGAG X CGAA IAUAAUAU 1821

1337 AUUAUCUC A UUUUUUAA 686 UUAAAAAA CUGAUGAG X CGAA IAGAUAAU 1822

1364 AUGAAUUC U CCAAAUAU 687 AUAUUUGG CUGAUGAG X CGAA IAAUUCAU 1823

1366 GAAUUCUC U AAAUAUUA 688 UAAUAUUU CUGAUGAG X CGAA IAGAAUUC 1824

1368 AUUCUCUC U AUAUUAAC 689 GUUAAUAU CUGAUGAG X CGAA IAGAGAAU 1825

1370 UCUCUCUC C AUUAACUA 690 UAGUUAAU CUGAUGAG X CGAA IAGAGAGA 1826

1371 CUCUCUCC A UUAACUAA 691 UUAGUUAA CUGAUGAG X CGAA IGAGAGAG 1827

1381 AUAUUAAC U AUUAGAUU 692 AAUCUAAU CUGAUGAG X CGAA IUUAAUAU 1828

1410 AAAUGAAC U GGCCCAUC 693 GAUGGGCC CUGAUGAG X CGAA IUUCAUUU 1829

1418 UUGUUGGC C UAUUACAU 694 AUGUAAUA CUGAUGAG X CGAA ICCAACAA 1830

1419 UGUUGGCC C AUUACAUC 695 GAUGUAAU CUGAUGAG X CGAA IGCCAACA 1831

1420 GUUGGCCC A UUACAUCU 696 AGAUGUAA CUGAUGAG X CGAA IGGCCAAC 1832

1423 GGCCCAUC U CAUCUACA 697 UGUAGAUG CUGAUGAG X CGAA IAUGGGCC 1833

1429 UCUAUUAC A CAGCUGAC 698 GUCAGCUG CUGAUGAG X CGAA IUAAUAGA 1834

1432 AUUACAUC U CUGACCCU 699 AGGGUCAG CUGAUGAG X CGAA IAUGUAAU 1835

1435 ACAUCUAC A ACCCUUGA 700 UCAAGGGU CUGAUGAG X CGAA IUAGAUGU 1836

1438 UCUACAGC U CUUGAACA 701 UGUUCAAG CUGAUGAG X CGAA ICUGUAGA 1837

1442 CAGCUGAC C AACAUGGG 702 CCCAUGUU CUGAUGAG X CGAA IUCAGCUG 1838

1443 AGCUGACC C ACAUGGGG 703 CCCCAUGU CUGAUGAG X CGAA IGUCAGCU 1839

1444 GCUGACCC u CAUGGGGG 704 CCCCCAUG CUGAUGAG X CGAA IGGUCAGC 1840

1450 CCUUGAAC A GGUUAGGG 705 CCCUAACC CUGAUGAG X CGAA IUUCAAGG 1841

1467 AGGGGAGC U AUUCGUGG 706 CCACGAAU CUGAUGAG X CGAA ICUCCCCU 1842

1471 GAGCUGAC A GUGGGUCC 707 GGACCCAC CUGAUGAG X CGAA IUCAGCUC 1843

1483 CGUGGGUC C AAUCUUAA 708 UUAAGAUU CUGAUGAG X CGAA IACCCACG 1844

1486 GGGUCCGC A CUUAACUA 709 UAGUUAAG CUGAUGAG X CGAA ICGGACCC 1845

1492 GCAAAAUC U UACCUAAU 710 AUUAGGUA CUGAUGAG X CGAA IAUUUUGC 1846

1497 AUCUUAAC U AAUAGCCU 711 AGGCUAUU CUGAUGAG X CGAA lUUAAGAU 1847

1500 UUAACUAC C AGCCUACU 712 AGUAGGCU CUGAUGAG X CGAA lUAGUUAA 1848 Table 25

1501 UAACUACC U GCCUACUA 713 UAGUAGGC CUGAUGAG X CGAA IGUAGUUA 1849

1508 CUAAUAGC C AUUGACCA 714 UGGUCAAU CUGAUGAG X CGAA ICUAUUAG 1850

1509 UAAUAGCC U UUGACCAU 715 AUGGUCAA CUGAUGAG X CGAA IGCUAUUA 1851

1512 UAGCCUAC U ACCAUAAA 716 UUUAUGGU CUGAUGAG X CGAA IUAGGCUA 1852

1519 CUAUUGAC C ACCUUACU 717 AGUAAGGU CUGAUGAG X CGAA IUCAAUAG 1853

1520 UAUUGACC A CCUUACUG 718 CAGUAAGG CUGAUGAG X CGAA IGUCAAUA 1854

1526 CCAUAAAC C UGAUAACA 719 UGUUAUCA CUGAUGAG X CGAA IUUUAUGG 1855

1527 CAUAAACC U GAUAACAU 720 AUGUUAUC CUGAUGAG X CGAA IGUUUAUG 1856

1531 AACCUUAC U ACAUAAAC 721 GUUUAUGU CUGAUGAG X CGAA IUAAGGUU 1857

1538 CUGAUAAC A CAGUAAAU 722 AUUUACUG CUGAUGAG X CGAA IUUAUCAG 1858

1544 ACAUAAAC A AUUAACAC 723 GUGUUAAU CUGAUGAG X CGAA IUUUAUGU 1859

1555 AAAUUAAC A UUUUGCGU 724 ACGCAAAA CUGAUGAG X CGAA IUUAAUUU 1860

1557 AUUAACAC A UUGCGUGU 725 ACACGCAA CUGAUGAG X CGAA IUGUUAAU 1861

1584 UAUUAUAC A AUUCCUAC 726 GUAGGAAU CUGAUGAG X CGAA IUAUAAUA 1862

1586 UUAUACAC U UCCUACAA 727 UUGUAGGA CUGAUGAG X CGAA IUGUAUAA 1863

1593 CUAUAUUC C AUAAAGUA 728 UACUUUAU CUGAUGAG X CGAA IAAUAUAG 1864

1594 UAUAUUCC U UAAAGUAA 729 UUACUUUA CUGAUGAG X CGAA IGAAUAUA 1865

1597 AUUCCUAC A AGUAAGCU 730 AGCUUACU CUGAUGAG X CGAA IUAGGAAU 1866

1609 AAGUAAGC U AAAAUGUU 731 AACAUUUU CUGAUGAG X CGAA ICUUACUU 1867

Input Sequence = PLN. Cut Site = CH/.

Stem Length = 8 . Core Sequence = CUGAUGAG X CGAA (X = GCCGUUAGGC or other stem II)

PLN (Homo sapiens phospholamban (PLN) mRNA.; 1635 bp)

Table 26

Table 26: Human Phospholamban (PLN) G-cleaver Ribozyme and Target Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

64 UCUAUACU G UGAUGAUC 732 GAUCAUCA UGAUG GCAUGCACUAUGC GCG AGUAUAGA 1868

66 UAUACUGU G AUGAUCAC 733 GUGAUCAU UGAUG GCAUGCACUAUGC GCG ACAGUAUA 1869

69 ACUGUGAU G AUCACAGC 734 GCUGUGAU UGAUG GCAUGCACUAUGC GCG AUCACAGU 1870

79 UCACAGCU G CCAAGGCU 735 AGCCUUGG UGAUG GCAUGCACUAUGC GCG AGCUGUGA 1871

121 AUUUGGCU G CCAGCUUU 736 AAAGCUGG UGAUG GCAUGCACUAUGC GCG AGCCAAAU 1872

143 UUUCUCUC G ACCACUUA 737 UAAGUGGU UGAUG GCAUGCACUAUGC GCG GAGAGAAA 1873

168 GACUUCCU G UCCUGCUG 738 CAGCAGGA UGAUG GCAUGCACUAUGC GCG AGGAAGUC 1874

173 CCUGUCCU G CUGGUAUC 739 GAUACCAG UGAUG GCAUGCACUAUGC GCG AGGACAGG 1875

207 CCUCACUC G CUCAGCUA 740 UAGCUGAG UGAUG GCAUGCACUAUGC GCG GAGUGAGG 1876

236 CAACCAUU G AAAUGCCU 741 AGGCAUUU UGAUG GCAUGCACUAUGC GCG AAUGGUUG 1877

241 AUUGAAAU G CCUCAACA 742 UGUUGAGG UGAUG GCAUGCACUAUGC GCG AUUUCAAU 1878

288 CAAUUUCU G UCUCAUCU 743 AGAUGAGA UGAUG GCAUGCACUAUGC GCG AGAAAUUG 1879

303 CUUAAUAU G UCUCUUGC 744 GCAAGAGA UGAUG GCAUGCACUAUGC GCG AUAUUAAG 1880

310 UGUCUCUU G CUGAUCUG 745 CAGAUCAG UGAUG GCAUGCACUAUGC GCG AAGAGACA 1881

313 CUCUUGCU G AUCUGUAU 746 AUACAGAU UGAUG GCAUGCACUAUGC GCG AGCAAGAG 1882

318 GCUGAUCU G UAUCAUCG 747 CGAUGAUA UGAUG GCAUGCACUAUGC GCG AGAUCAGC 1883

328 AUCAUCGU G AUGCUUCU 748 AGAAGCAU UGAUG GCAUGCACUAUGC GCG ACGAUGAU 1884

331 AUCGUGAU G CUUCUCUG 749 CAGAGAAG UGAUG GCAUGCACUAUGC GCG AUCACGAU 1885

339 GCUUCUCU G AAGUUCUG 750 CAGAACUU UGAUG GCAUGCACUAUGC GCG AGAGAAGC 1886

347 GAAGUUCU G CUACAACC 751 GGUUGUAG UGAUG GCAUGCACUAUGC GCG AGAACUUC 1887

365 CUAGAUCU G CAGCUUGC 752 GCAAGCUG UGAUG GCAUGCACUAUGC GCG AGAUCUAG 1888

372 UGCAGCUU G CCACAUCA 753 UGAUGUGG UGAUG GCAUGCACUAUGC GCG AAGCUGCA 1889

392 UAAAAUCU G UCAUCCCA 754 UGGGAUGA UGAUG GCAUGCACUAUGC GCG AGAUUUUA 1890

402 CAUCCCAU G CAGACAGG 755 CCUGUCUG UGAUG GCAUGCACUAUGC GCG AUGGGAUG 1891

422 ACAAUAUU G UAUAACAG 756 CUGUUAUA UGAUG GCAUGCACUAUGC GCG AAUAUUGU 1892

441 CACUUCCU G AGUAGAAG 757 CUUCUACU UGAUG GCAUGCACUAUGC GCG AGGAAGUG 1893

459 GUUUCUUU G UGAAAAGG 758 CCUUUUCA UGAUG GCAUGCACUAUGC GCG AAAGAAAC 1894

461 UUCUUUGU G AAAAGGUC 759 GACCUUUU UGAUG GCAUGCACUAUGC GCG ACAAAGAA 1895

Table 26

492 AACUUAUU G UUACCAUA 760 UAUGGUAA UGAUG GCAUGCACUAUGC GCG AAUAAGUU 1896

502 UACCAUAU G UAUUCAUC 761 GAUGAAUA UGAUG GCAUGCACUAUGC GCG AUAUGGUA 1897

512 AUUCAUCU G UUGGAUCU 762 AGAUCCAA UGAUG GCAUGCACUAUGC GCG AGAUGAAU 1898

522 UGGAUCUU G UAAACAUG 763 CAUGUUUA UGAUG GCAUGCACUAUGC GCG AAGAUCCA 1899

530 GUAAACAU G AAAAGGGC 764 GCCCUUUU UGAUG GCAUGCACUAUGC GCG AUGUUUAC 1900

570 AAAUAAGU G UAUAAAAU 765 AUUUUAUA UGAUG GCAUGCACUAUGC GCG ACUUAUUU 1901

579 UAUAAAAU G CAACUGUU 766 AACAGUUG UGAUG GCAUGCACUAUGC GCG AUUUUAUA 1902

585 AUGCAACU G UUGAUUUC 767 GAAAUCAA UGAUG GCAUGCACUAUGC GCG AGUUGCAU 1903

588 CAACUGUU G AUUUCCUC 768 GAGGAAAU UGAUG GCAUGCACUAUGC GCG AACAGUUG 1904

633 UCUUUUCU G AAGAUGAA 769 UUCAUCUU UGAUG GCAUGCACUAUGC GCG AGAAAAGA 1905

639 CUGAAGAU G AAGAGUUU 770 AAACUCUU UGAUG GCAUGCACUAUGC GCG AUCUUCAG 1906

660 UUAAAACU G CACUGCCA 771 UGGCAGUG UGAUG GCAUGCACUAUGC GCG AGUUUUAA 1907

665 ACUGCACU G CCAACAAG 772 CUUGUUGG UGAUG GCAUGCACUAUGC GCG AGUGCAGU 1908

710 ACUCUUUU G AGGUGAAU 773 AUUCACCU UGAUG GCAUGCACUAUGC GCG AAAAGAGU 1909

715 UUUGAGGU G AAUAUAAU 774 AUUAUAUU UGAUG GCAUGCACUAUGC GCG ACCUCAAA 1910

736 AUUACAAU G UAAAAGCU 775 AGCUUUUA UGAUG GCAUGCACUAUGC GCG AUUGUAAU 1911

802 ACACAAAU G AAGUGUCA 776 UGACACUU UGAUG GCAUGCACUAUGC GCG AUUUGUGU 1912

807 AAUGAAGU G UCAUUAUU 777 AAUAAUGA UGAUG GCAUGCACUAUGC GCG ACUUCAUU 1913

830 AGUCCACU G ACUCCUCA 778 UGAGGAGU UGAUG GCAUGCACUAUGC GCG AGUGGACU 1914

844 UCACAUCU G UUAUCUUA 779 UAAGAUAA UGAUG GCAUGCACUAUGC GCG AGAUGUGA 1915

869 AACUAUUU G UAGUAACU 780 AGUUACUA UGAUG GCAUGCACUAUGC GCG AAAUAGUU 1916

907 CAGAAAUU G UAUUUUUU 781 AAAAAAUA UGAUG GCAUGCACUAUGC GCG AAUUUCUG 1917

920 UUUUCUAU G CCACAUUA 782 UAAUGUGG UGAUG GCAUGCACUAUGC GCG AUAGAAAA 1918

944 UUAAAGUU G AUGAGAAU 783 AUUCUCAU UGAUG GCAUGCACUAUGC GCG AACUUUAA 1919

947 AAGUUGAU G AGAAUCAA 784 UUGAUUCU UGAUG GCAUGCACUAUGC GCG AUCAACUU 1920

1039 UAGUACAU G UAGGUAAA 785 UUUACCUA UGAUG GCAUGCACUAUGC GCG AUGUACUA 1921

1058 AUAAAUCU G UUCUAAGA 786 UCUUAGAA UGAUG GCAUGCACUAUGC GCG AGAUUUAU 1922

1072 AGACAUAU G AUCAACAG 787 CUGUUGAU UGAUG GCAUGCACUAUGC GCG AUAUGUCU 1923

1083 CAACAGAU G AGAACUGG 788 CCAGUUCU UGAUG GCAUGCACUAUGC GCG AUCUGUUG 1924

1102 GUUAAUAU G UGACAGUG 789 CACUGUCA UGAUG GCAUGCACUAUGC GCG AUAUUAAC 1925

1104 UAAUAUGU G ACAGUGAG 790 CUCACUGU UGAUG GCAUGCACUAUGC GCG ACAUAUUA 1926

Table 26

1110 GUGACAGU G AGAUUAGU 791 ACUAAUCU UGAUG GCAUGCACUAUGC GCG ACUGUCAC 1927

1168 AAGGCACU G UAGUGAAU 792 AUUCACUA UGAUG GCAUGCACUAUGC GCG AGUGCCUU 1928

1173 ACUGUAGU G AAUUAUCU 793 AGAUAAUU UGAUG GCAUGCACUAUGC GCG ACUACAGU 1929

1182 AAUUAUCU G AGCUAGAG 794 CUCUAGCU UGAUG GCAUGCACUAUGC GCG AGAUAAUU 1930

1226 GGAAUCAU G AAACCUUA 795 UAAGGUUU UGAUG GCAUGCACUAUGC GCG AUGAUUCC 1931

1247 UUCAGAAU G AUUUUGCA 796 UGCAAAAU UGAUG GCAUGCACUAUGC GCG AUUCUGAA 1932

1253 AUGAUUUU G CAGGUUGU 797 ACAACCUG UGAUG GCAUGCACUAUGC GCG AAAAUCAU 1933

1260 UGCAGGUU G UCUUCCAU 798 AUGGAAGA UGAUG GCAUGCACUAUGC GCG AACCUGCA 1934

1287 CAUCCAAU G CAGGCAAG 799 CUUGCCUG UGAUG GCAUGCACUAUGC GCG AUUGGAUG 1935

1316 UUUCCAGU G ACAGAAAA 800 UUUUCUGU UGAUG GCAUGCACUAUGC GCG ACUGGAAA 1936

1358 AAAUAUAU G AAUUCUCU 801 AGAGAAUU UGAUG GCAUGCACUAUGC GCG AUAUAUUU 1937

1401 UAUAUUUU G AAAUGAAC 802 GUUCAUUU UGAUG GCAUGCACUAUGC GCG AAAAUAUA 1938

1406 UUUGAAAU G AACUUGUU 803 AACAAGUU UGAUG GCAUGCACUAUGC GCG AUUUCAAA 1939

1412 AUGAACUU G UUGGCCCA 804 UGGGCCAA UGAUG GCAUGCACUAUGC GCG AAGUUCAU 1940

1439 CUACAGCU G ACCCUUGA 805 UCAAGGGU UGAUG GCAUGCACUAUGC GCG AGCUGUAG 1941

1446 UGACCCUU G AACAUGGG 806 CCCAUGUU UGAUG GCAUGCACUAUGC GCG AAGGGUCA 1942

1468 GGGGAGCU G ACAAUUCG 807 CGAAUUGU UGAUG GCAUGCACUAUGC GCG AGCUCCCC 1943

1484 GUGGGUCC G CAAAAUCU 808 AGAUUUUG UGAUG GCAUGCACUAUGC GCG GGACCCAC 1944

1516 CUACUAUU G ACCAUAAA 809 UUUAUGGU UGAUG GCAUGCACUAUGC GCG AAUAGUAG 1945

1532 ^■ ACCUUACU G AUAACAUA 810 UAUGUUAU UGAUG GCAUGCACUAUGC GCG AGUAAGGU 1946

1564 CAUAUUUU G CGUGUUAU 811 AUAACACG UGAUG GCAUGCACUAUGC GCG AAAAUAUG 1947

1568 UUUUGCGU G UUAUAUGU 812 ACAUAUAA UGAUG GCAUGCACUAUGC GCG ACGCAAAA 1948

1575 UGUUAUAU G UAUUAUAC 813 GUAUAAUA UGAUG GCAUGCACUAUGC GCG AUAUAACA 1949

1619 GAGAAAAU G UUAUUUAG 814 CUAAAUAA UGAUG GCAUGCACUAUGC GCG AUUUUCUC 1950

Input Sequence = PLN. Cut Site = YG/M or UG/U.

Stem Length = 8. Core Sequence = UGAUG GCAUGCACUAUGC GCG

PLN (Homo sapiens phospholamban (PLN) mRNA.; 1635 bp)

Table 27

Table 27: Human Phospholamban (PLN) zinzyme Ribozyme and Target Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

64 UCUAUACU G UGAUGAUC 732 GAUCAUCA GCCGAAAGGCGAGUCAAGGUCU AGUAUAGA 1951

79 UCACAGCU G CCAAGGCU 735 AGCCUUGG GCCGAAAGGCGAGUCAAGGUCU AGCUGUGA 1952

121 AUUUGGCU G CCAGCUUU 736 AAAGCUGG GCCGAAAGGCGAGUCAAGGUCU AGCCAAAU 1953

168 GACUUCCU G UCCUGCUG 738 CAGCAGGA GCCGAAAGGCGAGUCAAGGUCU AGGAAGUC 1954

173 CCUGUCCU G CUGGUAUC 739 GAUACCAG GCCGAAAGGCGAGUCAAGGUCU AGGACAGG 1955

207 CCUCACUC G CUCAGCUA 740 UAGCUGAG GCCGAAAGGCGAGUCAAGGUCU GAGUGAGG 1956

241 AUUGAAAU G CCUCAACA 742 UGUUGAGG GCCGAAAGGCGAGUCAAGGUCU AUUUCAAU 1957

288 CAAUUUCU G UCUCAUCU 743 AGAUGAGA GCCGAAAGGCGAGUCAAGGUCU AGAAAUUG 1958

303 CUUAAUAU G UCUCUUGC 744 GCAAGAGA GCCGAAAGGCGAGUCAAGGUCU AUAUUAAG 1959

310 UGUCUCUU G CUGAUCUG 745 CAGAUCAG GCCGAAAGGCGAGUCAAGGUCU AAGAGACA 1960

318 GCUGAUCU G UAUCAUCG 747 CGAUGAUA GCCGAAAGGCGAGUCAAGGUCU AGAUCAGC 1961

331 AUCGUGAU G CUUCUCUG 749 CAGAGAAG GCCGAAAGGCGAGUCAAGGUCU AUCACGAU 1962

347 GAAGUUCU G CUACAACC 751 GGUUGUAG GCCGAAAGGCGAGUCAAGGUCU AGAACUUC 1963

365 CUAGAUCU G CAGCUUGC 752 GCAAGCUG GCCGAAAGGCGAGUCAAGGUCU AGAUCUAG 1964

372 UGCAGCUU G CCACAUCA 753 UGAUGUGG GCCGAAAGGCGAGUCAAGGUCU AAGCUGCA 1965

392 UAAAAUCU G UCAUCCCA 754 UGGGAUGA GCCGAAAGGCGAGUCAAGGUCU AGAUUUUA 1966

402 CAUCCCAU G CAGACAGG 755 CCUGUCUG GCCGAAAGGCGAGUCAAGGUCU AUGGGAUG 1967

422 ACAAUAUU G UAUAACAG 756 CUGUUAUA GCCGAAAGGCGAGUCAAGGUCU AAUAUUGU 1968

459 GUUUCUUU G UGAAAAGG 758 CCUUUUCA GCCGAAAGGCGAGUCAAGGUCU AAAGAAAC 1969

492 AACUUAUU G UUACCAUA 760 UAUGGUAA GCCGAAAGGCGAGUCAAGGUCU AAUAAGUU 1970

502 UACCAUAU G UAUUCAUC 761 GAUGAAUA GCCGAAAGGCGAGUCAAGGUCU AUAUGGUA 1971

512 AUUCAUCU G UUGGAUCU 762 AGAUCCAA GCCGAAAGGCGAGUCAAGGUCU AGAUGAAU 1972

522 UGGAUCUU G UAAACAUG 763 CAUGUUUA GCCGAAAGGCGAGUCAAGGUCU AAGAUCCA 1973

570 AAAUAAGU G UAUAAAAU 765 AUUUUAUA GCCGAAAGGCGAGUCAAGGUCU ACUUAUUU 1974

579 UAUAAAAU G CAACUGUU 766 AACAGUUG GCCGAAAGGCGAGUCAAGGUCU AUUUUAUA 1975

585 AUGCAACU G UUGAUUUC 767 GAAAUCAA GCCGAAAGGCGAGUCAAGGUCU AGUUGCAU 1976

660 UUAAAACU G CACUGCCA 771 UGGCAGUG GCCGAAAGGCGAGUCAAGGUCU AGUUUUAA 1977

665 ACUGCACU G CCAACAAG 772 CUUGUUGG GCCGAAAGGCGAGUCAAGGUCU AGUGCAGU 1978

Table 27

736 AUUACAAU G UAAAAGCU 775 AGCUUUUA GCCGAAAGGCGAGUCAAGGUCU AUUGUAAU 1979

807 AAUGAAGU G UCAUUAUU 777 AAUAAUGA GCCGAAAGGCGAGUCAAGGUCU ACUUCAUU 1980

844 UCACAUCU G UUAUCUUA 779 UAAGAUAA GCCGAAAGGCGAGUCAAGGUCU AGAUGUGA 1981

869 AACUAUUU G UAGUAACU 780 AGUUACUA GCCGAAAGGCGAGUCAAGGUCU AAAUAGUU 1982

907 CAGAAAUU G UAUUUUUU 781 AAAAAAUA GCCGAAAGGCGAGUCAAGGUCU AAUUUCUG 1983

920 UUUUCUAU G CCACAUUA 782 UAAUGUGG GCCGAAAGGCGAGUCAAGGUCU AUAGAAAA 1984

1039 UAGUACAU G UAGGUAAA 785 UUUACCUA GCCGAAAGGCGAGUCAAGGUCU AUGUACUA 1985

1058 AUAAAUCU G UUCUAAGA 786 UCUUAGAA GCCGAAAGGCGAGUCAAGGUCU AGAUUUAU 1986

1102 GUUAAUAU G UGACAGUG 789 CACUGUCA GCCGAAAGGCGAGUCAAGGUCU AUAUUAAC 1987

1168 AAGGCACU G UAGUGAAU 792 AUUCACUA GCCGAAAGGCGAGUCAAGGUCU AGUGCCUU 1988

1253 AUGAUUUU G CAGGUUGU 797 ACAACCUG GCCGAAAGGCGAGUCAAGGUCU AAAAUCAU 1989

1260 UGCAGGUU G UCUUCCAU 798 AUGGAAGA GCCGAAAGGCGAGUCAAGGUCU AACCUGCA 1990

1287 CAUCCAAU G CAGGCAAG 799 CUUGCCUG GCCGAAAGGCGAGUCAAGGUCU AUUGGAUG 1991

1412 AUGAACUU G UUGGCCCA 804 UGGGCCAA GCCGAAAGGCGAGUCAAGGUCU AAGUUCAU 1992

1484 GUGGGUCC G CAAAAUCU 808 AGAUUUUG GCCGAAAGGCGAGUCAAGGUCU GGACCCAC 1993

1564 CAUAUUUU G CGUGUUAU 811 AUAACACG GCCGAAAGGCGAGUCAAGGUCU AAAAUAUG 1994

1568 UUUUGCGU G UUAUAUGU 812 ACAUAUAA GCCGAAAGGCGAGUCAAGGUCU ACGCAAAA 1995

1575 UGUUAUAU G UAUUAUAC 813 GUAUAAUA GCCGAAAGGCGAGUCAAGGUCU AUAUAACA 1996

1619 GAGAAAAU G UUAUUUAG 814 CUAAAUAA GCCGAAAGGCGAGUCAAGGUCU AUUUUCUC 1997

21 ACUCCCCA G CUAAACAC 815 GUGUUUAG GCCGAAAGGCGAGUCAAGGUCU UGGGGAGU 1998

32 AAACACCC G UAAGACUU 816 AAGUCUUA GCCGAAAGGCGAGUCAAGGUCU GGGUGUUU 1999

76 UGAUCACA G CUGCCAAG 817 CUUGGCAG GCCGAAAGGCGAGUCAAGGUCU UGUGAUCA 2000

85 CUGCCAAG G CUACCUAA 818 UUAGGUAG GCCGAAAGGCGAGUCAAGGUCU CUUGGCAG 2001

103 AGAAGACA G UUAUCUCA 819 UGAGAUAA GCCGAAAGGCGAGUCAAGGUCU UGUCUUCU 2002

118 CAUAUUUG G CUGCCAGC 820 GCUGGCAG GCCGAAAGGCGAGUCAAGGUCU CAAAUAUG 2003

125 GGCUGCCA G CUUUUUAU 821 AUAAAAAG GCCGAAAGGCGAGUCAAGGUCU UGGCAGCC 2004

177 UCCUGCUG G UAUCAUGG 822 CCAUGAUA GCCGAAAGGCGAGUCAAGGUCU CAGCAGGA 2005

191 UGGAGAAA G UCCAAUAC 823 GUAUUGGA GCCGAAAGGCGAGUCAAGGUCU UUUCUCCA 2006

212 CUCGCUCA G CUAUAAGA 824 UCUUAUAG GCCGAAAGGCGAGUCAAGGUCU UGAGCGAG 2007

224 UAAGAAGA G CCUCAACC 825 GGUUGAGG GCCGAAAGGCGAGUCAAGGUCU UCUUCUUA 2008

251 CUCAACAA G CACGUCAA 826 UUGACGUG GCCGAAAGGCGAGUCAAGGUCU UUGUUGAG 2009

Table 27

255 ACAAGCAC G UCAAAAGC 827 GCUUUUGA GCCGAAAGGCGAGUCAAGGUCU GUGCUUGU 2010

262 CGUCAAAA G CUACAGAA 828 UUCUGUAG GCCGAAAGGCGAGUCAAGGUCU UUUUGACG 2011

326 GUAUCAUC G UGAUGCUU 829 AAGCAUCA GCCGAAAGGCGAGUCAAGGUCU GAUGAUAC 2012

342 UCUCUGAA G UUCUGCUA 830 UAGCAGAA GCCGAAAGGCGAGUCAAGGUCU UUCAGAGA 2013

368 GAUCUGCA G CUUGCCAC 831 GUGGCAAG GCCGAAAGGCGAGUCAAGGUCU UGCAGAUC 2014

381 CCACAUCA G CUUAAAAU 832 AUUUUAAG GCCGAAAGGCGAGUCAAGGUCU UGAUGUGG 2015

443 CUUCCUGA G UAGAAGAG 833 CUCUUCUA GCCGAAAGGCGAGUCAAGGUCU UCAGGAAG 2016

451 GUAGAAGA G UUUCUUUG 834 CAAAGAAA GCCGAAAGGCGAGUCAAGGUCU UCUUCUAC 2017

467 GUGAAAAG G UCAAGAUU 835 AAUCUUGA GCCGAAAGGCGAGUCAAGGUCU CUUUUCAC 2018

537 UGAAAAGG G CUUUAUUU 836 AAAUAAAG GCCGAAAGGCGAGUCAAGGUCU CCUUUUCA 2019

568 CAAAAUAA G UGUAUAAA 837 UUUAUACA GCCGAAAGGCGAGUCAAGGUCU UUAUUUUG 2020

603 UCAACAUG G CUCACAAA 838 UUUGUGAG GCCGAAAGGCGAGUCAAGGUCU CAUGUUGA 2021

644 GAUGAAGA G UUUAGUUU 839 AAACUAAA GCCGAAAGGCGAGUCAAGGUCU UCUUCAUC 2022

649 AGAGUUUA G UUUUAAAA 840 UUUUAAAA GCCGAAAGGCGAGUCAAGGUCU UAAACUCU 2023

673 GCCAACAA G UUCACUUC 841 GAAGUGAA GCCGAAAGGCGAGUCAAGGUCU UUGUUGGC 2024

691 UAUAUAAA G CAUUAUUU 842 AAAUAAUG GCCGAAAGGCGAGUCAAGGUCU UUUAUAUA 2025

713 CUUUUGAG G UGAAUAUA 843 UAUAUUCA GCCGAAAGGCGAGUCAAGGUCU CUCAAAAG 2026

742 AUGUAAAA G CUUCUUUA 844 UAAAGAAG GCCGAAAGGCGAGUCAAGGUCU UUUUACAU 2027

758 AAUACUAA G UAUUUUUC 845 GAAAAAUA GCCGAAAGGCGAGUCAAGGUCU UUAGUAUU 2028

769 UUUUUCAG G UCUUCACC 846 GGUGAAGA GCCGAAAGGCGAGUCAAGGUCU CUGAAAAA 2029

780 UUCACCAA G UAUCAAAG 847 CUUUGAUA GCCGAAAGGCGAGUCAAGGUCU UUGGUGAA 2030

788 GUAUCAAA G UAAUAACA 848 UGUUAUUA GCCGAAAGGCGAGUCAAGGUCU UUUGAUAC 2031

805 CAAAUGAA G UGUCAUUA 849 UAAUGACA GCCGAAAGGCGAGUCAAGGUCU UUCAUUUG 2032

823 UCAAAAUA G UCCACUGA 850 UCAGUGGA GCCGAAAGGCGAGUCAAGGUCU UAUUUUGA 2033

872 UAUUUGUA G UAACUAUC 851 GAUAGUUA GCCGAAAGGCGAGUCAAGGUCU UACAAAUA 2034

941 CUUUUAAA G UUGAUGAG 852 CUCAUCAA GCCGAAAGGCGAGUCAAGGUCU UUUAAAAG 2035

956 AGAAUCAA G UAUGGAAA 853 UUUCCAUA GCCGAAAGGCGAGUCAAGGUCU UUGAUUCU 2036

966 AUGGAAAA G UAAGGCCA 854 UGGCCUUA GCCGAAAGGCGAGUCAAGGUCU UUUUCCAU 2037

971 AAAGUAAG G CCAUACUC 855 GAGUAUGG GCCGAAAGGCGAGUCAAGGUCU CUUACUUU 2038

1003 CCUUUUAA G UAAUUUUU 856 AAAAAUUA GCCGAAAGGCGAGUCAAGGUCU UUAAAAGG 2039

1033 GAAUUCUA G UACAUGUA 857 UACAUGUA GCCGAAAGGCGAGUCAAGGUCU UAGAAUUC 2040

Table 27

1043 ACAUGUAG G UAAAUCAU 858 AUGAUUUA GCCGAAAGGCGAGUCAAGGUCU CUACAUGU 2041

1091 GAGAACUG G UGGUUAAU 859 AUUAACCA GCCGAAAGGCGAGUCAAGGUCU CAGUUCUC 2042

1094 AACUGGUG G UUAAUAUG 860 CAUAUUAA GCCGAAAGGCGAGUCAAGGUCU CACCAGUU 2043

1108 AUGUGACA G UGAGAUUA 861 UAAUCUCA GCCGAAAGGCGAGUCAAGGUCU UGUCACAU 2044

1117 UGAGAUUA G UCAUAUCA 862 UGAUAUGA GCCGAAAGGCGAGUCAAGGUCU UAAUCUCA 2045

1163 CAUUUAAG G CACUGUAG 863 CUACAGUG GCCGAAAGGCGAGUCAAGGUCU CUUAAAUG 2046

1171 GCACUGUA G UGAAUUAU 864 AUAAUUCA GCCGAAAGGCGAGUCAAGGUCU UACAGUGC 2047

1184 UUAUCUGA G CUAGAGUU 865 AACUCUAG GCCGAAAGGCGAGUCAAGGUCU UCAGAUAA 2048

1190 GAGCUAGA G UUACCUAG 866 CUAGGUAA GCCGAAAGGCGAGUCAAGGUCU UCUAGCUC 2049

1198 GUUACCUA G CUUACCAU 867 AUGGUAAG GCCGAAAGGCGAGUCAAGGUCU UAGGUAAC 2050

1257 UUUUGCAG G UUGUCUUC 868 GAAGACAA GCCGAAAGGCGAGUCAAGGUCU CUGCAAAA 2051

1273 CCAUUCCA G CCUAACAU 869 AUGUUAGG GCCGAAAGGCGAGUCAAGGUCU UGGAAUGG 2052

1291 CAAUGCAG G CAAGGAAA 870 UUUCCUUG GCCGAAAGGCGAGUCAAGGUCU CUGCAUUG 2053

1314 GAUUUCCA G UGACAGAA 871 UUCUGUCA GCCGAAAGGCGAGUCAAGGUCU UGGAAAUC 2054

1339 UAUCUCAA G UAUUUUUU 872 AAAAAAUA GCCGAAAGGCGAGUCAAGGUCU UUGAGAUA 2055

1416 ACUUGUUG G CCCAUCUA 873 UAGAUGGG GCCGAAAGGCGAGUCAAGGUCU CAACAAGU 2056

1436 CAUCUACA G CUGACCCU 874 AGGGUCAG GCCGAAAGGCGAGUCAAGGUCU UGUAGAUG 2057

1456 ACAUGGGG G UUAGGGGA 875 UCCCCUAA GCCGAAAGGCGAGUCAAGGUCU CCCCAUGU 2058

1465 UUAGGGGA G CUGACAAU 876 AUUGUCAG GCCGAAAGGCGAGUCAAGGUCU UCCCCUAA 2059

1476 GACAAUUC G UGGGUCCG 877 CGGACCCA GCCGAAAGGCGAGUCAAGGUCU GAAUUGUC 2060

1480 AUUCGUGG G UCCGCAAA 878 UUUGCGGA GCCGAAAGGCGAGUCAAGGUCU CCACGAAU 2061

1506 ACCUAAUA G CCUACUAU 879 AUAGUAGG GCCGAAAGGCGAGUCAAGGUCU UAUUAGGU 2062

1545 CAUAAACA G UAAAUUAA 880 UUAAUUUA GCCGAAAGGCGAGUCAAGGUCU UGUUUAUG 2063

1566 UAUUUUGC G UGUUAUAU 881 AUAUAACA GCCGAAAGGCGAGUCAAGGUCU GCAAAAUA 2064

1603 ACAAUAAA G UAAGCUAG 882 CUAGCUUA GCCGAAAGGCGAGUCAAGGUCU UUUAUUGU 2065

1607 UAAAGUAA G CUAGAGAA 883 UUCUCUAG GCCGAAAGGCGAGUCAAGGUCU UUACUUUA 2066

Input Sequence = PLN. Cut Site = G Y

Stem Length = 8 . Core Sequence = GCcgaaagGCGaGuCaaGGuCu

PLN (Homo sapiens phospholamban (PLN) mRNA.; 1635 bp)

Table 28

Table 28: Human Phospholamban (PLN) DNAzyme and Target Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

44 GACUUCAU A CAACACAA 6 TTGTGTTG GGCTAGCTACAACGA ATGAAGTC 2067

54 AACACAAU A CUCUAUAC 7 GTATAGAG GGCTAGCTACAACGA ATTGTGTT 2068

59 AAUACUCU A UACUGUGA 9 TCACAGTA GGCTAGCTACAACGA AGAGTATT 2069

61 UACUCUAU A CUGUGAUG 10 CATCACAG GGCTAGCTACAACGA ATAGAGTA 2070

88 CCAAGGCU A CCUAAAAG 12 CTTTTAGG GGCTAGCTACAACGA AGCCTTGG 2071

106 AGACAGUU A UCUCAUAU 15 ATATGAGA GGCTAGCTACAACGA AACTGTCT 2072

113 UAUCUCAU A UUUGGCUG 18 CAGCCAAA GGCTAGCTACAACGA ATGAGATA 2073

132 AGCUUUUU A UCUUUCUC 25 GAGAAAGA GGCTAGCTACAACGA AAAAAGCT 2074

179 CUGCUGGU A UCAUGGAG 39 CTCCATGA GGCTAGCTACAACGA ACCAGCAG 2075

198 AGUCCAAU A CCUCACUC 42 GAGTGAGG GGCTAGCTACAACGA ATTGGACT 2076

215 GCUCAGCU A UAAGAAGA 46 TCTTCTTA GGCTAGCTACAACGA AGCTGAGC 2077

265 CAAAAGCU A CAGAAUCU 52 AGATTCTG GGCTAGCTACAACGA AGCTTTTG 2078

274 CAGAAUCU A UUUAUCAA 54 TTGATAAA GGCTAGCTACAACGA AGATTCTG 2079

278 AUCUAUUU A UCAAUUUC 57 GAAATTGA GGCTAGCTACAACGA AAATAGAT 2080

301 AUCUUAAU A UGUCUCUU 67 AAGAGACA GGCTAGCTACAACGA ATTAAGAT 2081

320 UGAUCUGU A UCAUCGUG 72 CACGATGA GGCTAGCTACAACGA ACAGATCA 2082

350 GUUCUGCU A CAACCUCU 80 AGAGGTTG GGCTAGCTACAACGA AGCAGAAC 2083

419 AAAACAAU A UUGUAUAA 91 TTATACAA GGCTAGCTACAACGA ATTGTTTT 2084

424 AAUAUUGU A UAACAGAC 93 GTCTGTTA GGCTAGCTACAACGA ACAATATT 2085

489 UAAAACUU A UUGUUACC 108 GGTAACAA GGCTAGCTACAACGA AAGTTTTA 2086

495 UUAUUGUU A CCAUAUGU 111 ACATATGG GGCTAGCTACAACGA AACAATAA 2087

500 GUUACCAU A UGUAUUCA 112 TGAATACA GGCTAGCTACAACGA ATGGTAAC 2088

504 CCAUAUGU A UUCAUCUG 113 CAGATGAA GGCTAGCTACAACGA ACATATGG 2089

542 AGGGCUUU A UUUUCAAA 123 TTTGAAAA GGCTAGCTACAACGA AAAGCCCT 2090

572 AUAAGUGU A UAAAAUGC 133 GCATTTTA GGCTAGCTACAACGA ACACTTAT 2091

617 AAAUUUCU A UCCCAAAU 144 ATTTGGGA GGCTAGCTACAACGA AGAAATTT 2092

684 CACUUCAU A UAUAAAGC 162 GCTTTATA GGCTAGCTACAACGA ATGAAGTG 2093

686 CUUCAUAU A UAAAGCAU 163 ATGCTTTA GGCTAGCTACAACGA ATATGAAG 2094

696 AAAGCAUU A UUUUUACU 166 AGTAAAAA GGCTAGCTACAACGA AATGCTTT 2095

702 UUAUUUUU A CUCUUUUG 171 CAAAAGAG GGCTAGCTACAACGA AAAAATAA 2096

719 AGGUGAAU A UAAUUUAU 176 ATAAATTA GGCTAGCTACAACGA ATTCACCT 2097

726 UAUAAUUU A UAUUACAA 180 TTGTAATA GGCTAGCTACAACGA AAATTATA 2098

728 UAAUUUAU A UUACAAUG 181 CATTGTAA GGCTAGCTACAACGA ATAAATTA 2099

731 UUUAUAUU A CAAUGUAA 183 TTACATTG GGCTAGCTACAACGA AATATAAA 2100

753 UCUUUAAU A CUAAGUAU 190 ATACTTAG GGCTAGCTACAACGA ATTAAAGA 2101

760 UACUAAGU A UUUUUCAG 192 CTGAAAAA GGCTAGCTACAACGA ACTTAGTA 2102

782 CACCAAGU A UCAAAGUA 201 TACTTTGA GGCTAGCTACAACGA ACTTGGTG 2103

813 GUGUCAUU A UUCAAAAU 207 ATTTTGAA GGCTAGCTACAACGA AATGACAC 2104

847 CAUCUGUU A UCUUAUUA 216 TAATAAGA GGCTAGCTACAACGA AACAGATG 2105

852 GUUAUCUU A UUAUAAAG 219 CTTTATAA GGCTAGCTACAACGA AAGATAAC 2106

855 AUCUUAUU A UAAAGAAC 221 GTTCTTTA GGCTAGCTACAACGA AATAAGAT 2107

865 AAAGAACU A UUUGUAGU 223 ACTACAAA GGCTAGCTACAACGA AGTTCTTT 2108

878 UAGUAACU A UCAGAAUC 228 GATTCTGA GGCTAGCTACAACGA AGTTACTA 2109

888 CAGAAUCU A CAUUCUAA 231 TTAGAATG GGCTAGCTACAACGA AGATTCTG 2110 Table 28

909 GAAAUUGU A UUUUUUCU 236 AGAAAAAA GGCTAGCTACAACGA ACAATTTC 2111

918 UUUUUUCU A UGCCACAU 243 ATGTGGCA GGCTAGCTACAACGA AGAAAAAA 2112

958 AAUCAAGU A UGGAAAAG 253 CTTTTCCA GGCTAGCTACAACGA ACTTGATT 2113

976 AAGGCCAU A CUCUUACA 255 TGTAAGAG GGCTAGCTACAACGA ATGGCCTT 2114

982 AUACUCUU A CAUAAUAA 258 TTATTATG GGCTAGCTACAACGA AAGAGTAT 2115

1035 AUUCUAGU A CAUGUAGG 278 CCTACATG GGCTAGCTACAACGA ACTAGAAT 2116

1070 UAAGACAU A UGAUCAAC 287 GTTGATCA GGCTAGCTACAACGA ATGTCTTA 2117

1100 UGGUUAAU A UGUGACAG 291 CTGTCACA GGCTAGCTACAACGA ATTAACCA 2118

1122 UUAGUCAU A UCACUAAU 295 ATTAGTGA GGCTAGCTACAACGA ATGACTAA 2119

1131 UCACUAAU A UACUAACA 298 TGTTAGTA GGCTAGCTACAACGA ATTAGTGA 2120

1133 ACUAAUAU A CUAACAAC 299 GTTGTTAG GGCTAGCTACAACGA ATATTAGT 2121

1178 AGUGAAUU A UCUGAGCU 311 AGCTCAGA GGCTAGCTACAACGA AATTCACT 2122

1193 CUAGAGUU A CCUAGCUU 315 AAGCTAGG GGCTAGCTACAACGA AACTCTAG 2123

1202 CCUAGCUU A CCAUACUA 318 TAGTATGG GGCTAGCTACAACGA AAGCTAGG 2124

1207 CUUACCAU A CUAUAUCU 319 AGATATAG GGCTAGCTACAACGA ATGGTAAG 2125

1210 ACCAUACU A UAUCUUUG 320 CAAAGATA GGCTAGCTACAACGA AGTATGGT 2126

1212 CAUACUAU A UCUUUGGA 321 TCCAAAGA GGCTAGCTACAACGA ATAGTATG 2127

1327 AGAAAAAU A UAUUAUCU 345 AGATAATA GGCTAGCTACAACGA ATTTTTCT 2128

1329 AAAAAUAU A UUAUCUCA 346 TGAGATAA GGCTAGCTACAACGA ATATTTTT 2129

1332 AAUAUAUU A UCUCAAGU 348 ACTTGAGA GGCTAGCTACAACGA AATATATT 2130

1341 UCUCAAGU A UUUUUUAA 351 TTAAAAAA GGCTAGCTACAACGA ACTTGAGA 2131

1354 UUAAAAAU A UAUGAAUU 358 AATTCATA GGCTAGCTACAACGA ATTTTTAA 2132

1356 AAAAAUAU A UGAAUUCU 359 AGAATTCA GGCTAGCTACAACGA ATATTTTT 2133

1375 CUCCAAAU A UUAACUAA 365 TTAGTTAA GGCTAGCTACAACGA ATTTGGAG 2134

1386- AACUAAUU A UUAGAUUA 370 TAATCTAA GGCTAGCTACAACGA AATTAGTT 2135

1394 AUUAGAUU A UAUUUUGA 374 TCAAAATA GGCTAGCTACAACGA AATCTAAT 2136

1396 UAGAUUAU A UUUUGAAA 375 TTTCAAAA GGCTAGCTACAACGA ATAATCTA 2137

1424 GCCCAUCU A UUACAUCU 382 AGATGTAA GGCTAGCTACAACGA AGATGGGC 2138

1427 CAUCUAUU A CAUCUACA 384 TGTAGATG GGCTAGCTACAACGA AATAGATG 2139

1433 UUACAUCU A CAGCUGAC 386 GTCAGCTG GGCTAGCTACAACGA AGATGTAA 2140

1498 UCUUAACU A CCUAAUAG 396 CTATTAGG GGCTAGCTACAACGA AGTTAAGA 2141

1510 AAUAGCCU A CUAUUGAC 399 GTCAATAG GGCTAGCTACAACGA AGGCTATT 2142

1513 AGCCUACU A UUGACCAU 400 ATGGTCAA GGCTAGCTACAACGA AGTAGGCT 2143

1529 UAAACCUU A CUGAUAAC 404 GTTATCAG GGCTAGCTACAACGA AAGGTTTA 2144

1559 UAACACAU A UUUUGCGU 410 ACGCAAAA GGCTAGCTACAACGA ATGTGTTA 2145

1571 UGCGUGUU A UAUGUAUU 415 AATACATA GGCTAGCTACAACGA AACACGCA 2146

1573 CGUGUUAU A UGUAUUAU 416 ATAATACA GGCTAGCTACAACGA ATAACACG 2147

1577 UUAUAUGU A UUAUACAC 417 GTGTATAA GGCTAGCTACAACGA ACATATAA 2148

1580 UAUGUAUU A UACACUAU 419 ATAGTGTA GGCTAGCTACAACGA AATACATA 2149

1582 UGUAUUAU A CACUAUAU 420 ATATAGTG GGCTAGCTACAACGA ATAATACA 2150

1587 UAUACACU A UAUUCCUA 421 TAGGAATA GGCTAGCTACAACGA AGTGTATA 2151

1589 UACACUAU A UUCCUACA 422 TGTAGGAA GGCTAGCTACAACGA ATAGTGTA 2152

1595 AUAUUCCU A CAAUAAAG 425 CTTTATTG GGCTAGCTACAACGA AGGAATAT 2153

1622 AAAAUGUU A UUUAGAAA 430 TTTCTAAA GGCTAGCTACAACGA AACATTTT 2154

64 UCUAUACU G UGAUGAUC 732 GATCATCA GGCTAGCTACAACGA AGTATAGA 2155

79 UCACAGCU G CCAAGGCU 735 AGCCTTGG GGCTAGCTACAACGA AGCTGTGA 2156

121 AUUUGGCU G CCAGCUUU 736 AAAGCTGG GGCTAGCTACAACGA AGCCAAAT 2157 Table 28

168 GACUUCCU G UCCUGCUG 738 CAGCAGGA GGCTAGCTACAACGA AGGAAGTC 2158

173 CCUGUCCU G CUGGUAUC 739 GATACCAG GGCTAGCTACAACGA AGGACAGG 2159

207 CCUCACUC G CUCAGCUA 740 TAGCTGAG GGCTAGCTACAACGA GAGTGAGG 2160

241 AUUGAAAU G CCUCAACA 742 TGTTGAGG GGCTAGCTACAACGA ATTTCAAT 2161

288 CAAUUUCU G UCUCAUCU 743 AGATGAGA GGCTAGCTACAACGA AGAAATTG 2162

303 CUUAAUAU G UCUCUUGC 744 GCAAGAGA GGCTAGCTACAACGA ATATTAAG 2163

310 UGUCUCUU G CUGAUCUG 745 CAGATCAG GGCTAGCTACAACGA AAGAGACA 2164

318 GCUGAUCU G UAUCAUCG 747 CGATGATA GGCTAGCTACAACGA AGATCAGC 2165

331 AUCGUGAU G CUUCUCUG 749 CAGAGAAG GGCTAGCTACAACGA ATCACGAT 2166

347 GAAGUUCU G CUACAACC 751 GGTTGTAG GGCTAGCTACAACGA AGAACTTC 2167

365 CUAGAUCU G CAGCUUGC 752 GCAAGCTG GGCTAGCTACAACGA AGATCTAG 2168

372 UGCAGCUU G CCACAUCA 753 TGATGTGG GGCTAGCTACAACGA AAGCTGCA 2169

392 UAAAAUCU G UCAUCCCA 754 TGGGATGA GGCTAGCTACAACGA AGATTTTA 2170

402 CAUCCCAU G CAGACAGG 755 CCTGTCTG GGCTAGCTACAACGA ATGGGATG 2171

422 ACAAUAUU G UAUAACAG 756 CTGTTATA GGCTAGCTACAACGA AATATTGT 2172

459 GUUUCUUU G UGAAAAGG 758 CCTTTTCA GGCTAGCTACAACGA AAAGAAAC 2173

492 AACUUAUU G UUACCAUA 760 TATGGTAA GGCTAGCTACAACGA AATAAGTT 2174

502 UACCAUAU G UAUUCAUC 761 GATGAATA GGCTAGCTACAACGA ATATGGTA 2175

512 AUUCAUCU G UUGGAUCU 762 AGATCCAA GGCTAGCTACAACGA AGATGAAT 2176

522 UGGAUCUU G UAAACAUG 763 CATGTTTA GGCTAGCTACAACGA AAGATCCA 2177

570 AAAUAAGU G UAUAAAAU 765 ATTTTATA GGCTAGCTACAACGA ACTTATTT 2178

579 UAUAAAAU G CAACUGUU 766 AACAGTTG GGCTAGCTACAACGA ATTTTATA 2179

585 AUGCAACU G UUGAUUUC 767 GAAATCAA GGCTAGCTACAACGA AGTTGCAT 2180

660 UUAAAACU G CACUGCCA 771 TGGCAGTG GGCTAGCTACAACGA AGTTTTAA 2181

665 ACUGCACU G CCAACAAG 772 CTTGTTGG GGCTAGCTACAACGA AGTGCAGT 2182

736 AUUACAAU G UAAAAGCU 775 AGCTTTTA GGCTAGCTACAACGA ATTGTAAT 2183

807 AAUGAAGU G UCAUUAUU 777 AATAATGA GGCTAGCTACAACGA ACTTCATT 2184

844 UCACAUCU G UUAUCUUA 779' TAAGATAA GGCTAGCTACAACGA AGATGTGA 2185

869 AACUAUUU G UAGUAACU 780 AGTTACTA GGCTAGCTACAACGA AAATAGTT 2186

907 CAGAAAUU G UAUUUUUU 781 AAAAAATA GGCTAGCTACAACGA AATTTCTG 2187

920 UUUUCUAU G CCACAUUA 782 TAATGTGG GGCTAGCTACAACGA ATAGAAAA 2188

1039 UAGUACAU G UAGGUAAA 785 TTTACCTA GGCTAGCTACAACGA ATGTACTA 2189

1058 AUAAAUCU G UUCUAAGA 786 TCTTAGAA GGCTAGCTACAACGA AGATTTAT 2190

1102 GUUAAUAU G UGACAGUG 789 CACTGTCA GGCTAGCTACAACGA ATATTAAC 2191

1168 AAGGCACU G UAGUGAAU 792 ATTCACTA GGCTAGCTACAACGA AGTGCCTT 2192

1253 AUGAUUUU G CAGGUUGU 797 ACAACCTG GGCTAGCTACAACGA AAAATCAT 2193

1260 UGCAGGUU G UCUUCCAU 798 ATGGAAGA GGCTAGCTACAACGA AACCTGCA 2194

1287 CAUCCAAU G CAGGCAAG 799 CTTGCCTG GGCTAGCTACAACGA ATTGGATG 2195

1412 AUGAACUU G UUGGCCCA 804 TGGGCCAA GGCTAGCTACAACGA AAGTTCAT 2196

1484 GUGGGUCC G CAAAAUCU 808 AGATTTTG GGCTAGCTACAACGA GGACCCAC 2197

1564 CAUAUUUU G CGUGUUAU 811 ATAACACG GGCTAGCTACAACGA AAAATATG 2198

1568 UUUUGCGU G UUAUAUGU 812 ACATATAA GGCTAGCTACAACGA ACGCAAAA 2199

1575 UGUUAUAU G UAUUAUAC 813 GTATAATA GGCTAGCTACAACGA ATATAACA 2200

1619 GAGAAAAU G UUAUUUAG 814 CTAAATAA GGCTAGCTACAACGA ATTTTCTC 2201

21 ACUCCCCA G CUAAACAC 815 GTGTTTAG GGCTAGCTACAACGA TGGGGAGT 2202

32 AAACACCC G UAAGACUU 816 AAGTCTTA GGCTAGCTACAACGA GGGTGTTT 2203

76 UGAUCACA G CUGCCAAG 817 CTTGGCAG GGCTAGCTACAACGA TGTGATCA 2204 Table 28

85 CUGCCAAG G CUACCUAA 818 TTAGGTAG GGCTAGCTACAACGA CTTGGCAG 2205

103 AGAAGACA G UUAUCUCA 819 TGAGATAA GGCTAGCTACAACGA TGTCTTCT 2206

118 CAUAUUUG G CUGCCAGC 820 GCTGGCAG GGCTAGCTACAACGA CAAATATG 2207

125 GGCUGCCA G CUUUUUAU 821 ATAAAAAG GGCTAGCTACAACGA TGGCAGCC 2208

177 UCCUGCUG G UAUCAUGG 822 CCATGATA GGCTAGCTACAACGA CAGCAGGA 2209

191 UGGAGAAA G UCCAAUAC 823 GTATTGGA GGCTAGCTACAACGA TTTCTCCA 2210

212 CUCGCUCA G CUAUAAGA 824 TCTTATAG GGCTAGCTACAACGA TGAGCGAG 2211

224 UAAGAAGA G CCUCAACC 825 GGTTGAGG GGCTAGCTACAACGA TCTTCTTA 2212

251 CUCAACAA G CACGUCAA 826 TTGACGTG GGCTAGCTACAACGA TTGTTGAG 2213

255 ACAAGCAC G UCAAAAGC 827 GCTTTTGA GGCTAGCTACAACGA GTGCTTGT 2214

262 CGUCAAAA G CUACAGAA 828 TTCTGTAG GGCTAGCTACAACGA TTTTGACG 2215

326 GUAUCAUC G UGAUGCUU 829 AAGCATCA GGCTAGCTACAACGA GATGATAC 2216

342 UCUCUGAA G UUCUGCUA 830 TAGCAGAA GGCTAGCTACAACGA TTCAGAGA 2217

368 GAUCUGCA G CUUGCCAC 831 GTGGCAAG GGCTAGCTACAACGA TGCAGATC 2218

381 CCACAUCA G CUUAAAAU 832 ATTTTAAG GGCTAGCTACAACGA TGATGTGG 2219

443 CUUCCUGA G UAGAAGAG 833 CTCTTCTA GGCTAGCTACAACGA TCAGGAAG 2220

451 GUAGAAGA G UUUCUUUG 834 CAAAGAAA GGCTAGCTACAACGA TCTTCTAC 2221

467 GUGAAAAG G UCAAGAUU 835 AATCTTGA GGCTAGCTACAACGA CTTTTCAC 2222

537 UGAAAAGG G CUUUAUUU 836 AAATAAAG GGCTAGCTACAACGA CCTTTTCA 2223

568 CAAAAUAA G UGUAUAAA 837 TTTATACA GGCTAGCTACAACGA TTATTTTG 2224

603 UCAACAUG G CUCACAAA 838 TTTGTGAG GGCTAGCTACAACGA CATGTTGA 2225

644 GAUGAAGA G UUUAGUUU 839 AAACTAAA GGCTAGCTACAACGA TCTTCATC 2226

649 AGAGUUUA G UUUUAAAA 840 TTTTAAAA GGCTAGCTACAACGA TAAACTCT 2227

673 GCCAACAA G UUCACUUC 841 GAAGTGAA GGCTAGCTACAACGA TTGTTGGC 2228

691 UAUAUAAA G CAUUAUUU 842 AAATAATG GGCTAGCTACAACGA TTTATATA 2229

713 CUUUUGAG G UGAAUAUA 843 TATATTCA GGCTAGCTACAACGA CTCAAAAG 2230

742 AUGUAAAA G CUUCUUUA 844 TAAAGAAG GGCTAGCTACAACGA TTTTACAT 2231

758 AAUACUAA G UAUUUUUC 845 GAAAAATA GGCTAGCTACAACGA TTAGTATT 2232

769 UUUUUCAG G UCUUCACC 846 GGTGAAGA GGCTAGCTACAACGA CTGAAAAA 2233

780 UUCACCAA G UAUCAAAG 847 CTTTGATA GGCTAGCTACAACGA TTGGTGAA 2234

788 GUAUCAAA G UAAUAACA 848 TGTTATTA GGCTAGCTACAACGA TTTGATAC 2235

805 CAAAUGAA G UGUCAUUA 849 TAATGACA GGCTAGCTACAACGA TTCATTTG 2236

823 UCAAAAUA G UCCACUGA 850 TCAGTGGA GGCTAGCTACAACGA TATTTTGA 2237

872 UAUUUGUA G UAACUAUC 851 GATAGTTA GGCTAGCTACAACGA TACAAATA 2238

941 CUUUUAAA G UUGAUGAG 852 CTCATCAA GGCTAGCTACAACGA TTTAAAAG 2239

956 AGAAUCAA G UAUGGAAA 853 TTTCCATA GGCTAGCTACAACGA TTGATTCT 2240

966 AUGGAAAA G UAAGGCCA 854 TGGCCTTA GGCTAGCTACAACGA TTTTCCAT 2241

971 AAAGUAAG G CCAUACUC 855 GAGTATGG GGCTAGCTACAACGA CTTACTTT 2242

1003 CCUUUUAA G UAAUUUUU 856 AAAAATTA GGCTAGCTACAACGA TTAAAAGG 2243

1033 GAAUUCUA G UACAUGUA 857 TACATGTA GGCTAGCTACAACGA TAGAATTC 2244

1043 ACAUGUAG G UAAAUCAU 858 ATGATTTA GGCTAGCTACAACGA CTACATGT 2245

1091 GAGAACUG G UGGUUAAU 859 ATTAACCA GGCTAGCTACAACGA CAGTTCTC 2246

1094 AACUGGUG G UUAAUAUG 860 CATATTAA GGCTAGCTACAACGA CACCAGTT 2247

1108 AUGUGACA G UGAGAUUA 861 TAATCTCA GGCTAGCTACAACGA TGTCACAT 2248

1117 UGAGAUUA G UCAUAUCA 862 TGATATGA GGCTAGCTACAACGA TAATCTCA 2249

1163 CAUUUAAG G CACUGUAG 863 CTACAGTG GGCTAGCTACAACGA CTTAAATG 2250

1171 GCACUGUA G UGAAUUAU 864 ATAATTCA GGCTAGCTACAACGA TACAGTGC 2251 Table 28

1184 UUAUCUGA G CUAGAGUU 865 AACTCTAG GGCTAGCTACAACGA TCAGATAA 2252

1190 GAGCUAGA G UUACCUAG 866 CTAGGTAA GGCTAGCTACAACGA TCTAGCTC 2253

1198 GUUACCUA G CUUACCAU 867 ATGGTAAG GGCTAGCTACAACGA TAGGTAAC 2254

1257 UUUUGCAG G UUGUCUUC 868 GAAGACAA GGCTAGCTACAACGA CTGCAAAA 2255

1273 CCAUUCCA G CCUAACAU 869 ATGTTAGG GGCTAGCTACAACGA TGGAATGG 2256

1291 CAAUGCAG G CAAGGAAA 870 TTTCCTTG GGCTAGCTACAACGA CTGCATTG 2257

1314 GAUUUCCA G UGACAGAA 871 TTCTGTCA GGCTAGCTACAACGA TGGAAATC 2258

1339 UAUCUCAA G UAUUUUUU 872 AAAAAATA GGCTAGCTACAACGA TTGAGATA 2259

1416 ACUUGUUG G CCCAUCUA 873 TAGATGGG GGCTAGCTACAACGA CAACAAGT 2260

1436 CAUCUACA G CUGACCCU 874 AGGGTCAG GGCTAGCTACAACGA TGTAGATG 2261

1456 ACAUGGGG G UUAGGGGA 875 TCCCCTAA GGCTAGCTACAACGA CCCCATGT 2262

1465 UUAGGGGA G CUGACAAU 876 ATTGTCAG GGCTAGCTACAACGA TCCCCTAA 2263

1476 GACAAUUC G UGGGUCCG 877 CGGACCCA GGCTAGCTACAACGA GAATTGTC 2264

1480 AUUCGUGG G UCCGCAAA 878 TTTGCGGA GGCTAGCTACAACGA CCACGAAT 2265

1506 ACCUAAUA G CCUACUAU 879 ATAGTAGG GGCTAGCTACAACGA TATTAGGT 2266

1545 CAUAAACA G UAAAUUAA 880 TTAATTTA GGCTAGCTACAACGA TGTTTATG 2267

1566 UAUUUUGC G UGUUAUAU 881 ATATAACA GGCTAGCTACAACGA GCAAAATA 2268

1603 ACAAUAAA G UAAGCUAG 882 CTAGCTTA GGCTAGCTACAACGA TTTATTGT 2269

1607 UAAAGUAA G CUAGAGAA 883 TTCTCTAG GGCTAGCTACAACGA TTACTTTA 2270

13 GUCAGAAA A CUCCCCAG 884 CTGGGGAG GGCTAGCTACAACGA TTTCTGAC 2271

26 CCAGCUAA A CACCCGUA 885 TACGGGTG GGCTAGCTACAACGA TTAGCTGG 2272

28 AGCUAAAC A CCCGUAAG 886 CTTACGGG GGCTAGCTACAACGA GTTTAGCT 2273

37 CCCGUAAG A CUUCAUAC 887 GTATGAAG GGCTAGCTACAACGA CTTACGGG 2274

42 AAGACUUC A UACAACAC 888 GTGTTGTA GGCTAGCTACAACGA GAAGTCTT 2275

47 UUCAUACA A CACAAUAC 889 GTATTGTG GGCTAGCTACAACGA TGTATGAA 2276

49 CAUACAAC A CAAUACUC 890 GAGTATTG GGCTAGCTACAACGA GTTGTATG 2277

52 ACAACACA A UACUCUAU 891 ATAGAGTA GGCTAGCTACAACGA TGTGTTGT 2278

67 AUACUGUG A UGAUCACA 892 TGTGATCA GGCTAGCTACAACGA CACAGTAT 2279

70 CUGUGAUG A UCACAGCU 893 AGCTGTGA GGCTAGCTACAACGA CATCACAG 2280

73 UGAUGAUC A CAGCUGCC 894 GGCAGCTG GGCTAGCTACAACGA GATCATCA 2281

100 AAAAGAAG A CAGUUAUC 895 GATAACTG GGCTAGCTACAACGA CTTCTTTT 2282

111 GUUAUCUC A UAUUUGGC 896 GCCAAATA GGCTAGCTACAACGA GAGATAAC 2283

144 UUCUCUCG A CCACUUAA 897 TTAAGTGG GGCTAGCTACAACGA CGAGAGAA 2284

147 UCUCGACC A CUUAAAAC 898 GTTTTAAG GGCTAGCTACAACGA GGTCGAGA 2285

154 CACUUAAA A CUUCAGAC 899 GTCTGAAG GGCTAGCTACAACGA TTTAAGTG 2286

161 AACUUCAG A CUUCCUGU 900 ACAGGAAG GGCTAGCTACAACGA CTGAAGTT 2287

182 CUGGUAUC A UGGAGAAA 901 TTTCTCCA GGCTAGCTACAACGA GATACCAG 2288

196 AAAGUCCA A UACCUCAC 902 GTGAGGTA GGCTAGCTACAACGA TGGACTTT 2289

203 AAUACCUC A CUCGCUCA 903 TGAGCGAG GGCTAGCTACAACGA GAGGTATT 2290

230 GAGCCUCA A CCAUUGAA 904 TTCAATGG GGCTAGCTACAACGA TGAGGCTC 2291

233 CCUCAACC A UUGAAAUG 905 CATTTCAA GGCTAGCTACAACGA GGTTGAGG 2292

239 CCAUUGAA A UGCCUCAA 906 TTGAGGCA GGCTAGCTACAACGA TTCAATGG 2293

247 AUGCCUCA A CAAGCACG 907 CGTGCTTG GGCTAGCTACAACGA TGAGGCAT 2294

253 CAACAAGC A CGUCAAAA 908 TTTTGACG GGCTAGCTACAACGA GCTTGTTG 2295

270 GCUACAGA A UCUAUUUA 909 TAAATAGA GGCTAGCTACAACGA TCTGTAGC 2296

282 AUUUAUCA A UUUCUGUC 910 GACAGAAA GGCTAGCTACAACGA TGATAAAT 2297

293 UCUGUCUC A UCUUAAUA 911 TATTAAGA GGCTAGCTACAACGA GAGACAGA 2298 Table 28

299 UCAUCUUA A UAUGUCUC 912 GAGACATA GGCTAGCTACAACGA TAAGATGA 2299

314 UCUUGCUG A UCUGUAUC 913 GATACAGA GGCTAGCTACAACGA CAGCAAGA 2300

323 UCUGUAUC A UCGUGAUG 914 CATCACGA GGCTAGCTACAACGA GATACAGA 2301

329 UCAUCGUG A UGCUUCUC 915 GAGAAGCA GGCTAGCTACAACGA CACGATGA 2302

353 CUGCUACA A CCUCUAGA 916 TCTAGAGG GGCTAGCTACAACGA TGTAGCAG 2303

361 ACCUCUAG A UCUGCAGC 917 GCTGCAGA GGCTAGCTACAACGA CTAGAGGT 2304

375 AGCUUGCC A CAUCAGCU 918 AGCTGATG GGCTAGCTACAACGA GGCAAGCT 2305

377 CUUGCCAC A UCAGCUUA 919 TAAGCTGA GGCTAGCTACAACGA GTGGCAAG 2306

388 AGCUUAAA A UCUGUCAU 920 ATGACAGA GGCTAGCTACAACGA TTTAAGCT 2307

395 AAUCUGUC A UCCCAUGC 921 GCATGGGA GGCTAGCTACAACGA GACAGATT 2308

400 GUCAUCCC A UGCAGACA 922 TGTCTGCA GGCTAGCTACAACGA GGGATGAC 2309

406 CCAUGCAG A CAGGAAAA 923 TTTTCCTG GGCTAGCTACAACGA CTGCATGG 2310

414 ACAGGAAA A CAAUAUUG 924 CAATATTG GGCTAGCTACAACGA TTTCCTGT 2311

417 GGAAAACA A UAUUGUAU 925 ATACAATA GGCTAGCTACAACGA TGTTTTCC 2312

427 AUUGUAUA A CAGACCAC 926 GTGGTCTG GGCTAGCTACAACGA TATACAAT 2313

431 UAUAACAG A CCACUUCC 927 GGAAGTGG GGCTAGCTACAACGA CTGTTATA 2314

434 AACAGACC A CUUCCUGA 928 TCAGGAAG GGCTAGCTACAACGA GGTCTGTT 2315

473 AGGUCAAG A UUAAGACU 929 AGTCTTAA GGCTAGCTACAACGA CTTGACCT 2316

479 AGAUUAAG A CUAAAACU 930 AGTTTTAG GGCTAGCTACAACGA CTTAATCT 2317

485 AGACUAAA A CUUAUUGU 931 ACAATAAG GGCTAGCTACAACGA TTTAGTCT 2318

498 UUGUUACC A UAUGUAUU 932 AATACATA GGCTAGCTACAACGA GGTAACAA 2319

508 AUGUAUUC A UCUGUUGG 933 CCAACAGA GGCTAGCTACAACGA GAATACAT 2320

517 UCUGUUGG A UCUUGUAA 934 TTACAAGA GGCTAGCTACAACGA CCAACAGA 2321

526 UCUUGUAA A CAUGAAAA 935 TTTTCATG GGCTAGCTACAACGA TTACAAGA 2322

528 UUGUAAAC A UGAAAAGG 936 CCTTTTCA GGCTAGCTACAACGA GTTTACAA 2323

552 UUUCAAAA A UUAACUUC 937 GAAGTTAA GGCTAGCTACAACGA TTTTGAAA 2324

556 AAAAAUUA A CUUCAAAA 938 TTTTGAAG GGCTAGCTACAACGA TAATTTTT 2325

564 ACUUCAAA A UAAGUGUA 939 TACACTTA GGCTAGCTACAACGA TTTGAAGT 2326

577 UGUAUAAA A UGCAACUG 940 CAGTTGCA GGCTAGCTACAACGA TTTATACA 2327

582 AAAAUGCA A CUGUUGAU 941 ATCAACAG GGCTAGCTACAACGA TGCATTTT 2328

589 AACUGUUG A UUUCCUCA 942 TGAGGAAA GGCTAGCTACAACGA CAACAGTT 2329

598 UUUCCUCA A CAUGGCUC 943 GAGCCATG GGCTAGCTACAACGA TGAGGAAA 2330

600 UCCUCAAC A UGGCUCAC 944 GTGAGCCA GGCTAGCTACAACGA GTTGAGGA 2331

607 CAUGGCUC A CAAAUUUC 945 GAAATTTG GGCTAGCTACAACGA GAGCCATG 2332

611 GCUCACAA A UUUCUAUC 946 GATAGAAA GGCTAGCTACAACGA TTGTGAGC 2333

624 UAUCCCAA A UCUUUUCU 947 AGAAAAGA GGCTAGCTACAACGA TTGGGATA 2334

637 UUCUGAAG A UGAAGAGU 948 ACTCTTCA GGCTAGCTACAACGA CTTCAGAA 2335

657 GUUUUAAA A CUGCACUG 949 CAGTGCAG GGCTAGCTACAACGA TTTAAAAC 2336

662 AAAACUGC A CUGCCAAC 950 GTTGGCAG GGCTAGCTACAACGA GCAGTTTT 2337

669 CACUGCCA A CAAGUUCA 951 TGAACTTG GGCTAGCTACAACGA TGGCAGTG 2338

677 ACAAGUUC A CUUCAUAU 952 ATATGAAG GGCTAGCTACAACGA GAACTTGT 2339

682 UUCACUUC A UAUAUAAA 953 TTTATATA GGCTAGCTACAACGA GAAGTGAA 2340

693 UAUAAAGC A UUAUUUUU 954 AAAAATAA GGCTAGCTACAACGA GCTTTATA 2341

717 UGAGGUGA A UAUAAUUU 955 AAATTATA GGCTAGCTACAACGA TCACCTCA 2342

722 UGAAUAUA A UUUAUAUU 956 AATATAAA GGCTAGCTACAACGA TATATTCA 2343

734 AUAUUACA A UGUAAAAG 957 CTTTTACA GGCTAGCTACAACGA TGTAATAT 2344

751 CUUCUUUA A UACUAAGU 958 ACTTAGTA GGCTAGCTACAACGA TAAAGAAG 2345 Table 28

775 AGGUCUUC A CCAAGUAU 959 ATACTTGG GGCTAGCTACAACGA GAAGACCT 2346

791 UCAAAGUA A UAACACAA 960 TTGTGTTA GGCTAGCTACAACGA TACTTTGA 2347

794 AAGUAAUA A CACAAAUG 961 CATTTGTG GGCTAGCTACAACGA TATTACTT 2348

796 GUAAUAAC A CAAAUGAA 962 TTCATTTG GGCTAGCTACAACGA GTTATTAC 2349

800 UAACACAA A UGAAGUGU 963 ACACTTCA GGCTAGCTACAACGA TTGTGTTA 2350

810 GAAGUGUC A UUAUUCAA 964 TTGAATAA GGCTAGCTACAACGA GACACTTC 2351

820 UAUUCAAA A UAGUCCAC 965 GTGGACTA GGCTAGCTACAACGA TTTGAATA 2352

827 AAUAGUCC A CUGACUCC 966 GGAGTCAG GGCTAGCTACAACGA GGACTATT 2353

831 GUCCACUG A CUCCUCAC 967 GTGAGGAG GGCTAGCTACAACGA CAGTGGAC 2354

838 GACUCCUC A CAUCUGUU 968 AACAGATG GGCTAGCTACAACGA GAGGAGTC 2355

840 CUCCUCAC A UCUGUUAU 969 ATAACAGA GGCTAGCTACAACGA GTGAGGAG 2356

862 UAUAAAGA A CUAUUUGU 970 ACAAATAG GGCTAGCTACAACGA TCTTTATA 2357

875 UUGUAGUA A CUAUCAGA 971 TCTGATAG GGCTAGCTACAACGA TACTACAA 2358

884 CUAUCAGA A UCUACAUU 972 AATGTAGA GGCTAGCTACAACGA TCTGATAG 2359

890 GAAUCUAC A UUCUAAAA 973 TTTTAGAA GGCTAGCTACAACGA GTAGATTC 2360

898 AUUCUAAA A CAGAAAUU 974 AATTTCTG GGCTAGCTACAACGA TTTAGAAT 2361

904 AAACAGAA A UUGUAUUU 975 AAATACAA GGCTAGCTACAACGA TTCTGTTT 2362

923 UCUAUGCC A CAUUAACA 976 TGTTAATG GGCTAGCTACAACGA GGCATAGA 2363

925 UAUGCCAC A UUAACAUC 977 GATGTTAA GGCTAGCTACAACGA GTGGCATA 2364

929 CCACAUUA A CAUCUUUU 978 AAAAGATG GGCTAGCTACAACGA TAATGTGG 2365

931 ACAUUAAC A UCUUUUAA 979 TTAAAAGA GGCTAGCTACAACGA GTTAATGT 2366

945 UAAAGUUG A UGAGAAUC 980 GATTCTCA GGCTAGCTACAACGA CAACTTTA 2367

951 UGAUGAGA A UCAAGUAU 981 ATACTTGA GGCTAGCTACAACGA TCTCATCA 2368

974 GUAAGGCC A UACUCUUA 982 TAAGAGTA GGCTAGCTACAACGA GGCCTTAC 2369

984 ACUCUUAC A UAAUAAAA 983 TTTTATTA GGCTAGCTACAACGA GTAAGAGT 2370

987 CUUACAUA A UAAAAUUC 984 GAATTTTA GGCTAGCTACAACGA TATGTAAG 2371

992 AUAAUAAA A UUCCUUUU 985 AAAAGGAA GGCTAGCTACAACGA TTTATTAT 2372

1006 UUUAAGUA A UUUUUUCA 986 TGAAAAAA GGCTAGCTACAACGA TACTTAAA 2373

1019 UUCAAAGA A UCACAGAA 987 TTCTGTGA GGCTAGCTACAACGA TCTTTGAA 2374

1022 AAAGAAUC A CAGAAUUC 988 GAATTCTG GGCTAGCTACAACGA GATTCTTT 2375

1027 AUCACAGA A UUCUAGUA 989 TACTAGAA GGCTAGCTACAACGA TCTGTGAT 2376

1037 UCUAGUAC A UGUAGGUA 990 TACCTACA GGCTAGCTACAACGA GTACTAGA 2377

1047 GUAGGUAA A UCAUAAAU 991 ATTTATGA GGCTAGCTACAACGA TTACCTAC 2378

1050 GGUAAAUC A UAAAUCUG 992 CAGATTTA GGCTAGCTACAACGA GATTTACC 2379

1054 AAUCAUAA A UCUGUUCU 993 AGAACAGA GGCTAGCTACAACGA TTATGATT 2380

1066 GUUCUAAG A CAUAUGAU 994 ATCATATG GGCTAGCTACAACGA CTTAGAAC 2381

1068 UCUAAGAC A UAUGAUCA 995 TGATCATA GGCTAGCTACAACGA GTCTTAGA 2382

1073 GACAUAUG A UCAACAGA 996 TCTGTTGA GGCTAGCTACAACGA CATATGTC 2383

1077 UAUGAUCA A CAGAUGAG 997 CTCATCTG GGCTAGCTACAACGA TGATCATA 2384

1081 AUCAACAG A UGAGAACU 998 AGTTCTCA GGCTAGCTACAACGA CTGTTGAT 2385

1087 AGAUGAGA A CUGGUGGU 999 ACCACCAG GGCTAGCTACAACGA TCTCATCT 2386

1098 GGUGGUUA A UAUGUGAC 1000 GTCACATA GGCTAGCTACAACGA TAACCACC 2387

1105 AAUAUGUG A CAGUGAGA 1001 TCTCACTG GGCTAGCTACAACGA CACATATT 2388

1113 ACAGUGAG A UUAGUCAU 1002 ATGACTAA GGCTAGCTACAACGA CTCACTGT 2389

1120 GAUUAGUC A UAUCACUA 1003 TAGTGATA GGCTAGCTACAACGA GACTAATC 2390

1125 GUCAUAUC A CUAAUAUA 1004 TATATTAG GGCTAGCTACAACGA GATATGAC 2391

1129 UAUCACUA A UAUACUAA 1005 TTAGTATA GGCTAGCTACAACGA TAGTGATA 2392 Table 28

1137 AUAUACUA A CAACAGAA 1006 TTCTGTTG GGCTAGCTACAACGA TAGTATAT 2393

1140 UACUAACA A CAGAAUCU 1007 AGATTCTG GGCTAGCTACAACGA TGTTAGTA 2394

1145 ACAACAGA A UCUAAUCU 1008 AGATTAGA GGCTAGCTACAACGA TCTGTTGT 2395

1150 AGAAUCUA A UCUUCAUU 1009 AATGAAGA GGCTAGCTACAACGA TAGATTCT 2396

1156 UAAUCUUC A UUUAAGGC 1010 GCCTTAAA GGCTAGCTACAACGA GAAGATTA 2397

1165 UUUAAGGC A CUGUAGUG 1011 CACTACAG GGCTAGCTACAACGA GCCTTAAA 2398

1175 UGUAGUGA A UUAUCUGA 1012 TCAGATAA GGCTAGCTACAACGA TCACTACA 2399

1205 . AGCUUACC A UACUAUAU 1013 ATATAGTA GGCTAGCTACAACGA GGTAAGCT 2400

1221 UCUUUGGA A UCAUGAAA 1014 TTTCATGA GGCTAGCTACAACGA TCCAAAGA 2401

1224 UUGGAAUC A UGAAACCU 1015 AGGTTTCA GGCTAGCTACAACGA GATTCCAA 2402

1229 AUCAUGAA A CCUUAAGA 1016 TCTTAAGG GGCTAGCTACAACGA TTCATGAT 2403

1237 ACCUUAAG A CUUCAGAA 1017 TTCTGAAG GGCTAGCTACAACGA CTTAAGGT 2404

1245 ACUUCAGA A UGAUUUUG 1018 CAAAATCA GGCTAGCTACAACGA TCTGAAGT 2405

1248 UCAGAAUG A UUUUGCAG 1019 CTGCAAAA GGCTAGCTACAACGA CATTCTGA 2406

1267 UGUCUUCC A UUCCAGCC 1020 GGCTGGAA GGCTAGCTACAACGA GGAAGACA 2407

1278 CCAGCCUA A CAUCCAAU 1021 ATTGGATG GGCTAGCTACAACGA TAGGCTGG 2408

1280 AGCCUAAC A UCCAAUGC 1022 GCATTGGA GGCTAGCTACAACGA GTTAGGCT 2409

1285 AACAUCCA A UGCAGGCA 1023 TGCCTGCA GGCTAGCTACAACGA TGGATGTT 2410

1300 CAAGGAAA A UAAAAGAU 1024 ATCTTTTA GGCTAGCTACAACGA TTTCCTTG 2411

1307 AAUAAAAG A UUUCCAGU 1025 ACTGGAAA GGCTAGCTACAACGA CTTTTATT 2412

1317 UUCCAGUG A CAGAAAAA 1026 TTTTTCTG GGCTAGCTACAACGA CACTGGAA 2413

1325 ACAGAAAA A UAUAUUAU 1027 ATAATATA GGCTAGCTACAACGA TTTTCTGT 2414

1352 UUUUAAAA A UAUAUGAA 1028 TTCATATA GGCTAGCTACAACGA TTTTAAAA 2415

1360 AUAUAUGA A UUCUCUCU 1029 AGAGAGAA GGCTAGCTACAACGA TCATATAT 2416

1373 CUCUCCAA A UAUUAACU 1030 AGTTAATA GGCTAGCTACAACGA TTGGAGAG 2417

1379 AAAUAUUA A CUAAUUAU 1031 ATAATTAG GGCTAGCTACAACGA TAATATTT 2418

1383 AUUAACUA A UUAUUAGA 1032 TCTAATAA GGCTAGCTACAACGA TAGTTAAT 2419

1391 AUUAUUAG A UUAUAUUU 1033 AAATATAA GGCTAGCTACAACGA CTAATAAT 2420

1404 AUUUUGAA A UGAACUUG 1034 CAAGTTCA GGCTAGCTACAACGA TTCAAAAT 2421

1408 UGAAAUGA A CUUGUUGG 1035 CCAACAAG GGCTAGCTACAACGA TCATTTCA 2422

1420 GUUGGCCC A UCUAUUAC 1036 GTAATAGA GGCTAGCTACAACGA GGGCCAAC 2423

1429 UCUAUUAC A UCUACAGC 1037 GCTGTAGA GGCTAGCTACAACGA GTAATAGA 2424

1440 UACAGCUG A CCCUUGAA 1038 TTCAAGGG GGCTAGCTACAACGA CAGCTGTA 2425

1448 ACCCUUGA A CAUGGGGG 1039 CCCCCATG GGCTAGCTACAACGA TCAAGGGT 2426

1450 CCUUGAAC A UGGGGGUU 1040 AACCCCCA GGCTAGCTACAACGA GTTCAAGG 2427

1469 GGGAGCUG A CAAUUCGU 1041 ACGAATTG GGCTAGCTACAACGA CAGCTCCC 2428

1472 AGCUGACA A UUCGUGGG 1042 CCCACGAA GGCTAGCTACAACGA TGTCAGCT 2429

1489 UCCGCAAA A UCUUAACU 1043 AGTTAAGA GGCTAGCTACAACGA TTTGCGGA 2430

1495 AAAUCUUA A CUACCUAA 1044 TTAGGTAG GGCTAGCTACAACGA TAAGATTT 2431

1503 ACUACCUA A UAGCCUAC 1045 GTAGGCTA GGCTAGCTACAACGA TAGGTAGT 2432

1517 UACUAUUG A CCAUAAAC 1046 GTTTATGG GGCTAGCTACAACGA CAATAGTA 2433

1520 UAUUGACC A UAAACCUU 1047 AAGGTTTA GGCTAGCTACAACGA GGTCAATA 2434

1524 GACCAUAA A CCUUACUG 1048 CAGTAAGG GGCTAGCTACAACGA TTATGGTC 2435

1533 CCUUACUG A UAACAUAA 1049 TTATGTTA GGCTAGCTACAACGA CAGTAAGG 2436

1536 UACUGAUA A CAUAAACA 1050 TGTTTATG GGCTAGCTACAACGA TATCAGTA 2437

1538 CUGAUAAC A UAAACAGU 1051 ACTGTTTA GGCTAGCTACAACGA GTTATCAG 2438

1542 UAACAUAA A CAGUAAAU 1052 ATTTACTG GGCTAGCTACAACGA TTATGTTA 2439 Table 28

Input Sequence = PLN. Cut Site = R/Y

Stem Length = 8 . Core Sequence = GGCTAGCTACAACGA

PLN (Homo sapiens phospholamban (PLN) mRNA.; 1635 bp)

Table 29

Table 29: Human Phospholamban (PLN) amberzyme Ribozyme and Target Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

64 UCUAUACU G UGAUGAUC 732 GAUCAUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUAUAGA 2447

66 UAUACUGU G AUGAUCAC 733 GUGAUCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGUAUA 2448

69 ACUGUGAU G AUCACAGC 734 GCUGUGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCACAGU 2449

79 UCACAGCU G CCAAGGCU 735 AGCCUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUGUGA 2450

121 AUUUGGCU G CCAGCUUU 736 AAAGCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCAAAU 2451

143 UUUCUCUC G ACCACUUA 737 UAAGUGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGAGAAA 2452

168 GACUUCCU G UCCUGCUG 738 CAGCAGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAAGUC 2453

173 CCUGUCCU G CUGGUAUC 739 GAUACCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGACAGG 2454

207 CCUCACUC G CUCAGCUA 740 UAGCUGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGUGAGG 2455

236 CAACCAUU G AAAUGCCU 741 AGGCAUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUGGUUG 2456

241 AUUGAAAU G CCUCAACA 742 UGUUGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUCAAU 2457

288 CAAUUUCU G UCUCAUCU 743 AGAUGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAAUUG 2458

303 CUUAAUAU G UCUCUUGC 744 GCAAGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAUUAAG 2459

310 UGUCUCUU G CUGAUCUG 745 CAGAUCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGAGACA 2460

313 CUCUUGCU G AUCUGUAU 746 AUACAGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCAAGAG 2461

318 GCUGAUCU G UAUCAUCG 747 CGAUGAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAUCAGC 2462

328 AUCAUCGU G AUGCUUCU 748 AGAAGCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACGAUGAU 2463

331 AUCGUGAU G CUUCUCUG 749 CAGAGAAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCACGAU 2464

339 GCUUCUCU G AAGUUCUG 750 CAGAACUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAGAAGC 2465

347 GAAGUUCU G CUACAACC 751 GGUUGUAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAACUUC 2466

365 CUAGAUCU G CAGCUUGC 752 GCAAGCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAUCUAG 2467

372 UGCAGCUU G CCACAUCA 753 UGAUGUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGCUGCA 2468

392 UAAAAUCU G UCAUCCCA 754 UGGGAUGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAUUUUA 2469

402 CAUCCCAU G CAGACAGG 755 CCUGUCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGGGAUG 2470

422 ACAAUAUU G UAUAACAG 756 CUGUUAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUAUUGU 2471

441 CACUUCCU G AGUAGAAG 757 CUUCUACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGAAGUG 2472

459 GUUUCUUU G UGAAAAGG 758 CCUUUUCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAGAAAC 2473

461 UUCUUUGU G AAAAGGUC 759 GACCUUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAAAGAA 2474

Table 29

492 AACUUAUU G UUACCAUA 760 UAUGGUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUAAGUU 2475

502 UACCAUAU G UAUUCAUC 761 GAUGAAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAUGGUA 2476

512 AUUCAUCU G UUGGAUCU 762 AGAUCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAUGAAU 2477

522 UGGAUCUU G UAAACAUG 763 CAUGUUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAUCCA 2478

530 GUAAACAU G AAAAGGGC 764 GCCCUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGUUUAC 2479

570 AAAUAAGU G UAUAAAAU 765 AUUUUAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUUAUUU 2480

579 UAUAAAAU G CAACUGUU 766 AACAGUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUUAUA 2481

585 AUGCAACU G UUGAUUUC 767 GAAAUCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUGCAU 2482

588 CAACUGUU G AUUUCCUC 768 GAGGAAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAGUUG 2483

633 UCUUUUCU G AAGAUGAA 769 UUCAUCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAAAAGA 2484

639 CUGAAGAU G AAGAGUUU 770 AAACUCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCUUCAG 2485

660 UUAAAACU G CACUGCCA 771 UGGCAGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUUUUAA 2486

665 ACUGCACU G CCAACAAG 772 CUUGUUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUGCAGU 2487

710 ACUCUUUU G AGGUGAAU 773 AUUCACCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAAGAGU 2488

715 UUUGAGGU G AAUAUAAU 774 AUUAUAUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCUCAAA 2489

736 AUUACAAU G UAAAAGCU 775 AGCUUUUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUUGUAAU 2490

802 ACACAAAU G AAGUGUCA 776 UGACACUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUUUGUGU 2491

807 AAUGAAGU G UCAUUAUU 777 AAUAAUGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACUUCAUU 2492

830 AGUCCACU G ACUCCUCA 778 UGAGGAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUGGACU 2493

844 UCACAUCU G UUAUCUUA 779 UAAGAUAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAUGUGA 2494

869 AACUAUUU G UAGUAACU 780 AGUUACUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAUAGUU 2495

907 CAGAAAUU G UAUUUUUU 781 AAAAAAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUUUCUG 2496

920 UUUUCUAU G CCACAUUA 782 UAAUGUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAGAAAA 2497

944 UUAAAGUU G AUGAGAAU 783 AUUCUCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AACUUUAA 2498

947 AAGUUGAU G AGAAUCAA 784 UUGAUUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCAACUU 2499

1039 UAGUACAU G UAGGUAAA 785 UUUACCUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGUACUA 2500

1058 AUAAAUCU G UUCUAAGA 786 UCUUAGAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAUUUAU 2501

1072 AGACAUAU G AUCAACAG 787 CUGUUGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAUGUCU 2502

1083 CAACAGAU G AGAACUGG 788 CCAGUUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCUGUUG 2503

1102 GUUAAUAU G UGACAGUG 789 CACUGUCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAUUAAC 2504

1104 UAAUAUGU G ACAGUGAG 790 CUCACUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAUAUUA 2505

Table 29

1110 GUGACAGU G AGAUUAGU 791 ACUAAUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGUCAC 2506

1168 AAGGCACU G UAGUGAAU 792 AUUCACUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUGCCUU 2507

1173 ACUGUAGU G AAUUAUCU 793 AGAUAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUACAGU 2508

1182 AAUUAUCU G AGCUAGAG 794 CUCUAGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAUAAUU 2509

1226 GGAAUCAU G AAACCUUA 795 UAAGGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGAUUCC 2510

1247 UUCAGAAU G AUUUUGCA 796 UGCAAAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUCUGAA 2511

1253 AUGAUUUU G CAGGUUGU 797 ACAACCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAUCAU 2512

1260 UGCAGGUU G UCUUCCAU 798 AUGGAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACCUGCA 2513

1287 CAUCCAAU G CAGGCAAG 799 CUUGCCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUGGAUG 2514

1316 UUUCCAGU G ACAGAAAA 800 UUUUCUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGGAAA 2515

1358 AAAUAUAU G AAUUCUCU 801 AGAGAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAUAUUU 2516

1401 UAUAUUUU G AAAUGAAC 802 GUUCAUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAUAUA 2517

1406 UUUGAAAU G AACUUGUU 803 AACAAGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUCAAA 2518

1412 AUGAACUU G UUGGCCCA 804 UGGGCCAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGUUCAU 2519

1439 CUACAGCU G ACCCUUGA 805 UCAAGGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCUGUAG 2520

1446 UGACCCUU G AACAUGGG 806 CCCAUGUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGGGUCA 2521

1468 GGGGAGCU G ACAAUUCG 807 CGAAUUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCUCCCC 2522

1484 GUGGGUCC G CAAAAUCU 808 AGAUUUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGACCCAC 2523

1516 CUACUAUU G ACCAUAAA 809 UUUAUGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUAGUAG 2524

1532 ACCUUACU G AUAACAUA 810 UAUGUUAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUAAGGU 2525

1564 CAUAUUUU G CGUGUUAU 811 AUAACACG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAAUAUG 2526

1568 UUUUGCGU G UUAUAUGU 812 ACAUAUAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACGCAAAA 2527

1575 UGUUAUAU G UAUUAUAC 813 GUAUAAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAUAACA 2528

1619 GAGAAAAU G UUAUUUAG 814 CUAAAUAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUUUUCUC 2529

21 ACUCCCCA G CUAAACAC 815 GUGUUUAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGGGAGU 2530

32 AAACACCC G UAAGACUU 816 AAGUCUUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGUGUUU 2531

76 UGAUCACA G CUGCCAAG 817 CUUGGCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUGAUCA 2532

85 CUGCCAAG G CUACCUAA 818 UUAGGUAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUGGCAG 2533

103 AGAAGACA G UUAUCUCA 819 UGAGAUAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUCUUCU 2534

118 CAUAUUUG G CUGCCAGC 820 GCUGGCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAAUAUG 2535

125 GGCUGCCA G CUUUUUAU 821 AUAAAAAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGCAGCC 2536

Table 29

177 UCCUGCUG G UAUCAUGG 822 CCAUGAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCAGGA 2537

191 UGGAGAAA G UCCAAUAC 823 GUAUUGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUCUCCA 2538

212 CUCGCUCA G CUAUAAGA 824 UCUUAUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGCGAG 2539

224 UAAGAAGA G CCUCAACC 825 GGUUGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUCUUA 2540

251 CUCAACAA G CACGUCAA 826 UUGACGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUUGAG 2541

255 ACAAGCAC G UCAAAAGC 827 GCUUUUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUGCUUGU 2542

262 CGUCAAAA G CUACAGAA 828 UUCUGUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUGACG 2543

326 GUAUCAUC G UGAUGCUU 829 AAGCAUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUGAUAC 2544

342 UCUCUGAA G UUCUGCUA 830 UAGCAGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCAGAGA 2545

368 GAUCUGCA G CUUGCCAC 831 GUGGCAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAGAUC 2546

381 CCACAUCA G CUUAAAAU 832 AUUUUAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUGUGG 2547

443 CUUCCUGA G UAGAAGAG 833 CUCUUCUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAGGAAG 2548

451 GUAGAAGA G UUUCUUUG 834 CAAAGAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUCUAC 2549

467 GUGAAAAG G UCAAGAUU 835 AAUCUUGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUUUCAC 2550

537 UGAAAAGG G CUUUAUUU 836 AAAUAAAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUUUUCA 2551

568 CAAAAUAA G UGUAUAAA 837 UUUAUACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUAUUUUG 2552

603 UCAACAUG G CUCACAAA 838 UUUGUGAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUGUUGA 2553

644 GAUGAAGA G UUUAGUUU 839 AAACUAAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCUUCAUC 2554

649 AGAGUUUA G UUUUAAAA 840 UUUUAAAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAAACUCU 2555

673 GCCAACAA G UUCACUUC 841 GAAGUGAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGUUGGC 2556

691 UAUAUAAA G CAUUAUUU 842 AAAUAAUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUAUAUA 2557

713 CUUUUGAG G UGAAUAUA 843 UAUAUUCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCAAAAG 2558

742 AUGUAAAA G CUUCUUUA 844 UAAAGAAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUUACAU 2559

758 AAUACUAA G UAUUUUUC 845 GAAAAAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUAGUAUU 2560

769 UUUUUCAG G UCUUCACC 846 GGUGAAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGAAAAA 2561

780 UUCACCAA G UAUCAAAG 847 CUUUGAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGGUGAA 2562

788 GUAUCAAA G UAAUAACA 848 UGUUAUUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUGAUAC 2563

805 CAAAUGAA G UGUCAUUA 849 UAAUGACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCAUUUG 2564

823 UCAAAAUA G UCCACUGA 850 UCAGUGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAUUUUGA 2565

872 UAUUUGUA G UAACUAUC 851 GAUAGUUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UACAAAUA 2566

941 CUUUUAAA G UUGAUGAG 852 CUCAUCAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUAAAAG 2567

Table 29

956 AGAAUCAA G UAUGGAAA 853 UUUCCAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAUUCU 2568

966 AUGGAAAA G UAAGGCCA 854 UGGCCUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUCCAU 2569

971 AAAGUAAG G CCAUACUC 855 GAGUAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUACUUU 2570

1003 CCUUUUAA G UAAUUUUU 856 AAAAAUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAAAAGG 2571

1033 GAAUUCUA G UACAUGUA 857 UACAUGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGAAUUC 2572

1043 ACAUGUAG G UAAAUCAU 858 AUGAUUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUACAUGU 2573

1091 GAGAACUG G UGGUUAAU 859 AUUAACCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGUUCUC 2574

1094 AACUGGUG G UUAAUAUG 860 CAUAUUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCAGUU 2575

1108 AUGUGACA G UGAGAUUA 861 UAAUCUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUCACAU 2576

1117 UGAGAUUA G UCAUAUCA 862 UGAUAUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAUCUCA 2577

1163 CAUUUAAG G CACUGUAG 863 CUACAGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUAAAUG 2578

1171 GCACUGUA G UGAAUUAU 864 AUAAUUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACAGUGC 2579

1184 UUAUCUGA G CUAGAGUU 865 AACUCUAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCAGAUAA 2580

1190 GAGCUAGA G UUACCUAG 866 CUAGGUAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCUAGCUC 2581

1198 GUUACCUA G CUUACCAU 867 AUGGUAAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAGGUAAC 2582

1257 UUUUGCAG G UUGUCUUC 868 GAAGACAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGCAAAA 2583

1273 CCAUUCCA G CCUAACAU 869 AUGUUAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGAAUGG 2584

1291 CAAUGCAG G CAAGGAAA 870 UUUCCUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGCAUUG 2585

1314 GAUUUCCA G UGACAGAA 871 UUCUGUCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGAAAUC 2586

1339 UAUCUCAA G UAUUUUUU 872 AAAAAAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGAGAUA 2587

1416 ACUUGUUG G CCCAUCUA 873 UAGAUGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAACAAGU 2588

1436 CAUCUACA G CUGACCCU 874 AGGGUCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUAGAUG 2589

1456 ACAUGGGG G UUAGGGGA 875 UCCCCUAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCCAUGU 2590

1465 UUAGGGGA G CUGACAAU 876 AUUGUCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCCCUAA 2591

1476 GACAAUUC G UGGGUCCG 877 CGGACCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAAUUGUC 2592

1480 AUUCGUGG G UCCGCAAA 878 UUUGCGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCACGAAU 2593

1506 ACCUAAUA G CCUACUAU 879 AUAGUAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAUUAGGU 2594

1545 CAUAAACA G UAAAUUAA 880 UUAAUUUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUUUAUG 2595

1566 UAUUUUGC G UGUUAUAU 881 AUAUAACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCAAAAUA 2596

1603 ACAAUAAA G UAAGCUAG 882 CUAGCUUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUAUUGU 2597

1607 UAAAGUAA G CUAGAGAA 883 UUCUCUAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUACUUUA 2598

Table 29

CAGAGUCA G AAAACUCC 1060 GGAGUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGACUCUG 2599

ACCCGUAA G ACUUCAUA 1061 UAUGAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUACGGGU 2600

GCUGCCAA G GCUACCUA 1062 UAGGUAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGCAGC 2601

ACCUAAAA G AAGACAGU 1063 ACUGUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUAGGU 2602

UAAAAGAA G ACAGUUAU 1064 AUAACUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUUUUA 2603

UCAUAUUU G GCUGCCAG 1065 CUGGCAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUAUGA 2604

AAACUUCA σ ACUUCCUG 1066 CAGGAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAGUUU 2605

GUCCUGCU G GUAUCAUG 1067 CAUGAUAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAGGAC 2606

GGUAUCAU G GAGAAAGU 1068 ACUUUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGAUACC 2607

GUAUCAUG G AGAAAGUC 1069 GACUUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGAUAC 2608

AUCAUGGA G AAAGUCCA 1070 UGGACUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAUGAU 2609

AGCUAUAA G AAGAGCCU 1071 AGGCUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAUAGCU 2610

UAUAAGAA G AGCCUCAA 1072 UUGAGGCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCUUAUA 2611

AAGCUACA G AAUCUAUU 1073 AAUAGAUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUAGCUU 2612

AACCUCUA G AUCUGCAG 1074 CUGCAGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAGAGGUU 2613

CCCAUGCA G ACAGGAAA 1075 UUUCCUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCAUGGG 2614

UGCAGACA G GAAAACAA 1076 UUGUUUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUCUGCA 2615

GCAGACAG G AAAACAAU 1077 AUUGUUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGUCUGC 2616

GUAUAACA G ACCACUUC 1078 GAAGUGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUUAUAC 2617

CCUGAGUA G AAGAGUUU 1079 AAACUCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UACUCAGG 2618

GAGUAGAA G AGUUUCUU 1080 AAGAAACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCUACUC 2619

UGUGAAAA G GUCAAGAU 1081 AUCUUGAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUUCACA 2620

AAGGUCAA G AUUAAGAC 1082 GUCUUAAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGACCUU 2621

AAGAUUAA G ACUAAAAC 1083 GUUUUAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUAAUCUU 2622

CAUCUGUU G GAUCUUGU 1084 ACAAGAUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AACAGAUG 2623

AUCUGUUG G AUCUUGUA 1085 UACAAGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAACAGAU 2624

CAUGAAAA G GGCUUUAU 1086 AUAAAGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUUCAUG 2625

AUGAAAAG G GCUUUAUU 1087 AAUAAAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUUUCAU 2626

CUCAACAU G GCUCACAA 1088 UUGUGAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGUUGAG 2627

UUUCUGAA G AUGAAGAG 1089 CUCUUCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCAGAAA 2628

AAGAUGAA G AGUUUAGU 1090 ACUAAACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCAUCUU 2629

Table 29

712 UCUUUUGA G GUGAAUAU 1091 AUAUUCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAAAAGA 2630

768 AUUUUUCA G GUCUUCAC 1092 GUGAAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAAAAU 2631

860 AUUAUAAA G AACUAUUU 1093 AAAUAGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUAUAAU 2632

882 AACUAUCA G AAUCUACA 1094 UGUAGAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUAGUU 2633

901 CUAAAACA G AAAUUGUA 1095 UACAAUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUUAG 2634

949 GUUGAUGA G AAUCAAGU 1096 ACUUGAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAUCAAC 2635

960 UCAAGUAU G GAAAAGUA 1097 UACUUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUACUUGA 2636

961 CAAGUAUG G AAAAGUAA 1098 UUACUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUACUUG 2637

970 AAAAGUAA G GCCAUACU 1099 AGUAUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUACUUUU 2638

1017 UUUUCAAA G AAUCACAG 1100 CUGUGAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGAAAA 2639

1025 GAAUCACA G AAUUCUAG 1101 CUAGAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUGAUUC 2640

1042 UACAUGUA G GUAAAUCA 1102 UGAUUUAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UACAUGUA 2641

1065 UGUUCUAA G ACAUAUGA 1103 UCAUAUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUAGAACA 2642

1080 GAUCAACA G AUGAGAAC 1104 GUUCUCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUUGAUC 2643

1085 ACAGAUGA G AACUGGUG 1105 CACCAGUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCAUCUGU 2644

1090 UGAGAACU G GUGGUUAA 1106 UUAACCAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUUCUCA 2645

1093 GAACUGGU G GUUAAUAU 1107 AUAUUAAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCAGUUC 2646

1112 GACAGUGA G AUUAGUCA 1108 UGACUAAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCACUGUC 2647

1143 UAACAACA G AAUCUAAU 1109 AUUAGAUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUUGUUA 2648

1162 UCAUUUAA G GCACUGUA 1110 UACAGUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUAAAUGA 2649

1188 CUGAGCUA G AGUUACCU llll AGGUAACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAGCUCAG 2650

1218 AUAUCUUU G GAAUCAUG 1112 CAUGAUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAGAUAU 2651

1219 UAUCUUUG G AAUCAUGA 1113 UCAUGAUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAAGAUA 2652

1236 AACCUUAA G ACUUCAGA 1114 UCUGAAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUAAGGUU 2653

1243 AGACUUCA G AAUGAUUU 1115 AAAUCAUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGAAGUCU 2654

1256 AUUUUGCA G GUUGUCUU 1116 AAGACAAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCAAAAU 2655

1290 CCAAUGCA G GCAAGGAA 1117 UUCCUUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCAUUGG 2656

1295 GCAGGCAA G GAAAAUAA 1118 UUAUUUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGCCUGC 2657

1296 CAGGCAAG G AAAAUAAA 1119 UUUAUUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUGCCUG 2658

1306 AAAUAAAA G AUUUCCAG 1120 CUGGAAAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUUAUUU 2659

1320 CAGUGACA G AAAAAUAU 1121 AUAUUUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUCACUG 2660

Table 29

1390 AAUUAUUA G AUUAUAUU 1122 AAUAUAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAUAAUU 2661

1415 AACUUGUU G GCCCAUCU 1123 AGAUGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAAGUU 2662

1452 UUGAACAU G GGGGUUAG 1124 CUAACCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGUUCAA 2663

1453 UGAACAUG G GGGUUAGG 1125 CCUAACCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGUUCA 2664

1454 GAACAUGG G GGUUAGGG 1126 CCCUAACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAUGUUC 2665

1455 AACAUGGG G GUUAGGGG 1127 CCCCUAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAUGUU 2666

1460 GGGGGUUA G GGGAGCUG 1128 CAGCUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAACCCCC 2667

1461 GGGGUUAG G GGAGCUGA 1129 UCAGCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAACCCC 2668

1462 GGGUUAGG G GAGCUGAC 1130 GUCAGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUAACCC 2669

1463 GGUUAGGG G AGCUGACA 1131 UGUCAGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCUAACC 2670

1478 CAAUUCGU G GGUCCGCA 1132 UGCGGACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGAAUUG 2671

1479 AAUUCGUG G GUCCGCAA 1133 UUGCGGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACGAAUU 2672

1611 GUAAGCUA G AGAAAAUG 1134 CAUUUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGCUUAC 2673

1613 AAGCUAGA G AAAAUGUU 1135 AACAUUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCUAGCUU 2674

1627 GUUAUUUA G AAAAUCAU 1136 AUGAUUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAAAUAAC 2675

Input Sequence = PLN. Cut Site = Gl.

Stem Length = 8. Core Sequence = GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG

PLN (Homo sapiens phospholamban (PLN) mRNA.; 1635 bp)

Table 30 Table 30: Human Phospholamban (PLN) Antisense and Target Sequence

Table 30

Table 30

Table 30

Table 30

Table 30

Table 30

Table 30

Table 30

Table 30

Table 30

Table 30

Table 30

Input Sequence = PLN

Oligo Length = 25

PLN (Homo sapiens phospholamban (PLN) mRNA.; 1635 bp) Table 31

Table 31: Anti-Her2 Ribozyme and Substrate Sequence

RPI nt. Seq ID Seq ID NOS Position Nos Nos

NCH Ribozyme Sequence NCH Substrate Sequence

17214 175 asgscsuscca cUGAuGaggccguuaggccGaa Igugcuc B GAGCACC A UGGAGCU

17215 212 gsasgsgsgcg cUGAuGaggccguuaggccGaa Igaggag B CUCCUCC U CGCCCUC

17216 261 uscsasusguc cUGAuGaggccguuaggccGaa Iugccgg B CCGGCAC A GACAUGA

17217 297 cscsasgsgug cUGAuGaggccguuaggccGaa lucucgg B CCGAGAC C CACCUGG

17218 381 ascsasgsgcu cUGAuGaggccguuaggccGaa Icauugg B CCAAUGC C AGCCUGU

17219 619 cscsususuca cUGAuGaggccguuaggccGaa Iaucucu B AGAGAUC U UGAAAGG

17220 665 csgsusgsucc cUGAuGaggccguuaggccGaa Iguagca B UGCUACC A GGACACG

17221 943 ususgsasagu cUGAuGaggccguuaggccGaa Iaggcag B CUGCCUC C ACUUCAA

17222 944 gsususgsaag cUGAuGaggccguuaggccGaa Igaggca B UGCCUCC A CUUCAAC

17223 946 usgsgsusuga cUGAuGaggccguuaggccGaa Iuggagg B CCUCCAC U UCAACCA

17224 993 usgsususgua cUGAuGaggccguuaggccGaa Iugacca B UGGUCAC C UACAACA

17225 997 uscsusgsugu cUGAuGaggccguuaggccGaa Iuaggug B CACCUAC A ACACAGA

17226 1000 gsusgsuscug cUGAuGaggccguuaggccGaa Iuuguag B CUACAAC A CAGACAC

17227 1017 usgsgsgscau cUGAuGaggccguuaggccGaa lacucaa B UUGAGUC C AUGCCCA

17228 1078 asgsgsusagu cUGAuGaggccguuaggccGaa Iuaggga B UCCCUAC A ACUACCU

17229 1201 asgsascscau cUGAuGaggccguuaggccGaa Icacacu B AGUGUGC U AUGGUCU

17230 1285 csuscscscaa cUGAuGaggccguuaggccGaa Iaucuuc B GAAGAUC U UUGGGAG

17231 1395 gsgsusasacc cUGAuGaggccguuaggccGaa Iugaucu B AGAUCAC A GGUUACC

17232 1413 gscscsasugc cUGAuGaggccguuaggccGaa lagaugu B ^• ACAUCUC A GCAUGGC

17233 1450 asgsgsusucu cUGAuGaggccguuaggccGaa Iaagacg B CGUCUUC C AGAACCU

17234 1624 asasgsasgcu cUGAuGaggccguuaggccGaa Iucccag B CUGGGAC C AGCUCUU

17235 1787 gscsascsucc CUGAuGaggccguuaggccGaa Igccccg B CGGGGCC A GGAGUGC

17236 2001 gscsasusgua cUGAuGaggccguuaggccGaa Iagaggu B ACCUCUC C UACAUGC

17237 2002 gsgscsasugu cUGAuGaggccguuaggccGaa Igagagg B CCUCUCC U ACAUGCC

17238 2055 asgsususgau cUGAuGaggccguuaggccGaa Iggcaag B CUUGCCC C AUCAACU

Table 31

17239 2056 csasgsusuga cUGAuGaggccguuaggccGaa Igggcaa B UUGCCCC A UCAACUG

17240 2068 csasgsgsagu cUGAuGaggccguuaggccGaa Igugcag B CUGCACC C ACUCCUG

17241 2069 ascsasgsgag cUGAuGaggccguuaggccGaa Iggugca B UGCACCC A CUCCUGU

17242 2295 cscsusgsguu cUGAuGaggccguuaggccGaa Igcaucg B CGAUGCC C AACCAGG

17243 2351 asgsasuscca cUGAuGaggccguuaggccGaa Icaccuu B AAGGUGC U UGGAUCU

17244 2373 usgsusasgac cUGAuGaggccguuaggccGaa Iugccaa B UUGGCAC A GUCUACA

17245 2570 csasusasagc cUGAuGaggccguuaggccGaa Iugucac B GUGACAC A GCUUAUG

17246 2665 asuscscsccu cUGAuGaggccguuaggccGaa Igcaauc B GAUUGCC A AGGGGAU

17247 2702 gsuscscscug cUGAuGaggccguuaggccGaa luacgag B CUCGUAC A CAGGGAC

17248 2771 cscsgsasgcc cUGAuGaggccguuaggccGaa Icccgaa B UUCGGGC U GGCUCGG

18261 2780 gsuscscsagc cUGAuGaggccguuaggccGaa Iccgagc B GCUCGGC U GCUGGAC

17249 2783 asasusgsucc cUGAuGaggccguuaggccGaa Icagccg B CGGCUGC U GGACAUU

18265 2783 asusgsuscc cUGAuGaggccguuaggccGaa Icagcc B GGCUGC U GGACAU

18267 2783 asasusgsucc cUGAuGaggcguuagccGaa ' [cagccg B CGGCUGC U GGACAUU

18269 2783 asusgsuscc cUGAuGaggcguuagccGaa : [cagcc B GGCUGC U GGACAU

18271 2783 asasusgsucc cUGAuGaggccguuaggccGaa Icagccg B CGGCUGC U GGACAUU

18273 2783 asusgsuscc cUGAuGaggccguuaggccGaa Icagcc B GGCUGC U GGACAU

18275 2783 asasusgsucc cUGAuGaggcguuagccGaa [cagccg B CGGCUGC U GGACAUU

18277 2783 asusgsuscc cUGAuGaggcguuagccGaa [cagcc B GGCUGC U GGACAU

18262 2788 uscsgsuscaa cUGAuGaggccguuaggccGaa Iuccagc B GCUGGAC A UUGACGA

17250 2799 gsgsusascuc cUGAuGaggccguuaggccGaa lucucgu B ACGAGAC A GAGUACC

18263 2935 usasasgsguu cUGAuGaggccguuaggccGaa Igcccca B UGGGGCC A AACCUUA

17251 2939 asuscsgsuaa cUGAuGaggccguuaggccGaa Iuuuggc B GCCAAAC C UUACGAU

18266 2939 uscsgsusaa cUGAuGaggccguuaggccGaa Iuuugg B CCAAAC C UUACGA

18268 2939 asuscsgsuaa cUGAuGaggcguuagccGaa [uuuggc B GCCAAAC C UUACGAU

18270 2939 uscsgsusaa cUGAuGaggcguuagccGaa [uuugg B CCAAAC C UUACGA

18272 2939 asuscsgsuaa cUGAuGaggccguuaggccGaa Iuuuggc B GCCAAAC C UUACGAU

18274 2939 uscsgsusaa cUGAuGaggccguuaggccGaa Iuuugg B CCAAAC C UUACGA

18276 2939 asuscsgsuaa cUGAuGaggcguuagccGaa [uuuggc B GCCAAAC C UUACGAU

18278 2939 uscsgsusaa cUGAuGaggcguuagccGaa [uuugg B CCAAAC C UUACGA

18264 2940 csasuscsgua cUGAuGaggccguuaggccGaa Iguuugg B CCAAACC U UACGAUG

Table 31

Table 31

17194 2003 gsgsgscsaug cUGAuGaggccguuaggccGaa Aggagag B CUCUCCU A CAUGCCC

17205 2058 usgscsasguu cUGAuGaggccguuaggccGaa Auggggc B GCCCCAU C AACUGCA

17206 2072 csascsascag cUGAuGaggccguuaggccGaa Agugggu B ACCCACU C CUGUGUG

17195 2352 csasgsasucc cUGAuGaggccguuaggccGaa Agcaccu B AGGUGCU U GGAUCUG

17196 2575 usasgsgsgca cUGAuGaggccguuaggccGaa Aagcugu B ACAGCUU A UGCCCUA

17197 2697 usgsusgsuac cUGAuGaggccguuaggccGaa Agccgca B UGCGGCU C GUACACA

18257 2776 asgscsasgcc cUGAuGaggccguuaggccGaa Agccagc B GCUGGCU C GGCUGCU

18258 2790 uscsuscsguc cUGAuGaggccguuaggccGaa Augucca B UGGACAU U GACGAGA

17207 2926 gscscscscaa cUGAuGaggccguuaggccGaa Agucauc B GAUGACU U UUGGGGC

18259 2928 usgsgscsccc cUGAuGaggccguuaggccGaa Aaaguca B UGACUUU U GGGGCCA

18260 2942 cscscsasucg cUGAuGaggccguuaggccGaa Aagguuu B AAACCUU A CGAUGGG

17198 3089 asgsascsacc cUGAuGaggccguuaggccGaa Acucccg B CGGGAGU U GGUGUCU

17208 3155 usgsgsgsccc cUGAuGaggccguuaggccGaa Aguccuc B GAGGACU U GGGCCCA

17209 3499 csgscsusgua cUGAuGaggccguuaggccGaa Agggcug B CAGCCCU C UACAGCG

17210 3501 ascscsgscug cUGAuGaggccguuaggccGaa Agagggc B GCCCUCU A CAGCGGU

17211 3714 csusususgac cUGAuGaggccguuaggccGaa Accccau B AUGGGGU C GUCAAAG

17199 3802 gscsasgsgag cUGAuGaggccguuaggccGaa Agggugg B CCACCCU C CUCCUGC

17200 3825 gsgsususguc cUGAuGaggccguuaggccGaa Aaggcug B CAGCCUU C GACAACC

17201 3838 uscscscsagu cUGAuGaggccguuaggccGaa Auagagg B CCUCUAU U ACUGGGA

Lowercase = 2'-O-methyl Modifications

Uppercase: 1. Uppercase U under Ribozyme Sequence = 2'-C-Allyl U

2. All other Uppercases = Ribonucleotides I = Inosine

B = 3 '-3' Inverted abasic deoxyribose

Table 32

Table 32: RNA Cleavage by NCH-XYLO Ribozyme (Reaction: 50 mM TRIS-CI pH 7.5, 10 mM Mg²⁺, 37°C, 500 nM FINAL [Rz], Trace

Substrate)

DATA SUMMARY

Table 33

Table 33: Examples of NCH-Xylo Ribozyme and Substrate Sequences

Uppercase = Ribonucleotides

Lowercase = 2'-0-methyl nucleotides

I = Xylo -Inosine

B = 3'-3' inverted abasic

U = 2'-C-allyl-U

Table 34 Table 34: Anti-HER2 NCH Ribozyme and Target Sequences

Table 34

118 CGCGCCC C GCGCCCU AGGGCGC CUGAUGAG X CGAA IGGCGCG

123 CCCGCGC C CUCCCAG CUGGGAG CUGAUGAG X CGAA ICGCGGG

124 CCGCGCC C UCCCAGC GCUGGGA CUGAUGAG X CGAA IGCGCGG

125 CGCGCCC U CCCAGCC GGCUGGG CUGAUGAG X CGAA IGGCGCG

127 CGCCCUC C CAGCCGG CCGGCUG CUGAUGAG X CGAA IAGGGCG

128 GCCCUCC C AGCCGGG CCCGGCU CUGAUGAG X CGAA IGAGGGC

129 CCCUCCC A GCCGGGU ACCCGGC CUGAUGAG X CGAA IGGAGGG

132 UCCCAGC C GGGUCCA UGGACCC CUGAUGAG X CGAA ICUGGGA

138 CCGGGUC C AGCCGGA UCCGGCU CUGAUGAG X CGAA IACCCGG

139 CGGGUCC A GCCGGAG CUCCGGC CUGAUGAG X CGAA IGACCCG

142 GUCCAGC C GGAGCCA UGGCUCC CUGAUGAG X CGAA ICUGGAC

148 CCGGAGC C AUGGGGC GCCCCAU CUGAUGAG X CGAA ICUCCGG

149 CGGAGCC A UGGGGCC GGCCCCA CUGAUGAG X CGAA IGCUCCG

156 AUGGGGC C GGAGCCG CGGCUCC CUGAUGAG X CGAA ICCCCAU

162 CCGGAGC C GCAGUGA UCACUGC CUGAUGAG X CGAA ICUCCGG

165 GAGCCGC A GUGAGCA UGCUCAC CUGAUGAG X CGAA ICGGCUC

172 AGUGAGC A CCAUGGA UCCAUGG CUGAUGAG X CGAA ICUCACU

174 UGAGCAC C AUGGAGC GCUCCAU CUGAUGAG X CGAA IUGCUCA

175 GAGCACC A UGGAGCU AGCUCCA CUGAUGAG X CGAA IGUGCUC

182 AUGGAGC U GGCGGCC GGCCGCC CUGAUGAG X CGAA ICUCCAU

189 UGGCGGC C UUGUGCC GGCACAA CUGAUGAG X CGAA ICCGCCA

190 GGCGGCC U UGUGCCG CGGCACA CUGAUGAG X CGAA IGCCGCC

196 CUUGUGC C GCUGGGG CCCCAGC CUGAUGAG X CGAA ICACAAG

199 GUGCCGC U GGGGGCU AGCCCCC CUGAUGAG X CGAA ICGGCAC

206 UGGGGGC U CCUCCUC GAGGAGG CUGAUGAG X CGAA ICCCCCA

208 GGGGCUC C UCCUCGC GCGAGGA CUGAUGAG X CGAA IAGCCCC

209 GGGCUCC U CCUCGCC GGCGAGG CUGAUGAG X CGAA IGAGCCC

211 GCUCCUC C UCGCCCU AGGGCGA CUGAUGAG X CGAA IAGGAGC

212 CUCCUCC U CGCCCUC GAGGGCG CUGAUGAG X CGAA IGAGGAG

216 UCCUCGC C CUCUUGC GCAAGAG CUGAUGAG X CGAA ICGAGGA

217 CCUCGCC C UCUUGCC GGCAAGA CUGAUGAG X CGAA IGCGAGG

218 CUCGCCC U CUUGCCC GGGCAAG CUGAUGAG X CGAA IGGCGAG

220 CGCCCUC U UGCCCCC GGGGGCA CUGAUGAG X CGAA IAGGGCG

224 cucuuσc C CCCCGGA UCCGGGG CUGAUGAG X CGAA ICAAGAG

225 UCUUGCC C CCCGGAG CUCCGGG CUGAUGAG X CGAA IGCAAGA

226 CUUGCCC c CCGGAGC GCUCCGG CUGAUGAG X CGAA IGGCAAG

227 UUGCCCC c CGGAGCC GGCUCCG CUGAUGAG X CGAA IGGGCAA

228 UGCCCCC c GGAGCCG CGGCUCC CUGAUGAG X CGAA IGGGGCA

234 CCGGAGC c GCGAGCA UGCUCGC CUGAUGAG X CGAA ICUCCGG

241 CGCGAGC A CCCAAGU ACUUGGG CUGAUGAG X CGAA ICUCGCG

243 CGAGCAC C CAAGUGU ACACUUG CUGAUGAG X CGAA IUGCUCG

244 GAGCACC C AAGUGUG CACACUU CUGAUGAG X CGAA IGUGCUC

245 AGCACCC A AGUGUGC GCACACU CUGAUGAG X CGAA IGGUGCU

253 AGUGUGC A CCGGCAC GUGCCGG CUGAUGAG X CGAA ICACACU

255 UGUGCAC C GGCACAG CUGUGCC CUGAUGAG X CGAA IUGCACA

259 CACCGGC A CAGACAU AUGUCUG CUGAUGAG X CGAA ICCGGUG

261 CCGGCAC A GACAUGA UCAUGUC CUGAUGAG X CGAA IUGCCGG Table 34

265 CACAGAC A UGAAGCU AGCUUCA CUGAUGAG X CGAA IUCUGUG

272 AUGAAGC U GCGGCUC GAGCCGC CUGAUGAG X CGAA ICUUCAU

278 CUGCGGC u CCCUGCC GGCAGGG CUGAUGAG X CGAA ICCGCAG

280 GCGGCUC c CUGCCAG CUGGCAG CUGAUGAG X CGAA IAGCCGC

281 CGGCUCC c UGCCAGU ACUGGCA CUGAUGAG X CGAA IGAGCCG

282 GGCUCCC u GCCAGUC GACUGGC CUGAUGAG X CGAA IGGAGCC

285 UCCCUGC c AGUCCCG CGGGACU CUGAUGAG X CGAA ICAGGGA

286 CCCUGCC A GUCCCGA UCGGGAC CUGAUGAG X CGAA IGCAGGG

290 GCCAGUC C CGAGACC GGUCUCG CUGAUGAG X CGAA IACUGGC

291 CCAGUCC C GAGACCC GGGUCUC CUGAUGAG X CGAA IGACUGG

297 CCGAGAC C CACCUGG CCAGGUG CUGAUGAG X CGAA IUCUCGG

298 CGAGACC C ACCUGGA UCCAGGU CUGAUGAG X CGAA IGUCUCG

299 GAGACCC A CCUGGAC GUCCAGG CUGAUGAG X CGAA IGGUCUC

301 GACCCAC C UGGACAU AUGUCCA CUGAUGAG X CGAA IUGGGUC

302 ACCCACC U GGACAUG CAUGUCC CUGAUGAG X CGAA IGUGGGU

307 CCUGGAC A UGCUCCG CGGAGCA CUGAUGAG X CGAA IUCCAGG

311 GACAUGC U CCGCCAC GUGGCGG CUGAUGAG X CGAA ICAUGUC

313 CAUGCUC C GCCACCU AGGUGGC CUGAUGAG X CGAA IAGCAUG

316 GCUCCGC C ACCUCUA UAGAGGU CUGAUGAG X CGAA ICGGAGC

317 CUCCGCC A CCUCUAC GUAGAGG CUGAUGAG X CGAA IGCGGAG

319 CCGCCAC C UCUACCA UGGUAGA CUGAUGAG X CGAA IUGGCGG

320 CGCCACC U CUACCAG CUGGUAG CUGAUGAG X CGAA IGUGGCG

322 CCACCUC U ACCAGGG CCCUGGU CUGAUGAG X CGAA IAGGUGG

325 CCUCUAC C AGGGCUG CAGCCCU CUGAUGAG X CGAA IUAGAGG

326 CUCUACC A GGGCUGC GCAGCCC CUGAUGAG X CGAA IGUAGAG

331 CCAGGGC U GCCAGGU ACCUGGC CUGAUGAG X CGAA ICCCUGG

334 GGGCUGC C AGGUGGU ACCACCU CUGAUGAG X CGAA ICAGCCC

335 GGCUGCC A GGUGGUG CACCACC CUGAUGAG X CGAA IGCAGCC

344 GUGGUGC A GGGAAAC GUUUCCC CUGAUGAG X CGAA ICACCAC

352 GGGAAAC C UGGAACU AGUUCCA CUGAUGAG X CGAA IUUUCCC

353 GGAAACC U GGAACUC GAGUUCC CUGAUGAG X CGAA IGUUUCC

359 CUGGAAC U CACCUAC GUAGGUG CUGAUGAG X CGAA IUUCCAG

361 GGAACUC A CCUACCU AGGUAGG CUGAUGAG X CGAA IAGUUCC

363 AACUCAC C UACCUGC GCAGGUA CUGAUGAG X CGAA IUGAGUU

364 ACUCACC U ACCUGCC GGCAGGU CUGAUGAG X CGAA IGUGAGU

367 CACCUAC C UGCCCAC GUGGGCA CUGAUGAG X CGAA IUAGGUG

368 ACCUACC U GCCCACC GGUGGGC CUGAUGAG X CGAA IGUAGGU

371 UACCUGC C CACCAAU AUUGGUG CUGAUGAG X CGAA ICAGGUA

372 ACCUGCC C ACCAAUG CAUUGGU CUGAUGAG X CGAA IGCAGGU

373 CCUGCCC A CCAAUGC GCAUUGG CUGAUGAG X CGAA IGGCAGG

375 UGCCCAC C AAUGCCA UGGCAUU CUGAUGAG X CGAA IUGGGCA

376 GCCCACC A AUGCCAG CUGGCAU CUGAUGAG X CGAA IGUGGGC

381 CCAAUGC C AGCCUGU ACAGGCU CUGAUGAG X CGAA ICAUUGG

382 CAAUGCC A GCCUGUC GACAGGC CUGAUGAG X CGAA IGCAUUG

385 UGCCAGC C UGUCCUU AAGGACA CUGAUGAG X CGAA ICUGGCA

386 GCCAGCC U GUCCUUC GAAGGAC CUGAUGAG X CGAA IGCUGGC

390 GCCUGUC C UUCCUGC GCAGGAA CUGAUGAG X CGAA IACAGGC Table J

391 CCUGUCC U UCCUGCA UGCAGGA CUGAUGAG X CGAA IGACAGG

394 GUCCUUC C UGCAGGA UCCUGCA CUGAUGAG X CGAA IAAGGAC

395 UCCUUCC U GCAGGAU AUCCUGC CUGAUGAG X CGAA IGAAGGA

398 UUCCUGC A GGAUAUC GAUAUCC CUGAUGAG X CGAA ICAGGAA

406 GGAUAUC C AGGAGGU ACCUCCU CUGAUGAG X CGAA IAUAUCC

407 GAUAUCC A GGAGGUG CACCUCC CUGAUGAG X CGAA IGAUAUC

416 GAGGUGC A GGGCUAC GUAGCCC CUGAUGAG X CGAA ICACCUC

421 GCAGGGC U ACGUGCU AGCACGU CUGAUGAG X CGAA ICCCUGC

428 UACGUGC U CAUCGCU AGCGAUG CUGAUGAG X CGAA ICACGUA

430 CGUGCUC A UCGCUCA UGAGCGA CUGAUGAG X CGAA IAGCACG

435 UCAUCGC U CACAACC GGUUGUG CUGAUGAG X CGAA ICGAUGA

437 AUCGCUC A CAACCAA UUGGUUG CUGAUGAG X CGAA IAGCGAU

439 CGCUCAC A ACCAAGU ACUUGGU CUGAUGAG X CGAA IUGAGCG

442 UCACAAC C AAGUGAG CUCACUU CUGAUGAG X CGAA IUUGUGA

443 CACAACC A AGUGAGG CCUCACU CUGAUGAG X CGAA IGUUGUG

452 GUGAGGC A GGUCCCA UGGGACC CUGAUGAG X CGAA ICCUCAC

457 GCAGGUC C CACUGCA UGCAGUG CUGAUGAG X CGAA IACCUGC

458 CAGGUCC C ACUGCAG CUGCAGU CUGAUGAG X CGAA IGACCUG

459 AGGUCCC A CUGCAGA UCUGCAG CUGAUGAG X CGAA IGGACCU

461 GUCCCAC U GCAGAGG CCUCUGC CUGAUGAG X CGAA IUGGGAC

464 CCACUGC A GAGGCUG CAGCCUC CUGAUGAG X CGAA ICAGUGG

470 CAGAGGC U GCGGAUU AAUCCGC CUGAUGAG X CGAA ICCUCUG

487 GCGAGGC A CCCAGCU AGCUGGG CUGAUGAG X CGAA ICCUCGC

489 GAGGCAC C CAGCUCU AGAGCUG CUGAUGAG X CGAA IUGCCUC

490 AGGCACC C AGCUCUU AAGAGCU CUGAUGAG X CGAA IGUGCCU

491 GGCACCC A GCUCUUU AAAGAGC CUGAUGAG X CGAA IGGUGCC

494 ACCCAGC U CUUUGAG CUCAAAG CUGAUGAG X CGAA ICUGGGU

496 CCAGCUC U UUGAGGA UCCUCAA CUGAUGAG X CGAA IAGCUGG

505 UGAGGAC A ACUAUGC GCAUAGU CUGAUGAG X CGAA IUCCUCA

508 GGACAAC U AUGCCCU AGGGCAU CUGAUGAG X CGAA IUUGUCC

513 ACUAUGC C CUGGCCG CGGCCAG CUGAUGAG X CGAA ICAUAGU

514 CUAUGCC C UGGCCGU ACGGCCA CUGAUGAG X CGAA IGCAUAG

515 UAUGCCC U GGCCGUG CACGGCC CUGAUGAG X CGAA IGGCAUA

519 CCCUGGC C GUGCUAG CUAGCAC CUGAUGAG X CGAA ICCAGGG

524 GCCGUGC U AGACAAU AUUGUCU CUGAUGAG X CGAA ICACGGC

529 GCUAGAC A AUGGAGA UCUCCAU CUGAUGAG X CGAA IUCUAGC

538 UGGAGAC C CGCUGAA UUCAGCG CUGAUGAG X CGAA IUCUCCA

539 GGAGACC C GCUGAAC GUUCAGC CUGAUGAG X CGAA IGUCUCC

542 GACCCGC U GAACAAU AUUGUUC CUGAUGAG X CGAA ICGGGUC

547 GCUGAAC A AUACCAC GUGGUAU CUGAUGAG X CGAA IUUCAGC

552 ACAAUAC C ACCCCUG CAGGGGU CUGAUGAG X CGAA IUAUUGU

553 CAAUACC A CCCCUGU ACAGGGG CUGAUGAG X CGAA IGUAUUG

555 AUACCAC C CCUGUCA UGACAGG CUGAUGAG X CGAA IUGGUAU

556 UACCACC C CUGUCAC GUGACAG CUGAUGAG X CGAA IGUGGUA

557 ACCACCC C UGUCACA UGUGACA CUGAUGAG X CGAA IGGUGGU

558 CCACCCC U GUCACAG CUGUGAC CUGAUGAG X CGAA IGGGUGG

562 CCCUGUC A CAGGGGC GCCCCUG CUGAUGAG X CGAA IACAGGG Table 34

564 CUGUCAC A GGGGCCU AGGCCCC CUGAUGAG X CGAA IUGACAG

570 CAGGGGC C UCCCCAG CUGGGGA CUGAUGAG X CGAA ICCCCUG

571 AGGGGCC U CCCCAGG CCUGGGG CUGAUGAG X CGAA IGCCCCU

573 GGGCCUC C CCAGGAG CUCCUGG CUGAUGAG X CGAA IAGGCCC

574 GGCCUCC C CAGGAGG CCUCCUG CUGAUGAG X CGAA IGAGGCC

575 GCCUCCC C AGGAGGC GCCUCCU CUGAUGAG X CGAA IGGAGGC

576 CCUCCCC A GGAGGCC GGCCUCC CUGAUGAG X CGAA IGGGAGG

583 AGGAGGC C UGCGGGA UCCCGCA CUGAUGAG X CGAA ICCUCCU

584 GGAGGCC U GCGGGAG CUCCCGC CUGAUGAG X CGAA IGCCUCC

593 CGGGAGC U GCAGCUU AAGCUGC CUGAUGAG X CGAA ICUCCCG

596 GAGCUGC A GCUUCGA UCGAAGC CUGAUGAG X CGAA ICAGCUC

599 CUGCAGC U UCGAAGC GCUUCGA CUGAUGAG X CGAA ICUGCAG

607 UCGAAGC C UCACAGA UCUGUGA CUGAUGAG X CGAA ICUUCGA

608 CGAAGCC U CACAGAG CUCUGUG CUGAUGAG X CGAA IGCUUCG

610 AAGCCUC A CAGAGAU AUCUCUG CUGAUGAG X CGAA IAGGCUU

612 GCCUCAC A GAGAUCU AGAUCUC CUGAUGAG X CGAA IUGAGGC

619 AGAGAUC U UGAAAGG CCUUUCA CUGAUGAG X CGAA IAUCUCU

634 AGGGGUC U UGAUCCA UGGAUCA CUGAUGAG X CGAA IACCCCU

640 CUUGAUC C AGCGGAA UUCCGCU CUGAUGAG X CGAA IAUCAAG

641 UUGAUCC A GCGGAAC GUUCCGC CUGAUGAG X CGAA IGAUCAA

649 GCGGAAC C CCCAGCU AGCUGGG CUGAUGAG X CGAA IUUCCGC

650 CGGAACC C CCAGCUC GAGCUGG CUGAUGAG X CGAA IGUUCCG

651 GGAACCC C CAGCUCU AGAGCUG CUGAUGAG X CGAA IGGUUCC

652 GAACCCC C AGCUCUG CAGAGCU CUGAUGAG X CGAA IGGGUUC

653 AACCCCC A GCUCUGC GCAGAGC CUGAUGAG X CGAA IGGGGUU

656 CCCCAGC U CUGCUAC GUAGCAG CUGAUGAG X CGAA ICUGGGG

658 CCAGCUC U GCUACCA UGGUAGC CUGAUGAG X CGAA IAGCUGG

661 GCUCUGC U ACCAGGA UCCUGGU CUGAUGAG X CGAA ICAGAGC

664 CUGCUAC C AGGACAC GUGUCCU CUGAUGAG X CGAA IUAGCAG

665 UGCUACC A GGACACG CGUGUCC CUGAUGAG X CGAA IGUAGCA

670 CCAGGAC A CGAUUUU AAAAUCG CUGAUGAG X CGAA IUCCUGG

688 GAAGGAC A UCUUCCA UGGAAGA CUGAUGAG X CGAA IUCCUUC

691 GGACAUC U UCCACAA UUGUGGA CUGAUGAG X CGAA IAUGUCC

694 CAUCUUC C ACAAGAA UUCUUGU CUGAUGAG X CGAA IAAGAUG

695 AUCUUCC A CAAGAAC GUUCUUG CUGAUGAG X CGAA IGAAGAU

697 CUUCCAC A AGAACAA UUGUUCU CUGAUGAG X CGAA IUGGAAG

703 CAAGAAC A ACCAGCU AGCUGGU CUGAUGAG X CGAA IUUCUUG

706 GAACAAC C AGCUGGC GCCAGCU CUGAUGAG X CGAA IUUGUUC

707 AACAACC A GCUGGCU AGCCAGC CUGAUGAG X CGAA IGUUGUU

710 AACCAGC U GGCUCUC GAGAGCC CUGAUGAG X CGAA ICUGGUU

714 AGCUGGC U CUCACAC GUGUGAG CUGAUGAG X CGAA ICCAGCU

716 CUGGCUC U CACACUG CAGUGUG CUGAUGAG X CGAA IAGCCAG

718 GGCUCUC A CACUGAU AUCAGUG CUGAUGAG X CGAA IAGAGCC

720 CUCUCAC A CUGAUAG CUAUCAG CUGAUGAG X CGAA IUGAGAG

722 CUCACAC U GAUAGAC GUCUAUC CUGAUGAG X CGAA IUGUGAG

730 GAUAGAC A CCAACCG CGGUUGG CUGAUGAG X CGAA IUCUAUC

732 UAGACAC C AACCGCU AGCGGUU CUGAUGAG X CGAA IUGUCUA Table 34

733 AGACACC A ACCGCUC GAGCGGU CUGAUGAG X CGAA IGUGUCU

736 CACCAAC C GCUCUCG CGAGAGC CUGAUGAG X CGAA IUUGGUG

739 CAACCGC U CUCGGGC GCCCGAG CUGAUGAG X CGAA ICGGUUG

741 ACCGCUC U CGGGCCU AGGCCCG CUGAUGAG X CGAA IAGCGGU

747 CUCGGGC C UGCCACC GGUGGCA CUGAUGAG X CGAA ICCCGAG

748 UCGGGCC U GCCACCC GGGUGGC CUGAUGAG X CGAA IGCCCGA

751 GGCCUGC C ACCCCUG CAGGGGU CUGAUGAG X CGAA ICAGGCC

752 GCCUGCC A CCCCUGU ACAGGGG CUGAUGAG X CGAA IGCAGGC

754 CUGCCAC C CCUGUUC GAACAGG CUGAUGAG X CGAA IUGGCAG

755 UGCCACC C CUGUUCU AGAACAG CUGAUGAG X CGAA IGUGGCA

756 GCCACCC C UGUUCUC GAGAACA CUGAUGAG X CGAA IGGUGGC

757 CCACCCC U GUUCUCC GGAGAAC CUGAUGAG X CGAA IGGGUGG

762 CCUGUUC U CCGAUGU ACAUCGG CUGAUGAG X CGAA IAACAGG

764 UGUUCUC C GAUGUGU ACACAUC CUGAUGAG X CGAA IAGAACA

778 UAAGGGC U CCCGCUG CAGCGGG CUGAUGAG X CGAA ICCCUUA

780 AGGGCUC C CGCUGCU AGCAGCG CUGAUGAG X CGAA IAGCCCU

781 GGGCUCC C GCUGCUG CAGCAGC CUGAUGAG X CGAA IGAGCCC

784 CUCCCGC U GCUGGGG CCCCAGC CUGAUGAG X CGAA ICGGGAG

787 CCGCUGC U GGGGAGA UCUCCCC CUGAUGAG X CGAA ICAGCGG

801 AGAGUUC U GAGGAUU AAUCCUC CUGAUGAG X CGAA IAACUCU

812 GAUUGUC A GAGCCUG CAGGCUC CUGAUGAG X CGAA IACAAUC

817 UCAGAGC C UGACGCG CGCGUCA CUGAUGAG X CGAA ICUCUGA

818 CAGAGCC U GACGCGC GCGCGUC CUGAUGAG X CGAA IGCUCUG

826 GACGCGC A CUGUCUG CAGACAG CUGAUGAG X CGAA ICGCGUC

828 CGCGCAC U GUCUGUG CACAGAC CUGAUGAG X CGAA IUGCGCG

832 CACUGUC U GUGCCGG CCGGCAC CUGAUGAG X CGAA IACAGUG

837 UCUGUGC C GGUGGCU AGCCACC CUGAUGAG X CGAA ICACAGA

844 CGGUGGC U GUGCCCG CGGGCAC CUGAUGAG X CGAA ICCACCG

849 GCUGUGC C CGCUGCA UGCAGCG CUGAUGAG X CGAA ICACAGC

850 CUGUGCC C GCUGCAA UUGCAGC CUGAUGAG X CGAA IGCACAG

853 UGCCCGC U GCAAGGG CCCUUGC CUGAUGAG X CGAA ICGGGCA

856 CCGCUGC A AGGGGCC GGCCCCU CUGAUGAG X CGAA ICAGCGG

863 AAGGGGC C ACUGCCC GGGCAGU CUGAUGAG X CGAA ICCCCUU

864 AGGGGCC A CUGCCCA UGGGCAG CUGAUGAG X CGAA IGCCCCU

866 GGGCCAC U GCCCACU AGUGGGC CUGAUGAG X CGAA IUGGCCC

869 CCACUGC C CACUGAC _ GUCAGUG CUGAUGAG X CGAA ICAGUGG

870 ' CACUGCC C ACUGACU AGUCAGU CUGAUGAG X CGAA IGCAGUG

871 ACUGCCC A CUGACUG CAGUCAG CUGAUGAG X CGAA IGGCAGU

873 UGCCCAC U GACUGCU AGCAGUC CUGAUGAG X CGAA IUGGGCA

877 CACUGAC U GCUGCCA UGGCAGC CUGAUGAG X CGAA IUCAGUG

880 UGACUGC U GCCAUGA UCAUGGC CUGAUGAG X CGAA ICAGUCA

883 CUGCUGC C AUGAGCA UGCUCAU CUGAUGAG X CGAA ICAGCAG

884 UGCUGCC A UGAGCAG CUGCUCA CUGAUGAG X CGAA IGCAGCA

890 CAUGAGC A GUGUGCU AGCACAC CUGAUGAG X CGAA ICUCAUG

897 AGUGUGC U GCCGGCU AGCCGGC CUGAUGAG X CGAA ICACACU

900 GUGCUGC C GGCUGCA UGCAGCC CUGAUGAG X CGAA ICAGCAC

904 UGCCGGC U GCACGGG CCCGUGC CUGAUGAG X CGAA ICCGGCA Table 34

907 CGGCUGC A CGGGCCC GGGCCCG CUGAUGAG X CGAA ICAGCCG

913 CACGGGC C CCAAGCA UGCUUGG CUGAUGAG X CGAA ICCCGUG

914 ACGGGCC C CAAGCAC GUGCUUG CUGAUGAG X CGAA IGCCCGU

915 CGGGCCC C AAGCACU AGUGCUU CUGAUGAG X CGAA IGGCCCG

916 GGGCCCC A AGCACUC GAGUGCU CUGAUGAG X CGAA IGGGCCC

920 CCCAAGC A CUCUGAC GUCAGAG CUGAUGAG X CGAA ICUUGGG

922 CAAGCAC U CUGACUG CAGUCAG CUGAUGAG X CGAA IUGCUUG

924 AGCACUC U GACUGCC GGCAGUC CUGAUGAG X CGAA IAGUGCU

928 CUCUGAC U GCCUGGC GCCAGGC CUGAUGAG X CGAA IUCAGAG

931 UGACUGC C UGGCCUG CAGGCCA CUGAUGAG X CGAA ICAGUCA

932 GACUGCC U GGCCUGC GCAGGCC CUGAUGAG X CGAA IGCAGUC

936 GCCUGGC C UGCCUCC GGAGGCA CUGAUGAG X CGAA ICCAGGC

937 CCUGGCC U GCCUCCA UGGAGGC CUGAUGAG X CGAA IGCCAGG

940 GGCCUGC C UCCACUU AAGUGGA CUGAUGAG X CGAA ICAGGCC

941 GCCUGCC u CCACUUC GAAGUGG CUGAUGAG X CGAA IGCAGGC

943 CUGCCUC c ACUUCAA UUGAAGU CUGAUGAG X CGAA IAGGCAG

944 UGCCUCC A CUUCAAC GUUGAAG CUGAUGAG X CGAA IGAGGCA

946 CCUCCAC U UCAACCA UGGUUGA CUGAUGAG X CGAA IUGGAGG

949 CCACUUC A ACCACAG CUGUGGU CUGAUGAG X CGAA IAAGUGG

952 CUUCAAC C ACAGUGG CCACUGU CUGAUGAG X CGAA IUUGAAG

953 UUCAACC A CAGUGGC GCCACUG CUGAUGAG X CGAA IGUUGAA

955 CAACCAC A GUGGCAU AUGCCAC CUGAUGAG X CGAA IUGGUUG

961 CAGUGGC A UCUGUGA UCACAGA CUGAUGAG X CGAA ICCACUG

964 UGGCAUC U GUGAGCU AGCUCAC CUGAUGAG X CGAA IAUGCCA

971 UGUGAGC U GCACUGC GCAGUGC CUGAUGAG X CGAA ICUCACA

974 GAGCUGC A CUGCCCA UGGGCAG CUGAUGAG X CGAA ICAGCUC

976 GCUGCAC U GCCCAGC GCUGGGC CUGAUGAG X CGAA IUGCAGC

979 GCACUGC C CAGCCCU AGGGCUG CUGAUGAG X CGAA ICAGUGC

980 CACUGCC C AGCCCUG CAGGGCU CUGAUGAG X CGAA IGCAGUG

981 ACUGCCC A GCCCUGG CCAGGGC CUGAUGAG X CGAA IGGCAGU

984 GCCCAGC C CUGGUCA UGACCAG CUGAUGAG X CGAA ICUGGGC

985 CCCAGCC C UGGUCAC GUGACCA CUGAUGAG X CGAA IGCUGGG

986 CCAGCCC U GGUCACC GGUGACC CUGAUGAG X CGAA IGGCUGG

991 CCUGGUC A CCUACAA UUGUAGG CUGAUGAG X CGAA IACCAGG

993 UGGUCAC C UACAACA UGUUGUA CUGAUGAG X CGAA IUGACCA

994 GGUCACC U ACAACAC GUGUUGU CUGAUGAG X CGAA IGUGACC

997 CACCUAC A ACACAGA UCUGUGU CUGAUGAG X CGAA IUAGGUG

1000 CUACAAC A CAGACAC GUGUCUG CUGAUGAG X CGAA IUUGUAG

1002 ACAACAC A GACACGU ACGUGUC CUGAUGAG X CGAA IUGUUGU

1006 CACAGAC A CGUUUGA UCAAACG CUGAUGAG X CGAA IUCUGUG

1017 UUGAGUC C AUGCCCA UGGGCAU CUGAUGAG X CGAA IACUCAA

1018 UGAGUCC A UGCCCAA UUGGGCA CUGAUGAG X CGAA IGACUCA

1022 UCCAUGC C CAAUCCC GGGAUUG CUGAUGAG X CGAA ICAUGGA

1023 CCAUGCC C AAUCCCG CGGGAUU CUGAUGAG X CGAA IGCAUGG

1024 CAUGCCC A AUCCCGA UCGGGAU CUGAUGAG X CGAA IGGCAUG

1028 CCCAAUC C CGAGGGC GCCCUCG CUGAUGAG X CGAA IAUUGGG

1029 CCAAUCC C GAGGGCC GGCCCUC CUGAUGAG X CGAA IGAUUGG Table 34

1036 CGAGGGC C GGUAUAC GUAUACC CUGAUGAG X CGAA ICCCUCG

1044 GGUAUAC A UUCGGCG CGCCGAA CUGAUGAG X CGAA IUAUACC

1053 UCGGCGC C AGCUGUG CACAGCU CUGAUGAG X CGAA ICGCCGA

1054 CGGCGCC A GCUGUGU ACACAGC CUGAUGAG X CGAA IGCGCCG

1057 CGCCAGC U GUGUGAC GUCACAC CUGAUGAG X CGAA ICUGGCG

1065 GUGUGAC U GCCUGUC GACAGGC CUGAUGAG X CGAA IUCACAC

1068 UGACUGC C UGUCCCU AGGGACA CUGAUGAG X CGAA ICAGUCA

1069 GACUGCC U GUCCCUA UAGGGAC CUGAUGAG X CGAA IGCAGUC

1073 GCCUGUC C CUACAAC GUUGUAG CUGAUGAG X CGAA IACAGGC

1074 CCUGUCC C UACAACU AGUUGUA CUGAUGAG X CGAA IGACAGG

1075 CUGUCCC U ACAACUA UAGUUGU CUGAUGAG X CGAA IGGACAG

1078 UCCCUAC A ACUACCU AGGUAGU CUGAUGAG X CGAA IUAGGGA

1081 CUACAAC U ACCUUUC GAAAGGU CUGAUGAG X CGAA IUUGUAG

1084 CAACUAC C UUUCUAC GUAGAAA CUGAUGAG X CGAA IUAGUUG

1085 AACUACC U UUCUACG CGUAGAA CUGAUGAG X CGAA IGUAGUU

1089 ACCUUUC U ACGGACG CGUCCGU CUGAUGAG X CGAA IAAAGGU

1104 UGGGAUC C UGCACCC GGGUGCA CUGAUGAG X CGAA IAUCCCA

1105 GGGAUCC U GCACCCU AGGGUGC CUGAUGAG X CGAA IGAUCCC

1108 AUCCUGC A CCCUCGU ACGAGGG CUGAUGAG X CGAA ICAGGAU

1110 CCUGCAC C CUCGUCU AGACGAG CUGAUGAG X CGAA IUGCAGG llll CUGCACC C UCGUCUG CAGACGA CUGAUGAG X CGAA IGUGCAG

1112 UGCACCC U CGUCUGC GCAGACG CUGAUGAG X CGAA IGGUGCA

1117 CCUCGUC U GCCCCCU AGGGGGC CUGAUGAG X CGAA IACGAGG

1120 CGUCUGC C CCCUGCA UGCAGGG CUGAUGAG X CGAA ICAGACG

1121 GUCUGCC C CCUGCAC GUGCAGG CUGAUGAG X CGAA IGCAGAC

1122 UCUGCCC C CUGCACA UGUGCAG CUGAUGAG X CGAA IGGCAGA

1123 CUGCCCC C UGCACAA UUGUGCA CUGAUGAG X CGAA IGGGCAG

1124 UGCCCCC U GCACAAC GUUGUGC CUGAUGAG X CGAA IGGGGCA

1127 CCCCUGC A CAACCAA UUGGUUG CUGAUGAG X CGAA ICAGGGG

1129 CCUGCAC A ACCAAGA UCUUGGU CUGAUGAG X CGAA IUGCAGG

1132 GCACAAC C AAGAGGU ACCUCUU CUGAUGAG X CGAA IUUGUGC

1133 CACAACC A AGAGGUG CACCUCU CUGAUGAG X CGAA IGUUGUG

1143 AGGUGAC A GCAGAGG CCUCUGC CUGAUGAG X CGAA IUCACCU

1146 UGACAGC A GAGGAUG CAUCCUC CUGAUGAG X CGAA ICUGUCA

1158 AUGGAAC A CAGCGGU ACCGCUG CUGAUGAG X CGAA IUUCCAU

1160 GGAACAC A GCGGUGU ACACCGC CUGAUGAG X CGAA IUGUUCC

1177 GAAGUGC A GCAAGCC GGCUUGC CUGAUGAG X CGAA ICACUUC

1180 GUGCAGC A AGCCCUG CAGGGCU CUGAUGAG X CGAA ICUGCAC

1184 AGCAAGC C CUGUGCC GGCACAG CUGAUGAG X CGAA ICUUGCU

1185 GCAAGCC C UGUGCCC GGGCACA CUGAUGAG X CGAA IGCUUGC

1186 CAAGCCC U GUGCCCG CGGGCAC CUGAUGAG X CGAA IGGCUUG

1191 CCUGUGC c CGAGUGU ACACUCG CUGAUGAG X CGAA ICACAGG

1192 CUGUGCC c GAGUGUG CACACUC CUGAUGAG X CGAA IGCACAG

1201 AGUGUGC u AUGGUCU AGACCAU CUGAUGAG X CGAA ICACACU

1208 UAUGGUC u GGGCAUG CAUGCCC CUGAUGAG X CGAA IACCAUA

1213 UCUGGGC A UGGAGCA UGCUCCA CUGAUGAG X CGAA ICCCAGA

1220 AUGGAGC A CUUGCGA UCGCAAG CUGAUGAG X CGAA ICUCCAU Table 34

1222 GGAGCAC U UGCGAGA UCUCGCA CUGAUGAG X CGAA IUGCUCC

1239 UGAGGGC A GUUACCA UGGUAAC CUGAUGAG X CGAA ICCCUCA

1245 CAGUUAC C AGUGCCA UGGCACU CUGAUGAG X CGAA IUAACUG

1246 AGUUACC A GUGCCAA UUGGCAC CUGAUGAG X CGAA IGUAACU

1251 CCAGUGC C AAUAUCC GGAUAUU CUGAUGAG X CGAA ICACUGG

1252 CAGUGCC A AUAUCCA UGGAUAU CUGAUGAG X CGAA IGCACUG

1258 CAAUAUC C AGGAGUU AACUCCU CUGAUGAG X CGAA IAUAUUG

1259 AAUAUCC A GGAGUUU AAACUCC CUGAUGAG X CGAA IGAUAUU

1269 AGUUUGC U GGCUGCA UGCAGCC CUGAUGAG X CGAA ICAAACU

1273 UGCUGGC U GCAAGAA UUCUUGC CUGAUGAG X CGAA ICCAGCA

1276 UGGCUGC A AGAAGAU AUCUUCU CUGAUGAG X CGAA ICAGCCA

1285 GAAGAUC U UUGGGAG CUCCCAA CUGAUGAG X CGAA IAUCUUC

1294 UGGGAGC C UGGCAUU AAUGCCA CUGAUGAG X CGAA ICUCCCA

1295 GGGAGCC U GGCAUUU AAAUGCC CUGAUGAG X CGAA IGCUCCC

1299 GCCUGGC A UUUCUGC GCAGAAA CUGAUGAG X CGAA ICCAGGC

1304 GCAUUUC U GCCGGAG CUCCGGC CUGAUGAG X CGAA IAAAUGC

1307 UUUCUGC C GGAGAGC GCUCUCC CUGAUGAG X CGAA ICAGAAA

1315 GGAGAGC U UUGAUGG CCAUCAA CUGAUGAG X CGAA ICUCUCC

1327 UGGGGAC C CAGCCUC GAGGCUG CUGAUGAG X CGAA IUCCCCA

1328 GGGGACC C AGCCUCC •GGAGGCU CUGAUGAG X CGAA IGUCCCC

1329 GGGACCC A GCCUCCA UGGAGGC CUGAUGAG X CGAA IGGUCCC

1332 ACCCAGC C UCCAACA UGUUGGA CUGAUGAG X CGAA ICUGGGU

1333 CCCAGCC U CCAACAC GUGUUGG CUGAUGAG X CGAA IGCUGGG

1335 CAGCCUC C AACACUG CAGUGUU CUGAUGAG X CGAA IAGGCUG

1336 AGCCUCC A ACACUGC GCAGUGU CUGAUGAG X CGAA IGAGGCU

1339 CUCCAAC A CUGCCCC GGGGCAG CUGAUGAG X CGAA IUUGGAG

1341 CCAACAC U GCCCCGC GCGGGGC CUGAUGAG X CGAA IUGUUGG

1344 ACACUGC C CCGCUCC GGAGCGG CUGAUGAG X CGAA ICAGUGU

1345 CACUGCC C CGCUCCA UGGAGCG CUGAUGAG X CGAA IGCAGUG

1346 ACUGCCC C GCUCCAG CUGGAGC CUGAUGAG X CGAA IGGCAGU

1349 GCCCCGC U CCAGCCA UGGCUGG CUGAUGAG X CGAA ICGGGGC

1351 CCCGCUC C AGCCAGA UCUGGCU CUGAUGAG X CGAA IAGCGGG

1352 CCGCUCC A GCCAGAG CUCUGGC CUGAUGAG X CGAA IGAGCGG

1355 CUCCAGC C AGAGCAG CUGCUCU CUGAUGAG X CGAA ICUGGAG

1356 UCCAGCC A GAGCAGC GCUGCUC CUGAUGAG X CGAA IGCUGGA

1361 CCAGAGC A GCUCCAA UUGGAGC CUGAUGAG X CGAA ICUCUGG

1364 GAGCAGC U CCAAGUG CACUUGG CUGAUGAG X CGAA ICUGCUC

1366 GCAGCUC C AAGUGUU AACACUU CUGAUGAG X CGAA IAGCUGC

1367 CAGCUCC A AGUGUUU AAACACU CUGAUGAG X CGAA IGAGCUG

1380 UUGAGAC U CUGGAAG CUUCCAG CUGAUGAG X CGAA IUCUCAA

1382 GAGACUC U GGAAGAG CUCUUCC CUGAUGAG X CGAA IAGUCUC

1393 AGAGAUC A CAGGUUA UAACCUG CUGAUGAG X CGAA IAUCUCU

1395 AGAUCAC A GGUUACC GGUAACC CUGAUGAG X CGAA IUGAUCU

1402 AGGUUAC C UAUACAU AUGUAUA CUGAUGAG X CGAA IUAACCU

1403 GGUUACC U AUACAUC GAUGUAU CUGAUGAG X CGAA IGUAACC

1408 CCUAUAC A UCUCAGC GCUGAGA CUGAUGAG X CGAA IUAUAGG

1411 AUACAUC U CAGCAUG CAUGCUG CUGAUGAG X CGAA IAUGUAU Table 34

1413 ACAUCUC A GCAUGGC GCCAUGC CUGAUGAG X CGAA IAGAUGU

1416 UCUCAGC A UGGCCGG CCGGCCA CUGAUGAG X CGAA ICUGAGA

1421 GCAUGGC C GGACAGC GCUGUCC CUGAUGAG X CGAA ICCAUGC

1426 GCCGGAC A GCCUGCC GGCAGGC CUGAUGAG X CGAA IUCCGGC

1429 GGACAGC C UGCCUGA UCAGGCA CUGAUGAG X CGAA ICUGUCC

1430 GACAGCC U GCCUGAC GUCAGGC CUGAUGAG X CGAA IGCUGUC

1433 AGCCUGC C UGACCUC GAGGUCA CUGAUGAG X CGAA ICAGGCU

1434 GCCUGCC U GACCUCA UGAGGUC CUGAUGAG X CGAA IGCAGGC

1438 GCCUGAC C UCAGCGU ACGCUGA CUGAUGAG X CGAA IUCAGGC

1439 CCUGACC U CAGCGUC GACGCUG CUGAUGAG X CGAA IGUCAGG

1441 UGACCUC A GCGUCUU AAGACGC CUGAUGAG X CGAA IAGGUCA

1447 CAGCGUC U UCCAGAA UUCUGGA CUGAUGAG X CGAA IACGCUG

1450 CGUCUUC C AGAACCU AGGUUCU CUGAUGAG X CGAA IAAGACG

1451 GUCUUCC A GAACCUG CAGGUUC CUGAUGAG X CGAA IGAAGAC

1456 CCAGAAC C UGCAAGU ACUUGCA CUGAUGAG X CGAA IUUCUGG

1457 CAGAACC U GCAAGUA UACUUGC CUGAUGAG X CGAA IGUUCUG

1460 AACCUGC A AGUAAUC GAUUACU CUGAUGAG X CGAA ICAGGUU

1468 AGUAAUC C GGGGACG CGUCCCC CUGAUGAG X CGAA IAUUACU

1481 CGAAUUC U GCACAAU AUUGUGC CUGAUGAG X CGAA IAAUUCG

1484 AUUCUGC A CAAUGGC GCCAUUG CUGAUGAG X CGAA ICAGAAU

1486 UCUGCAC A AUGGCGC GCGCCAU CUGAUGAG X CGAA IUGCAGA

1494 AUGGCGC C UACUCGC GCGAGUA CUGAUGAG X CGAA ICGCCAU

1495 UGGCGCC U ACUCGCU AGCGAGU CUGAUGAG X CGAA IGCGCCA

1498 CGCCUAC U CGCUGAC GUCAGCG CUGAUGAG X CGAA IUAGGCG

1502 UACUCGC U GACCCUG CAGGGUC CUGAUGAG X CGAA ICGAGUA

1506 CGCUGAC C CUGCAAG CUUGCAG CUGAUGAG X CGAA IUCAGCG

1507 GCUGACC C UGCAAGG CCUUGCA CUGAUGAG X CGAA IGUCAGC

1508 CUGACCC U GCAAGGG CCCUUGC CUGAUGAG X CGAA IGGUCAG

1511 ACCCUGC A AGGGCUG CAGCCCU CUGAUGAG X CGAA ICAGGGU

1517 CAAGGGC U GGGCAUC GAUGCCC CUGAUGAG X CGAA ICCCUUG

1522 GCUGGGC A UCAGCUG CAGCUGA CUGAUGAG X CGAA ICCCAGC

1525 GGGCAUC A GCUGGCU AGCCAGC CUGAUGAG X CGAA IAUGCCC

1528 CAUCAGC U GGCUGGG CCCAGCC CUGAUGAG X CGAA ICUGAUG

1532 AGCUGGC U GGGGCUG CAGCCCC CUGAUGAG X CGAA ICCAGCU

1538 CUGGGGC U GCGCUCA UGAGCGC CUGAUGAG X CGAA ICCCCAG

1543 GCUGCGC U CACUGAG CUCAGUG CUGAUGAG X CGAA ICGCAGC

1545 UGCGCUC A CUGAGGG CCCUCAG CUGAUGAG X CGAA IAGCGCA

1547 CGCUCAC U GAGGGAA UUCCCUC CUGAUGAG X CGAA IUGAGCG

1556 AGGGAAC U GGGCAGU ACUGCCC CUGAUGAG X CGAA IUUCCCU

1561 ACUGGGC A GUGGACU AGUCCAC CUGAUGAG X CGAA ICCCAGU

1568 AGUGGAC U GGCCCUC GAGGGCC CUGAUGAG X CGAA IUCCACU

1572 GACUGGC C CUCAUCC GGAUGAG CUGAUGAG X CGAA ICCAGUC

1573 ACUGGCC C UCAUCCA UGGAUGA CUGAUGAG X CGAA IGCCAGU

1574 CUGGCCC U CAUCCAC GUGGAUG CUGAUGAG X CGAA IGGCCAG

1576 GGCCCUC A UCCACCA UGGUGGA CUGAUGAG X CGAA IAGGGCC

1579 CCUCAUC C ACCAUAA UUAUGGU CUGAUGAG X CGAA IAUGAGG

1580 CUCAUCC A CCAUAAC GUUAUGG CUGAUGAG X CGAA IGAUGAG Table 34

1582 CAUCCAC C AUAACAC GUGUUAU CUGAUGAG X CGAA IUGGAUG

1583 AUCCACC A UAACACC GGUGUUA CUGAUGAG X CGAA IGUGGAU

1588 CCAUAAC A CCCACCU AGGUGGG CUGAUGAG X CGAA IUUAUGG

1590 AUAACAC C CACCUCU AGAGGUG CUGAUGAG X CGAA IUGUUAU

1591 UAACACC C ACCUCUG CAGAGGU CUGAUGAG X CGAA IGUGUUA

1592 AACACCC A CCUCUGC GCAGAGG CUGAUGAG X CGAA IGGUGUU

1594 CACCCAC C UCUGCUU AAGCAGA CUGAUGAG X CGAA IUGGGUG

1595 ACCCACC U CUGCUUC GAAGCAG CUGAUGAG X CGAA IGUGGGU

1597 CCACCUC u GCUUCGU ACGAAGC CUGAUGAG X CGAA IAGGUGG

1600 CCUCUGC u UCGUGCA UGCACGA CUGAUGAG X CGAA ICAGAGG

1607 UUCGUGC A CACGGUG CACCGUG CUGAUGAG X CGAA ICACGAA

1609 CGUGCAC A CGGUGCC GGCACCG CUGAUGAG X CGAA IUGCACG

1616 ACGGUGC C CUGGGAC GUCCCAG CUGAUGAG X CGAA ICACCGU

1617 CGGUGCC C UGGGACC GGUCCCA CUGAUGAG X CGAA IGCACCG

1618 GGUGCCC U GGGACCA UGGUCCC CUGAUGAG X CGAA IGGCACC

1624 CUGGGAC C AGCUCUU AAGAGCU CUGAUGAG X CGAA IUCCCAG

1625 UGGGACC A GCUCUUU AAAGAGC CUGAUGAG X CGAA IGUCCCA

1628 GACCAGC U CUUUCGG CCGAAAG CUGAUGAG X CGAA ICUGGUC

1630 CCAGCUC U UUCGGAA UUCCGAA CUGAUGAG X CGAA IAGCUGG

1639 UCGGAAC C CGCACCA UGGUGCG CUGAUGAG X CGAA IUUCCGA

1640 CGGAACC C GCACCAA UUGGUGC CUGAUGAG X CGAA IGUUCCG

1643 AACCCGC A CCAAGCU AGCUUGG CUGAUGAG X CGAA ICGGGUU

1645 CCCGCAC C AAGCUCU AGAGCUU CUGAUGAG X CGAA IUGCGGG

1646 CCGCACC A AGCUCUG CAGAGCU CUGAUGAG X CGAA IGUGCGG

1650 ACCAAGC U CUGCUCC GGAGCAG CUGAUGAG X CGAA ICUUGGU

1652 CAAGCUC U GCUCCAC GUGGAGC CUGAUGAG X CGAA IAGCUUG

1655 GCUCUGC U CCACACU AGUGUGG CUGAUGAG X CGAA ICAGAGC

1657 UCUGCUC C ACACUGC GCAGUGU CUGAUGAG X CGAA IAGCAGA

1658 CUGCUCC A CACUGCC GGCAGUG CUGAUGAG X CGAA IGAGCAG

1660 GCUCCAC A CUGCCAA UUGGCAG CUGAUGAG X CGAA IUGGAGC

1662 UCCACAC U GCCAACC GGUUGGC CUGAUGAG X CGAA IUGUGGA

1665 ACACUGC C AACCGGC GCCGGUU CUGAUGAG X CGAA ICAGUGU

1666 CACUGCC A ACCGGCC GGCCGGU CUGAUGAG X CGAA IGCAGUG

1669 UGCCAAC C GGCCAGA UCUGGCC CUGAUGAG X CGAA IUUGGCA

1673 AACCGGC C AGAGGAC GUCCUCU CUGAUGAG X CGAA ICCGGUU

1674 ACCGGCC A GAGGACG CGUCCUC CUGAUGAG X CGAA IGCCGGU

1699 CGAGGGC C UGGCCUG CAGGCCA CUGAUGAG X CGAA ICCCUCG

1700 GAGGGCC U GGCCUGC GCAGGCC CUGAUGAG X CGAA IGCCCUC

1704 GCCUGGC C UGCCACC GGUGGCA CUGAUGAG X CGAA ICCAGGC

1705 CCUGGCC U GCCACCA UGGUGGC CUGAUGAG X CGAA IGCCAGG

1708 GGCCUGC C ACCAGCU AGCUGGU CUGAUGAG X CGAA ICAGGCC

1709 GCCUGCC A CCAGCUG CAGCUGG CUGAUGAG X CGAA IGCAGGC

1711 CUGCCAC C AGCUGUG CACAGCU CUGAUGAG X CGAA IUGGCAG

1712 UGCCACC A GCUGUGC GCACAGC CUGAUGAG X CGAA IGUGGCA

1715 CACCAGC U GUGCGCC GGCGCAC CUGAUGAG X CGAA ICUGGUG

1722 UGUGCGC C CGAGGGC GCCCUCG CUGAUGAG X CGAA ICGCACA

1723 GUGCGCC c GAGGGCA UGCCCUC CUGAUGAG X CGAA IGCGCAC Table 34

1730 CGAGGGC A CUGCUGG CCAGCAG CUGAUGAG X CGAA ICCCUCG

1732 AGGGCAC U GCUGGGG CCCCAGC CUGAUGAG X CGAA IUGCCCU

1735 GCACUGC U GGGGUCC GGACCCC CUGAUGAG X CGAA ICAGUGC

1742 UGGGGUC C AGGGCCC GGGCCCU CUGAUGAG X CGAA IACCCCA

1743 GGGGUCC A GGGCCCA UGGGCCC CUGAUGAG X CGAA IGACCCC

1748 CCAGGGC C CACCCAG CUGGGUG CUGAUGAG X CGAA ICCCUGG

1749 CAGGGCC C ACCCAGU ACUGGGU CUGAUGAG X CGAA IGCCCUG

1750 AGGGCCC A CCCAGUG CACUGGG CUGAUGAG X CGAA IGGCCCU

1752 GGCCCAC C CAGUGUG CACACUG CUGAUGAG X CGAA IUGGGCC

1753 GCCCACC C AGUGUGU ACACACU CUGAUGAG X CGAA IGUGGGC

1754 CCCACCC A GUGUGUC GACACAC CUGAUGAG X CGAA IGGUGGG

1762 GUGUGUC A ACUGCAG CUGCAGU CUGAUGAG X CGAA IACACAC

1765 UGUCAAC U GCAGCCA UGGCUGC CUGAUGAG X CGAA IUUGACA

1768 CAACUGC A GCCAGUU AACUGGC CUGAUGAG X CGAA ICAGUUG

1771 CUGCAGC C AGUUCCU AGGAACU CUGAUGAG X CGAA ICUGCAG

1772 UGCAGCC A GUUCCUU AAGGAAC CUGAUGAG X CGAA IGCUGCA

1777 CCAGUUC C UUCGGGG CCCCGAA CUGAUGAG X CGAA IAACUGG

1778 CAGUUCC U UCGGGGC GCCCCGA CUGAUGAG X CGAA IGAACUG

1786 UCGGGGC C AGGAGUG CACUCCU CUGAUGAG X CGAA ICCCCGA

1787 CGGGGCC A GGAGUGC GCACUCC CUGAUGAG X CGAA IGCCCCG

1807 GGAAUGC C GAGUACU AGUACUC CUGAUGAG X CGAA ICAUUCC

1814 CGAGUAC U GCAGGGG CCCCUGC CUGAUGAG X CGAA IUACUCG

1817 GUACUGC A GGGGCUC GAGCCCC CUGAUGAG X CGAA ICAGUAC

1823 CAGGGGC U CCCCAGG CCUGGGG CUGAUGAG X CGAA ICCCCUG

1825 GGGGCUC C CCAGGGA UCCCUGG CUGAUGAG X CGAA IAGCCCC

1826 GGGCUCC C CAGGGAG CUCCCUG CUGAUGAG X CGAA IGAGCCC

1827 GGCUCCC C AGGGAGU ACUCCCU CUGAUGAG X CGAA IGGAGCC

1828 GCUCCCC A GGGAGUA UACUCCC CUGAUGAG X CGAA IGGGAGC

1845 UGAAUGC C AGGCACU AGUGCCU CUGAUGAG X CGAA ICAUUCA

1846 GAAUGCC A GGCACUG CAGUGCC CUGAUGAG X CGAA IGCAUUC

1850 GCCAGGC A CUGUUUG CAAACAG CUGAUGAG X CGAA ICCUGGC

1852 CAGGCAC U GUUUGCC GGCAAAC CUGAUGAG X CGAA IUGCCUG

1859 UGUUUGC C GUGCCAC GUGGCAC CUGAUGAG X CGAA ICAAACA

1864 GCCGUGC C ACCCUGA UCAGGGU CUGAUGAG X CGAA ICACGGC

1865 CCGUGCC A CCCUGAG CUCAGGG CUGAUGAG X CGAA IGCACGG

1867 GUGCCAC C CUGAGUG CACUCAG CUGAUGAG X CGAA IUGGCAC

1868 UGCCACC C UGAGUGU ACACUCA CUGAUGAG X CGAA IGUGGCA

1869 GCCACCC U GAGUGUC GACACUC CUGAUGAG X CGAA IGGUGGC

1877 GAGUGUC A GCCCCAG CUGGGGC CUGAUGAG X CGAA IACACUC

1880 UGUCAGC C CCAGAAU AUUCUGG CUGAUGAG X CGAA ICUGACA

1881 GUCAGCC C CAGAAUG CAUUCUG CUGAUGAG X CGAA IGCUGAC

1882 UCAGCCC C AGAAUGG CCAUUCU CUGAUGAG X CGAA IGGCUGA

1883 CAGCCCC A GAAUGGC GCCAUUC CUGAUGAG X CGAA IGGGCUG

1891 GAAUGGC U CAGUGAC GUCACUG CUGAUGAG X CGAA ICCAUUC

1893 AUGGCUC A GUGACCU AGGUCAC CUGAUGAG X CGAA IAGCCAU

1899 CAGUGAC C UGUUUUG CAAAACA CUGAUGAG X CGAA IUCACUG

1900 AGUGACC U GUUUUGG CCAAAAC CUGAUGAG X CGAA IGUCACU Table 34

1910 UUUGGAC C GGAGGCU AGCCUCC CUGAUGAG X CGAA IUCCAAA

1917 CGGAGGC U GACCAGU ACUGGUC CUGAUGAG X CGAA ICCUCCG

1921 GGCUGAC C AGUGUGU ACACACU CUGAUGAG X CGAA IUCAGCC

1922 GCUGACC A GUGUGUG CACACAC CUGAUGAG X CGAA IGUCAGC

1932 GUGUGGC C UGUGCCC GGGCACA CUGAUGAG X CGAA ICCACAC

1933 UGUGGCC U GUGCCCA UGGGCAC CUGAUGAG X CGAA IGCCACA

1938 CCUGUGC C CACUAUA UAUAGUG CUGAUGAG X CGAA ICACAGG

1939 CUGUGCC C ACUAUAA UUAUAGU CUGAUGAG X CGAA IGCACAG

1940 UGUGCCC A CUAUAAG CUUAUAG CUGAUGAG X CGAA IGGCACA

1942 UGCCCAC U AUAAGGA UCCUUAU CUGAUGAG X CGAA IUGGGCA

1951 UAAGGAC C CUCCCUU AAGGGAG CUGAUGAG X CGAA IUCCUUA

1952 AAGGACC C UCCCUUC GAAGGGA CUGAUGAG X CGAA IGUCCUU

1953 AGGACCC U CCCUUCU AGAAGGG CUGAUGAG X CGAA IGGUCCU

1955 GACCCUC C CUUCUGC GCAGAAG CUGAUGAG X CGAA IAGGGUC

1956 ACCCUCC C UUCUGCG CGCAGAA CUGAUGAG X CGAA IGAGGGU

1957 CCCUCCC U UCUGCGU ACGCAGA CUGAUGAG X CGAA IGGAGGG

1960 UCCCUUC U GCGUGGC GCCACGC CUGAUGAG X CGAA IAAGGGA

1968 GCGUGGC C CGCUGCC GGCAGCG CUGAUGAG X CGAA ICCACGC

1969 CGUGGCC c GCUGCCC GGGCAGC CUGAUGAG X CGAA IGCCACG

1972 GGCCCGC u GCCCCAG CUGGGGC CUGAUGAG X CGAA ICGGGCC

1975 CCGCUGC c CCAGCGG CCGCUGG CUGAUGAG X CGAA ICAGCGG

1976 CGCUGCC c CAGCGGU ACCGCUG CUGAUGAG X CGAA IGCAGCG

1977 GCUGCCC c AGCGGUG CACCGCU CUGAUGAG X CGAA IGGCAGC

1978 CUGCCCC A GCGGUGU ACACCGC CUGAUGAG X CGAA IGGGCAG

1991 GUGAAAC C UGACCUC GAGGUCA CUGAUGAG X CGAA IUUUCAC

1992 UGAAACC U GACCUCU AGAGGUC CUGAUGAG X CGAA IGUUUCA

1996 ACCUGAC C UCUCCUA UAGGAGA CUGAUGAG X CGAA IUCAGGU

1997 CCUGACC u CUCCUAC GUAGGAG CUGAUGAG X CGAA IGUCAGG

1999 UGACCUC u CCUACAU AUGUAGG CUGAUGAG X CGAA IAGGUCA

2001 ACCUCUC c UACAUGC GCAUGUA CUGAUGAG X CGAA IAGAGGU

2002 CCUCUCC u ACAUGCC GGCAUGU CUGAUGAG X CGAA IGAGAGG

2005 CUCCUAC A UGCCCAU AUGGGCA CUGAUGAG X CGAA IUAGGAG

2009 UACAUGC C CAUCUGG CCAGAUG CUGAUGAG X CGAA ICAUGUA

2010 ACAUGCC C AUCUGGA UCCAGAU CUGAUGAG X CGAA IGCAUGU

2011 CAUGCCC A UCUGGAA UUCCAGA CUGAUGAG X CGAA IGGCAUG

2014 GCCCAUC U GGAAGUU AACUUCC CUGAUGAG X CGAA IAUGGGC

2024 AAGUUUC C AGAUGAG CUCAUCU CUGAUGAG X CGAA IAAACUU

2025 AGUUUCC A GAUGAGG CCUCAUC CUGAUGAG X CGAA IGAAACU

2040 AGGGCGC A UGCCAGC GCUGGCA CUGAUGAG X CGAA ICGCCCU

2044 CGCAUGC C AGCCUUG CAAGGCU CUGAUGAG X CGAA ICAUGCG

2045 GCAUGCC A GCCUUGC GCAAGGC CUGAUGAG X CGAA IGCAUGC

2048 UGCCAGC C UUGCCCC GGGGCAA CUGAUGAG X CGAA ICUGGCA

2049 GCCAGCC U UGCCCCA UGGGGCA CUGAUGAG X CGAA IGCUGGC

2053 GCCUUGC C CCAUCAA UUGAUGG CUGAUGAG X CGAA ICAAGGC

2054 CCUUGCC C CAUCAAC GUUGAUG CUGAUGAG X CGAA IGCAAGG

2055 CUUGCCC C AUCAACU AGUUGAU CUGAUGAG X CGAA IGGCAAG

2056 UUGCCCC A UCAACUG CAGUUGA CUGAUGAG X CGAA IGGGCAA Table 34

2059 CCCCAUC A ACUGCAC GUGCAGU CUGAUGAG X CGAA IAUGGGG

2062 CAUCAAC U GCACCCA UGGGUGC CUGAUGAG X CGAA IUUGAUG

2065 CAACUGC A CCCACUC GAGUGGG CUGAUGAG X CGAA ICAGUUG

2067 ACUGCAC C CACUCCU AGGAGUG CUGAUGAG X CGAA IUGCAGU

2068 CUGCACC C ACUCCUG CAGGAGU CUGAUGAG X CGAA IGUGCAG

2069 UGCACCC A CUCCUGU ACAGGAG CUGAUGAG X CGAA IGGUGCA

2071 CACCCAC U CCUGUGU ACACAGG CUGAUGAG X CGAA IUGGGUG

2073 ' CCCACUC C UGUGUGG CCACACA CUGAUGAG X CGAA IAGUGGG

2074 CCACUCC U GUGUGGA UCCACAC CUGAUGAG X CGAA IGAGUGG

2083 UGUGGAC C UGGAUGA UCAUCCA CUGAUGAG X CGAA IUCCACA

2084 GUGGACC U GGAUGAC GUCAUCC CUGAUGAG X CGAA IGUCCAC

2092 GGAUGAC A AGGGCUG CAGCCCU CUGAUGAG X CGAA IUCAUCC

2098 CAAGGGC U GCCCCGC GCGGGGC CUGAUGAG X CGAA ICCCUUG

2101 GGGCUGC C CCGCCGA UCGGCGG CUGAUGAG X CGAA ICAGCCC

2102 GGCUGCC C CGCCGAG CUCGGCG CUGAUGAG X CGAA IGCAGCC

2103 GCUGCCC C GCCGAGC GCUCGGC CUGAUGAG X CGAA IGGCAGC

2106 GCCCCGC C GAGCAGA UCUGCUC CUGAUGAG X CGAA ICGGGGC

2111 GCCGAGC A GAGAGCC GGCUCUC CUGAUGAG X CGAA ICUCGGC

2118 AGAGAGC C AGCCCUC GAGGGCU CUGAUGAG X CGAA ICUCUCU

2119 GAGAGCC A GCCCUCU AGAGGGC CUGAUGAG X CGAA IGCUCUC

2122 AGCCAGC C CUCUGAC GUCAGAG CUGAUGAG X CGAA ICUGGCU

2123 GCCAGCC C UCUGACG CGUCAGA CUGAUGAG X CGAA IGCUGGC

2124 CCAGCCC u CUGACGU ACGUCAG CUGAUGAG X CGAA IGGCUGG

2126 AGCCCUC u GACGUCC GGACGUC CUGAUGAG X CGAA IAGGGCU

2133 UGACGUC c AUCAUCU AGAUGAU CUGAUGAG X CGAA IACGUCA

2134 GACGUCC A UCAUCUC GAGAUGA CUGAUGAG X CGAA IGACGUC

2137 GUCCAUC A UCUCUGC GCAGAGA CUGAUGAG X CGAA IAUGGAC

2140 CAUCAUC U CUGCGGU ACCGCAG CUGAUGAG X CGAA IAUGAUG

2142 UCAUCUC U GCGGUGG CCACCGC CUGAUGAG X CGAA IAGAUGA

2155 GGUUGGC A UUCUGCU AGCAGAA CUGAUGAG X CGAA ICCAACC

2159 GGCAUUC U GCUGGUC GACCAGC CUGAUGAG X CGAA IAAUGCC

2162 AUUCUGC U GGUCGUG CACGACC CUGAUGAG X CGAA ICAGAAU

2173 CGUGGUC U UGGGGGU ACCCCCA CUGAUGAG X CGAA IACCACG

2185 GGUGGUC U UUGGGAU AUCCCAA CUGAUGAG X CGAA IACCACC

2194 UGGGAUC C UCAUCAA UUGAUGA CUGAUGAG X CGAA IAUCCCA

2195 GGGAUCC U CAUCAAG CUUGAUG CUGAUGAG X CGAA IGAUCCC

2197 GAUCCUC A UCAAGCG CGCUUGA CUGAUGAG X CGAA IAGGAUC

2200 CCUCAUC A AGCGACG CGUCGCU CUGAUGAG X CGAA IAUGAGG

2210 CGACGGC A GCAGAAG CUUCUGC CUGAUGAG X CGAA ICCGUCG

2213 CGGCAGC A GAAGAUC GAUCUUC CUGAUGAG X CGAA ICUGCCG

2221 GAAGAUC C GGAAGUA UACUUCC CUGAUGAG X CGAA IAUCUUC

2230 GAAGUAC A CGAUGCG CGCAUCG CUGAUGAG X CGAA IUACUUC

2243 CGGAGAC U GCUGCAG CUGCAGC CUGAUGAG X CGAA IUCUCCG

2246 AGACUGC U GCAGGAA UUCCUGC CUGAUGAG X CGAA ICAGUCU

2249 CUGCUGC A GGAAACG CGUUUCC CUGAUGAG X CGAA ICAGCAG

2261 ACGGAGC U GGUGGAG CUCCACC CUGAUGAG X CGAA ICUCCGU

2270 GUGGAGC C GCUGACA UGUCAGC CUGAUGAG X CGAA ICUCCAC Table .34

2273 GAGCCGC U GACACCU AGGUGUC CUGAUGAG X CGAA ICGGCUC

2277 CGCUGAC A CCUAGCG CGCUAGG CUGAUGAG X CGAA IUCAGCG

2279 CUGACAC C UAGCGGA UCCGCUA CUGAUGAG X CGAA IUGUCAG

2280 UGACACC U AGCGGAG CUCCGCU CUGAUGAG X CGAA IGUGUCA

2294 GCGAUGC C CAACCAG CUGGUUG CUGAUGAG X CGAA ICAUCGC

2295 CGAUGCC C AACCAGG CCUGGUU CUGAUGAG X CGAA IGCAUCG

2296 GAUGCCC A ACCAGGC GCCUGGU CUGAUGAG X CGAA IGGCAUC

2299 GCCCAAC C AGGCGCA UGCGCCU CUGAUGAG X CGAA IUUGGGC

2300 CCCAACC A GGCGCAG CUGCGCC CUGAUGAG X CGAA IGUUGGG

2306 CAGGCGC A GAUGCGG CCGCAUC CUGAUGAG X CGAA ICGCCUG

2317 GCGGAUC C UGAAAGA UCUUUCA CUGAUGAG X CGAA IAUCCGC

2318 CGGAUCC U GAAAGAG CUCUUUC CUGAUGAG X CGAA IGAUCCG

2333 ACGGAGC U GAGGAAG CUUCCUC CUGAUGAG X CGAA ICUCCGU

2351 AAGGUGC U UGGAUCU AGAUCCA CUGAUGAG X CGAA ICACCUU

2358 UUGGAUC U GGCGCUU AAGCGCC CUGAUGAG X CGAA IAUCCAA

2364 CUGGCGC U UUUGGCA UGCCAAA CUGAUGAG X CGAA ICGCCAG

2371 UUUUGGC A CAGUCUA UAGACUG CUGAUGAG X CGAA ICCAAAA

2373 UUGGCAC A GUCUACA UGUAGAC CUGAUGAG X CGAA IUGCCAA

2377 CACAGUC U ACAAGGG CCCUUGU CUGAUGAG X CGAA IACUGUG

2380 AGUCUAC A AGGGCAU AUGCCCU CUGAUGAG X CGAA IUAGACU

2386 CAAGGGC A UCUGGAU AUCCAGA CUGAUGAG X CGAA ICCCUUG

2389 GGGCAUC U GGAUCCC GGGAUCC CUGAUGAG X CGAA IAUGCCC

2395 CUGGAUC C CUGAUGG CCAUCAG CUGAUGAG X CGAA IAUCCAG

2396 UGGAUCC C UGAUGGG CCCAUCA CUGAUGAG X CGAA IGAUCCA

2397 GGAUCCC U GAUGGGG CCCCAUC CUGAUGAG X CGAA IGGAUCC

2420 AAAAUUC C AGUGGCC GGCCACU CUGAUGAG X CGAA IAAUUUU

2421 AAAUUCC A GUGGCCA UGGCCAC CUGAUGAG X CGAA IGAAUUU

2427 CAGUGGC C AUCAAAG CUUUGAU CUGAUGAG X CGAA ICCACUG

2428 AGUGGCC A UCAAAGU ACUUUGA CUGAUGAG X CGAA IGCCACU

2431 GGCCAUC A AAGUGUU AACACUU CUGAUGAG X CGAA IAUGGCC

2449 GGAAAAC A CAUCCCC GGGGAUG CUGAUGAG X CGAA IUUUUCC

2451 AAAACAC A UCCCCCA UGGGGGA CUGAUGAG X CGAA IUGUUUU

2454 ACACAUC C CCCAAAG CUUUGGG CUGAUGAG X CGAA IAUGUGU

2455 CACAUCC C CCAAAGC GCUUUGG CUGAUGAG X CGAA IGAUGUG

2456 ACAUCCC C CAAAGCC GGCUUUG CUGAUGAG X CGAA IGGAUGU

2457 CAUCCCC C AAAGCCA UGGCUUU CUGAUGAG X CGAA IGGGAUG

2458 AUCCCCC A AAGCCAA UUGGCUU CUGAUGAG X CGAA IGGGGAU

2463 CCAAAGC C AACAAAG CUUUGUU CUGAUGAG X CGAA ICUUUGG

2464 CAAAGCC A ACAAAGA UCUUUGU CUGAUGAG X CGAA IGCUUUG

2467 AGCCAAC A AAGAAAU AUUUCUU CUGAUGAG X CGAA IUUGGCU

2476 AGAAAUC U UAGACGA UCGUCUA CUGAUGAG X CGAA IAUUUCU

2487 ACGAAGC A UACGUGA UCACGUA CUGAUGAG X CGAA ICUUCGU

2499 UGAUGGC U GGUGUGG CCACACC CUGAUGAG X CGAA ICCAUCA

2509 UGUGGGC U CCCCAUA UAUGGGG CUGAUGAG X CGAA ICCCACA

2511 UGGGCUC C CCAUAUG CAUAUGG CUGAUGAG X CGAA IAGCCCA

2512 GGGCUCC C CAUAUGU ACAUAUG CUGAUGAG X CGAA IGAGCCC

2513 GGCUCCC C AUAUGUC GACAUAU CUGAUGAG X CGAA IGGAGCC Table 34

2514 GCUCCCC A UAUGUCU AGACAUA CUGAUGAG X CGAA IGGGAGC

2521 AUAUGUC U CCCGCCU AGGCGGG CUGAUGAG X CGAA IACAUAU

2523 AUGUCUC C CGCCUUC GAAGGCG CUGAUGAG X CGAA IAGACAU

2524 UGUCUCC C GCCUUCU AGAAGGC CUGAUGAG X CGAA IGAGACA

2527 CUCCCGC C UUCUGGG CCCAGAA CUGAUGAG X CGAA ICGGGAG

2528 UCCCGCC U UCUGGGC GCCCAGA CUGAUGAG X CGAA IGCGGGA

2531 CGCCUUC U GGGCAUC GAUGCCC CUGAUGAG X CGAA IAAGGCG

2536 UCUGGGC A UCUGCCU AGGCAGA CUGAUGAG X CGAA ICCCAGA

2539 GGGCAUC U GCCUGAC GUCAGGC CUGAUGAG X CGAA IAUGCCC

2542 CAUCUGC C UGACAUC GAUGUCA CUGAUGAG X CGAA ICAGAUG

2543 AUCUGCC U GACAUCC GGAUGUC CUGAUGAG X CGAA IGCAGAU

2547 GCCUGAC A UCCACGG CCGUGGA CUGAUGAG X CGAA IUCAGGC

2550 UGACAUC C ACGGUGC GCACCGU CUGAUGAG X CGAA IAUGUCA

2551 GACAUCC A CGGUGCA UGCACCG CUGAUGAG X CGAA IGAUGUC

2558 ACGGUGC A GCUGGUG CACCAGC CUGAUGAG X CGAA ICACCGU

2561 GUGCAGC U GGUGACA UGUCACC CUGAUGAG X CGAA ICUGCAC

2568 UGGUGAC A CAGCUUA UAAGCUG CUGAUGAG X CGAA IUCACCA

2570 GUGACAC A GCUUAUG CAUAAGC CUGAUGAG X CGAA IUGUCAC

2573 ACACAGC U UAUGCCC GGGCAUA CUGAUGAG X CGAA ICUGUGU

2579 CUUAUGC C CUAUGGC GCCAUAG CUGAUGAG X CGAA ICAUAAG

2580 UUAUGCC C UAUGGCU AGCCAUA CUGAUGAG X CGAA IGCAUAA

2581 UAUGCCC U AUGGCUG CAGCCAU CUGAUGAG X CGAA IGGCAUA

2587 CUAUGGC U GCCUCUU AAGAGGC CUGAUGAG X CGAA ICCAUAG

2590 UGGCUGC C UCUUAGA UCUAAGA CUGAUGAG X CGAA ICAGCCA

2591 GGCUGCC U CUUAGAC GUCUAAG CUGAUGAG X CGAA IGCAGCC

2593 CUGCCUC u UAGACCA UGGUCUA CUGAUGAG X CGAA IAGGCAG

2599 CUUAGAC c AUGUCCG CGGACAU CUGAUGAG X CGAA IUCUAAG

2600 UUAGACC A UGUCCGG CCGGACA CUGAUGAG X CGAA IGUCUAA

2605 CCAUGUC C GGGAAAA UUUUCCC CUGAUGAG X CGAA IACAUGG

2614 GGAAAAC C GCGGACG CGUCCGC CUGAUGAG X CGAA IUUUUCC

2623 CGGACGC C UGGGCUC GAGCCCA CUGAUGAG X CGAA ICGUCCG

2624 GGACGCC U GGGCUCC GGAGCCC CUGAUGAG X CGAA IGCGUCC

2629 CCUGGGC U CCCAGGA UCCUGGG CUGAUGAG X CGAA ICCCAGG

2631 UGGGCUC C CAGGACC GGUCCUG CUGAUGAG X CGAA IAGCCCA

2632 GGGCUCC C AGGACCU AGGUCCU CUGAUGAG X CGAA IGAGCCC

2633 GGCUCCC A GGACCUG CAGGUCC CUGAUGAG X CGAA IGGAGCC

2638 CCAGGAC C UGCUGAA UUCAGCA CUGAUGAG X CGAA IUCCUGG

2639 CAGGACC U GCUGAAC GUUCAGC CUGAUGAG X CGAA IGUCCUG

2642 GACCUGC U GAACUGG CCAGUUC CUGAUGAG X CGAA ICAGGUC

2647 GCUGAAC U GGUGUAU AUACACC CUGAUGAG X CGAA IUUCAGC

2657 UGUAUGC A GAUUGCC GGCAAUC CUGAUGAG X CGAA ICAUACA

2664 AGAUUGC C AAGGGGA UCCCCUU CUGAUGAG X CGAA ICAAUCU

2665 GAUUGCC A AGGGGAU AUCCCCU CUGAUGAG X CGAA IGCAAUC

2677 GAUGAGC U ACCUGGA UCCAGGU CUGAUGAG X CGAA ICUCAUC

2680 GAGCUAC C UGGAGGA UCCUCCA CUGAUGAG X CGAA IUAGCUC

2681 AGCUACC U GGAGGAU AUCCUCC CUGAUGAG X CGAA IGUAGCU

2696 GUGCGGC U CGUACAC GUGUACG CUGAUGAG X CGAA ICCGCAC Table 34

2702 CUCGUAC A CAGGGAC GUCCCUG CUGAUGAG X CGAA IUACGAG

2704 CGUACAC A GGGACUU AAGUCCC CUGAUGAG X CGAA IUGUACG

2710 CAGGGAC U UGGCCGC GCGGCCA CUGAUGAG X CGAA IUCCCUG

2715 ACUUGGC C GCUCGGA UCCGAGC CUGAUGAG X CGAA ICCAAGU

2718 UGGCCGC U CGGAACG CGUUCCG CUGAUGAG X CGAA ICGGCCA

2729 AACGUGC U GGUCAAG CUUGACC CUGAUGAG X CGAA ICACGUU

2734 GCUGGUC A AGAGUCC GGACUCU CUGAUGAG X CGAA IACCAGC

2741 AAGAGUC C CAACCAU AUGGUUG CUGAUGAG X CGAA IACUCUU

2742 AGAGUCC C AACCAUG CAUGGUU CUGAUGAG X CGAA IGACUCU

2743 GAGUCCC A ACCAUGU ACAUGGU CUGAUGAG X CGAA IGGACUC

2746 UCCCAAC C AUGUCAA UUGACAU CUGAUGAG X CGAA IUUGGGA

2747 CCCAACC A UGUCAAA UUUGACA CUGAUGAG X CGAA IGUUGGG

2752 CCAUGUC A AAAUUAC GUAAUUU CUGAUGAG X CGAA IACAUGG

2760 AAAUUAC A GACUUCG CGAAGUC CUGAUGAG X CGAA IUAAUUU

2764 UACAGAC U UCGGGCU AGCCCGA CUGAUGAG X CGAA IUCUGUA

2771 UUCGGGC U GGCUCGG CCGAGCC CUGAUGAG X CGAA ICCCGAA

2775 GGCUGGC U CGGCUGC GCAGCCG CUGAUGAG X CGAA ICCAGCC

2780 GCUCGGC U GCUGGAC GUCCAGC CUGAUGAG X CGAA ICCGAGC

2783 CGGCUGC U GGACAUU AAUGUCC CUGAUGAG X CGAA ICAGCCG

2788 GCUGGAC A UUGACGA UCGUCAA CUGAUGAG X CGAA IUCCAGC

2799 ACGAGAC A GAGUACC GGUACUC CUGAUGAG X CGAA IUCUCGU

2806 AGAGUAC C AUGCAGA UCUGCAU CUGAUGAG X CGAA IUACUCU

2807 GAGUACC A UGCAGAU AUCUGCA CUGAUGAG X CGAA IGUACUC

2811 ACCAUGC A GAUGGGG CCCCAUC CUGAUGAG X CGAA ICAUGGU

2821 UGGGGGC A AGGUGCC GGCACCU CUGAUGAG X CGAA ICCCCCA

2828 AAGGUGC C CAUCAAG CUUGAUG CUGAUGAG X CGAA ICACCUU

2829 AGGUGCC C AUCAAGU ACUUGAU CUGAUGAG X CGAA IGCACCU

2830 GGUGCCC A UCAAGUG CACUUGA CUGAUGAG X CGAA IGGCACC

2833 GCCCAUC A AGUGGAU AUCCACU CUGAUGAG X CGAA IAUGGGC

2846 AUGGCGC U GGAGUCC GGACUCC CUGAUGAG X CGAA ICGCCAU

2853 UGGAGUC C AUUCUCC GGAGAAU CUGAUGAG X CGAA IACUCCA

2854 GGAGUCC A UUCUCCG CGGAGAA CUGAUGAG X CGAA IGACUCC

2858 UCCAUUC U CCGCCGG CCGGCGG CUGAUGAG X CGAA IAAUGGA

2860 CAUUCUC C GCCGGCG CGCCGGC CUGAUGAG X CGAA IAGAAUG

2863 UCUCCGC C GGCGGUU AACCGCC CUGAUGAG X CGAA ICGGAGA

2872 GCGGUUC A CCCACCA UGGUGGG CUGAUGAG X CGAA IAACCGC

2874 GGUUCAC C CACCAGA UCUGGUG CUGAUGAG X CGAA IUGAACC

2875 GUUCACC C ACCAGAG CUCUGGU CUGAUGAG X CGAA IGUGAAC

2876 UUCACCC A CCAGAGU ACUCUGG CUGAUGAG X CGAA IGGUGAA

2878 CACCCAC C AGAGUGA UCACUCU CUGAUGAG X CGAA IUGGGUG

2879 ACCCACC A GAGUGAU AUCACUC CUGAUGAG X CGAA IGUGGGU

2907 GUGUGAC U GUGUGGG CCCACAC CUGAUGAG X CGAA IUCACAC

2918 UGGGAGC U GAUGACU AGUCAUC CUGAUGAG X CGAA ICUCCCA

2925 UGAUGAC U UUUGGGG CCCCAAA CUGAUGAG X CGAA IUCAUCA

2934 UUGGGGC C AAACCUU AAGGUUU CUGAUGAG X CGAA ICCCCAA

2935 UGGGGCC A AACCUUA UAAGGUU CUGAUGAG X CGAA IGCCCCA

2939 GCCAAAC C UUACGAU AUCGUAA CUGAUGAG X CGAA IUUUGGC Table 34

2940 CCAAACC U UACGAUG CAUCGUA CUGAUGAG X CGAA IGUUUGG

2953 UGGGAUC C CAGCCCG CGGGCUG CUGAUGAG X CGAA IAUCCCA

2954 GGGAUCC C AGCCCGG CCGGGCU CUGAUGAG X CGAA IGAUCCC

2955 GGAUCCC A GCCCGGG CCCGGGC CUGAUGAG X CGAA IGGAUCC

2958 UCCCAGC C CGGGAGA UCUCCCG CUGAUGAG X CGAA ICUGGGA

2959 CCCAGCC C GGGAGAU AUCUCCC CUGAUGAG X CGAA IGCUGGG

2968 GGAGAUC C CUGACCU AGGUCAG CUGAUGAG X CGAA IAUCUCC

2969 GAGAUCC C UGACCUG CAGGUCA CUGAUGAG X CGAA IGAUCUC

2970 AGAUCCC U GACCUGC GCAGGUC CUGAUGAG X CGAA IGGAUCU

2974 CCCUGAC C UGCUGGA UCCAGCA CUGAUGAG X CGAA IUCAGGG

2975 CCUGACC U GCUGGAA UUCCAGC CUGAUGAG X CGAA IGUCAGG

2978 GACCUGC U GGAAAAG CUUUUCC CUGAUGAG X CGAA ICAGGUC

2996 GAGCGGC U GCCCCAG CUGGGGC CUGAUGAG X CGAA ICCGCUC

2999 CGGCUGC C CCAGCCC GGGCUGG CUGAUGAG X CGAA ICAGCCG

3000 GGCUGCC C CAGCCCC GGGGCUG CUGAUGAG X CGAA IGCAGCC

3001 GCUGCCC C AGCCCCC GGGGGCU CUGAUGAG X CGAA IGGCAGC

3002 CUGCCCC A GCCCCCC GGGGGGC CUGAUGAG X CGAA IGGGCAG

3005 CCCCAGC C CCCCAUC GAUGGGG CUGAUGAG X CGAA ICUGGGG

3006 CCCAGCC C CCCAUCU AGAUGGG CUGAUGAG X CGAA IGCUGGG

3007 CCAGCCC C CCAUCUG CAGAUGG CUGAUGAG X CGAA IGGCUGG

3008 CAGCCCC C CAUCUGC GCAGAUG CUGAUGAG X CGAA IGGGCUG

3009 AGCCCCC C AUCUGCA UGCAGAU CUGAUGAG X CGAA IGGGGCU

3010 GCCCCCC A UCUGCAC GUGCAGA CUGAUGAG X CGAA IGGGGGC

3013 CCCCAUC U GCACCAU AUGGUGC CUGAUGAG X CGAA IAUGGGG

3016 CAUCUGC A CCAUUGA UCAAUGG CUGAUGAG X CGAA ICAGAUG

3018 UCUGCAC C AUUGAUG CAUCAAU CUGAUGAG X CGAA IUGCAGA

3019 CUGCACC A UUGAUGU ACAUCAA CUGAUGAG X CGAA IGUGCAG

3028 UGAUGUC U ACAUGAU AUCAUGU CUGAUGAG X CGAA IACAUCA

3031 UGUCUAC A UGAUCAU AUGAUCA CUGAUGAG X CGAA IUAGACA

3037 CAUGAUC A UGGUCAA UUGACCA CUGAUGAG X CGAA IAUCAUG

3043 CAUGGUC A AAUGUUG CAACAUU CUGAUGAG X CGAA IACCAUG

3061 GAUUGAC U CUGAAUG CAUUCAG CUGAUGAG X CGAA IUCAAUC

3063 UUGACUC U GAAUGUC GACAUUC CUGAUGAG X CGAA IAGUCAA

3074 UGUCGGC C AAGAUUC GAAUCUU CUGAUGAG X CGAA ICCGACA

3075 GUCGGCC A AGAUUCC GGAAUCU CUGAUGAG X CGAA IGCCGAC

3082 AAGAUUC C GGGAGUU AACUCCC CUGAUGAG X CGAA IAAUCUU

3096 UGGUGUC U GAAUUCU AGAAUUC CUGAUGAG X CGAA IACACCA

3103 UGAAUUC U CCCGCAU AUGCGGG CUGAUGAG X CGAA IAAUUCA

3105 AAUUCUC C CGCAUGG CCAUGCG CUGAUGAG X CGAA IAGAAUU

3106 AUUCUCC C GCAUGGC GCCAUGC CUGAUGAG X CGAA IGAGAAU

3109 CUCCCGC A UGGCCAG CUGGCCA CUGAUGAG X CGAA ICGGGAG

3114 GCAUGGC C AGGGACC GGUCCCU CUGAUGAG X CGAA ICCAUGC

3115 CAUGGCC A GGGACCC GGGUCCC CUGAUGAG X CGAA IGCCAUG

3121 CAGGGAC C CCCAGCG CGCUGGG CUGAUGAG X CGAA IUCCCUG

3122 AGGGACC C CCAGCGC GCGCUGG CUGAUGAG X CGAA IGUCCCU

3123 GGGACCC C CAGCGCU AGCGCUG CUGAUGAG X CGAA IGGUCCC

3124 GGACCCC C AGCGCUU AAGCGCU CUGAUGAG X CGAA IGGGUCC Table 34

3125 GACCCCC A GCGCUUU AAAGCGC CUGAUGAG X CGAA IGGGGUC

3130 CCAGCGC U UUGUGGU ACCACAA CUGAUGAG X CGAA ICGCUGG

3139 UGUGGUC A UCCAGAA UUCUGGA CUGAUGAG X CGAA IACCACA

3142 GGUCAUC C AGAAUGA UCAUUCU CUGAUGAG X CGAA IAUGACC

3143 GUCAUCC A GAAUGAG CUCAUUC CUGAUGAG X CGAA IGAUGAC

3154 UGAGGAC U UGGGCCC GGGCCCA CUGAUGAG X CGAA IUCCUCA

3160 CUUGGGC C CAGCCAG CUGGCUG CUGAUGAG X CGAA ICCCAAG

3161 UUGGGCC C AGCCAGU ACUGGCU CUGAUGAG X CGAA IGCCCAA

3162 UGGGCCC A GCCAGUC GACUGGC CUGAUGAG X CGAA IGGCCCA

3165 GCCCAGC C AGUCCCU AGGGACU CUGAUGAG X CGAA ICUGGGC

3166 CCCAGCC A GUCCCUU AAGGGAC CUGAUGAG X CGAA IGCUGGG

3170 GCCAGUC C CUUGGAC GUCCAAG CUGAUGAG X CGAA IACUGGC

3171 CCAGUCC C UUGGACA UGUCCAA CUGAUGAG X CGAA IGACUGG

3172 CAGUCCC U UGGACAG CUGUCCA CUGAUGAG X CGAA IGGACUG

3178 CUUGGAC A GCACCUU AAGGUGC CUGAUGAG X CGAA IUCCAAG

3181 GGACAGC A CCUUCUA UAGAAGG CUGAUGAG X CGAA ICUGUCC

3183 ACAGCAC C UUCUACC GGUAGAA CUGAUGAG X CGAA IUGCUGU

3184 CAGCACC U UCUACCG CGGUAGA CUGAUGAG X CGAA IGUGCUG

3187 CACCUUC U ACCGCUC GAGCGGU CUGAUGAG X CGAA IAAGGUG

3190 CUUCUAC C GCUCACU AGUGAGC CUGAUGAG X CGAA IUAGAAG

3193 CUACCGC U CACUGCU AGCAGUG CUGAUGAG X CGAA ICGGUAG

3195 ACCGCUC A CUGCUGG CCAGCAG CUGAUGAG X CGAA IAGCGGU

3197 CGCUCAC U GCUGGAG CUCCAGC CUGAUGAG X CGAA IUGAGCG

3200 UCACUGC U GGAGGAC GUCCUCC CUGAUGAG X CGAA ICAGUGA

3214 CGAUGAC A UGGGGGA UCCCCCA CUGAUGAG X CGAA IUCAUCG

3223 GGGGGAC C UGGUGGA UCCACCA CUGAUGAG X CGAA IUCCCCC

3224 GGGGACC U GGUGGAU AUCCACC CUGAUGAG X CGAA IGUCCCC

3234 UGGAUGC U GAGGAGU ACUCCUC CUGAUGAG X CGAA ICAUCCA

3245 GAGUAUC U GGUACCC GGGUACC CUGAUGAG X CGAA IAUACUC

3251 CUGGUAC C CCAGCAG CUGCUGG CUGAUGAG X CGAA IUACCAG

3252 UGGUACC C CAGCAGG CCUGCUG CUGAUGAG X CGAA IGUACCA

3253 GGUACCC G AGCAGGG CCCUGCU CUGAUGAG X CGAA IGGUACC

3254 GUACCCC A GCAGGGC GCCCUGC CUGAUGAG X CGAA IGGGUAC

3257 CCCCAGC A GGGCUUC GAAGCCC CUGAUGAG X CGAA ICUGGGG

3262 GCAGGGC U UCUUCUG CAGAAGA CUGAUGAG X CGAA ICCCUGC

3265 GGGCUUC U UCUGUCC GGACAGA CUGAUGAG X CGAA IAAGCCC

3268 CUUCUUC U GUCCAGA UCUGGAC CUGAUGAG X CGAA IAAGAAG

3272 UUCUGUC C AGACCCU AGGGUCU CUGAUGAG X CGAA IACAGAA

3273 UCUGUCC A GACCCUG CAGGGUC CUGAUGAG X CGAA IGACAGA

3277 UCCAGAC C CUGCCCC GGGGCAG CUGAUGAG X CGAA IUCUGGA

3278 CCAGACC C UGCCCCG CGGGGCA CUGAUGAG X CGAA IGUCUGG

3279 CAGACCC U GCCCCGG CCGGGGC CUGAUGAG X CGAA IGGUCUG

3282 ACCCUGC C CCGGGCG CGCCCGG CUGAUGAG X CGAA ICAGGGU

3283 CCCUGCC C CGGGCGC GCGCCCG CUGAUGAG X CGAA IGCAGGG

3284 CCUGCCC C GGGCGCU AGCGCCC CUGAUGAG X CGAA IGGCAGG

3291 CGGGCGC U GGGGGCA UGCCCCC CUGAUGAG X CGAA ICGCCCG

3298 UGGGGGC A UGGUCCA UGGACCA CUGAUGAG X CGAA ICCCCCA Table j4

3304 CAUGGUC C ACCACAG CUGUGGU CUGAUGAG X CGAA IACCAUG

3305 AUGGUCC A CCACAGG CCUGUGG CUGAUGAG X CGAA IGACCAU

3307 GGUCCAC C ACAGGCA UGCCUGU CUGAUGAG X CGAA IUGGACC

3308 GUCCACC A CAGGCAC GUGCCUG CUGAUGAG X CGAA IGUGGAC

3310 CCACCAC A GGCACCG CGGUGCC CUGAUGAG X CGAA IUGGUGG

3314 CACAGGC A CCGCAGC GCUGCGG CUGAUGAG X CGAA ICCUGUG

3316 CAGGCAC C GCAGCUC GAGCUGC CUGAUGAG X CGAA IUGCCUG

3319 GCACCGC A GCUCAUC GAUGAGC CUGAUGAG X CGAA ICGGUGC

3322 CCGCAGC U CAUCUAC GUAGAUG CUGAUGAG ^•X CGAA ICUGCGG

3324 GCAGCUC A UCUACCA UGGUAGA CUGAUGAG X CGAA IAGCUGC

3327 GCUCAUC U ACCAGGA UCCUGGU CUGAUGAG X CGAA IAUGAGC

3330 CAUCUAC C AGGAGUG CACUCCU CUGAUGAG X CGAA IUAGAUG

3331 AUCUACC A GGAGUGG CCACUCC CUGAUGAG X CGAA IGUAGAU

3349 UGGGGAC C UGACACU AGUGUCA CUGAUGAG X CGAA IUCCCCA

3350 GGGGACC U GACACUA UAGUGUC CUGAUGAG X CGAA IGUCCCC

3354 ACCUGAC A CUAGGGC GCCCUAG CUGAUGAG X CGAA IUCAGGU

3356 CUGACAC U AGGGCUG CAGCCCU CUGAUGAG X CGAA IUGUCAG

3362 CUAGGGC U GGAGCCC GGGCUCC CUGAUGAG X CGAA ICCCUAG

3368 CUGGAGC C CUCUGAA UUCAGAG CUGAUGAG X CGAA ICUCCAG

3369 UGGAGCC C UCUGAAG CUUCAGA CUGAUGAG X CGAA IGCUCCA

3370 GGAGCCC U CUGAAGA UCUUCAG CUGAUGAG X CGAA IGGCUCC

3372 AGCCCUC U GAAGAGG CCUCUUC CUGAUGAG X CGAA IAGGGCU

3384 AGGAGGC C CCCAGGU ACCUGGG CUGAUGAG X CGAA ICCUCCU

3385 GGAGGCC C CCAGGUC GACCUGG CUGAUGAG X CGAA IGCCUCC

3386 GAGGCCC C CAGGUCU AGACCUG CUGAUGAG X CGAA IGGCCUC

3387 AGGCCCC C AGGUCUC GAGACCU CUGAUGAG X CGAA IGGGCCU

3388 GGCCCCC A GGUCUCC GGAGACC CUGAUGAG X CGAA IGGGGCC

3393 CCAGGUC U CCACUGG CCAGUGG CUGAUGAG X CGAA IACCUGG

3395 AGGUCUC C ACUGGCA UGCCAGU CUGAUGAG X CGAA IAGACCU

3396 GGUCUCC A CUGGCAC GUGCCAG CUGAUGAG X CGAA IGAGACC

3398 UCUCCAC U GGCACCC GGGUGCC CUGAUGAG X CGAA IUGGAGA

3402 CACUGGC A CCCUCCG CGGAGGG CUGAUGAG X CGAA ICCAGUG

3404 CUGGCAC C CUCCGAA UUCGGAG CUGAUGAG X CGAA IUGCCAG

3405 UGGCACC C UCCGAAG CUUCGGA CUGAUGAG X CGAA IGUGCCA

3406 GGCACCC U CCGAAGG CCUUCGG CUGAUGAG X CGAA IGGUGCC

3408 CACCCUC C GAAGGGG CCCCUUC CUGAUGAG X CGAA IAGGGUG

3417 AAGGGGC U GGCUCCG CGGAGCC CUGAUGAG X CGAA ICCCCUU

3421 GGCUGGC U CCGAUGU ACAUCGG CUGAUGAG X CGAA ICCAGCC

3423 CUGGCUC C GAUGUAU AUACAUC CUGAUGAG X CGAA IAGCCAG

3442 UGGUGAC C UGGGAAU AUUCCCA CUGAUGAG X CGAA IUCACCA

3443 GGUGACC U GGGAAUG CAUUCCC CUGAUGAG X CGAA IGUCACC

3456 UGGGGGC A GCCAAGG CCUUGGC CUGAUGAG X CGAA ICCCCCA

3459 GGGCAGC C AAGGGGC GCCCCUU CUGAUGAG X CGAA ICUGCCC

3460 GGCAGCC A AGGGGCU AGCCCCU CUGAUGAG X CGAA IGCUGCC

3467 AAGGGGC U GCAAAGC GCUUUGC CUGAUGAG X CGAA ICCCCUU

3470 GGGCUGC A AAGCCUC GAGGCUU CUGAUGAG X CGAA ICAGCCC

3475 GCAAAGC C UCCCCAC GUGGGGA CUGAUGAG X CGAA ICUUUGC Table 34

3476 CAAAGCC U CCCCACA UGUGGGG CUGAUGAG X CGAA IGCUUUG

3478 AAGCCUC C CCACACA UGUGUGG CUGAUGAG X CGAA IAGGCUU

3479 AGCCUCC C CACACAU AUGUGUG CUGAUGAG X CGAA IGAGGCU

3480 GCCUCCC C ACACAUG CAUGUGU CUGAUGAG X CGAA IGGAGGC

3481 CCUCCCC A CACAUGA UCAUGUG CUGAUGAG X CGAA IGGOAGG

3483 UCCCCAC A CAUGACC GGUCAUG CUGAUGAG X CGAA IUGGGGA

3485 CCCACAC A UGACCCC GGGGUCA CUGAUGAG X CGAA IUGUGGG

3490 ACAUGAC C CCAGCCC GGGCUGG CUGAUGAG X CGAA IUCAUGU

3491 CAUGACC C CAGCCCU AGGGCUG CUGAUGAG X CGAA IGUCAUG

3492 AUGACCC C AGCCCUC GAGGGCU CUGAUGAG X CGAA IGGUCAU

3493 UGACCCC A GCCCUCU AGAGGGC CUGAUGAG X CGAA IGGGUCA

3496 CCCCAGC C CUCUACA UGUAGAG CUGAUGAG X CGAA ICUGGGG

3497 CCCAGCC C UCUACAG CUGUAGA CUGAUGAG X CGAA IGCUGGG

3498 CCAGCCC U CUACAGC GCUGUAG CUGAUGAG X CGAA IGGCUGG

3500 AGCCCUC U ACAGCGG CCGCUGU CUGAUGAG X CGAA IAGGGCU

3503 CCUCUAC A GCGGUAC GUACCGC CUGAUGAG X CGAA IUAGAGG

3511 GCGGUAC A GUGAGGA UCCUCAC CUGAUGAG X CGAA IUACCGC

3520 UGAGGAC C CCACAGU ACUGUGG CUGAUGAG X CGAA IUCCUCA

3521 GAGGACC C CACAGUA UACUGUG CUGAUGAG X CGAA IGUCCUC

3522 AGGACCC C ACAGUAC GUACUGU CUGAUGAG X CGAA IGGUCCU

3523 GGACCCC A CAGUACC GGUACUG CUGAUGAG X CGAA IGGGUCC

3525 ACCCCAC A GUACCCC GGGGUAC CUGAUGAG X CGAA IUGGGGU

3530 ACAGUAC C CCUGCCC GGGCAGG CUGAUGAG X CGAA IUACUGU

3531 CAGUACC C CUGCCCU AGGGCAG CUGAUGAG X CGAA IGUACUG

3532 AGUACCC C UGCCCUC GAGGGCA CUGAUGAG X CGAA IGGUACU

3533 GUACCCC U GCCCUCU AGAGGGC CUGAUGAG X CGAA IGGGUAC

3536 CCCCUGC C CUCUGAG CUCAGAG CUGAUGAG X CGAA ICAGGGG

3537 CCCUGCC C UCUGAGA UCUCAGA CUGAUGAG X CGAA IGCAGGG

3538 CCUGCCC U CUGAGAC GUCUCAG CUGAUGAG X CGAA IGGCAGG

3540 UGCCCUC U GAGACUG CAGUCUC CUGAUGAG X CGAA IAGGGCA

3546 CUGAGAC U GAUGGCU AGCCAUC CUGAUGAG X CGAA IUCUCAG

3553 UGAUGGC U ACGUUGC GCAACGU CUGAUGAG X CGAA ICCAUCA

3561 ACGUUGC C CCCCUGA UCAGGGG CUGAUGAG X CGAA ICAACGU

3562 CGUUGCC C CCCUGAC GUCAGGG CUGAUGAG X CGAA IGCAACG

3563 GUUGCCC C CCUGACC GGUCAGG CUGAUGAG X CGAA IGGCAAC

3564 UUGCCCC C CUGACCU AGGUCAG CUGAUGAG X CGAA IGGGCAA

3565 UGCCCCC C UGACCUG CAGGUCA CUGAUGAG X CGAA IGGGGCA

3566 GCCCCCC U GACCUGC GCAGGUC CUGAUGAG X CGAA IGGGGGC

3570 CCCUGAC C UGCAGCC GGCUGCA CUGAUGAG X CGAA IUCAGGG

3571 CCUGACC U GCAGCCC GGGCUGC CUGAUGAG X CGAA IGUCAGG

3574 GACCUGC A GCCCCCA UGGGGGC CUGAUGAG X CGAA ICAGGUC

3577 CUGCAGC C CCCAGCC GGCUGGG CUGAUGAG X CGAA ICUGCAG

3578 UGCAGCC C CCAGCCU AGGCUGG CUGAUGAG X CGAA IGCUGCA

3579 GCAGCCC C CAGCCUG CAGGCUG CUGAUGAG X CGAA IGGCUGC

3580 CAGCCCC C AGCCUGA UCAGGCU CUGAUGAG X CGAA IGGGCUG

3581 AGCCCCC A GCCUGAA UUCAGGC CUGAUGAG X CGAA IGGGGCU

3584 CCCCAGC C UGAAUAU AUAUUCA CUGAUGAG X CGAA ICUGGGG Table 34

3585 CCCAGCC U GAAUAUG CAUAUUC CUGAUGAG X CGAA IGCUGGG

3598 UGUGAAC C AGCCAGA UCUGGCU CUGAUGAG X CGAA IUUCACA

3599 GUGAACC A GCCAGAU AUCUGGC CUGAUGAG X CGAA IGUUCAC

3602 AACCAGC C AGAUGUU AACAUCU CUGAUGAG X CGAA ICUGGUU

3603 ACCAGCC A GAUGUUC GAACAUC CUGAUGAG X CGAA IGCUGGU

3614 GUUCGGC C CCAGCCC GGGCUGG CUGAUGAG X CGAA ICCGAAC

3615 UUCGGCC C CAGCCCC GGGGCUG CUGAUGAG X CGAA IGCCGAA

3616 UCGGCCC C AGCCCCC GGGGGCU CUGAUGAG X CGAA IGGCCGA

3617 CGGCCCC A GCCCCCU AGGGGGC CUGAUGAG X CGAA IGGGCCG

3620 CCCCAGC C CCCUUCG CGAAGGG CUGAUGAG X CGAA ICUGGGG

3621 CCCAGCC C CCUUCGC GCGAAGG CUGAUGAG X CGAA IGCUGGG

3622 CCAGCCC C CUUCGCC GGCGAAG CUGAUGAG X CGAA IGGCUGG

3623 CAGCCCC C UUCGCCC GGGCGAA CUGAUGAG X CGAA IGGGCUG

3624 AGCCCCC U UCGCCCC GGGGCGA CUGAUGAG X CGAA IGGGGCU

3629 CCUUCGC C CCGAGAG CUCUCGG CUGAUGAG X CGAA ICGAAGG

3630 CUUCGCC C CGAGAGG CCUCUCG CUGAUGAG X CGAA IGCGAAG

3631 UUCGCCC C GAGAGGG CCCUCUC CUGAUGAG X CGAA IGGCGAA

3640 AGAGGGC C CUCUGCC GGCAGAG CUGAUGAG X CGAA ICCCUCU

3641 GAGGGCC C UCUGCCU AGGCAGA CUGAUGAG X CGAA IGCCCUC

3642 AGGGCCC U CUGCCUG CAGGCAG CUGAUGAG X CGAA IGGCCCU

3644 GGCCCUC U GCCUGCU AGCAGGC CUGAUGAG X CGAA IAGGGCC

3647 CCUCUGC C UGCUGCC GGCAGCA CUGAUGAG X CGAA ICAGAGG

3648 CUCUGCC U GCUGCCC GGGCAGC CUGAUGAG X CGAA IGCAGAG

3651 UGCCUGC U GCCCGAC GUCGGGC CUGAUGAG X CGAA ICAGGCA

3654 CUGCUGC c CGACCUG CAGGUCG CUGAUGAG X CGAA ICAGCAG

3655 UGCUGCC c GACCUGC GCAGGUC CUGAUGAG X CGAA IGCAGCA

3659 GCCCGAC c UGCUGGU ACCAGCA CUGAUGAG X CGAA IUCGGGC

3660 CCCGACC u GCUGGUG CACCAGC CUGAUGAG X CGAA IGUCGGG

3663 GACCUGC u GGUGCCA UGGCACC CUGAUGAG X CGAA ICAGGUC

3669 CUGGUGC c ACUCUGG CCAGAGU CUGAUGAG X CGAA ICACCAG

3670 UGGUGCC A CUCUGGA UCCAGAG CUGAUGAG X CGAA IGCACCA

3672 GUGCCAC U CUGGAAA UUUCCAG CUGAUGAG X CGAA IUGGCAC

3674 GCCACUC U GGAAAGG CCUUUCC CUGAUGAG X CGAA IAGUGGC

3683 GAAAGGC C CAAGACU AGUCUUG CUGAUGAG X CGAA ICCUUUC

3684 AAAGGCC c AAGACUC GAGUCUU CUGAUGAG X CGAA IGCCUUU

3685 AAGGCCC A AGACUCU AGAGUCU CUGAUGAG X CGAA IGGCCUU

3690 CCAAGAC U CUCUCCC GGGAGAG CUGAUGAG X CGAA IUCUUGG

3692 AAGACUC U CUCCCCA UGGGGAG CUGAUGAG X CGAA IAGUCUU

3694 GACUCUC U CCCCAGG CCUGGGG CUGAUGAG X CGAA IAGAGUC

3696 CUCUCUC C CCAGGGA UCCCUGG CUGAUGAG X CGAA IAGAGAG

3697 UCUCUCC C CAGGGAA UUCCCUG CUGAUGAG X CGAA IGAGAGA

3698 CUCUCCC C AGGGAAG CUUCCCU CUGAUGAG X CGAA IGGAGAG

3699 ucucccc A GGGAAGA UCUUCCC CUGAUGAG X CGAA IGGGAGA

3718 GGUCGUC A AAGACGU ACGUCUU CUGAUGAG X CGAA IACGACC

3732 UUUUUGC C UUUGGGG CCCCAAA CUGAUGAG X CGAA ICAAAAA

3733 UUUUGCC U UUGGGGG CCCCCAA CUGAUGAG X CGAA IGCAAAA

3744 GGGGUGC C GUGGAGA UCUCCAC CUGAUGAG X CGAA ICACCCC Table 34

3754 GGAGAAC C CCGAGUA UACUCGG CUGAUGAG X CGAA IUUCUCC

3755 GAGAACC C CGAGUAC GUACUCG CUGAUGAG X CGAA IGUUCUC

3756 AGAACCC C GAGUACU AGUACUC CUGAUGAG X CGAA IGGUUCU

3763 CGAGUAC U UGACACC GGUGUCA CUGAUGAG X CGAA IUACUCG

3768 ACUUGAC A CCCCAGG CCUGGGG CUGAUGAG X CGAA IUCAAGU

3770 UUGACAC C CCAGGGA UCCCUGG CUGAUGAG X CGAA IUGUCAA

3771 UGACACC C CAGGGAG CUCCCUG CUGAUGAG X CGAA IGUGUCA

3772 GACACCC C AGGGAGG CCUCCCU CUGAUGAG X CGAA IGGUGUC

3773 ACACCCC A GGGAGGA UCCUCCC CUGAUGAG X CGAA IGGGUGU

3783 GAGGAGC U GCCCCUC GAGGGGC CUGAUGAG X CGAA ICUCCUC

3786 GAGCUGC C CCUCAGC GCUGAGG CUGAUGAG X CGAA ICAGCUC

3787 AGCUGCC C CUCAGCC GGCUGAG CUGAUGAG X CGAA IGCAGCU

3788 GCUGCCC C UCAGCCC GGGCUGA CUGAUGAG X CGAA IGGCAGC

3789 CUGCCCC U CAGCCCC GGGGCUG CUGAUGAG X CGAA IGGGCAG

3791 GCCCCUC A GCCCCAC GUGGGGC CUGAUGAG X CGAA IAGGGGC

3794 CCUCAGC C CCACCCU AGGGUGG CUGAUGAG X CGAA ICUGAGG

3795 CUCAGCC C CACCCUC GAGGGUG CUGAUGAG X CGAA IGCUGAG

3796 UCAGCCC C ACCCUCC GGAGGGU CUGAUGAG X CGAA IGGCUGA

3797 CAGCCCC A CCCUCCU AGGAGGG CUGAUGAG X CGAA IGGGCUG

3799 GCCCCAC C CUCCUCC GGAGGAG CUGAUGAG X CGAA IUGGGGC

3800 CCCCACC C uccuccu AGGAGGA CUGAUGAG X CGAA IGUGGGG

3801 CCCACCC U CCUCCUG CAGGAGG CUGAUGAG X CGAA IGGUGGG

3803 CACCCUC C UCCUGCC GGCAGGA CUGAUGAG X CGAA IAGGGUG

3804 ACCCUCC U CCUGCCU AGGCAGG CUGAUGAG X CGAA IGAGGGU

3806 CCUCCUC C UGCCUUC GAAGGCA CUGAUGAG X CGAA IAGGAGG

3807 cuccucc U GCCUUCA UGAAGGC CUGAUGAG X CGAA IGAGGAG

3810 CUCCUGC C UUCAGCC GGCUGAA CUGAUGAG X CGAA ICAGGAG

3811 UCCUGCC U UCAGCCC GGGCUGA CUGAUGAG X CGAA IGCAGGA

3814 UGCCUUC A GCCCAGC GCUGGGC CUGAUGAG X CGAA IAAGGCA

3817 CUUCAGC C CAGCCUU AAGGCUG CUGAUGAG X CGAA ICUGAAG

3818 UUCAGCC C AGCCUUC GAAGGCU CUGAUGAG X CGAA IGCUGAA

3819 UCAGCCC A GCCUUCG CGAAGGC CUGAUGAG X CGAA IGGCUGA

3822 GCCCAGC C UUCGACA UGUCGAA CUGAUGAG X CGAA ICUGGGC

3823 CCCAGCC U UCGACAA UUGUCGA CUGAUGAG X CGAA IGCUGGG

3829 CUUCGAC A ACCUCUA UAGAGGU CUGAUGAG X CGAA IUCGAAG

3832 CGACAAC C UCUAUUA UAAUAGA CUGAUGAG X CGAA IUUGUCG

3833 GACAACC U CUAUUAC GUAAUAG CUGAUGAG X CGAA IGUUGUC

3835 CAACCUC U AUUACUG CAGUAAU CUGAUGAG X CGAA IAGGUUG

3841 CUAUUAC U GGGACCA UGGUCCC CUGAUGAG X CGAA IUAAUAG

3847 CUGGGAC C AGGACCC GGGUCCU CUGAUGAG X CGAA IUCCCAG

3848 UGGGACC A GGACCCA UGGGUCC CUGAUGAG X CGAA IGUCCCA

3853 CCAGGAC C CACCAGA UCUGGUG CUGAUGAG X CGAA IUCCUGG

3854 CAGGACC C ACCAGAG CUCUGGU CUGAUGAG X CGAA IGUCCUG

3855 AGGACCC A CCAGAGC GCUCUGG CUGAUGAG X CGAA IGGUCCU

3857 GACCCAC C AGAGCGG CCGCUCU CUGAUGAG X CGAA IUGGGUC

3858 ACCCACC A GAGCGGG CCCGCUC CUGAUGAG X CGAA IGUGGGU

3870 GGGGGGC U CCACCCA UGGGUGG CUGAUGAG X CGAA ICCCCCC Table 34

3872 GGGGCUC C ACCCAGC GCUGGGU CUGAUGAG X CGAA IAGCCCC

3873 GGGCUCC A CCCAGCA UGCUGGG CUGAUGAG X CGAA IGAGCCC

3875 GCUCCAC C CAGCACC GGUGCUG CUGAUGAG X CGAA IUGGAGC

3876 CUCCACC C AGCACCU AGGUGCU CUGAUGAG X CGAA IGUGGAG

3877 UCCACCC A GCACCUU AAGGUGC CUGAUGAG X CGAA IGGUGGA

3880 ACCCAGC A CCUUCAA UUGAAGG CUGAUGAG X CGAA ICUGGGU

3882 CCAGCAC C UUCAAAG CUUUGAA CUGAUGAG X CGAA IUGCUGG

3883 CAGCACC U UCAAAGG CCUUUGA CUGAUGAG X CGAA IGUGCUG

3886 CACCUUC A AAGGGAC GUCCCUU CUGAUGAG X CGAA IAAGGUG

3894 AAGGGAC A CCUACGG CCGUAGG CUGAUGAG X CGAA IUCCCUU

3896 GGGACAC C UACGGCA UGCCGUA CUGAUGAG X CGAA IUGUCCC

3897 GGACACC U ACGGCAG CUGCCGU CUGAUGAG X CGAA IGUGUCC

3903 CUACGGC A GAGAACC GGUUCUC CUGAUGAG X CGAA ICCGUAG

3910 AGAGAAC C CAGAGUA UACUCUG CUGAUGAG X CGAA IUUCUCU

3911 GAGAACC C AGAGUAC GUACUCU CUGAUGAG X CGAA IGUUCUC

3912 AGAACCC A GAGUACC GGUACUC CUGAUGAG X CGAA IGGUUCU

3919 AGAGUAC C UGGGUCU AGACCCA CUGAUGAG X CGAA IUACUCU

3920 GAGUACC U GGGUCUG CAGACCC CUGAUGAG X CGAA IGUACUC

3926 CUGGGUC U GGACGUG CACGUCC CUGAUGAG X CGAA IACCCAG

3935 GACGUGC C AGUGUGA UCACACU CUGAUGAG X CGAA ICACGUC

3936 ACGUGCC A GUGUGAA UUCACAC CUGAUGAG X CGAA IGCACGU

3945 UGUGAAC C AGAAGGC GCCUUCU CUGAUGAG X CGAA IUUCACA

3946 GUGAACC A GAAGGCC GGCCUUC CUGAUGAG X CGAA IGUUCAC

3953 AGAAGGC C AAGUCCG CGGACUU CUGAUGAG X CGAA ICCUUCU

3954 GAAGGCC A AGUCCGC GCGGACU CUGAUGAG X CGAA IGCCUUC

3959 CCAAGUC C GCAGAAG CUUCUGC CUGAUGAG X CGAA IACUUGG

3962 AGUCCGC A GAAGCCC GGGCUUC CUGAUGAG X CGAA ICGGACU

3968 CAGAAGC C CUGAUGU ACAUCAG CUGAUGAG X CGAA ICUUCUG

3969 AGAAGCC C UGAUGUG CACAUCA CUGAUGAG X CGAA IGCUUCU

3970 GAAGCCC U GAUGUGU ACACAUC CUGAUGAG X CGAA IGGCUUC

3979 AUGUGUC C UCAGGGA UCCCUGA CUGAUGAG X CGAA IACACAU

3980 UGUGUCC U CAGGGAG CUCCCUG CUGAUGAG X CGAA IGACACA

3982 UGUCCUC A GGGAGCA UGCUCCC CUGAUGAG X CGAA IAGGACA

3989 AGGGAGC A GGGAAGG CCUUCCC CUGAUGAG X CGAA ICUCCCU

3998 GGAAGGC C UGACUUC GAAGUCA CUGAUGAG X CGAA ICCUUCC

3999 GAAGGCC U GACUUCU AGAAGUC CUGAUGAG X CGAA IGCCUUC

4003 GCCUGAC U UCUGCUG CAGCAGA CUGAUGAG X CGAA IUCAGGC

4006 UGACUUC U GCUGGCA UGCCAGC CUGAUGAG X CGAA IAAGUCA

4009 CUUCUGC U GGCAUCA UGAUGCC CUGAUGAG X CGAA ICAGAAG

4013 UGCUGGC A UCAAGAG CUCUUGA CUGAUGAG X CGAA ICCAGCA

4016 UGGCAUC A AGAGGUG CACCUCU CUGAUGAG X CGAA IAUGCCA

4031 GGAGGGC C CUCCGAC GUCGGAG CUGAUGAG X CGAA ICCCUCC

4032 GAGGGCC C UCCGACC GGUCGGA CUGAUGAG X CGAA IGCCCUC

4033 AGGGCCC U CCGACCA UGGUCGG CUGAUGAG X CGAA IGGCCCU

4035 GGCCCUC C GACCACU AGUGGUC CUGAUGAG X CGAA IAGGGCC

4039 CUCCGAC C ACUUCCA UGGAAGU CUGAUGAG X CGAA IUCGGAG

4040 UCCGACC A CUUCCAG CUGGAAG CUGAUGAG X CGAA IGUCGGA Table 34

4042 CGACCAC U UCCAGGG CCCUGGA CUGAUGAG X CGAA IUGGUCG

4045 CCACUUC C AGGGGAA UUCCCCU CUGAUGAG X CGAA IAAGUGG

4046 CACUUCC A GGGGAAC GUUCCCC CUGAUGAG X CGAA IGAAGUG

4054 GGGGAAC C UGCCAUG CAUGGCA CUGAUGAG X CGAA IUUCCCC

4055 GGGAACC U GCCAUGC GCAUGGC CUGAUGAG X CGAA IGUUCCC

4058 AACCUGC C AUGCCAG CUGGCAU CUGAUGAG X CGAA ICAGGUU

4059 ACCUGCC A UGCCAGG CCUGGCA CUGAUGAG X CGAA IGCAGGU

4063 GCCAUGC C AGGAACC GGUUCCU CUGAUGAG X CGAA ICAUGGC

4064 CCAUGCC A GGAACCU AGGUUCC CUGAUGAG X CGAA IGCAUGG

4070 CAGGAAC C UGUCCUA UAGGACA CUGAUGAG X CGAA IUUCCUG

4071 AGGAACC U GUCCUAA UUAGGAC CUGAUGAG X CGAA IGUUCCU

4075 ACCUGUC C UAAGGAA UUCCUUA CUGAUGAG X CGAA IACAGGU

4076 CCUGUCC U AAGGAAC GUUCCUU CUGAUGAG X CGAA IGACAGG

4084 AAGGAAC C UUCCUUC GAAGGAA CUGAUGAG X CGAA IUUCCUU

4085 AGGAACC U UCCUUCC GGAAGGA CUGAUGAG X CGAA IGUUCCU

4088 AACCUUC C UUCCUGC GCAGGAA CUGAUGAG X CGAA IAAGGUU

4089 ACCUUCC U UCCUGCU AGCAGGA CUGAUGAG X CGAA IGAAGGU

4092 UUCCUUC C UGCUUGA UCAAGCA CUGAUGAG X CGAA IAAGGAA

4093 UCCUUCC U GCUUGAG CUCAAGC CUGAUGAG X CGAA IGAAGGA

4096 UUCCUGC U UGAGUUC GAACUCA CUGAUGAG X CGAA ICAGGAA

4104 UGAGUUC C CAGAUGG CCAUCUG CUGAUGAG X CGAA IAACUCA

4105 GAGUUCC C AGAUGGC GCCAUCU CUGAUGAG X CGAA IGAACUC

4106 AGUUCCC A GAUGGCU AGCCAUC CUGAUGAG X CGAA IGGAACU

4113 AGAUGGC U GGAAGGG CCCUUCC CUGAUGAG X CGAA ICCAUCU

4124 AGGGGUC C AGCCUCG CGAGGCU CUGAUGAG X CGAA IACCCCU

4125 GGGGUCC A GCCUCGU ACGAGGC CUGAUGAG X CGAA IGACCCC

4128 GUCCAGC C UCGUUGG CCAACGA CUGAUGAG X CGAA ICUGGAC

4129 UCCAGCC U CGUUGGA UCCAACG CUGAUGAG X CGAA IGCUGGA

4145 GAGGAAC A GCACUGG CCAGUGC CUGAUGAG X CGAA IUUCCUC

4148 GAACAGC A CUGGGGA UCCCCAG CUGAUGAG X CGAA ICUGUUC

4150 ACAGCAC U GGGGAGU ACUCCCC CUGAUGAG X CGAA IUGCUGU

4159 GGGAGUC U UUGUGGA UCCACAA CUGAUGAG X CGAA IACUCCC

4170 UGGAUUC U GAGGCCC GGGCCUC CUGAUGAG X CGAA IAAUCCA

4176 CUGAGGC C CUGCCCA UGGGCAG CUGAUGAG X CGAA ICCUCAG

4177 UGAGGCC C UGCCCAA UUGGGCA CUGAUGAG X CGAA IGCCUCA

4178 GAGGCCC U GCCCAAU AUUGGGC CUGAUGAG X CGAA IGGCCUC

4181 GCCCUGC C CAAUGAG CUCAUUG CUGAUGAG X CGAA ICAGGGC

4182 CCCUGCC C AAUGAGA UCUCAUU CUGAUGAG X CGAA IGCAGGG

4183 CCUGCCC A AUGAGAC GUCUCAU CUGAUGAG X CGAA IGGCAGG

4191 AUGAGAC U CUAGGGU ACCCUAG CUGAUGAG X CGAA IUCUCAU

4193 GAGACUC U AGGGUCC GGACCCU CUGAUGAG X CGAA IAGUCUC

4200 UAGGGUC C AGUGGAU AUCCACU CUGAUGAG X CGAA IACCCUA

4201 AGGGUCC A GUGGAUG CAUCCAC CUGAUGAG X CGAA IGACCCU

4210 UGGAUGC C ACAGCCC GGGCUGU CUGAUGAG X CGAA ICAUCCA

4211 GGAUGCC A CAGCCCA UGGGCUG CUGAUGAG X CGAA IGCAUCC

4213 AUGCCAC A GCCCAGC GCUGGGC CUGAUGAG X CGAA IUGGCAU

4216 CCACAGC C CAGCUUG CAAGCUG CUGAUGAG X CGAA ICUGUGG Table 34

4217 CACAGCC C AGCUUGG CCAAGCU CUGAUGAG X CGAA IGCUGUG

4218 ACAGCCC A GCUUGGC GCCAAGC CUGAUGAG X CGAA IGGCUGU

4221 GCCCAGC U UGGCCCU AGGGCCA CUGAUGAG X CGAA ICUGGGC

4226 GCUUGGC C CUUUCCU AGGAAAG CUGAUGAG X CGAA ICCAAGC

4227 CUUGGCC C UUUCCUU AAGGAAA CUGAUGAG X CGAA IGCCAAG

4228 UUGGCCC U UUCCUUC GAAGGAA CUGAUGAG X CGAA IGGCCAA

4232 CCCUUUC C UUCCAGA UCUGGAA CUGAUGAG X CGAA IAAAGGG

4233 CCUUUCC U UCCAGAU AUCUGGA CUGAUGAG X CGAA IGAAAGG

4236 UUCCUUC C AGAUCCU AGGAUCU CUGAUGAG X CGAA IAAGGAA

4237 UCCUUCC A GAUCCUG CAGGAUC CUGAUGAG X CGAA IGAAGGA

4242 CCAGAUC C UGGGUAC GUACCCA CUGAUGAG X CGAA IAUCUGG

4243 CAGAUCC U GGGUACU AGUACCC CUGAUGAG X CGAA IGAUCUG

4250 UGGGUAC U GAAAGCC GGCUUUC CUGAUGAG X CGAA IUACCCA

4257 UGAAAGC C UUAGGGA UCCCUAA CUGAUGAG X CGAA ICUUUCA

4258 GAAAGCC u UAGGGAA UUCCCUA CUGAUGAG X CGAA IGCUUUC

4268 GGGAAGC u GGCCUGA UCAGGCC CUGAUGAG X CGAA ICUUCCC

4272 AGCUGGC c UGAGAGG CCUCUCA CUGAUGAG X CGAA ICCAGCU

4273 GCUGGCC u GAGAGGG CCCUCUC CUGAUGAG X CGAA IGCCAGC

4289 AAGCGGC c CUAAGGG CCCUUAG CUGAUGAG X CGAA ICCGCUU

4290 AGCGGCC c UAAGGGA UCCCUUA CUGAUGAG X CGAA IGCCGCU

4291 GCGGCCC u AAGGGAG CUCCCUU CUGAUGAG X CGAA IGGCCGC

4303 GAGUGUC u AAGAACA UGUUCUU CUGAUGAG X CGAA IACACUC

4310 UAAGAAC A AAAGCGA UCGCUUU CUGAUGAG X CGAA IUUCUUA

4319 AAGCGAC C CAUUCAG CUGAAUG CUGAUGAG X CGAA IUCGCUU

4320 AGCGACC C AUUCAGA UCUGAAU CUGAUGAG X CGAA IGUCGCU

4321 GCGACCC A UUCAGAG CUCUGAA CUGAUGAG X CGAA IGGUCGC

4325 CCCAUUC A GAGACUG CAGUCUC CUGAUGAG X CGAA IAAUGGG

4331 CAGAGAC U GUCCCUG CAGGGAC CUGAUGAG X CGAA IUCUCUG

4335 GACUGUC C CUGAAAC GUUUCAG CUGAUGAG X CGAA IACAGUC

4336 ACUGUCC C UGAAACC GGUUUCA CUGAUGAG X CGAA IGACAGU

4337 CUGUCCC U GAAACCU AGGUUUC CUGAUGAG X CGAA IGGACAG

4343 CUGAAAC G UAGUACU AGUACUA CUGAUGAG X CGAA IUUUCAG

4344 UGAAACC U AGUACUG CAGUACU CUGAUGAG X CGAA IGUUUCA

4350 CUAGUAC U GCCCCCC GGGGGGC CUGAUGAG X CGAA IUACUAG

4353 GUACUGC C CCCCAUG CAUGGGG CUGAUGAG X CGAA ICAGUAC

4354 UACUGCC C CCCAUGA UCAUGGG CUGAUGAG X CGAA IGCAGUA

4355 ACUGCCC C CCAUGAG CUCAUGG CUGAUGAG X CGAA IGGCAGU

4356 CUGCCCC C CAUGAGG CCUCAUG CUGAUGAG X CGAA IGGGCAG

4357 UGCCCCC C AUGAGGA UCCUCAU CUGAUGAG X CGAA IGGGGCA

4358 GCCCCCC A UGAGGAA UUCCUCA CUGAUGAG X CGAA IGGGGGC

4371 AAGGAAC A GCAAUGG CCAUUGC CUGAUGAG X CGAA IUUCCUU

4374 GAACAGC A AUGGUGU ACACCAU CUGAUGAG X CGAA ICUGUUC

4383 UGGUGUC A GUAUCCA UGGAUAC CUGAUGAG X CGAA IACACCA

4389 CAGUAUC C AGGCUUU AAAGCCU CUGAUGAG X CGAA IAUACUG

4390 AGUAUCC A GGCUUUG CAAAGCC CUGAUGAG X CGAA IGAUACU

4394 UCCAGGC U UUGUACA UGUACAA CUGAUGAG X CGAA ICCUGGA

4401 UUUGUAC A GAGUGCU AGCACUC CUGAUGAG X CGAA IUACAAA Table 34

Seq Accession No. = HSERB2R (Human c-erb-B-2 mRNA; 4473 bp) Core Sequence = CUGAUGAG X CGAA (X = GCCGAAAGGC or other stem II)

Table 35 Table 35: HBV Strains and Accession numbers

Table 35

Table 36

Table 36: HBV Substrate Sequence

LOCUS HPBADR1CG 3221 bp DNA circular VRL

06-MAR-1995

DEFINITION Hepatitis B virus , complete genome.

ACCESSION M38454

*The nucleotide number referred to in that table is the position of the 5' end of the oligo in this sequence. Table 37 Table 37: Human HBV Hammerhead Ribozyme and Target Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

13 CCACCACT T TCCACCAA 34 UUGGUGGA CUGAUGAG X CGAA AGUGGUGG 2543

14 CACCACTT T CCACCAAA 35 UUUGGUGG CUGAUGAG X CGAA AAGUGGUG 2544

15 ACCACTTT C CACCAAAC 36 GUUUGGUG CUGAUGAG X CGAA AAAGUGGU 2545

25 ACCAAACT C TTCAAGAT 37 AUCUUGAA CUGAUGAG X CGAA AGUUUGGU 2546

27 CAAACTCT T CAAGATCC 38 GGAUCUUG CUGAUGAG X CGAA AGAGUUUG 2547

28 AAACTCTT C AAGATCCC 39 GGGAUCUU CUGAUGAG X CGAA AAGAGUUU 2548

34 TTCAAGAT C CCAGAGTC 40 GACUCUGG CUGAUGAG X CGAA AUCUUGAA 2549

42 CCCAGAGT C AGGGCCCT 41 AGGGCCCU CUGAUGAG X CGAA ACUCUGGG 2550

53 GGCCCTGT A CTTTCCTG 42 CAGGAAAG CUGAUGAG X CGAA ACAGGGCC 2551

56 CCTGTACT T TCCTGCTG 43 CAGCAGGA CUGAUGAG X CGAA AGUACAGG 2552

57 CTGTACTT T CCTGCTGG 44 CCAGCAGG CUGAUGAG X CGAA AAGUACAG 2553

58 TGTACTTT C CTGCTGGT 45 ACCAGCAG CUGAUGAG X CGAA AAAGUACA 2554

71 TGGTGGCT C CAGTTCAG 46 CUGAACUG CUGAUGAG X CGAA AGCCACCA 2555

76 GCTCCAGT T CAGGAACA 47 UGUUCCUG CUGAUGAG X CGAA ACUGGAGC 2556

77 CTCCAGTT C AGGAACAG 48 CUGUUCCU CUGAUGAG X CGAA AACUGGAG 2557

97 GCCCTGCT C AGAATACT 49 AGUAUUCU CUGAUGAG X CGAA AGCAGGGC 2558

103 CTCAGAAT A CTGTCTCT 50 AGAGACAG CUGAUGAG X CGAA AUUCUGAG 2559

108 AATACTGT C TCTGCCAT 51 AUGGCAGA CUGAUGAG X CGAA ACAGUAUU 2560

110 TACTGTCT C TGCCATAT 52 AUAUGGCA CUGAUGAG X CGAA AGACAGUA 2561

117 TCTGCCAT A TCGTCAAT 53 AUUGACGA CUGAUGAG X CGAA AUGGCAGA 2562

119 TGCCATAT C GTCAATCT 54 AGAUUGAC CUGAUGAG X CGAA AUAUGGCA 2563

122 CATATCGT C AATCTTAT 55 AUAAGAUU CUGAUGAG X CGAA ACGAUAUG 2564

126 TCGTCAAT C TTATCGAA 56 UUCGAUAA CUGAUGAG X CGAA AUUGACGA 2565

128 GTCAATCT T ATCGAAGA 57 UCUUCGAU CUGAUGAG X CGAA AGAUUGAC 2566

129 TCAATCTT A TCGAAGAC 58 GUCUUCGA CUGAUGAG X CGAA AAGAUUGA 2567

131 AATCTTAT C GAAGACTG 59 CAGUCUUC CUGAUGAG X CGAA AUAAGAUU 2568

150 GACCCTGT A CCGAACAT 60 AUGUUCGG CUGAUGAG X CGAA ACAGGGUC 2569

168 GAGAACAT C GCATCAGG 61 CCUGAUGC CUGAUGAG X CGAA AUGUUCUC 2570

173 CATCGCAT C AGGACTCC 62 GGAGUCCU CUGAUGAG X CGAA AUGCGAUG 2571

180 TCAGGACT C CTAGGACC 63 GGUCCUAG CUGAUGAG X CGAA AGUCCUGA 2572

183 GGACTCCT A GGACCCCT 64 AGGGGUCC CUGAUGAG X CGAA AGGAGUCC 2573

195 CCCCTGCT C GTGTTACA 65 UGUAACAC CUGAUGAG X CGAA AGCAGGGG 2574

200 GCTCGTGT T ACAGGCGG 66 CCGCCUGU CUGAUGAG X CGAA ACACGAGC 2575

201 CTCGTGTT A CAGGCGGG 67 CCCGCCUG CUGAUGAG X CGAA AACACGAG 2576

212 GGCGGGGT T TTTCTTGT 68 ACAAGAAA CUGAUGAG X CGAA ACCCCGCC 2577

213 GCGGGGTT T TTCTTGTT 69 AACAAGAA CUGAUGAG X CGAA AACCCCGC 2578

214 CGGGGTTT T TCTTGTTG 70 CAACAAGA CUGAUGAG X CGAA AAACCCCG 2579

215 GGGGTTTT T CTTGTTGA 71 UCAACAAG CUGAUGAG X CGAA AAAACCCC 2580

216 GGGTTTTT c TTGTTGAC 72 GUCAACAA CUGAUGAG X CGAA AAAAACCC 2581

218 GTTTTTCT T GTTGACAA 73 UUGUCAAC CUGAUGAG X CGAA AGAAAAAC 2582

221 TTTCTTGT T GACAAAAA 74 UUUUUGUC CUGAUGAG X CGAA ACAAGAAA 2583

231 ACAAAAAT c CTCACAAT 75 AUUGUGAG CUGAUGAG X CGAA AUUUUUGU 2584

234 AAAATCCT c ACAATACC 76 GGUAUUGU CUGAUGAG X CGAA AGGAUUUU 2585

240 CTCACAAT A CCACAGAG 77 CUCUGUGG CUGAUGAG X CGAA AUUGUGAG 2586

250 CACAGAGT C TAGACTCG 78 CGAGUCUA CUGAUGAG X CGAA ACUCUGUG 2587

252 CAGAGTCT A GACTCGTG 79 CACGAGUC CUGAUGAG X CGAA AGACUCUG 2588

257 TCTAGACT C GTGGTGGA 80 UCCACCAC CUGAUGAG X CGAA AGUCUAGA 2589

268 GGTGGACT T CTCTCAAT 81 AUUGAGAG CUGAUGAG X CGAA AGUCCACC 2590 Table 37

269 GTGGACTT C TCTCAATT 82 AAUUGAGA CUGAUGAG X CGAA AAGUCCAC 2591

271 GGACTTCT C TCAATTTT 83 AAAAUUGA CUGAUGAG X CGAA AGAAGUCC 2592

273 ACTTCTCT C AATTTTCT 84 AGAAAAUU CUGAUGAG X CGAA AGAGAAGU 2593

277 CTCTCAAT T TTCTAGGG 85 CCCUAGAA CUGAUGAG X CGAA AUUGAGAG 2594

278 TCTCAATT T TCTAGGGG 86 CCCCUAGA CUGAUGAG X CGAA AAUUGAGA 2595

279 CTCAATTT T CTAGGGGG 87 CCCCCUAG CUGAUGAG X CGAA AAAUUGAG 2596

280 TCAATTTT C TAGGGGGA 88 UCCCCCUA CUGAUGAG X CGAA AAAAUUGA 2597

282 AATTTTCT A GGGGGAAC 89 GUUCCCCC CUGAUGAG X CGAA AGAAAAUU 2598

301 CCGTGTGT C TTGGCCAA 90 UUGGCCAA CUGAUGAG X CGAA ACACACGG 2599

303 GTGTGTCT T GGCCAAAA 91 UUUUGGCC CUGAUGAG X CGAA AGACACAC 2600

313 GCCAAAAT T CGCAGTCC 92 GGACUGCG CUGAUGAG X CGAA AUUUUGGC 2601

314 CCAAAATT c GCAGTCCC 93 GGGACUGC CUGAUGAG X CGAA AAUUUUGG 2602

320 TTCGCAGT c CCAAATCT 94 AGAUUUGG CUGAUGAG X CGAA ACUGCGAA 2603

327 TCCCAAAT c TCCAGTCA 95 UGACUGGA CUGAUGAG X CGAA AUUUGGGA 2604

329 CCAAATCT c CAGTCACT 96 AGUGACUG CUGAUGAG X CGAA AGAUUUGG 2605

334 TCTCCAGT c ACTCACCA 97 UGGUGAGU CUGAUGAG X CGAA ACUGGAGA 2606

338 CAGTCACT c ACCAACCT 98 AGGUUGGU CUGAUGAG X CGAA AGUGACUG 2607

349 CAACCTGT T GTCCTCCA 99 UGGAGGAC CUGAUGAG X CGAA ACAGGUUG 2608

352 CCTGTTGT c CTCCAATT 100 AAUUGGAG CUGAUGAG X CGAA ACAACAGG 2609

355 GTTGTCCT c CAATTTGT 101 ACAAAUUG CUGAUGAG X CGAA AGGACAAC 2610

360 CCTCCAAT T TGTCCTGG 102 CCAGGACA CUGAUGAG X CGAA AUUGGAGG 2611

361 CTCCAATT T GTCCTGGT 103 ACCAGGAC CUGAUGAG X CGAA AAUUGGAG 2612

364 CAATTTGT c CTGGTTAT 104 AUAACCAG CUGAUGAG X CGAA ACAAAUUG 2613

370 GTCCTGGT T ATCGCTGG 105 CCAGCGAU CUGAUGAG X CGAA ACCAGGAC 2614

371 TCCTGGTT A TCGCTGGA 106 UCCAGCGA CUGAUGAG X CGAA AACCAGGA 2615

373 CTGGTTAT c GCTGGATG 107 CAUCCAGC CUGAUGAG X CGAA AUAACCAG 2616

385 GGATGTGT c TGCGGCGT 108 ACGCCGCA CUGAUGAG X CGAA ACACAUCC 2617

394 TGCGGCGT T TTATCATC 109 GAUGAUAA CUGAUGAG X CGAA ACGCCGCA 2618

395 GCGGCGTT T TATCATCT 110 AGAUGAUA CUGAUGAG X CGAA AACGCCGC 2619

396 CGGCGTTT T ATCATCTT 111 AAGAUGAU CUGAUGAG X CGAA AAACGCCG 2620

397 GGCGTTTT A TCATCTTC 112 GAAGAUGA CUGAUGAG X CGAA AAAACGCC 2621

399 CGTTTTAT C ATCTTCCT 113 AGGAAGAU CUGAUGAG X CGAA AUAAAACG 2622

402 TTTATCAT c TTCCTCTG 114 CAGAGGAA CUGAUGAG X CGAA AUGAUAAA 2623

404 TATCATCT T CCTCTGCA 115 UGCAGAGG CUGAUGAG X CGAA AGAUGAUA 2624

405 ATCATCTT c CTCTGCAT 116 AUGCAGAG CUGAUGAG X CGAA AAGAUGAU 2625

408 ATCTTCCT c TGCATCCT 117 AGGAUGCA CUGAUGAG X CGAA AGGAAGAU 2626

414 CTCTGCAT c CTGCTGCT 118 AGCAGCAG CUGAUGAG X CGAA AUGCAGAG 2627

423 CTGCTGCT A TGCCTCAT 119 AUGAGGCA CUGAUGAG X CGAA AGCAGCAG 2628

429 CTATGCCT C ATCTTCTT 120 AAGAAGAU CUGAUGAG X CGAA AGGCAUAG 2629

432 TGCCTCAT C TTCTTGTT 121 AACAAGAA CUGAUGAG X CGAA AUGAGGCA 2630

434 CCTCATCT T CTTGTTGG 122 CCAACAAG CUGAUGAG X CGAA AGAUGAGG 2631

435 CTCATCTT c TTGTTGGT 123 ACCAACAA CUGAUGAG X CGAA AAGAUGAG 2632

437 CATCTTCT T GTTGGTTC 124 GAACCAAC CUGAUGAG X CGAA AGAAGAUG 2633

440 CTTCTTGT T GGTTCTTC 125 GAAGAACC CUGAUGAG X CGAA ACAAGAAG 2634

444 TTGTTGGT T CTTCTGGA 126 UCCAGAAG CUGAUGAG X CGAA ACCAACAA 2635

445 TGTTGGTT c TTCTGGAC 127 GUCCAGAA CUGAUGAG X CGAA AACCAACA 2636

447 TTGGTTCT T CTGGACTA 128 UAGUCCAG CUGAUGAG X CGAA AGAACCAA 2637

448 TGGTTCTT c TGGACTAT 129 AUAGUCCA CUGAUGAG X CGAA AAGAACCA 2638

455 TCTGGACT A TCAAGGTA 130 UACCUUGA CUGAUGAG X CGAA AGUCCAGA 2639

457 TGGACTAT C AAGGTATG 131 CAUACCUU CUGAUGAG X CGAA AUAGUCCA 2640

463 ATCAAGGT A TGTTGCCC 132 GGGCAACA CUGAUGAG X CGAA ACCUUGAU 2641 Table 3/

467 AGGTATGT T GCCCGTTT 133 AAACGGGC CUGAUGAG X CGAA ACAUACCU 2642

474 TTGCCCGT T TGTCCTCT 134 AGAGGACA CUGAUGAG X CGAA ACGGGCAA 2643

475 TGCCCGTT T GTCCTCTA 135 UAGAGGAC CUGAUGAG X CGAA AACGGGCA 2644

478 CCGTTTGT c CTCTAATT 136 AAUUAGAG CUGAUGAG X CGAA ACAAACGG 2645

481 TTTGTCCT c TAATTCCA 137 UGGAAUUA CUGAUGAG X CGAA AGGACAAA 2646

483 TGTCCTCT A ATTCCAGG 138 CCUGGAAU CUGAUGAG X CGAA AGAGGACA 2647

486 CCTCTAAT T CCAGGATC 139 GAUCCUGG CUGAUGAG X CGAA AUUAGAGG 2648

487 CTCTAATT C CAGGATCA 140 UGAUCCUG CUGAUGAG X CGAA AAUUAGAG 2649

494 TCCAGGAT C ATCAACAA 141 UUGUUGAU CUGAUGAG X CGAA AUCCUGGA 2650

497 AGGATCAT C AACAACCA 142 UGGUUGUU CUGAUGAG X CGAA AUGAUCCU 2651

535 GCACAACT C CTGCTCAA 143 UUGAGCAG CUGAUGAG X CGAA AGUUGUGC 2652

541 CTCCTGCT C AAGGAACC 144 GGUUCCUU CUGAUGAG X CGAA AGCAGGAG 2653

551 AGGAACCT C TATGTTTC 145 GAAACAUA CUGAUGAG X CGAA AGGUUCCU 2654

553 GAACCTCT A TGTTTCCC 146 GGGAAACA CUGAUGAG X CGAA AGAGGUUC 2655

557 CTCTATGT T TCCCTCAT 147 AUGAGGGA CUGAUGAG X CGAA ACAUAGAG 2656

558 TCTATGTT T CCCTCATG 148 CAUGAGGG CUGAUGAG X CGAA AACAUAGA 2657

559 CTATGTTT C CCTCATGT 149 ACAUGAGG CUGAUGAG X CGAA AAACAUAG 2658

563 GTTTCCCT C ATGTTGCT 150 AGCAACAU CUGAUGAG X CGAA AGGGAAAC 2659

568 CCTCATGT T GCTGTACA 151 UGUACAGC CUGAUGAG X CGAA ACAUGAGG 2660

574 GTTGCTGT A CAAAACCT 152 AGGUUUUG CUGAUGAG X CGAA ACAGCAAC 2661

583 CAAAACCT A CGGACGGA 153 UCCGUCCG CUGAUGAG X CGAA AGGUUUUG 2662

604 GCACCTGT A TTCCCATC 154 GAUGGGAA CUGAUGAG X CGAA ACAGGUGC 2663

606 ACCTGTAT T CCCATCCC 155 GGGAUGGG CUGAUGAG X CGAA AUACAGGU 2664

607 CCTGTATT C CCATCCCA 156 UGGGAUGG CUGAUGAG X CGAA AAUACAGG 2665

612 ATTCCCAT C CCATCATC 157 GAUGAUGG CUGAUGAG X CGAA AUGGGAAU 2666

617 CATCCCAT C ATCTTGGG 158 CCCAAGAU CUGAUGAG X CGAA AUGGGAUG 2667

620 CCCATCAT C TTGGGCTT 159 AAGCCCAA CUGAUGAG X CGAA AUGAUGGG 2668

622 CATCATCT T GGGCTTTC 160 GAAAGCCC CUGAUGAG X CGAA AGAUGAUG 2669

628 CTTGGGCT T TCGCAAAA 161 UUUUGCGA CUGAUGAG X CGAA AGCCCAAG 2670

629 TTGGGCTT T CGCAAAAT 162 AUUUUGCG CUGAUGAG X CGAA AAGCCCAA 2671

630 TGGGCTTT C GCAAAATA 163 UAUUUUGC CUGAUGAG X CGAA AAAGCCCA 2672

638 CGCAAAAT A CCTATGGG 164 CCCAUAGG CUGAUGAG X CGAA AUUUUGCG 2673

642 AAATACCT A TGGGAGTG 165 CACUCCCA CUGAUGAG X CGAA AGGUAUUU 2674

656 GTGGGCCT C AGTCCGTT 166 AACGGACU CUGAUGAG X CGAA AGGCCCAC 2675

660 GCCTCAGT C CGTTTCTC 167 GAGAAACG CUGAUGAG X CGAA ACUGAGGC 2676

664 CAGTCCGT T TCTCTTGG 168 CCAAGAGA CUGAUGAG X CGAA ACGGACUG 2677

665 AGTCCGTT T CTCTTGGC 169 GCCAAGAG CUGAUGAG X CGAA AACGGACU 2678

666 GTCCGTTT c TCTTGGCT 170 AGCCAAGA CUGAUGAG X CGAA AAACGGAC 2679

668 CCGTTTCT c TTGGCTCA 171 UGAGCCAA CUGAUGAG X CGAA AGAAACGG 2680

670 GTTTCTCT T GGCTCAGT 172 ACUGAGCC CUGAUGAG X CGAA AGAGAAAC 2681

675 TCTTGGCT c AGTTTACT 173 AGUAAACU CUGAUGAG X CGAA AGCCAAGA 2682

679 GGCTCAGT T TACTAGTG 174 CACUAGUA CUGAUGAG X CGAA ACUGAGCC 2683

680 GCTCAGTT T ACTAGTGC 175 GCACUAGU CUGAUGAG X CGAA AACUGAGC 2684

681 CTCAGTTT A CTAGTGCC 176 GGCACUAG CUGAUGAG X CGAA AAACUGAG 2685

684 AGTTTACT A GTGCCATT 177 AAUGGCAC CUGAUGAG X CGAA AGUAAACU 2686

692 AGTGCCAT T TGTTCAGT 178 ACUGAACA CUGAUGAG X CGAA AUGGCACU 2687

693 GTGCCATT T GTTCAGTG 179 CACUGAAC CUGAUGAG X CGAA AAUGGCAC 2688

696 CCATTTGT T CAGTGGTT 180 AACCACUG CUGAUGAG X CGAA ACAAAUGG 2689

697 CATTTGTT C AGTGGTTC 181 GAACCACU CUGAUGAG X CGAA AACAAAUG 2690

704 TCAGTGGT T CGTAGGGC 182 GCCCUACG CUGAUGAG X CGAA ACCACUGA 2691

705 CAGTGGTT C GTAGGGCT 183 AGCCCUAC CUGAUGAG X CGAA AACCACUG 2692 Table 37

708 TGGTTCGT A GGGCTTTC 184 GAAAGCCC CUGAUGAG X CGAA ACGAACCA 2693

714 GTAGGGCT T TCCCCCAC 185 GUGGGGGA CUGAUGAG X CGAA AGCCCUAC 2694

715 TAGGGCTT T CCCCCACT 186 AGUGGGGG CUGAUGAG X CGAA AAGCCCUA 2695

716 AGGGCTTT C CCCCACTG 187 CAGUGGGG CUGAUGAG X CGAA AAAGCCCU 2696

726 CCCACTGT C TGGCTTTC 188 GAAAGCCA CUGAUGAG X CGAA ACAGUGGG 2697

732 GTCTGGCT T TCAGTTAT 189 AUAACUGA CUGAUGAG X CGAA AGCCAGAC 2698

733 TCTGGCTT T CAGTTATA 190 UAUAACUG CUGAUGAG X CGAA AAGCCAGA 2699

734 CTGGCTTT C AGTTATAT 191 AUAUAACU CUGAUGAG X CGAA AAAGCCAG 2700

738 CTTTCAGT T ATATGGAT 192 AUCCAUAU CUGAUGAG X CGAA ACUGAAAG 2701

739 TTTCAGTT A TATGGATG 193 CAUCCAUA CUGAUGAG X CGAA AACUGAAA 2702

741 TCAGTTAT A TGGATGAT 194 AUCAUCCA CUGAUGAG X CGAA AUAACUGA 2703

755 GATGTGGT T TTGGGGGC 195 GCCCCCAA CUGAUGAG X CGAA ACCACAUC 2704

756 ATGTGGTT T TGGGGGCC 196 GGCCCCCA CUGAUGAG X CGAA AACCACAU 2705

757 TGTGGTTT T GGGGGCCA 197 UGGCCCCC CUGAUGAG X CGAA AAACCACA 2706

769 GGCCAAGT C TGTACAAC 198 GUUGUACA CUGAUGAG X CGAA ACUUGGCC 2707

773 AAGTCTGT A CAACATCT 199 AGAUGUUG CUGAUGAG X CGAA ACAGACUU 2708

780 TACAACAT C TTGAGTCC 200 GGACUCAA CUGAUGAG X CGAA AUGUUGUA 2709

782 CAACATCT T GAGTCCCT 201 AGGGACUC CUGAUGAG X CGAA AGAUGUUG 2710

787 TCTTGAGT C CCTTTATG 202 CAUAAAGG CUGAUGAG X CGAA ACUCAAGA 2711

791 GAGTCCCT T TATGCCGC 203 GCGGCAUA CUGAUGAG X CGAA AGGGACUC 2712

792 AGTCCCTT T ATGCCGCT 204 AGCGGCAU CUGAUGAG X CGAA AAGGGACU 2713

793 GTCCCTTT A TGCCGCTG 205 CAGCGGCA CUGAUGAG X CGAA AAAGGGAC 2714

803 GCCGCTGT T ACCAATTT 206 AAAUUGGU CUGAUGAG X CGAA ACAGCGGC 2715

804 CCGCTGTT A CCAATTTT 207 AAAAUUGG CUGAUGAG X CGAA AACAGCGG 2716

810 TTACCAAT T TTCTTTTG 208 CAAAAGAA CUGAUGAG X CGAA AUUGGUAA 2717

811 TACCAATT T TCTTTTGT 209 ACAAAAGA CUGAUGAG X CGAA AAUUGGUA 2718

812 ACCAATTT T CTTTTGTC 210 GACAAAAG CUGAUGAG X CGAA AAAUUGGU 2719

813 CCAATTTT C TTTTGTCT 211 AGACAAAA CUGAUGAG X CGAA AAAAUUGG 2720

815 AATTTTCT T TTGTCTTT 212 AAAGACAA CUGAUGAG X CGAA AGAAAAUU 2721

816 ATTTTCTT T TGTCTTTG 213 CAAAGACA CUGAUGAG X CGAA AAGAAAAU 2722

817 TTTTCTTT T GTCTTTGG 214 CCAAAGAC CUGAUGAG X CGAA AAAGAAAA 2723

820 TCTTTTGT c TTTGGGTA 215 UACCCAAA CUGAUGAG X CGAA ACAAAAGA 2724

822 TTTTGTCT T TGGGTATA 216 UAUACCCA CUGAUGAG X CGAA AGACAAAA 2725

823 TTTGTCTT T GGGTATAC 217 GUAUACCC CUGAUGAG X CGAA AAGACAAA 2726

828 CTTTGGGT A TACATTTA 218 UAAAUGUA CUGAUGAG X CGAA ACCCAAAG 2727

830 TTGGGTAT A CATTTAAA 219 UUUAAAUG CUGAUGAG X CGAA AUACCCAA 2728

834 GTATACAT T TAAACCCT 220 AGGGUUUA CUGAUGAG X CGAA AUGUAUAC 2729

835 TATACATT T AAACCCTC 221 GAGGGUUU CUGAUGAG X CGAA AAUGUAUA 2730

836 ATACATTT A AACCCTCA 222 UGAGGGUU CUGAUGAG X CGAA AAAUGUAU 2731

843 TAAACCCT C ACAAAACA 223 UGUUUUGU CUGAUGAG X CGAA AGGGUUUA 2732

865 ATGGGGAT A TTCCCTTA 224 UAAGGGAA CUGAUGAG X CGAA AUCCCCAU 2733

867 GGGGATAT T CCCTTAAC 225 GUUAAGGG CUGAUGAG X CGAA AUAUCCCC 2734

868 GGGATATT C CCTTAACT 226 AGUUAAGG CUGAUGAG X CGAA AAUAUCCC 2735

872 TATTCCCT T AACTTCAT 227 AUGAAGUU CUGAUGAG X CGAA AGGGAAUA 2736

873 ATTCCCTT A ACTTCATG 228 CAUGAAGU CUGAUGAG X CGAA AAGGGAAU 2737

877 CCTTAACT T CATGGGAT 229 AUCCCAUG CUGAUGAG X CGAA AGUUAAGG 2738

878 CTTAACTT C ATGGGATA 230 UAUCCCAU CUGAUGAG X CGAA AAGUUAAG 2739

886 CATGGGAT A TGTAATTG 231 CAAUUACA CUGAUGAG X CGAA AUCCCAUG 2740

890 GGATATGT A ATTGGGAG 232 CUCCCAAU CUGAUGAG X CGAA ACAUAUCC 2741

893 TATGTAAT T GGGAGTTG 233 CAACUCCC CUGAUGAG X CGAA AUUACAUA 2742

900 TTGGGAGT T GGGGCACA 234 UGUGCCCC CUGAUGAG X CGAA ACUCCCAA 2743 Table 5/

910 GGGCACAT T GCCACAGG 235 CCUGUGGC CUGAUGAG X CGAA AUGUGCCC 2744

924 AGGAACAT A TTGTACAA 236 UUGUACAA CUGAUGAG X CGAA AUGUUCCU 2745

926 GAACATAT T GTACAAAA 237 UUUUGUAC CUGAUGAG X CGAA AUAUGUUC 2746

929 CATATTGT A CAAAAAAT 238 AUUUUUUG CUGAUGAG X CGAA ACAAUAUG 2747

938 CAAAAAAT C AAAATGTG 239 CACAUUUU CUGAUGAG X CGAA AUUUUUUG 2748

948 AAATGTGT T TTAGGAAA 240 UUUCCUAA CUGAUGAG X CGAA ACACAUUU 2749

949 AATGTGTT T TAGGAAAC 241 GUUUCCUA CUGAUGAG X CGAA AACACAUU 2750

950 ATGTGTTT T AGGAAACT 242 AGUUUCCU CUGAUGAG X CGAA AAACACAU 2751

951 TGTGTTTT A GGAAACTT 243 AAGUUUCC CUGAUGAG X CGAA AAAACACA 2752

959 AGGAAACT T CCTGTAAA 244 UUUACAGG CUGAUGAG X CGAA AGUUUCCU 2753

960 GGAAACTT C CTGTAAAC 245 GUUUACAG CUGAUGAG X CGAA AAGUUUCC 2754

965 CTTCCTGT A AACAGGCC 246 GGCCUGUU CUGAUGAG X CGAA ACAGGAAG 2755

975 ACAGGCCT A TTGATTGG 247 CCAAUCAA CUGAUGAG X CGAA AGGCCUGU 2756

977 AGGCCTAT T GATTGGAA 248 UUCCAAUC CUGAUGAG X CGAA AUAGGCCU 2757

981 CTATTGAT T GGAAAGTA 249 UACUUUCC CUGAUGAG X CGAA AUCAAUAG 2758

989 TGGAAAGT A TGTCAACG 250 CGUUGACA CUGAUGAG X CGAA ACUUUCCA 2759

993 AAGTATGT C AACGAATT 251 AAUUCGUU CUGAUGAG X CGAA ACAUACUU 2760

1001 CAACGAAT T GTGGGTCT 252 AGACCCAC CUGAUGAG X CGAA AUUCGUUG 2761

1008 TTGTGGGT C TTTTGGGG 253 CCCCAAAA CUGAUGAG X CGAA ACCCACAA 2762

1010 GTGGGTCT T TTGGGGTT 254 AACCCCAA CUGAUGAG X CGAA AGACCCAC 2763

1011 TGGGTCTT T TGGGGTTT 255 AAACCCCA CUGAUGAG X CGAA AAGACCCA 2764

1012 GGGTCTTT T GGGGTTTG 256 CAAACCCC CUGAUGAG X CGAA AAAGACCC 2765

1018 TTTGGGGT T TGCCGCCC 257 GGGCGGCA CUGAUGAG X CGAA ACCCCAAA 2766

1019 TTGGGGTT T GCCGCCCC 258 GGGGCGGC CUGAUGAG X CGAA AACCCCAA 2767

1029 CCGCCCCT T TCACGCAA 259 UUGCGUGA CUGAUGAG X CGAA AGGGGCGG 2768

1030 CGCCCCTT T CACGCAAT 260 AUUGCGUG CUGAUGAG X CGAA AAGGGGCG 2769

1031 GCCCCTTT c ACGCAATG 261^' CAUUGCGU CUGAUGAG X CGAA AAAGGGGC 2770

1045 ATGTGGAT A TTCTGCTT 262 AAGCAGAA CUGAUGAG X CGAA AUCCACAU 2771

1047 GTGGATAT T CTGCTTTA 263 UAAAGCAG CUGAUGAG X CGAA AUAUCCAC 2772

1048 TGGATATT C TGCTTTAA 264 UUAAAGCA CUGAUGAG X CGAA AAUAUCCA 2773

1053 ATTCTGCT T TAATGCCT 265 AGGCAUUA CUGAUGAG X CGAA AGCAGAAU 2774

1054 TTCTGCTT T AATGCCTT 266 AAGGCAUU CUGAUGAG X CGAA AAGCAGAA 2775

1055 TCTGCTTT A ATGCCTTT 267 AAAGGCAU CUGAUGAG X CGAA AAAGCAGA 2776

1062 TAATGCCT T TATATGCA 268 UGCAUAUA CUGAUGAG X CGAA AGGCAUUA 2777

1063 AATGCCTT T ATATGCAT 269 AUGCAUAU CUGAUGAG X CGAA AAGGCAUU 2778

1064 ATGCCTTT A TATGCATG 270 CAUGCAUA CUGAUGAG X CGAA AAAGGCAU 2779

1066 GCCTTTAT A TGCATGCA 271 UGCAUGCA CUGAUGAG X CGAA AUAAAGGC 2780

1076 GCATGCAT A CAAGCAAA 272 UUUGCUUG CUGAUGAG X CGAA AUGCAUGC 2781

1092 AACAGGCT T TTACTTTC 273 GAAAGUAA CUGAUGAG X CGAA AGCCUGUU 2782

1093 ACAGGCTT T TACTTTCT 274 AGAAAGUA CUGAUGAG X CGAA AAGCCUGU 2783

1094 CAGGCTTT T ACTTTCTC 275 GAGAAAGU CUGAUGAG X CGAA AAAGCCUG 2784

1095 AGGCTTTT A CTTTCTCG 276 CGAGAAAG CUGAUGAG X CGAA AAAAGCCU 2785

1098 CTTTTACT T TCTCGCCA 277 UGGCGAGA CUGAUGAG X CGAA AGUAAAAG 2786

1099 TTTTACTT T CTCGCCAA 278 UUGGCGAG CUGAUGAG X CGAA AAGUAAAA 2787

1100 TTTACTTT C TCGCCAAC 279 GUUGGCGA CUGAUGAG X CGAA AAAGUAAA 2788

1102 TACTTTCT C GCCAACTT 280 AAGUUGGC CUGAUGAG X CGAA AGAAAGUA 2789

1110 CGCCAACT T ACAAGGCC 281 GGCCUUGU CUGAUGAG X CGAA AGUUGGCG 2790 llll GCCAACTT A CAAGGCCT 282 AGGCCUUG CUGAUGAG X CGAA AAGUUGGC 2791

1120 CAAGGCCT T TCTAAGTA 283 UACUUAGA CUGAUGAG X CGAA AGGCCUUG 2792

1121 AAGGCCTT T CTAAGTAA 284 UUACUUAG CUGAUGAG X CGAA AAGGCCUU 2793

1122 AGGCCTTT C TAAGTAAA 285 UUUACUUA CUGAUGAG X CGAA AAAGGCCU 2794 Table 37

1124 GCCTTTCT A AGTAAACA 286 UGUUUACU CUGAUGAG X CGAA AGAAAGGC 2795

1128 TTCTAAGT A AACAGTAT 287 AUACUGUU CUGAUGAG X CGAA ACUUAGAA 2796

1135 TAAACAGT A TGTGAACC 288 GGUUCACA CUGAUGAG X CGAA ACUGUUUA 2797

1145 GTGAACCT T TACCCCGT 289 ACGGGGUA CUGAUGAG X CGAA AGGUUCAC 2798

1146 TGAACCTT T ACCCCGTT 290 AACGGGGU CUGAUGAG X CGAA AAGGUUCA 2799

1147 GAACCTTT A CCCCGTTG 291 CAACGGGG CUGAUGAG X CGAA AAAGGUUC 2800

1154 TACCCCGT T GCTCGGCA 292 UGCCGAGC CUGAUGAG X CGAA ACGGGGUA 2801

1158 CCGTTGCT C GGCAACGG 293 CCGUUGCC CUGAUGAG X CGAA AGCAACGG 2802

1173 GGCCTGGT C TATGCCAA 294 UUGGCAUA CUGAUGAG X CGAA ACCAGGCC 2803

1175 CCTGGTCT A TGCCAAGT 295 ACUUGGCA CUGAUGAG X CGAA AGACCAGG 2804

1186 CCAAGTGT T TGCTGACG 296 CGUCAGCA CUGAUGAG X CGAA ACACUUGG 2805

1187 CAAGTGTT T GCTGACGC 297 GCGUCAGC CUGAUGAG X CGAA AACACUUG 2806

1209 CCACTGGT T GGGGCTTG 298 CAAGCCCC CUGAUGAG X CGAA ACCAGUGG 2807

1216 TTGGGGCT T GGCCATAG 299 CUAUGGCC CUGAUGAG X CGAA AGCCCCAA 2808

1223 TTGGCCAT A GGCCATCA 300 UGAUGGCC CUGAUGAG X CGAA AUGGCCAA 2809

1230 TAGGCCAT C AGCGCATG 301 CAUGCGCU CUGAUGAG X CGAA AUGGCCUA 2810

1249 TGGAACCT T TGTGTCTC 302 GAGACACA CUGAUGAG X CGAA AGGUUCCA 2811

1250 GGAACCTT T GTGTCTCC 303 GGAGACAC CUGAUGAG X CGAA AAGGUUCC 2812

1255 CTTTGTGT C TCCTCTGC 304 GCAGAGGA CUGAUGAG X CGAA ACACAAAG 2813

1257 TTGTGTCT C CTCTGCCG 305 CGGCAGAG CUGAUGAG X CGAA AGACACAA 2814

1260 TGTCTCCT C TGCCGATC 306 GAUCGGCA CUGAUGAG X CGAA AGGAGACA 2815

1268 CTGCCGAT C CATACCGC 307 GCGGUAUG CUGAUGAG X CGAA AUCGGCAG 2816

1272 CGATCCAT A CCGCGGAA 308 UUCCGCGG CUGAUGAG X CGAA AUGGAUCG 2817

1283 GCGGAACT C CTAGCCGC 309 GCGGCUAG CUGAUGAG X CGAA AGUUCCGC 2818

1286 GAACTCCT A GCCGCTTG 310 CAAGCGGC CUGAUGAG X CGAA AGGAGUUC 2819

1293 TAGCCGCT T GTTTTGCT 311 AGCAAAAC CUGAUGAG X CGAA AGCGGCUA 2820

1296 CCGCTTGT T TTGCTCGC 312 GCGAGCAA CUGAUGAG X CGAA ACAAGCGG 2821

1297 CGCTTGTT T TGCTCGCA 313 UGCGAGCA CUGAUGAG X CGAA AACAAGCG 2822

1298 GCTTGTTT T GCTCGCAG 314 CUGCGAGC CUGAUGAG X CGAA AAACAAGC 2823

1302 GTTTTGCT C GCAGCAGG 315 CCUGCUGC CUGAUGAG X CGAA AGCAAAAC 2824

1312 CAGCAGGT C TGGGGCAA 316 UUGCCCCA CUGAUGAG X CGAA ACCUGCUG 2825

1325 GCAAAACT C ATCGGGAC 317 GUCCCGAU CUGAUGAG X CGAA AGUUUUGC 2826

1328 AAACTCAT C GGGACTGA 318 UCAGUCCC CUGAUGAG X CGAA AUGAGUUU 2827

1341 CTGACAAT T CTGTCGTG 319 CACGACAG CUGAUGAG X CGAA AUUGUCAG 2828

1342 TGACAATT c TGTCGTGC 320 GCACGACA CUGAUGAG X CGAA AAUUGUCA 2829

1346 AATTCTGT c GTGCTCTC 321 GAGAGCAC CUGAUGAG X CGAA ACAGAAUU 2830

1352 GTCGTGCT c TCCCGCAA 322 UUGCGGGA CUGAUGAG X CGAA AGCACGAC 2831

1354 CGTGCTCT c CCGCAAAT 323 AUUUGCGG CUGAUGAG X CGAA AGAGCACG 2832

1363 CCGCAAAT A TACATCAT 324 AUGAUGUA CUGAUGAG X CGAA AUUUGCGG 2833

1365 GCAAATAT A CATCATTT 325 AAAUGAUG CUGAUGAG X CGAA AUAUUUGC 2834

1369 ATATACAT C ATTTCCAT 326 AUGGAAAU CUGAUGAG X CGAA AUGUAUAU 2835

1372 TACATCAT T TCCATGGC 327 GCCAUGGA CUGAUGAG X CGAA AUGAUGUA 2836

1373 ACATCATT T CCATGGCT 328 AGCCAUGG CUGAUGAG X CGAA AAUGAUGU 2837

1374 CATCATTT c CATGGCTG 329 CAGCCAUG CUGAUGAG X CGAA AAAUGAUG 2838

1385 TGGCTGCT A GGCTGTGC 330 GCACAGCC CUGAUGAG X CGAA AGCAGCCA 2839

1406 AACTGGAT C CTACGCGG 331 CCGCGUAG CUGAUGAG X CGAA AUCCAGUU 2840

1409 TGGATCCT A CGCGGGAC 332 GUCCCGCG CUGAUGAG X CGAA AGGAUCCA 2841

1420 CGGGACGT C CTTTGTTT 333 AAACAAAG CUGAUGAG X CGAA ACGUCCCG 2842

1423 GACGTCCT T TGTTTACG 334 CGUAAACA CUGAUGAG X CGAA AGGACGUC 2843

1424 ACGTCCTT T GTTTACGT 335 ACGUAAAC CUGAUGAG X CGAA AAGGACGU 2844

1427 TCCTTTGT T TACGTCCC 336 GGGACGUA CUGAUGAG X CGAA ACAAAGGA 2845 Table 37

1428 CCTTTGTT T ACGTCCCG 337 CGGGACGU CUGAUGAG X CGAA AACAAAGG 2846

1429 CTTTGTTT A CGTCCCGT 338 ACGGGACG CUGAUGAG X CGAA AAACAAAG 2847

1433 GTTTACGT C CCGTCGGC 339 GCCGACGG CUGAUGAG X CGAA ACGUAAAC 2848

1438 CGTCCCGT C GGCGCTGA 340 UCAGCGCC CUGAUGAG X CGAA ACGGGACG 2849

1449 CGCTGAAT C CCGCGGAC 341 GUCCGCGG CUGAUGAG X CGAA AUUCAGCG 2850

1465 CGACCCCT C CCGGGGCC 342 GGCCCCGG CUGAUGAG X CGAA AGGGGUCG 2851

1477 GGGCCGCT T GGGGCTCT 343 AGAGCCCC CUGAUGAG X CGAA AGCGGCCC 2852

1484 TTGGGGCT C TACCGCCC 344 GGGCGGUA CUGAUGAG X CGAA AGCCCCAA 2853

1486 GGGGCTCT A CCGCCCGC 345 GCGGGCGG CUGAUGAG X CGAA AGAGCCCC 2854

1496 CGCCCGCT T CTCCGCCT 346 AGGCGGAG CUGAUGAG X CGAA AGCGGGCG 2855

1497 GCCCGCTT c TCCGCCTA 347 UAGGCGGA CUGAUGAG X CGAA AAGCGGGC 2856

1499 CCGCTTCT c CGCCTATT 348 AAUAGGCG CUGAUGAG X CGAA AGAAGCGG 2857

1505 CTCCGCCT A TTGTACCG 349 CGGUACAA CUGAUGAG X CGAA AGGCGGAG 2858

1507 CCGCCTAT T GTACCGAC 350 GUCGGUAC CUGAUGAG X CGAA AUAGGCGG 2859

1510 CCTATTGT A CCGACCGT 351 ACGGUCGG CUGAUGAG X CGAA ACAAUAGG 2860

1519 CCGACCGT C CACGGGGC 352 GCCCCGUG CUGAUGAG X CGAA ACGGUCGG 2861

1534 GCGCACCT C TCTTTACG 353 CGUAAAGA CUGAUGAG X CGAA AGGUGCGC 2862

1536 GCACCTCT C TTTACGCG 354 CGCGUAAA CUGAUGAG X CGAA AGAGGUGC 2863

1538 ACCTCTCT T TACGCGGA 355 UCCGCGUA CUGAUGAG X CGAA AGAGAGGU 2864

1539 CCTCTCTT T ACGCGGAC 356 GUCCGCGU CUGAUGAG X CGAA AAGAGAGG 2865

1540 CTCTCTTT A CGCGGACT 357 AGUCCGCG CUGAUGAG X CGAA AAAGAGAG 2866

1549 CGCGGACT C CCCGTCTG 358 CAGACGGG CUGAUGAG X CGAA AGUCCGCG 2867

1555 CTCCCCGT C TGTGCCTT 359 AAGGCACA CUGAUGAG X CGAA ACGGGGAG 2868

1563 CTGTGCCT T CTCATCTG 360 CAGAUGAG CUGAUGAG X CGAA AGGCACAG 2869

1564 TGTGCCTT c TCATCTGC 361 GCAGAUGA CUGAUGAG X CGAA AAGGCACA 2870

1566 TGCCTTCT c ATCTGCCG 362 CGGCAGAU CUGAUGAG .X CGAA AGAAGGCA 2871

1569 CTTCTCAT c TGCCGGAC 363 GUCCGGCA CUGAUGAG X CGAA AUGAGAAG 2872

1588 TGTGCACT T CGCTTCAC 364 GUGAAGCG CUGAUGAG X CGAA AGUGCACA 2873

1589 GTGCACTT c GCTTCACC 365 GGUGAAGC CUGAUGAG X CGAA AAGUGCAC 2874

1593 ACTTCGCT T CACCTCTG 366 CAGAGGUG CUGAUGAG X CGAA AGCGAAGU 2875

1594 CTTCGCTT c ACCTCTGC 367 GCAGAGGU CUGAUGAG X CGAA AAGCGAAG 2876

1599 CTTCACCT c TGCACGTC 368 GACGUGCA CUGAUGAG X CGAA AGGUGAAG 2877

1607 CTGCACGT c GCATGGAG 369 CUCCAUGC CUGAUGAG X CGAA ACGUGCAG 2878

1651 CCCAAGGT c TTGCATAA 370 UUAUGCAA CUGAUGAG X CGAA ACCUUGGG 2879

1653 CAAGGTCT T GCATAAGA 371 UCUUAUGC CUGAUGAG X CGAA AGACCUUG 2880

1658 TCTTGCAT A AGAGGACT 372 AGUCCUCU CUGAUGAG X CGAA AUGCAAGA 2881

1667 AGAGGACT c TTGGACTT 373 AAGUCCAA CUGAUGAG X CGAA AGUCCUCU 2882

1669 AGGACTCT T GGACTTTC 374 GAAAGUCC CUGAUGAG X CGAA AGAGUCCU 2883

1675 CTTGGACT T TCAGCAAT 375 AUUGCUGA CUGAUGAG X CGAA AGUCCAAG 2884

1676 TTGGACTT T CAGCAATG 376 CAUUGCUG CUGAUGAG X CGAA AAGUCCAA 2885

1677 TGGACTTT c AGCAATGT 377 ACAUUGCU CUGAUGAG X CGAA AAAGUCCA 2886

1686 AGCAATGT c AACGACCG 378 CGGUCGUU CUGAUGAG X CGAA ACAUUGCU 2887

1699 ACCGACCT T GAGGCATA 379 UAUGCCUC CUGAUGAG X CGAA AGGUCGGU 2888

1707 TGAGGCAT A CTTCAAAG 380 CUUUGAAG CUGAUGAG X CGAA AUGCCUCA 2889

1710 GGCATACT T CAAAGACT 381 AGUCUUUG CUGAUGAG X CGAA AGUAUGCC 2890

1711 GCATACTT c AAAGACTG 382 CAGUCUUU CUGAUGAG X CGAA AAGUAUGC 2891

1725 CTGTGTGT T TAATGAGT 383 ACUCAUUA CUGAUGAG X CGAA ACACACAG 2892

1726 TGTGTGTT T AATGAGTG 384 CACUCAUU CUGAUGAG X CGAA AACACACA 2893

1727 GTGTGTTT A ATGAGTGG 385 CCACUCAU CUGAUGAG X CGAA AAACACAC 2894

1743 GGAGGAGT T GGGGGAGG 386 CCUCCCCC CUGAUGAG X CGAA ACUCCUCC 2895

1756 GAGGAGGT T AGGTTAAA 387 UUUAACCU CUGAUGAG X CGAA ACCUCCUC 2896 Table 37

1757 AGGAGGTT A GGTTAAAG 388 CUUUAACC CUGAUGAG X CGAA AACCUCCU 2897

1761 GGTTAGGT T AAAGGTCT 389 AGACCUUU CUGAUGAG X CGAA ACCUAACC 2898

1762 GTTAGGTT A AAGGTCTT 390 AAGACCUU CUGAUGAG X CGAA AACCUAAC 2899

1768 TTAAAGGT C TTTGTACT 391 AGUACAAA CUGAUGAG X CGAA ACCUUUAA 2900

1770 AAAGGTCT T TGTACTAG 392 CUAGUACA CUGAUGAG X CGAA AGACCUUU 2901

1771 AAGGTCTT T GTACTAGG 393 CCUAGUAC CUGAUGAG X CGAA AAGACCUU 2902

1774 GTCTTTGT A CTAGGAGG 394 CCUCCUAG CUGAUGAG X CGAA ACAAAGAC 2903

1777 TTTGTACT A GGAGGCTG 395 CAGCCUCC CUGAUGAG X CGAA AGUACAAA 2904

1787 GAGGCTGT A GGCATAAA 396 UUUAUGCC CUGAUGAG X CGAA ACAGCCUC 2905

1793 GTAGGCAT A AATTGGTG 397 CACCAAUU CUGAUGAG X CGAA AUGCCUAC 2906

1797 GCATAAAT T GGTGTGTT 398 AACACACC CUGAUGAG X CGAA AUUUAUGC 2907

1805 TGGTGTGT T CACCAGCA 399 UGCUGGUG CUGAUGAG X CGAA ACACACCA 2908

1806 GGTGTGTT C ACCAGCAC 400 GUGCUGGU CUGAUGAG X CGAA AACACACC 2909

1824 ATGCAACT T TTTCACCT 401 AGGUGAAA CUGAUGAG X CGAA AGUUGCAU 2910

1825 TGCAACTT T TTCACCTC 402 GAGGUGAA CUGAUGAG X CGAA AAGUUGCA 2911

1826 GCAACTTT T TCACCTCT 403 AGAGGUGA CUGAUGAG X CGAA AAAGUUGC 2912

1827 CAACTTTT T CACCTCTG 404 CAGAGGUG CUGAUGAG X CGAA AAAAGUUG 2913

1828 AACTTTTT C ACCTCTGC 405 GCAGAGGU CUGAUGAG X CGAA AAAAAGUU 2914

1833 TTTCACCT C TGCCTAAT 406 AUUAGGCA CUGAUGAG X CGAA AGGUGAAA 2915

1839 CTCTGCCT A ATCATCTC 407 GAGAUGAU CUGAUGAG X CGAA AGGCAGAG 2916

1842 TGCCTAAT C ATCTCATG 408 CAUGAGAU CUGAUGAG X CGAA AUUAGGCA 2917

1845 CTAATCAT C TCATGTTC 409 GAACAUGA CUGAUGAG X CGAA AUGAUUAG 2918

1847 AATCATCT C ATGTTCAT 410 AUGAACAU CUGAUGAG X CGAA AGAUGAUU 2919

1852 TCTCATGT T CATGTCCT 411 AGGACAUG CUGAUGAG X CGAA ACAUGAGA 2920

1853 CTCATGTT C ATGTCCTA 412 UAGGACAU CUGAUGAG X CGAA AACAUGAG 2921

1858 GTTCATGT C CTACTGTT 413 AACAGUAG CUGAUGAG X CGAA ACAUGAAC 2922

1861 CATGTCCT A CTGTTCAA 414 UUGAACAG CUGAUGAG X CGAA AGGACAUG 2923

1866 CCTACTGT T CAAGCCTC 415 GAGGCUUG CUGAUGAG X CGAA ACAGUAGG 2924

1867 CTACTGTT C AAGCCTCC 416 GGAGGCUU CUGAUGAG X CGAA AACAGUAG 2925

1874 TCAAGCCT C CAAGCTGT 417 ACAGCUUG CUGAUGAG X CGAA AGGCUUGA 2926

1887 CTGTGCCT T GGGTGGCT 418 AGCCACCC CUGAUGAG X CGAA AGGCACAG 2927

1896 GGGTGGCT T TGGGGCAT 419 AUGCCCCA CUGAUGAG X CGAA AGCCACCC 2928

1897 GGTGGCTT T GGGGCATG 420 CAUGCCCC CUGAUGAG X CGAA AAGCCACC 2929

1911 ATGGACAT T GACCCGTA 421 UACGGGUC CUGAUGAG X CGAA AUGUCCAU 2930

1919 TGACCCGT A TAAAGAAT 422 AUUCUUUA CUGAUGAG X CGAA ACGGGUCA 2931

1921 ACCCGTAT A AAGAATTT 423 AAAUUCUU CUGAUGAG X CGAA AUACGGGU 2932

1928 TAAAGAAT T TGGAGCTT 424 AAGCUCCA CUGAUGAG X CGAA AUUCUUUA 2933

1929 AAAGAATT T GGAGCTTC 425 GAAGCUCC CUGAUGAG X CGAA AAUUCUUU 2934

1936 TTGGAGCT T CTGTGGAG 426 CUCCACAG CUGAUGAG X CGAA AGCUCCAA 2935

1937 TGGAGCTT c TGTGGAGT 427 ACUCCACA CUGAUGAG X CGAA AAGCUCCA 2936

1946 TGTGGAGT T ACTCTCTT 428 AAGAGAGU CUGAUGAG X CGAA ACUCCACA 2937

1947 GTGGAGTT A CTCTCTTT 429 AAAGAGAG CUGAUGAG X CGAA AACUCCAC 2938

1950 GAGTTACT C TCTTTTTT 430 AAAAAAGA CUGAUGAG X CGAA AGUAACUC 2939

1952 GTTACTCT C TTTTTTGC 431 GCAAAAAA CUGAUGAG X CGAA AGAGUAAC 2940

1954 TACTCTCT T TTTTGCCT 432 AGGCAAAA CUGAUGAG X CGAA AGAGAGUA 2941

1955 ACTCTCTT T TTTGCCTT 433 AAGGCAAA CUGAUGAG X CGAA AAGAGAGU 2942

1956 CTCTCTTT T TTGCCTTC 434 GAAGGCAA CUGAUGAG X CGAA AAAGAGAG 2943

1957 TCTCTTTT T TGCCTTCT 435 AGAAGGCA CUGAUGAG X CGAA AAAAGAGA 2944

1958 CTCTTTTT T GCCTTCTG 436 CAGAAGGC CUGAUGAG X CGAA AAAAAGAG 2945

1963 TTTTGCCT T CTGACTTC 437 GAAGUCAG CUGAUGAG X CGAA AGGCAAAA 2946

1964 TTTGCCTT c TGACTTCT 438 AGAAGUCA CUGAUGAG X CGAA AAGGCAAA 2947 Table 37

1970 TTCTGACT T CTTTCCTT 439 AAGGAAAG CUGAUGAG X CGAA AGUCAGAA 2948

1971 TCTGACTT C TTTCCTTC 440 GAAGGAAA CUGAUGAG X CGAA AAGUCAGA 2949

1973 TGACTTCT T TCCTTCTA 441 UAGAAGGA CUGAUGAG X CGAA AGAAGUCA 2950

1974 GACTTCTT T CCTTCTAT 442 AUAGAAGG CUGAUGAG-X CGAA AAGAAGUC 2951

1975 ACTTCTTT c CTTCTATT 443 AAUAGAAG CUGAUGAG X CGAA AAAGAAGU 2952

1978 TCTTTCCT T CTATTCGA 444 UCGAAUAG CUGAUGAG X CGAA AGGAAAGA 2953

1979 CTTTCCTT c TATTCGAG 445 CUCGAAUA CUGAUGAG X CGAA AAGGAAAG 2954

1981 TTCCTTCT A TTCGAGAT 446 AUCUCGAA CUGAUGAG X CGAA AGAAGGAA 2955

1983 CCTTCTAT T CGAGATCT 447 AGAUCUCG CUGAUGAG X CGAA AUAGAAGG 2956

1984 CTTCTATT C GAGATCTC 448 GAGAUCUC CUGAUGAG X CGAA AAUAGAAG 2957

1990 TTCGAGAT C TCCTCGAC 449 GUCGAGGA CUGAUGAG X CGAA AUCUCGAA 2958

1992 CGAGATCT C CTCGACAC 450 GUGUCGAG CUGAUGAG X CGAA AGAUCUCG 2959

1995 GATCTCCT c GACACCGC 451 GCGGUGUC CUGAUGAG X CGAA AGGAGAUC 2960

2006 CACCGCCT c TGCTCTGT 452 ACAGAGCA CUGAUGAG X CGAA AGGCGGUG 2961

2011 CCTCTGCT c TGTATCGG 453 CCGAUACA CUGAUGAG X CGAA AGCAGAGG 2962

2015 TGCTCTGT A TCGGGGGG 454 CCCCCCGA CUGAUGAG X CGAA ACAGAGCA 2963

2017 CTCTGTAT C GGGGGGCC 455 GGCCCCCC CUGAUGAG X CGAA AUACAGAG 2964

2027 GGGGGCCT T AGAGTCTC 456 GAGACUCU CUGAUGAG X CGAA AGGCCCCC 2965

2028 GGGGCCTT A GAGTCTCC 457 GGAGACUC CUGAUGAG X CGAA AAGGCCCC 2966

2033 CTTAGAGT C TCCGGAAC 458 GUUCCGGA CUGAUGAG X CGAA ACUCUAAG 2967

2035 TAGAGTCT C CGGAACAT 459 AUGUUCCG CUGAUGAG X CGAA AGACUCUA 2968

2044 CGGAACAT T GTTCACCT 460 AGGUGAAC CUGAUGAG X CGAA AUGUUCCG 2969

2047 AACATTGT T CACCTCAC 461 GUGAGGUG CUGAUGAG X CGAA ACAAUGUU 2970

2048 ACATTGTT C ACCTCACC 462 GGUGAGGU CUGAUGAG X CGAA AACAAUGU 2971

2053 GTTCACCT C ACCATACG 463 CGUAUGGU CUGAUGAG X CGAA AGGUGAAC 2972

2059 CTCACCAT A CGGCACTC 464 GAGUGCCG CUGAUGAG X CGAA AUGGUGAG 2973

2067 ACGGCACT C AGGCAAGC 465 GCUUGCCU CUGAUGAG X CGAA AGUGCCGU 2974

2077 GGCAAGCT A TTCTGTGT 466 ACACAGAA CUGAUGAG X CGAA AGCUUGCC 2975

2079 CAAGCTAT T CTGTGTTG 467 CAACACAG CUGAUGAG X CGAA AUAGCUUG 2976

2080 AAGCTATT C TGTGTTGG 468 CCAACACA CUGAUGAG X CGAA AAUAGCUU 2977

2086 TTCTGTGT T GGGGTGAG 469 j CUCACCCC CUGAUGAG X CGAA ACACAGAA 2978

2096 GGGTGAGT T GATGAATC 470 GAUUCAUC CUGAUGAG X CGAA ACUCACCC 2979

2104 TGATGAAT C TAGCCACC 471 GGUGGCUA CUGAUGAG X CGAA AUUCAUCA 2980

2106 ATGAATCT A GCCACCTG 472 CAGGUGGC CUGAUGAG X CGAA AGAUUCAU 2981

2125 TGGGAAGT A ATTTGGAA 473 UUCCAAAU CUGAUGAG X CGAA ACUUCCCA 2982

2128 GAAGTAAT T TGGAAGAT 474 AUCUUCCA CUGAUGAG X CGAA AUUACUUC 2983

2129 AAGTAATT T GGAAGATC 475 GAUCUUCC CUGAUGAG X CGAA AAUUACUU 2984

2137 TGGAAGAT C CAGCATCC 476 GGAUGCUG CUGAUGAG X CGAA AUCUUCCA 2985

2144 TCCAGCAT C CAGGGAAT 477 AUUCCCUG CUGAUGAG X CGAA AUGCUGGA 2986

2153 CAGGGAAT T AGTAGTCA 478 UGACUACU CUGAUGAG X CGAA AUUCCCUG 2987

2154 AGGGAATT A GTAGTCAG 479 CUGACUAC CUGAUGAG X CGAA AAUUCCCU 2988

2157 GAATTAGT A GTCAGCTA 480 UAGCUGAC CUGAUGAG X CGAA ACUAAUUC 2989

2160 TTAGTAGT C AGCTATGT 481 ACAUAGCU CUGAUGAG X CGAA ACUACUAA 2990

2165 AGTCAGCT A TGTCAACG 482 CGUUGACA CUGAUGAG X CGAA AGCUGACU 2991

2169 AGCTATGT C AACGTTAA 483 UUAACGUU CUGAUGAG X CGAA ACAUAGCU 2992

2175 GTCAACGT T AATATGGG 484 CCCAUAUU CUGAUGAG X CGAA ACGUUGAC 2993

2176 TCAACGTT A ATATGGGC 485 GCCCAUAU CUGAUGAG X CGAA AACGUUGA 2994

2179 ACGTTAAT A TGGGCCTA 486 UAGGCCCA CUGAUGAG X CGAA AUUAACGU 2995

2187 ATGGGCCT A AAAATCAG 487 CUGAUUUU CUGAUGAG X CGAA AGGCCCAU 2996

2193 CTAAAAAT C AGACAACT 488 AGUUGUCU CUGAUGAG X CGAA AUUUUUAG 2997

2202 AGACAACT A TTGTGGTT 489 AACCACAA CUGAUGAG X CGAA AGUUGUCU 2998 Tauie __)/

2204 ACAACTAT T GTGGTTTC 490 GAAACCAC CUGAUGAG X CGAA AUAGUUGU 2999

2210 ATTGTGGT T TCACATTT 491 AAAUGUGA CUGAUGAG X CGAA ACCACAAU 3000

2211 TTGTGGTT T CACATTTC 492 GAAAUGUG CUGAUGAG X CGAA AACCACAA 3001

2212 TGTGGTTT C ACATTTCC 493 GGAAAUGU CUGAUGAG X CGAA AAACCACA 3002

2217 TTTCACAT T TCCTGTCT 494 AGACAGGA CUGAUGAG X CGAA AUGUGAAA 3003

2218 TTCACATT T CCTGTCTT 495 AAGACAGG CUGAUGAG X CGAA AAUGUGAA 3004

2219 TCACATTT C CTGTCTTA 496 UAAGACAG CUGAUGAG X CGAA AAAUGUGA 3005

2224 TTTCCTGT C TTACTTTT 497 AAAAGUAA CUGAUGAG X CGAA ACAGGAAA 3006

2226 TCCTGTCT T ACTTTTGG 498 CCAAAAGU CUGAUGAG X CGAA AGACAGGA 3007

2227 CCTGTCTT A CTTTTGGG 499 CCCAAAAG CUGAUGAG X CGAA AAGACAGG 3008

2230 GTCTTACT T TTGGGCGA 500 UCGCCCAA CUGAUGAG X CGAA AGUAAGAC 3009

2231 TCTTACTT T TGGGCGAG 501 CUCGCCCA CUGAUGAG X CGAA AAGUAAGA 3010

2232 CTTACTTT T GGGCGAGA 502 UCUCGCCC CUGAUGAG X CGAA AAAGUAAG 3011

2247 GAAACTGT T CTTGAATA 503 UAUUCAAG CUGAUGAG X CGAA ACAGUUUC 3012

2248 AAACTGTT C TTGAATAT 504 AUAUUCAA CUGAUGAG X CGAA AACAGUUU 3013

2250 ACTGTTCT T GAATATTT 505 AAAUAUUC CUGAUGAG X CGAA AGAACAGU 3014

2255 TCTTGAAT A TTTGGTGT 506 ACACCAAA CUGAUGAG X CGAA AUUCAAGA 3015

2257 TTGAATAT T TGGTGTCT 507 AGACACCA CUGAUGAG X CGAA AUAUUCAA 3016

2258 TGAATATT T GGTGTCTT 508 AAGACACC CUGAUGAG X CGAA AAUAUUCA 3017

2264 TTTGGTGT C TTTTGGAG 509 CUCCAAAA CUGAUGAG X CGAA ACACCAAA 3018

2266 TGGTGTCT T TTGGAGTG 510 CACUCCAA CUGAUGAG X CGAA AGACACCA 3019

2267 GGTGTCTT T TGGAGTGT 511 ACACUCCA CUGAUGAG X CGAA AAGACACC 3020

2268 GTGTCTTT T GGAGTGTG 512 CACACUCC CUGAUGAG X CGAA AAAGACAC 3021

2280 GTGTGGAT T CGCACTCC 513 GGAGUGCG CUGAUGAG X CGAA AUCCACAC 3022

2281 TGTGGATT C GCACTCCT 514 AGGAGUGC CUGAUGAG X CGAA AAUCCACA 3023

2287 TTCGCACT C CTCCTGCA 515 UGCAGGAG CUGAUGAG X CGAA AGUGCGAA 3024 _x2290 GCACTCCT c CTGCATAT 516 AUAUGCAG CUGAUGAG X CGAA AGGAGUGC 3025

2297 TCCTGCAT A TAGACCAC 517 GUGGUCUA CUGAUGAG X CGAA AUGCAGGA 3026

2299 CTGCATAT A GACCACCA 518 UGGUGGUC CUGAUGAG X CGAA AUAUGCAG 3027

2317 ATGCCCCT A TCTTATCA 519 UGAUAAGA CUGAUGAG X CGAA AGGGGCAU 3028

2319 GCCCCTAT C TTATCAAC 520 GUUGAUAA CUGAUGAG X CGAA AUAGGGGC 3029

2321 CCCTATCT T ATCAACAC 521 GUGUUGAU CUGAUGAG X CGAA AGAUAGGG 3030

2322 CCTATCTT A TCAACACT 522 AGUGUUGA CUGAUGAG X CGAA AAGAUAGG 3031

2324 TATCTTAT C AACACTTC 523 GAAGUGUU CUGAUGAG X CGAA AUAAGAUA 3032

2331 TCAACACT T CCGGAAAC 524 GUUUCCGG CUGAUGAG X CGAA AGUGUUGA 3033

2332 CAACACTT C CGGAAACT 525 AGUUUCCG CUGAUGAG X CGAA AAGUGUUG 3034

2341 CGGAAACT A CTGTTGTT 526 AACAACAG CUGAUGAG X CGAA AGUUUCCG 3035

2346 ACTACTGT T GTTAGACG 527 CGUCUAAC CUGAUGAG X CGAA ACAGUAGU 3036

2349 ACTGTTGT T AGACGAAG 528 CUUCGUCU CUGAUGAG X CGAA ACAACAGU 3037

2350 CTGTTGTT A GACGAAGA 529 UCUUCGUC CUGAUGAG X CGAA AACAACAG 3038

2366 AGGCAGGT C CCCTAGAA 530 UUCUAGGG CUGAUGAG X CGAA ACCUGCCU 3039

2371 GGTCCCCT A GAAGAAGA 531 UCUUCUUC CUGAUGAG X CGAA AGGGGACC 3040

2383 GAAGAACT C CCTCGCCT 532 AGGCGAGG CUGAUGAG X CGAA AGUUCUUC 3041

2387 AACTCCCT C GCCTCGCA 533 UGCGAGGC CUGAUGAG X CGAA AGGGAGUU 3042

2392 CCTCGCCT C GCAGACGA 534 UCGUCUGC CUGAUGAG X CGAA AGGCGAGG 3043

2405 ACGAAGGT C TCAATCGC 535 GCGAUUGA CUGAUGAG X CGAA ACCUUCGU 3044

2407 GAAGGTCT C AATCGCCG 536 CGGCGAUU CUGAUGAG X CGAA AGACCUUC 3045

2411 GTCTCAAT C GCCGCGTC 537 GACGCGGC CUGAUGAG X CGAA AUUGAGAC 3046

2419 CGCCGCGT C GCAGAAGA 538 UCUUCUGC CUGAUGAG X CGAA ACGCGGCG 3047

2429 CAGAAGAT C TCAATCTC 539 GAGAUUGA CUGAUGAG X CGAA AUCUUCUG 3048

2431 GAAGATCT C AATCTCGG 540 CCGAGAUU CUGAUGAG X CGAA AGAUCUUC 3049 Table 3/

2435 ATCTCAAT C TCGGGAAT 541 AUUCCCGA CUGAUGAG X CGAA AUUGAGAU 3050

2437 CTCAATCT C GGGAATCT 542 AGAUUCCC CUGAUGAG X CGAA AGAUUGAG 3051

2444 TCGGGAAT C TCAATGTT 543 AACAUUGA CUGAUGAG X CGAA AUUCCCGA 3052

2446 GGGAATCT C AATGTTAG 544 CUAACAUU CUGAUGAG X CGAA AGAUUCCC 3053

2452 CTCAATGT T AGTATTCC 545 GGAAUACU CUGAUGAG X CGAA ACAUUGAG 3054

2453 TCAATGTT A GTATTCCT 546 AGGAAUAC CUGAUGAG X CGAA AACAUUGA 3055

2456 ATGTTAGT A TTCCTTGG 547 CCAAGGAA CUGAUGAG X CGAA ACUAACAU 3056

2458 GTTAGTAT T CCTTGGAC 548 GUCCAAGG CUGAUGAG X CGAA AUACUAAC 3057

2459 TTAGTATT C CTTGGACA 549 UGUCCAAG CUGAUGAG X CGAA AAUACUAA 3058

2462 GTATTCCT T GGACACAT 550 AUGUGUCC CUGAUGAG X CGAA AGGAAUAC 3059

2471 GGACACAT A AGGTGGGA 551 UCCCACCU CUGAUGAG X CGAA AUGUGUCC 3060

2484 GGGAAACT T TACGGGGC 552 GCCCCGUA CUGAUGAG X CGAA AGUUUCCC 3061

2485 GGAAACTT T ACGGGGCT 553 AGCCCCGU CUGAUGAG X CGAA AAGUUUCC 3062

2486 GAAACTTT A CGGGGCTT 554 AAGCCCCG CUGAUGAG X CGAA AAAGUUUC 3063

2494 ACGGGGCT T TATTCTTC 555 GAAGAAUA CUGAUGAG X CGAA AGCCCCGU 3064

2495 CGGGGCTT T ATTCTTCT 556 AGAAGAAU CUGAUGAG X CGAA AAGCCCCG 3065

2496 GGGGCTTT A TTCTTCTA 557 UAGAAGAA CUGAUGAG X CGAA AAAGCCCC 3066

2498 GGCTTTAT T CTTCTACG 558 CGUAGAAG CUGAUGAG X CGAA AUAAAGCC 3067

2499 GCTTTATT C TTCTACGG 559 CCGUAGAA CUGAUGAG X CGAA AAUAAAGC 3068

2501 TTTATTCT T CTACGGTA 560 UACCGUAG CUGAUGAG X CGAA AGAAUAAA 3069

2502 TTATTCTT C TACGGTAC 561 GUACCGUA CUGAUGAG X CGAA AAGAAUAA 3070

2504 ATTCTTCT A CGGTACCT 562 AGGUACCG CUGAUGAG X CGAA AGAAGAAU 3071

2509 TCTACGGT A CCTTGCTT 563 AAGCAAGG CUGAUGAG X CGAA ACCGUAGA 3072

2513 CGGTACCT T GCTTTAAT 564 AUUAAAGC CUGAUGAG X CGAA AGGUACCG 3073

2517 ACCTTGCT T TAATCCTA 565 UAGGAUUA CUGAUGAG X CGAA AGCAAGGU 3074

2518 CCTTGCTT T AATCCTAA 566 UUAGGAUU CUGAUGAG X CGAA AAGCAAGG 3075

2519 CTTGCTTT A ATCCTAAA 567 UUUAGGAU CUGAUGAG X CGAA AAAGCAAG 3076

2522 GCTTTAAT C CTAAATGG 568 CCAUUUAG CUGAUGAG X CGAA AUUAAAGC 3077

2525 TTAATCCT A AATGGCAA 569 UUGCCAUU CUGAUGAG X CGAA AGGAUUAA 3078

2537 GGCAAACT C CTTCTTTT 570 AAAAGAAG CUGAUGAG X CGAA AGUUUGCC 3079

2540 AAACTCCT T CTTTTCCT 571 AGGAAAAG CUGAUGAG X CGAA AGGAGUUU 3080

2541 AACTCCTT C TTTTCCTG 572 CAGGAAAA CUGAUGAG X CGAA AAGGAGUU 3081

2543 CTCCTTCT T TTCCTGAC 573 GUCAGGAA CUGAUGAG X CGAA AGAAGGAG 3082

2544 TCCTTCTT T TCCTGACA 574 UGUCAGGA CUGAUGAG X CGAA AAGAAGGA 3083

2545 CCTTCTTT T CCTGACAT 575 AUGUCAGG CUGAUGAG X CGAA AAAGAAGG 3084

2546 CTTCTTTT C CTGACATT 576 AAUGUCAG CUGAUGAG X CGAA AAAAGAAG 3085

2554 CCTGACAT T CATTTGCA 577 UGCAAAUG CUGAUGAG X CGAA AUGUCAGG 3086

2555 CTGACATT C ATTTGCAG 578 CUGCAAAU CUGAUGAG X CGAA AAUGUCAG 3087

2558 ACATTCAT T TGCAGGAG 579 CUCCUGCA CUGAUGAG X CGAA AUGAAUGU 3088

2559 CATTCATT T GCAGGAGG 580 CCUCCUGC CUGAUGAG X CGAA AAUGAAUG 3089

2572 GAGGACAT T GTTGATAG 581 CUAUCAAC CUGAUGAG X CGAA AUGUCCUC 3090

2575 GACATTGT T GATAGATG 582 CAUCUAUC CUGAUGAG X CGAA ACAAUGUC 3091

2579 TTGTTGAT A GATGTAAG 583 CUUACAUC CUGAUGAG X CGAA AUCAACAA 3092

2585 ATAGATGT A AGCAATTT 584 AAAUUGCU CUGAUGAG X CGAA ACAUCUAU 3093

2592 TAAGCAAT T TGTGGGGC 585 GCCCCACA CUGAUGAG X CGAA AUUGCUUA 3094

2593 AAGCAATT T GTGGGGCC 586 GGCCCCAC CUGAUGAG X CGAA AAUUGCUU 3095

2605 GGGCCCCT T ACAGTAAA 587 UUUACUGU CUGAUGAG X CGAA AGGGGCCC 3096

2606 GGCCCCTT A CAGTAAAT 588 AUUUACUG CUGAUGAG X CGAA AAGGGGCC 3097

2611 CTTACAGT A AATGAAAA 589 UUUUCAUU CUGAUGAG X CGAA ACUGUAAG 3098

2629 AGGAGACT T AAATTAAC 590 GUUAAUUU CUGAUGAG X CGAA AGUCUCCU 3099

2630 GGAGACTT A AATTAACT 591 AGUUAAUU CUGAUGAG X CGAA AAGUCUCC 3100 Table 37

2634 ACTTAAAT T AACTATGC 592 GCAUAGUU CUGAUGAG X CGAA AUUUAAGU 3101

2635 CTTAAATT A ACTATGCC 593 GGCAUAGU CUGAUGAG X CGAA AAUUUAAG 3102

2639 AATTAACT A TGCCTGCT 594 AGCAGGCA CUGAUGAG X CGAA AGUUAAUU 3103

2648 TGCCTGCT A GGTTTTAT 595 AUAAAACC CUGAUGAG X CGAA AGCAGGCA 3104

2652 TGCTAGGT T TTATCCCA 596 UGGGAUAA CUGAUGAG X CGAA ACCUAGCA 3105

2653 GCTAGGTT T TATCCCAA 597 UUGGGAUA CUGAUGAG X CGAA AACCUAGC 3106

2654 CTAGGTTT T ATCCCAAT 598 AUUGGGAU CUGAUGAG X CGAA AAACCUAG 3107

2655 TAGGTTTT A TCCCAATG 599 CAUUGGGA CUGAUGAG X CGAA AAAACCUA 3108

2657 GGTTTTAT C CCAATGTT 600 AACAUUGG CUGAUGAG X CGAA AUAAAACC 3109

2665 CCCAATGT T ACTAAATA 601 UAUUUAGU CUGAUGAG X CGAA ACAUUGGG 3110

2666 CCAATGTT A CTAAATAT 602 AUAUUUAG CUGAUGAG X CGAA AACAUUGG 3111

2669 ATGTTACT A AATATTTG 603 CAAAUAUU CUGAUGAG X CGAA AGUAACAU 3112

2673 TACTAAAT A TTTGCCCT 604 AGGGCAAA CUGAUGAG X CGAA AUUUAGUA 3113

2675 CTAAATAT T TGCCCTTA 605 UAAGGGCA CUGAUGAG X CGAA AUAUUUAG 3114

2676 TAAATATT T GCCCTTAG 606 CUAAGGGC CUGAUGAG X CGAA AAUAUUUA 3115

2682 TTTGCCCT T AGATAAAG 607 CUUUAUCU CUGAUGAG X CGAA AGGGCAAA 3116

2683 TTGCCCTT A GATAAAGG 608 CCUUUAUC CUGAUGAG X CGAA AAGGGCAA 3117

2687 CCTTAGAT A AAGGGATC 609 GAUCCCUU CUGAUGAG X CGAA AUCUAAGG 3118

2695 AAAGGGAT C AAACCGTA 610 UACGGUUU CUGAUGAG X CGAA AUCCCUUU 3119

2703 CAAACCGT A TTATCCAG 611 CUGGAUAA CUGAUGAG X CGAA ACGGUUUG 3120

2705 AACCGTAT T ATCCAGAG 612 CUCUGGAU CUGAUGAG X CGAA AUACGGUU 3121

2706 ACCGTATT A TCCAGAGT 613 ACUCUGGA CUGAUGAG X CGAA AAUACGGU 3122

2708 CGTATTAT C CAGAGTAT 614 AUACUCUG CUGAUGAG X CGAA AUAAUACG 3123

2715 TCCAGAGT A TGTAGTTA 615 UAACUACA CUGAUGAG X CGAA ACUCUGGA 3124

2719 GAGTATGT A GTTAATCA 616 UGAUUAAC CUGAUGAG X CGAA ACAUACUC 3125

2722 TATGTAGT T AATCATTA 617 UAAUGAUU CUGAUGAG X CGAA ACUACAUA 3126

2723 ATGTAGTT A ATCATTAC 618 GUAAUGAU CUGAUGAG X CGAA AACUACAU 3127

2726 TAGTTAAT C ATTACTTC 619 GAAGUAAU CUGAUGAG X CGAA AUUAACUA 3128

2729 TTAATCAT T ACTTCCAG 620 CUGGAAGU CUGAUGAG X CGAA AUGAUUAA 3129

2730 TAATCATT A CTTCCAGA 621 UCUGGAAG CUGAUGAG X CGAA AAUGAUUA 3130

2733 TCATTACT T CCAGACGC 622 GCGUCUGG CUGAUGAG X CGAA AGUAAUGA 3131

2734 CATTACTT c CAGACGCG 623 CGCGUCUG CUGAUGAG X CGAA AAGUAAUG 3132

2747 CGCGACAT T ATTTACAC 624 GUGUAAAU CUGAUGAG X CGAA AUGUCGCG 3133

2748 GCGACATT A TTTACACA 625 UGUGUAAA CUGAUGAG X CGAA AAUGUCGC 3134

2750 GACATTAT T TACACACT 626 AGUGUGUA CUGAUGAG X CGAA AUAAUGUC 3135

2751 ACATTATT T ACACACTC 627 GAGUGUGU CUGAUGAG X CGAA AAUAAUGU 3136

2752 CATTATTT A CACACTCT 628 AGAGUGUG CUGAUGAG X CGAA AAAUAAUG 3137

2759 TACACACT C TTTGGAAG 629 CUUCCAAA CUGAUGAG X CGAA AGUGUGUA 3138

2761 CACACTCT T TGGAAGGC 630 GCCUUCCA CUGAUGAG X CGAA AGAGUGUG 3139

2762 ACACTCTT T GGAAGGCG 631 CGCCUUCC CUGAUGAG X CGAA AAGAGUGU 3140

2776 GCGGGGAT C TTATATAA 632 UUAUAUAA CUGAUGAG X CGAA AUCCCCGC 3141

2778 GGGGATCT T ATATAAAA 633 UUUUAUAU CUGAUGAG X CGAA AGAUCCCC 3142

2779 GGGATCTT A TATAAAAG 634 CUUUUAUA CUGAUGAG X CGAA AAGAUCCC 3143

2781 GATCTTAT A TAAAAGAG 635 CUCUUUUA CUGAUGAG X CGAA AUAAGAUC 3144

2783 TCTTATAT A AAAGAGAG 636 CUCUCUUU CUGAUGAG X CGAA AUAUAAGA 3145

2793 AAGAGAGT C CACACGTA 637 UACGUGUG CUGAUGAG X CGAA ACUCUCUU 3146

2801 CCACACGT A GCGCCTCA 638 UGAGGCGC CUGAUGAG X CGAA ACGUGUGG 3147

2808 TAGCGCCT C ATTTTGCG 639 CGCAAAAU CUGAUGAG X CGAA AGGCGCUA 3148

2811 CGCCTCAT T TTGCGGGT 640 ACCCGCAA CUGAUGAG X CGAA AUGAGGCG 3149

2812 GCCTCATT T TGCGGGTC 641 GACCCGCA CUGAUGAG X CGAA AAUGAGGC 3150

2813 CCTCATTT T GCGGGTCA 642 UGACCCGC CUGAUGAG X CGAA AAAUGAGG 3151 Table 37

2820 TTGCGGGT C ACCATATT 643 AAUAUGGU CUGAUGAG X CGAA ACCCGCAA 3152

2826 GTCACCAT A TTCTTGGG 644 CCCAAGAA CUGAUGAG X CGAA AUGGUGAC 3153

2828 CACCATAT T CTTGGGAA 645 UUCCCAAG CUGAUGAG X CGAA AUAUGGUG 3154

2829 ACCATATT C TTGGGAAC 646 GUUCCCAA CUGAUGAG X CGAA AAUAUGGU 3155

2831 CATATTCT T GGGAACAA 647 UUGUUCCC CUGAUGAG X CGAA AGAAUAUG 3156

2843 AACAAGAT C TACAGCAT 648 AUGCUGUA CUGAUGAG X CGAA AUCUUGUU 3157

2845 CAAGATCT A CAGCATGG 649 CCAUGCUG CUGAUGAG X CGAA AGAUCUUG 3158

2859 TGGGAGGT T GGTCTTCC 650 GGAAGACC CUGAUGAG X CGAA ACCUCCCA 3159

2863 AGGTTGGT c TTCCAAAC 651 GUUUGGAA CUGAUGAG X CGAA ACCAACCU 3160

2865 GTTGGTCT T CCAAACCT 652 AGGUUUGG CUGAUGAG X CGAA AGACCAAC 3161

2866 TTGGTCTT c CAAACCTC 653 GAGGUUUG CUGAUGAG X CGAA AAGACCAA 3162

2874 CCAAACCT c GAAAAGGC 654 GCCUUUUC CUGAUGAG X CGAA AGGUUUGG 3163

2895 GGACAAAT c TTTCTGTC 655 GACAGAAA CUGAUGAG X CGAA AUUUGUCC 3164

2897 ACAAATCT T TCTGTCCC 656 GGGACAGA CUGAUGAG X CGAA AGAUUUGU 3165

2898 CAAATCTT T CTGTCCCC 657 GGGGACAG CUGAUGAG X CGAA AAGAUUUG 3166

2899 AAATCTTT c TGTCCCCA 658 UGGGGACA CUGAUGAG X CGAA AAAGAUUU 3167

2903 CTTTCTGT c CCCAATCC 659 GGAUUGGG CUGAUGAG X CGAA ACAGAAAG 3168

2910 TCCCCAAT c CCCTGGGA 660 UCCCAGGG CUGAUGAG X CGAA AUUGGGGA 3169

2920 CCTGGGAT T CTTCCCCG 661 CGGGGAAG CUGAUGAG X CGAA AUCCCAGG 3170

2921 CTGGGATT c TTCCCCGA 662 UCGGGGAA CUGAUGAG X CGAA AAUCCCAG 3171

2923 GGGATTCT T CCCCGATC 663 GAUCGGGG CUGAUGAG X CGAA AGAAUCCC 3172

2924 GGATTCTT c CCCGATCA 664 UGAUCGGG CUGAUGAG X CGAA AAGAAUCC 3173

2931 TCCCCGAT c ATCAGTTG 665 CAACUGAU CUGAUGAG X CGAA AUCGGGGA 3174

2934 CCGATCAT c AGTTGGAC 666 GUCCAACU CUGAUGAG X CGAA AUGAUCGG 3175

2938 TCATCAGT T GGACCCTG 667 CAGGGUCC CUGAUGAG X CGAA ACUGAUGA 3176

2950 CCCTGCAT T CAAAGCCA 668 UGGCUUUG CUGAUGAG X CGAA AUGCAGGG 3177

2951 CCTGCATT c AAAGCCAA 669 UUGGCUUU CUGAUGAG X CGAA AAUGCAGG 3178

2962 AGCCAACT c AGTAAATC 670 GAUUUACU CUGAUGAG X CGAA AGUUGGCU 3179

2966 AACTCAGT A AATCCAGA 671 UCUGGAUU CUGAUGAG X CGAA ACUGAGUU 3180

2970 CAGTAAAT c CAGATTGG 672 CCAAUCUG CUGAUGAG X CGAA AUUUACUG 3181

2976 ATCCAGAT T GGGACCTC 673 GAGGUCCC CUGAUGAG X CGAA AUCUGGAU 3182

2984 TGGGACCT c AACCCGCA 674 UGCGGGUU CUGAUGAG X CGAA AGGUCCCA 3183

3037 GGGAGCAT T CGGGCCAG 675 CUGGCCCG CUGAUGAG X CGAA AUGCUCCC 3184

3038 GGAGCATT c GGGCCAGG 676 CCUGGCCC CUGAUGAG X CGAA AAUGCUCC 3185

3049 GCCAGGGT T CACCCCTC 677 GAGGGGUG CUGAUGAG X CGAA ACCCUGGC 3186

3050 CCAGGGTT c ACCCCTCC 678 GGAGGGGU CUGAUGAG X CGAA AACCCUGG 3187

3057 TCACCCCT c CCCATGGG 679 CCCAUGGG CUGAUGAG X CGAA AGGGGUGA 3188

3073 GGGACTGT T GGGGTGGA 680 UCCACCCC CUGAUGAG X CGAA ACAGUCCC 3189

3087 GGAGCCCT c ACGCTCAG 681 CUGAGCGU CUGAUGAG X CGAA AGGGCUCC 3190

3093 CTCACGCT c AGGGCCTA 682 UAGGCCCU CUGAUGAG X CGAA AGCGUGAG 3191

3101 CAGGGCCT A CTCACAAC 683 GUUGUGAG CUGAUGAG X CGAA AGGCCCUG 3192

3104 GGCCTACT c ACAACTGT 684 ACAGUUGU CUGAUGAG X CGAA AGUAGGCC 3193

3123 CAGCAGCT c CTCCTCCT 685 AGGAGGAG CUGAUGAG X CGAA AGCUGCUG 3194

3126 CAGCTCCT c CTCCTGCC 686 GGCAGGAG CUGAUGAG X CGAA AGGAGCUG 3195

3129 CTCCTCCT c CTGCCTCC 687 GGAGGCAG CUGAUGAG X CGAA AGGAGGAG 3196

3136 TCCTGCCT c CACCAATC 688 GAUUGGUG CUGAUGAG X CGAA AGGCAGGA 3197

3144 CCACCAAT c GGCAGTCA 689 UGACUGCC CUGAUGAG X CGAA AUUGGUGG 3198

3151 TCGGCAGT c AGGAAGGC 690 GCCUUCCU CUGAUGAG X CGAA ACUGCCGA 3199

3165 GGCAGCCT A CTCCCTTA 691 UAAGGGAG CUGAUGAG X CGAA AGGCUGCC 3200

3168 AGCCTACT c CCTTATCT 692 AGAUAAGG CUGAUGAG X CGAA AGUAGGCU 3201

3172 TACTCCCT T ATCTCCAC 693 GUGGAGAU CUGAUGAG X CGAA AGGGAGUA 3202 Taoie 5/

Input Sequence = AF100308. Cut Site = UH/ .

Stem Length = 8 . Core Sequence = CUGAUGAG X CGAA (X = GCCGUUAGGC or other stem II)

AF100308 (Hepatitis B virus strain 2-18, 3215 bp)

Table 38 Table 38: Human HBV Inozyme and Substrate Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

9 AACTCCAC C ACTTTCCA 702 UGGAAAGU CUGAUGAG X CGAA IUGGAGUU 3211

10 ACTCCACC A CTTTCCAC 703 GUGGAAAG CUGAUGAG X CGAA IGUGGAGU 3212

12 TCCACCAC T TTCCACCA 704 UGGUGGAA CUGAUGAG X CGAA IUGGUGGA 3213

16 CCACTTTC c ACCAAACT 705 AGUUUGGU CUGAUGAG X CGAA IAAAGUGG 3214

17 CACTTTCC A CCAAACTC 706 GAGUUUGG CUGAUGAG X CGAA IGAAAGUG 3215

19 CTTTCCAC C AAACTCTT 707 AAGAGUUU CUGAUGAG X CGAA IUGGAAAG 3216

20 TTTCCACC A AACTCTTC 708 GAAGAGUU CUGAUGAG X CGAA IGUGGAAA 3217

24 CACCAAAC T CTTCAAGA 709 UCUUGAAG CUGAUGAG X CGAA IUUUGGUG 3218

26 CCAAACTC T TCAAGATC 710 GAUCUUGA CUGAUGAG X CGAA IAGUUUGG 3219

29 AACTCTTC A AGATCCCA 711 UGGGAUCU CUGAUGAG X CGAA IAAGAGUU 3220

35 TCAAGATC C CAGAGTCA 712 UGACUCUG CUGAUGAG X CGAA IAUCUUGA 3221

36 CAAGATCC C AGAGTCAG 713 CUGACUCU CUGAUGAG X CGAA IGAUCUUG 3222

37 AAGATCCC A GAGTCAGG 714 CCUGACUC CUGAUGAG X CGAA IGGAUCUU 3223

43 CCAGAGTC A GGGCCCTG 715 CAGGGCCC CUGAUGAG X CGAA IACUCUGG 3224

48 GTCAGGGC C CTGTACTT 716 AAGUACAG CUGAUGAG X CGAA ICCCUGAC 3225

49 TCAGGGCC C TGTACTTT 717 AAAGUACA CUGAUGAG X CGAA IGCCCUGA 3226

50 CAGGGCCC T GTACTTTC 718 GAAAGUAC CUGAUGAG X CGAA IGGCCCUG 3227

55 CCCTGTAC T TTCCTGCT 719 AGCAGGAA CUGAUGAG X CGAA IUACAGGG 3228

59 GTACTTTC C TGCTGGTG 720 CACCAGCA CUGAUGAG X CGAA IAAAGUAC 3229

60 TACTTTCC T GCTGGTGG 721 CCACCAGC CUGAUGAG X CGAA IGAAAGUA 3230

63 TTTCCTGC T GGTGGCTC 722 GAGCCACC CUGAUGAG X CGAA ICAGGAAA 3231

70 CTGGTGGC T CCAGTTCA 723 UGAACUGG CUGAUGAG X CGAA ICCACCAG 3232

72 GGTGGCTC C AGTTCAGG 724 CCUGAACU CUGAUGAG X CGAA IAGCCACC 3233

73 GTGGCTCC A GTTCAGGA 725 UCCUGAAC CUGAUGAG X CGAA IGAGCCAC 3234

78 TCCAGTTC A GGAACAGT 726 ACUGUUCC CUGAUGAG X CGAA lAACUGGA 3235

84 TCAGGAAC A GTGAGCCC 727 GGGCUCAC CUGAUGAG X CGAA IUUCCUGA 3236

91 CAGTGAGC C CTGCTCAG 728 CUGAGCAG CUGAUGAG X CGAA ICUCACUG 3237

92 AGTGAGCC C TGCTCAGA 729 UCUGAGCA CUGAUGAG X CGAA IGCUCACU 3238

93 GTGAGCCC T GCTCAGAA 730 UUCUGAGC CUGAUGAG X CGAA IGGCUCAC 3239

96 AGCCCTGC T CAGAATAC 731 GUAUUCUG CUGAUGAG X CGAA ICAGGGCU 3240

98 CCCTGCTC A GAATACTG 732 CAGUAUUC CUGAUGAG X CGAA IAGCAGGG 3241

105 CAGAATAC T GTCTCTGC 733 GCAGAGAC CUGAUGAG X CGAA IUAUUCUG 3242

109 ATACTGTC T CTGCCATA 734 UAUGGCAG CUGAUGAG X CGAA IACAGUAU 3243

111 ACTGTCTC T GCCATATC 735 GAUAUGGC CUGAUGAG X CGAA IAGACAGU 3244

114 GTCTCTGC C ATATCGTC 736 GACGAUAU CUGAUGAG X CGAA ICAGAGAC 3245

115 TCTCTGCC A TATCGTCA 737 UGACGAUA CUGAUGAG X CGAA IGCAGAGA 3246

123 ATATCGTC A ATCTTATC 738 GAUAAGAU CUGAUGAG X CGAA IACGAUAU 3247

127 l CGTCAATC T TATCGAAG 739 CUUCGAUA CUGAUGAG X CGAA IAUUGACG 3248

138 TCGAAGAC T GGGGACCC 740 GGGUCCCC CUGAUGAG X CGAA IUCUUCGA 3249

145 CTGGGGAC C CTGTACCG 741 CGGUACAG CUGAUGAG X CGAA IUCCCCAG 3250

146 TGGGGACC C TGTACCGA 742 UCGGUACA CUGAUGAG X CGAA IGUCCCCA 3251

147 GGGGACCC T GTACCGAA 743 UUCGGUAC CUGAUGAG X CGAA IGGUCCCC 3252

152 CCCTGTAC C GAACATGG 744 CCAUGUUC CUGAUGAG X CGAA IUACAGGG 3253

157 TACCGAAC A TGGAGAAC 745 GUUCUCCA CUGAUGAG X CGAA IUUCGGUA 3254

166 TGGAGAAC A TCGCATCA 746 UGAUGCGA CUGAUGAG X CGAA lUUCUCCA 3255

171 AACATCGC A TCAGGACT 747 AGUCCUGA CUGAUGAG X CGAA ICGAUGUU 3256

174 ATCGCATC A GGACTCCT 748 AGGAGUCC CUGAUGAG X CGAA IAUGCGAU 3257 Table 38

179 ATCAGGAC T CCTAGGAC 749 GUCCUAGG CUGAUGAG X CGAA IUCCUGAU 3258

181 CAGGACTC C TAGGACCC 750 GGGUCCUA CUGAUGAG X CGAA IAGUCCUG 3259

182 AGGACTCC T AGGACCCC 751 GGGGUCCU CUGAUGAG X CGAA IGAGUCCU 3260

188 CCTAGGAC c CCTGCTCG 752 CGAGCAGG CUGAUGAG X CGAA IUCCUAGG 3261

189 CTAGGACC c CTGCTCGT 753 ACGAGCAG CUGAUGAG X CGAA IGUCCUAG 3262

190 TAGGACCC c TGCTCGTG 754 CACGAGCA CUGAUGAG X CGAA IGGUCCUA 3263

191 AGGACCCC T GCTCGTGT 755 ACACGAGC CUGAUGAG X CGAA IGGGUCCU 3264

194 ACCCCTGC T CGTGTTAC 756 GUAACACG CUGAUGAG X CGAA ICAGGGGU 3265

203 CGTGTTAC A GGCGGGGT 757 ACCCCGCC CUGAUGAG X CGAA IUAACACG 3266

217 GGTTTTTC T TGTTGACA 758 UGUCAACA CUGAUGAG X CGAA IAAAAACC 3267

225 TTGTTGAC A AAAATCCT 759 AGGAUUUU CUGAUGAG X CGAA lUCAACAA 3268

232 CAAAAATC C TCACAATA 760 UAUUGUGA CUGAUGAG X CGAA IAUUUUUG 3269

233 AAAAATCC T CACAATAC 761 GUAUUGUG CUGAUGAG X CGAA IGAUUUUU 3270

235 AAATCCTC A CAATACCA 762 UGGUAUUG CUGAUGAG X CGAA IAGGAUUU 3271

237 ATCCTCAC A ATACCACA 763 UGUGGUAU CUGAUGAG X CGAA IUGAGGAU 3272

242 CACAATAC C ACAGAGTC 764 GACUCUGU CUGAUGAG X CGAA IUAUUGUG 3273

243 ACAATACC A CAGAGTCT 765 AGACUCUG CUGAUGAG X CGAA IGUAUUGU 3274

245 AATACCAC A GAGTCTAG 766 CUAGACUC CUGAUGAG X CGAA IUGGUAUU 3275

251 ACAGAGTC T AGACTCGT 767 ACGAGUCU CUGAUGAG X CGAA IACUCUGU 3276

256 GTCTAGAC T CGTGGTGG 768 CCACCACG CUGAUGAG X CGAA IUCUAGAC 3277

267 TGGTGGAC T TCTCTCAA 769 UUGAGAGA CUGAUGAG X CGAA IUCCACCA 3278

270 TGGACTTC T CTCAATTT 770 AAAUUGAG CUGAUGAG X CGAA IAAGUCCA 3279

272 GACTTCTC T CAATTTTC 771 GAAAAUUG CUGAUGAG X CGAA IAGAAGUC 3280

274 CTTCTCTC A ATTTTCTA 772 UAGAAAAU CUGAUGAG X CGAA IAGAGAAG 3281

281 CAATTTTC T AGGGGGAA 773 UUCCCCCU CUGAUGAG X CGAA IAAAAUUG 3282

291 GGGGGAAC A CCCGTGTG 774 CACACGGG CUGAUGAG X CGAA IUUCCCCC 3283

293 GGGAACAC C CGTGTGTC 775 GACACACG CUGAUGAG X CGAA IUGUUCCC 3284

294 GGAACACC C GTGTGTCT 776 AGACACAC CUGAUGAG X CGAA IGUGUUCC 3285

302 CGTGTGTC T TGGCCAAA 777 UUUGGCCA CUGAUGAG X CGAA IACACACG 3286

307 GTCTTGGC C AAAATTCG 778 CGAAUUUU CUGAUGAG X CGAA ICCAAGAC 3287

308 TCTTGGCC A AAATTCGC 779 GCGAAUUU CUGAUGAG X CGAA IGCCAAGA 3288

317 AAATTCGC A GTCCCAAA 780 UUUGGGAC CUGAUGAG X CGAA ICGAAUUU 3289

321 TCGCAGTC C CAAATCTC 781 GAGAUUUG CUGAUGAG X CGAA IACUGCGA 3290

322 CGCAGTCC C AAATCTCC 782 GGAGAUUU CUGAUGAG X CGAA IGACUGCG 3291

323 GCAGTCCC A AATCTCCA 783 UGGAGAUU CUGAUGAG X CGAA IGGACUGC 3292

328 CCCAAATC T CCAGTCAC 784 GUGACUGG CUGAUGAG X CGAA IAUUUGGG 3293

330 CAAATCTC C AGTCACTC 785 GAGUGACU CUGAUGAG X CGAA IAGAUUUG 3294

331 AAATCTCC A GTCACTCA 786 UGAGUGAC CUGAUGAG X CGAA IGAGAUUU 3295

335 CTCCAGTC A CTCACCAA 787 UUGGUGAG CUGAUGAG X CGAA IACUGGAG 3296

337 CCAGTCAC T CACCAACC 788 GGUUGGUG CUGAUGAG X CGAA IUGACUGG 3297

339 AGTCACTC A CCAACCTG 789 CAGGUUGG CUGAUGAG X CGAA IAGUGACU 3298

341 TCACTCAC C AACCTGTT 790 AACAGGUU CUGAUGAG X CGAA lUGAGUGA 3299

342 CACTCACC A ACCTGTTG 791 CAACAGGU CUGAUGAG X CGAA IGUGAGUG 3300

345 TCACCAAC C TGTTGTCC 792 GGACAACA CUGAUGAG X CGAA IUUGGUGA 3301

346 CACCAACC T GTTGTCCT 793 AGGACAAC CUGAUGAG X CGAA IGUUGGUG 3302

353 CTGTTGTC C TCCAATTT 794 AAAUUGGA CUGAUGAG X CGAA lACAACAG 3303

354 TGTTGTCC T CCAATTTG 795 CAAAUUGG CUGAUGAG X CGAA IGACAACA 3304

356 TTGTCCTC C AATTTGTC 796 GACAAAUU CUGAUGAG X CGAA IAGGACAA 3305

357 TGTCCTCC A ATTTGTCC 797 GGACAAAU CUGAUGAG X CGAA IGAGGACA 3306

365 AATTTGTC C TGGTTATC 798 GAUAACCA CUGAUGAG X CGAA IACAAAUU 3307

366 ATTTGTCC T GGTTATCG 799 CGAUAACC CUGAUGAG X CGAA IGACAAAU 3308 Table 38

376 GTTATCGC T GGATGTGT 800 ACACAUCC CUGAUGAG X CGAA ICGAUAAC 3309

386 GATGTGTC T GCGGCGTT 801 AACGCCGC CUGAUGAG X CGAA IACACAUC 3310

400 GTTTTATC A TCTTCCTC 802 GAGGAAGA CUGAUGAG X CGAA IAUAAAAC 3311

403 TTATCATC T TCCTCTGC 803 GCAGAGGA CUGAUGAG X CGAA IAUGAUAA 3312

406 TCATCTTC C TCTGCATC 804 GAUGCAGA CUGAUGAG X CGAA IAAGAUGA 3313

407 CATCTTCC T CTGCATCC 805 GGAUGCAG CUGAUGAG X CGAA IGAAGAUG 3314

409 TCTTCCTC T GCATCCTG 806 CAGGAUGC CUGAUGAG X CGAA IAGGAAGA 3315

412 TCCTCTGC A TCCTGCTG 807 CAGCAGGA CUGAUGAG X CGAA ICAGAGGA 3316

415 TCTGCATC C TGCTGCTA 808 UAGCAGCA CUGAUGAG X CGAA IAUGCAGA 3317

416 CTGCATCC T GCTGCTAT 809 AUAGCAGC CUGAUGAG X CGAA IGAUGCAG 3318

419 CATCCTGC T GCTATGCC 810 GGCAUAGC CUGAUGAG X CGAA ICAGGAUG 3319

422 CCTGCTGC T ATGCCTCA 811 UGAGGCAU CUGAUGAG X CGAA ICAGCAGG 3320

427 TGCTATGC C TCATCTTC 812 GAAGAUGA CUGAUGAG X CGAA ICAUAGCA 3321

428 GCTATGCC T CATCTTCT 813 AGAAGAUG CUGAUGAG X CGAA IGCAUAGC 3322

430 TATGCCTC A TCTTCTTG 814 CAAGAAGA CUGAUGAG X CGAA IAGGCAUA 3323

433 GCCTCATC T TCTTGTTG 815 CAACAAGA CUGAUGAG X CGAA IAUGAGGC 3324

436 TCATCTTC T TGTTGGTT 816 AACCAACA CUGAUGAG X CGAA IAAGAUGA 3325

446 GTTGGTTC T TCTGGACT 817 AGUCCAGA CUGAUGAG X CGAA IAACCAAC 3326

449 GGTTCTTC T GGACTATC 818 GAUAGUCC CUGAUGAG X CGAA IAAGAACC 3327

454 TTCTGGAC T ATCAAGGT 819 ACCUUGAU CUGAUGAG X CGAA IUCCAGAA 3328

458 GGACTATC A AGGTATGT 820 ACAUACCU CUGAUGAG X CGAA IAUAGUCC 3329

470 TATGTTGC C CGTTTGTC 821 GACAAACG CUGAUGAG X CGAA ICAACAUA 3330

471 ATGTTGCC C GTTTGTCC 822 GGACAAAC CUGAUGAG X CGAA IGCAACAU 3331

479 CGTTTGTC C TCTAATTC 823 GAAUUAGA CUGAUGAG X CGAA IACAAACG 3332

480 GTTTGTCC T CTAATTCC 824 GGAAUUAG CUGAUGAG X CGAA IGACAAAC 3333

482 TTGTCCTC T AATTCCAG 825 CUGGAAUU CUGAUGAG X CGAA IAGGACAA 3334

488 TCTAATTC c AGGATCAT 826 AUGAUCCU CUGAUGAG X CGAA lAAUUAGA 3335

489 CTAATTCC A GGATCATC 827 GAUGAUCC CUGAUGAG X CGAA IGAAUUAG 3336

495 CCAGGATC A TCAACAAC j 828 GUUGUUGA CUGAUGAG X CGAA IAUCCUGG 3337

498 GGATCATC A ACAACCAG 829 CUGGUUGU CUGAUGAG X CGAA IAUGAUCC 3338

501 TCATCAAC A ACCAGCAC 830 GUGCUGGU CUGAUGAG X CGAA IUUGAUGA 3339

504 TCAACAAC c AGCACCGG 831 CCGGUGCU CUGAUGAG X CGAA IUUGUUGA 3340

505 CAACAACC A GCACCGGA 832 UCCGGUGC CUGAUGAG X CGAA IGUUGUUG 3341

508 CAACCAGC A CCGGACCA 833 UGGUCCGG CUGAUGAG X CGAA ICUGGUUG 3342

510 ACCAGCAC C GGACCATG 834 CAUGGUCC CUGAUGAG X CGAA IUGCUGGU 3343

515 CACCGGAC C ATGCAAAA 835 UUUUGCAU CUGAUGAG X CGAA IUCCGGUG 3344

516 ACCGGACC A TGCAAAAC 836 GUUUUGCA CUGAUGAG X CGAA IGUCCGGU 3345

520 GACCATGC A AAACCTGC 837 GCAGGUUU CUGAUGAG X CGAA ICAUGGUC 3346

525 TGCAAAAC C TGCACAAC 838 GUUGUGCA CUGAUGAG X CGAA IUUUUGCA 3347

526 GCAAAACC T GCACAACT 839 AGUUGUGC CUGAUGAG X CGAA IGUUUUGC 3348

529 AAACCTGC A CAACTCCT 840 AGGAGUUG CUGAUGAG X CGAA ICAGGUUU 3349

531 ACCTGCAC A ACTCCTGC 841 GCAGGAGU CUGAUGAG X CGAA IUGCAGGU 3350

534 TGCACAAC T CCTGCTCA 842 UGAGCAGG CUGAUGAG X CGAA IUUGUGCA 3351

536 CACAACTC C TGCTCAAG 843 CUUGAGCA CUGAUGAG X CGAA IAGUUGUG 3352

537 ACAACTCC T GCTCAAGG 844 CCUUGAGC CUGAUGAG X CGAA IGAGUUGU 3353

540 ACTCCTGC T CAAGGAAC 845 GUUCCUUG CUGAUGAG X CGAA ICAGGAGU 3354

542 TCCTGCTC A AGGAACCT 846 AGGUUCCU CUGAUGAG X CGAA lAGCAGGA 3355

549 CAAGGAAC C TCTATGTT 847 AACAUAGA CUGAUGAG X CGAA IUUCCUUG 3356

550 AAGGAACC T CTATGTTT 848 AAACAUAG CUGAUGAG X CGAA IGUUCCUU 3357

552 GGAACCTC T ATGTTTCC 849 GGAAACAU CUGAUGAG X CGAA IAGGUUCC 3358

560 TATGTTTC C CTCATGTT 850 AACAUGAG CUGAUGAG X CGAA IAAACAUA 3359 Table 38

561 ATGTTTCC C TCATGTTG 851 CAACAUGA CUGAUGAG X CGAA IGAAACAU 3360

562 TGTTTCCC T CATGTTGC 852 GCAACAUG CUGAUGAG X CGAA IGGAAACA 3361

564 TTTCCCTC A TGTTGCTG 853 CAGCAACA CUGAUGAG X CGAA IAGGGAAA 3362

571 CATGTTGC T GTACAAAA 854 UUUUGUAC CUGAUGAG X CGAA ICAACAUG 3363

576 TGCTGTAC A AAACCTAC 855 GUAGGUUU CUGAUGAG X CGAA IUACAGCA 3364

581 TACAAAAC C TACGGACG 856 CGUCCGUA CUGAUGAG X CGAA IUUUUGUA 3365

582 ACAAAACC T ACGGACGG 857 CCGUCCGU CUGAUGAG X CGAA IGUUUUGU 3366

595 ACGGAAAC T GCACCTGT 858 ACAGGUGC CUGAUGAG X CGAA IUUUCCGU 3367

598 GAAACTGC A CCTGTATT 859 AAUACAGG CUGAUGAG X CGAA ICAGUUUC 3368

600 AACTGCAC C TGTATTCC 860 GGAAUACA CUGAUGAG X CGAA IUGCAGUU 3369

601 ACTGCACC T GTATTCCC 861 GGGAAUAC CUGAUGAG X CGAA IGUGCAGU 3370

608 CTGTATTC C CATCCCAT 862 AUGGGAUG CUGAUGAG X CGAA IAAUACAG 3371

609 TGTATTCC C ATCCCATC 863 GAUGGGAU CUGAUGAG X CGAA IGAAUACA 3372

610 GTATTCCC A TCCCATCA 864 UGAUGGGA CUGAUGAG X CGAA IGGAAUAC 3373

613 TTCCCATC C CATCATCT 865 AGAUGAUG CUGAUGAG X CGAA IAUGGGAA 3374

614 TCCCATCC C ATCATCTT 866 AAGAUGAU CUGAUGAG X CGAA IGAUGGGA 3375

615 CCCATCCC A TCATCTTG 867 CAAGAUGA CUGAUGAG X CGAA IGGAUGGG 3376

618 ATCCCATC A TCTTGGGC 868 GCCCAAGA CUGAUGAG X CGAA IAUGGGAU 3377

621 CCATCATC T TGGGCTTT 869 AAAGCCCA CUGAUGAG X CGAA IAUGAUGG 3378

627 TCTTGGGC T TTCGCAAA 870 UUUGCGAA CUGAUGAG X CGAA ICCCAAGA 3379

633 GCTTTCGC A AAATACCT 871 AGGUAUUU CUGAUGAG X CGAA ICGAAAGC 3380

640 CAAAATAC C TATGGGAG 872 CUCCCAUA CUGAUGAG X CGAA IUAUUUUG 3381

641 AAAATACC T ATGGGAGT 873 ACUCCCAU CUGAUGAG X CGAA IGUAUUUU 3382

654 GAGTGGGC C TCAGTCCG 874 CGGACUGA CUGAUGAG X CGAA ICCCACUC 3383

655 AGTGGGCC T CAGTCCGT 875 ACGGACUG CUGAUGAG X CGAA IGCCCACU 3384

657 TGGGCCTC A GTCCGTTT 876 AAACGGAC CUGAUGAG X CGAA lAGGCCCA 3385

661 CCTCAGTC C GTTTCTCT 877 AGAGAAAC CUGAUGAG X CGAA IACUGAGG 3386

667 TCCGTTTC T CTTGGCTC 878 GAGCCAAG CUGAUGAG X CGAA lAAACGGA 3387

669 CGTTTCTC T TGGCTCAG 879 CUGAGCCA CUGAUGAG X CGAA IAGAAACG 3388

674 CTCTTGGC T CAGTTTAC 880 GUAAACUG CUGAUGAG X CGAA ICCAAGAG 3389

676 CTTGGCTC A GTTTACTA 881 UAGUAAAC CUGAUGAG X CGAA IAGCCAAG 3390

683 CAGTTTAC T AGTGCCAT 882 AUGGCACU CUGAUGAG X CGAA IUAAACUG 3391

689 ACTAGTGC C ATTTGTTC 883 GAACAAAU CUGAUGAG X CGAA ICACUAGU 3392

690 CTAGTGCC A TTTGTTCA 884 UGAACAAA CUGAUGAG X CGAA IGCACUAG 3393

698 ATTTGTTC A GTGGTTCG 885 CGAACCAC CUGAUGAG X CGAA IAACAAAU 3394

713 CGTAGGGC T TTCCCCCA 886 UGGGGGAA CUGAUGAG X CGAA ICCCUACG 3395

717 GGGCTTTC C CCCACTGT 887 ACAGUGGG CUGAUGAG X CGAA IAAAGCCC 3396

718 GGCTTTCC C CCACTGTC 888 GACAGUGG CUGAUGAG X CGAA IGAAAGCC 3397

719 GCTTTCCC C CACTGTCT 889 AGACAGUG CUGAUGAG X CGAA IGGAAAGC 3398

720 CTTTCCCC C ACTGTCTG 890 CAGACAGU CUGAUGAG X CGAA IGGGAAAG 3399

721 TTTCCCCC A CTGTCTGG 891 CCAGACAG CUGAUGAG X CGAA IGGGGAAA 3400

723 TCCCCCAC T GTCTGGCT 892 AGCCAGAC CUGAUGAG X CGAA IUGGGGGA 3401

727 CCACTGTC T GGCTTTCA 893 UGAAAGCC CUGAUGAG X CGAA IACAGUGG 3402

731 TGTCTGGC T TTCAGTTA 894 UAACUGAA CUGAUGAG X CGAA ICCAGACA 3403

735 TGGCTTTC A GTTATATG 895 CAUAUAAC CUGAUGAG X CGAA IAAAGCCA 3404

764 TTGGGGGC C AAGTCTGT 896 ACAGACUU CUGAUGAG X CGAA ICCCCCAA 3405

765 TGGGGGCC A AGTCTGTA 897 UACAGACU CUGAUGAG X CGAA IGCCCCCA 3406

770 GCCAAGTC T GTACAACA 898 UGUUGUAC CUGAUGAG X CGAA IACUUGGC 3407

775 GTCTGTAC A ACATCTTG 899 CAAGAUGU CUGAUGAG X CGAA IUACAGAC 3408

778 TGTACAAC A TCTTGAGT 900 ACUCAAGA CUGAUGAG X CGAA IUUGUACA 3409

781 ACAACATC T TGAGTCCC 901 GGGACUCA CUGAUGAG X CGAA IAUGUUGU 3410 Table 38

788 CTTGAGTC C CTTTATGC 902 GCAUAAAG CUGAUGAG X CGAA IACUCAAG 3411

789 TTGAGTCC C TTTATGCC 903 GGCAUAAA CUGAUGAG X CGAA IGACUCAA 3412

790 TGAGTCCC T TTATGCCG 904 CGGCAUAA CUGAUGAG X CGAA IGGACUCA 3413

797 CTTTATGC C GCTGTTAC 905 GUAACAGC CUGAUGAG X CGAA ICAUAAAG 3414

800 TATGCCGC T GTTACCAA 906 UUGGUAAC CUGAUGAG X CGAA ICGGCAUA 3415

806 GCTGTTAC C AATTTTCT 907 AGAAAAUU CUGAUGAG X CGAA IUAACAGC 3416

807 CTGTTACC A ATTTTCTT 908 AAGAAAAU CUGAUGAG X CGAA IGUAACAG 3417

814 CAATTTTC T TTTGTCTT 909 AAGACAAA CUGAUGAG X CGAA IAAAAUUG 3418

821 CTTTTGTC T TTGGGTAT 910 AUACCCAA CUGAUGAG X CGAA IACAAAAG 3419

832 GGGTATAC A TTTAAACC 911 GGUUUAAA CUGAUGAG X CGAA IUAUACCC 3420

840 ATTTAAAC C CTCACAAA 912 UUUGUGAG CUGAUGAG X CGAA IUUUAAAU 3421

841 TTTAAACC C TCACAAAA 913 UUUUGUGA CUGAUGAG X CGAA IGUUUAAA 3422

842 TTAAACCC T CACAAAAC 914 GUUUUGUG CUGAUGAG X CGAA IGGUUUAA 3423

844 AAACCCTC A CAAAACAA 915 UUGUUUUG CUGAUGAG X CGAA IAGGGUUU 3424

846 ACCCTCAC A AAACAAAA 916 UUUUGUUU CUGAUGAG X CGAA IUGAGGGU 3425

851 CACAAAAC A AAAAGATG 917 CAUCUUUU CUGAUGAG X CGAA IUUUUGUG 3426

869 GGATATTC C CTTAACTT 918 AAGUUAAG CUGAUGAG X CGAA IAAUAUCC 3427

870 GATATTCC C TTAACTTC 919 GAAGUUAA CUGAUGAG X CGAA IGAAUAUC 3428

871 ATATTCCC T TAACTTCA 920 UGAAGUUA CUGAUGAG X CGAA IGGAAUAU 3429

876 CCCTTAAC T TCATGGGA 921 UCCCAUGA CUGAUGAG X CGAA IUUAAGGG 3430

879 TTAACTTC A TGGGATAT 922 AUAUCCCA CUGAUGAG X CGAA IAAGUUAA 3431

906 GTTGGGGC A CATTGCCA 923 UGGCAAUG CUGAUGAG X CGAA ICCCCAAC 3432

908 TGGGGCAC A TTGCCACA 924 UGUGGCAA CUGAUGAG X CGAA IUGCCCCA 3433

913 CACATTGC C ACAGGAAC 925 GUUCCUGU CUGAUGAG X CGAA ICAAUGUG 3434

914 ACATTGCC A CAGGAACA 926 UGUUCCUG CUGAUGAG X CGAA IGCAAUGU 3435

916 ATTGCCAC A GGAACATA 927 UAUGUUCC CUGAUGAG X CGAA lUGGCAAU 3436

922 ACAGGAAC A TATTGTAC 928 GUACAAUA CUGAUGAG X CGAA IUUCCUGU 3437

931 TATTGTAC A AAAAATCA 929 UGAUUUUU CUGAUGAG X CGAA IUACAAUA 3438

939 AAAAAATC A AAATGTGT 930 ACACAUUU CUGAUGAG X CGAA IAUUUUUU 3439

958 TAGGAAAC T TCCTGTAA 931 UUACAGGA CUGAUGAG X CGAA IUUUCCUA 3440

961 GAAACTTC C TGTAAACA 932 UGUUUACA CUGAUGAG X CGAA IAAGUUUC 3441

962 AAACTTCC T GTAAACAG 933 CUGUUUAC CUGAUGAG X CGAA IGAAGUUU 3442

969 CTGTAAAC A GGCCTATT 934 AAUAGGCC CUGAUGAG X CGAA IUUUACAG 3443

973 AAACAGGC C TATTGATT 935 AAUCAAUA CUGAUGAG X CGAA ICCUGUUU 3444

974 AACAGGCC T ATTGATTG 936 CAAUCAAU CUGAUGAG X CGAA IGCCUGUU 3445

994 AGTATGTC A ACGAATTG 937 CAAUUCGU CUGAUGAG X CGAA IACAUACU 3446

1009 TGTGGGTC T TTTGGGGT 938 ACCCCAAA CUGAUGAG X CGAA lACCCACA 3447

1022 GGGTTTGC C GCCCCTTT 939 AAAGGGGC CUGAUGAG X CGAA ICAAACCC 3448

1025 TTTGCCGC C CCTTTCAC 940 GUGAAAGG CUGAUGAG X CGAA ICGGCAAA 3449

1026 TTGCCGCC C CTTTCACG 941 CGUGAAAG CUGAUGAG X CGAA IGCGGCAA 3450

1027 TGCCGCCC C TTTCACGC 942 GCGUGAAA CUGAUGAG X CGAA IGGCGGCA 3451

1028 GCCGCCCC T TTCACGCA 943 UGCGUGAA CUGAUGAG X CGAA IGGGCGGC 3452

1032 CCCCTTTC A CGCAATGT 944 ACAUUGCG CUGAUGAG X CGAA IAAAGGGG 3453

1036 TTTCACGC A ATGTGGAT 945 AUCCACAU CUGAUGAG X CGAA ICGUGAAA 3454

1049 GGATATTC T GCTTTAAT 946 AUUAAAGC CUGAUGAG X CGAA IAAUAUCC 3455

1052 TATTCTGC T TTAATGCC 947 GGCAUUAA CUGAUGAG X CGAA ICAGAAUA 3456

1060 TTTAATGC C TTTATATG 948 CAUAUAAA CUGAUGAG X CGAA ICAUUAAA 3457

1061 TTAATGCC T TTATATGC 949 GCAUAUAA CUGAUGAG X CGAA IGCAUUAA 3458

1070 TTATATGC A TGCATACA 950 UGUAUGCA CUGAUGAG X CGAA ICAUAUAA 3459

1074 ATGCATGC A TACAAGCA 951 UGCUUGUA CUGAUGAG X CGAA ICAUGCAU 3460

1078 ATGCATAC A AGCAAAAC 952 GUUUUGCU CUGAUGAG X CGAA IUAUGCAU 3461 Table 38

1082 ATACAAGC A AAACAGGC 953 GCCUGUUU CUGAUGAG X CGAA ICUUGUAU 3462

1087 AGCAAAAC A GGCTTTTA 954 UAAAAGCC CUGAUGAG X CGAA IUUUUGCU 3463

1091 AAACAGGC T TTTACTTT 955 AAAGUAAA CUGAUGAG X CGAA ICCUGUUU 3464

1097 GCTTTTAC T TTCTCGCC 956 GGCGAGAA CUGAUGAG X CGAA lUAAAAGC 3465

1101 TTACTTTC T CGCCAACT 957 AGUUGGCG CUGAUGAG X CGAA IAAAGUAA 3466

1105 TTTCTCGC C AACTTACA 958 UGUAAGUU CUGAUGAG X CGAA ICGAGAAA 3467

1106 TTCTCGCC A ACTTACAA 959 UUGUAAGU CUGAUGAG X CGAA IGCGAGAA 3468

1109 TCGCCAAC T TACAAGGC 960 GCCUUGUA CUGAUGAG X CGAA IUUGGCGA 3469

1113 CAACTTAC A AGGCCTTT 961 AAAGGCCU CUGAUGAG X CGAA IUAAGUUG 3470

1118 TACAAGGC C TTTCTAAG 962 CUUAGAAA CUGAUGAG X CGAA ICCUUGUA 3471

1119 ACAAGGCC T TTCTAAGT 963 ACUUAGAA CUGAUGAG X CGAA IGCCUUGU 3472

1123 GGCCTTTC T AAGTAAAC 964 GUUUACUU CUGAUGAG X CGAA IAAAGGCC 3473

1132 AAGTAAAC A GTATGTGA 965 UCACAUAC CUGAUGAG X CGAA IUUUACUU 3474

1143 ATGTGAAC C TTTACCCC 966 GGGGUAAA CUGAUGAG X CGAA IUUCACAU 3475

1144 TGTGAACC T TTACCCCG 967 CGGGGUAA CUGAUGAG X CGAA IGUUCACA 3476

1149 ACCTTTAC C CCGTTGCT 968 AGCAACGG CUGAUGAG X CGAA IUAAAGGU 3477

1150 CCTTTACC C CGTTGCTC 969 GAGCAACG CUGAUGAG X CGAA IGUAAAGG 3478

1151 CTTTACCC C GTTGCTCG 970 CGAGCAAC CUGAUGAG X CGAA IGGUAAAG 3479

1157 CCCGTTGC T CGGCAACG 971 CGUUGCCG CUGAUGAG X CGAA ICAACGGG 3480

1162 TGCTCGGC A ACGGCCTG 972 CAGGCCGU CUGAUGAG X CGAA ICCGAGCA 3481

1168 GCAACGGC C TGGTCTAT 973 AUAGACCA CUGAUGAG X CGAA ICCGUUGC 3482

1169 CAACGGCC T GGTCTATG 974 CAUAGACC CUGAUGAG X CGAA IGCCGUUG 3483

1174 GCCTGGTC T ATGCCAAG 975 CUUGGCAU CUGAUGAG X CGAA IACCAGGC 3484

1179 GTCTATGC C AAGTGTTT 976 AAACACUU CUGAUGAG X CGAA ICAUAGAC 3485

1180 TCTATGCC A AGTGTTTG 977 CAAACACU CUGAUGAG X CGAA IGCAUAGA 3486

1190 GTGTTTGC T GACGCAAC 978 GUUGCGUC CUGAUGAG X CGAA ICAAACAC 3487

1196 GCTGACGC A ACCCCCAC 979 GUGGGGGU CUGAUGAG X CGAA ICGUCAGC 3488

1199 GACGCAAC C CCCACTGG 980 CCAGUGGG CUGAUGAG X CGAA IUUGCGUC 3489

1200 ACGCAACC C CCACTGGT 981 ACCAGUGG CUGAUGAG X CGAA IGUUGCGU 3490

1201 CGCAACCC C CACTGGTT 982 AACCAGUG CUGAUGAG X CGAA IGGUUGCG 3491

1202 GCAACCCC C ACTGGTTG 983 CAACCAGU CUGAUGAG X CGAA IGGGUUGC 3492

1203 CAACCCCC A CTGGTTGG 984 CCAACCAG CUGAUGAG X CGAA IGGGGUUG 3493

1205 ACCCCCAC T GGTTGGGG 985 CCCCAACC CUGAUGAG X CGAA IUGGGGGU 3494

1215 GTTGGGGC T TGGCCATA 986 UAUGGCCA CUGAUGAG X CGAA ICCCCAAC 3495

1220 GGCTTGGC C ATAGGCCA 987 UGGCCUAU CUGAUGAG X CGAA ICCAAGCC 3496

1221 GCTTGGCC A TAGGCCAT 988 AUGGCCUA CUGAUGAG X CGAA IGCCAAGC 3497

1227 CCATAGGC C ATCAGCGC 989 GCGCUGAU CUGAUGAG X CGAA ICCUAUGG 3498

1228 CATAGGCC A TCAGCGCA 990 UGCGCUGA CUGAUGAG X CGAA IGCCUAUG 3499

1231 AGGCCATC A GCGCATGC 991 GCAUGCGC CUGAUGAG X CGAA IAUGGCCU 3500

1236 ATCAGCGC A TGCGTGGA 992 UCCACGCA CUGAUGAG X CGAA ICGCUGAU 3501

1247 CGTGGAAC C TTTGTGTC 993 GACACAAA CUGAUGAG X CGAA IUUCCACG 3502

1248 GTGGAACC T TTGTGTCT 994 AGACACAA CUGAUGAG X CGAA IGUUCCAC 3503

1256 TTTGTGTC T CCTCTGCC 995 GGCAGAGG CUGAUGAG X CGAA lACACAAA 3504

1258 TGTGTCTC C TCTGCCGA 996 UCGGCAGA CUGAUGAG X CGAA lAGACACA 3505

1259 GTGTCTCC T CTGCCGAT 997 AUCGGCAG CUGAUGAG X CGAA IGAGACAC 3506

1261 GTCTCCTC T GCCGATCC 998 GGAUCGGC CUGAUGAG X CGAA IAGGAGAC 3507

1264 TCCTCTGC C GATCCATA 999 UAUGGAUC CUGAUGAG X CGAA ICAGAGGA 3508

1269 TGCCGATC C ATACCGCG 1000 CGCGGUAU CUGAUGAG X CGAA IAUCGGCA 3509

1270 GCCGATCC A TACCGCGG 1001 CCGCGGUA CUGAUGAG X CGAA IGAUCGGC 3510

1274 ATCCATAC C GCGGAACT 1002 AGUUCCGC CUGAUGAG X CGAA IUAUGGAU 3511

1282 CGCGGAAC T CCTAGCCG 1003 CGGCUAGG CUGAUGAG X CGAA IUUCCGCG 3512 Table 38

1284 CGGAACTC C TAGCCGCT 1004 AGCGGCUA CUGAUGAG X CGAA IAGUUCCG 3513

1285 GGAACTCC T AGCCGCTT 1005 AAGCGGCU CUGAUGAG X CGAA IGAGUUCC 3514

1289 CTCCTAGC C GCTTGTTT 1006 AAACAAGC CUGAUGAG X CGAA ICUAGGAG 3515

1292 CTAGCCGC T TGTTTTGC 1007 GCAAAACA CUGAUGAG X CGAA ICGGCUAG 3516

1301 TGTTTTGC T CGCAGCAG 1008 CUGCUGCG CUGAUGAG X CGAA ICAAAACA 3517

1305 TTGCTCGC A GCAGGTCT 1009 AGACCUGC CUGAUGAG X CGAA ICGAGCAA 3518

1308 CTCGCAGC A GGTCTGGG 1010 CCCAGACC CUGAUGAG X CGAA ICUGCGAG 3519

1313 AGCAGGTC T GGGGCAAA 1011 UUUGCCCC CUGAUGAG X CGAA IACCUGCU 3520

1319 TCTGGGGC A AAACTCAT 1012 AUGAGUUU CUGAUGAG X CGAA ICCCCAGA 3521

1324 GGCAAAAC T CATCGGGA 1013 UCCCGAUG CUGAUGAG X CGAA IUUUUGCC 3522

1326 CAAAACTC A TCGGGACT 1014 AGUCCCGA CUGAUGAG X CGAA lAGUUUUG 3523

1334 ATCGGGAC T GACAATTC 1015 GAAUUGUC CUGAUGAG X CGAA IUCCCGAU 3524

1338 GGACTGAC A ATTCTGTC 1016 GACAGAAU CUGAUGAG X CGAA IUCAGUCC 3525

1343 GACAATTC T GTCGTGCT 1017 AGCACGAC CUGAUGAG X CGAA IAAUUGUC 3526

1351 TGTCGTGC T CTCCCGCA 1018 UGCGGGAG CUGAUGAG X CGAA ICACGACA 3527

1353 TCGTGCTC T CCCGCAAA 1019 UUUGCGGG CUGAUGAG X CGAA IAGCACGA 3528

1355 GTGCTCTC C CGCAAATA 1020 UAUUUGCG CUGAUGAG X CGAA IAGAGCAC 3529

1356 TGCTCTCC C GCAAATAT 1021 AUAUUUGC CUGAUGAG X CGAA IGAGAGCA 3530

1359 TCTCCCGC A AATATACA 1022 UGUAUAUU CUGAUGAG X CGAA ICGGGAGA 3531

1367 AAATATAC A TCATTTCC 1023 GGAAAUGA CUGAUGAG X CGAA IUAUAUUU 3532

1370 TATACATC A TTTCCATG 1024 CAUGGAAA CUGAUGAG X CGAA IAUGUAUA 3533

1375 ATCATTTC C ATGGCTGC 1025 GCAGCCAU CUGAUGAG X CGAA IAAAUGAU 3534

1376 TCATTTCC A TGGCTGCT 1026 AGCAGCCA CUGAUGAG X CGAA IGAAAUGA 3535

1381 TCCATGGC T GCTAGGCT 1027 AGCCUAGC CUGAUGAG X CGAA ICCAUGGA 3536

1384 ATGGCTGC T AGGCTGTG 1028 CACAGCCU CUGAUGAG X CGAA ICAGCCAU 3537

1389 TGCTAGGC T GTGCTGCC 1029 GGCAGCAC CUGAUGAG X CGAA ICCUAGCA 3538

1394 GGCTGTGC T GCCAACTG 1030 CAGUUGGC CUGAUGAG X CGAA ICACAGCC 3539

1397 TGTGCTGC C AACTGGAT 1031 AUCCAGUU CUGAUGAG X CGAA ICAGCACA 3540

1398 GTGCTGCC A ACTGGATC 1032 GAUCCAGU CUGAUGAG X CGAA IGCAGCAC 3541

1401 CTGCCAAC T GGATCCTA 1033 UAGGAUCC CUGAUGAG X CGAA IUUGGCAG 3542

1407 ACTGGATC C TACGCGGG 1034 CCCGCGUA CUGAUGAG X CGAA IAUCCAGU 3543

1408 CTGGATCC T ACGCGGGA 1035 UCCCGCGU CUGAUGAG X CGAA IGAUCCAG 3544

1421 GGGACGTC C TTTGTTTA 1036 UAAACAAA CUGAUGAG X CGAA IACGUCCC 3545

1422 GGACGTCC T TTGTTTAC 1037 GUAAACAA CUGAUGAG X CGAA IGACGUCC 3546

1434 TTTACGTC c CGTCGGCG 1038 CGCCGACG CUGAUGAG X CGAA IACGUAAA 3547

1435 TTACGTCC c GTCGGCGC 1039 GCGCCGAC CUGAUGAG X CGAA IGACGUAA 3548

1444 GTCGGCGC T GAATCCCG 1040 CGGGAUUC CUGAUGAG X CGAA ICGCCGAC 3549

1450 GCTGAATC c CGCGGACG 1041 CGUCCGCG CUGAUGAG X CGAA IAUUCAGC 3550

1451 CTGAATCC c GCGGACGA 1042 UCGUCCGC CUGAUGAG X CGAA IGAUUCAG 3551

1461 CGGACGAC c CCTCCCGG 1043 CCGGGAGG CUGAUGAG X CGAA IUCGUCCG 3552

1462 GGACGACC c CTCCCGGG 1044 CCCGGGAG CUGAUGAG X CGAA IGUCGUCC 3553

1463 GACGACCC c TCCCGGGG 1045 CCCCGGGA CUGAUGAG X CGAA IGGUCGUC 3554

1464 ACGACCCC T CCCGGGGC 1046 GCCCCGGG CUGAUGAG X CGAA IGGGUCGU 3555

1466 GACCCCTC c CGGGGCCG 1047 CGGCCCCG CUGAUGAG X CGAA IAGGGGUC 3556

1467 ACCCCTCC c GGGGCCGC 1048 GCGGCCCC CUGAUGAG X CGAA IGAGGGGU 3557

1473 CCCGGGGC c GCTTGGGG 1049 CCCCAAGC CUGAUGAG X CGAA ICCCCGGG 3558

1476 GGGGCCGC T TGGGGCTC 1050 GAGCCCCA CUGAUGAG X CGAA ICGGCCCC 3559

1483 CTTGGGGC T CTACCGCC 1051 GGCGGUAG CUGAUGAG X CGAA ICCCCAAG 3560

1485 TGGGGCTC T ACCGCCCG 1052 CGGGCGGU CUGAUGAG X CGAA IAGCCCCA 3561

1488 GGCTCTAC c GCCCGCTT 1053 AAGCGGGC CUGAUGAG X CGAA IUAGAGCC 3562

1491 TCTACCGC c CGCTTCTC 1054 GAGAAGCG CUGAUGAG X CGAA ICGGUAGA 3563 Table 38

1492 CTACCGCC C GCTTCTCC 1055 GGAGAAGC CUGAUGAG X CGAA IGCGGUAG 3564

1495 CCGCCCGC T TCTCCGCC 1056 GGCGGAGA CUGAUGAG X CGAA ICGGGCGG 3565

1498 CCCGCTTC T CCGCCTAT 1057 AUAGGCGG CUGAUGAG X CGAA IAAGCGGG 3566

1500 CGCTTCTC C GCCTATTG 1058 CAAUAGGC CUGAUGAG X CGAA IAGAAGCG 3567

1503 TTCTCCGC C TATTGTAC 1059 GUACAAUA CUGAUGAG X CGAA ICGGAGAA 3568

1504 TCTCCGCC T ATTGTACC 1060 GGUACAAU CUGAUGAG X CGAA IGCGGAGA 3569

1512 TATTGTAC C GACCGTCC 1061 GGACGGUC CUGAUGAG X CGAA IUACAAUA 3570

1516 GTACCGAC C GTCCACGG 1062 CCGUGGAC CUGAUGAG X CGAA IUCGGUAC 3571

1520 CGACCGTC C ACGGGGCG 1063 CGCCCCGU CUGAUGAG X CGAA IACGGUCG 3572

1521 GACCGTCC A CGGGGCGC 1064 GCGCCCCG CUGAUGAG X CGAA IGACGGUC 3573

1530 CGGGGCGC A CCTCTCTT 1065 AAGAGAGG CUGAUGAG X CGAA ICGCCCCG 3574

1532 GGGCGCAC C TCTCTTTA 1066 UAAAGAGA CUGAUGAG X CGAA IUGCGCCC 3575

1533 GGCGCACC T CTCTTTAC 1067 GUAAAGAG' CUGAUGAG X CGAA IGUGCGCC 3576

1535 CGCACCTC T CTTTACGC 1068 GCGUAAAG CUGAUGAG X CGAA IAGGUGCG 3577

1537 CACCTCTC T TTACGCGG 1069 CCGCGUAA CUGAUGAG X CGAA IAGAGGUG 3578

1548 ACGCGGAC T CCCCGTCT 1070 AGACGGGG CUGAUGAG X CGAA IUCCGCGU 3579

1550 GCGGACTC c CCGTCTGT 1071 ACAGACGG CUGAUGAG X CGAA IAGUCCGC 3580

1551 CGGACTCC c CGTCTGTG 1072 CACAGACG CUGAUGAG X CGAA IGAGUCCG 3581

1552 GGACTCCC c GTCTGTGC 1073 GCACAGAC CUGAUGAG X CGAA IGGAGUCC 3582

1556 TCCCCGTC T GTGCCTTC 1074 GAAGGCAC CUGAUGAG X CGAA IACGGGGA 3583

1561 GTCTGTGC c TTCTCATC 1075 GAUGAGAA CUGAUGAG X CGAA ICACAGAC 3584

1562 TCTGTGCC T TCTCATCT 1076 AGAUGAGA CUGAUGAG X CGAA IGCACAGA 3585

1565 GTGCCTTC T CATCTGCC 1077 GGCAGAUG CUGAUGAG X CGAA IAAGGCAC 3586

1567 GCCTTCTC A TCTGCCGG 1078 CCGGCAGA CUGAUGAG X CGAA IAGAAGGC 3587

1570 TTCTCATC T GCCGGACC 1079 GGUCCGGC CUGAUGAG X CGAA IAUGAGAA 3588

1573 TCATCTGC c GGACCGTG 1080 CACGGUCC CUGAUGAG X CGAA ICAGAUGA 3589

1578 TGCCGGAC c GTGTGCAC 1081 GUGCACAC CUGAUGAG X CGAA IUCCGGCA 3590

1585 CCGTGTGC A CTTCGCTT 1082 AAGCGAAG CUGAUGAG X CGAA ICACACGG 3591

1587 GTGTGCAC T TCGCTTCA 1083 UGAAGCGA CUGAUGAG X CGAA IUGCACAC 3592

1592 CACTTCGC T TCACCTCT 1084 AGAGGUGA CUGAUGAG X CGAA ICGAAGUG 3593

1595 TTCGCTTC A CCTCTGCA 1085 UGCAGAGG CUGAUGAG X CGAA IAAGCGAA 3594

1597 CGCTTCAC C TCTGCACG 1086 CGUGCAGA CUGAUGAG X CGAA IUGAAGCG 3595

1598 GCTTCACC T CTGCACGT 1087 ACGUGCAG CUGAUGAG X CGAA IGUGAAGC 3596

1600 TTCACCTC T GCACGTCG 1088 CGACGUGC CUGAUGAG X CGAA IAGGUGAA 3597

1603 ACCTCTGC A CGTCGCAT 1089 AUGCGACG CUGAUGAG X CGAA ICAGAGGU 3598

1610 CACGTCGC A TGGAGACC 1090 GGUCUCCA CUGAUGAG X CGAA ICGACGUG 3599

1618 ATGGAGAC C ACCGTGAA 1091 UUCACGGU CUGAUGAG X CGAA IUCUCCAU 3600

1619 TGGAGACC A CCGTGAAC 1092 GUUCACGG CUGAUGAG X CGAA IGUCUCCA 3601

1621 GAGACCAC C GTGAACGC 1093 GCGUUCAC CUGAUGAG X CGAA IUGGUCUC 3602

1630 GTGAACGC C CACAGGAA 1094 UUCCUGUG CUGAUGAG X CGAA ICGUUCAC 3603

1631 TGAACGCC C ACAGGAAC 1095 GUUCCUGU CUGAUGAG X CGAA IGCGUUCA 3604

1632 GAACGCCC A CAGGAACC 1096 GGUUCCUG CUGAUGAG X CGAA IGGCGUUC 3605

1634 ACGCCCAC A GGAACCTG 1097 CAGGUUCC CUGAUGAG X CGAA IUGGGCGU 3606

1640 ACAGGAAC C TGCCCAAG 1098 CUUGGGCA CUGAUGAG X CGAA IUUCCUGU 3607

1641 CAGGAACC T GCCCAAGG 1099 CCUUGGGC CUGAUGAG X CGAA IGUUCCUG 3608

1644 GAACCTGC C CAAGGTCT 1100 AGACCUUG CUGAUGAG X CGAA ICAGGUUC 3609

1645 AACCTGCC C AAGGTCTT 1101 AAGACCUU CUGAUGAG X CGAA IGCAGGUU 3610

1646 ACCTGCCC A AGGTCTTG 1102 CAAGACCU CUGAUGAG X CGAA IGGCAGGU 3611

1652 CCAAGGTC T TGCATAAG 1103 CUUAUGCA CUGAUGAG X CGAA IACCUUGG 3612

1656 GGTCTTGC A TAAGAGGA 1104 UCCUCUUA CUGAUGAG X CGAA ICAAGACC 3613

1666 AAGAGGAC T CTTGGACT 1105 AGUCCAAG CUGAUGAG X CGAA IUCCUCUU 3614 Table 38

1668 GAGGACTC T TGGACTTT 1106 AAAGUCCA CUGAUGAG X CGAA IAGUCCUC 3615

1674 TCTTGGAC T TTCAGCAA 1107 UUGCUGAA CUGAUGAG X CGAA IUCCAAGA 3616

1678 GGACTTTC A GCAATGTC 1108 GACAUUGC CUGAUGAG X CGAA IAAAGUCC 3617

1681 CTTTCAGC A ATGTCAAC 1109 GUUGACAU CUGAUGAG X CGAA ICUGAAAG 3618

1687 GCAATGTC A ACGACCGA 1110 UCGGUCGU CUGAUGAG X CGAA IACAUUGC 3619

1693 TCAACGAC C GACCTTGA llll UCAAGGUC CUGAUGAG X CGAA IUCGUUGA 3620

1697 CGACCGAC C TTGAGGCA 1112 UGCCUCAA CUGAUGAG X CGAA IUCGGUCG 3621

1698 GACCGACC T TGAGGCAT 1113 AUGCCUCA CUGAUGAG X CGAA IGUCGGUC 3622

1705 CTTGAGGC A TACTTCAA 1114 UUGAAGUA CUGAUGAG X CGAA ICCUCAAG 3623

1709 AGGCATAC T TCAAAGAC 1115 GUCUUUGA CUGAUGAG X CGAA IUAUGCCU 3624

1712 CATACTTC A AAGACTGT 1116 ACAGUCUU CUGAUGAG X CGAA IAAGUAUG 3625

1718 TCAAAGAC T GTGTGTTT 1117 AAACACAC CUGAUGAG X CGAA IUCUUUGA 3626

1769 TAAAGGTC T TTGTACTA 1118 UAGUACAA CUGAUGAG X CGAA IACCUUUA 3627

1776 CTTTGTAC T AGGAGGCT 1119 AGCCUCCU CUGAUGAG X CGAA IUACAAAG 3628

1784 TAGGAGGC T GTAGGCAT 1120 AUGCCUAC CUGAUGAG X CGAA ICCUCCUA 3629

1791 CTGTAGGC A TAAATTGG 1121 CCAAUUUA CUGAUGAG X CGAA ICCUACAG 3630

1807 GTGTGTTC A CCAGCACC 1122 GGUGCUGG CUGAUGAG X CGAA IAACACAC 3631

1809 GTGTTCAC C AGCACCAT 1123 AUGGUGCU CUGAUGAG X CGAA IUGAACAC 3632

1810 TGTTCACC A GCACCATG 1124 CAUGGUGC CUGAUGAG X CGAA IGUGAACA 3633

1813 TCACCAGC A CCATGCAA 1125 UUGCAUGG CUGAUGAG X CGAA ICUGGUGA 3634

1815 ACCAGCAC C ATGCAACT 1126 AGUUGCAU CUGAUGAG X CGAA IUGCUGGU 3635

1816 CCAGCACC A TGCAACTT 1127 AAGUUGCA CUGAUGAG X CGAA IGUGCUGG 3636

1820 CACCATGC A ACTTTTTC 1128 GAAAAAGU CUGAUGAG X CGAA ICAUGGUG 3637

1823 CATGCAAC T TTTTCACC 1129 GGUGAAAA CUGAUGAG X CGAA IUUGCAUG 3638

1829 ACTTTTTC A CCTCTGCC 1130 GGCAGAGG CUGAUGAG X CGAA IAAAAAGU 3639

1831 TTTTTCAC C TCTGCCTA 1131 UAGGCAGA CUGAUGAG X CGAA IUGAAAAA 3640

1832 TTTTCACC T CTGCCTAA 1132 UUAGGCAG CUGAUGAG X CGAA IGUGAAAA 3641

1834 TTCACCTC T GCCTAATC 1133 GAUUAGGC CUGAUGAG X CGAA IAGGUGAA 3642

1837 ACCTCTGC C TAATCATC 1134 GAUGAUUA CUGAUGAG X CGAA ICAGAGGU 3643

1838 CCTCTGCC T AATCATCT 1135 AGAUGAUU CUGAUGAG X CGAA IGCAGAGG 3644

1843 GCCTAATC A TCTCATGT 1136 ACAUGAGA CUGAUGAG X CGAA IAUUAGGC 3645

1846 TAATCATC T CATGTTCA 1137 UGAACAUG CUGAUGAG X CGAA IAUGAUUA 3646

1848 ATCATCTC A TGTTCATG 1138 CAUGAACA CUGAUGAG X CGAA IAGAUGAU 3647

1854 TCATGTTC A TGTCCTAC 1139 GUAGGACA CUGAUGAG X CGAA IAACAUGA 3648

1859 TTCATGTC C TACTGTTC 1140 GAACAGUA CUGAUGAG X CGAA IACAUGAA 3649

1860 TCATGTCC T ACTGTTCA 1141 UGAACAGU CUGAUGAG X CGAA IGACAUGA 3650

1863 TGTCCTAC T GTTCAAGC 1142 GCUUGAAC CUGAUGAG X CGAA IUAGGACA 3651

1868 TACTGTTC A AGCCTCCA 1143 UGGAGGCU CUGAUGAG X CGAA IAACAGUA 3652

1872 GTTCAAGC C TCCAAGCT 1144 AGCUUGGA CUGAUGAG X CGAA ICUUGAAC 3653

1873 TTCAAGCC T CCAAGCTG 1145 CAGCUUGG CUGAUGAG X CGAA IGCUUGAA 3654

1875 CAAGCCTC C AAGCTGTG 1146 CACAGCUU CUGAUGAG X CGAA IAGGCUUG 3655

1876 AAGCCTCC A AGCTGTGC 1147 GCACAGCU CUGAUGAG X CGAA IGAGGCUU 3656

1880 CTCCAAGC T GTGCCTTG 1148 CAAGGCAC CUGAUGAG X CGAA ICUUGGAG 3657

1885 AGCTGTGC C TTGGGTGG 1149 CCACCCAA CUGAUGAG X CGAA ICACAGCU 3658

1886 GCTGTGCC T TGGGTGGC 1150 GCCACCCA CUGAUGAG X CGAA IGCACAGC 3659

1895 TGGGTGGC T TTGGGGCA 1151 UGCCCCAA CUGAUGAG X CGAA ICCACCCA 3660

1903 TTTGGGGC A TGGACATT 1152 AAUGUCCA CUGAUGAG X CGAA ICCCCAAA 3661

1909 GCATGGAC A TTGACCCG 1153 CGGGUCAA CUGAUGAG X CGAA IUCCAUGC 3662

1915 ACATTGAC C CGTATAAA 1154 UUUAUACG CUGAUGAG X CGAA IUCAAUGU 3663

1916 CATTGACC C GTATAAAG 1155 CUUUAUAC CUGAUGAG X CGAA IGUCAAUG 3664

1935 TTTGGAGC T TCTGTGGA 1156 UCCACAGA CUGAUGAG X CGAA ICUCCAAA 3665 Table 38

1938 GGAGCTTC T GTGGAGTT 1157 AACUCCAC CUGAUGAG X CGAA IAAGCUCC 3666

1949 GGAGTTAC T CTCTTTTT 1158 AAAAAGAG CUGAUGAG X CGAA IUAACUCC 3667

1951 AGTTACTC T CTTTTTTG 1159 CAAAAAAG CUGAUGAG X CGAA IAGUAACU 3668

1953 TTACTCTC T TTTTTGCC 1160 GGCAAAAA CUGAUGAG X CGAA IAGAGUAA 3669

1961 TTTTTTGC c TTCTGACT 1161 AGUCAGAA CUGAUGAG X CGAA ICAAAAAA 3670

1962 TTTTTGCC T TCTGACTT 1162 AAGUCAGA CUGAUGAG X CGAA IGCAAAAA 3671

1965 TTGCCTTC T GACTTCTT 1163 AAGAAGUC CUGAUGAG X CGAA IAAGGCAA 3672

1969 CTTCTGAC T TCTTTCCT 1164 AGGAAAGA CUGAUGAG X CGAA IUCAGAAG 3673

1972 CTGACTTC T TTCCTTCT 1165 AGAAGGAA CUGAUGAG X CGAA IAAGUCAG 3674

1976 CTTCTTTC c TTCTATTC 1166 GAAUAGAA CUGAUGAG X CGAA IAAAGAAG 3675

1977 TTCTTTCC T TCTATTCG 1167 CGAAUAGA CUGAUGAG X CGAA IGAAAGAA 3676

1980 TTTCCTTC T ATTCGAGA 1168 UCUCGAAU CUGAUGAG X CGAA IAAGGAAA 3677

1991 TCGAGATC T CCTCGACA 1169 UGUCGAGG CUGAUGAG X CGAA IAUCUCGA 3678

1993 GAGATCTC c TCGACACC 1170 GGUGUCGA CUGAUGAG X CGAA IAGAUCUC 3679

1994 AGATCTCC T CGACACCG 1171 CGGUGUCG CUGAUGAG X CGAA IGAGAUCU 3680

1999 TCCTCGAC A CCGCCTCT 1172 AGAGGCGG CUGAUGAG X CGAA IUCGAGGA 3681

2001 CTCGACAC c GCCTCTGC 1173 GCAGAGGC CUGAUGAG X CGAA IUGUCGAG 3682

2004 GACACCGC c TCTGCTCT 1174 AGAGCAGA CUGAUGAG X CGAA ICGGUGUC 3683

2005 ACACCGCC T CTGCTCTG 1175 CAGAGCAG CUGAUGAG X CGAA IGCGGUGU 3684

2007 ACCGCCTC T GCTCTGTA 1176 UACAGAGC CUGAUGAG X CGAA IAGGCGGU 3685

2010 GCCTCTGC T CTGTATCG 1177 CGAUACAG CUGAUGAG X CGAA ICAGAGGC 3686

2012 CTCTGCTC T GTATCGGG 1178 CCCGAUAC CUGAUGAG X CGAA IAGCAGAG 3687

2025 CGGGGGGC c TTAGAGTC 1179 GACUCUAA CUGAUGAG X CGAA ICCCCCCG 3688

2026 GGGGGGCC T TAGAGTCT 1180 AGACUCUA CUGAUGAG X CGAA IGCCCCCC 3689

2034 TTAGAGTC T CCGGAACA 1181 UGUUCCGG CUGAUGAG X CGAA lACUCUAA 3690

2036 AGAGTCTC c GGAACATT 1182 AAUGUUCC CUGAUGAG X CGAA IAGACUCU 3691

2042 TCCGGAAC A TTGTTCAC ^' 1183 GUGAACAA CUGAUGAG X CGAA IUUCCGGA 3692

2049 CATTGTTC A CCTCACCA 1184 UGGUGAGG CUGAUGAG X CGAA IAACAAUG 3693

2051 TTGTTCAC C TCACCATA 1185 UAUGGUGA CUGAUGAG X CGAA IUGAACAA 3694

2052 TGTTCACC T CACCATAC 1186 GUAUGGUG CUGAUGAG X CGAA IGUGAACA 3695

2054 TTCACCTC A CCATACGG 1187 CCGUAUGG CUGAUGAG X CGAA IAGGUGAA 3696

2056 CACCTCAC C ATACGGCA 1188 UGCCGUAU CUGAUGAG X CGAA IUGAGGUG 3697

2057 ACCTCACC A TACGGCAC 1189 GUGCCGUA CUGAUGAG X CGAA IGUGAGGU 3698

2064 CATACGGC A CTCAGGCA 1190 UGCCUGAG CUGAUGAG X CGAA ICCGUAUG 3699

2066 TACGGCAC T CAGGCAAG 1191 CUUGCCUG CUGAUGAG X CGAA IUGCCGUA 3700

2068 CGGCACTC A GGCAAGCT 1192 AGCUUGCC CUGAUGAG X CGAA IAGUGCCG 3701

2072 ACTCAGGC A AGCTATTC 1193 GAAUAGCU CUGAUGAG X CGAA ICCUGAGU 3702

2076 AGGCAAGC T ATTCTGTG 1194 CACAGAAU CUGAUGAG X CGAA ICUUGCCU 3703

2081 AGCTATTC T GTGTTGGG 1195 CCCAACAC CUGAUGAG X CGAA IAAUAGCU 3704

2105 GATGAATC T AGCCACCT 1196 AGGUGGCU CUGAUGAG X CGAA IAUUCAUC 3705

2109 AATCTAGC c ACCTGGGT 1197 ACCCAGGU CUGAUGAG X CGAA ICUAGAUU 3706

2110 ATCTAGCC A CCTGGGTG 1198 CACCCAGG CUGAUGAG X CGAA IGCUAGAU 3707

2112 CTAGCCAC C TGGGTGGG 1199 CCCACCCA CUGAUGAG X CGAA IUGGCUAG 3708

2113 TAGCCACC T GGGTGGGA 1200 UCCCACCC CUGAUGAG X CGAA IGUGGCUA 3709

2138 GGAAGATC C AGCATCCA 1201 UGGAUGCU CUGAUGAG X CGAA IAUCUUCC 3710

2139 GAAGATCC A GCATCCAG 1202 CUGGAUGC CUGAUGAG X CGAA IGAUCUUC 3711

2142 GATCCAGC A TCCAGGGA 1203 UCCCUGGA CUGAUGAG X CGAA ICUGGAUC 3712

2145 CCAGCATC C AGGGAATT 1204 AAUUCCCU CUGAUGAG X CGAA IAUGCUGG 3713

2146 CAGCATCC A GGGAATTA 1205 UAAUUCCC CUGAUGAG X CGAA IGAUGCUG 3714

2161 TAGTAGTC A GCTATGTC 1206 GACAUAGC CUGAUGAG X CGAA IACUACUA 3715

2164 TAGTCAGC T ATGTCAAC 1207 GUUGACAU CUGAUGAG X CGAA ICUGACUA 3716 Table 38

2170 GCTATGTC A ACGTTAAT 1208 AUUAACGU CUGAUGAG X CGAA IACAUAGC 3717

2185 ATATGGGC C TAAAAATC 1209 GAUUUUUA CUGAUGAG X CGAA ICCCAUAU 3718

2186 TATGGGCC T AAAAATCA 1210 UGAUUUUU CUGAUGAG X CGAA IGCCCAUA 3719

2194 TAAAAATC A GACAACTA 1211 UAGUUGUC CUGAUGAG X CGAA IAUUUUUA 3720

2198 AATCAGAC A ACTATTGT 1212 ACAAUAGU CUGAUGAG X CGAA IUCUGAUU 3721

2201 CAGACAAC T ATTGTGGT 1213 ACCACAAU CUGAUGAG X CGAA IUUGUCUG 3722

2213 GTGGTTTC A CATTTCCT 1214 AGGAAAUG CUGAUGAG X CGAA IAAACCAC 3723

2215 GGTTTCAC A TTTCCTGT 1215 ACAGGAAA CUGAUGAG X CGAA IUGAAACC 3724

2220 CACATTTC C TGTCTTAC 1216 GUAAGACA CUGAUGAG X CGAA IAAAUGUG 3725

2221 ACATTTCC T GTCTTACT 1217 AGUAAGAC CUGAUGAG X CGAA IGAAAUGU 3726

2225 TTCCTGTC T TACTTTTG 1218 CAAAAGUA CUGAUGAG X CGAA lACAGGAA 3727

2229 TGTCTTAC T TTTGGGCG 1219 CGCCCAAA CUGAUGAG X CGAA IUAAGACA 3728

2244 CGAGAAAC T GTTCTTGA 1220 UCAAGAAC CUGAUGAG X CGAA IUUUCUCG 3729

2249 AACTGTTC T TGAATATT 1221 AAUAUUCA CUGAUGAG X CGAA IAACAGUU 3730

2265 TTGGTGTC T TTTGGAGT 1222 ACUCCAAA CUGAUGAG X CGAA IACACCAA 3731

2284 GGATTCGC A CTCCTCCT 1223 AGGAGGAG CUGAUGAG X CGAA ICGAAUCC 3732

2286 ATTCGCAC T CCTCCTGC 1224 GCAGGAGG CUGAUGAG X CGAA IUGCGAAU 3733

2288 TCGCACTC C TCCTGCAT 1225 AUGCAGGA CUGAUGAG X CGAA lAGUGCGA 3734

2289 CGCACTCC T CCTGCATA 1226 UAUGCAGG CUGAUGAG X CGAA IGAGUGCG 3735

2291 CACTCCTC c TGCATATA 1227 UAUAUGCA CUGAUGAG X CGAA IAGGAGUG 3736

2292 ACTCCTCC T GCATATAG 1228 CUAUAUGC CUGAUGAG X CGAA IGAGGAGU 3737

2295 CCTCCTGC A TATAGACC 1229 GGUCUAUA CUGAUGAG X CGAA ICAGGAGG 3738

2303 ATATAGAC C ACCAAATG 1230 CAUUUGGU CUGAUGAG X CGAA IUCUAUAU 3739

2304 TATAGACC A CCAAATGC 1231 GCAUUUGG CUGAUGAG X CGAA IGUCUAUA 3740

2306 TAGACCAC C AAATGCCC 1232 GGGCAUUU CUGAUGAG X CGAA IUGGUCUA 3741

2307 AGACCACC A AATGCCCC 1233 GGGGCAUU CUGAUGAG X CGAA IGUGGUCU 3742

2313 CCAAATGC C CCTATCTT 1234 AAGAUAGG CUGAUGAG X CGAA ICAUUUGG 3743

2314 CAAATGCC C CTATCTTA 1235 UAAGAUAG CUGAUGAG X CGAA IGCAUUUG 3744

2315 AAATGCCC C TATCTTAT 1236 AUAAGAUA CUGAUGAG X CGAA IGGCAUUU 3745

2316 AATGCCCC T ATCTTATC 1237 GAUAAGAU CUGAUGAG X CGAA IGGGCAUU 3746

2320 CCCCTATC T TATCAACA 1238 UGUUGAUA CUGAUGAG X CGAA IAUAGGGG 3747

2325 ATCTTATC A ACACTTCC 1239 GGAAGUGU CUGAUGAG X CGAA IAUAAGAU 3748

2328 TTATCAAC A CTTCCGGA 1240 UCCGGAAG CUGAUGAG X CGAA lUUGAUAA 3749

2330 ATCAACAC T TCCGGAAA 1241 UUUCCGGA CUGAUGAG X CGAA IUGUUGAU 3750

2333 AACACTTC C GGAAACTA 1242 UAGUUUCC CUGAUGAG X CGAA IAAGUGUU 3751

2340 CCGGAAAC T ACTGTTGT 1243 ACAACAGU CUGAUGAG X CGAA IUUUCCGG 3752

2343 GAAACTAC T GTTGTTAG 1244 CUAACAAC CUGAUGAG X CGAA IUAGUUUC 3753

2362 GAAGAGGC A GGTCCCCT 1245 AGGGGACC CUGAUGAG X CGAA ICCUCUUC 3754

2367 GGCAGGTC C CCTAGAAG 1246 CUUCUAGG CUGAUGAG X CGAA IACCUGCC 3755

2368 GCAGGTCC c CTAGAAGA 1247 UCUUCUAG CUGAUGAG X CGAA IGACCUGC 3756

2369 CAGGTCCC c TAGAAGAA 1248 UUCUUCUA CUGAUGAG X CGAA IGGACCUG 3757

2370 AGGTCCCC T AGAAGAAG 1249 CUUCUUCU CUGAUGAG X CGAA IGGGACCU 3758

2382 AGAAGAAC T CCCTCGCC 1250 GGCGAGGG CUGAUGAG X CGAA IUUCUUCU 3759

2384 AAGAACTC c CTCGCCTC 1251 GAGGCGAG CUGAUGAG X CGAA IAGUUCUU 3760

2385 AGAACTCC c TCGCCTCG 1252 CGAGGCGA CUGAUGAG X CGAA IGAGUUCU 3761

2386 GAACTCCC T CGCCTCGC 1253 GCGAGGCG CUGAUGAG X CGAA IGGAGUUC 3762

2390 TCCCTCGC c TCGCAGAC 1254 GUCUGCGA CUGAUGAG X CGAA ICGAGGGA 3763

2391 CCCTCGCC T CGCAGACG 1255 CGUCUGCG CUGAUGAG X CGAA IGCGAGGG 3764

2395 CGCCTCGC A GACGAAGG 1256 CCUUCGUC CUGAUGAG X CGAA ICGAGGCG 3765

2406 CGAAGGTC T CAATCGCC 1257 GGCGAUUG CUGAUGAG X CGAA IACCUUCG 3766

2408 AAGGTCTC A ATCGCCGC 1258 GCGGCGAU CUGAUGAG X CGAA IAGACCUU 3767 Table 38

2414 TCAATCGC C GCGTCGCA 1259 UGCGACGC CUGAUGAG X CGAA ICGAUUGA 3768

2422 CGCGTCGC A GAAGATCT 1260 AGAUCUUC CUGAUGAG X CGAA ICGACGCG 3769

2430 AGAAGATC T CAATCTCG 1261 CGAGAUUG CUGAUGAG X CGAA IAUCUUCU 3770

2432 AAGATCTC A ATCTCGGG 1262 CCCGAGAU CUGAUGAG X CGAA IAGAUCUU 3771

2436 TCTCAATC T CGGGAATC 1263 GAUUCCCG CUGAUGAG X CGAA IAUUGAGA 3772

2445 CGGGAATC T CAATGTTA 1264 UAACAUUG CUGAUGAG X CGAA IAUUCCCG 3773

2447 GGAATCTC A ATGTTAGT 1265 ACUAACAU CUGAUGAG X CGAA IAGAUUCC 3774

2460 TAGTATTC C TTGGACAC 1266 GUGUCCAA CUGAUGAG X CGAA IAAUACUA 3775

2461 AGTATTCC T TGGACACA 1267 UGUGUCCA CUGAUGAG X CGAA IGAAUACU 3776

2467 CCTTGGAC A CATAAGGT 1268 ACCUUAUG CUGAUGAG X CGAA IUCCAAGG 3777

2469 TTGGACAC A TAAGGTGG 1269 CCACCUUA CUGAUGAG X CGAA IUGUCCAA 3778

2483 TGGGAAAC T TTACGGGG 1270 CCCCGUAA CUGAUGAG X CGAA IUUUCCCA 3779

2493 TACGGGGC T TTATTCTT 1271 AAGAAUAA CUGAUGAG X CGAA ICCCCGUA 3780

2500 CTTTATTC T TCTACGGT 1272 ACCGUAGA CUGAUGAG X CGAA IAAUAAAG 3781

2503 TATTCTTC T ACGGTACC 1273 GGUACCGU CUGAUGAG X CGAA IAAGAAUA 3782

2511 TACGGTAC C TTGCTTTA 1274 UAAAGCAA CUGAUGAG X CGAA IUACCGUA 3783

2512 ACGGTACC T TGCTTTAA 1275 UUAAAGCA CUGAUGAG X CGAA IGUACCGU 3784

2516 TACCTTGC T TTAATCCT 1276 AGGAUUAA CUGAUGAG X CGAA ICAAGGUA 3785

2523 CTTTAATC c TAAATGGC 1277 GCCAUUUA CUGAUGAG X CGAA IAUUAAAG 3786

2524 TTTAATCC T AAATGGCA 1278 UGCCAUUU CUGAUGAG X CGAA IGAUUAAA 3787

2532 TAAATGGC A AACTCCTT 1279 AAGGAGUU CUGAUGAG X CGAA ICCAUUUA 3788

2536 TGGCAAAC T CCTTCTTT 1280 AAAGAAGG CUGAUGAG X CGAA IUUUGCCA 3789

2538 GCAAACTC C TTCTTTTC 1281 GAAAAGAA CUGAUGAG X CGAA IAGUUUGC 3790

2539 CAAACTCC T TCTTTTCC 1282 GGAAAAGA CUGAUGAG X CGAA IGAGUUUG 3791

2542 ACTCCTTC T TTTCCTGA 1283 UCAGGAAA CUGAUGAG X CGAA IAAGGAGU 3792

2547 TTCTTTTC c TGACATTC 1284 GAAUGUCA CUGAUGAG X CGAA IAAAAGAA 3793

2548 TCTTTTCC T GACATTCA 1285 UGAAUGUC CUGAUGAG X CGAA IGAAAAGA 3794

2552 TTCCTGAC A TTCATTTG 1286 CAAAUGAA CUGAUGAG X CGAA IUCAGGAA 3795

2556 TGACATTC A TTTGCAGG 1287 CCUGCAAA CUGAUGAG X CGAA IAAUGUCA 3796

2562 TCATTTGC A GGAGGACA 1288 UGUCCUCC CUGAUGAG X CGAA ICAAAUGA 3797

2570 AGGAGGAC A TTGTTGAT 1289 AUCAACAA CUGAUGAG X CGAA IUCCUCCU 3798

2589 ATGTAAGC A ATTTGTGG 1290 CCACAAAU CUGAUGAG X CGAA ICUUACAU 3799

2601 TGTGGGGC C CCTTACAG 1291 CUGUAAGG CUGAUGAG X CGAA ICCCCACA 3800

2602 GTGGGGCC C CTTACAGT 1292 ACUGUAAO CUGAUGAG X CGAA IGCCCCAC 3801

2603 TGGGGCCC C TTACAGTA 1293 UACUGUAA CUGAUGAG X CGAA IGGCCCCA 3802

2604 GGGGCCCC T TACAGTAA 1294 UUACUGUA CUGAUGAG X CGAA IGGGCCCC 3803

2608 CCCCTTAC A GTAAATGA 1295 UCAUUUAC CUGAUGAG X CGAA IUAAGGGG 3804

2621 ATGAAAAC A GGAGACTT 1296 AAGUCUCC CUGAUGAG X CGAA lUUUUCAU 3805

2628 CAGGAGAC T TAAATTAA 1297 UUAAUUUA CUGAUGAG X CGAA IUCUCCUG 3806

2638 AAATTAAC T ATGCCTGC 1298 GCAGGCAU CUGAUGAG X CGAA IUUAAUUU 3807

2643 AACTATGC C TGCTAGGT 1299 ACCUAGCA CUGAUGAG X CGAA ICAUAGUU 3808

2644 ACTATGCC T GCTAGGTT 1300 AACCUAGC CUGAUGAG X CGAA IGCAUAGU 3809

2647 ATGCCTGC T AGGTTTTA 1301 UAAAACCU CUGAUGAG X CGAA ICAGGCAU 3810

2658 GTTTTATC C CAATGTTA 1302 UAACAUUG CUGAUGAG X CGAA IAUAAAAC 3811

2659 TTTTATCC C AATGTTAC 1303 GUAACAUU CUGAUGAG X CGAA IGAUAAAA 3812

2660 TTTATCCC A ATGTTACT 1304 AGUAACAU CUGAUGAG X CGAA IGGAUAAA 3813

2668 AATGTTAC T AAATATTT 1305 AAAUAUUU CUGAUGAG X CGAA IUAACAUU 3814

2679 ATATTTGC C CTTAGATA 1306 UAUCUAAG CUGAUGAG X CGAA ICAAAUAU 3815

2680 TATTTGCC C TTAGATAA 1307 UUAUCUAA CUGAUGAG X CGAA IGCAAAUA 3816

2681 ATTTGCCC T TAGATAAA 1308 UUUAUCUA CUGAUGAG X CGAA IGGCAAAU 3817

2696 AAGGGATC A AACCGTAT 1309 AUACGGUU CUGAUGAG X CGAA IAUCCCUU 3818 Table 38

2700 GATCAAAC C GTATTATC 1310 GAUAAUAC CUGAUGAG X CGAA IUUUGAUC 3819

2709 GTATTATC C AGAGTATG 1311 CAUACUCU CUGAUGAG X CGAA IAUAAUAC 3820

2710 TATTATCC A GAGTATGT 1312 ACAUACUC CUGAUGAG X CGAA IGAUAAUA 3821

2727 AGTTAATC A TTACTTCC 1313 GGAAGUAA CUGAUGAG X CGAA IAUUAACU 3822

2732 ATCATTAC T TCCAGACG 1314 CGUCUGGA CUGAUGAG X CGAA IUAAUGAU 3823

2735 ATTACTTC C AGACGCGA 1315 UCGCGUCU CUGAUGAG X CGAA IAAGUAAU 3824

2736 TTACTTCC A GACGCGAC 1316 GUCGCGUC CUGAUGAG X CGAA IGAAGUAA 3825

2745 GACGCGAC A TTATTTAC 1317 GUAAAUAA CUGAUGAG X CGAA IUCGCGUC 3826

2754 TTATTTAC A CACTCTTT 1318 AAAGAGUG CUGAUGAG X CGAA IUAAAUAA 3827

2756 ATTTACAC A CTCTTTGG 1319 CCAAAGAG CUGAUGAG X CGAA IUGUAAAU 3828

2758 TTACACAC T CTTTGGAA 1320 UUCCAAAG CUGAUGAG X CGAA IUGUGUAA 3829

2760 ACACACTC T TTGGAAGG 1321 CCUUCCAA CUGAUGAG X CGAA IAGUGUGU 3830

2777 CGGGGATC T TATATAAA 1322 UUUAUAUA CUGAUGAG X CGAA IAUCCCCG 3831

2794 AGAGAGTC C ACACGTAG 1323 CUACGUGU CUGAUGAG X CGAA IACUCUCU 3832

2795 GAGAGTCC A CACGTAGC 1324 GCUACGUG CUGAUGAG X CGAA IGACUCUC 3833

2797 GAGTCCAC A CGTAGCGC 1325 GCGCUACG CUGAUGAG X CGAA IUGGACUC 3834

2806 CGTAGCGC C TCATTTTG 1326 CAAAAUGA CUGAUGAG X CGAA ICGCUACG 3835

2807 GTAGCGCC T CATTTTGC 1327 GCAAAAUG CUGAUGAG X CGAA IGCGCUAC 3836

2809 AGCGCCTC A TTTTGCGG 1328 CCGCAAAA CUGAUGAG X CGAA IAGGCGCU 3837

2821 TGCGGGTC A CCATATTC 1329 GAAUAUGG CUGAUGAG X CGAA IACCCGCA 3838

2823 CGGGTCAC C ATATTCTT 1330 AAGAAUAU CUGAUGAG X CGAA IUGACCCG 3839

2824 GGGTCACC A TATTCTTG 1331 CAAGAAUA CUGAUGAG X CGAA IGUGACCC 3840

2830 CCATATTC T TGGGAACA 1332 UGUUCCCA CUGAUGAG X CGAA IAAUAUGG 3841

2838 TTGGGAAC A AGATCTAC 1333 GUAGAUCU CUGAUGAG X CGAA IUUCCCAA 3842

2844 ACAAGATC T ACAGCATG 1334 CAUGCUGU CUGAUGAG X CGAA IAUCUUGU 3843

2847 AGATCTAC A GCATGGGA 1335 UCCCAUGC CUGAUGAG X CGAA IUAGAUCU 3844

2850 TCTACAGC. A TGGGAGGT 1336 ACCUCCCA CUGAUGAG X CGAA ICUGUAGA 3845

2864 GGTTGGTC T TCCAAACC 1337 GGUUUGGA CUGAUGAG X CGAA IACCAACC 3846

2867 TGGTCTTC C AAACCTCG 1338 CGAGGUUU CUGAUGAG X CGAA IAAGACCA 3847

2868 GGTCTTCC A AACCTCGA 1339 UCGAGGUU CUGAUGAG X CGAA IGAAGACC 3848

2872 TTCCAAAC C TCGAAAAG 1340 CUUUUCGA CUGAUGAG X CGAA IUUUGGAA 3849

2873 TCCAAACC T CGAAAAGG 1341 CCUUUUCG CUGAUGAG X CGAA IGUUUGGA 3850

2883 GAAAAGGC A TGGGGACA 1342 UGUCCCCA CUGAUGAG X CGAA ICCUUUUC 3851

2891 ATGGGGAC A AATCTTTC 1343 GAAAGAUU CUGAUGAG X CGAA IUCCCCAU 3852

2896 GACAAATC T TTCTGTCC 1344 GGACAGAA CUGAUGAG X CGAA IAUUUGUC 3853

2900 AATCTTTC T GTCCCCAA 1345 UUGGGGAC CUGAUGAG X CGAA IAAAGAUU 3854

2904 TTTCTGTC C CCAATCCC 1346 GGGAUUGG CUGAUGAG X CGAA IACAGAAA 3855

2905 TTCTGTCC C CAATCCCC 1347 GGGGAUUG CUGAUGAG X CGAA IGACAGAA 3856

2906 TCTGTCCC C AATCCCCT 1348 AGGGGAUU CUGAUGAG X CGAA IGGACAGA 3857

2907 CTGTCCCC A ATCCCCTG 1349 CAGGGGAU CUGAUGAG X CGAA IGGGACAG 3858

2911 CCCCAATC C CCTGGGAT 1350 AUCCCAGG CUGAUGAG X CGAA IAUUGGGG 3859

2912 CCCAATCC C CTGGGATT 1351 AAUCCCAG CUGAUGAG X CGAA IGAUUGGG 3860

2913 CCAATCCC C TGGGATTC 1352 GAAUCCCA CUGAUGAG X CGAA IGGAUUGG 3861

2914 CAATCCCC T GGGATTCT 1353 AGAAUCCC CUGAUGAG X CGAA IGGGAUUG 3862

2922 TGGGATTC T TCCCCGAT 1354 AUCGGGGA CUGAUGAG X CGAA IAAUCCCA 3863

2925 GATTCTTC c CCGATCAT 1355 AUGAUCGG CUGAUGAG X CGAA IAAGAAUC 3864

2926 ATTCTTCC c CGATCATC 1356 GAUGAUCG CUGAUGAG X CGAA IGAAGAAU 3865

2927 TTCTTCCC c GATCATCA 1357 UGAUGAUC CUGAUGAG X CGAA IGGAAGAA 3866

2932 CCCCGATC A TCAGTTGG 1358 CCAACUGA CUGAUGAG X CGAA IAUCGGGG 3867

2935 CGATCATC A GTTGGACC 1359 GGUCCAAC CUGAUGAG X CGAA IAUGAUCG 3868

2943 AGTTGGAC C CTGCATTC 1360 GAAUGCAG CUGAUGAG X CGAA IUCCAACU 3869 Table 38

2944 GTTGGACC C TGCATTCA 1361 UGAAUGCA CUGAUGAG X CGAA IGUCCAAC 3870

2945 TTGGACCC T GCATTCAA 1362 UUGAAUGC CUGAUGAG X CGAA IGGUCCAA 3871

2948 GACCCTGC A TTCAAAGC 1363 GCUUUGAA CUGAUGAG X CGAA ICAGGGUC 3872

2952 CTGCATTC A AAGCCAAC 1364 GUUGGCUU CUGAUGAG X CGAA IAAUGCAG 3873

2957 TTCAAAGC C AACTCAGT 1365 ACUGAGUU CUGAUGAG X CGAA ICUUUGAA 3874

2958 TCAAAGCC A ACTCAGTA 1366 UACUGAGU CUGAUGAG X CGAA IGCUUUGA 3875

2961 AAGCCAAC T CAGTAAAT 1367 AUUUACUG CUGAUGAG X CGAA IUUGGCUU 3876

2963 GCCAACTC A GTAAATCC 1368 GGAUUUAC CUGAUGAG X CGAA IAGUUGGC 3877

2971 AGTAAATC C AGATTGGG 1369 CCCAAUCU CUGAUGAG X CGAA IAUUUACU 3878

2972 GTAAATCC A GATTGGGA 1370 UCCCAAUC CUGAUGAG X CGAA IGAUUUAC 3879

2982 ATTGGGAC C TCAACCCG 1371 CGGGUUGA CUGAUGAG X CGAA IUCCCAAU 3880

2983 TTGGGACC T CAACCCGC 1372 GCGGGUUG CUGAUGAG X CGAA IGUCCCAA 3881

2985 GGGACCTC A ACCCGCAC 1373 GUGCGGGU CUGAUGAG X CGAA IAGGUCCC 3882

2988 ACCTCAAC C CGCACAAG 1374 CUUGUGCG CUGAUGAG X CGAA IUUGAGGU 3883

2989 CCTCAACC C GCACAAGG 1375 CCUUGUGC CUGAUGAG X CGAA IGUUGAGG 3884

2992 CAACCCGC A CAAGGACA 1376 UGUCCUUG CUGAUGAG X CGAA ICGGGUUG 3885

2994 ACCCGCAC A AGGACAAC 1377 GUUGUCCU CUGAUGAG X CGAA IUGCGGGU 3886

3000 ACAAGGAC A ACTGGCCG 1378 CGGCCAGU CUGAUGAG X CGAA IUCCUUGU 3887

3003 AGGACAAC T GGCCGGAC 1379 GUCCGGCC CUGAUGAG X CGAA IUUGUCCU 3888

3007 CAACTGGC C GGACGCCA 1380 UGGCGUCC CUGAUGAG X CGAA ICCAGUUG 3889

3014 CCGGACGC C AACAAGGT 1381 ACCUUGUU CUGAUGAG X CGAA ICGUCCGG 3890

3015 CGGACGCC A ACAAGGTG 1382 CACCUUGU CUGAUGAG X CGAA IGCGUCCG 3891

3018 ACGCCAAC A AGGTGGGA 1383 UCCCACCU CUGAUGAG X CGAA IUUGGCGU 3892

3035 GTGGGAGC A TTCGGGCC 1384 GGCCCGAA CUGAUGAG X CGAA ICUCCCAC 3893

3043 ATTCGGGC C AGGGTTCA 1385 UGAACCCU CUGAUGAG X CGAA ICCCGAAU 3894

3044 TTCGGGCC A GGGTTCAC 1386 GUGAACCC CUGAUGAG X CGAA IGCCCGAA 3895

3051 CAGGGTTC A CCCCTCCC 1387 GGGAGGGG CUGAUGAG X CGAA IAACCCUG 3896

3053 GGGTTCAC C CCTCCCCA 1388 UGGGGAGG CUGAUGAG X CGAA IUGAACCC 3897

3054 GGTTCACC C CTCCCCAT 1389 AUGGGGAG CUGAUGAG X CGAA IGUGAACC 3898

3055 GTTCACCC C TCCCCATG 1390 CAUGGGGA CUGAUGAG X CGAA IGGUGAAC 3899

3056 TTCACCCC T CCCCATGG 1391 CCAUGGGG CUGAUGAG X CGAA IGGGUGAA 3900

3058 CACCCCTC C CCATGGGG 1392 CCCCAUGG CUGAUGAG X CGAA IAGGGGUG 3901

3059 ACCCCTCC C CATGGGGG 1393 CCCCCAUG CUGAUGAG X CGAA IGAGGGGU 3902

3060 CCCCTCCC C ATGGGGGA 1394 UCCCCCAU CUGAUGAG X CGAA IGGAGGGG 3903

3061 CCCTCCCC A TGGGGGAC 1395 GUCCCCCA CUGAUGAG X CGAA IGGGAGGG 3904

3070 TGGGGGAC T GTTGGGGT 1396 ACCCCAAC CUGAUGAG X CGAA lUCCCCCA 3905

3084 GGTGGAGC c CTCACGCT 1397 AGCGUGAG CUGAUGAG X CGAA ICUCCACC 3906

3085 GTGGAGCC c TCACGCTC 1398 GAGCGUGA CUGAUGAG X CGAA IGCUCCAC 3907

3086 TGGAGCCC T CACGCTCA 1399 UGAGCGUG CUGAUGAG X CGAA IGGCUCCA 3908

3088 GAGCCCTC A CGCTCAGG 1400 CCUGAGCG CUGAUGAG X CGAA IAGGGCUC 3909

3092 CCTCACGC T CAGGGCCT 1401 AGGCCCUG CUGAUGAG X CGAA ICGUGAGG 3910

3094 TCACGCTC A GGGCCTAC 1402 GUAGGCCC CUGAUGAG X CGAA IAGCGUGA 3911

3099 CTCAGGGC C TACTCACA 1403 UGUGAGUA CUGAUGAG X CGAA ICCCUGAG 3912

3100 TCAGGGCC T ACTCACAA 1404 UUGUGAGU CUGAUGAG X CGAA IGCCCUGA 3913

3103 GGGCCTAC T CACAACTG 1405 CAGUUGUG CUGAUGAG X CGAA IUAGGCCC 3914

3105 GCCTACTC A CAACTGTG 1406 CACAGUUG CUGAUGAG X CGAA IAGUAGGC 3915

3107 CTACTCAC A ACTGTGCC 1407 GGCACAGU CUGAUGAG X CGAA IUGAGUAG 3916

3110 CTCACAAC T GTGCCAGC 1408 GCUGGCAC CUGAUGAG X CGAA IUUGUGAG 3917

3115 AACTGTGC C AGCAGCTC 1409 GAGCUGCU CUGAUGAG X CGAA ICACAGUU 3918

3116 ACTGTGCC A GCAGCTCC 1410 GGAGCUGC CUGAUGAG X CGAA IGCACAGU 3919

3119 GTGCCAGC A GCTCCTCC 1411 GGAGGAGC CUGAUGAG X CGAA ICUGGCAC 3920 Table 38

3122 CCAGCAGC T CCTCCTCC 1412 GGAGGAGG CUGAUGAG X CGAA ICUGCUGG 3921

3124 AGCAGCTC C TCCTCCTG 1413 CAGGAGGA CUGAUGAG X CGAA IAGCUGCU 3922

3125 GCAGCTCC T CCTCCTGC 1414 GCAGGAGG CUGAUGAG X CGAA IGAGCUGC 3923

3127 AGCTCCTC C TCCTGCCT 1415 AGGCAGGA CUGAUGAG X CGAA IAGGAGCU 3924

3128 GCTCCTCC T CCTGCCTC 1416 GAGGCAGG CUGAUGAG X CGAA IGAGGAGC 3925

3130 TCCTCCTC c TGCCTCCA 1417 UGGAGGCA CUGAUGAG X CGAA IAGGAGGA 3926

3131 CCTCCTCC T GCCTCCAC 1418 GUGGAGGC CUGAUGAG X CGAA IGAGGAGG 3927

3134 CCTCCTGC c TCCACCAA 1419 UUGGUGGA CUGAUGAG X CGAA ICAGGAGG 3928

3135 CTCCTGCC T CCACCAAT 1420 AUUGGUGG CUGAUGAG X CGAA IGCAGGAG 3929

3137 CCTGCCTC c ACCAATCG 1421 CGAUUGGU CUGAUGAG X CGAA IAGGCAGG 3930

3138 CTGCCTCC A CCAATCGG 1422 CCGAUUGG CUGAUGAG X CGAA IGAGGCAG 3931

3140 GCCTCCAC C AATCGGCA 1423 UGCCGAUU CUGAUGAG X CGAA IUGGAGGC 3932

3141 CCTCCACC A ATCGGCAG 1424 CUGCCGAU CUGAUGAG X CGAA IGUGGAGG 3933

3148 CAATCGGC A GTCAGGAA 1425 UUCCUGAC CUGAUGAG X CGAA ICCGAUUG 3934

3152 CGGCAGTC A GGAAGGCA 1426 UGCCUUCC CUGAUGAG X CGAA IACUGCCG 3935

3160 AGGAAGGC A GCCTACTC 1427 GAGUAGGC CUGAUGAG X CGAA ICCUUCCU 3936

3163 AAGGCAGC C TACTCCCT 1428 AGGGAGUA CUGAUGAG X CGAA ICUGCCUU 3937

3164 AGGCAGCC T ACTCCCTT 1429 AAGGGAGU CUGAUGAG X CGAA IGCUGCCU 3938

3167 CAGCCTAC T CCCTTATC 1430 GAUAAGGG CUGAUGAG X CGAA IUAGGCUG 3939

3169 GCCTACTC C CTTATCTC 1431 GAGAUAAG CUGAUGAG X CGAA IAGUAGGC 3940

3170 CCTACTCC C TTATCTCC 1432 GGAGAUAA CUGAUGAG X CGAA IGAGUAGG 3941

3171 CTACTCCC T TATCTCCA 1433 UGGAGAUA CUGAUGAG X CGAA IGGAGUAG 3942

3176 CCCTTATC T CCACCTCT 1434 AGAGGUGG CUGAUGAG X CGAA lAUAAGGG 3943

3178 CTTATCTC C ACCTCTAA 1435 UUAGAGGU CUGAUGAG X CGAA IAGAUAAG 3944

3179 TTATCTCC A CCTCTAAG 1436 CUUAGAGG CUGAUGAG X CGAA IGAGAUAA 3945

3181 ATCTCCAC C TCTAAGGG 1437 CCCUUAGA CUGAUGAG X CGAA IUGGAGAU 3946

3182 TCTCCACC T CTAAGGGA 1438 UCCCUUAG CUGAUGAG X CGAA IGUGGAGA 3947

3184 TCCACCTC T AAGGGACA 1439 UGUCCCUU CUGAUGAG X CGAA IAGGUGGA 3948

3192 TAAGGGAC A CTCATCCT 1440 AGGAUGAG CUGAUGAG X CGAA IUCCCUUA 3949

3194 AGGGACAC T CATCCTCA 1441 UGAGGAUG CUGAUGAG X CGAA IUGUCCCU 3950

3196 GGACACTC A TCCTCAGG 1442 CCUGAGGA CUGAUGAG X CGAA IAGUGUCC 3951

3199 CACTCATC C TCAGGCCA 1443 UGGCCUGA CUGAUGAG X CGAA IAUGAGUG 3952

3200 ACTCATCC T CAGGCCAT 1444 AUGGCCUG CUGAUGAG X CGAA IGAUGAGU 3953

3202 TCATCCTC A GGCCATGC 1445 GCAUGGCC CUGAUGAG X CGAA IAGGAUGA 3954

3206 CCTCAGGC C ATGCAGTG 1446 CACUGCAU CUGAUGAG X CGAA ICCUGAGG 3955

3207 CTCAGGCC A TGCAGTGG 1447 CCACUGCA CUGAUGAG X CGAA IGCCUGAG 3956

Input Sequence = AF100308. Cut Site = CH/ .

Stem Length = 8 . Core Sequence = CUGAUGAG X CGAA (X = GCCGUUAGGC or other stem II)

AF100308 (Hepatitis B virus strain 2-18, 3215 bp)

Table 39

Table 39: Human HBV G-cleaver Ribozyme and Substrate Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

61 ACUUUCCU G CUGGUGGC 1448 GCCACCAG UGAUG GCAUGCACUAUGC GCG AGGAAAGU 3957

87 GGAACAGU G AGCCCUGC 1449 GCAGGGCU UGAUG GCAUGCACUAUGC GCG ACUGUUCC 3958

94 UGAGCCCU G CUCAGAAU 1450 AUUCUGAG UGAUG GCAUGCACUAUGC GCG AGGGCUCA 3959

112 CUGUCUCU G CCAUAUCG 1451 CGAUAUGG UGAUG GCAUGCACUAUGC GCG AGAGACAG 3960

132 AUCUUAUC G AAGACUGG 1452 CCAGUCUU UGAUG GCAUGCACUAUGC GCG GAUAAGAU 3961

153 CCUGUACC G AACAUGGA 1453 UCCAUGUU UGAUG GCAUGCACUAUGC GCG GGUACAGG 3962

169 AGAACAUC G CAUCAGGA 1454 UCCUGAUG UGAUG GCAUGCACUAUGC GCG GAUGUUCU 3963

192 GGACCCCU G CUCGUGUU 1455 AACACGAG UGAUG GCAUGCACUAUGC GCG AGGGGUCC 3964

222 UUCUUGUU G ACAAAAAU 1456 AUUUUUGU UGAUG GCAUGCACUAUGC GCG AACAAGAA 3965

315 CAAAAUUC G CAGUCCCA 1457 UGGGACUG UGAUG GCAUGCACUAUGC GCG GAAUUUUG 3966

374 UGGUUAUC G CUGGAUGU 1458 ACAUCCAG UGAUG GCAUGCACUAUGC GCG GAUAACCA 3967

387 AUGUGUCU G CGGCGUUU 1459 AAACGCCG UGAUG GCAUGCACUAUGC GCG AGACACAU 3968

410 CUUCCUCU G CAUCCUGC 1460 GCAGGAUG UGAUG GCAUGCACUAUGC GCG AGAGGAAG 3969

417 UGCAUCCU G CUGCUAUG 1461 CAUAGCAG UGAUG GCAUGCACUAUGC GCG AGGAUGCA 3970

420 AUCCUGCU G CUAUGCCU 1462 AGGCAUAG UGAUG GCAUGCACUAUGC GCG AGCAGGAU 3971

425 GCUGCUAU G CCUCAUCU 1463 AGAUGAGG UGAUG GCAUGCACUAUGC GCG AUAGCAGC 3972

468 GGUAUGUU G CCCGUUUG 1464 CAAACGGG UGAUG GCAUGCACUAUGC GCG AACAUACC 3973

518 CGGACCAU G CAAAACCU 1465 AGGUUUUG UGAUG GCAUGCACUAUGC GCG AUGGUCCG 3974

527 CAAAACCU G CACAACUC 1466 GAGUUGUG UGAUG GCAUGCACUAUGC GCG AGGUUUUG 3975

538 CAACUCCU G CUCAAGGA 1467 UCCUUGAG UGAUG GCAUGCACUAUGC GCG AGGAGUUG 3976

569 CUCAUGUU G CUGUACAA 1468 UUGUACAG UGAUG GCAUGCACUAUGC GCG AACAUGAG 3977

596 CGGAAACU G CACCUGUA 1469 UACAGGUG UGAUG GCAUGCACUAUGC GCG AGUUUCCG 3978

631 GGGCUUUC G CAAAAUAC 1470 GUAUUUUG UGAUG GCAUGCACUAUGC GCG GAAAGCCC 3979

687 UUACUAGU G CCAUUUGU 1471 ACAAAUGG UGAUG GCAUGCACUAUGC GCG ACUAGUAA 3980

747 AUAUGGAU G AUGUGGUU 1472 AACCACAU UGAUG GCAUGCACUAUGC GCG AUCCAUAU 3981

783 AACAUCUU G AGUCCCUU 1473 AAGGGACU UGAUG GCAUGCACUAUGC GCG AAGAUGUU 3982

795 CCCUUUAU G CCGCUGUU 1474 AACAGCGG UGAUG GCAUGCACUAUGC GCG AUAAAGGG 3983

798 UUUAUGCC G CUGUUACC 1475 GGUAACAG UGAUG GCAUGCACUAUGC GCG GGCAUAAA 3984

911 GGCACAUU G CCACAGGA 1476 UCCUGUGG UGAUG GCAUGCACUAUGC GCG AAUGUGCC 3985

978 GGCCUAUU G AUUGGAAA 1477 UUUCCAAU UGAUG GCAUGCACUAUGC GCG AAUAGGCC 3986

Table 39

997 AUGUCAAC G AAUUGUGG 1478 CCACAAUU UGAUG GCAUGCACUAUGC GCG GUUGACAU 3987

1020 UGGGGUUU G CCGCCCCU 1479 AGGGGCGG UGAUG GCAUGCACUAUGC GCG AAACCCCA 3988

1023 GGUUUGCC G CCCCUUUC 1480 GAAAGGGG UGAUG GCAUGCACUAUGC GCG GGCAAACC 3989

1034 CCUUUCAC G CAAUGUGG 1481 CCACAUUG UGAUG GCAUGCACUAUGC GCG GUGAAAGG 3990

1050 GAUAUUCU G CUUUAAUG 1482 CAUUAAAG UGAUG GCAUGCACUAUGC GCG AGAAUAUC 3991

1058 GCUUUAAU G CCUUUAUA 1483 UAUAAAGG UGAUG GCAUGCACUAUGC GCG AUUAAAGC 3992

1068 CUUUAUAU G CAUGCAUA 1484 UAUGCAUG UGAUG GCAUGCACUAUGC GCG AUAUAAAG 3993

1072 AUAUGCAU G CAUACAAG 1485 CUUGUAUG UGAUG GCAUGCACUAUGC GCG AUGCAUAU 3994

1103 ACUUUCUC G CCAACUUA 1486 UAAGUUGG UGAUG GCAUGCACUAUGC GCG GAGAAAGU 3995

1139 CAGUAUGU G AACCUUUA 1487 UAAAGGUU UGAUG GCAUGCACUAUGC GCG ACAUACUG 3996

1155 ACCCCGUU G CUCGGCAA 1488 UUGCCGAG UGAUG GCAUGCACUAUGC GCG AACGGGGU 3997

1177 UGGUCUAU G CCAAGUGU 1489 ACACUUGG UGAUG GCAUGCACUAUGC GCG AUAGACCA 3998

1188 AAGUGUUU G CUGACGCA 1490 UGCGUCAG UGAUG GCAUGCACUAUGC GCG AAACACUU 3999

1191 UGUUUGCU G ACGCAACC 1491 GGUUGCGU UGAUG GCAUGCACUAUGC GCG AGCAAACA 4000

1194 UUGCUGAC G CAACCCCC 1492 GGGGGUUG UGAUG GCAUGCACUAUGC GCG GUCAGCAA 4001

1234 CCAUCAGC G CAUGCGUG 1493 CACGCAUG UGAUG GCAUGCACUAUGC GCG GCUGAUGG 4002

1238 CAGCGCAU G CGUGGAAC 1494 GUUCCACG UGAUG GCAUGCACUAUGC GCG AUGCGCUG 4003

1262 UCUCCUCU G CCGAUCCA 1495 UGGAUCGG UGAUG GCAUGCACUAUGC GCG AGAGGAGA 4004

1265 CCUCUGCC G AUCCAUAC 1496 GUAUGGAU UGAUG GCAUGCACUAUGC GCG GGCAGAGG 4005

1275 UCCAUACC G CGGAACUC 1497 GAGUUCCG UGAUG GCAUGCACUAUGC GCG GGUAUGGA 4006

1290 UCCUAGCC G CUUGUUUU 1498 AAAACAAG UGAUG GCAUGCACUAUGC GCG GGCUAGGA 4007

1299 CUUGUUUU G CUCGCAGC 1499 GCUGCGAG UGAUG GCAUGCACUAUGC GCG AAAACAAG 4008

1303 UUUUGCUC G CAGCAGGU 1500 ACCUGCUG UGAUG GCAUGCACUAUGC GCG GAGCAAAA 4009

1335 UCGGGACU G AGAAUUCU 1501 AGAAUUGU UGAUG GCAUGCACUAUGC GCG AGUCCCGA 4010

1349 UCUGUCGU G CUCUCCCG 1502 CGGGAGAG UGAUG GCAUGCACUAUGC GCG ACGACAGA 4011

1357 GCUCUCCC G CAAAUAUA 1503 UAUAUUUG UGAUG GCAUGCACUAUGC GCG GGGAGAGC 4012

1382 CCAUGGCU G CUAGGCUG 1504 CAGCCUAG UGAUG GCAUGCACUAUGC GCG AGCCAUGG 4013

1392 UAGGCUGU G CUGCCAAC 1505 GUUGGCAG UGAUG GCAUGCACUAUGC GCG ACAGCCUA 4014

1395 GCUGUGCU G CCAACUGG 1506 CCAGUUGG UGAUG GCAUGCACUAUGC GCG AGCACAGC 4015

1411 GAUCCUAC G CGGGACGU 1507 ACGUCCCG UGAUG GCAUGCACUAUGC GCG GUAGGAUC 4016

1442 CCGUCGGC G CUGAAUCC 1508 GGAUUCAG UGAUG GCAUGCACUAUGC GCG GCCGACGG 4017

1445 UCGGCGCU G AAUCCCGC 1509 GCGGGAUU UGAUG GCAUGCACUAUGC GCG AGCGCCGA 4018

1452 UGAAUCCC G CGGACGAC 1510 GUCGUCCG UGAUG GCAUGCACUAUGC GCG GGGAUUCA 4019

1458 CCGCGGAC G ACCCCUCC 1511 GGAGGGGU UGAUG GCAUGCACUAUGC GCG GUCCGCGG 4020

Table 39

1474 CCGGGGCC G CUUGGGGC 1512 GCCCCAAG UGAUG GCAUGCACUAUGC GCG GGCCCCGG 4021

1489 GCUCUACC G CCCGCUUC 1513 GAAGCGGG UGAUG GCAUGCACUAUGC GCG GGUAGAGC 4022

1493 UACCGCCC G CUUCUCCG 1514 CGGAGAAG UGAUG GCAUGCACUAUGC GCG GGGCGGUA 4023

1501 GCUUCUCC G CCUAUUGU 1515 ACAAUAGG UGAUG GCAUGCACUAUGC GCG GGAGAAGC 4024

1513 AUUGUACC G ACCGUCCA 1516 UGGACGGU UGAUG GCAUGCACUAUGC GCG GGUACAAU 4025

1528 CACGGGGC G CACCUCUC 1517 GAGAGGUG UGAUG GCAUGCACUAUGC GCG GCCCCGUG 4026

1542 CUCUUUAC G CGGACUCC 1518 GGAGUCCG UGAUG GCAUGCACUAUGC GCG GUAAAGAG 4027

1559 CCGUCUGU G CCUUCUCA 1519 UGAGAAGG UGAUG GCAUGCACUAUGC GCG ACAGACGG 4028

1571 UCUCAUCU G CCGGACCG 1520 CGGUCCGG UGAUG GCAUGCACUAUGC GCG AGAUGAGA 4029

1583 GACCGUGU G CACUUCGC 1521 GCGAAGUG UGAUG GCAUGCACUAUGC GCG ACACGGUC 4030

1590 UGCACUUC G CUUCACCU 1522 AGGUGAAG UGAUG GCAUGCACUAUGC GCG GAAGUGCA 4031

1601 UCACCUCU G CACGUCGC 1523 GCGACGUG UGAUG GCAUGCACUAUGC GCG AGAGGUGA 4032

1608 UGCACGUC G CAUGGAGA 1524 UCUCCAUG UGAUG GCAUGCACUAUGC GCG GACGUGCA 4033

1624 ACCACCGU G AACGCCCA 1525 UGGGCGUU UGAUG GCAUGCACUAUGC GCG ACGGUGGU 4034

1628 CCGUGAAC G CCCACAGG 1526 CCUGUGGG UGAUG GCAUGCACUAUGC GCG GUUCACGG 4035

1642 AGGAACCU G CCCAAGGU 1527 ACCUUGGG UGAUG GCAUGCACUAUGC GCG AGGUUCCU 4036

1654 AAGGUCUU G CAUAAGAG 1528 CUCUUAUG UGAUG GCAUGCACUAUGC GCG AAGACCUU 4037

1690 AUGUCAAC G ACCGACCU 1529 AGGUCGGU UGAUG GCAUGCACUAUGC GCG GUUGACAU 4038

1694 CAACGACC G ACCUUGAG 1530 CUCAAGGU UGAUG GCAUGCACUAUGC GCG GGUCGUUG 4039

1700 CCGACCUU G AGGCAUAC 1531 GUAUGCCU UGAUG GCAUGCACUAUGC GCG AAGGUCGG 4040

1730 UGUUUAAU G AGUGGGAG 1532 CUCCCACU UGAUG GCAUGCACUAUGC GCG AUUAAACA 4041

1818 AGCACCAU G CAACUUUU 1533 AAAAGUUG UGAUG GCAUGCACUAUGC GCG AUGGUGCU 4042

1835 UCACCUCU G CCUAAUCA 1534 UGAUUAGG UGAUG GCAUGCACUAUGC GCG AGAGGUGA 4043

1883 CAAGCUGU G CCUUGGGU 1535 ACCCAAGG UGAUG GCAUGCACUAUGC GCG ACAGCUUG 4044

1912 UGGACAUU G ACCCGUAU 1536 AUACGGGU UGAUG GCAUGCACUAUGC GCG AAUGUCCA 4045

1959 UCUUUUUU G CCUUCUGA 1537 UCAGAAGG UGAUG GCAUGCACUAUGC GCG AAAAAAGA 4046

1966 UGCCUUCU G ACUUCUUU 1538 AAAGAAGU UGAUG GCAUGCACUAUGC GCG AGAAGGCA 4047

1985 UUCUAUUC G AGAUCUCC 1539 GGAGAUCU UGAUG GCAUGCACUAUGC GCG GAAUAGAA 4048

1996 AUCUCCUC G ACACCGCC 1540 GGCGGUGU UGAUG GCAUGCACUAUGC GCG GAGGAGAU 4049

2002 UCGACACC G CCUCUGCU 1541 AGCAGAGG UGAUG GCAUGCACUAUGC GCG GGUGUCGA 4050

2008 CCGCCUCU G CUCUGUAU 1542 AUACAGAG UGAUG GCAUGCACUAUGC GCG AGAGGCGG 4051

2092 GUUGGGGU G AGUUGAUG 1543 CAUCAACU UGAUG GCAUGCACUAUGC GCG ACCCCAAC 4052

2097 GGUGAGUU G AUGAAUCU 1544 AGAUUCAU UGAUG GCAUGCACUAUGC GCG AACUCACC 4053

2100 GAGUUGAU G AAUCUAGC 1545 GCUAGAUU UGAUG GCAUGCACUAUGC GCG AUCAACUC 4054

Table 39

2237 UUUUGGGC G AGAAACUG 1546 CAGUUUCU UGAUG GCAUGCACUAUGC GCG GCCCAAAA 4055

2251 CUGUUCUU G AAUAUUUG 1547 CAAAUAUU UGAUG GCAUGCACUAUGC GCG AAGAACAG 4056

2282 GUGGAUUC G CACUCCUC 1548 GAGGAGUG UGAUG GCAUGCACUAUGC GCG GAAUCCAC 4057

2293 CUCCUCCU G CAUAUAGA 1549 UCUAUAUG UGAUG GCAUGCACUAUGC GCG AGGAGGAG 4058

2311 CACCAAAU G CCCCUAUC 1550 GAUAGGGG UGAUG GCAUGCACUAUGC GCG AUUUGGUG 4059

2354 UGUUAGAC G AAGAGGCA 1551 UGCCUCUU UGAUG GCAUGCACUAUGC GCG GUCUAACA 4060

2388 ACUCCCUC G CCUCGCAG 1552 CUGCGAGG UGAUG GCAUGCACUAUGC GCG GAGGGAGU 4061

2393 CUCGCCUC G CAGACGAA 1553 UUCGUCUG UGAUG GCAUGCACUAUGC GCG GAGGCGAG 4062

2399 UCGCAGAC G AAGGUCUC 1554 GAGACCUU UGAUG GCAUGCACUAUGC GCG GUCUGCGA 4063

2412 UCUCAAUC G CCGCGUCG 1555 CGACGCGG UGAUG GCAUGCACUAUGC GCG GAUUGAGA 4064

2415 CAAUCGCC G CGUCGCAG 1556 CUGCGACG UGAUG GCAUGCACUAUGC GCG GGCGAUUG 4065

2420 GCCGCGUC G CAGAAGAU 1557 AUCUUCUG UGAUG GCAUGCACUAUGC GCG GACGCGGC 4066

2514 GGUACCUU G CUUUAAUC 1558 GAUUAAAG UGAUG GCAUGCACUAUGC GCG AAGGUACC 4067

2549 CUUUUCCU G ACAUUCAU 1559 AUGAAUGU UGAUG GCAUGCACUAUGC GCG AGGAAAAG 4068

2560 AUUCAUUU G CAGGAGGA 1560 UCCUCCUG UGAUG GCAUGCACUAUGC GCG AAAUGAAU 4069

2576 ACAUUGUU G AUAGAUGU 1561 ACAUCUAU UGAUG GCAUGCACUAUGC GCG AACAAUGU 4070

2615 CAGUAAAU G AAAACAGG 1562 CCUGUUUU UGAUG GCAUGCACUAUGC GCG AUUUACUG 4071

2641 UUAACUAU G CCUGCUAG 1563 CUAGCAGG UGAUG GCAUGCACUAUGC GCG AUAGUUAA 4072

2645 CUAUGCCU G CUAGGUUU 1564 AAACCUAG UGAUG GCAUGCACUAUGC GCG AGGCAUAG 4073

2677 AAAUAUUU G CCCUUAGA 1565 UCUAAGGG UGAUG GCAUGCACUAUGC GCG AAAUAUUU 4074

2740 UUCCAGAC G CGACAUUA 1566 UAAUGUCG UGAUG GCAUGCACUAUGC GCG GUCUGGAA 4075

2742 CCAGACGC G ACAUUAUU 1567 AAUAAUGU UGAUG GCAUGCACUAUGC GCG GCGUCUGG 4076

2804 CACGUAGC G CCUCAUUU 1568 AAAUGAGG UGAUG GCAUGCACUAUGC GCG GCUACGUG 4077

2814 CUCAUUUU G CGGGUCAC 1569 GUGACCCG UGAUG GCAUGCACUAUGC GCG AAAAUGAG 4078

2875 CAAACCUC G AAAAGGCA 1570 UGCCUUUU UGAUG GCAUGCACUAUGC GCG GAGGUUUG 4079

2928 UCUUCCCC G AUCAUCAG 1571 CUGAUGAU UGAUG GCAUGCACUAUGC GCG GGGGAAGA 4080

2946 UGGACCCU G CAUUCAAA 1572 UUUGAAUG UGAUG GCAUGCACUAUGC GCG AGGGUCCA 4081

2990 CUCAACCC G CACAAGGA 1573 UCCUUGUG UGAUG GCAUGCACUAUGC GCG GGGUUGAG 4082

3012 GGCCGGAC G CCAACAAG 1574 CUUGUUGG UGAUG GCAUGCACUAUGC GCG GUCCGGCC 4083

3090 GCCCUCAC G CUCAGGGC 1575 GCCCUGAG UGAUG GCAUGCACUAUGC GCG GUGAGGGC 4084

3113 ACAACUGU G CCAGCAGC 1576 GCUGCUGG UGAUG GCAUGCACUAUGC GCG ACAGUUGU 4085

3132 CUCCUCCU G CCUCCACC 1577 GGUGGAGG UGAUG GCAUGCACUAUGC GCG AGGAGGAG 4086

51 AGGGCCCU G UACUUUCC 1578 GGAAAGUA UGAUG GCAUGCACUAUGC GCG AGGGCCCU 4087

106 AGAAUACU G UCUCUGCC 1579 GGCAGAGA UGAUG GCAUGCACUAUGC GCG AGUAUUCU 4088

Table 39

148 GGGACCCU G UACCGAAC 1580 GUUCGGUA UGAUG GCAUGCACUAUGC GCG AGGGUCCC 4089

198 CUGCUCGU G UUACAGGC 1581 GCCUGUAA UGAUG GCAUGCACUAUGC GCG ACGAGCAG 4090

219 UUUUUCUU G UUGACAAA 1582 UUUGUCAA UGAUG GCAUGCACUAUGC GCG AAGAAAAA 4091

297 ACACCCGU G UGUCUUGG 1583 CCAAGACA UGAUG GCAUGCACUAUGC GCG ACGGGUGU 4092

299 ACCCGUGU G UCUUGGCC 1584 GGCCAAGA UGAUG GCAUGCACUAUGC GCG ACACGGGU 4093

347 ACCAACCU G UUGUCCUC 1585 GAGGACAA UGAUG GCAUGCACUAUGC GCG AGGUUGGU 4094

350 AACCUGUU G UCCUCCAA 1586 UUGGAGGA UGAUG GCAUGCACUAUGC GCG AACAGGUU 4095

362 UCCAAUUU G UCCUGGUU 1587 AACCAGGA UGAUG GCAUGCACUAUGC GCG AAAUUGGA 4096

381 CGCUGGAU G UGUCUGCG 1588 CGCAGACA UGAUG GCAUGCACUAUGC GCG AUCCAGCG 4097

383 CUGGAUGU G UCUGCGGC 1589 GCCGCAGA UGAUG GCAUGCACUAUGC GCG ACAUCCAG 4098

438 AUCUUCUU G UUGGUUCU 1590 AGAACCAA UGAUG GCAUGCACUAUGC GCG AAGAAGAU 4099

465 CAAGGUAU G UUGCCCGU 1591 ACGGGCAA UGAUG GCAUGCACUAUGC GCG AUACCUUG 4100

476 GCCCGUUU G UCCUCUAA 1592 UUAGAGGA UGAUG GCAUGCACUAUGC GCG AAACGGGC 4101

555 ACCUCUAU G UUUCCCUC 1593 GAGGGAAA UGAUG GCAUGCACUAUGC GCG AUAGAGGU 4102

566 UCCCUCAU G UUGCUGUA 1594 UACAGCAA UGAUG GCAUGCACUAUGC GCG AUGAGGGA 4103

572 AUGUUGCU G UACAAAAC 1595 GUUUUGUA UGAUG GCAUGCACUAUGC GCG AGCAACAU 4104

602 CUGCACCU G UAUUCCCA 1596 UGGGAAUA UGAUG GCAUGCACUAUGC GCG AGGUGCAG 4105

694 UGCCAUUU G UUCAGUGG 1597 CCACUGAA UGAUG GCAUGCACUAUGC GCG AAAUGGCA 4106

724 CCCCCACU G UCUGGCUU 1598 AAGCCAGA UGAUG GCAUGCACUAUGC GCG AGUGGGGG 4107

750 UGGAUGAU G UGGUUUUG 1599 CAAAACCA UGAUG GCAUGCACUAUGC GCG AUCAUCCA 4108

771 CCAAGUCU G UACAACAU 1600 AUGUUGUA UGAUG GCAUGCACUAUGC GCG AGACUUGG 4109

801 AUGCCGCU G UUACCAAU 1601 AUUGGUAA UGAUG GCAUGCACUAUGC GCG AGCGGCAU 4110

818 UUUCUUUU G UCUUUGGG 1602 CCCAAAGA UGAUG GCAUGCACUAUGC GCG AAAAGAAA 4111

888 UGGGAUAU G UAAUUGGG 1603 CCCAAUUA UGAUG GCAUGCACUAUGC GCG AUAUCCCA 4112

927 AACAUAUU G UACAAAAA 1604 UUUUUGUA UGAUG GCAUGCACUAUGC GCG AAUAUGUU 4113

944 AUCAAAAU G UGUUUUAG 1605 CUAAAACA UGAUG GCAUGCACUAUGC GCG AUUUUGAU 4114

946 CAAAAUGU G UUUUAGGA 1606 UCCUAAAA UGAUG GCAUGCACUAUGC GCG ACAUUUUG 4115

963 AACUUCCU G UAAACAGG 1607 CCUGUUUA UGAUG GCAUGCACUAUGC GCG AGGAAGUU 4116

991 GAAAGUAU G UCAACGAA 1608 UUCGUUGA UGAUG GCAUGCACUAUGC GCG AUACUUUC 4117

1002 AACGAAUU G UGGGUCUU 1609 AAGACCCA UGAUG GCAUGCACUAUGC GCG AAUUCGUU 4118

1039 CACGCAAU G UGGAUAUU 1610 AAUAUCCA UGAUG GCAUGCACUAUGC GCG AUUGCGUG 4119

1137 AACAGUAU G UGAACCUU 1611 AAGGUUCA UGAUG GCAUGCACUAUGC GCG AUACUGUU 4120

1184 UGCCAAGU G UUUGCUGA 1612 UCAGCAAA UGAUG GCAUGCACUAUGC GCG ACUUGGCA 4121

1251 GAACCUUU G UGUCUCCU 1613 AGGAGACA UGAUG GCAUGCACUAUGC GCG AAAGGUUC 4122

Table 39

1253 ACCUUUGU G UCUCCUCU 1614 AGAGGAGA UGAUG GCAUGCACUAUGC GCG ACAAAGGU 4123

1294 AGCCGCUU G UUUUGCUC 1615 GAGCAAAA UGAUG GCAUGCACUAUGC GCG AAGCGGCU 4124

1344 ACAAUUCU G UCGUGCUC 1616 GAGCACGA UGAUG GCAUGCACUAUGC GCG AGAAUUGU 4125

1390 GCUAGGCU G UGCUGCCA 1617 UGGCAGCA UGAUG GCAUGCACUAUGC GCG AGCCUAGC 4126

1425 CGUCCUUU G UUUACGUC 1618 GACGUAAA UGAUG GCAUGCACUAUGC GCG AAAGGACG 4127

1508 CGCCUAUU G UACCGACC 1619 GGUCGGUA UGAUG GCAUGCACUAUGC GCG AAUAGGCG 4128

1557 CCCCGUCU G UGCCUUCU 1620 AGAAGGCA UGAUG GCAUGCACUAUGC GCG AGACGGGG 4129

1581 CGGACCGU G UGCACUUC 1621 GAAGUGCA UGAUG GCAUGCACUAUGC GCG ACGGUCCG 4130

1684 UCAGCAAU G UCAACGAC 1622 GUCGUUGA UGAUG GCAUGCACUAUGC GCG AUUGCUGA 4131

1719 CAAAGACU G UGUGUUUA 1623 UAAACACA UGAUG GCAUGCACUAUGC GCG AGUCUUUG 4132

1721 AAGACUGU G UGUUUAAU 1624 AUUAAACA UGAUG GCAUGCACUAUGC GCG ACAGUCUU 4133

1723 GACUGUGU G UUUAAUGA 1625 UCAUUAAA UGAUG GCAUGCACUAUGC GCG ACACAGUC 4134

1772 AGGUCUUU G UACUAGGA 1626 UCCUAGUA UGAUG GCAUGCACUAUGC GCG AAAGACCU 4135

1785 AGGAGGCU G UAGGCAUA 1627 UAUGCCUA UGAUG GCAUGCACUAUGC GCG AGCCUCCU 4136

1801 AAAUUGGU G UGUUCACC 1628 GGUGAACA UGAUG GCAUGCACUAUGC GCG ACCAAUUU 4137

1803 AUUGGUGU G UUCACCAG 1629 CUGGUGAA UGAUG GCAUGCACUAUGC GCG ACACCAAU 4138

1850 CAUCUCAU G UUCAUGUC 1630 GACAUGAA UGAUG GCAUGCACUAUGC GCG AUGAGAUG 4139

1856 AUGUUCAU G UCCUACUG 1631 CAGUAGGA UGAUG GCAUGCACUAUGC GCG AUGAACAU 4140

1864 GUCCUACU G UUCAAGCC 1632 GGCUUGAA UGAUG GCAUGCACUAUGC GCG AGUAGGAC 4141

1881 UCCAAGCU G UGCCUUGG 1633 CCAAGGCA UGAUG GCAUGCACUAUGC GCG AGCUUGGA 4142

1939 GAGCUUCU G UGGAGUUA 1634 UAACUCCA UGAUG GCAUGCACUAUGC GCG AGAAGCUC 4143

2013 UCUGCUCU G UAUCGGGG 1635 CCCCGAUA UGAUG GCAUGCACUAUGC GCG AGAGCAGA 4144

2045 GGAACAUU G UUCACCUC 1636 GAGGUGAA UGAUG GCAUGCACUAUGC GCG AAUGUUCC 4145

2082 GCUAUUCU G UGUUGGGG 1637 CCCCAACA UGAUG GCAUGCACUAUGC GCG AGAAUAGC 4146

2084 UAUUCUGU G UUGGGGUG 1638 CACCCCAA UGAUG GCAUGCACUAUGC GCG ACAGAAUA 4147

2167 UCAGCUAU G UCAACGUU 1639 AACGUUGA UGAUG GCAUGCACUAUGC GCG AUAGCUGA 4148

2205 CAACUAUU G UGGUUUCA 1640 UGAAACCA UGAUG GCAUGCACUAUGC GCG AAUAGUUG 4149

2222 CAUUUCCU G UCUUACUU 1641 AAGUAAGA UGAUG GCAUGCACUAUGC GCG AGGAAAUG 4150

2245 GAGAAACU G UUCUUGAA 1642 UUCAAGAA UGAUG GCAUGCACUAUGC GCG AGUUUCUC 4151

2262 UAUUUGGU G UCUUUUGG 1643 CCAAAAGA UGAUG GCAUGCACUAUGC GCG ACCAAAUA 4152

2274 UUUGGAGU G UGGAUUCG 1644 CGAAUCCA UGAUG GCAUGCACUAUGC GCG ACUCCAAA 4153

2344 AAACUACU G UUGUUAGA 1645 UCUAACAA UGAUG GCAUGCACUAUGC GCG AGUAGUUU 4154

2347 CUACUGUU G UUAGACGA 1646 UCGUCUAA UGAUG GCAUGCACUAUGC GCG AACAGUAG 4155

2450 AUCUCAAU G UUAGUAUU 1647 AAUACUAA UGAUG GCAUGCACUAUGC GCG AUUGAGAU 4156

Table 39

2573 AGGACAUU G UUGAUAGA 1648 UCUAUCAA UGAUG GCAUGCACUAUGC GCG AAUGUCCU 4157

2583 UGAUAGAU G UAAGCAAU 1649 AUUGCUUA UGAUG GCAUGCACUAUGC GCG AUCUAUCA 4158

2594 AGCAAUUU G UGGGGCCC 1650 GGGCCCCA UGAUG GCAUGCACUAUGC GCG AAAUUGCU 4159

2663 AUCCCAAU G UUACUAAA 1651 UUUAGUAA UGAUG GCAUGCACUAUGC GCG AUUGGGAU 4160

2717 CAGAGUAU G UAGUUAAU 1652 AUUAACUA UGAUG GCAUGCACUAUGC GCG AUACUCUG 4161

2901 AUCUUUCU G UCCCCAAU 1653 AUUGGGGA UGAUG GCAUGCACUAUGC GCG AGAAAGAU 4162

3071 GGGGGACU G UUGGGGUG 1654 CACCCCAA UGAUG GCAUGCACUAUGC GCG AGUCCCCC 4163

3111 UCACAACU G UGCCAGCA 1655 UGCUGGCA UGAUG GCAUGCACUAUGC GCG AGUUGUGA 4164

Input Sequence = AF100308. Cut Site = YG/M or UG/U.

Stem Length = 8. Core Sequence = UGAUG GCAUGCACUAUGC GCG

AF100308 (Hepatitis B virus strain 2-18, 3215 bp)

Table 40

Table 40: Human HBV Zinzyme Ribozyme and Substrate Sequence

Pos Substrate Seq ID Ribozyme Rz Seq

ID

61 ACUUUCCU G CUGGUGGC 1448 GCCACCAG GCcgaaagGCGaGuCaaGGuCu AGGAAAGU 4165

94 UGAGCCCU G CUCAGAAU 1450 AUUCUGAG GCcgaaagGCGaGuCaaGGuCu AGGGCUCA 4166

112 CUGUCUCU G CCAUAUCG 1451 CGAUAUGG GCcgaaagGCGaGuCaaGGuCu AGAGACAG 4167

169 AGAACAUC G CAUCAGGA 1454 UCCUGAUG GCcgaaagGCGaGuCaaGGuCu GAUGUUCU 4168

192 GGACCCCU G CUCGUGUU 1455 AACACGAG GCcgaaagGCGaGuCaaGGuCu AGGGGUCC 4169

315 CAAAAUUC G CAGUCCCA 1457 UGGGACUG GCcgaaagGCGaGuCaaGGuCu GAAUUUUG 4170

374 UGGUUAUC G CUGGAUGU 1458 ACAUCCAG GCcgaaagGCGaGuCaaGGuCu GAUAACCA 4171

387 AUGUGUCU G CGGCGUUU 1459 AAACGCCG GCcgaaagGCGaGuCaaGGuCu AGACACAU 4172

410 CUUCCUCU G CAUCCUGC 1460 GCAGGAUG GCcgaaagGCGaGuCaaGGuCu AGAGGAAG 4173

417 UGCAUCCU G CUGCUAUG 1461 CAUAGCAG GCcgaaagGCGaGuCaaGGuCu AGGAUGCA 4174

420 AUCCUGCU G CUAUGCCU 1462 AGGCAUAG GCcgaaagGCGaGuCaaGGuCu AGCAGGAU 4175

425 GCUGCUAU G CCUCAUCU 1463 AGAUGAGG GCcgaaagGCGaGuCaaGGuCu AUAGCAGC 4176

468 GGUAUGUU G CCCGUUUG 1464 CAAACGGG GCcgaaagGCGaGuCaaGGuCu AACAUACC 4177

518 CGGACCAU G CAAAACCU 1465 AGGUUUUG GCcgaaagGCGaGuCaaGGuCu AUGGUCCG 4178

527 CAAAACCU G CACAACUC 1466 GAGUUGUG GCcgaaagGCGaGuCaaGGuCu AGGUUUUG 4179

538 CAACUCCU G CUCAAGGA 1467 UCCUUGAG GCcgaaagGCGaGuCaaGGuCu AGGAGUUG 4180

569 CUCAUGUU G CUGUACAA 1468 UUGUACAG GCcgaaagGCGaGuCaaGGuCu AACAUGAG 4181

596 CGGAAACU G CACCUGUA 1469 UACAGGUG GCcgaaagGCGaGuCaaGGuCu AGUUUCCG 4182

631 GGGCUUUC G CAAAAUAC 1470 GUAUUUUG GCcgaaagGCGaGuCaaGGuCu GAAAGCCC 4183

687 UUACUAGU G CCAUUUGU 1471 ACAAAUGG GCcgaaagGCGaGuCaaGGuCu ACUAGUAA 4184

795 CCCUUUAU G CCGCUGUU 1474 AACAGCGG GCcgaaagGCGaGuCaaGGuCu AUAAAGGG 4185

798 UUUAUGCC G CUGUUACC 1475 GGUAACAG GCcgaaagGCGaGuCaaGGuCu GGCAUAAA 4186

911 GGCACAUU G CCACAGGA 1476 UCCUGUGG GCcgaaagGCGaGuCaaGGuCu AAUGUGCC 4187

1020 UGGGGUUU G CCGCCCCU 1479 AGGGGCGG GCcgaaagGCGaGuCaaGGuCu AAACCCCA 4188

1023 GGUUUGCC G CCCCUUUC 1480 GAAAGGGG GCcgaaagGCGaGuCaaGGuCu GGCAAACC 4189

1034 CCUUUCAC G CAAUGUGG 1481 CCACAUUG GCcgaaagGCGaGuCaaGGuCu GUGAAAGG 4190

1050 GAUAUUCU G CUUUAAUG 1482 CAUUAAAG GCcgaaagGCGaGuCaaGGuCu AGAAUAUC 4191

1058 GCUUUAAU G CCUUUAUA 1483 UAUAAAGG GCcgaaagGCGaGuCaaGGuCu AUUAAAGC 4192

1068 CUUUAUAU G CAUGCAUA 1484 UAUGCAUG GCcgaaagGCGaGuCaaGGuCu AUAUAAAG 4193

1072 AUAUGCAU G CAUACAAG 1485 CUUGUAUG GCcgaaagGCGaGuCaaGGuCu AUGCAUAU 4194

Table 40

1103 ACUUUCUC G CCAACUUA 1486 UAAGUUGG GCcgaaagGCGaGuCaaGGuCu GAGAAAGU 4195

1155 ACCCCGUU G CUCGGCAA 1488 UUGCCGAG GCcgaaagGCGaGuCaaGGuCu AACGGGGU 4196

1177 UGGUCUAU G CCAAGUGU 1489 ACACUUGG GCcgaaagGCGaGuCaaGGuCu AUAGACCA 4197

1188 AAGUGUUU G CUGACGCA 1490 UGCGUCAG GCcgaaagGCGaGuCaaGGuCu AAACACUU 4198

1194 UUGCUGAC G CAACCCCC 1492 GGGGGUUG GCcgaaagGCGaGuCaaGGuCu GUCAGCAA 4199

1234 CCAUCAGC G CAUGCGUG 1493 CACGCAUG GCcgaaagGCGaGuCaaGGuCu GCUGAUGG 4200

1238 CAGCGCAU G CGUGGAAC 1494 GUUCCACG GCcgaaagGCGaGuCaaGGuCu AUGCGCUG 4201

1262 UCUCCUCU G CCGAUCCA 1495 UGGAUCGG GCcgaaagGCGaGuCaaGGuCu AGAGGAGA 4202

1275 UCCAUACC G CGGAACUC 1497 GAGUUCCG GCcgaaagGCGaGuCaaGGuCu GGUAUGGA 4203

1290 UCCUAGCC G CUUGUUUU 1498 AAAACAAG GCcgaaagGCGaGuCaaGGuCu GGCUAGGA 4204

1299 CUUGUUUU G CUCGCAGC 1499 GCUGCGAG GCcgaaagGCGaGuCaaGGuCu AAAACAAG 4205

1303 UUUUGCUC G CAGCAGGU 1500 ACCUGCUG GCcgaaagGCGaGuCaaGGuCu GAGCAAAA 4206

1349 UCUGUCGU G CUCUCCCG 1502 CGGGAGAG GCcgaaagGCGaGuCaaGGuCu ACGACAGA 4207

1357 GCUCUCCC G CAAAUAUA 1503 UAUAUUUG GCcgaaagGCGaGuCaaGGuCu GGGAGAGC 4208

1382 CCAUGGCU G CUAGGCUG 1504 CAGCCUAG GCcgaaagGCGaGuCaaGGuCu AGCCAUGG 4209

1392 UAGGCUGU G CUGCCAAC 1505 GUUGGCAG GCcgaaagGCGaGuCaaGGuCu ACAGCCUA 4210

1395 GCUGUGCU G CCAACUGG 1506 CCAGUUGG GCcgaaagGCGaGuCaaGGuCu AGCACAGC 4211

1411 GAUCCUAC G CGGGACGU 1507 ACGUCCCG GCcgaaagGCGaGuCaaGGuCu GUAGGAUC 4212

1442 CCGUCGGC G CUGAAUCC 1508 GGAUUCAG GCcgaaagGCGaGuCaaGGuCu GCCGACGG 4213

1452 UGAAUCCC G CGGACGAC 1510 GUCGUCCG GCcgaaagGCGaGuCaaGGuCu GGGAUUCA 4214

1474 CCGGGGCC G CUUGGGGC 1512 GCCCCAAG GCcgaaagGCGaGuCaaGGuCu GGCCCCGG 4215

1489 GCUCUACC G CCCGCUUC 1513 GAAGCGGG GCcgaaagGCGaGuCaaGGuCu GGUAGAGC 4216

1493 UACCGCCC G CUUCUCCG 1514 CGGAGAAG GCcgaaagGCGaGuCaaGGuCu GGGCGGUA 4217

1501 GCUUCUCC G CCUAUUGU 1515 ACAAUAGG GCcgaaagGCGaGuCaaGGuCu GGAGAAGC 4218

1528 CACGGGGC G CACCUCUC 1517 GAGAGGUG GCcgaaagGCGaGuCaaGGuCu GCCCCGUG 4219

1542 CUCUUUAC G CGGACUCC 1518 GGAGUCCG GCcgaaagGCGaGuCaaGGuCu GUAAAGAG 4220

1559 CCGUCUGU G CCUUCUCA 1519 UGAGAAGG GCcgaaagGCGaGuCaaGGuCu ACAGACGG 4221

1571 UCUCAUCU G CCGGACCG 1520 CGGUCCGG GCcgaaagGCGaGuCaaGGuCu AGAUGAGA 4222

1583 GACCGUGU G CACUUCGC 1521 GCGAAGUG GCcgaaagGCGaGuCaaGGuCu ACACGGUC 4223

1590 UGCACUUC G CUUCACCU 1522 AGGUGAAG GCcgaaagGCGaGuCaaGGuCu GAAGUGCA 4224

1601 UCACCUCU G CACGUCGC 1523 GCGACGUG GCcgaaagGCGaGuCaaGGuCu AGAGGUGA 4225

1608 UGCACGUC G CAUGGAGA 1524 UCUCCAUG GCcgaaagGCGaGuCaaGGuCu GACGUGCA 4226

1628 CCGUGAAC G CCCACAGG 1526 CCUGUGGG GCcgaaagGCGaGuCaaGGuCu GUUCACGG 4227

1642 AGGAACCU G CCCAAGGU 1527 ACCUUGGG GCcgaaagGCGaGuCaaGGuCu AGGUUCCU 4228

Table 40

1654 AAGGUCUU G CAUAAGAG 1528 CUCUUAUG GCcgaaagGCGaGuCaaGGuCu AAGACCUU 4229

1818 AGCACCAU G CAACUUUU 1533 AAAAGUUG GCcgaaagGCGaGuCaaGGuCu AUGGUGCU 4230

1835 UCACCUCU G CCUAAUCA 1534 UGAUUAGG GCcgaaagGCGaGuCaaGGuCu AGAGGUGA 4231

1883 CAAGCUGU G CCUUGGGU 1535 ACCCAAGG GCcgaaagGCGaGuCaaGGuCu ACAGCUUG 4232

1959 UCUUUUUU G CCUUCUGA 1537 UCAGAAGG GCcgaaagGCGaGuCaaGGuCu AAAAAAGA 4233

2002 UCGACACC G CCUCUGCU 1541 AGCAGAGG GCcgaaagGCGaGuCaaGGuCu GGUGUCGA 4234

2008 CCGCCUCU G CUCUGUAU 1542 AUACAGAG GCcgaaagGCGaGuCaaGGuCu AGAGGCGG 4235

2282 GUGGAUUC G CACUCCUC 1548 GAGGAGUG GCcgaaagGCGaGuCaaGGuCu GAAUCCAC 4236

2293 CUCCUCCU G CAUAUAGA 1549 UCUAUAUG GCcgaaagGCGaGuCaaGGuCu AGGAGGAG 4237

2311 CACCAAAU G CCCCUAUC 1550 GAUAGGGG GCcgaaagGCGaGuCaaGGuCu AUUUGGUG 4238

2388 ACUCCCUC G CCUCGCAG 1552 CUGCGAGG GCcgaaagGCGaGuCaaGGuCu GAGGGAGU 4239

2393 CUCGCCUC G CAGACGAA 1553 UUCGUCUG GCcgaaagGCGaGuCaaGGuCu GAGGCGAG 4240

2412 UCUCAAUC G CCGCGUCG 1555 CGACGCGG GCcgaaagGCGaGuCaaGGuCu GAUUGAGA 4241

2415 CAAUCGCC G CGUCGCAG 1556 CUGCGACG GCcgaaagGCGaGuCaaGGuCu GGCGAUUG 4242

2420 GCCGCGUC G CAGAAGAU 1557 AUCUUCUG GCcgaaagGCGaGuCaaGGuCu GACGCGGC 4243

2514 GGUACCUU G CUUUAAUC 1558 GAUUAAAG GCcgaaagGCGaGuCaaGGuCu AAGGUACC 4244

2560 AUUCAUUU G CAGGAGGA 1560 UCCUCCUG GCcgaaagGCGaGuCaaGGuCu AAAUGAAU 4245

2641 UUAACUAU G CCUGCUAG 1563 CUAGCAGG GCcgaaagGCGaGuCaaGGuCu AUAGUUAA 4246

2645 CUAUGCCU G CUAGGUUU 1564 AAACCUAG GCcgaaagGCGaGuCaaGGuCu AGGCAUAG 4247

2677 AAAUAUUU G CCCUUAGA 1565 UCUAAGGG GCcgaaagGCGaGuCaaGGuCu AAAUAUUU 4248

2740 UUCCAGAC G CGACAUUA 1566 UAAUGUCG GCcgaaagGCGaGuCaaGGuCu GUCUGGAA 4249

2804 CACGUAGC G CCUCAUUU 1568 AAAUGAGG GCcgaaagGCGaGuCaaGGuCu GCUACGUG 4250

2814 CUCAUUUU G CGGGUCAC 1569 GUGACCCG GCcgaaagGCGaGuCaaGGuCu AAAAUGAG 4251

2946 UGGACCCU G CAUUCAAA 1572 UUUGAAUG GCcgaaagGCGaGuCaaGGuCu AGGGUCCA 4252

2990 CUCAACCC G CACAAGGA 1573 UCCUUGUG GCcgaaagGCGaGuCaaGGuCu GGGUUGAG 4253

3012 GGCCGGAC G CCAACAAG 1574 CUUGUUGG GCcgaaagGCGaGuCaaGGuCu GUCCGGCC 4254

3090 GCCCUCAC G CUCAGGGC 1575 GCCCUGAG GCcgaaagGCGaGuCaaGGuCu GUGAGGGC 4255

3113 ACAACUGU G CCAGCAGC 1576 GCUGCUGG GCcgaaagGCGaGuCaaGGuCu ACAGUUGU 4256

3132 CUCCUCCU G CCUCCACC 1577 GGUGGAGG GCcgaaagGCGaGuCaaGGuCu AGGAGGAG 4257

51 AGGGCCCU G UACUUUCC 1578 GGAAAGUA GCcgaaagGCGaGuCaaGGuCu AGGGCCCU 4258

106 AGAAUACU G UCUCUGCC 1579 GGCAGAGA GCcgaaagGCGaGuCaaGGuCu AGUAUUCU 4259

148 GGGACCCU G UACCGAAC 1580 GUUCGGUA GCcgaaagGCGaGuCaaGGuCu AGGGUCCC 4260

198 CUGCUCGU G UUACAGGC 1581 GCCUGUAA GCcgaaagGCGaGuCaaGGuCu ACGAGCAG 4261

219 UUUUUCUU G UUGACAAA 1582 UUUGUCAA GCcgaaagGCGaGuCaaGGuCu AAGAAAAA 4262

Table 40

297 ACACCCGU G UGUCUUGG 1583 CCAAGACA GCcgaaagGCGaGuCaaGGuCu ACGGGUGU 4263

299 ACCCGUGU G UCUUGGCC 1584 GGCCAAGA GCcgaaagGCGaGuCaaGGuCu ACACGGGU 4264

347 ACCAACCU G UUGUCCUC 1585 GAGGACAA GCcgaaagGCGaGuCaaGGuCu AGGUUGGU 4265

350 AACCUGUU G UCCUCCAA 1586 UUGGAGGA GCcgaaagGCGaGuCaaGGuCu AACAGGUU 4266

362 UCCAAUUU G UCCUGGUU 1587 AACCAGGA GCcgaaagGCGaGuCaaGGuCu AAAUUGGA 4267

381 CGCUGGAU G UGUCUGCG 1588 CGCAGACA GCcgaaagGCGaGuCaaGGuCu AUCCAGCG 4268

383 CUGGAUGU G UCUGCGGC 1589 GCCGCAGA GCcgaaagGCGaGuCaaGGuCu ACAUCCAG 4269

438 AUCUUCUU G UUGGUUCU 1590 AGAACCAA GCcgaaagGCGaGuCaaGGuCu AAGAAGAU 4270

465 CAAGGUAU G UUGCCCGU 1591 ACGGGCAA GCcgaaagGCGaGuCaaGGuCu AUACCUUG 4271

476 GCCCGUUU G UCCUCUAA 1592 UUAGAGGA GCcgaaagGCGaGuCaaGGuCu AAACGGGC 4272

555 ACCUCUAU G UUUCCCUC 1593 GAGGGAAA GCcgaaagGCGaGuCaaGGuCu AUAGAGGU 4273

566 UCCCUCAU G UUGCUGUA 1594 UACAGCAA GCcgaaagGCGaGuCaaGGuCu AUGAGGGA 4274

572 AUGUUGCU G UACAAAAC 1595 GUUUUGUA GCcgaaagGCGaGuCaaGGuCu AGCAACAU 4275

602 CUGCACCU G UAUUCCCA 1596 UGGGAAUA GCcgaaagGCGaGuCaaGGuCu AGGUGCAG 4276

694 UGCCAUUU G UUCAGUGG 1597 CCACUGAA GCcgaaagGCGaGuCaaGGuCu AAAUGGCA 4277

724 CCCCCACU G UCUGGCUU 1598 AAGCCAGA GCcgaaagGCGaGuCaaGGuCu AGUGGGGG 4278

750 UGGAUGAU G UGGUUUUG 1599 CAAAACCA GCcgaaagGCGaGuCaaGGuCu AUCAUCCA 4279

771 CCAAGUCU G UACAACAU 1600 AUGUUGUA GCcgaaagGCGaGuCaaGGuCu AGACUUGG 4280

801 AUGCCGCU G UUACCAAU 1601 AUUGGUAA GCcgaaagGCGaGuCaaGGuCu AGCGGCAU 4281

818 UUUCUUUU G UCUUUGGG 1602 CCCAAAGA ■GCcgaaagGCGaGuCaaGGuCu AAAAGAAA 4282

888 UGGGAUAU G UAAUUGGG 1603 CCCAAUUA GCcgaaagGCGaGuCaaGGuCu AUAUCCCA 4283

927 AACAUAUU G UACAAAAA 1604 UUUUUGUA GCcgaaagGCGaGuCaaGGuCu AAUAUGUU 4284

944 AUCAAAAU G UGUUUUAG 1605 CUAAAACA GCcgaaagGCGaGuCaaGGuCu AUUUUGAU 4285

946 CAAAAUGU G UUUUAGGA 1606 UCCUAAAA GCcgaaagGCGaGuCaaGGuCu ACAUUUUG 4286

963 AACUUCCU G UAAACAGG 1607 CCUGUUUA GCcgaaagGCGaGuCaaGGuCu AGGAAGUU 4287

991 GAAAGUAU G UCAACGAA 1608 UUCGUUGA GCcgaaagGCGaGuCaaGGuCu AUACUUUC 4288

1002 AACGAAUU G UGGGUCUU 1609 AAGACCCA GCcgaaagGCGaGuCaaGGuCu AAUUCGUU 4289

1039 CACGCAAU G UGGAUAUU 1610 AAUAUCCA GCcgaaagGCGaGuCaaGGuCu AUUGCGUG 4290

1137 AACAGUAU G UGAACCUU 1611 AAGGUUCA GCcgaaagGCGaGuCaaGGuCu AUACUGUU 4291

1184 UGCCAAGU G UUUGCUGA 1612 UCAGCAAA GCcgaaagGCGaGuCaaGGuCu ACUUGGCA 4292

1251 GAACCUUU G UGUCUCCU 1613 AGGAGACA GCcgaaagGCGaGuCaaGGuCu AAAGGUUC 4293

1253 ACCUUUGU G UCUCCUCU 1614 AGAGGAGA GCcgaaagGCGaGuCaaGGuCu ACAAAGGU 4294

1294 AGCCGCUU G UUUUGCUC 1615 GAGCAAAA GCcgaaagGCGaGuCaaGGuCu AAGCGGCU 4295

1344 ACAAUUCU G UCGUGCUC 1616 GAGCACGA GCcgaaagGCGaGuCaaGGuCu AGAAUUGU 4296

Table 40

1390 GCUAGGCU G UGCUGCCA 1617 UGGCAGCA GCcgaaagGCGaGuCaaGGuCu AGCCUAGC 4297

1425 CGUCCUUU G UUUACGUC 1618 GACGUAAA GCcgaaagGCGaGuCaaGGuCu AAAGGACG 4298

1508 CGCCUAUU G UACCGACC 1619 GGUCGGUA GCcgaaagGCGaGuCaaGGuCu AAUAGGCG 4299

1557 CCCCGUCU G UGCCUUCU 1620 AGAAGGCA GCcgaaagGCGaGuCaaGGuCu AGACGGGG 4300

1581 CGGACCGU G UGCACUUC 1621 GAAGUGCA GCcgaaagGCGaGuCaaGGuCu ACGGUCCG 4301

1684 UCAGCAAU G UCAACGAC 1622 GUCGUUGA GCcgaaagGCGaGuCaaGGuCu AUUGCUGA 4302

1719 CAAAGACU G UGUGUUUA 1623 UAAACACA GCcgaaagGCGaGuCaaGGuCu AGUCUUUG 4303

1721 AAGACUGU G UGUUUAAU 1624 AUUAAACA GCcgaaagGCGaGuCaaGGuCu ACAGUCUU 4304

1723 GACUGUGU G UUUAAUGA 1625 UCAUUAAA GCcgaaagGCGaGuCaaGGuCu ACACAGUC 4305

1772 AGGUCUUU G UACUAGGA 1626 UCCUAGUA GCcgaaagGCGaGuCaaGGuCu AAAGACCU 4306

1785 AGGAGGCU G UAGGCAUA 1627 UAUGCCUA GCcgaaagGCGaGuCaaGGuCu AGCCUCCU 4307

1801 AAAUUGGU G UGUUCACC 1628 GGUGAACA GCcgaaagGCGaGuCaaGGuCu ACCAAUUU 4308

1803 AUUGGUGU G UUCACCAG 1629 CUGGUGAA GCcgaaagGCGaGuCaaGGuCu ACACCAAU 4309

1850 CAUCUCAU G UUCAUGUC 1630 GACAUGAA GCcgaaagGCGaGuCaaGGuCu AUGAGAUG 4310

1856 AUGUUCAU G UCCUACUG 1631 CAGUAGGA GCcgaaagGCGaGuCaaGGuCu AUGAACAU 4311

1864 GUCCUACU G UUCAAGCC 1632 GGCUUGAA GCcgaaagGCGaGuCaaGGuCu AGUAGGAC 4312

1881 UCCAAGCU G UGCCUUGG 1633 CCAAGGCA GCcgaaagGCGaGuCaaGGuCu AGCUUGGA 4313

1939 GAGCUUCU G UGGAGUUA 1634 UAACUCCA GCcgaaagGCGaGuCaaGGuCu AGAAGCUC 4314

2013 UCUGCUCU G UAUCGGGG 1635 CCCCGAUA GCcgaaagGCGaGuCaaGGuCu AGAGCAGA 4315

2045 GGAACAUU G UUCACCUC 1636 GAGGUGAA GCcgaaagGCGaGuCaaGGuCu AAUGUUCC 4316

2082 GCUAUUCU G UGUUGGGG 1637 CCCCAACA GCcgaaagGCGaGuCaaGGuCu AGAAUAGC 4317

2084 UAUUCUGU G UUGGGGUG 1638 CACCCCAA GCcgaaagGCGaGuCaaGGuCu ACAGAAUA 4318

2167 UCAGCUAU G UCAACGUU 1639 AACGUUGA GCcgaaagGCGaGuCaaGGuCu AUAGCUGA 4319

2205 CAACUAUU G UGGUUUCA 1640 UGAAACCA GCcgaaagGCGaGuCaaGGuCu AAUAGUUG 4320

2222 CAUUUCCU G UCUUACUU 1641 AAGUAAGA GCcgaaagGCGaGuCaaGGuCu AGGAAAUG 4321

2245 GAGAAACU G UUCUUGAA 1642 UUCAAGAA GCcgaaagGCGaGuCaaGGuCu AGUUUCUC 4322

2262 UAUUUGGU G UCUUUUGG 1643 CCAAAAGA GCcgaaagGCGaGuCaaGGuCu ACCAAAUA 4323

2274 UUUGGAGU G UGGAUUCG 1644 CGAAUCCA GCcgaaagGCGaGuCaaGGuCu ACUCCAAA 4324

2344 AAACUACU G UUGUUAGA 1645 UCUAACAA GCcgaaagGCGaGuCaaGGuCu AGUAGUUU 4325

2347 CUACUGUU G UUAGACGA 1646 UCGUCUAA GCcgaaagGCGaGuCaaGGuCu AACAGUAG 4326

2450 AUCUCAAU G UUAGUAUU 1647 AAUACUAA GCcgaaagGCGaGuCaaGGuCu AUUGAGAU 4327

2573 AGGACAUU G UUGAUAGA 1648 UCUAUCAA GCcgaaagGCGaGuCaaGGuCu AAUGUCCU 4328

2583 UGAUAGAU G UAAGCAAU 1649 AUUGCUUA GCcgaaagGCGaGuCaaGGuCu AUCUAUCA 4329

2594 AGCAAUUU G UGGGGCCC 1650 GGGCCCCA GCcgaaagGCGaGuCaaGGuCu AAAUUGCU 4330

Table 40

2663 AUCCCAAU G UUACUAAA 1651 UUUAGUAA GCcgaaagGCGaGuCaaGGuCu AUUGGGAU 4331

2717 CAGAGUAU G UAGUUAAU 1652 AUUAACUA GCcgaaagGCGaGuCaaGGuCu AUACUCUG 4332

2901 AUCUUUCU G UCCCCAAU 1653 AUUGGGGA GCcgaaagGCGaGuCaaGGuCu AGAAAGAU 4333

3071 GGGGGACU G UUGGGGUG 1654 CACCCCAA GCcgaaagGCGaGuCaaGGuCu AGUCCCCC 4334

3111 UCACAACU G UGCCAGCA 1655 UGCUGGCA GCcgaaagGCGaGuCaaGGuCu AGUUGUGA 4335

40 AUCCCAGA G UCAGGGCC 1656 GGCCCUGA GCcgaaagGCGaGuCaaGGuCu UCUGGGAU 4336

46 GAGUCAGG G CCCUGUAC 1657 GUACAGGG GCcgaaagGCGaGuCaaGGuCu CCUGACUC 4337

65 UCCUGCUG G UGGCUCCA 1658 UGGAGCCA GCcgaaagGCGaGuCaaGGuCu CAGCAGGA 4338

68 UGCUGGUG G CUCCAGUU 1659 AACUGGAG GCcgaaagGCGaGuCaaGGuCu CACCAGCA 4339

74 UGGCUCCA G UUCAGGAA 1660 UUCCUGAA GCcgaaagGCGaGuCaaGGuCu UGGAGCCA 4340

85 CAGGAACA G UGAGCCCU 1661 AGGGCUCA GCcgaaagGCGaGuCaaGGuCu UGUUCCUG 4341

89 AACAGUGA G CCCUGCUC 1662 GAGCAGGG GCcgaaagGCGaGuCaaGGuCu UCACUGUU 4342

120 GCCAUAUC G UCAAUCUU 1663 AAGAUUGA GCcgaaagGCGaGuCaaGGuCu GAUAUGGC 4343

196 CCCUGCUC G UGUUACAG 1664 CUGUAACA GCcgaaagGCGaGuCaaGGuCu GAGCAGGG 4344

205 UGUUACAG G CGGGGUUU 1665 AAACCCCG GCcgaaagGCGaGuCaaGGuCu CUGUAACA 4345

210 CAGGCGGG G UUUUUCUU 1666 AAGAAAAA GCcgaaagGCGaGuCaaGGuCu CCCGCCUG 4346

248 ACCACAGA G UCUAGACU 1667 AGUCUAGA GCcgaaagGCGaGuCaaGGuCu UCUGUGGU 4347

258 CUAGACUC G UGGUGGAC 1668 GUCCACCA GCcgaaagGCGaGuCaaGGuCu GAGUCUAG 4348

261 GACUCGUG G UGGACUUC 1669 GAAGUCCA GCcgaaagGCGaGuCaaGGuCu CACGAGUC 4349

295 GAACACCC G UGUGUCUU 1670 AAGACACA GCcgaaagGCGaGuCaaGGuCu GGGUGUUC 4350

305 GUGUCUUG G CCAAAAUU 1671 AAUUUUGG GCcgaaagGCGaGuCaaGGuCu CAAGACAC 4351

318 AAUUCGCA G UCCCAAAU 1672 AUUUGGGA GCcgaaagGCGaGuCaaGGuCu UGCGAAUU 4352

332 AAUCUCCA G UCACUCAC 1673 GUGAGUGA GCcgaaagGCGaGuCaaGGuCu UGGAGAUU 4353

368 UUGUCCUG G UUAUCGCU 1674 AGCGAUAA GCcgaaagGCGaGuCaaGGuCu CAGGACAA 4354

390 UGUCUGCG G CGUUUUAU 1675 AUAAAACG GCcgaaagGCGaGuCaaGGuCu CGCAGACA 4355

392 UCUGCGGC G UUUUAUCA 1676 UGAUAAAA GCcgaaagGCGaGuCaaGGuCu GCCGCAGA 4356

442 UCUUGUUG G UUCUUCUG 1677 CAGAAGAA GCcgaaagGCGaGuCaaGGuCu CAACAAGA 4357

461 CUAUCAAG G UAUGUUGC 1678 GCAACAUA GCcgaaagGCGaGuCaaGGuCu CUUGAUAG 4358

472 UGUUGCCC G UUUGUCCU 1679 AGGACAAA GCcgaaagGCGaGuCaaGGuCu GGGCAACA 4359

506 AACAACCA G CACCGGAC 1680 GUCCGGUG GCcgaaagGCGaGuCaaGGuCu UGGUUGUU 4360

625 CAUCUUGG G CUUUCGCA 1681 UGCGAAAG GCcgaaagGCGaGuCaaGGuCu CCAAGAUG 4361

648 CUAUGGGA G UGGGCCUC 1682 GAGGCCCA GCcgaaagGCGaGuCaaGGuCu UCCCAUAG 4362

652 GGGAGUGG G CCUCAGUC 1683 GACUGAGG GCcgaaagGCGaGuCaaGGuCu CCACUCCC 4363

658 GGGCCUCA G UCCGUUUC 1684 GAAACGGA GCcgaaagGCGaGuCaaGGuCu UGAGGCCC 4364

Table 40

662 CUCAGUCC G UUUCUCUU 1685 AAGAGAAA GCcgaaagGCGaGuCaaGGuCu GGACUGAG 4365

672 UUCUCUUG G CUCAGUUU 1686 AAACUGAG GCcgaaagGCGaGuCaaGGuCu CAAGAGAA 4366

677 UUGGCUCA G UUUACUAG 1687 CUAGUAAA GCcgaaagGCGaGuCaaGGuCu UGAGCCAA 4367

685 GUUUACUA G UGCCAUUU 1688 AAAUGGCA GCcgaaagGCGaGuCaaGGuCu UAGUAAAC 4368

699 UUUGUUCA G UGGUUCGU 1689 ACGAACCA GCcgaaagGCGaGuCaaGGuCu UGAACAAA 4369

702 GUUCAGUG G UUCGUAGG 1690 CCUACGAA GCcgaaagGCGaGuCaaGGuCu CACUGAAC 4370

706 AGUGGUUC G UAGGGCUU 1691 AAGCCCUA GCcgaaagGCGaGuCaaGGuCu GAACCACU 4371

711 UUCGUAGG G CUUUCCCC 1692 GGGGAAAG GCcgaaagGCGaGuCaaGGuCu CCUACGAA 4372

729 ACUGUCUG G CUUUCAGU 1693 ACUGAAAG GCcgaaagGCGaGuCaaGGuCu CAGACAGU 4373

736 GGCUUUCA G UUAUAUGG 1694 CCAUAUAA GCcgaaagGCGaGuCaaGGuCu UGAAAGCC 4374

753 AUGAUGUG G UUUUGGGG 1695 CCCCAAAA GCcgaaagGCGaGuCaaGGuCu CACAUCAU 4375

762 UUUUGGGG G CCAAGUCU 1696 AGACUUGG GCcgaaagGCGaGuCaaGGuCu CCCCAAAA 4376

767 GGGGCCAA G UCUGUACA 1697 UGUACAGA GCcgaaagGCGaGuCaaGGuCu UUGGCCCC 4377

785 CAUCUUGA G UCCCUUUA 1698 UAAAGGGA GCcgaaagGCGaGuCaaGGuCu UCAAGAUG 4378

826 GUCUUUGG G UAUACAUU 1699 AAUGUAUA GCcgaaagGCGaGuCaaGGuCu CCAAAGAC 4379

898 AAUUGGGA G UUGGGGCA 1700 UGCCCCAA GCcgaaagGCGaGuCaaGGuCu UCCCAAUU 4380

904 GAGUUGGG G CACAUUGC 1701 GCAAUGUG GCcgaaagGCGaGuCaaGGuCu CCCAACUC 4381

971 GUAAACAG G CCUAUUGA 1702 UCAAUAGG GCcgaaagGCGaGuCaaGGuCu CUGUUUAC 4382

987 AUUGGAAA G UAUGUCAA 1703 UUGACAUA GCcgaaagGCGaGuCaaGGuCu UUUCCAAU 4383

1006 AAUUGUGG G UCUUUUGG 1704 CCAAAAGA GCcgaaagGCGaGuCaaGGuCu CCACAAUU 4384

1016 CUUUUGGG G UUUGCCGC 1705 GCGGCAAA GCcgaaagGCGaGuCaaGGuCu CCCAAAAG 4385

1080 GCAUACAA G CAAAACAG 1706 CUGUUUUG GCcgaaagGCGaGuCaaGGuCu UUGUAUGC 4386

1089 CAAAACAG G CUUUUACU 1707 AGUAAAAG GCcgaaagGCGaGuCaaGGuCu CUGUUUUG 4387

1116 CUUACAAG G CCUUUCUA 1708 UAGAAAGG GCcgaaagGCGaGuCaaGGuCu CUUGUAAG 4388

1126 CUUUCUAA G UAAACAGU 1709 ACUGUUUA GCcgaaagGCGaGuCaaGGuCu UUAGAAAG 4389

1133 AGUAAACA G UAUGUGAA 1710 UUCACAUA GCcgaaagGCGaGuCaaGGuCu UGUUUACU 4390

1152 UUUACCCC G UUGCUCGG 1711 CCGAGCAA GCcgaaagGCGaGuCaaGGuCu GGGGUAAA 4391

1160 GUUGCUCG G CAACGGCC 1712 GGCCGUUG GCcgaaagGCGaGuCaaGGuCu CGAGCAAC 4392

1166 CGGCAACG G CCUGGUCU 1713 AGACCAGG GCcgaaagGCGaGuCaaGGuCu CGUUGCCG 4393

1171 ACGGCCUG G UCUAUGCC 1714 GGCAUAGA GCcgaaagGCGaGuCaaGGuCu CAGGCCGU 4394

1182 UAUGCCAA G UGUUUGCU 1715 AGCAAACA GCcgaaagGCGaGuCaaGGuCu UUGGCAUA 4395

1207 CCCCACUG G UUGGGGCU 1716 AGCCCCAA GCcgaaagGCGaGuCaaGGuCu CAGUGGGG 4396

1213 UGGUUGGG G CUUGGCCA 1717 UGGCCAAG GCcgaaagGCGaGuCaaGGuCu CCCAACCA 4397

1218 GGGGCUUG G CCAUAGGC 1718 GCCUAUGG GCcgaaagGCGaGuCaaGGuCu CAAGCCCC 4398

Table 40

1225 GGCCAUAG G CCAUCAGC 1719 GCUGAUGG GCcgaaagGCGaGuCaaGGuCu CUAUGGCC 4399

1232 GGCCAUCA G CGCAUGCG 1720 CGCAUGCG GCcgaaagGCGaGuCaaGGuCu UGAUGGCC 4400

1240 GCGCAUGC G UGGAACCU 1721 AGGUUCCA GCcgaaagGCGaGuCaaGGuCu GCAUGCGC 4401

1287 AACUCCUA G CCGCUUGU 1722 ACAAGCGG GCcgaaagGCGaGuCaaGGuCu UAGGAGUU 4402

1306 UGCUCGCA G CAGGUCUG 1723 CAGACCUG GCcgaaagGCGaGuCaaGGuCu UGCGAGCA 4403

1310 CGCAGCAG G UCUGGGGC 1724 GCCCCAGA GCcgaaagGCGaGuCaaGGuCu CUGCUGCG 4404

1317 GGUCUGGG G CAAAACUC 1725 GAGUUUUG GCcgaaagGCGaGuCaaGGuCu CCCAGACC 4405

1347 AUUCUGUC G UGCUCUCC 1726 GGAGAGCA GCcgaaagGCGaGuCaaGGuCu GACAGAAU 4406

1379 UUUCCAUG G CUGCUAGG 1727 CCUAGCAG GCcgaaagGCGaGuCaaGGuCu CAUGGAAA 4407

1387 GCUGCUAG G CUGUGCUG 1728 CAGCACAG GCcgaaagGCGaGuCaaGGuCu CUAGCAGC 4408

1418 CGCGGGAC G UCCUUUGU 1729 ACAAAGGA GCcgaaagGCGaGuCaaGGuCu GUCCCGCG 4409

1431 UUGUUUAC G UCCCGUCG 1730 CGACGGGA GCcgaaagGCGaGuCaaGGuCu GUAAACAA 4410

1436 UACGUCCC G UCGGCGCU 1731 AGCGCCGA GCcgaaagGCGaGuCaaGGuCu GGGACGUA 4411

1440 UCCCGUCG G CGCUGAAU 1732 AUUCAGCG GCcgaaagGCGaGuCaaGGuCu CGACGGGA 4412

1471 CUCCCGGG G CCGCUUGG 1733 CCAAGCGG GCcgaaagGCGaGuCaaGGuCu CCCGGGAG 4413

1481 CGCUUGGG G CUCUACCG 1734 CGGUAGAG GCcgaaagGCGaGuCaaGGuCu CCCAAGCG 4414

1517 UACCGACC G UCCACGGG 1735 CCCGUGGA GCcgaaagGCGaGuCaaGGuCu GGUCGGUA 4415

1526 UCCACGGG G CGCACCUC 1736 GAGGUGCG GCcgaaagGCGaGuCaaGGuCu CCCGUGGA 4416

1553 GACUCCCC G UCUGUGCC 1737 GGCACAGA GCcgaaagGCGaGuCaaGGuCu GGGGAGUC 4417

1579 GCCGGACC G UGUGCACU 1738 AGUGCACA GCcgaaagGCGaGuCaaGGuCu GGUCCGGC 4418

1605 CUCUGCAC G UCGCAUGG 1739 CCAUGCGA GCcgaaagGCGaGuCaaGGuCu GUGCAGAG 4419

1622 AGACCACC G UGAACGCC 1740 GGCGUUCA GCcgaaagGCGaGuCaaGGuCu GGUGGUCU 4420

1649 UGCCCAAG G UCUUGCAU 1741 AUGCAAGA GCcgaaagGCGaGuCaaGGuCu CUUGGGCA 4421

1679 GACUUUCA G CAAUGUCA 1742 UGACAUUG GCcgaaagGCGaGuCaaGGuCu UGAAAGUC 4422

1703 ACCUUGAG G CAUACUUC 1743 GAAGUAUG GCcgaaagGCGaGuCaaGGuCu CUCAAGGU 4423

1732 UUUAAUGA G UGGGAGGA 1744 UCCUCCCA GCcgaaagGCGaGuCaaGGuCu UCAUUAAA 4424

1741 UGGGAGGA G UUGGGGGA 1745 UCCCCCAA GCcgaaagGCGaGuCaaGGuCu UCCUCCCA 4425

1754 GGGAGGAG G UUAGGUUA 1746 UAACCUAA GCcgaaagGCGaGuCaaGGuCu CUCCUCCC 4426

1759 GAGGUUAG G UUAAAGGU 1747 ACCUUUAA GCcgaaagGCGaGuCaaGGuCu CUAACCUC 4427

1766 GGUUAAAG G UCUUUGUA 1748 UACAAAGA GCcgaaagGCGaGuCaaGGuCu CUUUAACC 4428

1782 ACUAGGAG G CUGUAGGC 1749 GCCUACAG GCcgaaagGCGaGuCaaGGuCu CUCCUAGU 4429

1789 GGCUGUAG G CAUAAAUU 1750 AAUUUAUG GCcgaaagGCGaGuCaaGGuCu CUACAGCC 4430

1799 AUAAAUUG G UGUGUUCA 1751 UGAACACA GCcgaaagGCGaGuCaaGGuCu CAAUUUAU 4431

1811 GUUCACCA G CACCAUGC 1752 GCAUGGUG GCcgaaagGCGaGuCaaGGuCu UGGUGAAC 4432

Table 40

1870 CUGUUCAA G CCUCCAAG 1753 CUUGGAGG GCcgaaagGCGaGuCaaGGuCu UUGAACAG 4433

1878 GCCUCCAA G CUGUGCCU 1754 AGGCACAG GCcgaaagGCGaGuCaaGGuCu UUGGAGGC 4434

1890 UGCCUUGG G UGGCUUUG 1755 CAAAGCCA GCcgaaagGCGaGuCaaGGuCu CCAAGGCA 4435

1893 CUUGGGUG G CUUUGGGG 1756 CCCCAAAG GCcgaaagGCGaGuCaaGGuCu CACCCAAG 4436

1901 GCUUUGGG G CAUGGACA 1757 UGUCCAUG GCcgaaagGCGaGuCaaGGuCu CCCAAAGC 4437

1917 AUUGACCC G UAUAAAGA 1758 UCUUUAUA GCcgaaagGCGaGuCaaGGuCu GGGUCAAU 4438

1933 AAUUUGGA G CUUCUGUG 1759 CACAGAAG GCcgaaagGCGaGuCaaGGuCu UCCAAAUU 4439

1944 UCUGUGGA G UUACUCUC 1760 GAGAGUAA GCcgaaagGCGaGuCaaGGuCu UCCACAGA 4440

2023 AUCGGGGG G CCUUAGAG 1761 CUCUAAGG GCcgaaagGCGaGuCaaGGuCu CCCCCGAU 4441

2031 GCCUUAGA G UCUCCGGA 1762 UCCGGAGA GCcgaaagGCGaGuCaaGGuCu UCUAAGGC 4442

2062 ACCAUACG G CACUCAGG 1763 CCUGAGUG GCcgaaagGCGaGuCaaGGuCu CGUAUGGU 4443

2070 GCACUCAG G CAAGCUAU 1764 AUAGCUUG GCcgaaagGCGaGuCaaGGuCu CUGAGUGC 4444

2074 UCAGGCAA G CUAUUCUG 1765 CAGAAUAG GCcgaaagGCGaGuCaaGGuCu UUGCCUGA 4445

2090 GUGUUGGG G UGAGUUGA 1766 UCAACUCA GCcgaaagGCGaGuCaaGGuCu CCCAACAC 4446

2094 UGGGGUGA G UUGAUGAA 1767 UUCAUCAA GCcgaaagGCGaGuCaaGGuCu UCACCCCA 4447

2107 UGAAUCUA G CCACCUGG 1768 CCAGGUGG GCcgaaagGCGaGuCaaGGuCu UAGAUUCA 4448

2116 CCACCUGG G UGGGAAGU 1769 ACUUCCCA GCcgaaagGCGaGuCaaGGuCu CCAGGUGG 4449

2123 GGUGGGAA G UAAUUUGG 1770 CCAAAUUA GCcgaaagGCGaGuCaaGGuCu UUCCCACC 4450

2140 AAGAUCCA G CAUCCAGG 1771 CCUGGAUG GCcgaaagGCGaGuCaaGGuCu UGGAUCUU 4451

2155 GGGAAUUA G UAGUCAGC 1772 GCUGACUA GCcgaaagGCGaGuCaaGGuCu UAAUUCCC 4452

2158 AAUUAGUA G UCAGCUAU 1773 AUAGCUGA GCcgaaagGCGaGuCaaGGuCu UACUAAUU 4453

2162 AGUAGUCA G CUAUGUCA 1774 UGACAUAG GCcgaaagGCGaGuCaaGGuCu UGACUACU 4454

2173 AUGUCAAC G UUAAUAUG 1775 CAUAUUAA GCcgaaagGCGaGuCaaGGuCu GUUGACAU 4455

2183 UAAUAUGG G CCUAAAAA 1776 UUUUUAGG GCcgaaagGCGaGuCaaGGuCu CCAUAUUA 4456

2208 CUAUUGUG G UUUCACAU 1777 AUGUGAAA GCcgaaagGCGaGuCaaGGuCu CACAAUAG 4457

2235 ACUUUUGG G CGAGAAAC 1778 GUUUCUCG GCcgaaagGCGaGuCaaGGuCu CCAAAAGU 4458

2260 AAUAUUUG G UGUCUUUU 1779 AAAAGACA GCcgaaagGCGaGuCaaGGuCu CAAAUAUU 4459

2272 CUUUUGGA G UGUGGAUU 1780 AAUCCACA GCcgaaagGCGaGuCaaGGuCu UCCAAAAG 4460

2360 ACGAAGAG G CAGGUCCC 1781 GGGACCUG GCcgaaagGCGaGuCaaGGuCu CUCUUCGU 4461

2364 AGAGGCAG G UCCCCUAG 1782 CUAGGGGA GCcgaaagGCGaGuCaaGGuCu CUGCCUCU 4462

2403 AGACGAAG G UCUCAAUC 1783 GAUUGAGA GCcgaaagGCGaGuCaaGGuCu CUUCGUCU 4463

2417 AUCGCCGC G UCGCAGAA 1784 UUCUGCGA GCcgaaagGCGaGuCaaGGuCu GCGGCGAU 4464

2454 CAAUGUUA G UAUUCCUU 1785 AAGGAAUA GCcgaaagGCGaGuCaaGGuCu UAACAUUG 4465

2474 CACAUAAG G UGGGAAAC 1786 GUUUCCCA GCcgaaagGCGaGuCaaGGuCu CUUAUGUG 4466

Table 40

2491 UUUACGGG G CUUUAUUC 1787 GAAUAAAG GCcgaaagGCGaGuCaaGGuCu CCCGUAAA 4467

2507 CUUCUACG G UACCUUGC 1788 GCAAGGUA GCcgaaagGCGaGuCaaGGuCu CGUAGAAG 4468

2530 CCUAAAUG G CAAACUCC 1789 GGAGUUUG GCcgaaagGCGaGuCaaGGuCu CAUUUAGG 4469

2587 AGAUGUAA G CAAUUUGU 1790 ACAAAUUG GCcgaaagGCGaGuCaaGGuCu UUACAUCU 4470

2599 UUUGUGGG G CCCCUUAC 1791 GUAAGGGG GCcgaaagGCGaGuCaaGGuCu CCCACAAA 4471

2609 CCCUUACA G UAAAUGAA 1792 UUCAUUUA GCcgaaagGCGaGuCaaGGuCu UGUAAGGG 4472

2650 CCUGCUAG G UUUUAUCC 1793 GGAUAAAA GCcgaaagGCGaGuCaaGGuCu CUAGCAGG 4473

2701 AUCAAACC G UAUUAUCC 1794 GGAUAAUA GCcgaaagGCGaGuCaaGGuCu GGUUUGAU 4474

2713 UAUCCAGA G UAUGUAGU 1795 ACUACAUA GCcgaaagGCGaGuCaaGGuCu UCUGGAUA 4475

2720 AGUAUGUA G UUAAUCAU 1796 AUGAUUAA GCcgaaagGCGaGuCaaGGuCu UACAUACU 4476

2768 UUUGGAAG G CGGGGAUC 1797 GAUCCCCG GCcgaaagGCGaGuCaaGGuCu CUUCCAAA 4477

2791 AAAAGAGA G UCCACACG 1798 CGUGUGGA GCcgaaagGCGaGuCaaGGuCu UCUCUUUU 4478

2799 GUCCACAC G UAGCGCCU 1799 AGGCGCUA GCcgaaagGCGaGuCaaGGuCu GUGUGGAC 4479

2802 CACACGUA G CGCCUCAU 1800 AUGAGGCG GCcgaaagGCGaGuCaaGGuCu UACGUGUG 4480

2818 UUUUGCGG G UCACCAUA 1801 UAUGGUGA GCcgaaagGCGaGuCaaGGuCu CCGCAAAA 4481

2848 GAUCUACA G CAUGGGAG 1802 CUCCCAUG GCcgaaagGCGaGuCaaGGuCu UGUAGAUC 4482

2857 CAUGGGAG G UUGGUCUU 1803 AAGACCAA GCcgaaagGCGaGuCaaGGuCu CUCCCAUG 4483

2861 GGAGGUUG G UCUUCCAA 1804 UUGGAAGA GCcgaaagGCGaGuCaaGGuCu CAACCUCC 4484

2881 UCGAAAAG G CAUGGGGA 1805 UCCCCAUG GCcgaaagGCGaGuCaaGGuCu CUUUUCGA 4485

2936 GAUCAUCA G UUGGACCC 1806 GGGUCCAA GCcgaaagGCGaGuCaaGGuCu UGAUGAUC 4486

2955 CAUUCAAA G CCAACUCA 1807 UGAGUUGG GCcgaaagGCGaGuCaaGGuCu UUUGAAUG 4487

2964 CCAACUCA G UAAAUCCA 1808 UGGAUUUA GCcgaaagGCGaGuCaaGGuCu UGAGUUGG 4488

3005 GACAACUG G CCGGACGC 1809 GCGUCCGG GCcgaaagGCGaGuCaaGGuCu CAGUUGUC 4489

3021 CCAACAAG G UGGGAGUG 1810 CACUCCCA GCcgaaagGCGaGuCaaGGuCu CUUGUUGG 4490

3027 AGGUGGGA G UGGGAGCA 1811 UGCUCCCA GCcgaaagGCGaGuCaaGGuCu UCCCACCU 4491

3033 GAGUGGGA G CAUUCGGG 1812 CCCGAAUG GCcgaaagGCGaGuCaaGGuCu UCCCACUC 4492

3041 GCAUUCGG G CCAGGGUU 1813 AACCCUGG GCcgaaagGCGaGuCaaGGuCu CCGAAUGC 4493

3047 GGGCCAGG G UUCACCCC 1814 GGGGUGAA GCcgaaagGCGaGuCaaGGuCu CCUGGCCC 4494

3077 CUGUUGGG G UGGAGCCC 1815 GGGCUCCA GCcgaaagGCGaGuCaaGGuCu CCCAACAG 4495

3082 GGGGUGGA G CCCUCACG 1816 CGUGAGGG GCcgaaagGCGaGuCaaGGuCu UCCACCCC 4496

3097 CGCUCAGG G CCUACUCA 1817 UGAGUAGG GCcgaaagGCGaGuCaaGGuCu CCUGAGCG 4497

3117 CUGUGCCA G CAGCUCCU 1818 AGGAGCUG GCcgaaagGCGaGuCaaGGuCu UGGCACAG 4498

3120 UGCCAGCA G CUCCUCCU 1819 AGGAGGAG GCcgaaagGCGaGuCaaGGuCu UGCUGGCA 4499

3146 ACCAAUCG G CAGUCAGG 1820 CCUGACUG GCcgaaagGCGaGuCaaGGuCu CGAUUGGU 4500

Table 40

Input Sequence = AF100308. Cut Site = YG/M or UG/U.

Stem Length = 8 . Core Sequence = GCcgaaagGCGaGuCaaGGuCu

AF100308 (Hepatitis B virus strain 2-18, 3215 bp)

Table 41 Table 41: Human HBV DNAzyme and Substrate Sequence

Pos Substrate Seq ID DNAzyme Rz Seq ID

508 CAACCAGC A CCGGACCA 833 TGGTCCGG GGCTAGCTACAACGA GCTGGTTG 4505

1632 GAACGCCC A CAGGAACC 1096 GGTTCCTG GGCTAGCTACAACGA GGGCGTTC 4506

2992 CAACCCGC A CAAGGACA 1376 TGTCCTTG GGCTAGCTACAACGA GCGGGTTG 4507

61 ACUUUCCU G CUGGUGGC 1448 GCCACCAG GGCTAGCTACAACGA AGGAAAGT 4508

94 UGAGCCCU G CUCAGAAU 1450 ATTCTGAG GGCTAGCTACAACGA AGGGCTCA 4509

112 CUGUCUCU G CCAUAUCG 1451 CGATATGG GGCTAGCTACAACGA AGAGACAG 4510

169 AGAACAUC G CAUCAGGA 1454 TCCTGATG GGCTAGCTACAACGA GATGTTCT 4511

192 GGACCCCU G CUCGUGUU 1455 AACACGAG GGCTAGCTACAACGA AGGGGTCC 4512

315 CAAAAUUC G CAGUCCCA 1457 TGGGACTG GGCTAGCTACAACGA GAATTTTG 4513

374 UGGUUAUC G CUGGAUGU 1458 ACATCCAG GGCTAGCTACAACGA GATAACCA 4514

387 AUGUGUCU G CGGCGUUU 1459 AAACGCCG GGCTAGCTACAACGA AGACACAT 4515

410 CUUCCUCU G CAUCCUGC 1460 GCAGGATG GGCTAGCTACAACGA AGAGGAAG 4516

417 UGCAUCCU G CUGCUAUG 1461 CATAGCAG GGCTAGCTACAACGA AGGATGCA 4517

420 AUCCUGCU G CUAUGCCU 1462 AGGCATAG GGCTAGCTACAACGA AGCAGGAT 4518

425 GCUGCUAU G CCUCAUCU 1463 AGATGAGG GGCTAGCTACAACGA ATAGCAGC 4519

468 GGUAUGUU G CCCGUUUG 1464 CAAACGGG GGCTAGCTACAACGA AACATACC 4520

518 CGGACCAU G CAAAACCU 1465 AGGTTTTG GGCTAGCTACAACGA ATGGTCCG 4521

527 CAAAACCU G CACAACUC 1466 GAGTTGTG GGCTAGCTACAACGA AGGTTTTG 4522

538 CAACUCCU G CUCAAGGA 1467 TCCTTGAG GGCTAGCTACAACGA AGGAGTTG 4523

569 CUCAUGUU G CUGUACAA 1468 TTGTACAG GGCTAGCTACAACGA AACATGAG 4524

596 CGGAAACU G CACCUGUA 1469 TACAGGTG GGCTAGCTACAACGA AGTTTCCG 4525

631 GGGCUUUC G CAAAAUAC 1470 GTATTTTG GGCTAGCTACAACGA GAAAGCCC 4526

687 UUACUAGU G CCAUUUGU 1471 ACAAATGG GGCTAGCTACAACGA ACTAGTAA 4527

795 CCCUUUAU G CCGCUGUU 1474 AACAGCGG GGCTAGCTACAACGA ATAAAGGG 4528

798 UUUAUGCC G CUGUUACC 1475 GGTAACAG GGCTAGCTACAACGA GGCATAAA 4529

911 GGCACAUU G CCACAGGA 1476 TCCTGTGG GGCTAGCTACAACGA AATGTGCC 4530

1020 UGGGGUUU G CCGCCCCU 1479 AGGGGCGG GGCTAGCTACAACGA AAACCCCA 4531

1023 GGUUUGCC G CCCCUUUC 1480 GAAAGGGG GGCTAGCTACAACGA GGCAAACC 4532

1034 CCUUUCAC G CAAUGUGG 1481 CCACATTG GGCTAGCTACAACGA GTGAAAGG 4533

1050 GAUAUUCU G CUUUAAUG 1482 CATTAAAG GGCTAGCTACAACGA AGAATATC 4534

1058 GCUUUAAU G CCUUUAUA 1483 TATAAAGG GGCTAGCTACAACGA ATTAAAGC 4535

1068 CUUUAUAU G CAUGCAUA 1484 TATGCATG GGCTAGCTACAACGA ATATAAAG 4536

1072 AUAUGCAU G CAUACAAG 1485 CTTGTATG GGCTAGCTACAACGA ATGCATAT 4537

1103 ACUUUCUC G CCAACUUA 1486 TAAGTTGG GGCTAGCTACAACGA GAGAAAGT 4538

1155 ACCCCGUU G CUCGGCAA 1488 TTGCCGAG GGCTAGCTACAACGA AACGGGGT 4539

1177 UGGUCUAU G CCAAGUGU 1489 ACACTTGG GGCTAGCTACAACGA ATAGACCA 4540

1188 AAGUGUUU G CUGACGCA 1490 TGCGTCAG GGCTAGCTACAACGA AAACACTT 4541

1194 UUGCUGAC G CAACCCCC 1492 GGGGGTTG GGCTAGCTACAACGA GTCAGCAA 4542

1234 CCAUCAGC G CAUGCGUG 1493 CACGCATG GGCTAGCTACAACGA GCTGATGG 4543

1238 CAGCGCAU G CGUGGAAC 1494 GTTCCACG GGCTAGCTACAACGA ATGCGCTG 4544

1262 UCUCCUCU G CCGAUCCA 1495 TGGATCGG GGCTAGCTACAACGA AGAGGAGA 4545

1275 UCCAUACC G CGGAACUC 1497 GAGTTCCG GGCTAGCTACAACGA GGTATGGA 4546

1290 UCCUAGCC G CUUGUUUU 1498 AAAACAAG GGCTAGCTACAACGA GGCTAGGA 4547

1299 CUUGUUUU G CUCGCAGC 1499 GCTGCGAG GGCTAGCTACAACGA AAAACAAG 4548

1303 UUUUGCUC G CAGCAGGU 1500 ACCTGCTG GGCTAGCTACAACGA GAGCAAAA 4549

1349 UCUGUCGU G CUCUCCCG 1502 CGGGAGAG GGCTAGCTACAACGA ACGACAGA 4550

1357 GCUCUCCC G CAAAUAUA 1503 TATATTTG GGCTAGCTACAACGA GGGAGAGC 4551 Taσie i

1382 CCAUGGCU G CUAGGCUG 1504 CAGCCTAG GGCTAGCTACAACGA AGCCATGG 4552

1392 UAGGCUGU G CUGCCAAC 1505 GTTGGCAG GGCTAGCTACAACGA ACAGCCTA 4553

1395 GCUGUGCU G CCAACUGG 1506 CCAGTTGG GGCTAGCTACAACGA AGCACAGC 4554

1411 GAUCCUAC G CGGGACGU 1507 ACGTCCCG GGCTAGCTACAACGA GTAGGATC 4555

1442 CCGUCGGC G CUGAAUCC 1508 GGATTCAG GGCTAGCTACAACGA GCCGACGG 4556

1452 UGAAUCCC G CGGACGAC 1510 GTCGTCCG GGCTAGCTACAACGA GGGATTCA 4557

1474 CCGGGGCC G CUUGGGGC 1512 GCCCCAAG GGCTAGCTACAACGA GGCCCCGG 4558

1489 GCUCUACC G CCCGCUUC 1513 GAAGCGGG GGCTAGCTACAACGA GGTAGAGC 4559

1493 UACCGCCC G CUUCUCCG 1514 CGGAGAAG GGCTAGCTACAACGA GGGCGGTA 4560

1501 GCUUCUCC G CCUAUUGU 1515 ACAATAGG GGCTAGCTACAACGA GGAGAAGC 4561

1528 CACGGGGC G CACCUCUC 1517 GAGAGGTG GGCTAGCTACAACGA GCCCCGTG 4562

1542 CUCUUUAC G CGGACUCC 1518 GGAGTCCG GGCTAGCTACAACGA GTAAAGAG 4563

1559 CCGUCUGU G CCUUCUCA 1519 TGAGAAGG GGCTAGCTACAACGA ACAGACGG 4564

1571 UCUCAUCU G CCGGACCG 1520 CGGTCCGG GGCTAGCTACAACGA AGATGAGA 4565

1583 GACCGUGU G CACUUCGC 1521 GCGAAGTG GGCTAGCTACAACGA ACACGGTC 4566

1590 UGCACUUC G CUUCACCU 1522 AGGTGAAG GGCTAGCTACAACGA GAAGTGCA 4567

1601 UCACCUCU G CACGUCGC 1523 GCGACGTG GGCTAGCTACAACGA AGAGGTGA 4568

1608 UGCACGUC G CAUGGAGA 1524 TCTCCATG GGCTAGCTACAACGA GACGTGCA 4569

1628 CCGUGAAC G CCCACAGG 1526 CCTGTGGG GGCTAGCTACAACGA GTTCACGG 4570

1642 AGGAACCU G CCCAAGGU 1527 ACCTTGGG GGCTAGCTACAACGA AGGTTCCT 4571

1654 AAGGUCUU G CAUAAGAG 1528 CTCTTATG GGCTAGCTACAACGA AAGACCTT 4572

1818 AGCACCAU G CAACUUUU 1533 AAAAGTTG GGCTAGCTACAACGA ATGGTGCT 4573

1835 UCACCUCU G CCUAAUCA 1534 TGATTAGG GGCTAGCTACAACGA AGAGGTGA 4574

1883 CAAGCUGU G CCUUGGGU 1535 ACCCAAGG GGCTAGCTACAACGA ACAGCTTG 4575

1959 UCUUUUUU G CCUUCUGA 1537 TCAGAAGG GGCTAGCTACAACGA AAAAAAGA 4576

2002 UCGACACC G CCUCUGCU 1541 AGCAGAGG GGCTAGCTACAACGA GGTGTCGA 4577

2008 CCGCCUCU G CUCUGUAU 1542 ATACAGAG GGCTAGCTACAACGA AGAGGCGG 4578

2282 GUGGAUUC G CACUCCUC 1548 GAGGAGTG GGCTAGCTACAACGA GAATCCAC 4579

2293 CUCCUCCU G CAUAUAGA 1549 TCTATATG GGCTAGCTACAACGA AGGAGGAG 4580

2311 CACCAAAU G CCCCUAUC 1550 GATAGGGG GGCTAGCTACAACGA ATTTGGTG 4581

2388 ACUCCCUC G CCUCGCAG 1552 CTGCGAGG GGCTAGCTACAACGA GAGGGAGT 4582

2393 CUCGCCUC G CAGACGAA 1553 TTCGTCTG GGCTAGCTACAACGA GAGGCGAG 4583

2412 UCUCAAUC G CCGCGUCG 1555 CGACGCGG GGCTAGCTACAACGA GATTGAGA 4584

2415 CAAUCGCC G CGUCGCAG 1556 CTGCGACG GGCTAGCTACAACGA GGCGATTG 4585

2420 GCCGCGUC G CAGAAGAU 1557 ATCTTCTG GGCTAGCTACAACGA GACGCGGC 4586

2514 GGUACCUU G CUUUAAUC 1558 GATTAAAG GGCTAGCTACAACGA AAGGTACC 4587

2560 AUUCAUUU G CAGGAGGA 1560 TCCTCCTG GGCTAGCTACAACGA AAATGAAT 4588

2641 UUAACUAU G CCUGCUAG 1563 CTAGCAGG GGCTAGCTACAACGA ATAGTTAA 4589

2645 CUAUGCCU G CUAGGUUU 1564 AAACCTAG GGCTAGCTACAACGA AGGCATAG 4590

2677 AAAUAUUU G CCCUUAGA 1565 TCTAAGGG GGCTAGCTACAACGA AAATATTT 4591

2740 UUCCAGAC G CGACAUUA 1566 TAATGTCG GGCTAGCTACAACGA GTCTGGAA 4592

2804 CACGUAGC G CCUCAUUU 1568 AAATGAGG GGCTAGCTACAACGA GCTACGTG 4593

2814 CUCAUUUU G CGGGUCAC 1569 GTGACCCG GGCTAGCTACAACGA AAAATGAG 4594

2946 UGGACCCU G CAUUCAAA 1572 TTTGAATG GGCTAGCTACAACGA AGGGTCCA 4595

2990 CUCAACCC G CACAAGGA 1573 TCCTTGTG GGCTAGCTACAACGA GGGTTGAG 4596

3012 GGCCGGAC G CCAACAAG 1574 CTTGTTGG GGCTAGCTACAACGA GTCCGGCC 4597

3090 GCCCUCAC G CUCAGGGC 1575 GCCCTGAG GGCTAGCTACAACGA GTGAGGGC 4598

3113 ACAACUGU G CCAGCAGC 1576 GCTGCTGG GGCTAGCTACAACGA ACAGTTGT 4599

3132 CUCCUCCU G CCUCCACC 1577 GGTGGAGG GGCTAGCTACAACGA AGGAGGAG 4600

51 AGGGCCCU G UACUUUCC 1578 GGAAAGTA GGCTAGCTACAACGA AGGGCCCT 4601

106 AGAAUACU G UCUCUGCC 1579 GGCAGAGA GGCTAGCTACAACGA AGTATTCT 4602 TaDie i

148 GGGACCCU G UACCGAAC 1580 GTTCGGTA GGCTAGCTACAACGA AGGGTCCC 4603

198 CUGCUCGU G UUACAGGC 1581 GCCTGTAA GGCTAGCTACAACGA ACGAGCAG 4604

219 UUUUUCUU G UUGACAAA 1582 TTTGTCAA GGCTAGCTACAACGA AAGAAAAA 4605

297 ACACCCGU G UGUCUUGG 1583 CCAAGACA GGCTAGCTACAACGA ACGGGTGT 4606

299 ACCCGUGU G UCUUGGCC 1584 GGCCAAGA GGCTAGCTACAACGA ACACGGGT 4607

347 ACCAACCU G UUGUCCUC 1585 GAGGACAA GGCTAGCTACAACGA AGGTTGGT 4608

350 AACCUGUU G UCCUCCAA 1586 TTGGAGGA GGCTAGCTACAACGA AACAGGTT 4609

362 UCCAAUUU G UCCUGGUU 1587 AACCAGGA GGCTAGCTACAACGA AAATTGGA 4610

381 CGCUGGAU G UGUCUGCG 1588 CGCAGACA GGCTAGCTACAACGA ATCCAGCG 4611

383 CUGGAUGU G UCUGCGGC 1589 GCCGCAGA GGCTAGCTACAACGA ACATCCAG 4612

438 AUCUUCUU G UUGGUUCU 1590 AGAACCAA GGCTAGCTACAACGA AAGAAGAT 4613

465 CAAGGUAU G UUGCCCGU 1591 ACGGGCAA GGCTAGCTACAACGA ATACCTTG 4614

476 GCCCGUUU G UCCUCUAA 1592 TTAGAGGA GGCTAGCTACAACGA AAACGGGC 4615

555 ACCUCUAU G UUUCCCUC 1593 GAGGGAAA GGCTAGCTACAACGA ATAGAGGT 4616

566 UCCCUCAU G UUGCUGUA 1594 TACAGCAA GGCTAGCTACAACGA ATGAGGGA 4617

572 AUGUUGCU G UACAAAAC 1595 GTTTTGTA GGCTAGCTACAACGA AGCAACAT 4618

602 CUGCACCU G UAUUCCCA 1596 TGGGAATA GGCTAGCTACAACGA AGGTGCAG 4619

694 UGCCAUUU G UUCAGUGG 1597 CCACTGAA GGCTAGCTACAACGA AAATGGCA 4620

724 CCCCCACU G UCUGGCUU 1598 AAGCCAGA GGCTAGCTACAACGA AGTGGGGG 4621

750 UGGAUGAU G UGGUUUUG 1599 CAAAACCA GGCTAGCTACAACGA ATCATCCA 4622

771 CCAAGUCU G UACAACAU 1600 ATGTTGTA GGCTAGCTACAACGA AGACTTGG 4623

801 AUGCCGCU G UUACCAAU 1601 ATTGGTAA GGCTAGCTACAACGA AGCGGCAT 4624

818 UUUCUUUU G UCUUUGGG 1602 CCCAAAGA GGCTAGCTACAACGA AAAAGAAA 4625

888 UGGGAUAU G UAAUUGGG 1603 CCCAATTA GGCTAGCTACAACGA ATATCCCA 4626

927 AACAUAUU G UACAAAAA 1604 TTTTTGTA GGCTAGCTACAACGA AATATGTT 4627

944 AUCAAAAU G UGUUUUAG 1605 CTAAAACA GGCTAGCTACAACGA ATTTTGAT 4628

946 CAAAAUGU G UUUUAGGA 1606 TCCTAAAA GGCTAGCTACAACGA ACATTTTG 4629

963 AACUUCCU G UAAACAGG 1607 CCTGTTTA GGCTAGCTACAACGA AGGAAGTT 4630

991 GAAAGUAU G UCAACGAA 1608 TTCGTTGA GGCTAGCTACAACGA ATACTTTC 4631

1002 AACGAAUU G UGGGUCUU 1609 AAGACCCA GGCTAGCTACAACGA AATTCGTT 4632

1039 CACGCAAU G UGGAUAUU 1610 AATATCCA GGCTAGCTACAACGA ATTGCGTG 4633

1137 AACAGUAU G UGAACCUU 1611 AAGGTTCA GGCTAGCTACAACGA ATACTGTT 4634

1184 UGCCAAGU G UUUGCUGA 1612 TCAGCAAA GGCTAGCTACAACGA ACTTGGCA 4635

1251 GAACCUUU G UGUCUCCU 1613 AGGAGACA GGCTAGCTACAACGA AAAGGTTC 4636

1253 ACCUUUGU G UCUCCUCU 1614 AGAGGAGA GGCTAGCTACAACGA ACAAAGGT 4637

1294 AGCCGCUU G UUUUGCUC 1615 GAGCAAAA GGCTAGCTACAACGA AAGCGGCT 4638

1344 ACAAUUCU G UCGUGCUC 1616 GAGCACGA GGCTAGCTACAACGA AGAATTGT 4639

1390 GCUAGGCU G UGCUGCCA 1617 TGGCAGCA GGCTAGCTACAACGA AGCCTAGC 4640

1425 CGUCCUUU G UUUACGUC 1618 GACGTAAA GGCTAGCTACAACGA AAAGGACG 4641

1508 CGCCUAUU G UACCGACC 1619 GGTCGGTA GGCTAGCTACAACGA AATAGGCG 4642

1557 CCCCGUCU G UGCCUUCU 1620 AGAAGGCA GGCTAGCTACAACGA AGACGGGG 4643

1581 CGGACCGU G UGCACUUC 1621 GAAGTGCA GGCTAGCTACAACGA ACGGTCCG 4644

1684 UCAGCAAU G UCAACGAC 1622 GTCGTTGA GGCTAGCTACAACGA ATTGCTGA 4645

1719 CAAAGACU G UGUGUUUA 1623 TAAACACA GGCTAGCTACAACGA AGTCTTTG 4646

1721 AAGACUGU G UGUUUAAU 1624 ATTAAACA GGCTAGCTACAACGA ACAGTCTT 4647

1723 GACUGUGU G UUUAAUGA 1625 TCATTAAA GGCTAGCTACAACGA ACACAGTC 4648

1772 AGGUCUUU G UACUAGGA 1626 TCCTAGTA GGCTAGCTACAACGA AAAGACCT 4649

1785 AGGAGGCU G UAGGCAUA 1627 TATGCCTA GGCTAGCTACAACGA AGCCTCCT 4650

1801 AAAUUGGU G UGUUCACC 1628 GGTGAACA GGCTAGCTACAACGA ACCAATTT 4651

1803 AUUGGUGU G UUCACCAG 1629 CTGGTGAA GGCTAGCTACAACGA ACACCAAT 4652

1850 CAUCUCAU G UUCAUGUC 1630 GACATGAA GGCTAGCTACAACGA ATGAGATG 4653 Taσie 4 1

1856 AUGUUCAU G UCCUACUG 1631 CAGTAGGA GGCTAGCTACAACGA ATGAACAT 4654

1864 GUCCUACU G UUCAAGCC 1632 GGCTTGAA GGCTAGCTACAACGA AGTAGGAC 4655

1881 UCCAAGCU G UGCCUUGG 1633 CCAAGGCA GGCTAGCTACAACGA AGCTTGGA 4656

1939 GAGCUUCU G UGGAGUUA 1634 TAACTCCA GGCTAGCTACAACGA AGAAGCTC 4657

2013 UCUGCUCU G UAUCGGGG 1635 CCCCGATA GGCTAGCTACAACGA AGAGCAGA 4658

2045 GGAACAUU G UUCACCUC 1636 GAGGTGAA GGCTAGCTACAACGA AATGTTCC 4659

2082 GCUAUUCU G UGUUGGGG 1637 CCCCAACA GGCTAGCTACAACGA AGAATAGC 4660

2084 UAUUCUGU G UUGGGGUG 1638 CACCCCAA GGCTAGCTACAACGA ACAGAATA 4661

2167 UCAGCUAU G UCAACGUU 1639 AACGTTGA GGCTAGCTACAACGA ATAGCTGA 4662

2205 CAACUAUU G UGGUUUCA 1640 TGAAACCA GGCTAGCTACAACGA AATAGTTG 4663

2222 CAUUUCCU G UCUUACUU 1641 AAGTAAGA GGCTAGCTACAACGA AGGAAATG 4664

2245 GAGAAACU G UUCUUGAA 1642 TTCAAGAA GGCTAGCTACAACGA AGTTTCTC 4665

2262 UAUUUGGU G UCUUUUGG 1643 CCAAAAGA GGCTAGCTACAACGA ACCAAATA 4666

2274 UUUGGAGU G UGGAUUCG 1644 CGAATCCA GGCTAGCTACAACGA ACTCCAAA 4667

2344 AAACUACU G UUGUUAGA 1645 TCTAACAA GGCTAGCTACAACGA AGTAGTTT 4668

2347 CUACUGUU G UUAGACGA 1646 TCGTCTAA GGCTAGCTACAACGA AACAGTAG 4669

2450 AUCUCAAU G UUAGUAUU 1647 AATACTAA GGCTAGCTACAACGA ATTGAGAT 4670

2573 AGGACAUU G UUGAUAGA 1648 TCTATCAA GGCTAGCTACAACGA AATGTCCT 4671

2583 UGAUAGAU G UAAGCAAU 1649 ATTGCTTA GGCTAGCTACAACGA ATCTATCA 4672

2594 AGCAAUUU G UGGGGCCC 1650 GGGCCCCA GGCTAGCTACAACGA AAATTGCT 4673

2663 AUCCCAAU G UUACUAAA 1651 TTTAGTAA GGCTAGCTACAACGA ATTGGGAT 4674

2717 CAGAGUAU G UAGUUAAU 1652 ATTAACTA GGCTAGCTACAACGA ATACTCTG 4675

2901 AUCUUUCU G UCCCCAAU 1653 ATTGGGGA GGCTAGCTACAACGA AGAAAGAT 4676

3071 GGGGGACU G UUGGGGUG 1654 CACCCCAA GGCTAGCTACAACGA AGTCCCCC 4677

3111 UCACAACU G UGCCAGCA 1655 TGCTGGCA GGCTAGCTACAACGA AGTTGTGA 4678

40 AUCCCAGA G UCAGGGCC 1656 GGCCCTGA GGCTAGCTACAACGA TCTGGGAT 4679

46 GAGUCAGG G CCCUGUAC 1657 GTACAGGG GGCTAGCTACAACGA CCTGACTC 4680

65 UCCUGCUG G UGGCUCCA 1658 TGGAGCCA GGCTAGCTACAACGA CAGCAGGA 4681

68 UGCUGGUG G CUCCAGUU 1659 AACTGGAG GGCTAGCTACAACGA CACCAGCA 4682

74 UGGCUCCA G UUCAGGAA 1660 TTCCTGAA GGCTAGCTACAACGA TGGAGCCA 4683

85 CAGGAACA G UGAGCCCU 1661 AGGGCTCA GGCTAGCTACAACGA TGTTCCTG 4684

89 AACAGUGA G CCCUGCUC 1662 GAGCAGGG GGCTAGCTACAACGA TCACTGTT 4685

120 GCCAUAUC G UCAAUCUU 1663 AAGATTGA GGCTAGCTACAACGA GATATGGC 4686

196 CCCUGCUC G UGUUACAG 1664 CTGTAACA GGCTAGCTACAACGA GAGCAGGG 4687

205 UGUUACAG G CGGGGUUU 1665 AAACCCCG GGCTAGCTACAACGA CTGTAACA 4688

210 CAGGCGGG G UUUUUCUU 1666 AAGAAAAA GGCTAGCTACAACGA CCCGCCTG 4689

248 ACCACAGA G UCUAGACU 1667 AGTCTAGA GGCTAGCTACAACGA TCTGTGGT 4690

258 CUAGACUC G UGGUGGAC 1668 GTCCACCA GGCTAGCTACAACGA GAGTCTAG 4691

261 GACUCGUG G UGGACUUC 1669 GAAGTCCA GGCTAGCTACAACGA CACGAGTC 4692

295 GAACACCC G UGUGUCUU 1670 AAGACACA GGCTAGCTACAACGA GGGTGTTC 4693

305 GUGUCUUG G CCAAAAUU 1671 AATTTTGG GGCTAGCTACAACGA CAAGACAC 4694

318 AAUUCGCA G UCCCAAAU 1672 ATTTGGGA GGCTAGCTACAACGA TGCGAATT 4695

332 AAUCUCCA G UCACUCAC 1673 GTGAGTGA GGCTAGCTACAACGA TGGAGATT 4696

368 UUGUCCUG G UUAUCGCU 1674 AGCGATAA GGCTAGCTACAACGA CAGGACAA 4697

390 UGUCUGCG G CGUUUUAU 1675 ATAAAACG GGCTAGCTACAACGA CGCAGACA 4698

392 UCUGCGGC G UUUUAUCA 1676 TGATAAAA GGCTAGCTACAACGA GCCGCAGA 4699

442 UCUUGUUG G UUCUUCUG 1677 CAGAAGAA GGCTAGCTACAACGA CAACAAGA 4700

461 CUAUCAAG G UAUGUUGC 1678 GCAACATA GGCTAGCTACAACGA CTTGATAG 4701

472 UGUUGCCC G UUUGUCCU 1679 AGGACAAA GGCTAGCTACAACGA GGGCAACA 4702

506 AACAACCA G CACCGGAC 1680 GTCCGGTG GGCTAGCTACAACGA TGGTTGTT 4703

625 CAUCUUGG G CUUUCGCA 1681 TGCGAAAG GGCTAGCTACAACGA CCAAGATG 4704 Taoie 1

648 CUAUGGGA G UGGGCCUC 1682 GAGGCCCA GGCTAGCTACAACGA TCCCATAG 4705

652 GGGAGUGG G CCUCAGUC 1683 GACTGAGG GGCTAGCTACAACGA CCACTCCC 4706

658 GGGCCUCA G UCCGUUUC 1684 GAAACGGA GGCTAGCTACAACGA TGAGGCCC 4707

662 CUCAGUCC G UUUCUCUU 1685 AAGAGAAA GGCTAGCTACAACGA GGACTGAG 4708

672 UUCUCUUG G CUCAGUUU 1686 AAACTGAG GGCTAGCTACAACGA CAAGAGAA 4709

677 UUGGCUCA G UUUACUAG 1687 CTAGTAAA GGCTAGCTACAACGA TGAGCCAA 4710

685 GUUUACUA G UGCCAUUU 1688 AAATGGCA GGCTAGCTACAACGA TAGTAAAC 4711

699 UUUGUUCA G UGGUUCGU 1689 ACGAACCA GGCTAGCTACAACGA TGAACAAA 4712

702 GUUCAGUG G UUCGUAGG 1690 CCTACGAA GGCTAGCTACAACGA CACTGAAC 4713

706 AGUGGUUC G UAGGGCUU 1691 AAGCCCTA GGCTAGCTACAACGA GAACCACT 4714

711 UUCGUAGG G CUUUCCCC 1692 GGGGAAAG GGCTAGCTACAACGA CCTACGAA 4715

729 ACUGUCUG G CUUUCAGU 1693 ACTGAAAG GGCTAGCTACAACGA CAGACAGT 4716

736 GGCUUUCA G UUAUAUGG 1694 CCATATAA GGCTAGCTACAACGA TGAAAGCC 4717

753 AUGAUGUG G UUUUGGGG 1695 CCCCAAAA GGCTAGCTACAACGA CACATCAT 4718

762 UUUUGGGG G CCAAGUCU 1696 AGACTTGG GGCTAGCTACAACGA CCCCAAAA 4719

767 GGGGCCAA G UCUGUACA 1697 TGTACAGA GGCTAGCTACAACGA TTGGCCCC 4720

785 CAUCUUGA G UCCCUUUA 1698 TAAAGGGA GGCTAGCTACAACGA TCAAGATG 4721

826 GUCUUUGG G UAUACAUU 1699 AATGTATA GGCTAGCTACAACGA CCAAAGAC 4722

898 AAUUGGGA G UUGGGGCA 1700 TGCCCCAA GGCTAGCTACAACGA TCCCAATT 4723

904 GAGUUGGG G CACAUUGC 1701 GCAATGTG GGCTAGCTACAACGA CCCAACTC 4724

971 GUAAACAG G CCUAUUGA 1702 TCAATAGG GGCTAGCTACAACGA CTGTTTAC 4725

987 AUUGGAAA G UAUGUCAA 1703 TTGACATA GGCTAGCTACAACGA TTTCCAAT 4726

1006 AAUUGUGG G UCUUUUGG 1704 CCAAAAGA GGCTAGCTACAACGA CCACAATT 4727

1016 CUUUUGGG G UUUGCCGC 1705 GCGGCAAA GGCTAGCTACAACGA CCCAAAAG 4728

1080 GCAUACAA G CAAAACAG 1706 CTGTTTTG GGCTAGCTACAACGA TTGTATGC 4729

1089 CAAAACAG G CUUUUACU 1707 AGTAAAAG GGCTAGCTACAACGA CTGTTTTG 4730

1116 CUUACAAG G CCUUUCUA 1708 TAGAAAGG GGCTAGCTACAACGA CTTGTAAG 4731

1126 CUUUCUAA G UAAACAGU 1709 ACTGTTTA GGCTAGCTACAACGA TTAGAAAG 4732

1133 AGUAAACA G UAUGUGAA 1710 TTCACATA GGCTAGCTACAACGA TGTTTACT 4733

1152 UUUACCCC G UUGCUCGG 1711 CCGAGCAA GGCTAGCTACAACGA GGGGTAAA 4734

1160 GUUGCUCG G CAACGGCC 1712 GGCCGTTG GGCTAGCTACAACGA CGAGCAAC 4735

1166 CGGCAACG G CCUGGUCU 1713 AGACCAGG GGCTAGCTACAACGA CGTTGCCG 4736

1171 ACGGCCUG G UCUAUGCC 1714 GGCATAGA GGCTAGCTACAACGA CAGGCCGT 4737

1182 UAUGCCAA G UGUUUGCU 1715 AGCAAACA GGCTAGCTACAACGA TTGGCATA 4738

1207 CCCCACUG G UUGGGGCU 1716 AGCCCCAA GGCTAGCTACAACGA CAGTGGGG 4739

1213 UGGUUGGG G CUUGGCCA 1717 TGGCCAAG GGCTAGCTACAACGA CCCAACCA 4740

1218 GGGGCUUG G CCAUAGGC 1718 GCCTATGG GGCTAGCTACAACGA CAAGCCCC 4741

1225 GGCCAUAG G CCAUCAGC 1719 GCTGATGG GGCTAGCTACAACGA CTATGGCC 4742

1232 GGCCAUCA G CGCAUGCG 1720 CGCATGCG GGCTAGCTACAACGA TGATGGCC 4743

1240 GCGCAUGC G UGGAACCU 1721 AGGTTCCA GGCTAGCTACAACGA GCATGCGC 4744

1287 AACUCCUA G CCGCUUGU 1722 ACAAGCGG GGCTAGCTACAACGA TAGGAGTT 4745

1306 UGCUCGCA G CAGGUCUG 1723 CAGACCTG GGCTAGCTACAACGA TGCGAGCA 4746

1310 CGCAGCAG G UCUGGGGC 1724 GCCCCAGA GGCTAGCTACAACGA CTGCTGCG 4747

1317 GGUCUGGG G CAAAACUC 1725 GAGTTTTG GGCTAGCTACAACGA CCCAGACC 4748

1347 AUUCUGUC G UGCUCUCC 1726 GGAGAGCA GGCTAGCTACAACGA GACAGAAT 4749

1379 UUUCCAUG G CUGCUAGG 1727 CCTAGCAG GGCTAGCTACAACGA CATGGAAA 4750

1387 GCUGCUAG G CUGUGCUG 1728 CAGCACAG GGCTAGCTACAACGA CTAGCAGC 4751

1418 CGCGGGAC G UCCUUUGU 1729 ACAAAGGA GGCTAGCTACAACGA GTCCCGCG 4752

1431 UUGUUUAC G UCCCGUCG 1730 CGACGGGA GGCTAGCTACAACGA GTAAACAA 4753

1436 UACGUCCC G UCGGCGCU 1731 AGCGCCGA GGCTAGCTACAACGA GGGACGTA 4754

1440 UCCCGUCG G CGCUGAAU 1732 ATTCAGCG GGCTAGCTACAACGA CGACGGGA 4755 Taoie 4 1

1471 CUCCCGGG G CCGCUUGG 1733 CCAAGCGG GGCTAGCTACAACGA CCCGGGAG 4756

1481 CGCUUGGG G CUCUACCG 1734 CGGTAGAG GGCTAGCTACAACGA CCCAAGCG 4757

1517 UACCGACC G UCCACGGG 1735 CCCGTGGA GGCTAGCTACAACGA GGTCGGTA 4758

1526 UCCACGGG G CGCACCUC 1736 GAGGTGCG GGCTAGCTACAACGA CCCGTGGA 4759

1553 GACUCCCC G UCUGUGCC 1737 GGCACAGA GGCTAGCTACAACGA GGGGAGTC 4760

1579 GCCGGACC G UGUGCACU 1738 AGTGCACA GGCTAGCTACAACGA GGTCCGGC 4761

1605 CUCUGCAC G UCGCAUGG 1739 CCATGCGA GGCTAGCTACAACGA GTGCAGAG 4762

1622 AGACCACC G UGAACGCC 1740 GGCGTTCA GGCTAGCTACAACGA GGTGGTCT 4763

1649 UGCCCAAG G UCUUGCAU 1741 ATGCAAGA GGCTAGCTACAACGA CTTGGGCA 4764

1679 GACUUUCA G CAAUGUCA 1742 TGACATTG GGCTAGCTACAACGA TGAAAGTC 4765

1703 ACCUUGAG G CAUACUUC 1743 GAAGTATG GGCTAGCTACAACGA CTCAAGGT 4766

1732 UUUAAUGA G UGGGAGGA 1744 TCCTCCCA GGCTAGCTACAACGA TCATTAAA 4767

1741 UGGGAGGA G UUGGGGGA 1745 TCCCCCAA GGCTAGCTACAACGA TCCTCCCA 4768

1754 GGGAGGAG G UUAGGUUA 1746 TAACCTAA GGCTAGCTACAACGA CTCCTCCC 4769

1759 GAGGUUAG G UUAAAGGU 1747 ACCTTTAA GGCTAGCTACAACGA CTAACCTC 4770

1766 GGUUAAAG G UCUUUGUA 1748 TACAAAGA GGCTAGCTACAACGA CTTTAACC 4771

1782 ACUAGGAG G CUGUAGGC 1749 GCCTACAG GGCTAGCTACAACGA CTCCTAGT 4772

1789 GGCUGUAG G CAUAAAUU 1750 AATTTATG GGCTAGCTACAACGA CTACAGCC 4773

1799 AUAAAUUG G UGUGUUCA 1751 TGAACACA GGCTAGCTACAACGA CAATTTAT 4774

1811 GUUCACCA G CACCAUGC 1752 GCATGGTG GGCTAGCTACAACGA TGGTGAAC 4775

1870 CUGUUCAA G CCUCCAAG 1753 CTTGGAGG GGCTAGCTACAACGA TTGAACAG 4776

1878 GCCUCCAA G CUGUGCCU 1754 AGGCACAG GGCTAGCTACAACGA TTGGAGGC 4777

1890 UGCCUUGG G UGGCUUUG 1755 CAAAGCCA GGCTAGCTACAACGA CCAAGGCA 4778

1893 CUUGGGUG G CUUUGGGG 1756 CCCCAAAG GGCTAGCTACAACGA CACCCAAG 4779

1901 GCUUUGGG G CAUGGACA 1757 TGTCCATG GGCTAGCTACAACGA CCCAAAGC 4780

1917 AUUGACCC G UAUAAAGA 1758 TCTTTATA GGCTAGCTACAACGA GGGTCAAT 4781

1933 AAUUUGGA G CUUCUGUG 1759 CACAGAAG GGCTAGCTACAACGA TCCAAATT 4782

1944 UCUGUGGA G UUACUCUC 1760 GAGAGTAA GGCTAGCTACAACGA TCCACAGA 4783

2023 AUCGGGGG G CCUUAGAG 1761 CTCTAAGG GGCTAGCTACAACGA CCCCCGAT 4784

2031 GCCUUAGA G UCUCCGGA 1762 TCCGGAGA GGCTAGCTACAACGA TCTAAGGC 4785

2062 ACCAUACG G CACUCAGG 1763 CCTGAGTG GGCTAGCTACAACGA CGTATGGT 4786

2070 GCACUCAG G CAAGCUAU 1764 ATAGCTTG GGCTAGCTACAACGA CTGAGTGC 4787

2074 UCAGGCAA G CUAUUCUG 1765 CAGAATAG GGCTAGCTACAACGA TTGCCTGA 4788

2090 GUGUUGGG G UGAGUUGA 1766 TCAACTCA GGCTAGCTACAACGA CCCAACAC 4789

2094 UGGGGUGA G UUGAUGAA 1767 TTCATCAA GGCTAGCTACAACGA TCACCCCA 4790

2107 UGAAUCUA G CCACCUGG 1768 CCAGGTGG GGCTAGCTACAACGA TAGATTCA 4791

2116 CCACCUGG G UGGGAAGU 1769 ACTTCCCA GGCTAGCTACAACGA CCAGGTGG 4792

2123 GGUGGGAA G UAAUUUGG 1770 CCAAATTA GGCTAGCTACAACGA TTCCCACC 4793

2140 AAGAUCCA G CAUCCAGG 1771 CCTGGATG GGCTAGCTACAACGA TGGATCTT 4794

2155 GGGAAUUA G UAGUCAGC 1772 GCTGACTA GGCTAGCTACAACGA TAATTCCC 4795

2158 AAUUAGUA G UCAGCUAU 1773 ATAGCTGA GGCTAGCTACAACGA TACTAATT 4796

2162 AGUAGUCA G CUAUGUCA 1774 TGACATAG GGCTAGCTACAACGA TGACTACT 4797

2173 AUGUCAAC G UUAAUAUG 1775 CATATTAA GGCTAGCTACAACGA GTTGACAT 4798

2183 UAAUAUGG G CCUAAAAA 1776 TTTTTAGG GGCTAGCTACAACGA CCATATTA 4799

2208 CUAUUGUG G UUUCACAU 1777 ATGTGAAA GGCTAGCTACAACGA CACAATAG 4800

2235 ACUUUUGG G CGAGAAAC 1778 GTTTCTCG GGCTAGCTACAACGA CCAAAAGT 4801

2260 AAUAUUUG G UGUCUUUU 1779 AAAAGACA GGCTAGCTACAACGA CAAATATT 4802

2272 CUUUUGGA G UGUGGAUU 1780 AATCCACA GGCTAGCTACAACGA TCCAAAAG 4803

2360 ACGAAGAG G CAGGUCCC 1781 GGGACCTG GGCTAGCTACAACGA CTCTTCGT 4804

2364 AGAGGCAG G UCCCCUAG 1782 CTAGGGGA GGCTAGCTACAACGA CTGCCTCT 4805

2403 AGACGAAG G UCUCAAUC 1783 GATTGAGA GGCTAGCTACAACGA CTTCGTCT 4806 Taoie 4 1

2417 AUCGCCGC G UCGCAGAA 1784 TTCTGCGA GGCTAGCTACAACGA GCGGCGAT 4807

2454 CAAUGUUA G UAUUCCUU 1785 AAGGAATA GGCTAGCTACAACGA TAACATTG 4808

2474 CACAUAAG G UGGGAAAC 1786 GTTTCCCA GGCTAGCTACAACGA CTTATGTG 4809

2491 UUUACGGG G CUUUAUUC 1787 GAATAAAG GGCTAGCTACAACGA CCCGTAAA 4810

2507 CUUCUACG G UACCUUGC 1788 GCAAGGTA GGCTAGCTACAACGA CGTAGAAG 4811

2530 CCUAAAUG G CAAACUCC 1789 GGAGTTTG GGCTAGCTACAACGA CATTTAGG 4812

2587 AGAUGUAA G CAAUUUGU 1790 ACAAATTG GGCTAGCTACAACGA TTACATCT 4813

2599 UUUGUGGG G CCCCUUAC 1791 GTAAGGGG GGCTAGCTACAACGA CCCACAAA 4814

2609 CCCUUACA G UAAAUGAA 1792 TTCATTTA GGCTAGCTACAACGA TGTAAGGG 4815

2650 CCUGCUAG G UUUUAUCC 1793 GGATAAAA GGCTAGCTACAACGA CTAGCAGG 4816

2701 AUCAAACC G UAUUAUCC 1794 GGATAATA GGCTAGCTACAACGA GGTTTGAT 4817

2713 UAUCCAGA G UAUGUAGU 1795 ACTACATA GGCTAGCTACAACGA TCTGGATA 4818

2720 AGUAUGUA G UUAAUCAU 1796 ATGATTAA GGCTAGCTACAACGA TACATACT 4819

2768 UUUGGAAG G CGGGGAUC 1797 GATCCCCG GGCTAGCTACAACGA CTTCCAAA 4820

2791 AAAAGAGA G UCCACACG 1798 CGTGTGGA GGCTAGCTACAACGA TCTCTTTT 4821

2799 GUCCACAC G UAGCGCCU 1799 AGGCGCTA GGCTAGCTACAACGA GTGTGGAC 4822

2802 CACACGUA G CGCCUCAU 1800 ATGAGGCG GGCTAGCTACAACGA TACGTGTG 4823

2818 UUUUGCGG G UCACCAUA 1801 TATGGTGA GGCTAGCTACAACGA CCGCAAAA 4824

2848 GAUCUACA G CAUGGGAG 1802 CTCCCATG GGCTAGCTACAACGA TGTAGATC 4825

2857 CAUGGGAG G UUGGUCUU 1803 AAGACCAA GGCTAGCTACAACGA CTCCCATG 4826

2861 GGAGGUUG G UCUUCCAA 1804 TTGGAAGA GGCTAGCTACAACGA CAACCTCC 4827

2881 UCGAAAAG G CAUGGGGA 1805 TCCCCATG GGCTAGCTACAACGA CTTTTCGA 4828

2936 GAUCAUCA G UUGGACCC 1806 GGGTCCAA GGCTAGCTACAACGA TGATGATC 4829

2955 CAUUCAAA G CCAACUCA 1807 TGAGTTGG GGCTAGCTACAACGA TTTGAATG 4830

2964 CCAACUCA G UAAAUCCA 1808 TGGATTTA GGCTAGCTACAACGA TGAGTTGG 4831

3005 GACAACUG G CCGGACGC 1809 GCGTCCGG GGCTAGCTACAACGA CAGTTGTC 4832

3021 CCAACAAG G UGGGAGUG 1810 CACTCCCA GGCTAGCTACAACGA CTTGTTGG 4833

3027 AGGUGGGA G UGGGAGCA 1811 TGCTCCCA GGCTAGCTACAACGA TCCCACCT 4834

3033 GAGUGGGA G CAUUCGGG 1812 CCCGAATG GGCTAGCTACAACGA TCCCACTC 4835

3041 GCAUUCGG G CCAGGGUU 1813 AACCCTGG GGCTAGCTACAACGA CCGAATGC 4836

3047 GGGCCAGG G UUCACCCC 1814 GGGGTGAA GGCTAGCTACAACGA CCTGGCCC 4837

3077 CUGUUGGG G UGGAGCCC 1815 GGGCTCCA GGCTAGCTACAACGA CCCAACAG 4838

3082 GGGGUGGA G CCCUCACG 1816 CGTGAGGG GGCTAGCTACAACGA TCCACCCC 4839

3097 CGCUCAGG G CCUACUCA 1817 TGAGTAGG GGCTAGCTACAACGA CCTGAGCG 4840

3117 CUGUGCCA G CAGCUCCU 1818 AGGAGCTG GGCTAGCTACAACGA TGGCACAG 4841

3120 UGCCAGCA G CUCCUCCU 1819 AGGAGGAG GGCTAGCTACAACGA TGCTGGCA 4842

3146 ACCAAUCG G CAGUCAGG 1820 CCTGACTG GGCTAGCTACAACGA CGATTGGT 4843

3149 AAUCGGCA G UCAGGAAG 1821 CTTCCTGA GGCTAGCTACAACGA TGCCGATT 4844

3158 UCAGGAAG G CAGCCUAC 1822 GTAGGCTG GGCTAGCTACAACGA CTTCCTGA 4845

3161 GGAAGGCA G CCUACUCC 1823 GGAGTAGG GGCTAGCTACAACGA TGCCTTCC 4846

3204 AUCCUCAG G CCAUGCAG 1824 CTGCATGG GGCTAGCTACAACGA CTGAGGAT 4847

10 ACUCCACC A CUUUCCAC 1825 GTGGAAAG GGCTAGCTACAACGA GGTGGAGT 4848

17 CACUUUCC A CCAAACUC 1826 GAGTTTGG GGCTAGCTACAACGA GGAAAGTG 4849

22 UCCACCAA A CUCUUCAA 1827 TTGAAGAG GGCTAGCTACAACGA TTGGTGGA 4850

32 UCUUCAAG A UCCCAGAG 1828 CTCTGGGA GGCTAGCTACAACGA CTTGAAGA 4851

53 GGCCCUGU A CUUUCCUG 1829 CAGGAAAG GGCTAGCTACAACGA ACAGGGCC 4852

82 GUUCAGGA A CAGUGAGC 1830 GCTCACTG GGCTAGCTACAACGA TCCTGAAC 4853

101 UGCUCAGA A UACUGUCU 1831 AGACAGTA GGCTAGCTACAACGA TCTGAGCA 4854

103 CUCAGAAU A CUGUCUCU 1832 AGAGACAG GGCTAGCTACAACGA ATTCTGAG 4855

115 UCUCUGCC A UAUCGUCA 1833 TGACGATA GGCTAGCTACAACGA GGCAGAGA 4856

117 UCUGCCAU A UCGUCAAU 1834 ATTGACGA GGCTAGCTACAACGA ATGGCAGA 4857 Taoie 4 1

124 UAUCGUCA A UCUUAUCG 1835 CGATAAGA GGCTAGCTACAACGA TGACGATA 4858

129 UCAAUCUU A UCGAAGAC 1836 GTCTTCGA GGCTAGCTACAACGA AAGATTGA 4859

136 UAUCGAAG A CUGGGGAC 1837 GTCCCCAG GGCTAGCTACAACGA CTTCGATA 4860

143 GACUGGGG A CCCUGUAC 1838 GTACAGGG GGCTAGCTACAACGA CCCCAGTC 4861

150 GACCCUGU A CCGAACAU 1839 ATGTTCGG GGCTAGCTACAACGA ACAGGGTC 4862

155 UGUACCGA A CAUGGAGA 1840 TCTCCATG GGCTAGCTACAACGA TCGGTACA 4863

157 UACCGAAC A UGGAGAAC 1841 GTTCTCCA GGCTAGCTACAACGA GTTCGGTA 4864

164 CAUGGAGA A CAUCGCAU 1842 ATGCGATG GGCTAGCTACAACGA TCTCCATG 4865

166 UGGAGAAC A UCGCAUCA 1843 TGATGCGA GGCTAGCTACAACGA GTTCTCCA 4866

171 AACAUCGC A UCAGGACU 1844 AGTCCTGA GGCTAGCTACAACGA GCGATGTT 4867

177 GCAUCAGG A CUCCUAGG 1845 CCTAGGAG GGCTAGCTACAACGA CCTGATGC 4868

186 CUCCUAGG A CCCCUGCU 1846 AGCAGGGG GGCTAGCTACAACGA CCTAGGAG 4869

201 CUCGUGUU A CAGGCGGG 1847 CCCGCCTG GGCTAGCTACAACGA AACACGAG 4870

223 UCUUGUUG A CAAAAAUC 1848 GATTTTTG GGCTAGCTACAACGA CAACAAGA 4871

229 UGACAAAA A UCCUCACA 1849 TGTGAGGA GGCTAGCTACAACGA TTTTGTCA 4872

235 AAAUCCUC A CAAUACCA 1850 TGGTATTG GGCTAGCTACAACGA GAGGATTT 4873

238 UCCUCACA A UACCACAG 1851 CTGTGGTA GGCTAGCTACAACGA TGTGAGGA 4874

240 CUCACAAU A CCACAGAG 1852 CTCTGTGG GGCTAGCTACAACGA ATTGTGAG 4875

243 ACAAUACC A CAGAGUCU 1853 AGACTCTG GGCTAGCTACAACGA GGTATTGT 4876

254 GAGUCUAG A CUCGUGGU 1854 ACCACGAG GGCTAGCTACAACGA CTAGACTC 4877

265 CGUGGUGG A CUUCUCUC 1855 GAGAGAAG GGCTAGCTACAACGA CCACCACG 4878

275 UUCUCUCA A UUUUCUAG 1856 CTAGAAAA GGCTAGCTACAACGA TGAGAGAA 4879

289 UAGGGGGA A CACCCGUG 1857 CACGGGTG GGCTAGCTACAACGA TCCCCCTA 4880

291 GGGGGAAC A CCCGUGUG 1858 CACACGGG GGCTAGCTACAACGA GTTCCCCC 4881

311 UGGCCAAA A UUCGCAGU 1859 ACTGCGAA GGCTAGCTACAACGA TTTGGCCA 4882

325 AGUCCCAA A UCUCCAGU 1860 ACTGGAGA GGCTAGCTACAACGA TTGGGACT 4883

335 CUCCAGUC A CUCACCAA 1861 TTGGTGAG GGCTAGCTACAACGA GACTGGAG 4884

339 AGUCACUC A CCAACCUG 1862 CAGGTTGG GGCTAGCTACAACGA GAGTGACT 4885

343 ACUCACCA A CCUGUUGU 1863 ACAACAGG GGCTAGCTACAACGA TGGTGAGT 4886

358 GUCCUCCA A UUUGUCCU 1864 AGGACAAA GGCTAGCTACAACGA TGGAGGAC 4887

371 UCCUGGUU A UCGCUGGA 1865 TCCAGCGA GGCTAGCTACAACGA AACCAGGA 4888

379 AUCGCUGG A UGUGUCUG 1866 CAGACACA GGCTAGCTACAACGA CCAGCGAT 4889

397 GGCGUUUU A UCAUCUUC 1867 GAAGATGA GGCTAGCTACAACGA AAAACGCC 4890

400 GUUUUAUC A UCUUCCUC 1868 GAGGAAGA GGCTAGCTACAACGA GATAAAAC 4891

412 UCCUCUGC A UCCUGCUG 1869 CAGCAGGA GGCTAGCTACAACGA GCAGAGGA 4892

423 CUGCUGCU A UGCCUCAU 1870 ATGAGGCA GGCTAGCTACAACGA AGCAGCAG 4893

430 UAUGCCUC A UCUUCUUG 1871 CAAGAAGA GGCTAGCTACAACGA GAGGCATA 4894

452 UCUUCUGG A CUAUCAAG 1872 CTTGATAG GGCTAGCTACAACGA CCAGAAGA 4895

455 UCUGGACU A UCAAGGUA 1873 TACCTTGA GGCTAGCTACAACGA AGTCCAGA 4896

463 AUCAAGGU A UGUUGCCC 1874 GGGCAACA GGCTAGCTACAACGA ACCTTGAT 4897

484 GUCCUCUA A UUCCAGGA 1875 TCCTGGAA GGCTAGCTACAACGA TAGAGGAC 4898

492 AUUCCAGG A UCAUCAAC 1876 GTTGATGA GGCTAGCTACAACGA CCTGGAAT 4899

495 CCAGGAUC A UCAACAAC 1877 GTTGTTGA GGCTAGCTACAACGA GATCCTGG 4900

499 GAUCAUCA A CAACCAGC 1878 GCTGGTTG GGCTAGCTACAACGA TGATGATC 4901

502 CAUCAACA A CCAGCACC 1879 GGTGCTGG GGCTAGCTACAACGA TGTTGATG 4902

513 AGCACCGG A CCAUGCAA 1880 TTGCATGG GGCTAGCTACAACGA CCGGTGCT 4903

516 ACCGGACC A UGCAAAAC 1881 GTTTTGCA GGCTAGCTACAACGA GGTCCGGT 4904

523 CAUGCAAA A CCUGCACA 1882 TGTGCAGG GGCTAGCTACAACGA TTTGCATG 4905

529 AAACCUGC A CAACUCCU 1883 AGGAGTTG GGCTAGCTACAACGA GCAGGTTT 4906

532 CCUGCACA A CUCCUGCU 1884 AGCAGGAG GGCTAGCTACAACGA TGTGCAGG 4907

547 CUCAAGGA A CCUCUAUG 1885 CATAGAGG GGCTAGCTACAACGA TCCTTGAG 4908 Taoie 4 i

553 GAACCUCU A UGUUUCCC 1886 GGGAAACA GGCTAGCTACAACGA AGAGGTTC 4909

564 UUUCCCUC A UGUUGCUG 1887 CAGCAACA GGCTAGCTACAACGA GAGGGAAA 4910

574 GUUGCUGU A CAAAACCU 1888 AGGTTTTG GGCTAGCTACAACGA ACAGCAAC 4911

579 UGUACAAA A CCUACGGA 1889 TCCGTAGG GGCTAGCTACAACGA TTTGTACA 4912

583 CAAAACCU A CGGACGGA 1890 TCCGTCCG GGCTAGCTACAACGA AGGTTTTG 4913

587 ACCUACGG A CGGAAACU 1891 AGTTTCCG GGCTAGCTACAACGA CCGTAGGT 4914

593 GGACGGAA A CUGCACCU 1892 AGGTGCAG GGCTAGCTACAACGA TTCCGTCC 4915

598 GAAACUGC A CCUGUAUU 1893 AATACAGG GGCTAGCTACAACGA GCAGTTTC 4916

604 GCACCUGU A UUCCCAUC 1894 GATGGGAA GGCTAGCTACAACGA ACAGGTGC 4917

610 GUAUUCCC A UCCCAUCA 1895 TGATGGGA GGCTAGCTACAACGA GGGAATAC 4918

615 CCCAUCCC A UCAUCUUG 1896 CAAGATGA GGCTAGCTACAACGA GGGATGGG 4919

618 AUCCCAUC A UCUUGGGC 1897 GCCCAAGA GGCTAGCTACAACGA GATGGGAT 4920

636 UUCGCAAA A UACCUAUG 1898 CATAGGTA GGCTAGCTACAACGA TTTGCGAA 4921

638 CGCAAAAU A CCUAUGGG 1899 CCCATAGG GGCTAGCTACAACGA ATTTTGCG 4922

642 AAAUACCU A UGGGAGUG 1900 CACTCCCA GGCTAGCTACAACGA AGGTATTT 4923

681 CUCAGUUU A CUAGUGCC 1901 GGCACTAG GGCTAGCTACAACGA AAACTGAG 4924

690 CUAGUGCC A UUUGUUCA 1902 TGAACAAA GGCTAGCTACAACGA GGCACTAG 4925

721 UUUCCCCC A CUGUCUGG 1903 CCAGACAG GGCTAGCTACAACGA GGGGGAAA 4926

739 UUUCAGUU A UAUGGAUG 1904 CATCCATA GGCTAGCTACAACGA AACTGAAA 4927

741 UCAGUUAU A UGGAUGAU 1905 ATCATCCA GGCTAGCTACAACGA ATAACTGA 4928

745 UUAUAUGG A UGAUGUGG 1906 CCACATCA GGCTAGCTACAACGA CCATATAA 4929

748 UAUGGAUG A UGUGGUUU 1907 AAACCACA GGCTAGCTACAACGA CATCCATA 4930

773 AAGUCUGU A CAACAUCU 1908 AGATGTTG GGCTAGCTACAACGA ACAGACTT 4931

776 UCUGUACA A CAUCUUGA 1909 TCAAGATG GGCTAGCTACAACGA TGTACAGA 4932

778 UGUACAAC A UCUUGAGU 1910 ACTCAAGA GGCTAGCTACAACGA GTTGTACA 4933

793 GUCCCUUU A UGCCGCUG 1911 CAGCGGCA GGCTAGCTACAACGA AAAGGGAC 4934

804 CCGCUGUU A CCAAUUUU 1912 AAAATTGG GGCTAGCTACAACGA AACAGCGG 4935

808 UGUUACCA A UUUUCUUU 1913 AAAGAAAA GGCTAGCTACAACGA TGGTAACA 4936

828 CUUUGGGU A UACAUUUA 1914 TAAATGTA GGCTAGCTACAACGA ACCCAAAG 4937

830 UUGGGUAU A CAUUUAAA 1915 TTTAAATG GGCTAGCTACAACGA ATACCCAA 4938

832 GGGUAUAC A UUUAAACC 1916 GGTTTAAA GGCTAGCTACAACGA GTATACCC 4939

838 ACAUUUAA A CCCUCACA 1917 TGTGAGGG GGCTAGCTACAACGA TTAAATGT 4940

844 AAACCCUC A CAAAACAA 1918 TTGTTTTG GGCTAGCTACAACGA GAGGGTTT 4941

849 CUCACAAA A CAAAAAGA 1919 TCTTTTTG GGCTAGCTACAACGA TTTGTGAG 4942

857 ACAAAAAG A UGGGGAUA 1920 TATCCCCA GGCTAGCTACAACGA CTTTTTGT 4943

863 AGAUGGGG A UAUUCCCU 1921 AGGGAATA GGCTAGCTACAACGA CCCCATCT 4944

865 AUGGGGAU A UUCCCUUA 1922 TAAGGGAA GGCTAGCTACAACGA ATCCCCAT 4945

874 UUCCCUUA A CUUCAUGG 1923 CCATGAAG GGCTAGCTACAACGA TAAGGGAA 4946

879 UUAACUUC A UGGGAUAU 1924 ATATCCCA GGCTAGCTACAACGA GAAGTTAA 4947

884 UUCAUGGG A UAUGUAAU 1925 ATTACATA GGCTAGCTACAACGA CCCATGAA 4948

886 CAUGGGAU A UGUAAUUG 1926 CAATTACA GGCTAGCTACAACGA ATCCCATG 4949

891 GAUAUGUA A UUGGGAGU 1927 ACTCCCAA GGCTAGCTACAACGA TACATATC 4950

906 GUUGGGGC A CAUUGCCA 1928 TGGCAATG GGCTAGCTACAACGA GCCCCAAC 4951

908 UGGGGCAC A UUGCCACA 1929 TGTGGCAA GGCTAGCTACAACGA GTGCCCCA 4952

914 ACAUUGCC A CAGGAACA 1930 TGTTCCTG GGCTAGCTACAACGA GGCAATGT 4953

920 CCACAGGA A CAUAUUGU 1931 ACAATATG GGCTAGCTACAACGA TCCTGTGG 4954

922 ACAGGAAC A UAUUGUAC 1932 GTACAATA GGCTAGCTACAACGA GTTCCTGT 4955

924 AGGAACAU A UUGUACAA 1933 TTGTACAA GGCTAGCTACAACGA ATGTTCCT 4956

929 CAUAUUGU A CAAAAAAU 1934 ATTTTTTG GGCTAGCTACAACGA ACAATATG 4957

936 UACAAAAA A UCAAAAUG 1935 CATTTTGA GGCTAGCTACAACGA TTTTTGTA 4958

942 AAAUCAAA A UGUGUUUU 1936 AAAACACA GGCTAGCTACAACGA TTTGATTT 4959 Taoie 4 i

956 UUUAGGAA A CUUCCUGU 1937 ACAGGAAG GGCTAGCTACAACGA TTCCTAAA 4960

967 UCCUGUAA A CAGGCCUA 1938 TAGGCCTG GGCTAGCTACAACGA TTACAGGA 4961

975 ACAGGCCU A UUGAUUGG 1939 CCAATCAA GGCTAGCTACAACGA AGGCCTGT 4962

979 GCCUAUUG A UUGGAAAG 1940 CTTTCCAA GGCTAGCTACAACGA CAATAGGC 4963

989 UGGAAAGU A UGUCAACG 1941 CGTTGACA GGCTAGCTACAACGA ACTTTCCA 4964

995 GUAUGUCA A CGAAUUGU 1942 ACAATTCG GGCTAGCTACAACGA TGACATAC 4965

999 GUCAACGA A UUGUGGGU 1943 ACCCACAA GGCTAGCTACAACGA TCGTTGAC 4966

1032 CCCCUUUC A CGCAAUGU 1944 ACATTGCG GGCTAGCTACAACGA GAAAGGGG 4967

1037 UUCACGCA A UGUGGAUA 1945 TATCCACA GGCTAGCTACAACGA TGCGTGAA 4968

1043 CAAUGUGG A UAUUCUGC 1946 GCAGAATA GGCTAGCTACAACGA CCACATTG 4969

1045 AUGUGGAU A UUCUGCUU 1947 AAGCAGAA GGCTAGCTACAACGA ATCCACAT 4970

1056 CUGCUUUA A UGCCUUUA 1948 TAAAGGCA GGCTAGCTACAACGA TAAAGCAG 4971

1064 AUGCCUUU A UAUGCAUG 1949 CATGCATA GGCTAGCTACAACGA AAAGGCAT 4972

1066 GCCUUUAU A UGCAUGCA 1950 TGCATGCA GGCTAGCTACAACGA ATAAAGGC 4973

1070 UUAUAUGC A UGCAUACA 1951 TGTATGCA GGCTAGCTACAACGA GCATATAA 4974

1074 AUGCAUGC A UACAAGCA 1952 TGCTTGTA GGCTAGCTACAACGA GCATGCAT 4975

1076 GCAUGCAU A CAAGCAAA 1953 TTTGCTTG GGCTAGCTACAACGA ATGCATGC 4976

1085 CAAGCAAA A CAGGCUUU 1954 AAAGCCTG GGCTAGCTACAACGA TTTGCTTG 4977

1095 AGGCUUUU A CUUUCUCG 1955 CGAGAAAG GGCTAGCTACAACGA AAAAGCCT 4978

1107 UCUCGCCA A CUUACAAG 1956 CTTGTAAG GGCTAGCTACAACGA TGGCGAGA 4979 llll GCCAACUU A CAAGGCCU 1957 AGGCCTTG GGCTAGCTACAACGA AAGTTGGC 4980

1130 CUAAGUAA A CAGUAUGU 1958 ACATACTG GGCTAGCTACAACGA TTACTTAG 4981

1135 UAAACAGU A UGUGAACC 1959 GGTTCACA GGCTAGCTACAACGA ACTGTTTA 4982

1141 GUAUGUGA A CCUUUACC 1960 GGTAAAGG GGCTAGCTACAACGA TCACATAC 4983

1147 GAACCUUU A CCCCGUUG 1961 CAACGGGG GGCTAGCTACAACGA AAAGGTTC 4984

1163 GCUCGGCA A CGGCCUGG 1962 CCAGGCCG GGCTAGCTACAACGA TGCCGAGC 4985

1175 CCUGGUCU A UGCCAAGU 1963 ACTTGGCA GGCTAGCTACAACGA AGACCAGG 4986

1192 GUUUGCUG A CGCAACCC 1964 GGGTTGCG GGCTAGCTACAACGA CAGCAAAC 4987

1197 CUGACGCA A CCCCCACU 1965 AGTGGGGG GGCTAGCTACAACGA TGCGTCAG 4988

1203 CAACCCCC A CUGGUUGG 1966 CCAACCAG GGCTAGCTACAACGA GGGGGTTG 4989

1221 GCUUGGCC A UAGGCCAU 1967 ATGGCCTA GGCTAGCTACAACGA GGCCAAGC 4990

1228 CAUAGGCC A UCAGCGCA 1968 TGCGCTGA GGCTAGCTACAACGA GGCCTATG 4991

1236 AUCAGCGC A UGCGUGGA 1969 TCCACGCA GGCTAGCTACAACGA GCGCTGAT 4992

1245 UGCGUGGA A CCUUUGUG 1970 CACAAAGG GGCTAGCTACAACGA TCCACGCA 4993

1266 CUCUGCCG A UCCAUACC 1971 GGTATGGA GGCTAGCTACAACGA CGGCAGAG 4994

1270 GCCGAUCC A UACCGCGG 1972 CCGCGGTA GGCTAGCTACAACGA GGATCGGC 4995

1272 CGAUCCAU A CCGCGGAA 1973 TTCCGCGG GGCTAGCTACAACGA ATGGATCG 4996

1280 ACCGCGGA A CUCCUAGC 1974 GCTAGGAG GGCTAGCTACAACGA TCCGCGGT 4997

1322 GGGGCAAA A CUCAUCGG 1975 CCGATGAG GGCTAGCTACAACGA TTTGCCCC 4998

1326 CAAAACUC A UCGGGACU 1976 AGTCCCGA GGCTAGCTACAACGA GAGTTTTG 4999

1332 UCAUCGGG A CUGACAAU 1977 ATTGTCAG GGCTAGCTACAACGA CCCGATGA 5000

1336 CGGGACUG A CAAUUCUG 1978 CAGAATTG GGCTAGCTACAACGA CAGTCCCG 5001

1339 GACUGACA A UUCUGUCG 1979 CGACAGAA GGCTAGCTACAACGA TGTCAGTC 5002

1361 UCCCGCAA A UAUACAUC 1980 GATGTATA GGCTAGCTACAACGA TTGCGGGA 5003

1363 CCGCAAAU A UACAUCAU 1981 ATGATGTA GGCTAGCTACAACGA ATTTGCGG 5004

1365 GCAAAUAU A CAUCAUUU 1982 AAATGATG GGCTAGCTACAACGA ATATTTGC 5005

1367 AAAUAUAC A UCAUUUCC 1983 GGAAATGA GGCTAGCTACAACGA GTATATTT 5006

1370 UAUACAUC A UUUCCAUG 1984 CATGGAAA GGCTAGCTACAACGA GATGTATA 5007

1376 UCAUUUCC A UGGCUGCU 1985 AGCAGCCA GGCTAGCTACAACGA GGAAATGA 5008

1399 UGCUGCCA A CUGGAUCC 1986 GGATCCAG GGCTAGCTACAACGA TGGCAGCA 5009

1404 CCAACUGG A UCCUACGC 1987 GCGTAGGA GGCTAGCTACAACGA CCAGTTGG 5010 Table 41

1409 UGGAUCCU A CGCGGGAC 1988 GTCCCGCG GGCTAGCTACAACGA AGGATCCA 5011

1416 UACGCGGG A CGUCCUUU 1989 AAAGGACG GGCTAGCTACAACGA CCCGCGTA 5012

1429 CUUUGUUU A CGUCCCGU 1990 ACGGGACG GGCTAGCTACAACGA AAACAAAG 5013

1447 GGCGCUGA A UCCCGCGG 1991 CCGCGGGA GGCTAGCTACAACGA TCAGCGCC 5014

1456 UCCCGCGG A CGACCCCU 1992 AGGGGTCG GGCTAGCTACAACGA CCGCGGGA 5015

1459 CGCGGACG A CCCCUCCC 1993 GGGAGGGG GGCTAGCTACAACGA CGTCCGCG 5016

1486 GGGGCUCU A CCGCCCGC 1994 GCGGGCGG GGCTAGCTACAACGA AGAGCCCC 5017

1505 CUCCGCCU A UUGUACCG 1995 CGGTACAA GGCTAGCTACAACGA AGGCGGAG 5018

1510 CCUAUUGU A CCGACCGU 1996 ACGGTCGG GGCTAGCTACAACGA ACAATAGG 5019

1514 UUGUACCG A CCGUCCAC 1997 GTGGACGG GGCTAGCTACAACGA CGGTACAA 5020

1521 GACCGUCC A CGGGGCGC 1998 GCGCCCCG GGCTAGCTACAACGA GGACGGTC 5021

1530 CGGGGCGC A CCUCUCUU 1999 AAGAGAGG GGCTAGCTACAACGA GCGCCCCG 5022

1540 CUCUCUUU A CGCGGACU 2000 AGTCCGCG GGCTAGCTACAACGA AAAGAGAG 5023

1546 UUACGCGG A CUCCCCGU 2001 ACGGGGAG GGCTAGCTACAACGA CCGCGTAA 5024

1567 GCCUUCUC A UCUGCCGG 2002 CCGGCAGA GGCTAGCTACAACGA GAGAAGGC 5025

1576 UCUGCCGG A CCGUGUGC 2003 GCACACGG GGCTAGCTACAACGA CCGGCAGA 5026

1585 CCGUGUGC A CUUCGCUU 2004 AAGCGAAG GGCTAGCTACAACGA GCACACGG 5027

1595 UUCGCUUC A CCUCUGCA 2005 TGCAGAGG GGCTAGCTACAACGA GAAGCGAA 5028

1603 ACCUCUGC A CGUCGCAU 2006 ATGCGACG GGCTAGCTACAACGA GCAGAGGT 5029

1610 CACGUCGC A UGGAGACC 2007 GGTCTCCA GGCTAGCTACAACGA GCGACGTG 5030

1616 GCAUGGAG A CCACCGUG 2008 CACGGTGG GGCTAGCTACAACGA CTCCATGC 5031

1619 UGGAGACC A CCGUGAAC 2009 GTTCACGG GGCTAGCTACAACGA GGTCTCCA 5032

1626 CACCGUGA A CGCCCACA 2010 TGTGGGCG GGCTAGCTACAACGA TCACGGTG 5033

1638 CCACAGGA A CCUGCCCA 2011 TGGGCAGG GGCTAGCTACAACGA TCCTGTGG 5034

1656 GGUCUUGC A UAAGAGGA 2012 TCCTCTTA GGCTAGCTACAACGA GCAAGACC 5035

1664 AUAAGAGG A CUCUUGGA 2013 TCCAAGAG GGCTAGCTACAACGA CCTCTTAT 5036

1672 ACUCUUGG A CUUUCAGC 2014 GCTGAAAG GGCTAGCTACAACGA CCAAGAGT 5037

1682 UUUCAGCA A UGUCAACG 2015 CGTTGACA GGCTAGCTACAACGA TGCTGAAA 5038

1688 CAAUGUCA A CGACCGAC 2016 GTCGGTCG GGCTAGCTACAACGA TGACATTG 5039

1691 UGUCAACG A CCGACCUU 2017 AAGGTCGG GGCTAGCTACAACGA CGTTGACA 5040

1695 AACGACCG A CCUUGAGG 2018 CCTCAAGG GGCTAGCTACAACGA CGGTCGTT 5041

1705 CUUGAGGC A UACUUCAA 2019 TTGAAGTA GGCTAGCTACAACGA GCCTCAAG 5042

1707 UGAGGCAU A CUUCAAAG 2020 CTTTGAAG GGCTAGCTACAACGA ATGCCTCA 5043

1716 CUUCAAAG A CUGUGUGU 2021 ACACACAG GGCTAGCTACAACGA CTTTGAAG 5044

1728 UGUGUUUA A UGAGUGGG 2022 CCCACTCA GGCTAGCTACAACGA TAAACACA 5045

1774 GUCUUUGU A CUAGGAGG 2023 CCTCCTAG GGCTAGCTACAACGA ACAAAGAC 5046

1791 CUGUAGGC A UAAAUUGG 2024 CCAATTTA GGCTAGCTACAACGA GCCTACAG 5047

1795 AGGCAUAA A UUGGUGUG 2025 CACACCAA GGCTAGCTACAACGA TTATGCCT 5048

1807 GUGUGUUC A CCAGCACC 2026 GGTGCTGG GGCTAGCTACAACGA GAACACAC 5049

1813 UCACCAGC A CCAUGCAA 2027 TTGCATGG GGCTAGCTACAACGA GCTGGTGA 5050

1816 CCAGCACC A UGCAACUU 2028 AAGTTGCA GGCTAGCTACAACGA GGTGCTGG 5051

1821 ACCAUGCA A CUUUUUCA 2029 TGAAAAAG GGCTAGCTACAACGA TGCATGGT 5052

1829 ACUUUUUC A CCUCUGCC 2030 GGCAGAGG GGCTAGCTACAACGA GAAAAAGT 5053

1840 UCUGCCUA A UCAUCUCA 2031 TGAGATGA GGCTAGCTACAACGA TAGGCAGA 5054

1843 GCCUAAUC A UCUCAUGU 2032 ACATGAGA GGCTAGCTACAACGA GATTAGGC 5055

1848 AUCAUCUC A UGUUCAUG 2033 CATGAACA GGCTAGCTACAACGA GAGATGAT 5056

1854 UCAUGUUC A UGUCCUAC 2034 GTAGGACA GGCTAGCTACAACGA GAACATGA 5057

1861 CAUGUCCU A CUGUUCAA 2035 TTGAACAG GGCTAGCTACAACGA AGGACATG 5058

1903 UUUGGGGC A UGGACAUU 2036 AATGTCCA GGCTAGCTACAACGA GCCCCAAA 5059

1907 GGGCAUGG A CAUUGACC 2037 GGTCAATG GGCTAGCTACAACGA CCATGCCC 5060

1909 GCAUGGAC A UUGACCCG 2038 CGGGTCAA GGCTAGCTACAACGA GTCCATGC 5061 TaDie 4 1

1913 GGACAUUG A CCCGUAUA 2039 TATACGGG GGCTAGCTACAACGA CAATGTCC 5062

1919 UGACCCGU A UAAAGAAU 2040 ATTCTTTA GGCTAGCTACAACGA ACGGGTCA 5063

1926 UAUAAAGA A UUUGGAGC 2041 GCTCCAAA GGCTAGCTACAACGA TCTTTATA 5064

1947 GUGGAGUU A CUCUCUUU 2042 AAAGAGAG GGCTAGCTACAACGA AACTCCAC 5065

1967 GCCUUCUG A CUUCUUUC 2043 GAAAGAAG GGCTAGCTACAACGA CAGAAGGC 5066

1981 UUCCUUCU A UUCGAGAU 2044 ATCTCGAA GGCTAGCTACAACGA AGAAGGAA 5067

1988 UAUUCGAG A UCUCCUCG 2045 CGAGGAGA GGCTAGCTACAACGA CTCGAATA 5068

1997 UCUCCUCG A CACCGCCU 2046 AGGCGGTG GGCTAGCTACAACGA CGAGGAGA 5069

1999 UCCUCGAC A CCGCCUCU 2047 AGAGGCGG GGCTAGCTACAACGA GTCGAGGA 5070

2015 UGCUCUGU A UCGGGGGG 2048 CCCCCCGA GGCTAGCTACAACGA ACAGAGCA 5071

2040 UCUCCGGA A CAUUGUUC 2049 GAACAATG GGCTAGCTACAACGA TCCGGAGA 5072

2042 UCCGGAAC A UUGUUCAC 2050 GTGAACAA GGCTAGCTACAACGA GTTCCGGA 5073

2049 CAUUGUUC A CCUCACCA 2051 TGGTGAGG GGCTAGCTACAACGA GAACAATG 5074

2054 UUCACCUC A CCAUACGG 2052 CCGTATGG GGCTAGCTACAACGA GAGGTGAA 5075

2057 ACCUCACC A UACGGCAC 2053 GTGCCGTA GGCTAGCTACAACGA GGTGAGGT 5076

2059 CUCACCAU A CGGCACUC 2054 GAGTGCCG GGCTAGCTACAACGA ATGGTGAG 5077

2064 CAUACGGC A CUCAGGCA 2055 TGCCTGAG GGCTAGCTACAACGA GCCGTATG 5078

2077 GGCAAGCU A UUCUGUGU 2056 ACACAGAA GGCTAGCTACAACGA AGCTTGCC 5079

2098 GUGAGUUG A UGAAUCUA 2057 TAGATTCA GGCTAGCTACAACGA CAACTCAC 5080

2102 GUUGAUGA A UCUAGCCA 2058 TGGCTAGA GGCTAGCTACAACGA TCATCAAC 5081

2110 AUCUAGCC A CCUGGGUG 2059 CACCCAGG GGCTAGCTACAACGA GGCTAGAT 5082

2126 GGGAAGUA A UUUGGAAG 2060 CTTCCAAA GGCTAGCTACAACGA TACTTCCC 5083

2135 UUUGGAAG A UCCAGCAU 2061 ATGCTGGA GGCTAGCTACAACGA CTTCCAAA 5084

2142 GAUCCAGC A UCCAGGGA 2062 TCCCTGGA GGCTAGCTACAACGA GCTGGATC 5085

2151 UCCAGGGA A UUAGUAGU 2063 ACTACTAA GGCTAGCTACAACGA TCCCTGGA 5086

2165 AGUCAGCU A UGUCAACG 2064 CGTTGACA GGCTAGCTACAACGA AGCTGACT 5087

2171 CUAUGUCA A CGUUAAUA 2065 TATTAACG GGCTAGCTACAACGA TGACATAG 5088

2177 CAACGUUA A UAUGGGCC 2066 GGCCCATA GGCTAGCTACAACGA TAACGTTG 5089

2179 ACGUUAAU A UGGGCCUA 2067 TAGGCCCA GGCTAGCTACAACGA ATTAACGT 5090

2191 GCCUAAAA A UCAGACAA 2068 TTGTCTGA GGCTAGCTACAACGA TTTTAGGC 5091

2196 AAAAUCAG A CAACUAUU 2069 AATAGTTG GGCTAGCTACAACGA CTGATTTT 5092

2199 AUCAGACA A CUAUUGUG 2070 CACAATAG GGCTAGCTACAACGA TGTCTGAT 5093

2202 AGACAACU A UUGUGGUU 2071 AACCACAA GGCTAGCTACAACGA AGTTGTCT 5094

2213 GUGGUUUC A CAUUUCCU 2072 AGGAAATG GGCTAGCTACAACGA GAAACCAC 5095

2215 GGUUUCAC A UUUCCUGU 2073 ACAGGAAA GGCTAGCTACAACGA GTGAAACC 5096

2227 CCUGUCUU A CUUUUGGG 2074 CCCAAAAG GGCTAGCTACAACGA AAGACAGG 5097

2242 GGCGAGAA A CUGUUCUU 2075 AAGAACAG GGCTAGCTACAACGA TTCTCGCC 5098

2253 GUUCUUGA A UAUUUGGU 2076 ACCAAATA GGCTAGCTACAACGA TCAAGAAC 5099

2255 UCUUGAAU A UUUGGUGU 2077 ACACCAAA GGCTAGCTACAACGA ATTCAAGA 5100

2278 GAGUGUGG A UUCGCACU 2078 AGTGCGAA GGCTAGCTACAACGA CCACACTC 5101

2284 GGAUUCGC A CUCCUCCU 2079 AGGAGGAG GGCTAGCTACAACGA GCGAATCC 5102

2295 CCUCCUGC A UAUAGACC 2080 GGTCTATA GGCTAGCTACAACGA GCAGGAGG 5103

2297 UCCUGCAU A UAGACCAC 2081 GTGGTCTA GGCTAGCTACAACGA ATGCAGGA 5104

2301 GCAUAUAG A CCACCAAA 2082 TTTGGTGG GGCTAGCTACAACGA CTATATGC 5105

2304 UAUAGACC A CCAAAUGC 2083 GCATTTGG GGCTAGCTACAACGA GGTCTATA 5106

2309 ACCACCAA A UGCCCCUA 2084 TAGGGGCA GGCTAGCTACAACGA TTGGTGGT 5107

2317 AUGCCCCU A UCUUAUCA 2085 TGATAAGA GGCTAGCTACAACGA AGGGGCAT 5108

2322 CCUAUCUU A UCAACACU 2086 AGTGTTGA GGCTAGCTACAACGA AAGATAGG 5109

2326 UCUUAUCA A CACUUCCG 2087 CGGAAGTG GGCTAGCTACAACGA TGATAAGA 5110

2328 UUAUCAAC A CUUCCGGA 2088 TCCGGAAG GGCTAGCTACAACGA GTTGATAA 5111

2338 UUCCGGAA A CUACUGUU 2089 AACAGTAG GGCTAGCTACAACGA TTCCGGAA 5112 TaDie 4 i

2341 CGGAAACU A CUGUUGUU 2090 AACAACAG GGCTAGCTACAACGA AGTTTCCG 5113

2352 GUUGUUAG A CGAAGAGG 2091 CCTCTTCG GGCTAGCTACAACGA CTAACAAC 5114

2380 GAAGAAGA A CUCCCUCG 2092 CGAGGGAG GGCTAGCTACAACGA TCTTCTTC 5115

2397 CCUCGCAG A CGAAGGUC 2093 GACCTTCG GGCTAGCTACAACGA CTGCGAGG 5116

2409 AGGUCUCA A UCGCCGCG 2094 CGCGGCGA GGCTAGCTACAACGA TGAGACCT 5117

2427 CGCAGAAG A UCUCAAUC 2095 GATTGAGA GGCTAGCTACAACGA CTTCTGCG 5118

2433 AGAUCUCA A UCUCGGGA 2096 TCCCGAGA GGCTAGCTACAACGA TGAGATCT 5119

2442 UCUCGGGA A UCUCAAUG 2097 CATTGAGA GGCTAGCTACAACGA TCCCGAGA 5120

2448 GAAUCUCA A UGUUAGUA 2098 TACTAACA GGCTAGCTACAACGA TGAGATTC 5121

2456 AUGUUAGU A UUCCUUGG 2099 CCAAGGAA GGCTAGCTACAACGA ACTAACAT 5122

2465 UUCCUUGG A CACAUAAG 2100 CTTATGTG GGCTAGCTACAACGA CCAAGGAA 5123

2467 CCUUGGAC A CAUAAGGU 2101 ACCTTATG GGCTAGCTACAACGA GTCCAAGG 5124

2469 UUGGACAC A UAAGGUGG 2102 CCACCTTA GGCTAGCTACAACGA GTGTCCAA 5125

2481 GGUGGGAA A CUUUACGG 2103 CCGTAAAG GGCTAGCTACAACGA TTCCCACC 5126

2486 GAAACUUU A CGGGGCUU 2104 AAGCCCCG GGCTAGCTACAACGA AAAGTTTC 5127

2496 GGGGCUUU A UUCUUCUA 2105 TAGAAGAA GGCTAGCTACAACGA AAAGCCCC 5128

2504 AUUCUUCU A CGGUACCU 2106 AGGTACCG GGCTAGCTACAACGA AGAAGAAT 5129

2509 UCUACGGU A CCUUGCUU 2107 AAGCAAGG GGCTAGCTACAACGA ACCGTAGA 5130

2520 UUGCUUUA A UCCUAAAU 2108 ATTTAGGA GGCTAGCTACAACGA TAAAGCAA 5131

2527 AAUCCUAA A UGGCAAAC 2109 GTTTGCCA GGCTAGCTACAACGA TTAGGATT 5132

2534 AAUGGCAA A CUCCUUCU 2110 AGAAGGAG GGCTAGCTACAACGA TTGCCATT 5133

2550 UUUUCCUG A CAUUCAUU 2111 AATGAATG GGCTAGCTACAACGA CAGGAAAA 5134

2552 UUCCUGAC A UUCAUUUG 2112 CAAATGAA GGCTAGCTACAACGA GTCAGGAA 5135

2556 UGACAUUC A UUUGCAGG 2113 CCTGCAAA GGCTAGCTACAACGA GAATGTCA 5136

2568 GCAGGAGG A CAUUGUUG 2114 CAACAATG GGCTAGCTACAACGA CCTCCTGC 5137

2570 AGGAGGAC A UUGUUGAU 2115 ATCAACAA GGCTAGCTACAACGA GTCCTCCT 5138

2577 CAUUGUUG A UAGAUGUA 2116 TACATCTA GGCTAGCTACAACGA CAACAATG 5139

2581 GUUGAUAG A UGUAAGCA 2117 TGCTTACA GGCTAGCTACAACGA CTATCAAC 5140

2590 UGUAAGCA A UUUGUGGG 2118 CCCACAAA GGCTAGCTACAACGA TGCTTACA 5141

2606 GGCCCCUU A CAGUAAAU 2119 ATTTACTG GGCTAGCTACAACGA AAGGGGCC 5142

2613 UACAGUAA A UGAAAACA 2120 TGTTTTCA GGCTAGCTACAACGA TTACTGTA 5143

2619 AAAUGAAA A CAGGAGAC 2121 GTCTCCTG GGCTAGCTACAACGA TTTCATTT 5144

2626 AACAGGAG A CUUAAAUU 2122 AATTTAAG GGCTAGCTACAACGA CTCCTGTT 5145

2632 AGACUUAA A UUAACUAU 2123 ATAGTTAA GGCTAGCTACAACGA TTAAGTCT 5146

2636 UUAAAUUA A CUAUGCCU 2124 AGGCATAG GGCTAGCTACAACGA TAATTTAA 5147

2639 AAUUAACU A UGCCUGCU 2125 AGCAGGCA GGCTAGCTACAACGA AGTTAATT 5148

2655 UAGGUUUU A UCCCAAUG 2126 CATTGGGA GGCTAGCTACAACGA AAAACCTA 5149

2661 UUAUCCCA A UGUUACUA 2127 TAGTAACA GGCTAGCTACAACGA TGGGATAA 5150

2666 CCAAUGUU A CUAAAUAU 2128 ATATTTAG GGCTAGCTACAACGA AACATTGG 5151

2671 GUUACUAA A UAUUUGCC 2129 GGCAAATA GGCTAGCTACAACGA TTAGTAAC 5152

2673 UACUAAAU A UUUGCCCU 2130 AGGGCAAA GGCTAGCTACAACGA ATTTAGTA 5153

2685 GCCCUUAG A UAAAGGGA 2131 TCCCTTTA GGCTAGCTACAACGA CTAAGGGC 5154

2693 AUAAAGGG A UCAAACCG 2132 CGGTTTGA GGCTAGCTACAACGA CCCTTTAT 5155

2698 GGGAUCAA A CCGUAUUA 2133 TAATACGG GGCTAGCTACAACGA TTGATCCC 5156

2703 CAAACCGU A UUAUCCAG 2134 CTGGATAA GGCTAGCTACAACGA ACGGTTTG 5157

2706 ACCGUAUU A UCCAGAGU 2135 ACTCTGGA GGCTAGCTACAACGA AATACGGT 5158

2715 UCCAGAGU A UGUAGUUA 2136 TAACTACA GGCTAGCTACAACGA ACTCTGGA 5159

2724 UGUAGUUA A UCAUUACU 2137 AGTAATGA GGCTAGCTACAACGA TAACTACA 5160

2727 AGUUAAUC A UUACUUCC 2138 GGAAGTAA GGCTAGCTACAACGA GATTAACT 5161

2730 UAAUCAUU A CUUCCAGA 2139 TCTGGAAG GGCTAGCTACAACGA AATGATTA 5162

2738 ACUUCCAG A CGCGACAU 2140 ATGTCGCG GGCTAGCTACAACGA CTGGAAGT 5163 Taoie 4 1

2743 CAGACGCG A CAUUAUUU 2141 AAATAATG GGCTAGCTACAACGA CGCGTCTG 5164

2745 GACGCGAC A UUAUUUAC 2142 GTAAATAA GGCTAGCTACAACGA GTCGCGTC 5165

2748 GCGACAUU A UUUACACA 2143 TGTGTAAA GGCTAGCTACAACGA AATGTCGC 5166

2752 CAUUAUUU A CACACUCU 2144 AGAGTGTG GGCTAGCTACAACGA AAATAATG 5167

2754 UUAUUUAC A CACUCUUU 2145 AAAGAGTG GGCTAGCTACAACGA GTAAATAA 5168

2756 AUUUACAC A CUCUUUGG 2146 CCAAAGAG GGCTAGCTACAACGA GTGTAAAT 5169

2774 AGGCGGGG A UCUUAUAU 2147 ATATAAGA GGCTAGCTACAACGA CCCCGCCT 5170

2779 GGGAUCUU A UAUAAAAG 2148 CTTTTATA GGCTAGCTACAACGA AAGATCCC 5171

2781 GAUCUUAU A UAAAAGAG 2149 CTCTTTTA GGCTAGCTACAACGA ATAAGATC 5172

2795 GAGAGUCC A CACGUAGC 2150 GCTACGTG GGCTAGCTACAACGA GGACTCTC 5173

2797 GAGUCCAC A CGUAGCGC 2151 GCGCTACG GGCTAGCTACAACGA GTGGACTC 5174

2809 AGCGCCUC A UUUUGCGG 2152 CCGCAAAA GGCTAGCTACAACGA GAGGCGCT 5175

2821 UGCGGGUC A CCAUAUUC 2153 GAATATGG GGCTAGCTACAACGA GACCCGCA 5176

2824 GGGUCACC A UAUUCUUG 2154 CAAGAATA GGCTAGCTACAACGA GGTGACCC 5177

2826 GUCACCAU A UUCUUGGG 2155 CCCAAGAA GGCTAGCTACAACGA ATGGTGAC 5178

2836 UCUUGGGA A CAAGAUCU 2156 AGATCTTG GGCTAGCTACAACGA TCCCAAGA 5179

2841 GGAACAAG A UCUACAGC 2157 GCTGTAGA GGCTAGCTACAACGA CTTGTTCC 5180

2845 CAAGAUCU A CAGCAUGG 2158 CCATGCTG GGCTAGCTACAACGA AGATCTTG 5181

2850 UCUACAGC A UGGGAGGU 2159 ACCTCCCA GGCTAGCTACAACGA GCTGTAGA 5182

2870 UCUUCCAA A CCUCGAAA 2160 TTTCGAGG GGCTAGCTACAACGA TTGGAAGA 5183

2883 GAAAAGGC A UGGGGACA 2161 TGTCCCCA GGCTAGCTACAACGA GCCTTTTC 5184

2889 GCAUGGGG A CAAAUCUU 2162 AAGATTTG GGCTAGCTACAACGA CCCCATGC 5185

2893 GGGGACAA A UCUUUCUG 2163 CAGAAAGA GGCTAGCTACAACGA TTGTCCCC 5186

2908 UGUCCCCA A UCCCCUGG 2164 CCAGGGGA GGCTAGCTACAACGA TGGGGACA 5187

2918 CCCCUGGG A UUCUUCCC 2165 GGGAAGAA GGCTAGCTACAACGA CCCAGGGG 5188

2929 CUUCCCCG A UCAUCAGU 2166 ACTGATGA GGCTAGCTACAACGA CGGGGAAG 5189

2932 CCCCGAUC A UCAGUUGG 2167 CCAACTGA GGCTAGCTACAACGA GATCGGGG 5190

2941 UCAGUUGG A CCCUGCAU 2168 ATGCAGGG GGCTAGCTACAACGA CCAACTGA 5191

2948 GACCCUGC A UUCAAAGC 2169 GCTTTGAA GGCTAGCTACAACGA GCAGGGTC 5192

2959 CAAAGCCA A CUCAGUAA 2170 TTACTGAG GGCTAGCTACAACGA TGGCTTTG 5193

2968 CUCAGUAA A UCCAGAUU 2171 AATCTGGA GGCTAGCTACAACGA TTACTGAG 5194

2974 AAAUCCAG A UUGGGACC 2172 GGTCCCAA GGCTAGCTACAACGA CTGGATTT 5195

2980 AGAUUGGG A CCUCAACC 2173 GGTTGAGG GGCTAGCTACAACGA CCCAATCT 5196

2986 GGACCUCA A CCCGCACA 2174 TGTGCGGG GGCTAGCTACAACGA TGAGGTCC 5197

2998 GCACAAGG A CAACUGGC 2175 GCCAGTTG GGCTAGCTACAACGA CCTTGTGC 5198

3001 CAAGGACA A CUGGCCGG 2176 CCGGCCAG GGCTAGCTACAACGA TGTCCTTG 5199

3010 CUGGCCGG A CGCCAACA 2177 TGTTGGCG GGCTAGCTACAACGA CCGGCCAG 5200

3016 GGACGCCA A CAAGGUGG 2178 CCACCTTG GGCTAGCTACAACGA TGGCGTCC 5201

3035 GUGGGAGC A UUCGGGCC 2179 GGCCCGAA GGCTAGCTACAACGA GCTCCCAC 5202

3051 CAGGGUUC A CCCCUCCC 2180 GGGAGGGG GGCTAGCTACAACGA GAACCCTG 5203

3061 CCCUCCCC A UGGGGGAC 2181 GTCCCCCA GGCTAGCTACAACGA GGGGAGGG 5204

3068 CAUGGGGG A CUGUUGGG 2182 CCCAACAG GGCTAGCTACAACGA CCCCCATG 5205

3088 GAGCCCUC A CGCUCAGG 2183 CCTGAGCG GGCTAGCTACAACGA GAGGGCTC 5206

3101 CAGGGCCU A CUCACAAC 2184 GTTGTGAG GGCTAGCTACAACGA AGGCCCTG 5207

3105 GCCUACUC A CAACUGUG 2185 CACAGTTG GGCTAGCTACAACGA GAGTAGGC 5208

3108 UACUCACA A CUGUGCCA 2186 TGGCACAG GGCTAGCTACAACGA TGTGAGTA 5209

3138 CUGCCUCC A CCAAUCGG 2187 CCGATTGG GGCTAGCTACAACGA GGAGGCAG 5210

3142 CUCCACCA A UCGGCAGU 2188 ACTGCCGA GGCTAGCTACAACGA TGGTGGAG 5211

3165 GGCAGCCU A CUCCCUUA 2189 TAAGGGAG GGCTAGCTACAACGA AGGCTGCC 5212

3173 ACUCCCUU A UCUCCACC 2190 GGTGGAGA GGCTAGCTACAACGA AAGGGAGT 5213

3179 UUAUCUCC A CCUCUAAG 2191 CTTAGAGG GGCTAGCTACAACGA GGAGATAA 5214 Taσie 4

Input Sequence = AF100308. Cut Site = YG/M or UG/U. Stem Length = 8 . Core Sequence = GGCTAGCTACAACGA AF100308 (Hepatitis B virus strain 2-18, 3215 bp)

Table 42

Table 42: Human HBV Amberzyme Ribozyme and Substrate Sequence

Pos Substrate Seq ID Ribozyme Rz Seq ID

61 ACUUUCCU G CUGGUGGC 1448 GCCACCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAAAGU 5219

87 GGAACAGU G AGCCCUGC 1449 GCAGGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGUUCC 5220

94 UGAGCCCU G CUCAGAAU 1450 AUUCUGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGCUCA 5221

112 CUGUCUCU G CCAUAUCG 1451 CGAUAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGACAG 5222

132 AUCUUAUC G AAGACUGG 1452 CCAGUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUAAGAU 5223

153 CCUGUACC G AACAUGGA 1453 UCCAUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUACAGG 5224

169 AGAACAUC G CAUCAGGA 1454 UCCUGAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUGUUCU 5225

192 GGACCCCU G CUCGUGUU 1455 AACACGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGGUCC 5226

222 UUCUUGUU G ACAAAAAU 1456 AUUUUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAAGAA 5227

315 CAAAAUUC G CAGUCCCA 1457 UGGGACUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAUUUUG 5228

374 UGGUUAUC G CUGGAUGU 1458 ACAUCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUAACCA 5229

387 AUGUGUCU G CGGCGUUU 1459 AAACGCCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGACACAU 5230

410 CUUCCUCU G CAUCCUGC 1460 GCAGGAUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAGGAAG 5231

417 UGCAUCCU G CUGCUAUG 1461 CAUAGCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGAUGCA 5232

420 AUCCUGCU G CUAUGCCU 1462 AGGCAUAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCAGGAU 5233

425 GCUGCUAU G CCUCAUCU 1463 AGAUGAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAGCAGC 5234

468 GGUAUGUU G CCCGUUUG 1464 CAAACGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AACAUACC 5235

518 CGGACCAU G CAAAACCU 1465 AGGUUUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGGUCCG 5236

527 CAAAACCU G CACAACUC 1466 GAGUUGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGUUUUG 5237

538 CAACUCCU G CUCAAGGA 1467 UCCUUGAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGAGUUG 5238

569 CUCAUGUU G CUGUACAA 1468 UUGUACAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AACAUGAG 5239

596 CGGAAACU G CACCUGUA 1469 UACAGGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUUUCCG 5240

631 GGGCUUUC G CAAAAUAC 1470 GUAUUUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAAAGCCC 5241

687 UUACUAGU G CCAUUUGU 1471 ACAAAUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACUAGUAA 5242

747 AUAUGGAU G AUGUGGUU 1472 AACCACAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCCAUAU 5243

783 AACAUCUU G AGUCCCUU 1473 AAGGGACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGAUGUU 5244

795 CCCUUUAU G CCGCUGUU 1474 AACAGCGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAAAGGG 5245

798 UUUAUGCC G CUGUUACC 1475 GGUAACAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGCAUAAA 5246

911 GGCACAUU G CCACAGGA 1476 UCCUGUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUGUGCC 5247

978 GGCCUAUU G AUUGGAAA 1477 UUUCCAAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUAGGCC 5248

Table 42

997 AUGUCAAC G AAUUGUGG 1478 CCACAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUGACAU 5249

1020 UGGGGUUU G CCGCCCCU 1479 AGGGGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAACCCCA 5250

1023 GGUUUGCC G CCCCUUUC 1480 GAAAGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCAAACC 5251

1034 CCUUUCAC G CAAUGUGG 1481 CCACAUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUGAAAGG 5252

1050 GAUAUUCU G CUUUAAUG 1482 CAUUAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAUAUC 5253

1058 GCUUUAAU G CCUUUAUA 1483 UAUAAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUAAAGC 5254

1068 CUUUAUAU G CAUGCAUA 1484 UAUGCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAUAAAG 5255

1072 AUAUGCAU G CAUACAAG 1485 CUUGUAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCAUAU 5256

1103 ACUUUCUC G CCAACUUA 1486 UAAGUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGAAAGU 5257

1139 CAGUAUGU G AACCUUUA 1487 UAAAGGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUACUG 5258

1155 ACCCCGUU G CUCGGCAA 1488 UUGCCGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACGGGGU 5259

1177 UGGUCUAU G CCAAGUGU 1489 ACACUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAGACCA 5260

1188 AAGUGUUU G CUGACGCA 1490 UGCGUCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAACACUU 5261

1191 UGUUUGCU G ACGCAACC 1491 GGUUGCGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCAAACA 5262

1194 UUGCUGAC G CAACCCCC 1492 GGGGGUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUCAGCAA 5263

1234 CCAUCAGC G CAUGCGUG 1493 CACGCAUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCUGAUGG 5264

1238 CAGCGCAU G CGUGGAAC 1494 GUUCCACG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGCGCUG 5265

1262 UCUCCUCU G CCGAUCCA 1495 UGGAUCGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAGGAGA 5266

1265 CCUCUGCC G AUCCAUAC 1496 GUAUGGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGCAGAGG 5267

1275 UCCAUACC G CGGAACUC 1497 GAGUUCCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGUAUGGA 5268

1290 UCCUAGCC G CUUGUUUU 1498 AAAACAAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGCUAGGA 5269

1299 CUUGUUUU G CUCGCAGC 1499 GCUGCGAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAACAAG 5270

1303 UUUUGCUC G CAGCAGGU 1500 ACCUGCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAGCAAAA 5271

1335 UCGGGACU G AGAAUUCU 1501 AGAAUUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUCCCGA 5272

1349 UCUGUCGU G CUCUCCCG 1502 CGGGAGAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACGACAGA 5273

1357 GCUCUCCC G CAAAUAUA 1503 UAUAUUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGAGAGC 5274

1382 CCAUGGCU G CUAGGCUG 1504 CAGCCUAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCCAUGG 5275

1392 UAGGCUGU G CUGCCAAC 1505 GUUGGCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAGCCUA 5276

1395 GCUGUGCU G CCAACUGG 1506 CCAGUUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCACAGC 5277

1411 GAUCCUAC G CGGGACGU 1507 ACGUCCCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUAGGAUC 5278

1442 CCGUCGGC G CUGAAUCC 1508 GGAUUCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCCGACGG 5279

1445 UCGGCGCU G AAUCCCGC 1509 GCGGGAUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCGCCGA 5280

1452 UGAAUCCC G CGGACGAC 1510 GUCGUCCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGAUUCA 5281

1458 CCGCGGAC G ACCCCUCC 1511 GGAGGGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUCCGCGG 5282

Table 42

1474 CCGGGGCC G CUUGGGGC 1512 GCCCCAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCCCCGG 5283

1489 GCUCUACC G CCCGCUUC 1513 GAAGCGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUAGAGC 5284

1493 UACCGCCC G CUUCUCCG 1514 CGGAGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGCGGUA 5285

1501 GCUUCUCC G CCUAUUGU 1515 ACAAUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAGAAGC 5286

1513 AUUGUACC G ACCGUCCA 1516 UGGACGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUACAAU 5287

1528 CACGGGGC G CACCUCUC 1517 GAGAGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCCCGUG 5288

1542 CUCUUUAC G CGGACUCC 1518 GGAGUCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAAAGAG 5289

1559 CCGUCUGU G CCUUCUCA 1519 UGAGAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGACGG 5290

1571 UCUCAUCU G CCGGACCG 1520 CGGUCCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAUGAGA 5291

1583 GACCGUGU G CACUUCGC 1521 GCGAAGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACGGUC 5292

1590 UGCACUUC G CUUCACCU 1522 AGGUGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAGUGCA 5293

1601 UCACCUCU G CACGUCGC 1523 GCGACGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGGUGA 5294

1608 UGCACGUC G CAUGGAGA 1524 UCUCCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACGUGCA 5295

1624 ACCACCGU G AACGCCCA 1525 UGGGCGUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACGGUGGU 5296

1628 CCGUGAAC G CCCACAGG 1526 CCUGUGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUUCACGG 5297

1642 AGGAACCU G CCCAAGGU 1527 ACCUUGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGUUCCU 5298

1654 AAGGUCUU G CAUAAGAG 1528 CUCUUAUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGACCUU 5299

1690 AUGUCAAC G ACCGACCU 1529 AGGUCGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUUGACAU 5300

1694 CAACGACC G ACCUUGAG 1530 CUCAAGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGUCGUUG 5301

1700 CCGACCUU G AGGCAUAC 1531 GUAUGCCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGGUCGG 5302

1730 UGUUUAAU G AGUGGGAG 1532 CUCCCACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUUAAACA 5303

1818 AGCACCAU G CAACUUUU 1533 AAAAGUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGGUGCU 5304

1835 UCACCUCU G CCUAAUCA 1534 UGAUUAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAGGUGA 5305

1883 CAAGCUGU G CCUUGGGU 1535 ACCCAAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAGCUUG 5306

1912 UGGACAUU G ACCCGUAU 1536 AUACGGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUGUCCA 5307

1959 UCUUUUUU G CCUUCUGA 1537 UCAGAAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAAAAGA 5308

1966 UGCCUUCU G ACUUCUUU 1538 AAAGAAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAAGGCA 5309

1985 UUCUAUUC G AGAUCUCC 1539 GGAGAUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAAUAGAA 5310

1996 AUCUCCUC G ACACCGCC 1540 GGCGGUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAGGAGAU 5311

2002 UCGACACC G CCUCUGCU 1541 AGCAGAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGUGUCGA 5312

2008 CCGCCUCU G CUCUGUAU 1542 AUACAGAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAGGCGG 5313

2092 GUUGGGGU G AGUUGAUG 1543 CAUCAACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCCCAAC 5314

2097 GGUGAGUU G AUGAAUCU 1544 AGAUUCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AACUCACC 5315

2100 GAGUUGAU G AAUCUAGC 1545 GCUAGAUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCAACUC 5316

Table 42

2237 UUUUGGGC G AGAAACUG 1546 CAGUUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCCAAAA 5317

2251 CUGUUCUU G AAUAUUUG 1547 CAAAUAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAACAG 5318

2282 GUGGAUUC G CACUCCUC 1548 GAGGAGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAUCCAC 5319

2293 CUCCUCCU G CAUAUAGA 1549 UCUAUAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAGGAG 5320

2311 CACCAAAU G CCCCUAUC 1550 GAUAGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUGGUG 5321

2354 UGUUAGAC G AAGAGGCA 1551 UGCCUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCUAACA 5322

2388 ACUCCCUC G CCUCGCAG 1552 CUGCGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGGGAGU 5323

2393 CUCGCCUC G CAGACGAA 1553 UUCGUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGGCGAG 5324

2399 UCGCAGAC G AAGGUCUC 1554 GAGACCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCUGCGA 5325

2412 UCUCAAUC G CCGCGUCG 1555 CGACGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUUGAGA 5326

2415 CAAUCGCC G CGUCGCAG 1556 CUGCGACG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCGAUUG 5327

2420 GCCGCGUC G CAGAAGAU 1557 AUCUUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACGCGGC 5328

2514 GGUACCUU G CUUUAAUC 1558 GAUUAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGUACC 5329

2549 CUUUUCCU G ACAUUCAU 1559 AUGAAUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGAAAAG 5330

2560 AUUCAUUU G CAGGAGGA 1560 UCCUCCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAUGAAU 5331

2576 ACAUUGUU G AUAGAUGU 1561 ACAUCUAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AACAAUGU 5332

2615 CAGUAAAU G AAAACAGG 1562 CCUGUUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUUUACUG 5333

2641 UUAACUAU G CCUGCUAG 1563 CUAGCAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAGUUAA 5334

2645 CUAUGCCU G CUAGGUUU 1564 AAACCUAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGCAUAG 5335

2677 AAAUAUUU G CCCUUAGA 1565 UCUAAGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAUAUUU 5336

2740 UUCCAGAC G CGACAUUA 1566 UAAUGUCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUCUGGAA 5337

2742 CCAGACGC G ACAUUAUU 1567 AAUAAUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCGUCUGG 5338

2804 CACGUAGC G CCUCAUUU 1568 AAAUGAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCUACGUG 5339

2814 CUCAUUUU G CGGGUCAC 1569 GUGACCCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAAUGAG 5340

2875 CAAACCUC G AAAAGGCA 1570 UGCCUUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAGGUUUG 5341

2928 UCUUCCCC G AUCAUCAG 1571 CUGAUGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGGAAGA 5342

2946 UGGACCCU G CAUUCAAA 1572 UUUGAAUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGGUCCA 5343

2990 CUCAACCC G CACAAGGA 1573 UCCUUGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGUUGAG 5344

3012 GGCCGGAC G CCAACAAG 1574 CUUGUUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUCCGGCC 5345

3090 GCCCUCAC G CUCAGGGC 1575 GCCCUGAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUGAGGGC 5346

3113 ACAACUGU G CCAGCAGC 1576 GCUGCUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAGUUGU 5347

3132 CUCCUCCU G CCUCCACC 1577 GGUGGAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGAGGAG 5348

51 AGGGCCCU G UACUUUCC 1578 GGAAAGUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGGCCCU 5349

106 AGAAUACU G UCUCUGCC 1579 GGCAGAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUAUUCU 5350

Table 42

148 GGGACCCU G UACCGAAC 1580 GUUCGGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGUCCC 5351

198 CUGCUCGU G UUACAGGC 1581 GCCUGUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGAGCAG 5352

219 UUUUUCUU G UUGACAAA 1582 UUUGUCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAAAAA 5353

297 ACACCCGU G UGUCUUGG 1583 CCAAGACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGGGUGU 5354

299 ACCCGUGU G UCUUGGCC 1584 GGCCAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACGGGU 5355

347 ACCAACCU G UUGUCCUC 1585 GAGGACAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUUGGU 5356

350 AACCUGUU G UCCUCCAA 1586 UUGGAGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAGGUU 5357

362 UCCAAUUU G UCCUGGUU 1587 AACCAGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUUGGA 5358

381 CGCUGGAU G UGUCUGCG 1588 CGCAGACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCCAGCG 5359

383 CUGGAUGU G UCUGCGGC 1589 GCCGCAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUCCAG 5360

438 AUCUUCUU G UUGGUUCU 1590 AGAACCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAAGAU 5361

465 CAAGGUAU G UUGCCCGU 1591 ACGGGCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUACCUUG 5362

476 GCCCGUUU G UCCUCUAA 1592 UUAGAGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAACGGGC 5363

555 ACCUCUAU G UUUCCCUC 1593 GAGGGAAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAGAGGU 5364

566 UCCCUCAU G UUGCUGUA 1594 UACAGCAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGAGGGA 5365

572 AUGUUGCU G UACAAAAC 1595 GUUUUGUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCAACAU 5366

602 CUGCACCU G UAUUCCCA 1596 UGGGAAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGUGCAG 5367

694 UGCCAUUU G UUCAGUGG 1597 CCACUGAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAUGGCA 5368

724 CCCCCACU G UCUGGCUU 1598 AAGCCAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUGGGGG 5369

750 UGGAUGAU G UGGUUUUG 1599 CAAAACCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCAUCCA 5370

771 CCAAGUCU G UACAACAU 1600 AUGUUGUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGACUUGG 5371

801 AUGCCGCU G UUACCAAU 1601 AUUGGUAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCGGCAU 5372

818 UUUCUUUU G UCUUUGGG 1602 CCCAAAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAAGAAA 5373

888 UGGGAUAU G UAAUUGGG 1603 CCCAAUUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAUCCCA 5374

927 AACAUAUU G UACAAAAA 1604 UUUUUGUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUAUGUU 5375

944 AUCAAAAU G UGUUUUAG 1605 CUAAAACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUUUUGAU 5376

946 CAAAAUGU G UUUUAGGA 1606 UCCUAAAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAUUUUG 5377

963 AACUUCCU G UAAACAGG 1607 CCUGUUUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGAAGUU 5378

991 GAAAGUAU G UCAACGAA 1608 UUCGUUGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUACUUUC 5379

1002 AACGAAUU G UGGGUCUU 1609 AAGACCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUUCGUU 5380

1039 CACGCAAU G UGGAUAUU 1610 AAUAUCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUUGCGUG 5381

1137 AACAGUAU G UGAACCUU 1611 AAGGUUCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUACUGUU 5382

1184 UGCCAAGU G UUUGCUGA 1612 UCAGCAAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACUUGGCA 5383

1251 GAACCUUU G UGUCUCCU 1613 AGGAGACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAGGUUC 5384

Table 42

1253 ACCUUUGU G UCUCCUCU 1614 AGAGGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAAAGGU 5385

1294 AGCCGCUU G UUUUGCUC 1615 GAGCAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGCGGCU 5386

1344 ACAAUUCU G UCGUGCUC 1616 GAGCACGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAUUGU 5387

1390 GCUAGGCU G UGCUGCCA 1617 UGGCAGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCUAGC 5388

1425 CGUCCUUU G UUUACGUC 1618 GACGUAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGGACG 5389

1508 CGCCUAUU G UACCGACC 1619 GGUCGGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUAGGCG 5390

1557 CCCCGUCU G UGCCUUCU 1620 AGAAGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGACGGGG 5391

1581 CGGACCGU G UGCACUUC 1621 GAAGUGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGGUCCG 5392

1684 UCAGCAAU G UCAACGAC 1622 GUCGUUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUGCUGA 5393

1719 CAAAGACU G UGUGUUUA 1623 UAAACACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUCUUUG 5394

1721 AAGACUGU G UGUUUAAU 1624 AUUAAACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGUCUU 5395

1723 GACUGUGU G UUUAAUGA 1625 UCAUUAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACAGUC 5396

1772 AGGUCUUU G UACUAGGA 1626 UCCUAGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGACCU 5397

1785 AGGAGGCU G UAGGCAUA 1627 UAUGCCUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCCUCCU 5398

1801 AAAUUGGU G UGUUCACC 1628 GGUGAACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCAAUUU 5399

1803 AUUGGUGU G UUCACCAG 1629 CUGGUGAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACACCAAU 5400

1850 CAUCUCAU G UUCAUGUC 1630 GACAUGAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGAGAUG 5401

1856 AUGUUCAU G UCCUACUG 1631 CAGUAGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGAACAU 5402

1864 GUCCUACU G UUCAAGCC 1632 GGCUUGAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUAGGAC 5403

1881 UCCAAGCU G UGCCUUGG 1633 CCAAGGCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGCUUGGA 5404

1939 GAGCUUCU G UGGAGUUA 1634 UAACUCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAAGCUC 5405

2013 UCUGCUCU G UAUCGGGG 1635 CCCCGAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAGCAGA 5406

2045 GGAACAUU G UUCACCUC 1636 GAGGUGAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUGUUCC 5407

2082 GCUAUUCU G UGUUGGGG 1637 CCCCAACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAAUAGC 5408

2084 UAUUCUGU G UUGGGGUG 1638 CACCCCAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAGAAUA 5409

2167 UCAGCUAU G UCAACGUU 1639 AACGUUGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAGCUGA 5410

2205 CAACUAUU G UGGUUUCA 1640 UGAAACCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUAGUUG 5411

2222 CAUUUCCU G UCUUACUU 1641 AAGUAAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGGAAAUG 5412

2245 GAGAAACU G UUCUUGAA 1642 UUCAAGAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUUUCUC 5413

2262 UAUUUGGU G UCUUUUGG 1643 CCAAAAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCAAAUA 5414

2274 UUUGGAGU G UGGAUUCG 1644 CGAAUCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACUCCAAA 5415

2344 AAACUACU G UUGUUAGA 1645 UCUAACAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUAGUUU 5416

2347 CUACUGUU G UUAGACGA 1646 UCGUCUAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AACAGUAG 5417

2450 AUCUCAAU G UUAGUAUU 1647 AAUACUAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUUGAGAU 5418

Table 42

2573 AGGACAUU G UUGAUAGA 1648 UCUAUCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUGUCCU 5419

2583 UGAUAGAU G UAAGCAAU 1649 AUUGCUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCUAUCA 5420

2594 AGCAAUUU G UGGGGCCC 1650 GGGCCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUUGCU 5421

2663 AUCCCAAU G UUACUAAA 1651 UUUAGUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUGGGAU 5422

2717 CAGAGUAU G UAGUUAAU 1652 AUUAACUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUACUCUG 5423

2901 AUCUUUCU G UCCCCAAU 1653 AUUGGGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAAGAU 5424

3071 GGGGGACU G UUGGGGUG 1654 CACCCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUCCCCC 5425

3111 UCACAACU G UGCCAGCA 1655 UGCUGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUGUGA 5426

40 AUCCCAGA G UCAGGGCC 1656 GGCCCUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGGGAU 5427

46 GAGUCAGG G CCCUGUAC 1657 GUACAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGACUC 5428

65 UCCUGCUG G UGGCUCCA 1658 UGGAGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCAGGA 5429

68 UGCUGGUG G CUCCAGUU 1659 AACUGGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCAGCA 5430

74 UGGCUCCA G UUCAGGAA 1660 UUCCUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAGCCA 5431

85 CAGGAACA G UGAGCCCU 1661 AGGGCUCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUUCCUG 5432

89 AACAGUGA G CCCUGCUC 1662 GAGCAGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCACUGUU 5433

120 GCCAUAUC G UCAAUCUU 1663 AAGAUUGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAUAUGGC 5434

196 CCCUGCUC G UGUUACAG 1664 CUGUAACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAGCAGGG 5435

205 UGUUACAG G CGGGGUUU 1665 AAACCCCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGUAACA 5436

210 CAGGCGGG G UUUUUCUU 1666 AAGAAAAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCGCCUG 5437

248 ACCACAGA G UCUAGACU 1667 AGUCUAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCUGUGGU 5438

258 CUAGACUC G UGGUGGAC 1668 GUCCACCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAGUCUAG 5439

261 GACUCGUG G UGGACUUC 1669 GAAGUCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACGAGUC 5440

295 GAACACCC G UGUGUCUU 1670 AAGACACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGUGUUC 5441

305 GUGUCUUG G CCAAAAUU 1671 AAUUUUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAGACAC 5442

318 AAUUCGCA G UCCCAAAU 1672 AUUUGGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCGAAUU 5443

332 AAUCUCCA G UCACUCAC 1673 GUGAGUGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGAGAUU 5444

368 UUGUCCUG G UUAUCGCU 1674 AGCGAUAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGGACAA 5445

390 UGUCUGCG G CGUUUUAU 1675 AUAAAACG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGCAGACA 5446

392 UCUGCGGC G UUUUAUCA 1676 UGAUAAAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCCGCAGA 5447

442 UCUUGUUG G UUCUUCUG 1677 CAGAAGAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAACAAGA 5448

461 CUAUCAAG G UAUGUUGC 1678 GCAACAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUGAUAG 5449

472 UGUUGCCC G UUUGUCCU 1679 AGGACAAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGCAACA 5450

506 AACAACCA G CACCGGAC 1680 GUCCGGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGUUGUU 5451

625 CAUCUUGG G CUUUCGCA 1681 UGCGAAAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAAGAUG 5452

Table 42

648 CUAUGGGA G UGGGCCUC 1682 GAGGCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCAUAG 5453

652 GGGAGUGG G CCUCAGUC 1683 GACUGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACUCCC 5454

658 GGGCCUCA G UCCGUUUC 1684 GAAACGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGGCCC 5455

662 CUCAGUCC G UUUCUCUU 1685 AAGAGAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGACUGAG 5456

672 UUCUCUUG G CUCAGUUU 1686 AAACUGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGAGAA 5457

677 UUGGCUCA G UUUACUAG 1687 CUAGUAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGCCAA 5458

685 GUUUACUA G UGCCAUUU 1688 AAAUGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGUAAAC 5459

699 UUUGUUCA G UGGUUCGU 1689 ACGAACCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAACAAA 5460

702 GUUCAGUG G UUCGUAGG 1690 CCUACGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUGAAC 5461

706 AGUGGUUC G UAGGGCUU 1691 AAGCCCUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAACCACU 5462

711 UUCGUAGG G CUUUCCCC 1692 GGGGAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUACGAA 5463

729 ACUGUCUG G CUUUCAGU 1693 ACUGAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGACAGU 5464

736 GGCUUUCA G UUAUAUGG 1694 CCAUAUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAAGCC 5465

753 AUGAUGUG G UUUUGGGG 1695 CCCCAAAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACAUCAU 5466

762 UUUUGGGG G CCAAGUCU 1696 AGACUUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCCAAAA 5467

767 GGGGCCAA G UCUGUACA 1697 UGUACAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGGCCCC 5468

785 CAUCUUGA G UCCCUUUA 1698 UAAAGGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCAAGAUG 5469

826 GUCUUUGG G UAUACAUU 1699 AAUGUAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAAAGAC 5470

898 AAUUGGGA G UUGGGGCA 1700 UGCCCCAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCCAAUU 5471

904 GAGUUGGG G CACAUUGC 1701 GCAAUGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCAACUC 5472

971 GUAAACAG G CCUAUUGA 1702 UCAAUAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGUUUAC 5473

987 AUUGGAAA G UAUGUCAA 1703 UUGACAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUCCAAU 5474

1006 AAUUGUGG G UCUUUUGG 1704 CCAAAAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCACAAUU 5475

1016 CUUUUGGG G UUUGCCGC 1705 GCGGCAAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCAAAAG 5476

1080 GCAUACAA G CAAAACAG 1706 CUGUUUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGUAUGC 5477

1089 CAAAACAG G CUUUUACU 1707 AGUAAAAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGUUUUG 5478

1116 CUUACAAG G CCUUUCUA 1708 UAGAAAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUGUAAG 5479

1126 CUUUCUAA G UAAACAGU 1709 ACUGUUUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUAGAAAG 5480

1133 AGUAAACA G UAUGUGAA 1710 UUCACAUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUUUACU 5481

1152 UUUACCCC G UUGCUCGG 1711 CCGAGCAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGGUAAA 5482

1160 GUUGCUCG G CAACGGCC 1712 GGCCGUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGAGCAAC 5483

1166 CGGCAACG G CCUGGUCU 1713 AGACCAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGUUGCCG 5484

1171 ACGGCCUG G UCUAUGCC 1714 GGCAUAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGGCCGU 5485

1182 UAUGCCAA G UGUUUGCU 1715 AGCAAACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGGCAUA 5486

Table 42

1207 CCCCACUG G UUGGGGCU 1716 AGCCCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGUGGGG 5487

1213 UGGUUGGG G CUUGGCCA 1717 UGGCCAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAACCA 5488

1218 GGGGCUUG G CCAUAGGC 1718 GCCUAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGCCCC 5489

1225 GGCCAUAG G CCAUCAGC 1719 GCUGAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAUGGCC 5490

1232 GGCCAUCA G CGCAUGCG 1720 CGCAUGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUGGCC 5491

1240 GCGCAUGC G UGGAACCU 1721 AGGUUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAUGCGC 5492

1287 AACUCCUA G CCGCUUGU 1722 ACAAGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGGAGUU 5493

1306 UGCUCGCA G CAGGUCUG 1723 CAGACCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCGAGCA 5494

1310 CGCAGCAG G UCUGGGGC 1724 GCCCCAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCUGCG 5495

1317 GGUCUGGG G CAAAACUC 1725 GAGUUUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCAGACC 5496

1347 AUUCUGUC G UGCUCUCC 1726 GGAGAGCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GACAGAAU 5497

1379 UUUCCAUG G CUGCUAGG 1727 CCUAGCAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUGGAAA 5498

1387 GCUGCUAG G CUGUGCUG 1728 CAGCACAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUAGCAGC 5499

1418 CGCGGGAC G UCCUUUGU 1729 ACAAAGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUCCCGCG 5500

1431 UUGUUUAC G UCCCGUCG 1730 CGACGGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUAAACAA 5501

1436 UACGUCCC G UCGGCGCU 1731 AGCGCCGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGACGUA 5502

1440 UCCCGUCG G CGCUGAAU 1732 AUUCAGCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGACGGGA 5503

1471 CUCCCGGG G CCGCUUGG 1733 CCAAGCGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCGGGAG 5504

1481 CGCUUGGG G CUCUACCG 1734 CGGUAGAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCAAGCG 5505

1517 UACCGACC G UCCACGGG 1735 CCCGUGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGUCGGUA 5506

1526 UCCACGGG G CGCACCUC 1736 GAGGUGCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCGUGGA 5507

1553 GACUCCCC G UCUGUGCC 1737 GGCACAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGGGAGUC 5508

1579 GCCGGACC G UGUGCACU 1738 AGUGCACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGUCCGGC 5509

1605 CUCUGCAC G UCGCAUGG 1739 CCAUGCGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUGCAGAG 5510

1622 AGACCACC G UGAACGCC 1740 GGCGUUCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGUGGUCU 5511

1649 UGCCCAAG G UCUUGCAU 1741 AUGCAAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUGGGCA 5512

1679 GACUUUCA G CAAUGUCA 1742 UGACAUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGAAAGUC 5513

1703 ACCUUGAG G CAUACUUC 1743 GAAGUAUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCAAGGU 5514

1732 UUUAAUGA G UGGGAGGA 1744 UCCUCCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCAUUAAA 5515

1741 UGGGAGGA G UUGGGGGA 1745 UCCCCCAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCUCCCA 5516

1754 GGGAGGAG G UUAGGUUA 1746 UAACCUAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCCUCCC 5517

1759 GAGGUUAG G UUAAAGGU 1747 ACCUUUAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUAACCUC 5518

1766 GGUUAAAG G UCUUUGUA 1748 UACAAAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUUAACC 5519

1782 ACUAGGAG G CUGUAGGC 1749 GCCUACAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCCUAGU 5520

Table 42

1789 GGCUGUAG G CAUAAAUU 1750 AAUUUAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUACAGCC 5521

1799 AUAAAUUG G UGUGUUCA 1751 UGAACACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAUUUAU 5522

1811 GUUCACCA G CACCAUGC 1752 GCAUGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUGAAC 5523

1870 CUGUUCAA G CCUCCAAG 1753 CUUGGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAACAG 5524

1878 GCCUCCAA G CUGUGCCU 1754 AGGCACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGAGGC 5525

1890 UGCCUUGG G UGGCUUUG 1755 CAAAGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAGGCA 5526

1893 CUUGGGUG G CUUUGGGG 1756 CCCCAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCCAAG 5527

1901 GCUUUGGG G CAUGGACA 1757 UGUCCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAAAGC 5528

1917 AUUGACCC G UAUAAAGA 1758 UCUUUAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGUCAAU 5529

1933 AAUUUGGA G CUUCUGUG 1759 CACAGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAAAUU 5530

1944 UCUGUGGA G UUACUCUC 1760 GAGAGUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCACAGA 5531

2023 AUCGGGGG G CCUUAGAG 1761 CUCUAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCCGAU 5532

2031 GCCUUAGA G UCUCCGGA 1762 UCCGGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUAAGGC 5533

2062 ACCAUACG G CACUCAGG 1763 CCUGAGUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGUAUGGU 5534

2070 GCACUCAG G CAAGCUAU 1764 AUAGCUUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGAGUGC 5535

2074 UCAGGCAA G CUAUUCUG 1765 CAGAAUAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGCCUGA 5536

2090 GUGUUGGG G UGAGUUGA 1766 UCAACUCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCAACAC 5537

2094 UGGGGUGA G UUGAUGAA 1767 UUCAUCAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCACCCCA 5538

2107 UGAAUCUA G CCACCUGG 1768 CCAGGUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAGAUUCA 5539

2116 CCACCUGG G UGGGAAGU 1769 ACUUCCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAGGUGG 5540

2123 GGUGGGAA G UAAUUUGG 1770 CCAAAUUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCCCACC 5541

2140 AAGAUCCA G CAUCCAGG 1771 CCUGGAUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGAUCUU 5542

2155 GGGAAUUA G UAGUCAGC 1772 GCUGACUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAAUUCCC 5543

2158 AAUUAGUA G UCAGCUAU 1773 AUAGCUGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UACUAAUU 5544

2162 AGUAGUCA G CUAUGUCA 1774 UGACAUAG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGACUACU 5545

2173 AUGUCAAC G UUAAUAUG 1775 CAUAUUAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUUGACAU 5546

2183 UAAUAUGG G CCUAAAAA 1776 UUUUUAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAUAUUA 5547

2208 CUAUUGUG G UUUCACAU 1777 AUGUGAAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACAAUAG 5548

2235 ACUUUUGG G CGAGAAAC 1778 GUUUCUCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAAAAGU 5549

2260 AAUAUUUG G UGUCUUUU 1779 AAAAGACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAAUAUU 5550

2272 CUUUUGGA G UGUGGAUU 1780 AAUCCACA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCAAAAG 5551

2360 ACGAAGAG G CAGGUCCC 1781 GGGACCUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCUUCGU 5552

2364 AGAGGCAG G UCCCCUAG 1782 CUAGGGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGCCUCU 5553

2403 AGACGAAG G UCUCAAUC 1783 GAUUGAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUCGUCU 5554

Table 42

2417 AUCGCCGC G UCGCAGAA 1784 UUCUGCGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGGCGAU 5555

2454 CAAUGUUA G UAUUCCUU 1785 AAGGAAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAACAUUG 5556

2474 CACAUAAG G UGGGAAAC 1786 GUUUCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUAUGUG 5557

2491 UUUACGGG G CUUUAUUC 1787 GAAUAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCGUAAA 5558

2507 CUUCUACG G UACCUUGC 1788 GCAAGGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUAGAAG 5559

2530 CCUAAAUG G CAAACUCC 1789 GGAGUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUUUAGG 5560

2587 AGAUGUAA G CAAUUUGU 1790 ACAAAUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUACAUCU 5561

2599 UUUGUGGG G CCCCUUAC 1791 GUAAGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCACAAA 5562

2609 CCCUUACA G UAAAUGAA 1792 UUCAUUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUAAGGG 5563

2650 CCUGCUAG G UUUUAUCC 1793 GGAUAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAGCAGG 5564

2701 AUCAAACC G UAUUAUCC 1794 GGAUAAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUUUGAU 5565

2713 UAUCCAGA G UAUGUAGU 1795 ACUACAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGGAUA 5566

2720 AGUAUGUA G UUAAUCAU 1796 AUGAUUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACAUACU 5567

2768 UUUGGAAG G CGGGGAUC 1797 GAUCCCCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUCCAAA 5568

2791 AAAAGAGA G UCCACACG 1798 CGUGUGGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCUCUUUU 5569

2799 GUCCACAC G UAGCGCCU 1799 AGGCGCUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUGUGGAC 5570

2802 CACACGUA G CGCCUCAU 1800 AUGAGGCG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UACGUGUG 5571

2818 UUUUGCGG G UCACCAUA 1801 UAUGGUGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGCAAAA 5572

2848 GAUCUACA G CAUGGGAG 1802 CUCCCAUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUAGAUC 5573

2857 CAUGGGAG G UUGGUCUU 1803 AAGACCAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCCCAUG 5574

2861 GGAGGUUG G UCUUCCAA 1804 UUGGAAGA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAACCUCC 5575

2881 UCGAAAAG G CAUGGGGA 1805 UCCCCAUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUUUCGA 5576

2936 GAUCAUCA G UUGGACCC 1806 GGGUCCAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGAUGAUC 5577

2955 CAUUCAAA G CCAACUCA 1807 UGAGUUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUGAAUG 5578

2964 CCAACUCA G UAAAUCCA 1808 UGGAUUUA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGAGUUGG 5579

3005 GACAACUG G CCGGACGC 1809 GCGUCCGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGUUGUC 5580

3021 CCAACAAG G UGGGAGUG 1810 CACUCCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUGUUGG 5581

3027 AGGUGGGA G UGGGAGCA 1811 UGCUCCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCCACCU 5582

3033 GAGUGGGA G CAUUCGGG 1812 CCCGAAUG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCCACUC 5583

3041 GCAUUCGG G CCAGGGUU 1813 AACCCUGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGAAUGC 5584

3047 GGGCCAGG G UUCACCCC 1814 GGGGUGAA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUGGCCC 5585

3077 CUGUUGGG G UGGAGCCC 1815 GGGCUCCA GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCAACAG 5586

3082 GGGGUGGA G CCCUCACG 1816 CGUGAGGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCACCCC 5587

3097 CGCUCAGG G CCUACUCA 1817 UGAGUAGG GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUGAGCG 5588

Table 42

3117 CUGUGCCA G CAGCUCCU 1818 AGGAGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCACAG 5589

3120 UGCCAGCA G CUCCUCCU 1819 AGGAGGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUGGCA 5590

3146 ACCAAUCG G CAGUCAGG 1820 CCUGACUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGAUUGGU 5591

3149 AAUCGGCA G UCAGGAAG 1821 CUUCCUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCGAUU 5592

3158 UCAGGAAG G CAGCCUAC 1822 GUAGGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCCUGA 5593

3161 GGAAGGCA G CCUACUCC 1823 GGAGUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCUUCC 5594

3204 AUCCUCAG G CCAUGCAG 1824 CUGCAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAGGAU 5595

31 CUCUUCAA G AUCCCAGA 2196 UCUGGGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAAGAG 5596

38 AGAUCCCA G AGUCAGGG 2197 CCCUGACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGAUCU 5597

44 CAGAGUCA G GGCCCUGU 2198 ACAGGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGACUCUG 5598

45 AGAGUCAG G GCCCUGUA 2199 UACAGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGACUCU 5599

64 UUCCUGCU G GUGGCUCC 2200 GGAGCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAGGAA 5600

67 CUGCUGGU G GCUCCAGU 2201 ACUGGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCAGCAG 5601

79 CCAGUUCA G GAACAGUG 2202 CACUGUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGAACUGG 5602

80 CAGUUCAG G AACAGUGA 2203 UCACUGUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGAACUG 5603

99 CCUGCUCA G AAUACUGU 2204 ACAGUAUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGAGCAGG 5604

135 UUAUCGAA G ACUGGGGA 2205 UCCCCAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCGAUAA 5605

139 CGAAGACU G GGGACCCU 2206 AGGGUCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUCUUCG 5606

140 GAAGACUG G GGACCCUG 2207 CAGGGUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGUCUUC 5607

141 AAGACUGG G GACCCUGU 2208 ACAGGGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAGUCUU 5608

142 AGACUGGG G ACCCUGUA 2209 UACAGGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCAGUCU 5609

159 CCGAACAU G GAGAACAU 2210 AUGUUCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGUUCGG 5610

160 CGAACAUG G AGAACAUC 2211 GAUGUUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUGUUCG 5611

162 AACAUGGA G AACAUCGC 2212 GCGAUGUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCAUGUU 5612

175 UCGCAUCA G GACUCCUA 2213 UAGGAGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGAUGCGA 5613

176 CGCAUCAG G ACUCCUAG 2214 CUAGGAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGAUGCG 5614

184 GACUCCUA G GACCCCUG 2215 CAGGGGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAGGAGUC 5615

185 ACUCCUAG G ACCCCUGC 2216 GCAGGGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUAGGAGU 5616

204 GUGUUACA G GCGGGGUU 2217 AACCCCGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUAACAC 5617

207 UUACAGGC G GGGUUUUU 2218 AAAAACCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCCUGUAA 5618

208 UACAGGCG G GGUUUUUC 2219 GAAAAACC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGCCUGUA 5619

209 ACAGGCGG G GUUUUUCU 2220 AGAAAAAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGCCUGU 5620

246 AUACCACA G AGUCUAGA 2221 UCUAGACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUGGUAU 5621

253 AGAGUCUA G ACUCGUGG 2222 CCACGAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAGACUCU 5622

Table 42

260 AGACUCGU G GUGGACUU 2223 AAGUCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGAGUCU 5623

263 CUCGUGGU G GACUUCUC 2224 GAGAAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCACGAG 5624

264 UCGUGGUG G ACUUCUCU 2225 AGAGAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCACGA 5625

283 AUUUUCUA G GGGGAACA 2226 UGUUCCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGAAAAU 5626

284 UUUUCUAG G GGGAACAC 2227 GUGUUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAGAAAA 5627

285 UUUCUAGG G GGAACACC 2228 GGUGUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUAGAAA 5628

286 UUCUAGGG G GAACACCC 2229 GGGUGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCUAGAA 5629

287 UCUAGGGG G AACACCCG 2230 CGGGUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCUAGA 5630

304 UGUGUCUU G GCCAAAAU 2231 AUUUUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGACACA 5631

367 UUUGUCCU G GUUAUCGC 2232 GCGAUAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGACAAA 5632

377 UUAUCGCU G GAUGUGUC 2233 GACACAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCGAUAA 5633

378 UAUCGCUG G AUGUGUCU 2234 AGACACAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCGAUA 5634

389 GUGUCUGC G GCGUUUUA 2235 UAAAACGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAGACAC 5635

441 UUCUUGUU G GUUCUUCU 2236 AGAAGAAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AACAAGAA 5636

450 GUUCUUCU G GACUAUCA 2237 UGAUAGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGAAGAAC 5637

451 UUCUUCUG G ACUAUCAA 2238 UUGAUAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGAAGAA 5638

460 ACUAUCAA G GUAUGUUG 2239 CAACAUAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGAUAGU 5639

490 UAAUUCCA G GAUCAUCA 2240 UGAUGAUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGAAUUA 5640

491 AAUUCCAG G AUCAUCAA 2241 UUGAUGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGGAAUU 5641

511 CCAGCACC G GACCAUGC 2242 GCAUGGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGUGCUGG 5642

512 CAGCACCG G ACCAUGCA 2243 UGCAUGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGGUGCUG 5643

544 CUGCUCAA G GAACCUCU 2244 AGAGGUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGAGCAG 5644

545 UGCUCAAG G AACCUCUA 2245 UAGAGGUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUGAGCA 5645

585 AAACCUAC G GACGGAAA 2246 UUUCCGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUAGGUUU 5646

586 AACCUACG G ACGGAAAC 2247 GUUUCCGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGUAGGUU 5647

589 CUACGGAC G GAAACUGC 2248 GCAGUUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUCCGUAG 5648

590 UACGGACG G AAACUGCA 2249 UGCAGUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGUCCGUA 5649

623 AUCAUCUU G GGCUUUCG 2250 CGAAAGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGAUGAU 5650

624 UCAUCUUG G GCUUUCGC 2251 GCGAAAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAGAUGA 5651

644 AUACCUAU G GGAGUGGG 2252 CCCACUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAGGUAU 5652

645 UACCUAUG G GAGUGGGC 2253 GCCCACUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUAGGUA 5653

646 ACCUAUGG G AGUGGGCC 2254 GGCCCACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAUAGGU 5654

650 AUGGGAGU G GGCCUCAG 2255 CUGAGGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACUCCCAU 5655

651 UGGGAGUG G GCCUCAGU 2256 ACUGAGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACUCCCA 5656

Table 42

671 UUUCUCUU G GCUCAGUU 2257 AACUGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAGAAA 5657

701 UGUUCAGU G GUUCGUAG 2258 CUACGAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGAACA 5658

709 GGUUCGUA G GGCUUUCC 2259 GGAAAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACGAACC 5659

710 GUUCGUAG G GCUUUCCC 2260 GGGAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUACGAAC 5660

728 CACUGUCU G GCUUUCAG 2261 CUGAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGACAGUG 5661

743 AGUUAUAU G GAUGAUGU 2262 ACAUCAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAUAACU 5662

744 GUUAUAUG G AUGAUGUG 2263 CACAUCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUAUAAC 5663

752 GAUGAUGU G GUUUUGGG 2264 CCCAAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUCAUC 5664

758 GUGGUUUU G GGGGCCAA 2265 UUGGCCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAACCAC 5665

759 UGGUUUUG G GGGCCAAG 2266 CUUGGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAACCA 5666

760 GGUUUUGG G GGCCAAGU 2267 ACUUGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAAACC 5667

761 GUUUUGGG G GCCAAGUC 2268 GACUUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAAAAC 5668

824 UUGUCUUU G GGUAUACA 2269 UGUAUACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGACAA 5669

825 UGUCUUUG G GUAUACAU 2270 AUGUAUAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAAGACA 5670

856 AACAAAAA G AUGGGGAU 2271 AUCCCCAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUUUGUU 5671

859 AAAAAGAU G GGGAUAUU 2272 AAUAUCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUCUUUUU 5672

860 AAAAGAUG G GGAUAUUC 2273 GAAUAUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUCUUUU 5673

861 AAAGAUGG G GAUAUUCC 2274 GGAAUAUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAUCUUU 5674

862 AAGAUGGG G AUAUUCCC 2275 GGGAAUAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCAUCUU 5675

881 AACUUCAU G GGAUAUGU 2276 ACAUAUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGAAGUU 5676

882 ACUUCAUG G GAUAUGUA 2277 UACAUAUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUGAAGU 5677

883 CUUCAUGG G AUAUGUAA 2278 UUACAUAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAUGAAG 5678

894 AUGUAAUU G GGAGUUGG 2279 CCAACUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUUACAU 5679

895 UGUAAUUG G GAGUUGGG 2280 CCCAACUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAUUACA 5680

896 GUAAUUGG G AGUUGGGG 2281 CCCCAACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAAUUAC 5681

901 UGGGAGUU G GGGCACAU 2282 AUGUGCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AACUCCCA 5682

902 GGGAGUUG G GGCACAUU 2283 AAUGUGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAACUCCC 5683

903 GGAGUUGG G GCACAUUG 2284 CAAUGUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAACUCC 5684

917 UUGCCACA G GAACAUAU 2285 AUAUGUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUGGCAA 5685

918 UGCCACAG G AACAUAUU 2286 AAUAUGUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGUGGCA 5686

952 GUGUUUUA G GAAACUUC 2287 GAAGUUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAAAACAC 5687

953 UGUUUUAG G AAACUUCC 2288 GGAAGUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUAAAACA 5688

970 UGUAAACA G GCCUAUUG 2289 CAAUAGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUUUACA 5689

982 UAUUGAUU G GAAAGUAU 2290 AUACUUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUCAAUA 5690

Table 42

983 AUUGAUUG G AAAGUAUG 2291 CAUACUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAUCAAU 5691

1004 CGAAUUGU G GGUCUUUU 2292 AAAAGACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAAUUCG 5692

1005 GAAUUGUG G GUCUUUUG 2293 CAAAAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAAUUC 5693

1013 GGUCUUUU G GGGUUUGC 2294 GCAAACCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAGACC 5694

1014 GUCUUUUG G GGUUUGCC 2295 GGCAAACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAAGAC 5695

1015 UCUUUUGG G GUUUGCCG 2296 CGGCAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAAAGA 5696

1041 CGCAAUGU G GAUAUUCU 2297 AGAAUAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUUGCG 5697

1042 GCAAUGUG G AUAUUCUG 2298 CAGAAUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAUUGC 5698

1088 GCAAAACA G GCUUUUAC 2299 GUAAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUUGC 5699

1115 ACUUACAA G GCCUUUCU 2300 AGAAAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUAAGU 5700

1159 CGUUGCUC G GCAACGGC 2301 GCCGUUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGCAACG 5701

1165 UCGGCAAC G GCCUGGUC 2302 GACCAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUGCCGA 5702

1170 AACGGCCU G GUCUAUGC 2303 GCAUAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGCCGUU 5703

1206 CCCCCACU G GUUGGGGC 2304 GCCCCAAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUGGGGG 5704

1210 CACUGGUU G GGGCUUGG 2305 CCAAGCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AACCAGUG 5705

1211 ACUGGUUG G GGCUUGGC 2306 GCCAAGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAACCAGU 5706

1212 CUGGUUGG G GCUUGGCC 2307 GGCCAAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAACCAG 5707

1217 UGGGGCUU G GCCAUAGG 2308 CCUAUGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGCCCCA 5708

1224 UGGCCAUA G GCCAUCAG 2309 CUGAUGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAUGGCCA 5709

1242 GCAUGCGU G GAACCUUU 2310 AAAGGUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACGCAUGC 5710

1243 CAUGCGUG G AACCUUUG 2311 CAAAGGUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACGCAUG 5711

1277 CAUACCGC G GAACUCCU 2312 AGGAGUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCGGUAUG 5712

1278 AUACCGCG G AACUCCUA 2313 UAGGAGUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGCGGUAU 5713

1309 UCGCAGCA G GUCUGGGG 2314 CCCCAGAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCUGCGA 5714

1314 GCAGGUCU G GGGCAAAA 2315 UUUUGCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGACCUGC 5715

1315 CAGGUCUG G GGCAAAAC 2316 GUUUUGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGACCUG 5716

1316 AGGUCUGG G GCAAAACU 2317 AGUUUUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAGACCU 5717

1329 AACUCAUC G GGACUGAC 2318 GUCAGUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAUGAGUU 5718

1330 ACUCAUCG G GACUGACA 2319 UGUCAGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGAUGAGU 5719

1331 CUCAUCGG G ACUGACAA 2320 UUGUCAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGAUGAG 5720

1378 AUUUCCAU G GCUGCUAG 2321 CUAGCAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGGAAAU 5721

1386 GGCUGCUA G GCUGUGCU 2322 AGCACAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAGCAGCC 5722

1402 UGCCAACU G GAUCCUAC 2323 GUAGGAUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUUGGCA 5723

1403 GCCAACUG G AUCCUACG 2324 CGUAGGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAGUUGGC 5724

Table 42

1413 UCCUACGC G GGACGUCC 2325 GGACGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGUAGGA 5725

1414 CCUACGCG G GACGUCCU 2326 AGGACGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCGUAGG 5726

1415 CUACGCGG G ACGUCCUU 2327 AAGGACGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGCGUAG 5727

1439 GUCCCGUC G GCGCUGAA 2328 UUCAGCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACGGGAC 5728

1454 AAUCCCGC G GACGACCC 2329 GGGUCGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGGGAUU 5729

1455 AUCCCGCG G ACGACCCC 2330 GGGGUCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCGGGAU 5730

1468 CCCCUCCC G GGGCCGCU 2331 AGCGGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGAGGGG 5731

1469 CCCUCCCG G GGCCGCUU 2332 AAGCGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGGAGGG 5732

1470 CCUCCCGG G GCCGCUUG 2333 CAAGCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGGGAGG 5733

1478 GGCCGCUU G GGGCUCUA 2334 UAGAGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGCGGCC 5734

1479 GCCGCUUG G GGCUCUAC 2335 GUAGAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGCGGC 5735

1480 CCGCUUGG G GCUCUACC 2336 GGUAGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAGCGG 5736

1523 CCGUCCAC G GGGCGCAC 2337 GUGCGCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUGGACGG 5737

1524 CGUCCACG G GGCGCACC 2338 GGUGCGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGUGGACG 5738

1525 GUCCACGG G GCGCACCU 2339 AGGUGCGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGUGGAC 5739

1544 CUUUACGC G GACUCCCC 2340 GGGGAGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCGUAAAG 5740

1545 UUUACGCG G ACUCCCCG 2341 CGGGGAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGCGUAAA 5741

1574 CAUCUGCC G GACCGUGU 2342 ACACGGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGCAGAUG 5742

1575 AUCUGCCG G ACCGUGUG 2343 CACACGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGGCAGAU 5743

1612 CGUCGCAU G GAGACCAC 2344 GUGGUCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGCGACG 5744

1613 GUCGCAUG G AGACCACC 2345 GGUGGUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUGCGAC 5745

1615 CGCAUGGA G ACCACCGU 2346 ACGGUGGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCAUGCG 5746

1635 CGCCCACA G GAACCUGC 2347 GCAGGUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGUGGGCG 5747

1636 GCCCACAG G AACCUGCC 2348 GGCAGGUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGUGGGC 5748

1648 CUGCCCAA G GUCUUGCA 2349 UGCAAGAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGGGCAG 5749

1660 UUGCAUAA G AGGACUCU 2350 AGAGUCCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUAUGCAA 5750

1662 GCAUAAGA G GACUCUUG 2351 CAAGAGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCUUAUGC 5751

1663 CAUAAGAG G ACUCUUGG 2352 CCAAGAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCUUAUG 5752

1670 GGACUCUU G GACUUUCA 2353 UGAAAGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGAGUCC 5753

1671 GACUCUUG G ACUUUCAG 2354 CUGAAAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAGAGUC 5754

1702 GACCUUGA G GCAUACUU 2355 AAGUAUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCAAGGUC 5755

1715 ACUUCAAA G ACUGUGUG 2356 CACACAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUGAAGU 5756

1734 UAAUGAGU G GGAGGAGU 2357 ACUCCUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACUCAUUA 5757

1735 AAUGAGUG G GAGGAGUU 2358 AACUCCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACUCAUU 5758

Table 42

1736 AUGAGUGG G AGGAGUUG 2359 CAACUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACUCAU 5759

1738 GAGUGGGA G GAGUUGGG 2360 CCCAACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCACUC 5760

1739 AGUGGGAG G AGUUGGGG 2361 CCCCAACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCCACU 5761

1744 GAGGAGUU G GGGGAGGA 2362 UCCUCCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACUCCUC 5762

1745 AGGAGUUG G GGGAGGAG 2363 CUCCUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACUCCU 5763

1746 GGAGUUGG G GGAGGAGG 2364 ccuccucc GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAACUCC 5764

1747 GAGUUGGG G GAGGAGGU 2365 ACCUCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAACUC 5765

1748 AGUUGGGG G AGGAGGUU 2366 AACCUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCAACU 5766

1750 UUGGGGGA G GAGGUUAG 2367 CUAACCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCCCAA 5767

1751 UGGGGGAG G AGGUUAGG 2368 CCUAACCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCCCCA 5768

1753 GGGGAGGA G GUUAGGUU 2369 AACCUAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCCCC 5769

1758 GGAGGUUA G GUUAAAGG 2370 CCUUUAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAACCUCC 5770

1765 AGGUUAAA G GUCUUUGU 2371 ACAAAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUAACCU 5771

1778 UUGUACUA G GAGGCUGU 2372 ACAGCCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAGUACAA 5772

1779 UGUACUAG G AGGCUGUA 2373 UACAGCCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUAGUACA 5773

1781 UACUAGGA G GCUGUAGG 2374 CCUACAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCUAGUA 5774

1788 AGGCUGUA G GCAUAAAU 2375 AUUUAUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UACAGCCU 5775

1798 CAUAAAUU G GUGUGUUC 2376 GAACACAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAUUUAUG 5776

1888 UGUGCCUU G GGUGGCUU 2377 AAGCCACC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGGCACA 5777

1889 GUGCCUUG G GUGGCUUU 2378 AAAGCCAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAGGCAC 5778

1892 CCUUGGGU G GCUUUGGG 2379 CCCAAAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCCAAGG 5779

1898 GUGGCUUU G GGGCAUGG 2380 CCAUGCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAGCCAC 5780

1899 UGGCUUUG G GGCAUGGA 2381 UCCAUGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAAGCCA 5781

1900 GGCUUUGG G GCAUGGAC 2382 GUCCAUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAAAGCC 5782

1905 UGGGGCAU G GACAUUGA 2383 UCAAUGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGCCCCA 5783

1906 GGGGCAUG G ACAUUGAC 2384 GUCAAUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUGCCCC 5784

1924 CGUAUAAA G AAUUUGGA 2385 UCCAAAUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUAUACG 5785

1930 AAGAAUUU G GAGCUUCU 2386 AGAAGCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAUUCUU 5786

1931 AGAAUUUG G AGCUUCUG 2387 CAGAAGCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAAUUCU 5787

1941 GCUUCUGU G GAGUUACU 2388 AGUAACUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAGAAGC 5788

1942 CUUCUGUG G AGUUACUC 2389 GAGUAACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACAGAAG 5789

1987 CUAUUCGA G AUCUCCUC 2390 GAGGAGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCGAAUAG 5790

2018 UCUGUAUC G GGGGGCCU 2391 AGGCCCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAUACAGA 5791

2019 CUGUAUCG G GGGGCCUU 2392 AAGGCCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGAUACAG 5792

Table 42

2020 UGUAUCGG G GGGCCUUA 2393 UAAGGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGAUACA 5793

2021 GUAUCGGG G GGCCUUAG 2394 CUAAGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCGAUAC 5794

2022 UAUCGGGG G GCCUUAGA 2395 UCUAAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCGAUA 5795

2029 GGGCCUUA G AGUCUCCG 2396 CGGAGACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAGGCCC 5796

2037 GAGUCUCC G GAACAUUG 2397 CAAUGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAGACUC 5797

2038 AGUCUCCG G AACAUUGU 2398 ACAAUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGAGACU 5798

2061 CACCAUAC G GCACUCAG 2399 CUGAGUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAUGGUG 5799

2069 GGCACUCA G GCAAGCUA 2400 UAGCUUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGUGCC 5800

2087 UCUGUGUU G GGGUGAGU 2401 ACUCACCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACACAGA 5801

2088 CUGUGUUG G GGUGAGUU 2402 AACUCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACACAG 5802

2089 UGUGUUGG G GUGAGUUG 2403 CAACUCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAACACA 5803

2114 AGCCACCU G GGUGGGAA 2404 UUCCCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUGGCU 5804

2115 GCCACCUG G GUGGGAAG 2405 CUUCCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGUGGC 5805

2118 ACCUGGGU G GGAAGUAA 2406 UUACUUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCCAGGU 5806

2119 CCUGGGUG G GAAGUAAU 2407 AUUACUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACCCAGG 5807

2120 CUGGGUGG G AAGUAAUU 2408 AAUUACUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCACCCAG 5808

2130 AGUAAUUU G GAAGAUCC 2409 GGAUCUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAUUACU 5809

2131 GUAAUUUG G AAGAUCCA 2410 UGGAUCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAAUUAC 5810

2134 AUUUGGAA G AUCCAGCA 2411 UGCUGGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCCAAAU 5811

2147 AGCAUCCA G GGAAUUAG 2412 CUAAUUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGAUGCU 5812

2148 GCAUCCAG G GAAUUAGU 2413 ACUAAUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGGAUGC 5813

2149 CAUCCAGG G AAUUAGUA 2414 UACUAAUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCUGGAUG 5814

2181 GUUAAUAU G GGCCUAAA 2415 UUUAGGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUAUUAAC 5815

2182 UUAAUAUG G GCCUAAAA 2416 UUUUAGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUAUUAA 5816

2195 AAAAAUCA G ACAACUAU 2417 AUAGUUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGAUUUUU 5817

2207 ACUAUUGU G GUUUCACA 2418 UGUGAAAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAAUAGU 5818

2233 UUACUUUU G GGCGAGAA 2419 UUCUCGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAAGUAA 5819

2234 UACUUUUG G GCGAGAAA 2420 UUUCUCGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAAAGUA 5820

2239 UUGGGCGA G AAACUGUU 2421 AACAGUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCGCCCAA 5821

2259 GAAUAUUU G GUGUCUUU 2422 AAAGACAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAUAUUC 5822

2269 UGUCUUUU G GAGUGUGG 2423 CCACACUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAAAGACA 5823

2270 GUCUUUUG G AGUGUGGA 2424 UCCACACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAAAGAC 5824

2276 UGGAGUGU G GAUUCGCA 2425 UGCGAAUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACACUCCA 5825

2277 GGAGUGUG G AUUCGCAC 2426 GUGCGAAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACACUCC 5826

Table 42

2300 UGCAUAUA G ACCACCAA 2427 UUGGUGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUAUGCA 5827

2334 ACACUUCC G GAAACUAC 2428 GUAGUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAAGUGU 5828

2335 CACUUCCG G AAACUACU 2429 AGUAGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGAAGUG 5829

2351 UGUUGUUA G ACGAAGAG 2430 CUCUUCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAACAACA 5830

2357 UAGACGAA G AGGCAGGU 2431 ACCUGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCGUCUA 5831

2359 GACGAAGA G GCAGGUCC 2432 GGACCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUCGUC 5832

2363 AAGAGGCA G GUCCCCUA 2433 UAGGGGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCUCUU 5833

2372 GUCCCCUA G AAGAAGAA 2434 UUCUUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGGGGAC 5834

2375 CCCUAGAA G AAGAACUC 2435 GAGUUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUAGGG 5835

2378 UAGAAGAA G AACUCCCU 2436 AGGGAGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUUCUA 5836

2396 GCCUCGCA G ACGAAGGU 2437 ACCUUCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCGAGGC 5837

2402 CAGACGAA G GUCUCAAU 2438 AUUGAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCGUCUG 5838

2423 GCGUCGCA G AAGAUCUC 2439 GAGAUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCGACGC 5839

2426 UCGCAGAA G AUCUCAAU 2440 AUUGAGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCUGCGA 5840

2438 UCAAUCUC G GGAAUCUC 2441 GAGAUUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAGAUUGA 5841

2439 CAAUCUCG G GAAUCUCA 2442 UGAGAUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGAGAUUG 5842

2440 AAUCUCGG G AAUCUCAA 2443 UUGAGAUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGAGAUU 5843

2463 UAUUCCUU G GACACAUA 2444 UAUGUGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGGAAUA 5844

2464 AUUCCUUG G ACACAUAA 2445 UUAUGUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAGGAAU 5845

2473 ACACAUAA G GUGGGAAA 2446 UUUCCCAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUAUGUGU 5846

2476 CAUAAGGU G GGAAACUU 2447 AAGUUUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCUUAUG 5847

2477 AUAAGGUG G GAAACUUU 2448 AAAGUUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACCUUAU 5848

2478 UAAGGUGG G AAACUUUA 2449 UAAAGUUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCACCUUA 5849

2488 AACUUUAC G GGGCUUUA 2450 UAAAGCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUAAAGUU 5850

2489 ACUUUACG G GGCUUUAU 2451 AUAAAGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGUAAAGU 5851

2490 CUUUACGG G GCUUUAUU 2452 AAUAAAGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGUAAAG 5852

2506 UCUUCUAC G GUACCUUG 2453 CAAGGUAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GUAGAAGA 5853

2529 UCCUAAAU G GCAAACUC 2454 GAGUUUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUUUAGGA 5854

2563 CAUUUGCA G GAGGACAU 2455 AUGUCCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGCAAAUG 5855

2564 AUUUGCAG G AGGACAUU 2456 AAUGUCCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGCAAAU 5856

2566 UUGCAGGA G GACAUUGU 2457 ACAAUGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCUGCAA 5857

2567 UGCAGGAG G ACAUUGUU 2458 AACAAUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUCCUGCA 5858

2580 UGUUGAUA G AUGUAAGC 2459 GCUUACAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UAUCAACA 5859

2596 CAAUUUGU G GGGCCCCU 2460 AGGGGCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACAAAUUG 5860

Table 42

2597 AAUUUGUG G GGCCCCUU 2461 AAGGGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAAAUU 5861

2598 AUUUGUGG G GCCCCUUA 2462 UAAGGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACAAAU 5862

2622 UGAAAACA G GAGACUUA 2463 UAAGUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUUCA 5863

2623 GAAAACAG G AGACUUAA 2464 UUAAGUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUUUUC 5864

2625 AAACAGGA G ACUUAAAU 2465 AUUUAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUGUUU 5865

2649 GCCUGCUA G GUUUUAUC 2466 GAUAAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGCAGGC 5866

2684 UGCCCUUA G AUAAAGGG 2467 CCCUUUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAGGGCA 5867

2690 UAGAUAAA G GGAUCAAA 2468 UUUGAUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUAUCUA 5868

2691 AGAUAAAG G GAUCAAAC 2469 GUUUGAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUUAUCU 5869

2692 GAUAAAGG G AUCAAACC 2470 GGUUUGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUUUAUC 5870

2711 AUUAUCCA G AGUAUGUA 2471 UACAUACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAUAAU 5871

2737 UACUUCCA G ACGCGACA 2472 UGUCGCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAAGUA 5872

2763 CACUCUUU G GAAGGCGG 2473 CCGCCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGAGUG 5873

2764 ACUCUUUG G AAGGCGGG 2474 CCCGCCUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAAGAGU 5874

2767 CUUUGGAA G GCGGGGAU 2475 AUCCCCGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUCCAAAG 5875

2770 UGGAAGGC G GGGAUCUU 2476 AAGAUCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCCUUCCA 5876

2771 GGAAGGCG G GGAUCUUA 2477 UAAGAUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGCCUUCC 5877

2772 GAAGGCGG G GAUCUUAU 2478 AUAAGAUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCGCCUUC 5878

2773 AAGGCGGG G AUCUUAUA 2479 UAUAAGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCGCCUU 5879

2787 AUAUAAAA G AGAGUCCA 2480 UGGACUCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUUAUAU 5880

2789 AUAAAAGA G AGUCCACA 2481 UGUGGACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCUUUUAU 5881

2816 CAUUUUGC G GGUCACCA 2482 UGGUGACC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GCAAAAUG 5882

2817 AUUUUGCG G GUCACCAU 2483 AUGGUGAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGCAAAAU 5883

2832 AUAUUCUU G GGAACAAG 2484 CUUGUUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AAGAAUAU 5884

2833 UAUUCUUG G GAACAAGA 2485 UCUUGUUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAAGAAUA 5885

2834 AUUCUUGG G AACAAGAU 2486 AUCUUGUU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAAGAAU 5886

2840 GGGAACAA G AUCUACAG 2487 CUGUAGAU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGUUCCC 5887

2852 UACAGCAU G GGAGGUUG 2488 CAACCUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGCUGUA 5888

2853 ACAGCAUG G GAGGUUGG 2489 CCAACCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUGCUGU 5889

2854 CAGCAUGG G AGGUUGGU 2490 ACCAACCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAUGCUG 5890

2856 GCAUGGGA G GUUGGUCU 2491 AGACCAAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UCCCAUGC 5891

2860 GGGAGGUU G GUCUUCCA 2492 UGGAAGAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AACCUCCC 5892

2880 CUCGAAAA G GCAUGGGG 2493 CCCCAUGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUUUCGAG 5893

2885 AAAGGCAU G GGGACAAA 2494 UUUGUCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGCCUUU 5894

Table 42

2886 AAGGCAUG G GGACAAAU 2495 AUUUGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGCCUU 5895

2887 AGGCAUGG G GACAAAUC 2496 GAUUUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAUGCCU 5896

2888 GGCAUGGG G ACAAAUCU 2497 AGAUUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAUGCC 5897

2915 AAUCCCCU G GGAUUCUU 2498 AAGAAUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGGAUU 5898

2916 AUCCCCUG G GAUUCUUC 2499 GAAGAAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGGGAU 5899

2917 UCCCCUGG G AUUCUUCC 2500 GGAAGAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGGGGA 5900

2939 CAUCAGUU G GACCCUGC 2501 GCAGGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACUGAUG 5901

2940 AUCAGUUG G ACCCUGCA 2502 UGCAGGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACUGAU 5902

2973 UAAAUCCA G AUUGGGAC 2503 GUCCCAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAUUUA 5903

2977 UCCAGAUU G GGACCUCA 2504 UGAGGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUCUGGA 5904

2978 CGAGAUUG G GACCUCAA 2505 UUGAGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAUCUGG 5905

2979 CAGAUUGG G ACCUCAAC 2506 GUUGAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAUCUG 5906

2996 CCGCACAA G GACAACUG 2507 CAGUUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUGCGG 5907

2997 CGCACAAG G ACAACUGG 2508 CCAGUUGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUUGUGCG 5908

3004 GGACAACU G GCCGGACG 2509 CGUCCGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AGUUGUCC 5909

3008 AACUGGCC G GACGCCAA 2510 UUGGCGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GGCCAGUU 5910

3009 ACUGGCCG G ACGCCAAC 2511 GUUGGCGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGGCCAGU 5911

3020 GCCAACAA G GUGGGAGU 2512 ACUCCCAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UUGUUGGC 5912

3023 AACAAGGU G GGAGUGGG 2513 CCCACUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACCUUGUU 5913

3024 ACAAGGUG G GAGUGGGA 2514 UCCCACUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACCUUGU 5914

3025 CAAGGUGG G AGUGGGAG 2515 CUCCCACU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCACCUUG 5915

3029 GUGGGAGU G GGAGCAUU 2516 AAUGCUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG ACUCCCAC 5916

3030 UGGGAGUG G GAGCAUUC 2517 GAAUGCUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CACUCCCA 5917

3031 GGGAGUGG G AGCAUUCG 2518 CGAAUGCU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCACUCCC 5918

3039 GAGCAUUC G GGCCAGGG 2519 CCCUGGCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG GAAUGCUC 5919

3040 AGCAUUCG G GCCAGGGU 2520 ACCCUGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CGAAUGCU 5920

3045 UCGGGCCA G GGUUCACC 2521 GGUGAACC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGGCCCGA 5921

3046 CGGGCCAG G GUUCACCC 2522 GGGUGAAC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CUGGCCCG 5922

3063 CUCCCCAU G GGGGACUG 2523 CAGUCCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AUGGGGAG 5923

3064 UCCCCAUG G GGGACUGU 2524 ACAGUCCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CAUGGGGA 5924

3065 CCCCAUGG G GGACUGUU 2525 AACAGUCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCAUGGGG 5925

3066 CCCAUGGG G GACUGUUG 2526 CAACAGUC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCAUGGG 5926

3067 CCAUGGGG G ACUGUUGG 2527 CCAACAGU GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG CCCCAUGG 5927

3074 GGACUGUU G GGGUGGAG 2528 CUCCACCC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG AACAGUCC 5928

Table 42

3075 GACUGUUG G GGUGGAGC 2529 GCUCCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACAGUC 5929

3076 ACUGUUGG G GUGGAGCC 2530 GGCUCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAACAGU 5930

3079 GUUGGGGU G GAGCCCUC 2531 GAGGGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCCCAAC 5931

3080 UUGGGGUG G AGCCCUCA 2532 UGAGGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCCCAA 5932

3095 CACGCUCA G GGCCUACU 2533 AGUAGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGCGUG 5933

3096 ACGCUCAG G GCCUACUC 2534 GAGUAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAGCGU 5934

3145 CACCAAUC G GCAGUCAG 2535 CUGACUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUUGGUG 5935

3153 GGCAGUCA G GAAGGCAG 2536 CUGCCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGACUGCC 5936

3154 GCAGUCAG G AAGGCAGC 2537 GCUGCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGACUGC 5937

3157 GUCAGGAA G GCAGCCUA 2538 UAGGCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCUGAC 5938

3187 ACCUCUAA G GGACACUC 2539 GAGUGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAGAGGU 5939

3188 CCUCUAAG G GACACUCA 2540 UGAGUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUAGAGG 5940

3189 CUCUAAGG G ACACUCAU 2541 AUGAGUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUUAGAG 5941

3203 CAUCCUCA G GCCAUGCA 2542 UGCAUGGC GGAGGAAACUCC cu UCAAGGACAUCGUCCGGG UGAGGAUG 5942

Input Sequence = AF100308. Cut Site = YG/M or UG/U.

Stem Length = 8. Core Sequence = GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG

AF100308 (Hepatitis B virus strain 2-18, 3215 bp)

Table 43

Table 43: Human HBV Ribozyme and Target Sequence

Table 43

Table 43

Table 43

Table 43

Table 43

Table 43

Table 43

Table 43

Table 43

Table 43

Table 43

UPPER CASE = RIBO lower case = 2'-0-methyl s = phosphorothioate linkage B = inverted deoxyabasic residue U = 2'-deoxy-2'-C-allyl Uridine U= 2 '-deoxy-2 '-amino Uridine C = 2'-deoxy-2'-amino Cytidine

Table 44 Table 44: Group Designation and Dosage levels for HBV transgenic mouse study

*administered via sc infusion using Alzet mini-osmotic pumps

Table 45

TABLE 45. NUCLEOSIDES USED FOR CHEMICAL SYNTHESIS OF MODIFIED NUCLEOTIDE TRIPHOSPHATES

Table 45

ouυ

Table 45

Table 45

Table 45

Table 45

Table 45

Table 46

Table 46: PHOSPHORYLATION OF URIDINE IN THE PRESENCE OF DMAP

Table 48

Table 48: INCORPORATION OF MODIFIED NUCLEOTIDE TRIPHOSPHATES

Table 48

Table 49

Table 49: INCORPORATION OF MODIFIED NUCLEOTIDE TRIPHOSPHATES USING WILD TYPE BACTERIOPHAGE T7 POLYMERASE

Table 50

Table 50 a: Incorporation of 2'-his-UTP and Modified CTP's

Table 50 b: Incorporation of 2'-his-UTP, 2-amino CTP, and Modified ATP's

Numbers shown are a percentage of incorporation compared to the all-RNA control

* -Bold number indicates best observed rate of modified nucleotide triphosphate incorporation

Table 51

Table 51: INCORPORATION OF 2'-his-UTP, 2'-NH₂-CTP, 2'-NH₂-DAP, and rGTP USING VARIOUS REACTION CONDITIONS

Numbers shown are a percentage of incorporation compared to the all-RNA control

* Two highest levels of incorporation contained both methanol and LiCl

Table 52

Table 52: Selection of Oligonucleotides with Ribozyme Activity

Table 53

Table 53: Kinetic Activity of Combinatorial Libraries

Table 54

Table 54: Kinetic Activity of Clones within N60 and N40 Combinatorial Libraries

Table 55 Table 55: Effect of Magnesium Concentration of the Cleavage Rate of N20

I able 56

Enzymatic Nucleic Acid Motifs Targeting HCV

Seq ID Al Las Sequence Rz Seq ID

:ucc 1 HCV.R1A-6 A b.Rz-10/5 ggagugucgc GgaggaaacucC CU UCAAGGACAUCGUCCGGG cccau B 39

3CGU 2 HCV.R1A-56 Amb.Rz-10/5 acgcuuucug GgaggaaacucC CU UCAAGGACAUCGUCCGGG gugaa B 40

3UAU 3 HCV.R1A-75 Amb.Rz-10/5 auacuaacgc GgaggaaacucC CU UCAAGGACAUCGUCCGGG auggc B 41

JAUG 4 HCV.R1A-76 Amb.Rz-10/5 cauacuaacg GgaggaaacucC cu UCAAGGACAUCGUCCGGG caugg B 42

:CAG 5 HCV.R1A-95 Amb.Rz-10/5 cuggaggcug GgaggaaacucC cu UCAAGGACAUCGUCCGGG acgac B 43

:GGU 6 HCV.R1A-138 Amb.Rz-10/5 accgguuccg GgaggaaacucC cu UCAAGGACAUCGUCCGGG agacc B 44

^CAC 7 HCV.R1A-146 Amb.Rz-10/5 guguacucac GgaggaaacucC cu UCAAGGACAUCGUCCGGG gguuc B 45 CAG 8 HCV.R1A-158 Amb.Rz-10/5 cuggcaauuc GgaggaaacucC cu UCAAGGACAUCGUCCGGG ggugu B 46

ΓGAC 9 HCV.R1A-164 Amb.Rz-10/5 gucguccugg GgaggaaacucC cu UCAAGGACAUCGUCCGGG aauuc B 47

JUCU 10 HCV.R1A-176 Amb.Rz-10/5 agaaaggacc GgaggaaacucC cu UCAAGGACAUCGUCCGGG ggucg B 48

JCUU 11 HCV.RlA-177 Amb.Rz-10/5 aagaaaggac GgaggaaacucC cu UCAAGGACAUCGUCCGGG cgguc B 49

JGGG 12 HCV.R1A-209 Amb.Rz-10/5 cccaaaucuc GgaggaaacucC cu UCAAGGACAUCGUCCGGG aggca B 50

3AGU 13 HCV.R1A-237 Amb.Rz-10/5 acucggcuag GgaggaaacucC cu UCAAGGACAUCGUCCGGG agucu B 51

3AAA 14 HCV.R1A-254 Amb.Rz-10/5 uuucgcgacc GgaggaaacucC cu UCAAGGACAUCGUCCGGG aacac B 52

!yyiG 15 HCV. RIA-255 Amb.Rz-10/5 cuuucgcgac GgaggaaacucC cu UCAAGGACAUCGUCCGGG caaca B 53

3CCU 16 HCV. RIA-259 Amb.Rz-10/5 aggccuuucg GgaggaaacucC cu UCAAGGACAUCGUCCGGG gaccc B 54

3GUA 17 HCV.R1A-266 Amb.Rz-10/5 uaccacaagg GgaggaaacucC cu UCAAGGACAUCGUCCGGG cuuuc B 55

_CUG 18 HCV.R1A-273 Amb.Rz-10/5 caggcaguac GgaggaaacucC cu UCAAGGACAUCGUCCGGG acaag B 56

3CGA 19 HCV.R1A-288 Amb.Rz-10/5 ucgcaagcac GgaggaaacucC cu UCAAGGACAUCGUCCGGG cuauc B 57

>-GUG 20 HCV.R1A-291 Amb.Rz-10/5 cacucgcaag GgaggaaacucC cu UCAAGGACAUCGUCCGGG acccu B 58

JCCA 21 HCV.R1A-7 Amb.Rz-10/5 uggagugucg GgaggaaacucC cu UCAAGGACAUCGUCCGGG cccca B 59

"CAU 22 HCV.R1A-119 Amb.Rz-10/5 auggcucucc GgaggaaacucC cu UCAAGGACAUCGUCCGGG gggag B 60 AUA 23 HCV.R1A-120 Amb.Rz-10/5 uauggcucuc GgaggaaacucC cu UCAAGGACAUCGUCCGGG cggga B 61

3GAA 24 HCV.R1A-133 Amb.Rz-10/5 uuccgcagac GgaggaaacucC cu UCAAGGACAUCGUCCGGG acuau B 62

3UGA 25 HCV.R1A-140 Amb.Rz-10/5 ucaccgguuc GgaggaaacucC cu UCAAGGACAUCGUCCGGG gcaga B 63

_CCG 26 HCV.R1A-188 Amb.Rz-10/5 cgggguuauc GgaggaaacucC cu UCAAGGACAUCGUCCGGG aagaa B 64

3CCU 27 HCV.R1A-198 Amb.Rz-10/5 aggcauugag GgaggaaacucC cu UCAAGGACAUCGUCCGGG 9999^U B 65

3AUU 28 HCV.R1A-205 Amb.Rz-10/5 aaucuccagg GgaggaaacucC cu UCAAGGACAUCGUCCGGG auuga B 66

ZCCC 29 HCV. RIA-217 Amb.Rz-10/5 ggggcacgcc GgaggaaacucC cu UCAAGGACAUCGUCCGGG aaauc B 67 CCC 30 HCV.R1A-218 Amb.Rz-10/5 gggggcacgc GgaggaaacucC cu UCAAGGACAUCGUCCGGG caaau B 68

:CCG 31 HCV.R1A-219 Amb.Rz-10/5 cgggggcacg GgaggaaacucC cu UCAAGGACAUCGUCCGGG ccaaa B 69

"AAG 32 HCV.R1A-223 Amb.Rz-10/5 cuugcggggg GgaggaaacucC cu UCAAGGACAUCGUCCGGG acgcc B 70

JGCU 33 HCV.R1A-229 Amb.Rz-10/5 agcagucuug GgaggaaacucC cu UCAAGGACAUCGUCCGGG ggggg B 71

^GGG 34 HCV.R1A-279 Amb.Rz-10/5 cccuaucagg GgaggaaacucC cu UCAAGGACAUCGUCCGGG aguac B 72

Table 56

lower case = 2'-O-methyl TJ, C = 2 '-deoxy-2 '-amino U, 2 '-deoxy-2 '-amino C

B = inverted deoxyabasic

Table 57 Table 57. Additional Class II enzymatic nucleic acid Motifs

Table 58

Table 58: Human Her2 Class II Ribozyme and Target Sequen

RPI# NTPos Substrate Seq ID Ribozyme Alias Ribozyme Sequence Seq ID

#

18722 180 CAUGGA G CUGGCG 85 erbB2-180 Zin Rz-6 amino stabl ^cs9s^cs^cs^a9 GccgaaagGCGaGucaaGGuCu uccaug B 194

18835 184 GAGCUG G CGGCCU 86 erbB2-184 Zin Rz-6 ammo stabl ^as9_S9s^cs°9 GccgaaagGCGaGucaaGGuCu cagcuc B 195

18828 276 AGCUGCG G CUCCCUG 87 erbB2-276 Zin Rz-7 amino stabl c_aa_ag_sg_ggag GccgaaagGCGaGucaaGGuCu cgcagcu B 196

18653 314 UGCUCC G CCACCU 88 erbB2-314 Zin Rz-6 ammo stabl ^as9s9s^us99 GccgaaagGCGaGucaaGGuCu ggagca B 197

18825 314 AUGCUCC G CCACCUC 89 erbB2-314 Zin Rz-7 amino stabl 9s^as9_{S s} ^u99 GccgaaagGCGaGucaaGGuCu ggagcau B 198

18831 379 ACCAAU G CCAGCC 90 erbB2-379 Zin Rz-6 amino stabl _s9s^cs^us99 GccgaaagGCGaGucaaGGuCu auuggu B 199

18680 433 GCUCAUC G CUCACAA 91 erbB2-433 Zin Rz-7 ammo stabl ^us^us9s^us9^a9 GccgaaagGCGaGucaaGGuCu gaugagc B 200

18711 594 GGAGCU G CAGCUU 92 erbB2-594 Zin Rz-6 amino stabl ^as^as9s^cs^u9 GccgaaagGCGaGucaaGGuCu agcucc B 201

18681 594 GGGAGCU G CAGCUUC 93 erbB2-594 Zm Rz-7 amino stabl 9_s ^as^as9s^cu9 GccgaaagGCGaGucaaGGuCu agcuccc B 202

18697 597 GCUGCA G CUUCGA 94 erbB2-597 Zin Rz-6 ammo stabl ^us^cs9s^as^a9 GccgaaagGCGaGucaaGGuCu ugcagc B 203

18665 597 AGCUGCA G CUUCGAA 95 erbB2-597 Zin Rz-7 amino stabl ^us^us^c _S9_S ^aa9 GccgaaagGCGaGucaaGGuCu ugcagcu B 204

18712 659 AGCUCU G CUACCA 96 erbB2-659 Zin Rz-6 ammo stabl ^us9_s9_su_sa GccgaaagGCGaGucaaGGuCu agagcu B 205

18682 659 CAGCUCU G CUACCAG 97 erbB2-659 Zin Rz-7 amino stabl ^cs^us9_s9s^ua9 GccgaaagGCGaGucaaGGuCu agagcug B 206

18683 878 CUGACU G CUGCCA 98 erbB2-878 Zin Rz-6 amino stabl ^us9_S9s^cs^a9 GccgaaagGCGaGucaaGGuCu agucag B 207

18654 878 ACUGACU G CUGCCAU 99 erbB2-878 Zin Rz-7 amino stabl ^as^us9_{a s} ^ca9 GccgaaagGCGaGucaaGGuCu agucagu B 208

18685 881 ACUGCU G CCAUGA 100 erbB2-881 Zin Rz-6 ammo stabl ^us^c _S ^as^us99 GccgaaagGCGaGucaaGGuCu agcagu B 209

18684 881 GACUGCU G CCAUGAG 101 erbB2-881 Zin Rz-7 ammo stabl ^cs^us^cs^as^u99 GccgaaagGCGaGucaaGGuCu agcaguc B 210

18723 888 GCCAUGA G CAGUGUG 102 erbB2-888 Zm Rz-7 amino stabl ^cs^as^cs^a3^CU9 GccgaaagGCGaGucaaGGuCu ucauggc B 211

18686 929 CUGACU G CCUGGC 103 erbB2-929 Zin Rz-6 amino stabl 9s^cs^cs^as99 GccgaaagGCGaGucaaGGuCu agucag B 212

18648 929 UCUGACU G CCUGGCC 104 erbB2-929 Zin Rz-7 amino stabl 9_s9₃ ^cs^cs^a99 GccgaaagGCGaGucaaGGuCu agucaga B 213

18666 934 UGCCUG G CCUGCC 105 erbB2-934 Zin Rz-6 ammo stabl 9₃9s^cs^as99 GccgaaagGCGaGucaaGGuCu caggca B 214

18651 934 CUGCCUG G CCUGCCU 106 erbB2-934 Zm Rz-7 amino stabl ^a _S9s9s^cs^a99 GccgaaagGCGaGucaaGGuCu caggcag B 215

18655 938 UGGCCU G CCUCCA 107 erbB2-938 Zin Rz-6 ammo stabl ^us9_s9_s ^as99 GccgaaagGCGaGucaaGGuCu aggcca B 216

18649 938 CUGGCCU G CCUCCAC 108 erbB2-938 Zin Rz 7 amino stabl 9s^us9_S9s^a99 GccgaaagGCGaGucaaGGuCu aggccag B 217

18667 969 CUGUGA G CUGCAC 109 erbB2-969 Zin Rz-6 amino stabl 9s^us9s^cs^a9 GccgaaagGCGaGucaaGGuCu ucacag B 218

18668 969 UCUGUGA G CUGCACU 110 erbB2-969 Zm Rz-7 amino stabl ^as9_a ^u ₃9s^ca9 GccgaaagGCGaGucaaGGuCu ucacaga B 219

18656 972 UGAGCU G CACUGC 111 erbB2-972 Zin Rz-6 amino stabl 9s^cs^as9s^u9 GccgaaagGCGaGucaaGGuCu agcuca B 220

18657 972 GUGAGCU G CACUGCC 112 erbB2-972 Zin Rz-7 amino stabl 9_s9s^cs^as9^u9 GccgaaagGCGaGucaaGGuCu agcucac B 221

19294 972 erbB2-972 Zm Rz-6 ammo stabl g c a g ug GccaauuugugGCGaGucaaGGuCu agcuca B 222

Table 58

19295 972 erbB2-972 Zm Rz-6 amino stabl g_gc_ga_sg₃ug GccAAuuuGuGGCGaGucaaGGuCu agcuca B 223

19293 972 erbB2-972 Zm Rz-6 amino stabl 9s^cs^a _S9s^u9 GccgaaagGCGaGuGaGGuCu agcuca B 224

19292 972 erbB2-972 Zin Rz-6 amino stabl 9s^cs^as9s^u9 GccgaaagGCGaGuGaGGuCu agcuca B 225

19296 972 erbB2-972 Zin Rz-6 amino stabl g c a g ug GccacAAuuuGuGGcagGCGaGucaaGGuCu agcuca B 226

19727 972 erbB2-972 Zm Rz-6 amino stabl 9s s^as9s^u9 gccgaaaggCgagugagguCu agcuca B 227

19728 972 erbB2-972 Zm Rz-6 amino stabl 9s^cs^as9s^u9 gccgaaaggCgagugagGuCu agcuca B 228

18659 1199 GAGUGU G CUAUGG 113 erbB2-1199 Zin Rz-6 amino stabl ^cs^cs^a3^Us^a9 GccgaaagGCGaGucaaGGuCu acacuc B 229

18658 1199 CGAGUGU G CUAUGGU 114 erbB2-1199 Zm Rz-7 ammo stabl ^as^cs^cs^as^ua9 GccgaaagGCGaGucaaGGuCu acacucg B 230

18724 1205 GCUAUG G UCUGGG 115 erbB2-1205 Zin Rz-6 ammo stabl ^cs^cs^cs^as9^a GccgaaagGCGaGucaaGGuCu cauagc B 231

18669 1205 UGCUAUG G UCUGGGC 116 erbB2-1205 Zin Rz-7 amino stabl 9s^c _S ^cs^cs^a9^a GccgaaagGCGaGucaaGGuCu cauagca B 232

18725 1211 GUCUGG G CAUGGA 117 erbB2-1211 Z Rz-6 amino stabl ^us^cs^cs^as^u9 GccgaaagGCGaGucaaGGuCu ccagac B 233

18726 1292 UUGGGA G CCUGGC 118 erbB2-1292 Zin Rz-6 amino stabl 9s^cs^cs^as99 GccgaaagGCGaGucaaGGuCu ucccaa B 234

18698 1292 UUUGGGA G CCUGGCA 119 erbB2-1292 Zin Rz-7 amino stabl ^us9s^cs^cs^a99 GccgaaagGCGaGucaaGGuCu ucccaaa B 235

18727 1313 CCGGAGA G CUUUGAU 120 erbB2-1313 Zin Rz-7 amino stabl ^as^us^cs^as^aa9 GccgaaagGCGaGucaaGGuCu ucuccgg B 236

18699 1397 UCACAG G UUACCU 121 erbB2-1397 Zin Rz-6 ammo stabl ^as9_s9s^u _S ^aa GccgaaagGCGaGucaaGGuCu cuguga B 237

18728 1414 AUCUCA G CAUGGC 122 erbB2-1414 Zin Rz-6 ammo stabl 9s^cs s^as^u9 GccgaaagGCGaGucaaGGuCu ugagau B 238

18670 1414 CAUCUCA G CAUGGCC 123 erbB2-1414 Zin Rz-7 amino stabl 9_s9_s ^cs^cs^au9 GccgaaagGCGaGucaaGGuCu ugagaug B 239

18671 1536 GCUGGG G CUGCGC 124 erbB2-1536 Zin Rz-6 amino stabl 9s^cs9s^cs^a9 GccgaaagGCGaGucaaGGuCu cccagc B 240

18687 1541 GGCUGC G CUCACU 125 erbB2-1541 Zin Rz-6 amino stabl ^as9s^us9s^a9 GccgaaagGCGaGucaaGGuCu gcagcc B 241

18829 1562 CUGGGCA G UGGACUG 126 erbB2-1562 Zin Rz-7 ammo stabl ^cs^as9s^us^cca GccgaaagGCGaGucaaGGuCu ugcccag B 242

18830 1626 GGGACCA G CUCUUUC 127 erbB2-1626 Zin Rz-7 amino stabl 9s^as^as s9^a9 GccgaaagGCGaGucaaGGuCu ugguccc B 243

18700 1755 CACCCA G UGUGUC 128 erbB2-1755 Zin Rz-6 amino stabl 9s^as^cs^as^ca GccgaaagGCGaGucaaGGuCu ugggug B 244

18672 1755 CCACCCA G UGUGUCA 129 erbB2-1755 Zin Rz-7 ammo stabl ^us9_a ^as^cs^aca GccgaaagGCGaGucaaGGuCu ugggugg B 245

18688 1757 CCCAGU G UGUCAA 130 erbB2-1757 Zm Rz-6 ammo stabl ^us^us9_s ^as^ca GccgaaagGCGaGucaaGGuCu acuggg B 246

18660 1757 ACCCAGU G UGUCAAC 131 erbB2-1757 Zin Rz-7 amino stabl 9_s ^us^us9_s ^aca GccgaaagGCGaGucaaGGuCu acugggu B 247

18689 1759 CAGUGU G UCAACU 132 erbB2-1759 Zin Rz-6 amino stabl ^as9_s ^us^u__9^a GccgaaagGCGaGucaaGGuCu acacug B 248

18690 1759 CCAGUGU G UCAACUG 133 erbB2-1759 Zin Rz-7 amino stabl ^cs^as9s^us^u9^a GccgaaagGCGaGucaaGGuCu acacugg B 249

18701 1784 UUCGGG G CCAGGA 134 erbB2-1784 Zin Rz-6 ammo stabl ^u _S ^cs^cs^us99 GccgaaagGCGaGucaaGGuCu cccgaa B 250

18673 1784 CUUCGGG G CCAGGAG 135 erbB2-1784 Zm Rz-7 amino stabl ^cs^us^cs^cs^u99 GccgaaagGCGaGucaaGGuCu cccgaag B 251

18691 2063 UCAACU G CACCCA 136 erbB2-2063 Zin Rz-6 ami o stabl ^u _S9_s9_s9s^u9 GccgaaagGCGaGucaaGGuCu aguuga B 252

18661 2063 AUCAACU G CACCCAC 137 erbB2-2063 Zin Rz-7 amino stabl 9s^us9s^g _s9^u9 GccgaaagGCGaGucaaGGuCu aguugau B 253

Table 58

18692 2075 ACUCCU G UGUGGA 138 erbB2-2075 Zin Rz 6 ammo stabl ^us^cs^cs^as^ca GccgaaagGCGaGucaaGGuCu aggagu B 254

18729 2116 CAGAGA G CCAGCC 139 erbB2-2116 Zin Rz-6 ammo stabl 9s9_a s^us99 GccgaaagGCGaGucaaGGuCu ucucug B 255

18832 2247 GACUGCU G CAGGAAA 140 erbB2-2247 Zm Rz-7 amino stabl ^u3^us^us^c _a ^cu9 GccgaaagGCGaGucaaGGuCu agcaguc B 256

18833 2271 UGGAGCC G CUGACAC 141 erbB2-2271 Zin Rz-7 amino stabl 9__^u _a9_a ^u _a ^ca9 GccgaaagGCGaGucaaGGuCu ggcucca B 257

18702 2341 AGGAAG G UGAAGG 142 erbB2-2341 Zin Rz-6 amino stabl c„ 8c3„u„8u„Sca GccgaaagGCGaGucaaGGuCu cuuccu B 258

18730 2347 GUGAAG G UGCUUG 143 erbB2-2347 Zin Rz-6 amino stabl ^c3^a _a ^a _a9₃ ^ca GccgaaagGCGaGucaaGGuCu cuucac B 259

18674 2347 GGUGAAG G UGCUUGG 144 erbB2-2347 Zm Rz-7 amino stabl ^cs^cs^as^as^gca GccgaaagGCGaGucaaGGuCu cuucacc B 260

18713 2349 GAAGGU G CUUGGA 145 erbB2-2349 Zm Rz-6 amino stabl u„ 3c_3c„3a_8ag³ GccgaaagGCGaGucaaGGuCu accuuc B 261

18693 2349 UGAAGGU G CUUGGAU 146 erbB2-2349 Zm Rz-7 amino stabl ^a3^us^cs^c _a ^aa9 GccgaaagGCGaGucaaGGuCu accuuca B 262

18731 2384 UACAAGG G CAUCUGG 147 erbB2-2384 Zin Rz 7 amino stabl ^C8^C3^as9s^au9 GccgaaagGCGaGucaaGGuCu ccuugua B 263

18714 2410 GGAGAAU G UGAAAAU 148 erbB2-2410 Zin Rz-7 ammo stabl a 8__u„3u_3_u,3_uca GccgaaagGCGaGucaaGGuCu auucucc B 264

18732 2497 GUGAUG G CUGGUG 149 erbB2-2497 Zin Rz-6 amino stabl c_ 8a_S_c8__c_3ag^J GccgaaagGCGaGucaaGGuCu caucac B 265

18703 2501 UGGCUG G UGUGGG 150 erbB2-2501 Zin Rz-6 amino stabl c_ 3c₌3c„8a„8ca GccgaaagGCGaGucaaGGuCu cagcca B 266

18715 2540 GCAUCU G CCUGAC 151 erbB2-2540 Zin Rz-6 amino stabl 9₈ ^us^cs^as99 GccgaaagGCGaGucaaGGuCu agaugc B 267

18733 2563 CAGCUG G UGACAC 152 erbB2-2563 Zin Rz-6 ammo stabl 9s^us9s^us^ca GccgaaagGCGaGucaaGGuCu cagcug B 268

18734 2571 GACACA G CUUAUG 153 erbB2 2571 Zin Rz-6 ammo stabl c_s_a„sus_,a_sag³ GccgaaagGCGaGucaaGGuCu uguguc B 269

18675 2571 UGACACA G CUUAUGC 154 erbB2-2571 Zm Rz-7 amino stabl 9s^cs^as^us^aa9 GccgaaagGCGaGucaaGGuCu uguguca B 270

18716 2662 CAGAUU G CCAAGG 155 erbB2-2662 Zin Rz-6 amino stabl ^c3^Cs^us^us99 GccgaaagGCGaGucaaGGuCu aaucug B 271

18704 2675 GGAUGA G CUACCU 156 erbB2-2675 Zin Rz-6 amino stabl ^as9s9a^us^a9 GccgaaagGCGaGucaaGGuCu ucaucc B 272

18676 2675 GGGAUGA G CUACCUG 157 erbB2 2675 Zin Rz-7 ammo stabl ^cs^a _S9_s9_sua GccgaaagGCGaGucaaGGuCu ucauccc B 273

18735 2738 GUCAAGA G UCCCAAC 158 erbB2 2738 Zin Rz-7 ammo stabl 9s^us^us9_S99^a GccgaaagGCGaGucaaGGuCu ucuugac B 274

18705 2773 GGGCUG G CUCGGC 159 erbB2-2773 Zm Rz-6 amino stabl 9s^cs^cs9s^a9 GccgaaagGCGaGucaaGGuCu cagccc B 275

18836 2778 UGGCUCG G CUGCUGG 160 erbB2-2778 Zin Rz-7 amino stabl ^cs^cs^a _S9_s ^ca9 GccgaaagGCGaGucaaGGuCu cgagcca B 276

18694 2781 UCGGCU G CUGGAC 161 erbB2-2781 Zin Rz-6 amino stabl 9s^us^cs^cs^a9 GccgaaagGCGaGucaaGGuCu agccga B 277

18662 2781 CUCGGCU G CUGGACA 162 erbB2 2781 Zin Rz-7 ammo stabl ^us9s^us^cs^ca9 GccgaaagGCGaGucaaGGuCu agccgag B 278

18737 2802 GACAGA G UACCAU 163 erbB2-2802 Zm Rz-6 amino stabl 8^Us9_a9s^ua GccgaaagGCGaGucaaGGuCu ucuguc B 279

18736 2802 AGACAGA G UACCAUG 164 erbB2-2802 Zin Rz-7 ammo stabl ^c ₃ ^as^us^gs9^ua GccgaaagGCGaGucaaGGuCu ucugucu B 280

18717 2809 GUACCAU G CAGAUGG 165 erbB2-2809 Zin Rz-7 ammo stabl ^cs^cs^as^us^cug GccgaaagGCGaGucaaGGuCu augguac B 281

18738 2819 AUGGGG G CAAGGU 166 erbB2-2819 Zin Rz-6 ammo stabl ^as^cs^cs^u3^u9 GccgaaagGCGaGucaaGGuCu ccccau B 282

18706 2819 GAUGGGG G CAAGGUG 167 erbB2-2819 Zin Rz-7 amino stabl ^cs^a3^cs^cs^uu9 GccgaaagGCGaGucaaGGuCu ccccauc B 283

18695 2887 GAGUGAU G UGUGGAG 168 erbB2-2887 Zin Rz-7 amino stabl ^C3^US^C _a ^C _a ^aCa GccgaaagGCGaGucaaGGuCu aucacuc B 284

Table 58

18663 2908 GUGACU G UGUGGG 169 erbB2-2908 Zin Rz-6 amino stabl c„ 3c3c_Λ3a„3ca GccgaaagGCGaGucaaGGuCu agucac B 285

18826 2908 UGUGACU G UGUGGGA 170 erbB2-2908 Zm Rz-7 ammo stabl u 8_c_ScS_c_3aca GccgaaagGCGaGucaaGGuCu agucaca B 286

18664 2910 GACUGU G UGGGAG 171 erbB2-2910 Zin Rz-6 amino stabl ^C8^U8^C8^C _a ^C GccgaaagGCGaGucaaGGuCu acaguc B 287

18650 2910 UGACUGU G UGGGAGC 172 erbB2-2910 Zin Rz-7 ammo stabl 9_a ^cs^us^cs^cca GccgaaagGCGaGucaaGGuCu acaguca B 288

18677 2916 GUGGGA G CUGAUG 173 erbB2-2916 Zin Rz-6 amino stabl ^C3^a8^U8^C8^a9 GccgaaagGCGaGucaaGGuCu ucccac B 289

18652 2916 UGUGGGA G CUGAUGA 174 erbB2-2916 Zm Rz-7 ammo stabl ^us^cs^as^us^ca9 GccgaaagGCGaGucaaGGuCu ucccaca B 290

18707 2932 UUUGGG G CCAAAC 175 erbB2-2932 Zin Rz-6 ammo stabl 9₃ ^uβ^us^u899 GccgaaagGCGaGucaaGGuCu cccaaa B 291

18678 2932 UUUUGGG G CCAAACC 176 erbB2-2932 Z Rz-7 amino stabl 9s9_s ^us^ua^u99 GccgaaagGCGaGucaaGGuCu cccaaaa B 292

18719 3025 AUUGAU G UCUACA 177 erbB2-3025 Zin Rz-6 amino stabl ^us9s^us^as9^a GccgaaagGCGaGucaaGGuCu aucaau B 293

18718 3025 CAUUGAU G UCUACAU 178 erbB2-3025 Zm Rz-7 amino stabl ^as^us9a^us^a9^a GccgaaagGCGaGucaaGGuCu aucaaug B 294

18720 3047 UCAAAU G UUGGAU 179 erbB2-3047 Zm Rz-6 ammo stabl a_ 3_u_8_c3__c_3aa GccgaaagGCGaGucaaGGuCu auuuga B 295

18696 3047 GUCAAAU G UUGGAUG 180 erbB2-3047 Zm Rz-7 amino stabl c 8_a_8u_Sc_8caa GccgaaagGCGaGucaaGGuCu auuugac B 296

18739 3087 CCGGGA G UUGGUG 181 erbB2-3087 Zin Rz-6 amino stabl c 3a3c8c8aa GccgaaagGCGaGucaaGGuCu ucccgg B 297

18708 3087 UCCGGGA G UUGGUGU 182 erbB2-3087 Zin Rz-7 amino stabl ^as^cs^as^cs^caa GccgaaagGCGaGucaaGGuCu ucccgga B 298

18740 3415 GAAGGG G CUGGCU 183 erbB2-3415 Zin Rz-6 am o stabl ^as9_s ^cs^cs^a9 GccgaaagGCGaGucaaGGuCu cccuuc B 299

18741 3419 GGGCUG G CUCCGA 184 erbB2-3419 Zin Rz-6 ammo stabl ^us^cs9s9s^a9 GccgaaagGCGaGucaaGGuCu cagccc B 300

18837 3419 GGGGCUG G CUCCGAU 185 erbB2-3419 Zm Rz-7 amino stabl ^as^us^cs9_s9^a9 GccgaaagGCGaGucaaGGuCu cagcccc B 301

18709 3437 UUGAUG G UGACCU 186 erbB2-3437 Zin Rz-6 amino stabl ^as9s9_s ^us^ca GccgaaagGCGaGucaaGGuCu caucaa B 302

18679 3437 UUUGAUG G UGACCUG 187 erbB2-3437 Zin Rz-7 ammo stabl ^cs^as9_a9s^uca GccgaaagGCGaGucaaGGuCu caucaaa B 303

18823 3504 UCUACA G CGGUAC 188 erbB2-3504 Zin Rz-6 amino stabl 9_s ^u ₈ ^a ₈ ^Cs^c9 GccgaaagGCGaGucaaGGuCu uguaga B 304

18710 3504 CUCUACA G CGGUACA 189 erbB2-3504 Zm Rz-7 amino stabl ^u _S9_a ^u ₈ ^a _a ^cc9 GccgaaagGCGaGucaaGGuCu uguagag B 305

18721 3724 CAAAGAC G UUUUUGC 190 erbB2-3724 Zin Rz-7 amino stabl 9_a ^cs 8^a _a ^aa GccgaaagGCGaGucaaGGuCu gucuuug B 306

18834 3808 CCUCCU G CCUUCA 191 erbB2-3808 Zin Rz-6 amino stabl ^u _a9_a ^a _a ^as99 GccgaaagGCGaGucaaGGuCu aggagg B 307

18827 3808 UCCUCCU G CCUUCAG 192 erbB2-3808 Zin Rz-7 amino stabl ^c ₈ ^u _S9s^as^a99 GccgaaagGCGaGucaaGGuCu aggagga B 308

18824 3996 GGGAAG G CCUGAC 193 erbB2-3996 Zin Rz-6 amino stabl 9s^us^c ₈ ^a _S99 GccgaaagGCGaGucaaGGuCu cuuccc B 309

UPPER CASE = RIBO Lower case = 2'-0-methyl C = 2'-deoxy-2'-amino Cytidine s = phosphorothioate B = inverted deoxyabasic

Table 59 Table 59: Human HER2 Class II (zinzyme) Ribozyme and Target Sequece

Pos Substrate Seq ID Ribozyme RzSeq ID

46 GGGCAGCC G CGCGCCCC 310 GGGGCGCG GCCGAAAGGCGAGUCAAGGUCU GGCUGCCC 895

48 GCAGCCGC G CGCCCCUU 311 AAGGGGCG GCCGAAAGGCGAGUCAAGGUCU GCGGCUGC 896

50 AGCCGCGC G CCCCUUCC 312 GGAAGGGG GCCGAAAGGCGAGUCAAGGUCU GCGCGGCU B97

75 CCUUUACU G CGCCGCGC 313 GCGCGGCG GCCGAAAGGCGAGUCAAGGUCU AGUAAAGG 898

77 UUUACUGC G CCGCGCGC 314 GCGCGCGG GCCGAAAGGCGAGUCAAGGUCU GCAGUAAA 899

80 ACUGCGCC G CGCGCCCG 315 CGGGCGCG GCCGAAAGGCGAGUCAAGGUCU GGCGCAGU 900

82 UGCGCCGC G CGCCCGGC 316 GCCGGGCG GCCGAAAGGCGAGUCAAGGUCU GCGGCGCA 901

84 CGCCGCGC G CCCGGCCC 317 GGGCCGGG GCCGAAAGGCGAGUCAAGGUCU GCGCGGCG 902

102 CACCCCUC G CAGCACCC 318 GGGUGCUG GCCGAAAGGCGAGUCAAGGUCU GAGGGGUG 903

112 AGCACCCC G CGCCCCGC 319 GCGGGGCG GCCGAAAGGCGAGUCAAGGUCU GGGGUGCU 904

114 CACCCCGC G CCCCGCGC 320 GCGCGGGG GCCGAAAGGCGAGUCAAGGUCU GCGGGGUG 905

119 cGcσcccc G CGCCCUCC 321 GGAGGGCG GCCGAAAGGCGAGUCAAGGUCU GGGGCGCG 906

121 CGCCCCGC G CCCUCCCA 322 UGGGAGGG GCCGAAAGGCGAGUCAAGGUCU GCGGGGCG 907

163 CCGGAGCC G CAGUGAGC 323 GCUCACUG GCCGAAAGGCGAGUCAAGGUCU GGCUCCGG 908

194 GGCCUUGU G CCGCUGGG 324 CCCAGCGG GCCGAAAGGCGAGUCAAGGUCU ACAAGGCC 909

197 CUUGUGCC G CUGGGGGC 325 GCCCCCAG GCCGAAAGGCGAGUCAAGGUCU GGCACAAG 910

214 UCCUCCUC G CCCUCUUG 326 CAAGAGGG GCCGAAAGGCGAGUCAAGGUCU GAGGAGGA 911

222 GCCCUCUU G CCCCCCGG 327 CCGGGGGG GCCGAAAGGCGAGUCAAGGUCU AAGAGGGC 912

235 CCGGAGCC G CGAGCACC 328 GGUGCUCG GCCGAAAGGCGAGUCAAGGUCU GGCUCCGG 913

251 CCAAGUGU G CACCGGCA 329 UGCCGGUG GCCGAAAGGCGAGUCAAGGUCU ACACUUGG 914

273 AUGAAGCU G CGGCUCCC 330 GGGAGCCG GCCGAAAGGCGAGUCAAGGUCU AGCUUCAU 915

283 GGCUCCCU G CCAGUCCC 331 GGGACUGG GCCGAAAGGCGAGUCAAGGUCU AGGGAGCC 916

309 CUGGACAU G CUCCGCCA 332 UGGCGGAG GCCGAAAGGCGAGUCAAGGUCU AUGUCCAG 917

314 CAUGCUCC G CCACCUCU 333 AGAGGUGG GCCGAAAGGCGAGUCAAGGUCU GGAGCAUG 918

332 CCAGGGCU G CCAGGUGG 334 CCACCUGG GCCGAAAGGCGAGUCAAGGUCU AGCCCUGG 919

342 CAGGUGGU G CAGGGAAA 335 UUUCCCUG GCCGAAAGGCGAGUCAAGGUCU ACCACCUG 920

369 ACCUACCU G CCCACCAA 336 UUGGUGGG GCCGAAAGGCGAGUCAAGGUCU AGGUAGGU 921

379 CCACCAAU G CCAGCCUG 337 CAGGCUGG GCCGAAAGGCGAGUCAAGGUCU AUUGGUGG 922

396 UCCUUCCU G CAGGAUAU 338 AUAUCCUG GCCGAAAGGCGAGUCAAGGUCU AGGAAGGA 923

414 CAGGAGGU G CAGGGCUA 339 UAGCCCUG GCCGAAAGGCGAGUCAAGGUCU ACCUCCUG 924

426 GGCUACGU G CUCAUCGC 340 GCGAUGAG GCCGAAAGGCGAGUCAAGGUCU ACGUAGCC 925

433 UGCUCAUC G CUCACAAC 341 GUUGUGAG GCCGAAAGGCGAGUCAAGGUCU GAUGAGCA 926

462 GUCCCACU G CAGAGGCU 342 AGCCUCUG GCCGAAAGGCGAGUCAAGGUCU AGUGGGAC 927

471 CAGAGGCU G CGGAUUGU 343 ACAAUCCG GCCGAAAGGCGAGUCAAGGUCU AGCCUCUG 928

480 CGGAUUGU G CGAGGCAC 344 GUGCCUCG GCCGAAAGGCGAGUCAAGGUCU ACAAUCCG 929

511 ACAACUAU G CCCUGGCC 345 GGCCAGGG GCCGAAAGGCGAGUCAAGGUCU AUAGUUGU 930

522 CUGGCCGU G CUAGACAA 346 UUGUCUAG GCCGAAAGGCGAGUCAAGGUCU ACGGCCAG 931

540 GGAGACCC G CUGAACAA 347 UUGUUCAG GCCGAAAGGCGAGUCAAGGUCU GGGUCUCC 932

585 GGAGGCCU G CGGGAGCU 348 AGCUCCCG GCCGAAAGGCGAGUCAAGGUCU AGGCCUCC 933

594 CGGGAGCU G CAGCUUCG 349 CGAAGCUG GCCGAAAGGCGAGUCAAGGUCU AGCUCCCG 934

659 CCAGCUCU G CUACCAGG 350 CCUGGUAG GCCGAAAGGCGAGUCAAGGUCU AGAGCUGG 935

737 CACCAACC G CUCUCGGG 351 CCCGAGAG GCCGAAAGGCGAGUCAAGGUCU GGUUGGUG 936

749 UCGGGCCU G CCACCCCU 352 AGGGGUGG GCCGAAAGGCGAGUCAAGGUCU AGGCCCGA 937 Table 59

782 GGGCUCCC G CUGCUGGG 353 CCCAGCAG GCCGAAAGGCGAGUCAAGGUCU GGGAGCCC 938

785 CUCCCGCU G CUGGGGAG 354 CUCCCCAG GCCGAAAGGCGAGUCAAGGUCU AGCGGGAG 939

822 AGCCUGAC G CGCACUGU 355 ACAGUGCG GCCGAAAGGCGAGUCAAGGUCU GUCAGGCU 940

824 CCUGACGC G CACUGUCU 356 AGACAGUG GCCGAAAGGCGAGUCAAGGUCU GCGUCAGG 941

835 CUGUCUGU G CCGGUGGC 357 GCCACCGG GCCGAAAGGCGAGUCAAGGUCU ACAGACAG 942

847 GUGGCUGU G CCCGCUGC 358 GCAGCGGG GCCGAAAGGCGAGUCAAGGUCU ACAGCCAC 943

851 CUGUGCCC G CUGCAAGG 359 CCUUGCAG GCCGAAAGGCGAGUCAAGGUCU GGGCACAG 944

854 UGCCCGCU G CAAGGGGC 360 GCCCCUUG GCCGAAAGGCGAGUCAAGGUCU AGCGGGCA 945

867 GGGCCACU G CCCACUGA 361 UCAGUGGG GCCGAAAGGCGAGUCAAGGUCU AGUGGCCC 946

878 CACUGACU G CUGCCAUG 362 CAUGGCAG GCCGAAAGGCGAGUCAAGGUCU AGUCAGUG 947

881 UGACUGCU G CCAUGAGC 363 GCUCAUGG GCCGAAAGGCGAGUCAAGGUCU AGCAGUCA 948

895 AGCAGUGU G CUGCCGGC 364 GCCGGCAG GCCGAAAGGCGAGUCAAGGUCU ACACUGCU 949

898 AGUGUGCU G CCGGCUGC 365 GCAGCCGG GCCGAAAGGCGAGUCAAGGUCU AGCACACU 950

905 UGCCGGCU G CACGGGCC 366 GGCCCGUG GCCGAAAGGCGAGUCAAGGUCU AGCCGGCA 951

929 CUCUGACU G CCUGGCCU 367 AGGCCAGG GCCGAAAGGCGAGUCAAGGUCU AGUCAGAG 952

938 CCUGGCCU G CCUCCACU 368 AGUGGAGG GCCGAAAGGCGAGUCAAGGUCU AGGCCAGG 953

972 UGUGAGCU G CACUGCCC 369 GGGCAGUG GCCGAAAGGCGAGUCAAGGUCU AGCUCACA 954

977 GCUGCACU G CCCAGCCC 370 GGGCUGGG GCCGAAAGGCGAGUCAAGGUCU AGUGCAGC 955

1020 GAGUCCAU G CCCAAUCC 371 GGAUUGGG GCCGAAAGGCGAGUCAAGGUCU AUGGACUC 956

1051 CAUUCGGC G CCAGCUGU 372 ACAGCUGG GCCGAAAGGCGAGUCAAGGUCU GCCGAAUG 957

1066 GUGUGACU G CCUGUCCC 373 GGGACAGG GCCGAAAGGCGAGUCAAGGUCU AGUCACAC 958

1106 GGGAUCCU G CACCCUCG 374 CGAGGGUG GCCGAAAGGCGAGUCAAGGUCU AGGAUCCC 959

1118 CCUCGUCU G CCCCCUGC 375 GCAGGGGG GCCGAAAGGCGAGUCAAGGUCU AGACGAGG 960

1125 UGCCCCCU G CACAACCA 376 UGGUUGUG GCCGAAAGGCGAGUCAAGGUCU AGGGGGCA 961

1175 UGAGAAGU G CAGCAAGC 377 GCUUGCUG GCCGAAAGGCGAGUCAAGGUCU ACUUCUCA 962

1189 AGCCCUGU G CCCGAGUG 378 CACUCGGG GCCGAAAGGCGAGUCAAGGUCU ACAGGGCU 963

1199 CCGAGUGU G CUAUGGUC 379 GACCAUAG GCCGAAAGGCGAGUCAAGGUCU ACACUCGG 964

1224 GAGCACUU G CGAGAGGU 380 ACCUCUCG GCCGAAAGGCGAGUCAAGGUCU AAGUGCUC 965

1249 UUACCAGU G CCAAUAUC 381 GAUAUUGG GCCGAAAGGCGAGUCAAGGUCU ACUGGUAA 966

1267 AGGAGUUU G CUGGCUGC 382 GCAGCCAG GCCGAAAGGCGAGUCAAGGUCU AAACUCCU 967

1274 UGCUGGCU G CAAGAAGA 383 UCUUCUUG GCCGAAAGGCGAGUCAAGGUCU AGCCAGCA 968

1305 GCAUUUCU G CCGGAGAG 384 CUCUCCGG GCCGAAAGGCGAGUCAAGGUCU AGAAAUGC 969

1342 CCAACACU G CCCCGCUC 385 GAGCGGGG GCCGAAAGGCGAGUCAAGGUCU AGUGUUGG 970

1347 ACUGCCCC G CUCCAGCC 386 GGCUGGAG GCCGAAAGGCGAGUCAAGGUCU GGGGCAGU 971

1431 GACAGCCU G CCUGACCU 387 AGGUCAGG GCCGAAAGGCGAGUCAAGGUCU AGGCUGUC 972

1458 CAGAACCU G CAAGUAAU 388 AUUACUUG GCCGAAAGGCGAGUCAAGGUCU AGGUUCUG 973

1482 CGAAUUCU G CACAAUGG 389 CCAUUGUG GCCGAAAGGCGAGUCAAGGUCU AGAAUUCG 974

1492 ACAAUGGC G CCUACUCG 390 CGAGUAGG GCCGAAAGGCGAGUCAAGGUCU GCCAUUGU 975

1500 GCCUACUC G CUGACCCU 391 AGGGUCAG GCCGAAAGGCGAGUCAAGGUCU GAGUAGGC 976

1509 CUGACCCU G CAAGGGCU 392 AGCCCUUG GCCGAAAGGCGAGUCAAGGUCU AGGGUCAG 977

1539 CUGGGGCU G CGCUCACU 393 AGUGAGCG GCCGAAAGGCGAGUCAAGGUCU AGCCCCAG 978

1541 GGGGCUGC G CUCACUGA 394 UCAGUGAG GCCGAAAGGCGAGUCAAGGUCU GCAGCCCC 979

1598 CCACCUCU G CUUCGUGC 395 GCACGAAG GCCGAAAGGCGAGUCAAGGUCU AGAGGUGG 980

1605 UGCUUCGU G CACACGGU 396 ACCGUGUG GCCGAAAGGCGAGUCAAGGUCU ACGAAGCA 981

1614 CACAcσσu G CCCUGGGA 397 UCCCAGGG GCCGAAAGGCGAGUCAAGGUCU ACCGUGUG 982

1641 CGGAACCC G CACCAAGC 398 GCUUGGUG GCCGAAAGGCGAGUCAAGGUCU GGGUUCCG 983

1653 CAAGCUCU G CUCCACAC 399 GUGUGGAG GCCGAAAGGCGAGUCAAGGUCU AGAGCUUG 984 Table 59

1663 UCCACACU G CCAACCGG 400 CCGGUUGG GCCGAAAGGCGAGUCAAGGUCU AGUGUGGA 985

1706 CCUGGCCU G CCACCAGC 401 GCUGGUGG GCCGAAAGGCGAGUCAAGGUCU AGGCCAGG 986

1718 CCAGCUGU G CGCCCGAG 402 CUCGGGCG GCCGAAAGGCGAGUCAAGGUCU ACAGCUGG 987

1720 AGCUGUGC G CCCGAGGG 403 CCCUCGGG GCCGAAAGGCGAGUCAAGGUCU GCACAGCU 988

1733 AGGGCACU G CUGGGGUC 404 GACCCCAG GCCGAAAGGCGAGUCAAGGUCU AGUGCCCU 989

1766 UGUCAACU G CAGCCAGU 405 ACUGGCUG GCCGAAAGGCGAGUCAAGGUCU AGUUGACA 990

1793 CCAGGAGU G CGUGGAGG 406 CCUCCACG GCCGAAAGGCGAGUCAAGGUCU ACUCCUGG 991

1805 GGAGGAAU G CCGAGUAC 407 GUACUCGG GCCGAAAGGCGAGUCAAGGUCU AUUCCUCC 992

1815 CGAGUACU G CAGGGGCU 408 AGCCCCUG GCCGAAAGGCGAGUCAAGGUCU AGUACUCG 993

1843 AUGUGAAU G CCAGGCAC 409 GUGCCUGG GCCGAAAGGCGAGUCAAGGUCU AUUCACAU 994

1857 CACUGUUU G CCGUGCCA 410 UGGCACGG GCCGAAAGGCGAGUCAAGGUCU AAACAGUG 995

1862 UUUGCCGU G CCACCCUG 411 CAGGGUGG GCCGAAAGGCGAGUCAAGGUCU ACGGCAAA 996

1936 UGGCCUGU G CCCACUAU 412 AUAGUGGG GCCGAAAGGCGAGUCAAGGUCU ACAGGCCA 997

1961 UCCCUUCU G CGUGGCCC 413 GGGCCACG GCCGAAAGGCGAGUCAAGGUCU AGAAGGGA 998

1970 CGUGGCCC G CUGCCCCA 414 UGGGGCAG GCCGAAAGGCGAGUCAAGGUCU GGGCCACG 999

1973 GGCCCGCU G CCCCAGCG 415 CGCUGGGG GCCGAAAGGCGAGUCAAGGUCU AGCGGGCC 1000

2007 UCCUACAU G CCCAUCUG 416 CAGAUGGG GCCGAAAGGCGAGUCAAGGUCU AUGUAGGA 1001

2038 AGGAGGGC G CAUGCCAG 417 CUGGCAUG GCCGAAAGGCGAGUCAAGGUCU GCCCUCCU 1002

2042 GGGCGCAU G CCAGCCUU 418 AAGGCUGG GCCGAAAGGCGAGUCAAGGUCU AUGCGCCC 1003

2051 CCAGCCUU G CCCCAUCA 419 UGAUGGGG GCCGAAAGGCGAGUCAAGGUCU AAGGCUGG 1004

2063 CAUCAACU G CACCCACU 420 AGUGGGUG GCCGAAAGGCGAGUCAAGGUCU AGUUGAUG 1005

2099 CAAGGGCU G CCCCGCCG 421 CGGCGGGG GCCGAAAGGCGAGUCAAGGUCU AGCCCUUG 1006

2104 GCUGCCCC G CCGAGCAG 422 CUGCUCGG GCCGAAAGGCGAGUCAAGGUCU GGGGCAGC 1007

2143 UCAUCUCU G CGGUGGUU 423 AACCACCG GCCGAAAGGCGAGUCAAGGUCU AGAGAUGA 1008

2160 GGCAUUCU G CUGGUCGU 424 ACGACCAG GCCGAAAGGCGAGUCAAGGUCU AGAAUGCC 1009

2235 UACACGAU G CGGAGACU 425 AGUCUCCG GCCGAAAGGCGAGUCAAGGUCU AUCGUGUA 1010

2244 CGGAGACU G CUGCAGGA 426 UCCUGCAG GCCGAAAGGCGAGUCAAGGUCU AGUCUCCG 1011

2247 AGACUGCU G CAGGAAAC 427 GUUUCCUG GCCGAAAGGCGAGUCAAGGUCU AGCAGUCU 1012

2271 GUGGAGCC G CUGACACC 428 GGUGUCAG GCCGAAAGGCGAGUCAAGGUCU GGCUCCAC 1013

2292 GGAGCGAU G CCCAACCA 429 UGGUUGGG GCCGAAAGGCGAGUCAAGGUCU AUCGCUCC 1014

2304 AACCAGGC G CAGAUGCG 430 CGCAUCUG GCCGAAAGGCGAGUCAAGGUCU GCCUGGUU 1015

2310 GCGCAGAU G CGGAUCCU 431 AGGAUCCG GCCGAAAGGCGAGUCAAGGUCU AUCUGCGC 1016

2349 GUGAAGGU G CUUGGAUC 432 GAUCCAAG GCCGAAAGGCGAGUCAAGGUCU ACCUUCAC 1017

2362 GAUCUGGC G CUUUUGGC 433 GCCAAAAG GCCGAAAGGCGAGUCAAGGUCU GCCAGAUC 1018

2525 UGUCUCCC G CCUUCUGG 434 CCAGAAGG GCCGAAAGGCGAGUCAAGGUCU GGGAGACA 1019

2540 GGGCAUCU G CCUGACAU 435 AUGUCAGG GCCGAAAGGCGAGUCAAGGUCU AGAUGCCC 1020

2556 UCCACGGU G CAGCUGGU 436 ACCAGCUG GCCGAAAGGCGAGUCAAGGUCU ACCGUGGA 1021

2577 CAGCUUAU G CCCUAUGG 437 CCAUAGGG GCCGAAAGGCGAGUCAAGGUCU AUAAGCUG 1022

2588 CUAUGGCU G CCUCUUAG 438 CUAAGAGG GCCGAAAGGCGAGUCAAGGUCU AGCCAUAG 1023

2615 GGAAAACC G CGGACGCC 439 GGCGUCCG GCCGAAAGGCGAGUCAAGGUCU GGUUUUCC 1024

2621 CCGCGGAC G CCUGGGCU 440 AGCCCAGG GCCGAAAGGCGAGUCAAGGUCU GUCCGCGG 1025

2640 CAGGACCU G CUGAACUG 441 CAGUUCAG GCCGAAAGGCGAGUCAAGGUCU AGGUCCUG 1026

2655 UGGUGUAU G CAGAUUGC 442 GCAAUCUG GCCGAAAGGCGAGUCAAGGUCU AUACACCA 1027

2662 UGCAGAUU G CCAAGGGG 443 CCCCUUGG GCCGAAAGGCGAGUCAAGGUCU AAUCUGCA 1028

2691 GAGGAUGU G CGGCUCGU 444 ACGAGCCG GCCGAAAGGCGAGUCAAGGUCU ACAUCCUC 1029

2716 ACUUGGCC G CUCGGAAC 445 GUUCCGAG GCCGAAAGGCGAGUCAAGGUCU GGCCAAGU 1030

2727 CGGAACGU G CUGGUCAA 446 UUGACCAG GCCGAAAGGCGAGUCAAGGUCU ACGUUCCG 1031 Table 59

2781 GCUCGGCU G CUGGACAU 447 AUGUCCAG GCCGAAAGGCGAGUCAAGGUCU AGCCGAGC 1032

2809 AGUACCAU G CAGAUGGG 448 CCCAUCUG GCCGAAAGGCGAGUCAAGGUCU AUGGUACU 1033

2826 GGCAAGGU G CCCAUCAA 449 UUGAUGGG GCCGAAAGGCGAGUCAAGGUCU ACCUUGCC 1034

2844 UGGAUGGC G CUGGAGUC 450 GACUCCAG GCCGAAAGGCGAGUCAAGGUCU GCCAUCCA 1035

2861 CAUUCUCC G CCGGCGGU 451 ACCGCCGG GCCGAAAGGCGAGUCAAGGUCU GGAGAAUG 1036

2976 CCUGACCU G CUGGAAAA 452 UUUUCCAG GCCGAAAGGCGAGUCAAGGUCU AGGUCAGG 1037

2997 GAGCGGCU G CCCCAGCC 453 GGCUGGGG GCCGAAAGGCGAGUCAAGGUCU AGCCGCUC 1038

3014 CCCCAUCU G CACCAUUG 454 CAAUGGUG GCCGAAAGGCGAGUCAAGGUCU AGAUGGGG 1039

3107 AUUCUCCC G CAUGGCCA 455 UGGCCAUG GCCGAAAGGCGAGUCAAGGUCU GGGAGAAU 1040

3128 CCCCCAGC G CUUUGUGG 456 CCACAAAG GCCGAAAGGCGAGUCAAGGUCU GCUGGGGG 1041

3191 CUUCUACC G CUCACUGC 457 GCAGUGAG GCCGAAAGGCGAGUCAAGGUCU GGUAGAAG 1042

3198 CGCUCACU G CUGGAGGA 458 UCCUCCAG GCCGAAAGGCGAGUCAAGGUCU AGUGAGCG 1043

3232 UGGUGGAU G CUGAGGAG 459 CUCCUCAG GCCGAAAGGCGAGUCAAGGUCU AUCCACCA 1044

3280 CAGACCCU G CCCCGGGC 460 GCCCGGGG GCCGAAAGGCGAGUCAAGGUCU AGGGUCUG 1045

3289 CCCCGGGC G CUGGGGGC 461 GCCCCCAG GCCGAAAGGCGAGUCAAGGUCU GCCCGGGG 1046

3317 CAGGCACC G CAGCUCAU 462 AUGAGCUG GCCGAAAGGCGAGUCAAGGUCU GGUGCCUG 1047

3468 AAGGGGCU G CAAAGCCU 463 AGGCUUUG GCCGAAAGGCGAGUCAAGGUCU AGCCCCUU 1048

3534 GUACCCCU G CCCUCUGA 464 UCAGAGGG GCCGAAAGGCGAGUCAAGGUCU AGGGGUAC 1049

3559 GCUACGUU G CCCCCCUG 465 CAGGGGGG GCCGAAAGGCGAGUCAAGGUCU AACGUAGC 1050

3572 CCUGACCU G CAGCCCCC 466 GGGGGCUG GCCGAAAGGCGAGUCAAGGUCU AGGUCAGG 1051

3627 CCCCCUUC G CCCCGAGA 467 UCUCGGGG GCCGAAAGGCGAGUCAAGGUCU GAAGGGGG 1052

3645 GGCCCUCU G CCUGCUGC 468 GCAGCAGG GCCGAAAGGCGAGUCAAGGUCU AGAGGGCC 1053

3649 CUCUGCCU G CUGCCCGA 469 UCGGGCAG GCCGAAAGGCGAGUCAAGGUCU AGGCAGAG 1054

3652 UGCCUGCU G CCCGACCU 470 AGGUCGGG GCCGAAAGGCGAGUCAAGGUCU AGCAGGCA 1055

3661 CCCGACCU G CUGGUGCC 471 GGCACCAG GCCGAAAGGCGAGUCAAGGUCU AGGUCGGG 1056

3667 CUGCUGGU G CCACUCUG 472 CAGAGUGG GCCGAAAGGCGAGUCAAGGUCU ACCAGCAG 1057

3730 ACGUUUUU G CCUUUGGG 473 CCCAAAGG GCCGAAAGGCGAGUCAAGGUCU AAAAACGU 1058

3742 UUGGGGGU G CCGUGGAG 474 CUCCACGG GCCGAAAGGCGAGUCAAGGUCU ACCCCCAA 1059

3784 GAGGAGCU G CCCCUCAG 475 CUGAGGGG GCCGAAAGGCGAGUCAAGGUCU AGCUCCUC 1060

3808 CUCCUCCU G CCUUCAGC 476 GCUGAAGG GCCGAAAGGCGAGUCAAGGUCU AGGAGGAG 1061

3933 CUGGACGU G CCAGUGUG 477 CACACUGG GCCGAAAGGCGAGUCAAGGUCU ACGUCCAG 1062

3960 CCAAGUCC G CAGAAGCC 478 GGCUUCUG GCCGAAAGGCGAGUCAAGGUCU GGACUUGG 1063

4007 UGACUUCU G CUGGCAUC 479 GAUGCCAG GCCGAAAGGCGAGUCAAGGUCU AGAAGUCA 1064

4056 GGGAACCU G CCAUGCCA 480 UGGCAUGG GCCGAAAGGCGAGUCAAGGUCU AGGUUCCC 1065

4061 CCUGCCAU G CCAGGAAC 481 GUUCCUGG GCCGAAAGGCGAGUCAAGGUCU AUGGCAGG 1066

4094 UCCUUCCU G CUUGAGUU 482 AACUCAAG GCCGAAAGGCGAGUCAAGGUCU AGGAAGGA 1067

4179 GAGGCCCU G CCCAAUGA 483 UCAUUGGG GCCGAAAGGCGAGUCAAGGUCU AGGGCCUC 1068

4208 CAGUGGAU G CCACAGCC 484 GGCUGUGG GCCGAAAGGCGAGUCAAGGUCU AUCCACUG 1069

4351 CUAGUACU G CCCCCCAU 485 AUGGGGGG GCCGAAAGGCGAGUCAAGGUCU AGUACUAG 1070

4406 UACAGAGU G CUUUUCUG 486 CAGAAAAG GCCGAAAGGCGAGUCAAGGUCU ACUCUGUA 1071

192 GCGGCCUU G UGCCGCUG 487 CAGCGGCA GCCGAAAGGCGAGUCAAGGUCU AAGGCCGC 1072

249 ACCCAAGU G UGCACCGG 488 CCGGUGCA GCCGAAAGGCGAGUCAAGGUCU ACUUGGGU 1073

387 GCCAGCCU G UCCUUCCU 489 AGGAAGGA GCCGAAAGGCGAGUCAAGGUCU AGGCUGGC 1074

478 UGCGGAUU G UGCGAGGC 490 GCCUCGCA GCCGAAAGGCGAGUCAAGGUCU AAUCCGCA 1075

559 CCACCCCU G UCACAGGG 491 CCCUGUGA GCCGAAAGGCGAGUCAAGGUCU AGGGGUGG 1076

678 ACGAUUUU G UGGAAGGA 492 UCCUUCCA GCCGAAAGGCGAGUCAAGGUCU AAAAUCGU 1077

758 CCACCCCU G UUCUCCGA 493 UCGGAGAA GCCGAAAGGCGAGUCAAGGUCU AGGGGUGG 1078 Table 59

768 UCUCCGAU G UGUAAGGG 494 CCCUUACA GCCGAAAGGCGAGUCAAGGUCU AUCGGAGA 1079

770 UCCGAUGU G UAAGGGCU 495 AGCCCUUA GCCGAAAGGCGAGUCAAGGUCU ACAUCGGA 1080

809 UGAGGAUU G UCAGAGCC 496 GGCUCUGA GCCGAAAGGCGAGUCAAGGUCU AAUCCUCA 1081

829 CGCGCACU G UCUGUGCC 497 GGCACAGA GCCGAAAGGCGAGUCAAGGUCU AGUGCGCG 1082

833 CACUGUCU G UGCCGGUG 498 CACCGGCA GCCGAAAGGCGAGUCAAGGUCU AGACAGUG 1083

845 CGGUGGCU G UGCCCGCU 499 AGCGGGCA GCCGAAAGGCGAGUCAAGGUCU AGCCACCG 1084

893 UGAGCAGU G UGCUGCCG 500 CGGCAGCA GCCGAAAGGCGAGUCAAGGUCU ACUGCUCA 1085

965 UGGCAUCU G UGAGCUGC 501 GCAGCUCA GCCGAAAGGCGAGUCAAGGUCU AGAUGCCA 1086

1058 CGCCAGCU G UGUGACUG 502 CAGUCACA GCCGAAAGGCGAGUCAAGGUCU AGCUGGCG 1087

1060 CCAGCUGU G UGACUGCC 503 GGCAGUCA GCCGAAAGGCGAGUCAAGGUCU ACAGCUGG 1088

1070 GACUGCCU G UCCCUACA 504 UGUAGGGA GCCGAAAGGCGAGUCAAGGUCU AGGCAGUC 1089

1166 ACAGCGGU G UGAGAAGU 505 ACUUCUCA GCCGAAAGGCGAGUCAAGGUCU ACCGCUGU 1090

1187 CAAGCCCU G UGCCCGAG 506 CUCGGGCA GCCGAAAGGCGAGUCAAGGUCU AGGGCUUG 1091

1197 GCCCGAGU G UGCUAUGG 507 CCAUAGCA GCCGAAAGGCGAGUCAAGGUCU ACUCGGGC 1092

1371 CUCCAAGU G UUUGAGAC 508 GUCUCAAA GCCGAAAGGCGAGUCAAGGUCU ACUUGGAG 1093

1685 GGACGAGU G UGUGGGCG 509 CGCCCACA GCCGAAAGGCGAGUCAAGGUCU ACUCGUCC 1094

1687 ACGAGUGU G UGGGCGAG 510 CUCGCCCA GCCGAAAGGCGAGUCAAGGUCU ACACUCGU 1095

1716 CACCAGCU G UGCGCCCG 511 CGGGCGCA GCCGAAAGGCGAGUCAAGGUCU AGCUGGUG 1096

1757 CACCCAGU G UGUCAACU 512 AGUUGACA GCCGAAAGGCGAGUCAAGGUCU ACUGGGUG 1097

1759 CCCAGUGU G UCAACUGC 513 GCAGUUGA GCCGAAAGGCGAGUCAAGGUCU ACACUGGG 1098

1837 GGGAGUAU G UGAAUGCC 514 GGCAUUCA GCCGAAAGGCGAGUCAAGGUCU AUACUCCC 1099

1853 CAGGCACU G UUUGCCGU 515 ACGGCAAA GCCGAAAGGCGAGUCAAGGUCU AGUGCCUG 1100

1874 CCCUGAGU G UCAGCCCC 516 GGGGCUGA GCCGAAAGGCGAGUCAAGGUCU ACUCAGGG 1101

1901 AGUGACCU G UUUUGGAC 517 GUCCAAAA GCCGAAAGGCGAGUCAAGGUCU AGGUCACU 1102

1925 UGACCAGU G UGUGGCCU 518 AGGCCACA GCCGAAAGGCGAGUCAAGGUCU ACUGGUCA 1103

1927 ACCAGUGU G UGGCCUGU 519 ACAGGCCA GCCGAAAGGCGAGUCAAGGUCU ACACUGGU 1104

1934 UGUGGCCU G UGCCCACU 520 AGUGGGCA GCCGAAAGGCGAGUCAAGGUCU AGGCCACA 1105

1984 CCAGCGGU G UGAAACCU 521 AGGUUUCA GCCGAAAGGCGAGUCAAGGUCU ACCGCUGG 1106

2075 CCACUCCU G UGUGGACC 522 GGUCCACA GCCGAAAGGCGAGUCAAGGUCU AGGAGUGG 1107

2077 ACUCCUGU G UGGACCUG 523 CAGGUCCA GCCGAAAGGCGAGUCAAGGUCU ACAGGAGU 1108

2410 GGGAGAAU G UGAAAAUU 524 AAUUUUCA GCCGAAAGGCGAGUCAAGGUCU AUUCUCCC 1109

2436 AUCAAAGU G UUGAGGGA 525 UCCCUCAA GCCGAAAGGCGAGUCAAGGUCU ACUUUGAU 1110

2503 UGGCUGGU G UGGGCUCC 526 GGAGCCCA GCCGAAAGGCGAGUCAAGGUCU ACCAGCCA llll

2518 CCCCAUAU G UCUCCCGC 527 GCGGGAGA GCCGAAAGGCGAGUCAAGGUCU AUAUGGGG 1112

2602 UAGACCAU G UCCGGGAA 528 UUCCCGGA GCCGAAAGGCGAGUCAAGGUCU AUGGUCUA 1113

2651 GAACUGGU G UAUGCAGA 529 UCUGCAUA GCCGAAAGGCGAGUCAAGGUCU ACCAGUUC 1114

2689 UGGAGGAU G UGCGGCUC 530 GAGCCGCA GCCGAAAGGCGAGUCAAGGUCU AUCCUCCA 1115

2749 CCAACCAU G UCAAAAUU 531 AAUUUUGA GCCGAAAGGCGAGUCAAGGUCU AUGGUUGG 1116

2887 AGAGUGAU G UGUGGAGU 532 ACUCCACA GCCGAAAGGCGAGUCAAGGUCU AUCACUCU 1117

2889 AGUGAUGU G UGGAGUUA 533 UAACUCCA GCCGAAAGGCGAGUCAAGGUCU ACAUCACU 1118

2902 GUUAUGGU G UGACUGUG 534 CACAGUCA GCCGAAAGGCGAGUCAAGGUCU ACCAUAAC 1119

2908 GUGUGACU G UGUGGGAG 535 CUCCCACA GCCGAAAGGCGAGUCAAGGUCU AGUCACAC 1120

2910 GUGACUGU G UGGGAGCU 536 AGCUCCCA GCCGAAAGGCGAGUCAAGGUCU ACAGUCAC 1121

3025 CCAUUGAU G UCUACAUG 537 CAUGUAGA GCCGAAAGGCGAGUCAAGGUCU AUCAAUGG 1122

3047 GGUCAAAU G UUGGAUGA 538 UCAUCCAA GCCGAAAGGCGAGUCAAGGUCU AUUUGACC 1123

3068 CUCUGAAU G UCGGCCAA 539 UUGGCCGA GCCGAAAGGCGAGUCAAGGUCU AUUCAGAG 1124

3093 GAGUUGGU G UCUGAAUU 540 AAUUCAGA GCCGAAAGGCGAGUCAAGGUCU ACCAACUC 1125 Table 59

3133 AGCGCUUU G UGGUCAUC 541 GAUGACCA GCCGAAAGGCGAGUCAAGGUCU AAAGCGCU 1126

3269 CUUCUUCU G UCCAGACC 542 GGUCUGGA GCCGAAAGGCGAGUCAAGGUCU AGAAGAAG 1127

3427 GCUCCGAU G UAUUUGAU 543 AUCAAAUA GCCGAAAGGCGAGUCAAGGUCU AUCGGAGC 1128

3592 CUGAAUAU G UGAACCAG 544 CUGGUUCA GCCGAAAGGCGAGUCAAGGUCU AUAUUCAG 1129

3607 AGCCAGAU G UUCGGCCC 545 GGGCCGAA GCCGAAAGGCGAGUCAAGGUCU AUCUGGCU 1130

3939 GUGCCAGU G UGAACCAG 546 CUGGUUCA GCCGAAAGGCGAGUCAAGGUCU ACUGGCAC 1131

3974 GCCCUGAU G UGUCCUCA 547 UGAGGACA GCCGAAAGGCGAGUCAAGGUCU AUCAGGGC 1132

3976 CCUGAUGU G UCCUCAGG 548 CCUGAGGA GCCGAAAGGCGAGUCAAGGUCU ACAUCAGG 1133

4072 AGGAACCU G UCCUAAGG 549 CCUUAGGA GCCGAAAGGCGAGUCAAGGUCU AGGUUCCU 1134

4162 GAGUCUUU G UGGAUUCU 550 AGAAUCCA GCCGAAAGGCGAGUCAAGGUCU AAAGACUC 1135

4300 AAGGGAGU G UCUAAGAA 551 UUCUUAGA GCCGAAAGGCGAGUCAAGGUCU ACUCCCUU 1136

4332 CAGAGACU G UCCCUGAA 552 UUCAGGGA GCCGAAAGGCGAGUCAAGGUCU AGUCUCUG 1137

4380 GCAAUGGU G UCAGUAUC 553 GAUACUGA GCCGAAAGGCGAGUCAAGGUCU ACCAUUGC 1138

4397 CAGGCUUU G UACAGAGU 554 ACUCUGUA GCCGAAAGGCGAGUCAAGGUCU AAAGCCUG 1139

4414 GCUUUUCU G UUUAGUUU 555 AAACUAAA GCCGAAAGGCGAGUCAAGGUCU AGAAAAGC 1140

4434 CUUUUUUU G UUUUGUUU 556 AAACAAAA GCCGAAAGGCGAGUCAAGGUCU AAAAAAAG 1141

4439 UUUGUUUU G UUUUUUUA 557 UAAAAAAA GCCGAAAGGCGAGUCAAGGUCU AAAACAAA 1142

9 AAGGGGAG G UAACCCUG 558 CAGGGUUA GCCGAAAGGCGAGUCAAGGUCU CUCCCCUU 1143

18 UAACCCUG G CCCCUUUG 559 CAAAGGGG GCCGAAAGGCGAGUCAAGGUCU CAGGGUUA 1144

27 CCCCUUUG G UCGGGGCC 560 GGCCCCGA GCCGAAAGGCGAGUCAAGGUCU CAAAGGGG 1145

33 UGGUCGGG G CCCCGGGC 561 GCCCGGGG GCCGAAAGGCGAGUCAAGGUCU CCCGACCA 1146

40 GGCCCCGG G CAGCCGCG 562 CGCGGCUG GCCGAAAGGCGAGUCAAGGUCU CCGGGGCC 1147

43 CCCGGGCA G CCGCGCGC 563 GCGCGCGG GCCGAAAGGCGAGUCAAGGUCU UGCCCGGG 1148

65 CCCACGGG G CCCUUUAC 564 GUAAAGGG GCCGAAAGGCGAGUCAAGGUCU CCCGUGGG 1149

89 CGCGCCCG G CCCCCACC 565 GGUGGGGG GCCGAAAGGCGAGUCAAGGUCU CGGGCGCG 1150

105 CCCUCGCA G CACCCCGC 566 GCGGGGUG GCCGAAAGGCGAGUCAAGGUCU UGCGAGGG 1151

130 CCCUCCCA G CCGGGUCC 567 GGACCCGG GCCGAAAGGCGAGUCAAGGUCU UGGGAGGG 1152

135 CCAGCCGG G UCCAGCCG 568 CGGCUGGA GCCGAAAGGCGAGUCAAGGUCU CCGGCUGG 1153

140 CGGGUCCA G CCGGAGCC 569 GGCUCCGG GCCGAAAGGCGAGUCAAGGUCU UGGACCCG 1154

146 CAGCCGGA G CCAUGGGG 570 CCCCAUGG GCCGAAAGGCGAGUCAAGGUCU UCCGGCUG 1155

154 GCCAUGGG G CCGGAGCC 571 GGCUCCGG GCCGAAAGGCGAGUCAAGGUCU CCCAUGGC 1156

160 GGGCCGGA G CCGCAGUG 572 CACUGCGG GCCGAAAGGCGAGUCAAGGUCU UCCGGCCC 1157

166 GAGCCGCA G UGAGCACC 573 GGUGCUCA GCCGAAAGGCGAGUCAAGGUCU UGCGGCUC 1158

170 CGCAGUGA G CACCAUGG 574 CCAUGGUG GCCGAAAGGCGAGUCAAGGUCU UCACUGCG 1159

180 ACCAUGGA G CUGGCGGC 575 GCCGCCAG GCCGAAAGGCGAGUCAAGGUCU UCCAUGGU 1160

184 UGGAGCUG G CGGCCUUG 576 CAAGGCCG GCCGAAAGGCGAGUCAAGGUCU CAGCUCCA 1161

187 AGCUGGCG G CCUUGUGC 577 GCACAAGG GCCGAAAGGCGAGUCAAGGUCU CGCCAGCU 1162

204 CGCUGGGG G CUCCUCCU 578 AGGAGGAG GCCGAAAGGCGAGUCAAGGUCU CCCCAGCG 1163

232 CCCCCGGA G CCGCGAGC 579 GCUCGCGG GCCGAAAGGCGAGUCAAGGUCU UCCGGGGG 1164

239 AGCCGCGA G CACCCAAG 580 CUUGGGUG GCCGAAAGGCGAGUCAAGGUCU UCGCGGCU 1165

247 GCACCCAA G UGUGCACC 581 GGUGCACA GCCGAAAGGCGAGUCAAGGUCU UUGGGUGC 1166

257 GUGCACCG G CACAGACA 582 UGUCUGUG GCCGAAAGGCGAGUCAAGGUCU CGGUGCAC 1167

270 GACAUGAA G CUGCGGCU 583 AGCCGCAG GCCGAAAGGCGAGUCAAGGUCU UUCAUGUC 1168

276 AAGCUGCG G CUCCCUGC 584 GCAGGGAG GCCGAAAGGCGAGUCAAGGUCU CGCAGCUU 1169

287 CCCUGCCA G UCCCGAGA 585 UCUCGGGA GCCGAAAGGCGAGUCAAGGUCU UGGCAGGG 1170

329 CUACCAGG G CUGCCAGG 586 CCUGGCAG GCCGAAAGGCGAGUCAAGGUCU CCUGGUAG 1171

337 GCUGCCAG G UGGUGCAG 587 CUGCACCA GCCGAAAGGCGAGUCAAGGUCU CUGGCAGC 1172 Table 59

340 GCCAGGUG G UGCAGGGA 588 UCCCUGCA GCCGAAAGGCGAGUCAAGGUCU CACCUGGC 1173

383 CAAUGCCA G CCUGUCCU 589 AGGACAGG GCCGAAAGGCGAGUCAAGGUCU UGGCAUUG 1174

412 UCCAGGAG G UGCAGGGC 590 GCCCUGCA GCCGAAAGGCGAGUCAAGGUCU CUCCUGGA 1175

419 GGUGCAGG G CUACGUGC 591 GCACGUAG GCCGAAAGGCGAGUCAAGGUCU CCUGCACC 1176

424 AGGGCUAC G UGCUCAUC 592 GAUGAGCA GCCGAAAGGCGAGUCAAGGUCU GUAGCCCU 1177

445 ACAACCAA G UGAGGCAG 593 CUGCCUCA GCCGAAAGGCGAGUCAAGGUCU UUGGUUGU 1178

450 CAAGUGAG G CAGGUCCC 594 GGGACCUG GCCGAAAGGCGAGUCAAGGUCU CUCACUUG 1179

454 UGAGGCAG G UCCCACUG 595 CAGUGGGA GCCGAAAGGCGAGUCAAGGUCU CUGCCUCA 1180

468 CUGCAGAG G CUGCGGAU 596 AUCCGCAG GCCGAAAGGCGAGUCAAGGUCU CUCUGCAG 1181

485 UGUGCGAG G CACCCAGC 597 GCUGGGUG GCCGAAAGGCGAGUCAAGGUCU CUCGCACA 1182

492 GGCACCCA G CUCUUUGA 598 UCAAAGAG GCCGAAAGGCGAGUCAAGGUCU UGGGUGCC 1183

517 AUGCCCUG G CCGUGCUA 599 UAGCACGG GCCGAAAGGCGAGUCAAGGUCU CAGGGCAU 1184

520 CCCUGGCC G UGCUAGAC 600 GUCUAGCA GCCGAAAGGCGAGUCAAGGUCU GGCCAGGG 1185

568 UCACAGGG G CCUCCCCA 601 UGGGGAGG GCCGAAAGGCGAGUCAAGGUCU CCCUGUGA 1186

581 CCCAGGAG G CCUGCGGG 602 CCCGCAGG GCCGAAAGGCGAGUCAAGGUCU CUCCUGGG 1187

591 CUGCGGGA G CUGCAGCU 603 AGCUGCAG GCCGAAAGGCGAGUCAAGGUCU UCCCGCAG 1188

597 GAGCUGCA G CUUCGAAG 604 CUUCGAAG GCCGAAAGGCGAGUCAAGGUCU UGCAGCUC 1189

605 GCUUCGAA G CCUCACAG 605 CUGUGAGG GCCGAAAGGCGAGUCAAGGUCU UUCGAAGC 1190

631 AAGGAGGG G UCUUGAUC 606 GAUCAAGA GCCGAAAGGCGAGUCAAGGUCU CCCUCCUU 1191

642 UUGAUCCA G CGGAACCC 607 GGGUUCCG GCCGAAAGGCGAGUCAAGGUCU UGGAUCAA 1192

654 AACCCCCA G CUCUGCUA 608 UAGCAGAG GCCGAAAGGCGAGUCAAGGUCU UGGGGGUU 1193

708 AACAACCA G CUGGCUCU 609 AGAGCCAG GCCGAAAGGCGAGUCAAGGUCU UGGUUGUU 1194

712 ACCAGCUG G CUCUCACA 610 UGUGAGAG GCCGAAAGGCGAGUCAAGGUCU CAGCUGGU 1195

745 GCUCUCGG G CCUGCCAC 611 GUGGCAGG GCCGAAAGGCGAGUCAAGGUCU CCGAGAGC 1196

776 GUGUAAGG G CUCCCGCU 612 AGCGGGAG GCCGAAAGGCGAGUCAAGGUCU CCUUACAC 1197

797 GGGAGAGA G UUCUGAGG 613 CCUCAGAA GCCGAAAGGCGAGUCAAGGUCU UCUCUCCC 1198

815 UUGUCAGA G CCUGACGC 614 GCGUCAGG GCCGAAAGGCGAGUCAAGGUCU UCUGACAA 1199

839 CUGUGCCG G UGGCUGUG 615 CACAGCCA GCCGAAAGGCGAGUCAAGGUCU CGGCACAG 1200

842 UGCCGGUG G CUGUGCCC 616 GGGCACAG GCCGAAAGGCGAGUCAAGGUCU CACCGGCA 1201

861 UGCAAGGG G CCACUGCC 617 GGCAGUGG GCCGAAAGGCGAGUCAAGGUCU CCCUUGCA 1202

888 UGCCAUGA G CAGUGUGC 618 GCACACUG GCCGAAAGGCGAGUCAAGGUCU UCAUGGCA 1203

891 CAUGAGCA G UGUGCUGC 619 GCAGCACA GCCGAAAGGCGAGUCAAGGUCU UGCUCAUG 1204

902 UGCUGCCG G CUGCACGG 620 CCGUGCAG GCCGAAAGGCGAGUCAAGGUCU CGGCAGCA 1205

911 CUGCACGG G CCCCAAGC 621 GCUUGGGG GCCGAAAGGCGAGUCAAGGUCU CCGUGCAG 1206

918 GGCCCCAA G CACUCUGA 622 UCAGAGUG GCCGAAAGGCGAGUCAAGGUCU UUGGGGCC 1207

934 ACUGCCUG G CCUGCCUC 623 GAGGCAGG GCCGAAAGGCGAGUCAAGGUCU CAGGCAGU 1208

956 CAACCACA G UGGCAUCU 624 AGAUGCCA GCCGAAAGGCGAGUCAAGGUCU UGUGGUUG 1209

959 CCACAGUG G CAUCUGUG 625 CACAGAUG GCCGAAAGGCGAGUCAAGGUCU CACUGUGG 1210

969 AUCUGUGA G CUGCACUG 626 CAGUGCAG GCCGAAAGGCGAGUCAAGGUCU UCACAGAU 1211

982 ACUGCCCA G CCCUGGUC 627 GACCAGGG GCCGAAAGGCGAGUCAAGGUCU UGGGCAGU 1212

988 CAGCCCUG G UCACCUAC 628 GUAGGUGA GCCGAAAGGCGAGUCAAGGUCU CAGGGCUG 1213

1008 ACAGACAC G UUUGAGUC 629 GACUCAAA GCCGAAAGGCGAGUCAAGGUCU GUGUCUGU 1214

1014 ACGUUUGA G UCCAUGCC 630 GGCAUGGA GCCGAAAGGCGAGUCAAGGUCU UCAAACGU 1215

1034 UCCCGAGG G CCGGUAUA 631 UAUACCGG GCCGAAAGGCGAGUCAAGGUCU CCUCGGGA 1216

1038 GAGGGCCG G UAUACAUU 632 AAUGUAUA GCCGAAAGGCGAGUCAAGGUCU CGGCCCUC 1217

1049 UACAUUCG G CGCCAGCU 633 AGCUGGCG GCCGAAAGGCGAGUCAAGGUCU CGAAUGUA 1218

1055 CGGCGCCA G CUGUGUGA 634 UCACACAG GCCGAAAGGCGAGUCAAGGUCU UGGCGCCG 1219 Table 59

1096 CUACGGAC G UGGGAUCC 635 GGAUCCCA GCCGAAAGGCGAGUCAAGGUCU GUCCGUAG 1220

1114 GCACCCUC G UCUGCCCC 636 GGGGCAGA GCCGAAAGGCGAGUCAAGGUCU GAGGGUGC 1221

1138 ACCAAGAG G UGACAGCA 637 UGCUGUCA GCCGAAAGGCGAGUCAAGGUCU CUCUUGGU 1222

1144 AGGUGACA G CAGAGGAU 638 AUCCUCUG GCCGAAAGGCGAGUCAAGGUCU UGUCACCU 1223

1161 GGAACACA G CGGUGUGA 639 UCACACCG GCCGAAAGGCGAGUCAAGGUCU UGUGUUCC 1224

1164 ACACAGCG G UGUGAGAA 640 UUCUCACA GCCGAAAGGCGAGUCAAGGUCU CGCUGUGU 1225

1173 UGUGAGAA G UGCAGCAA 641 UUGCUGCA GCCGAAAGGCGAGUCAAGGUCU UUCUCACA 1226

1178 GAAGUGCA G CAAGCCCU 642 AGGGCUUG GCCGAAAGGCGAGUCAAGGUCU UGCACUUC 1227

1182 UGCAGCAA G CCCUGUGC 643 GCACAGGG GCCGAAAGGCGAGUCAAGGUCU UUGCUGCA 1228

1195 GUGCCCGA G UGUGCUAU 644 AUAGCACA GCCGAAAGGCGAGUCAAGGUCU UCGGGCAC 1229

1205 GUGCUAUG G UCUGGGCA 645 UGCCCAGA GCCGAAAGGCGAGUCAAGGUCU CAUAGCAC 1230

1211 UGGUCUGG G CAUGGAGC 646 GCUCCAUG GCCGAAAGGCGAGUCAAGGUCU CCAGACCA 1231

1218 GGCAUGGA G CACUUGCG 647 CGCAAGUG GCCGAAAGGCGAGUCAAGGUCU UCCAUGCC 1232

1231 UGCGAGAG G UGAGGGCA 648 UGCCCUCA GCCGAAAGGCGAGUCAAGGUCU CUCUCGCA 1233

1237 AGGUGAGG G CAGUUACC 649 GGUAACUG GCCGAAAGGCGAGUCAAGGUCU CCUCACCU 1234

1240 UGAGGGCA G UUACCAGU 650 ACUGGUAA GCCGAAAGGCGAGUCAAGGUCU UGCCCUCA 1235

1247 AGUUACCA G UGCCAAUA 651 UAUUGGCA GCCGAAAGGCGAGUCAAGGUCU UGGUAACU 1236

1263 AUCCAGGA G UUUGCUGG 652 CCAGCAAA GCCGAAAGGCGAGUCAAGGUCU UCCUGGAU 1237

1271 GUUUGCUG G CUGCAAGA 653 UCUUGCAG GCCGAAAGGCGAGUCAAGGUCU CAGCAAAC 1238

1292 CUUUGGGA G CCUGGCAU 654 AUGCCAGG GCCGAAAGGCGAGUCAAGGUCU UCCCAAAG 1239

1297 GGAGCCUG G CAUUUCUG 655 CAGAAAUG GCCGAAAGGCGAGUCAAGGUCU CAGGCUCC 1240

1313 GCCGGAGA G CUUUGAUG 656 CAUCAAAG GCCGAAAGGCGAGUCAAGGUCU UCUCCGGC 1241

1330 GGGACCCA G CCUCCAAC 657 GUUGGAGG GCCGAAAGGCGAGUCAAGGUCU UGGGUCCC 1242

1353 CCGCUCCA G CCAGAGCA 658 UGCUCUGG GCCGAAAGGCGAGUCAAGGUCU UGGAGCGG 1243

1359 CAGCCAGA G CAGCUCCA 659 UGGAGCUG GCCGAAAGGCGAGUCAAGGUCU UCUGGCUG 1244

1362 CCAGAGCA G CUCCAAGU 660 ACUUGGAG GCCGAAAGGCGAGUCAAGGUCU UGCUCUGG 1245

1369 AGCUCCAA G UGUUUGAG 661 CUCAAACA GCCGAAAGGCGAGUCAAGGUCU UUGGAGCU 1246

1397 GAUCACAG G UUACCUAU 662 AUAGGUAA GCCGAAAGGCGAGUCAAGGUCU CUGUGAUC 1247

1414 ACAUCUCA G CAUGGCCG 663 CGGCCAUG GCCGAAAGGCGAGUCAAGGUCU UGAGAUGU 1248

1419 UCAGCAUG G CCGGACAG 664 CUGUCCGG GCCGAAAGGCGAGUCAAGGUCU CAUGCUGA 1249

1427 GCCGGACA G CCUGCCUG 665 CAGGCAGG GCCGAAAGGCGAGUCAAGGUCU UGUCCGGC 1250

1442 UGACCUCA G CGUCUUCC 666 GGAAGACG GCCGAAAGGCGAGUCAAGGUCU UGAGGUCA 1251

1444 ACCUCAGC G UCUUCCAG 667 CUGGAAOA GCCGAAAGGCGAGUCAAGGUCU GCUGAGGU 1252

1462 ACCUGCAA G UAAUCCGG 668 CCGGAUUA GCCGAAAGGCGAGUCAAGGUCU UUGCAGGU 1253

1490 GCACAAUG G CGCCUACU 669 AGUAGGCG GCCGAAAGGCGAGUCAAGGUCU CAUUGUGC 1254

1515 CUGCAAGG G CUGGGCAU 670 AUGCCCAG GCCGAAAGGCGAGUCAAGGUCU CCUUGCAG 1255

1520 AGGGCUGG G CAUCAGCU 671 AGCUGAUG GCCGAAAGGCGAGUCAAGGUCU CCAGCCCU 1256

1526 GGGCAUCA G CUGGCUGG 672 CCAGCCAG GCCGAAAGGCGAGUCAAGGUCU UGAUGCCC 1257

1530 AUCAGCUG G CUGGGGCU 673 AGCCCCAG GCCGAAAGGCGAGUCAAGGUCU CAGCUGAU 1258

1536 UGGCUGGG G CUGCGCUC 674 GAGCGCAG GCCGAAAGGCGAGUCAAGGUCU CCCAGCCA 1259

1559 GGAACUGG G CAGUGGAC 675 GUCCACUG GCCGAAAGGCGAGUCAAGGUCU CCAGUUCC 1260

1562 ACUGGGCA G UGGACUGG 676 CCAGUCCA GCCGAAAGGCGAGUCAAGGUCU UGCCCAGU 1261

1570 GUGGACUG G CCCUCAUC 677 GAUGAGGG GCCGAAAGGCGAGUCAAGGUCU CAGUCCAC 1262

1603 UCUGCUUC G UGCACACG 678 CGUGUGCA GCCGAAAGGCGAGUCAAGGUCU GAAGCAGA 1263

1612 UGCACACG G UGCCCUGG 679 CCAGGGCA GCCGAAAGGCGAGUCAAGGUCU CGUGUGCA 1264

1626 UGGGACCA G CUCUUUCG 680 CGAAAGAG GCCGAAAGGCGAGUCAAGGUCU UGGUCCCA 1265

1648 CGCACCAA G CUCUGCUC 681 GAGCAGAG GCCGAAAGGCGAGUCAAGGUCU UUGGUGCG 1266 Table 59

1671 GCCAACCG G CCAGAGGA 682 UCCUCUGG GCCGAAAGGCGAGUCAAGGUCU CGGUUGGC 1267

1683 GAGGACGA G UGUGUGGG 683 CCCACACA GCCGAAAGGCGAGUCAAGGUCU UCGUCCUC 1268

1691 GUGUGUGG G CGAGGGCC 684 GGCCCUCG GCCGAAAGGCGAGUCAAGGUCU CCACACAC 1269

1697 GGGCGAGG G CCUGGCCU 685 AGGCCAGG GCCGAAAGGCGAGUCAAGGUCU CCUCGCCC 1270

1702 AGGGCCUG G CCUGCCAC 686 GUGGCAGG GCCGAAAGGCGAGUCAAGGUCU CAGGCCCU 1271

1713 UGCCACCA G CUGUGCGC 687 GCGCACAG GCCGAAAGGCGAGUCAAGGUCU UGGUGGCA 1272

1728 GCCCGAGG G CACUGCUG 688 CAGCAGUG GCCGAAAGGCGAGUCAAGGUCU CCUCGGGC 1273

1739 CUGCUGGG G UCCAGGGC 689 GCCCUGGA GCCGAAAGGCGAGUCAAGGUCU CCCAGCAG 1274

1746 GGUCCAGG G CCCACCCA 690 UGGGUGGG GCCGAAAGGCGAGUCAAGGUCU CCUGGACC 1275

1755 CCCACCCA G UGUGUCAA 691 UUGACACA GCCGAAAGGCGAGUCAAGGUCU UGGGUGGG 1276

1769 CAACUGCA G CCAGUUCC 692 GGAACUGG GCCGAAAGGCGAGUCAAGGUCU UGCAGUUG 1277

1773 UGCAGCCA G UUCCUUCG 693 CGAAGGAA GCCGAAAGGCGAGUCAAGGUCU UGGCUGCA 1278

1784 CCUUCGGG G CCAGGAGU 694 ACUCCUGG GCCGAAAGGCGAGUCAAGGUCU CCCGAAGG 1279

1791 GGCCAGGA G UGCGUGGA 695 UCCACGCA GCCGAAAGGCGAGUCAAGGUCU UCCUGGCC 1280

1795 AGGAGUGC G UGGAGGAA 696 UUCCUCCA GCCGAAAGGCGAGUCAAGGUCU GCACUCCU 1281

1810 AAUGCCGA G UACUGCAG 697 CUGCAGUA GCCGAAAGGCGAGUCAAGGUCU UCGGCAUU 1282

1821 CUGCAGGG G CUCCCCAG 698 CUGGGGAG GCCGAAAGGCGAGUCAAGGUCU CCCUGCAG 1283

1833 CCCAGGGA G UAUGUGAA 699 UUCACAUA GCCGAAAGGCGAGUCAAGGUCU UCCCUGGG 1284

1848 AAUGCCAG G CACUGUUU 700 AAACAGUG GCCGAAAGGCGAGUCAAGGUCU CUGGCAUU 1285

1860 UGUUUGCC G UGCCACCC 701 GGGUGGCA GCCGAAAGGCGAGUCAAGGUCU GGCAAACA 1286

1872 CACCCUGA G UGUCAGCC 702 GGCUGACA GCCGAAAGGCGAGUCAAGGUCU UCAGGGUG 1287

1878 GAGUGUCA G CCCCAGAA 703 UUCUGGGG GCCGAAAGGCGAGUCAAGGUCU UGACACUC 1288

1889 CCAGAAUG G CUCAGUGA 704 UCACUGAG GCCGAAAGGCGAGUCAAGGUCU CAUUCUGG 1289

1894 AUGGCUCA G UGACCUGU 705 ACAGGUCA GCCGAAAGGCGAGUCAAGGUCU UGAGCCAU 1290

1915 GACCGGAG G CUGACCAG 706 CUGGUCAG GCCGAAAGGCGAGUCAAGGUCU CUCCGGUC 1291

1923 GCUGACCA G UGUGUGGC 707 GCCACACA GCCGAAAGGCGAGUCAAGGUCU UGGUCAGC 1292

1930 AGUGUGUG G CCUGUGCC 708 GGCACAGG GCCGAAAGGCGAGUCAAGGUCU CACACACU 1293

1963 CCUUCUGC G UGGCCCGC 709 GCGGGCCA GCCGAAAGGCGAGUCAAGGUCU GCAGAAGG 1294

1966 UCUGCGUG G CCCGCUGC 710 GCAGCGGG GCCGAAAGGCGAGUCAAGGUCU CACGCAGA 1295

1979 CUGCCCCA G CGGUGUGA 711 UCACACCG GCCGAAAGGCGAGUCAAGGUCU UGGGGCAG 1296

1982 CCCCAGCG G UGUGAAAC 712 GUUUCACA GCCGAAAGGCGAGUCAAGGUCU CGCUGGGG 1297

2019 AUCUGGAA G UUUCCAGA 713 UCUGGAAA GCCGAAAGGCGAGUCAAGGUCU UUCCAGAU 1298

2036 UGAGGAGG G CGCAUGCC 714 GGCAUGCG GCCGAAAGGCGAGUCAAGGUCU CCUCCUCA 1299

2046 GCAUGCCA G CCUUGCCC 715 GGGCAAGG GCCGAAAGGCGAGUCAAGGUCU UGGCAUGC 1300

2096 UGACAAGG G CUGCCCCG 716 CGGGGCAG GCCGAAAGGCGAGUCAAGGUCU CCUUGUCA 1301

2109 CCCGCCGA G CAGAGAGC 717 GCUCUCUG GCCGAAAGGCGAGUCAAGGUCU UCGGCGGG 1302

2116 AGCAGAGA G CCAGCCCU 718 AGGGCUGG GCCGAAAGGCGAGUCAAGGUCU UCUCUGCU 1303

2120 GAGAGCCA G CCCUCUGA 719 UCAGAGGG GCCGAAAGGCGAGUCAAGGUCU UGGCUCUC 1304

2130 CCUCUGAC G UCCAUCAU 720 AUGAUGGA GCCGAAAGGCGAGUCAAGGUCU GUCAGAGG 1305

2146 UCUCUGCG G UGGUUGGC 721 GCCAACCA GCCGAAAGGCGAGUCAAGGUCU CGCAGAGA 1306

2149 CUGCGGUG G UUGGCAUU 722 AAUGCCAA GCCGAAAGGCGAGUCAAGGUCU CACCGCAG 1307

2153 GGUGGUUG G CAUUCUGC 723 GCAGAAUG GCCGAAAGGCGAGUCAAGGUCU CAACCACC 1308

2164 UUCUGCUG G UCGUGGUC 724 GACCACGA GCCGAAAGGCGAGUCAAGGUCU CAGCAGAA 1309

2167 UGCUGGUC G UGGUCUUG 725 CAAGACCA GCCGAAAGGCGAGUCAAGGUCU GACCAGCA 1310

2170 UGGUCGUG G UCUUGGGG 726 CCCCAAGA GCCGAAAGGCGAGUCAAGGUCU CACGACCA 1311

2179 UCUUGGGG G UGGUCUUU 727 AAAGACCA GCCGAAAGGCGAGUCAAGGUCU CCCCAAGA 1312

2182 UGGGGGUG G UCUUUGGG 728 CCCAAAGA GCCGAAAGGCGAGUCAAGGUCU CACCCCCA 1313 Table 59

2202 CUCAUCAA G CGACGGCA 729 UGCCGUCG GCCGAAAGGCGAGUCAAGGUCU UUGAUGAG 1314

2208 AAGCGACG G CAGCAGAA 730 UUCUGCUG GCCGAAAGGCGAGUCAAGGUCU CGUCGCUU 1315

2211 CGACGGCA G CAGAAGAU 731 AUCUUCUG GCCGAAAGGCGAGUCAAGGUCU UGCCGUCG 1316

2226 AUCCGGAA G UACACGAU 732 AUCGUGUA GCCGAAAGGCGAGUCAAGGUCU UUCCGGAU 1317

2259 GAAACGGA G CUGGUGGA 733 UCCACCAG GCCGAAAGGCGAGUCAAGGUCU UCCGUUUC 1318

2263 CGGAGCUG G UGGAGCCG 734 CGGCUCCA GCCGAAAGGCGAGUCAAGGUCU CAGCUCCG 1319

2268 CUGGUGGA G CCGCUGAC 735 GUCAGCGG GCCGAAAGGCGAGUCAAGGUCU UCCACCAG 1320

2282 GACACCUA G CGGAGCGA 736 UCGCUCCG GCCGAAAGGCGAGUCAAGGUCU UAGGUGUC 1321

2287 CUAGCGGA G CGAUGCCC 737 GGGCAUCG GCCGAAAGGCGAGUCAAGGUCU UCCGCUAG 1322

2302 CCAACCAG G CGCAGAUG 738 CAUCUGCG GCCGAAAGGCGAGUCAAGGUCU CUGGUUGG 1323

2331 GAGACGGA G CUGAGGAA 739 UUCCUCAG GCCGAAAGGCGAGUCAAGGUCU UCCGUCUC 1324

2341 UGAGGAAG G UGAAGGUG 740 CACCUUCA GCCGAAAGGCGAGUCAAGGUCU CUUCCUCA 1325

2347 AGGUGAAG G UGCUUGGA 741 UCCAAGCA GCCGAAAGGCGAGUCAAGGUCU CUUCACCU 1326

2360 UGGAUCUG G CGCUUUUG 742 CAAAAGCG GCCGAAAGGCGAGUCAAGGUCU CAGAUCCA 1327

2369 CGCUUUUG G CACAGUCU 743 AGACUGUG GCCGAAAGGCGAGUCAAGGUCU CAAAAGCG 1328

2374 UUGGCACA G UCUACAAG 744 CUUGUAGA GCCGAAAGGCGAGUCAAGGUCU UGUGCCAA 1329

2384 CUACAAGG G CAUCUGGA 745 UCCAGAUG GCCGAAAGGCGAGUCAAGGUCU CCUUGUAG 1330

2422 AAAUUCCA G UGGCCAUC 746 GAUGGCCA GCCGAAAGGCGAGUCAAGGUCU UGGAAUUU 1331

2425 UUCCAGUG G CCAUCAAA 747 UUUGAUGG GCCGAAAGGCGAGUCAAGGUCU CACUGGAA 1332

2434 CCAUCAAA G UGUUGAGG 748 CCUCAACA GCCGAAAGGCGAGUCAAGGUCU UUUGAUGG 1333

2461 CCCCCAAA G CCAACAAA 749 UUUGUUGG GCCGAAAGGCGAGUCAAGGUCU UUUGGGGG 1334

2485 UAGACGAA G CAUACGUG 750 CACGUAUG GCCGAAAGGCGAGUCAAGGUCU UUCGUCUA 1335

2491 AAGCAUAC G UGAUGGCU 751 AGCCAUCA GCCGAAAGGCGAGUCAAGGUCU GUAUGCUU 1336

2497 ACGUGAUG G CUGGUGUG 752 CACACCAG GCCGAAAGGCGAGUCAAGGUCU CAUCACGU 1337

2501 GAUGGCUG G UGUGGGCU 753 AGCCCACA GCCGAAAGGCGAGUCAAGGUCU CAGCCAUC 1338

2507 UGGUGUGG G CUCCCCAU 754 AUGGGGAG GCCGAAAGGCGAGUCAAGGUCU CCACACCA 1339

2534 CCUUCUGG G CAUCUGCC 755 GGCAGAUG GCCGAAAGGCGAGUCAAGGUCU CCAGAAGG 1340

2554 CAUCCACG G UGCAGCUG 756 CAGCUGCA GCCGAAAGGCGAGUCAAGGUCU CGUGGAUG 1341

2559 ACGGUGCA G CUGGUGAC 757 GUCACCAG GCCGAAAGGCGAGUCAAGGUCU UGCACCGU 1342

2563 UGCAGCUG G UGACACAG 758 CUGUGUCA GCCGAAAGGCGAGUCAAGGUCU CAGCUGCA 1343

2571 GUGACACA G CUUAUGCC 759 GGCAUAAG GCCGAAAGGCGAGUCAAGGUCU UGUGUCAC 1344

2585 GCCCUAUG G CUGCCUCU 760 AGAGGCAG GCCGAAAGGCGAGUCAAGGUCU CAUAGGGC 1345

2627 ACGCCUGG G CUCCCAGG 761 CCUGGGAG GCCGAAAGGCGAGUCAAGGUCU CCAGGCGU 1346

2649 CUGAACUG G UGUAUGCA 762 UGCAUACA GCCGAAAGGCGAGUCAAGGUCU CAGUUCAG 1347

2675 GGGGAUGA G CUACCUGG 763 CCAGGUAG GCCGAAAGGCGAGUCAAGGUCU UCAUCCCC 1348

2694 GAUGUGCG G CUCGUACA 764 UGUACGAG GCCGAAAGGCGAGUCAAGGUCU CGCACAUC 1349

2698 UGCGGCUC G UACACAGG 765 CCUGUGUA GCCGAAAGGCGAGUCAAGGUCU GAGCCGCA 1350

2713 GGGACUUG G CCGCUCGG 766 CCGAGCGG GCCGAAAGGCGAGUCAAGGUCU CAAGUCCC 1351

2725 CUCGGAAC G UGCUGGUC 767 GACCAGCA GCCGAAAGGCGAGUCAAGGUCU GUUCCGAG 1352

2731 ACGUGCUG G UCAAGAGU 768 ACUCUUGA GCCGAAAGGCGAGUCAAGGUCU CAGCACGU 1353

2738 GGUCAAGA G UCCCAACC 769 GGUUGGGA GCCGAAAGGCGAGUCAAGGUCU UCUUGACC 1354

2769 GACUUCGG G CUGGCUCG 770 CGAGCCAG GCCGAAAGGCGAGUCAAGGUCU CCGAAGUC 1355

2773 UCGGGCUG G CUCGGCUG 771 CAGCCGAG GCCGAAAGGCGAGUCAAGGUCU CAGCCCGA 1356

2778 CUGGCUCG G CUGCUGGA 772 UCCAGCAG GCCGAAAGGCGAGUCAAGGUCU CGAGCCAG 1357

2802 GAGACAGA G UACCAUGC 773 GCAUGGUA GCCGAAAGGCGAGUCAAGGUCU UCUGUCUC 1358

2819 AGAUGGGG G CAAGGUGC 774 GCACCUUG GCCGAAAGGCGAGUCAAGGUCU CCCCAUCU 1359

2824 GGGGCAAG G UGCCCAUC 775 GAUGGGCA GCCGAAAGGCGAGUCAAGGUCU CUUGCCCC 1360 Table 59

2835 CCCAUCAA G UGGAUGGC 776 GCCAUCCA GCCGAAAGGCGAGUCAAGGUCU UUGAUGGG 1361

2842 AGUGGAUG G CGCUGGAG 777 CUCCAGCG GCCGAAAGGCGAGUCAAGGUCU CAUCCACU 1362

2850 GCGCUGGA G UCCAUUCU 778 AGAAUGGA GCCGAAAGGCGAGUCAAGGUCU UCCAGCGC 1363

2865 CUCCGCCG G CGGUUCAC 779 GUGAACCG GCCGAAAGGCGAGUCAAGGUCU CGGCGGAG 1364

2868 CGCCGGCG G UUCACCCA 780 UGGGUGAA GCCGAAAGGCGAGUCAAGGUCU CGCCGGCG 1365

2882 CCACCAGA G UGAUGUGU 781 ACACAUCA GCCGAAAGGCGAGUCAAGGUCU UCUGGUGG 1366

2894 UGUGUGGA G UUAUGGUG 782 CACCAUAA GCCGAAAGGCGAGUCAAGGUCU UCCACACA 1367

2900 GAGUUAUG G UGUGACUG 783 CAGUCACA GCCGAAAGGCGAGUCAAGGUCU CAUAACUC 1368

2916 GUGUGGGA G CUGAUGAC 784 GUCAUCAG GCCGAAAGGCGAGUCAAGGUCU UCCCACAC 1369

2932 CUUUUGGG G CCAAACCU 785 AGGUUUGG GCCGAAAGGCGAGUCAAGGUCU CCCAAAAG 1370

2956 GGAUCCCA G CCCGGGAG 786 CUCCCGGG GCCGAAAGGCGAGUCAAGGUCU UGGGAUCC 1371

2991 AAGGGGGA G CGGCUGCC 787 GGCAGCCG GCCGAAAGGCGAGUCAAGGUCU UCCCCCUU 1372

2994 GGGGAGCG G CUGCCCCA 788 UGGGGCAG GCCGAAAGGCGAGUCAAGGUCU CGCUCCCC 1373

3003 CUGCCCCA G CCCCCCAU 789 AUGGGGGG GCCGAAAGGCGAGUCAAGGUCU UGGGGCAG 1374

3040 UGAUCAUG G UCAAAUGU 790 ACAUUUGA GCCGAAAGGCGAGUCAAGGUCU CAUGAUCA 1375

3072 GAAUGUCG G CCAAGAUU 791 AAUCUUGG GCCGAAAGGCGAGUCAAGGUCU CGACAUUC 1376

3087 UUCCGGGA G UUGGUGUC 792 GACACCAA GCCGAAAGGCGAGUCAAGGUCU UCCCGGAA 1377

3091 GGGAGUUG G UGUCUGAA 793 UUCAGACA GCCGAAAGGCGAGUCAAGGUCU CAACUCCC 1378

3112 CCCGCAUG G CCAGGGAC 794 GUCCCUGG GCCGAAAGGCGAGUCAAGGUCU CAUGCGGG 1379

3126 GACCCCCA G CGCUUUGU 795 ACAAAGCG GCCGAAAGGCGAGUCAAGGUCU UGGGGGUC 1380

3136 GCUUUGUG G UCAUCCAG 796 CUGGAUGA GCCGAAAGGCGAGUCAAGGUCU CACAAAGC 1381

3158 GGACUUGG G CCCAGCCA 797 UGGCUGGG GCCGAAAGGCGAGUCAAGGUCU CCAAGUCC 1382

3163 UGGGCCCA G CCAGUCCC 798 GGGACUGG GCCGAAAGGCGAGUCAAGGUCU UGGGCCCA 1383

3167 CCCAGCCA G UCCCUUGG 799 CCAAGGGA GCCGAAAGGCGAGUCAAGGUCU UGGCUGGG 1384

3179 CUUGGACA G CACCUUCU 800 AGAAGGUG GCCGAAAGGCGAGUCAAGGUCU UGUCCAAG 1385

3226 GGGACCUG G UGGAUGCU 801 AGCAUCCA GCCGAAAGGCGAGUCAAGGUCU CAGGUCCC 1386

3240 GCUGAGGA G UAUCUGGU 802 ACCAGAUA GCCGAAAGGCGAGUCAAGGUCU UCCUCAGC 1387

3247 AGUAUCUG G UACCCCAG 803 CUGGGGUA GCCGAAAGGCGAGUCAAGGUCU CAGAUACU 1388

3255 GUACCCCA G CAGGGCUU 804 AAGCCCUG GCCGAAAGGCGAGUCAAGGUCU UGGGGUAC 1389

3260 CCAGCAGG G CUUCUUCU 805 AGAAGAAG GCCGAAAGGCGAGUCAAGGUCU CCUGCUGG 1390

3287 UGCCCCGG G CGCUGGGG 806 CCCCAGCG GCCGAAAGGCGAGUCAAGGUCU CCGGGGCA 1391

3296 CGCUGGGG G CAUGGUCC 807 GGACCAUG GCCGAAAGGCGAGUCAAGGUCU CCCCAGCG 1392

3301 GGGGCAUG G UCCACCAC 808 GUGGUGGA GCCGAAAGGCGAGUCAAGGUCU CAUGCCCC 1393

3312 CACCACAG G CACCGCAG 809 CUGCGGUG GCCGAAAGGCGAGUCAAGGUCU CUGUGGUG 1394

3320 GCACCGCA G CUCAUCUA 810 UAGAUGAG GCCGAAAGGCGAGUCAAGGUCU UGCGGUGC 1395

3335 UACCAGGA G UGGCGGUG 811 CACCGCCA GCCGAAAGGCGAGUCAAGGUCU UCCUGGUA 1396

3338 CAGGAGUG G CGGUGGGG 812 CCCCACCG GCCGAAAGGCGAGUCAAGGUCU CACUCCUG 1397

3341 GAGUGGCG G UGGGGACC 813 GGUCCCCA GCCGAAAGGCGAGUCAAGGUCU CGCCACUC 1398

3360 ACACUAGG G CUGGAGCC 814 GGCUCCAG GCCGAAAGGCGAGUCAAGGUCU CCUAGUGU 1399

3366 GGGCUGGA G CCCUCUGA 815 UCAGAGGG GCCGAAAGGCGAGUCAAGGUCU UCCAGCCC 1400

3382 AAGAGGAG G CCCCCAGG 816 CCUGGGGG GCCGAAAGGCGAGUCAAGGUCU CUCCUCUU 1401

3390 GCCCCCAG G UCUCCACU 817 AGUGGAGA GCCGAAAGGCGAGUCAAGGUCU CUGGGGGC 1402

3400 CUCCACUG G CACCCUCC 818 GGAGGGUG GCCGAAAGGCGAGUCAAGGUCU CAGUGGAG 1403

3415 CCGAAGGG G CUGGCUCC 819 GGAGCCAG GCCGAAAGGCGAGUCAAGGUCU CCCUUCGG 1404

3419 AGGGGCUG G CUCCGAUG 820 CAUCGGAG GCCGAAAGGCGAGUCAAGGUCU CAGCCCCU 1405

3437 AUUUGAUG G UGACCUGG 821 CCAGGUCA GCCGAAAGGCGAGUCAAGGUCU CAUCAAAU 1406

3454 GAAUGGGG G CAGCCAAG 822 CUUGGCUG GCCGAAAGGCGAGUCAAGGUCU CCCCAUUC 1407 Table 59

3457 UGGGGGCA G CCAAGGGG 823 CCCCUUGG GCCGAAAGGCGAGUCAAGGUCU UGCCCCCA 1408

3465 GCCAAGGG G CUGCAAAG 824 CUUUGCAG GCCGAAAGGCGAGUCAAGGUCU CCCUUGGC 1409

3473 GCUGCAAA G CCUCCCCA 825 UGGGGAGG GCCGAAAGGCGAGUCAAGGUCU UUUGCAGC 1410

3494 UGACCCCA G CCCUCUAC 826 GUAGAGGG GCCGAAAGGCGAGUCAAGGUCU UGGGGUCA 1411

3504 CCUCUACA G CGGUACAG 827 CUGUACCG GCCGAAAGGCGAGUCAAGGUCU UGUAGAGG 1412

3507 CUACAGCG G UACAGUGA 828 UCACUGUA GCCGAAAGGCGAGUCAAGGUCU CGCUGUAG 1413

3512 GCGGUACA G UGAGGACC 829 GGUCCUCA GCCGAAAGGCGAGUCAAGGUCU UGUACCGC 1414

3526 ACCCCACA G UACCCCUG 830 CAGGGGUA GCCGAAAGGCGAGUCAAGGUCU UGUGGGGU 1415

3551 GACUGAUG G CUACGUUG 831 CAACGUAG GCCGAAAGGCGAGUCAAGGUCU CAUCAGUC 1416

3556 AUGGCUAC G UUGCCCCC 832 GGGGGCAA GCCGAAAGGCGAGUCAAGGUCU GUAGCCAU 1417

3575 GACCUGCA G CCCCCAGC 833 GCUGGGGG GCCGAAAGGCGAGUCAAGGUCU UGCAGGUC 1418

3582 AGCCCCCA G CCUGAAUA 834 UAUUCAGG GCCGAAAGGCGAGUCAAGGUCU UGGGGGCU 1419

3600 GUGAACCA G CCAGAUGU 835 ACAUCUGG GCCGAAAGGCGAGUCAAGGUCU UGGUUCAC 1420

3612 GAUGUUCG G CCCCAGCC 836 GGCUGGGG GCCGAAAGGCGAGUCAAGGUCU CGAACAUC 1421

3618 CGGCCCCA G CCCCCUUC 837 GAAGGGGG GCCGAAAGGCGAGUCAAGGUCU UGGGGCCG 1422

3638 CCGAGAGG G CCCUCUGC 838 GCAGAGGG GCCGAAAGGCGAGUCAAGGUCU CCUCUCGG 1423

3665 ACCUGCUG G UGCCACUC 839 GAGUGGCA GCCGAAAGGCGAGUCAAGGUCU CAGCAGGU 1424

3681 CUGGAAAG G CCCAAGAC 840 GUCUUGGG GCCGAAAGGCGAGUCAAGGUCU CUUUCCAG 1425

3712 AGAAUGGG G UCGUCAAA 841 UUUGACGA GCCGAAAGGCGAGUCAAGGUCU CCCAUUCU 1426

3715 AUGGGGUC G UCAAAGAC 842 GUCUUUGA GCCGAAAGGCGAGUCAAGGUCU GACCCCAU 1427

3724 UCAAAGAC G UUUUUGCC 843 GGCAAAAA GCCGAAAGGCGAGUCAAGGUCU GUCUUUGA 1428

3740 CUUUGGGG G UGCCGUGG 844 CCACGGCA GCCGAAAGGCGAGUCAAGGUCU CCCCAAAG 1429

3745 GGGGUGCC G UGGAGAAC 845 GUUCUCCA GCCGAAAGGCGAGUCAAGGUCU GGCACCCC 1430

3759 AACCCCGA G UACUUGAC 846 GUCAAGUA GCCGAAAGGCGAGUCAAGGUCU UCGGGGUU 1431

3781 AGGGAGGA G CUGCCCCU 847 AGGGGCAG GCCGAAAGGCGAGUCAAGGUCU UCCUCCCU 1432

3792 GCCCCUCA G CCCCACCC 848 GGGUGGGG GCCGAAAGGCGAGUCAAGGUCU UGAGGGGC 1433

3815 UGCCUUCA G CCCAGCCU 849 AGGCUGGG GCCGAAAGGCGAGUCAAGGUCU UGAAGGCA 1434

3820 UCAGCCCA G CCUUCGAC 850 GUCGAAGG GCCGAAAGGCGAGUCAAGGUCU UGGGCUGA 1435

3861 CCACCAGA G CGGGGGGC 851 GCCCCCCG GCCGAAAGGCGAGUCAAGGUCU UCUGGUGG 1436

3868 AGCGGGGG G CUCCACCC 852 GGGUGGAG GCCGAAAGGCGAGUCAAGGUCU CCCCCGCU 1437

3878 UCCACCCA G CACCUUCA 853 UGAAGGUG GCCGAAAGGCGAGUCAAGGUCU UGGGUGGA 1438

3901 CACCUACG G CAGAGAAC 854 GUUCUCUG GCCGAAAGGCGAGUCAAGGUCU CGUAGGUG 1439

3915 AACCCAGA G UACCUGGG 855 CCCAGGUA GCCGAAAGGCGAGUCAAGGUCU UCUGGGUU 1440

3923 GUACCUGG G UCUGGACG 856 CGUCCAGA GCCGAAAGGCGAGUCAAGGUCU CCAGGUAC 1441

3931 GUCUGGAC G UGCCAGUG 857 CACUGGCA GCCGAAAGGCGAGUCAAGGUCU GUCCAGAC 1442

3937 ACGUGCCA G UGUGAACC 858 GGUUCACA GCCGAAAGGCGAGUCAAGGUCU UGGCACGU 1443

3951 ACCAGAAG G CCAAGUCC 859 GGACUUGG GCCGAAAGGCGAGUCAAGGUCU CUUCUGGU 1444

3956 AAGGCCAA G UCCGCAGA 860 UCUGCGGA GCCGAAAGGCGAGUCAAGGUCU UUGGCCUU 1445

3966 CCGCAGAA G CCCUGAUG 861 CAUCAGGG GCCGAAAGGCGAGUCAAGGUCU UUCUGCGG 1446

3987 CUCAGGGA G CAGGGAAG 862 CUUCCCUG GCCGAAAGGCGAGUCAAGGUCU UCCCUGAG 1447

3996 CAGGGAAG G CCUGACUU 863 AAGUCAGG GCCGAAAGGCGAGUCAAGGUCU CUUCCCUG 1448

4011 UUCUGCUG G CAUCAAGA 864 UCUUGAUG GCCGAAAGGCGAGUCAAGGUCU CAGCAGAA 1449

4021 AUCAAGAG G UGGGAGGG 865 CCCUCCCA GCCGAAAGGCGAGUCAAGGUCU CUCUUGAU 1450

4029 GUGGGAGG G CCCUCCGA 866 UCGGAGGG GCCGAAAGGCGAGUCAAGGUCU CCUCCCAC 1451

4100 CUGCUUGA G UUCCCAGA 867 UCUGGGAA GCCGAAAGGCGAGUCAAGGUCU UCAAGCAG 1452

4111 CCCAGAUG G CUGGAAGG 868 CCUUCCAG GCCGAAAGGCGAGUCAAGGUCU CAUCUGGG 1453

4121 UGGAAGGG G UCCAGCCU 869 AGGCUGGA GCCGAAAGGCGAGUCAAGGUCU CCCUUCCA 1454 Table 59

4126 GGGGUCCA G CCUCGUUG 870 CAACGAGG GCCGAAAGGCGAGUCAAGGUCU UGGACCCC 1455

4131 CCAGCCUC G UUGGAAGA 871 UCUUCCAA GCCGAAAGGCGAGUCAAGGUCU GAGGCUGG 1456

4146 GAGGAACA G CACUGGGG 872 CCCCAGUG GCCGAAAGGCGAGUCAAGGUCU UGUUCCUC 1457

4156 ACUGGGGA G UCUUUGUG 873 CACAAAGA GCCGAAAGGCGAGUCAAGGUCU UCCCCAGU 1458

4174 AUUCUGAG G CCCUGCCC 874 GGGCAGGG GCCGAAAGGCGAGUCAAGGUCU CUCAGAAU 1459

4197 ACUCUAGG G UCCAGUGG 875 CCACUGGA GCCGAAAGGCGAGUCAAGGUCU CCUAGAGU 1460

4202 AGGGUCCA G UGGAUGCC 876 GGCAUCCA GCCGAAAGGCGAGUCAAGGUCU UGGACCCU 1461

4214 AUGCCACA G CCCAGCUU 877 AAGCUGGG GCCGAAAGGCGAGUCAAGGUCU UGUGGCAU 1462

4219 ACAGCCCA G CUUGGCCC 878 GGGCCAAG GCCGAAAGGCGAGUCAAGGUCU UGGGCUGU 1463

4224 CCAGCUUG G CCCUUUCC 879 GGAAAGGG GCCGAAAGGCGAGUCAAGGUCU CAAGCUGG 1464

4246 GAUCCUGG G UACUGAAA 880 UUUCAGUA GCCGAAAGGCGAGUCAAGGUCU CCAGGAUC 1465

4255 UACUGAAA G CCUUAGGG 881 CCCUAAGG GCCGAAAGGCGAGUCAAGGUCU UUUCAGUA 1466

4266 UUAGGGAA G CUGGCCUG 882 CAGGCCAG GCCGAAAGGCGAGUCAAGGUCU UUCCCUAA 1467

4270 GGAAGCUG G CCUGAGAG 883 CUCUCAGG GCCGAAAGGCGAGUCAAGGUCU CAGCUUCC 1468

4284 GAGGGGAA G CGGCCCUA 884 UAGGGCCG GCCGAAAGGCGAGUCAAGGUCU UUCCCCUC 1469

4287 GGGAAGCG G CCCUAAGG 885 CCUUAGGG GCCGAAAGGCGAGUCAAGGUCU CGCUUCCC 1470

4298 CUAAGGGA G UGUCUAAG 886 CUUAGACA GCCGAAAGGCGAGUCAAGGUCU UCCCUUAG 1471

4314 GAACAAAA G CGACCCAU 887 AUGGGUCG GCCGAAAGGCGAGUCAAGGUCU UUUUGUUC 1472

4346 GAAACCUA G UACUGCCC 888 GGGCAGUA GCCGAAAGGCGAGUCAAGGUCU UAGGUUUC 1473

4372 AAGGAACA G CAAUGGUG 889 CACCAUUG GCCGAAAGGCGAGUCAAGGUCU UGUUCCUU 1474

4378 CAGCAAUG G UGUCAGUA 890 UACUGACA GCCGAAAGGCGAGUCAAGGUCU CAUUGCUG 1475

4384 UGGUGUCA G UAUCCAGG 891 CCUGGAUA GCCGAAAGGCGAGUCAAGGUCU UGACACCA 1476

4392 GUAUCCAG G CUUUGUAC 892 GUACAAAG GCCGAAAGGCGAGUCAAGGUCU CUGGAUAC 1477

4404 UGUACAGA G UGCUUUUC 893 GAAAAGCA GCCGAAAGGCGAGUCAAGGUCU UCUGUACA 1478

4419 UCUGUUUA G UUUUUACU 894 AGUAAAAA GCCGAAAGGCGAGUCAAGGUCU UAAACAGA 1479

Input Sequence = HSE B2 . Cut Site = G/Y

Stem Length = 8 . Core Sequence = GCcgaaagGCGaGuCaaGGuCu

HSERB2R (Human c-erb-B-2 mRNA; 4473 bp)

Table 60

Table 60: Substrate Specificity for Class I Ribozymes

Table 61

Table 61: Random region alignments/mutations for Class I ribozyme

Table 62

Table 62: Human Her2 Class II Ribozyme and Target Sequence

Table 62

lower case = 2'-0-methyl

U, C = 2'-deoxy-2'-amino U, = 2'-deoxy-2'-amino C

G,A = ribo G, A

B = inverted deoxyabasic

P= polyethylene glycol 18 (PEG 18) linker

Table 63 Table 63: Human PKCα NCH Ribozyme and Substrate Sequence

Table 63

224 AGGCUUCC A GUGCCAAG CUUGGCAC CUGAUGAG X CGAA IGAAGCCU

229 UCCAGUGC C AAGUUUGC GCAAACUU CUGAUGAG X CGAA ICACUGGA

230 CCAGUGCC A AGUUUGCU AGCAAACU CUGAUGAG X CGAA IGCACUGG

238 AAGUUUGC U GUUUUGUG CACAAAAC CUGAUGAG X CGAA ICAAACUU

250 UUGUGGUC C ACAAGAGG CCUCUUGU CUGAUGAG X CGAA IACCACAA

251 UGUGGUCC A CAAGAGGU ACCUCUUG CUGAUGAG X CGAA IGACCACA

253 UGGUCCAC A AGAGGUGC GCACCUCU CUGAUGAG X CGAA IUGGACCA

262 AGAGGUGC C AUGAAUUU AAAUUCAU CUGAUGAG X CGAA ICACCUCU

263 GAGGUGCC A UGAAUUUG CAAAUUCA CUGAUGAG X CGAA IGCACCUC

276 UUUGUUAC U UUUUCUUG CAAGAAAA CUGAUGAG X CGAA IUAACAAA

282 ACUUUUUC U UGUCCGGG CCCGGACA CUGAUGAG X CGAA IAAAAAGU

287 UUCUUGUC C GGGUGCGG CCGCACCC CUGAUGAG X CGAA IACAAGAA

305 UAAGGGAC C CGACACUG CAGUGUCG CUGAUGAG X CGAA IUCCCUUA

306 AAGGGACC C GACACUGA UCAGUGUC CUGAUGAG X CGAA IGUCCCUU

310 GACCCGAC A CUGAUGAC GUCAUCAG CUGAUGAG X CGAA IUCGGGUC

312 CCCGACAC U GAUGACCC GGGUCAUC CUGAUGAG X CGAA IUGUCGGG

319 CUGAUGAC C CCAGGAGC GCUCCUGG CUGAUGAG X CGAA IUCAUCAG

320 UGAUGACC C CAGGAGCA UGCUCCUG CUGAUGAG X CGAA IGUCAUCA

321 GAUGACCC C AGGAGCAA UUGCUCCU CUGAUGAG X CGAA IGGUCAUC

322 AUGACCCC A GGAGCAAG CUUGCUCC CUGAUGAG X CGAA IGGGUCAU

328 CCAGGAGC A AGCACAAG CUUGUGCU CUGAUGAG X CGAA ICUCCUGG

332 GAGCAAGC A CAAGUUCA UGAACUUG CUGAUGAG X CGAA ICUUGCUC

334 GCAAGCAC A AGUUCAAA UUUGAACU CUGAUGAG X CGAA IUGCUUGC

340 ACAAGUUC A AAAUCCAC GUGGAUUU CUGAUGAG X CGAA IAACUUGU

346 UCAAAAUC C ACACUUAC GUAAGUGU CUGAUGAG X CGAA lAUUUUGA

347 CAAAAUCC A CACUUACG CGUAAGUG CUGAUGAG X CGAA IGAUUUUG

349 AAAUCCAC A CUUACGGA UCCGUAAG CUGAUGAG X CGAA IUGGAUUU

351 AUCCACAC U UACGGAAG CUUCCGUA CUGAUGAG X CGAA IUGUGGAU

361 ACGGAAGC C CCACCUUC GAAGGUGG CUGAUGAG X CGAA ICUUCCGU

362 CGGAAGCC C CACCUUCU AGAAGGUG CUGAUGAG X CGAA IGCUUCCG

363 GGAAGCCC C ACCUUCUG CAGAAGGU CUGAUGAG X CGAA IGGCUUCC

364 GAAGCCCC A CCUUCUGC GCAGAAGG CUGAUGAG X CGAA IGGGCUUC

366 AGCCCCAC C UUCUGCGA UCGCAGAA CUGAUGAG X CGAA IUGGGGCU

367 GCCCCACC U UCUGCGAU AUCGCAGA CUGAUGAG X CGAA IGUGGGGC

370 CCACCUUC U GCGAUCAC GUGAUCGC CUGAUGAG X CGAA IAAGGUGG

₃77 CUGCGAUC A CUGUGGGU ACCCACAG CUGAUGAG X CGAA IAUCGCAG

379 GCGAUCAC U GUGGGUCA UGACCCAC CUGAUGAG X CGAA IUGAUCGC

387 UGUGGGUC A CUGCUCUA UAGAGCAG CUGAUGAG X CGAA lACCCACA

389 UGGGUCAC U GCUCUAUG CAUAGAGC CUGAUGAG X CGAA IUGACCCA

392 GUCACUGC U CUAUGGAC GUCCAUAG CUGAUGAG X CGAA ICAGUGAC

394 CACUGCUC U AUGGACUU AAGUCCAU CUGAUGAG X CGAA IAGCAGUG

401 CUAUGGAC U UAUCCAUC GAUGGAUA CUGAUGAG X CGAA IUCCAUAG

406 GACUUAUC C AUCAAGGG CCCUUGAU CUGAUGAG X CGAA IAUAAGUC

407 ACUUAUCC A UCAAGGGA UCCCUUGA CUGAUGAG X CGAA IGAUAAGU

410 UAUCCAUC A AGGGAUGA UCAUCCCU CUGAUGAG X CGAA lAUGGAUA

427 AAUGUGAC A CCUGCGAU AUCGCAGG CUGAUGAG X CGAA IUCACAUU

429 UGUGACAC C UGCGAUAU AUAUCGCA CUGAUGAG X CGAA lUGUCACA

430 GUGACACC U GCGAUAUG CAUAUCGC CUGAUGAG X CGAA IGUGUCAC

446 GAACGUUC A CAAGCAAU AUUGCUUG CUGAUGAG X CGAA IAACGUUC

448 ACGUUCAC A AGCAAUGC GCAUUGCU CUGAUGAG X CGAA IUGAACGU

452 UCACAAGC A AUGCGUCA UGACGCAU CUGAUGAG X CGAA ICUUGUGA Table 63

460 AAUGCGUC A UCAAUGUC GACAUUGA CUGAUGAG X CGAA IACGCAUU

463 GCGUCAUC A AUGUCCCC GGGGACAU CUGAUGAG X CGAA IAUGACGC

469 UCAAUGUC C CCAGCCUC GAGGCUGG CUGAUGAG X CGAA IACAUUGA

470 CAAUGUCC C CAGCCUCU AGAGGCUG CUGAUGAG X CGAA IGACAUUG

471 AAUGUCCC C AGCCUCUG CAGAGGCU CUGAUGAG X CGAA IGGACAUU

472 AUGUCCCC A GCCUCUGC GCAGAGGC CUGAUGAG X CGAA IGGGACAU

475 UCCCCAGC C UCUGCGGA UCCGCAGA CUGAUGAG X CGAA ICUGGGGA

476 CCCCAGCC U CUGCGGAA UUCCGCAG CUGAUGAG X CGAA IGCUGGGG

478 CCAGCCUC U GCGGAAUG CAUUCCGC CUGAUGAG X CGAA lAGGCUGG

491 AAUGGAUC A CACUGAGA UCUCAGUG CUGAUGAG X CGAA IAUCCAUU

493 UGGAUCAC A CUGAGAAG CUUCUCAG CUGAUGAG X CGAA IUGAUCCA

495 GAUCACAC U GAGAAGAG CUCUUCUC CUGAUGAG X CGAA IUGUGAUC

517 GGAUUUAC C UAAAGGCU AGCCUUUA CUGAUGAG X CGAA IUAAAUCC

518 GAUUUACC U AAAGGCUG CAGCCUUU CUGAUGAG X CGAA IGUAAAUC

525 CUAAAGGC U GAGGUUGC GCAACCUC CUGAUGAG X CGAA ICCUUUAG

534 GAGGUUGC U GAUGAAAA UUUUCAUC CUGAUGAG X CGAA ICAACCUC

545 UGAAAAGC U CCAUGUCA UGACAUGG CUGAUGAG X CGAA ICUUUUCA

547 AAAAGCUC C AUGUCACA UGUGACAU CUGAUGAG X CGAA IAGCUUUU

548 AAAGCUCC A UGUCACAG CUGUGACA CUGAUGAG X CGAA IGAGCUUU

553 UCCAUGUC A CAGUACGA UCGUACUG CUGAUGAG X CGAA IACAUGGA

555 CAUGUCAC A GUACGAGA UCUCGUAC CUGAUGAG X CGAA IUGACAUG

567 CGAGAUGC A AAAAAUCU AGAUUUUU CUGAUGAG X CGAA ICAUCUCG

575 AAAAAAUC U AAUCCCUA UAGGGAUU CUGAUGAG X CGAA IAUUUUUU

580 AUCUAAUC C CUAUGGAU AUCCAUAG CUGAUGAG X CGAA IAUUAGAU

581 UCUAAUCC C UAUGGAUC GAUCCAUA CUGAUGAG X CGAA IGAUUAGA

582 CUAAUCCC U AUGGAUCC GGAUCCAU CUGAUGAG X CGAA IGGAUUAG

590 UAUGGAUC C AAACGGGC GCCCGUUU CUGAUGAG X CGAA IAUCCAUA

591 AUGGAUCC A AACGGGCU AGCCCGUU CUGAUGAG X CGAA IGAUCCAU

599 AAACGGGC U UUCAGAUC GAUCUGAA CUGAUGAG X CGAA ICCCGUUU

603 GGGCUUUC A GAUCCUUA UAAGGAUC CUGAUGAG X CGAA IAAAGCCC

608 UUCAGAUC C UUAUGUGA UCACAUAA CUGAUGAG X CGAA IAUCUGAA

609 UCAGAUCC U UAUGUGAA UUCACAUA CUGAUGAG X CGAA IGAUCUGA

620 UGUGAAGC U GAAACUUA UAAGUUUC CUGAUGAG X CGAA ICUUCACA

626 GCUGAAAC U UAUUCCUG CAGGAAUA CUGAUGAG X CGAA IUUUCAGC

632 ACUUAUUC C UGAUCCCA UGGGAUCA CUGAUGAG X CGAA IAAUAAGU

633 CUUAUUCC U GAUCCCAA UUGGGAUC CUGAUGAG X CGAA IGAAUAAG

638 UCCUGAUC C CAAGAAUG CAUUCUUG CUGAUGAG X CGAA IAUCAGGA

639 CCUGAUCC C AAGAAUGA UCAUUCUU CUGAUGAG X CGAA IGAUCAGG

640 CUGAUCCC A AGAAUGAA UUCAUUCU CUGAUGAG X CGAA IGGAUCAG

652 AUGAAAGC A AGCAAAAA UUUUUGCU CUGAUGAG X CGAA ICUUUCAU

656 AAGCAAGC A AAAAACCA UGGUUUUU CUGAUGAG X CGAA ICUUGCUU

663 CAAAAAAC C AAAACCAU AUGGUUUU CUGAUGAG X CGAA IUUUUUUG

664 AAAAAACC A AAACCAUC GAUGGUUU CUGAUGAG X CGAA IGUUUUUU

669 ACCAAAAC C AUCCGCUC GAGCGGAU CUGAUGAG X CGAA IUUUUGGU

670 CCAAAACC A UCCGCUCC GGAGCGGA CUGAUGAG X CGAA IGUUUUGG

673 AAACCAUC C GCUCCACA UGUGGAGC CUGAUGAG X CGAA IAUGGUUU

676 CCAUCCGC U CCACACUA UAGUGUGG CUGAUGAG X CGAA ICGGAUGG

678 AUCCGCUC C ACACUAAA UUUAGUGU CUGAUGAG X CGAA IAGCGGAU

679 UCCGCUCC A CACUAAAU AUUUAGUG CUGAUGAG X CGAA IGAGCGGA

681 CGCUCCAC A CUAAAUCC GGAUUUAG CUGAUGAG X CGAA IUGGAGCG

683 CUCCACAC U AAAUCCGC GCGGAUUU CUGAUGAG X CGAA IUGUGGAG Table 63

689 ACUAAAUC C GCAGUGGA UCCACUGC CUGAUGAG X CGAA IAUUUAGU

692 AAAUCCGC A GUGGAAUG CAUUCCAC CUGAUGAG X CGAA ICGGAUUU

705 AAUGAGUC C UUUACAUU AAUGUAAA CUGAUGAG X CGAA IACUCAUU

706 AUGAGUCC U UUACAUUC GAAUGUAA CUGAUGAG X CGAA IGACUCAU

711 UCCUUUAC A UUCAAAUU AAUUUGAA CUGAUGAG X CGAA IUAAAGGA

715 UUACAUUC A AAUUGAAA UUUCAAUU CUGAUGAG X CGAA IAAUGUAA

725 AUUGAAAC C UUCAGACA UGUCUGAA CUGAUGAG X CGAA IUUUCAAU

726 UUGAAACC U UCAGACAA UUGUCUGA CUGAUGAG X CGAA IGUUUCAA

729 AAACCUUC A GACAAAGA UCUUUGUC CUGAUGAG X CGAA IAAGGUUU

733 CUUCAGAC A AAGACCGA UCGGUCUU CUGAUGAG X CGAA IUCUGAAG

739 ACAAAGAC C GACGACUG CAGUCGUC CUGAUGAG X CGAA IUCUUUGU

746 CCGACGAC U GUCUGUAG CUACAGAC CUGAUGAG X CGAA IUCGUCGG

750 CGACUGUC U GUAGAAAU AUUUCUAC CUGAUGAG X CGAA IACAGUCG

760 UAGAAAUC U GGGACUGG CCAGUCCC CUGAUGAG X CGAA IAUUUCUA

766 UCUGGGAC U GGGAUCGA UCGAUCCC CUGAUGAG X CGAA IUCCCAGA

777 GAUCGAAC A ACAAGGAA UUCCUUGU CUGAUGAG X CGAA IUUCGAUC

780 CGAACAAC A AGGAAUGA UCAUUCCU CUGAUGAG X CGAA IUUGUUCG

790 GGAAUGAC U UCAUGGGA UCCCAUGA CUGAUGAG X CGAA IUCAUUCC

793 AUGACUUC A UGGGAUCC GGAUCCCA CUGAUGAG X CGAA IAAGUCAU

801 AUGGGAUC C CUUUCCUU AAGGAAAG CUGAUGAG X CGAA IAUCCCAU

802 UGGGAUCC C UUUCCUUU AAAGGAAA CUGAUGAG X CGAA IGAUCCCA

803 GGGAUCCC U UUCCUUUG CAAAGGAA CUGAUGAG X CGAA IGGAUCCC

807 UCCCUUUC C UUUGGAGU ACUCCAAA CUGAUGAG X CGAA lAAAGGGA

808 CCCUUUCC U UUGGAGUU AACUCCAA CUGAUGAG X CGAA IGAAAGGG

824 UUCGGAGC U GAUGAAGA UCUUCAUC CUGAUGAG X CGAA ICUCCGAA

836 GAAGAUGC C GGCCAGUG CACUGGCC CUGAUGAG X CGAA ICAUCUUC

840 AUGCCGGC C AGUGGAUG CAUCCACU CUGAUGAG X CGAA ICCGGCAU

841 UGCCGGCC A GUGGAUGG CCAUCCAC CUGAUGAG X CGAA IGCCGGCA

853 GAUGGUAC A AGUUGCUU AAGCAACU CUGAUGAG X CGAA IUACCAUC

860 CAAGUUGC U UAACCAAG CUUGGUUA CUGAUGAG X CGAA ICAACUUG

865 UGCUUAAC C AAGAAGAA UUCUUCUU CUGAUGAG X CGAA lUUAAGCA

866 GCUUAACC A AGAAGAAG CUUCUUCU CUGAUGAG X CGAA IGUUAAGC

883 GUGAGUAC U ACAACGUA UACGUUGU CUGAUGAG X CGAA IUACUCAC

886 AGUACUAC A ACGUACCC GGGUACGU CUGAUGAG X CGAA IUAGUACU

893 CAACGUAC C CAUUCCGG CCGGAAUG CUGAUGAG X CGAA IUACGUUG

894 AACGUACC C AUUCCGGA UCCGGAAU CUGAUGAG X CGAA IGUACGUU

895 ACGUACCC A UUCCGGAA UUCCGGAA CUGAUGAG X CGAA IGGUACGU

899 ACCCAUUC C GGAAGGGG CCCCUUCC CUGAUGAG X CGAA IAAUGGGU

922 AAGGAAAC A UGGAACUC GAGUUCCA CUGAUGAG X CGAA IUUUCCUU

929 CAUGGAAC U CAGGCAGA UCUGCCUG CUGAUGAG X CGAA IUUCCAUG

931 UGGAACUC A GGCAGAAA UUUCUGCC CUGAUGAG X CGAA IAGUUCCA

935 ACUCAGGC A GAAAUUCG CGAAUUUC CUGAUGAG X CGAA ICCUGAGU

951 GAGAAAGC C AAACUUGG CCAAGUUU CUGAUGAG X CGAA ICUUUCUC

952 AGAAAGCC A AACUUGGC GCCAAGUU CUGAUGAG X CGAA IGCUUUCU

956 AGCCAAAC U UGGCCCUG CAGGGCCA CUGAUGAG X CGAA UUUGGCU

961 AACUUGGC C CUGCUGGC GCCAGCAG CUGAUGAG X CGAA ICCAAGUU

962 ACUUGGCC C UGCUGGCA UGCCAGCA CUGAUGAG X CGAA IGCCAAGU

963 CUUGGCCC u GCUGGCAA UUGCCAGC CUGAUGAG X CGAA IGGCCAAG

966 GGCCCUGC u GGCAACAA UUGUUGCC CUGAUGAG X CGAA ICAGGGCC

970 CUGCUGGC A ACAAAGUC GACUUUGU CUGAUGAG X CGAA ICCAGCAG

973 CUGGCAAC A AAGUCAUC GAUGACUU CUGAUGAG X CGAA IUUGCCAG Table 63

979 ACAAAGUC A UCAGUCCC GGGACUGA CUGAUGAG X CGAA IACUUUGU

982 AAGUCAUC A GUCCCUCU AGAGGGAC CUGAUGAG X CGAA IAUGACUU

986 CAUCAGUC C CUCUGAAG CUUCAGAG CUGAUGAG X CGAA IACUGAUG

987 AUCAGUCC C UCUGAAGA UCUUCAGA CUGAUGAG X CGAA IGACUGAU

988 UCAGUCCC U CUGAAGAC GUCUUCAG CUGAUGAG X CGAA IGGACUGA

990 AGUCCCUC U GAAGACAG CUGUCUUC CUGAUGAG X CGAA IAGGGACU

997 CUGAAGAC A GGAAACAA UUGUUUCC CUGAUGAG X CGAA IUCUUCAG

1004 CAGGAAAC A ACCUUCCA UGGAAGGU CUGAUGAG X CGAA IUUUCCUG

1007 GAAACAAC C UUCCAACA UGUUGGAA CUGAUGAG X CGAA IUUGUUUC

1008 AAACAACC U UCCAACAA UUGUUGGA CUGAUGAG X CGAA IGUUGUUU

1011 CAACCUUC C AACAACCU AGGUUGUU CUGAUGAG X CGAA IAAGGUUG

1012 AACCUUCC A ACAACCUU AAGGUUGU CUGAUGAG X CGAA IGAAGGUU

1015 CUUCCAAC A ACCUUGAC GUCAAGGU CUGAUGAG X CGAA IUUGGAAG

1018 CCAACAAC C UUGACCGA UCGGUCAA CUGAUGAG X CGAA IUUGUUGG

1019 CAACAACC U UGACCGAG CUCGGUCA CUGAUGAG X CGAA IGUUGUUG

1024 ACCUUGAC C GAGUGAAA UUUCACUC CUGAUGAG X CGAA IUCAAGGU

1034 AGUGAAAC U CACGGACU AGUCCGUG CUGAUGAG X CGAA IUUUCACU

1036 UGAAACUC A CGGACUUC GAAGUCCG CUGAUGAG X CGAA IAGUUUCA

1042 UCACGGAC U UCAAUUUC GAAAUUGA CUGAUGAG X CGAA IUCCGUGA

1045 CGGACUUC A AUUUCCUC GAGGAAAU CUGAUGAG X CGAA IAAGUCCG

1051 UCAAUUUC C UCAUGGUG CACCAUGA CUGAUGAG X CGAA IAAAUUGA

1052 CAAUUUCC U CAUGGUGU ACACCAUG CUGAUGAG X CGAA IGAAAUUG

1054 AUUUCCUC A UGGUGUUG CAACACCA CUGAUGAG X CGAA IAGGAAAU

^■ 1091 GGUGAUGC U UGCCGACA UGUCGGCA CUGAUGAG X CGAA ICAUCACC

1095 AUGCUUGC C GACAGGAA UUCCUGUC CUGAUGAG X CGAA ICAAGCAU

1099 UUGCCGAC A GGAAGGGC GCCCUUCC CUGAUGAG X CGAA IUCGGCAA

1108 GGAAGGGC A CAGAAGAA UUCUUCUG CUGAUGAG X CGAA ICCCUUCC

1110 AAGGGCAC A GAAGAACU AGUUCUUC CUGAUGAG X CGAA IUGCCCUU

1118 AGAAGAAC U GUAUGCAA UUGCAUAC CUGAUGAG X CGAA lUUCUUCU

1125 CUGUAUGC A AUCAAAAU AUUUUGAU CUGAUGAG X CGAA ICAUACAG

1129 AUGCAAUC A AAAUCCUG CAGGAUUU CUGAUGAG X CGAA IAUUGCAU

1135 UCAAAAUC C UGAAGAAG CUUCUUCA CUGAUGAG X CGAA lAUUUUGA

1136 CAAAAUCC U GAAGAAGG CCUUCUUC CUGAUGAG X CGAA IGAUUUUG

1157 GGUGAUUC A GGAUGAUG CAUCAUCC CUGAUGAG X CGAA IAAUCACC

1177 UGGAGUGC A CCAUGGUA UACCAUGG CUGAUGAG X CGAA ICACUCCA

1179 GAGUGCAC C AUGGUAGA UCUACCAU CUGAUGAG X CGAA IUGCACUC

1180 AGUGCACC A UGGUAGAA UUCUACCA CUGAUGAG X CGAA IGUGCACU

1198 AGCGAGUC U UGGCCCUG CAGGGCCA CUGAUGAG X CGAA IACUCGCU

1203 GUCUUGGC C CUGCUUGA UCAAGCAG CUGAUGAG X CGAA ICCAAGAC

1204 UCUUGGCC C UGCUUGAC GUCAAGCA CUGAUGAG X CGAA IGCCAAGA

1205 CUUGGCCC U GCUUGACA UGUCAAGC CUGAUGAG X CGAA IGGCCAAG

1208 GGCCCUGC U UGACAAAC GUUUGUCA CUGAUGAG X CGAA ICAGGGCC

1213 UGCUUGAC A AACCCCCG CGGGGGUU CUGAUGAG X CGAA IUCAAGCA

1217 UGACAAAC C CCCGUUCU AGAACGGG CUGAUGAG X CGAA IUUUGUCA

1218 GACAAACC C CCGUUCUU AAGAACGG CUGAUGAG X CGAA IGUUUGUC

1219 ACAAACCC C CGUUCUUG CAAGAACG CUGAUGAG X CGAA IGGUUUGU

1220 CAAACCCC C GUUCUUGA UCAAGAAC CUGAUGAG X CGAA IGGGUUUG

1225 CCCCGUUC U UGACGCAG CUGCGUCA CUGAUGAG X CGAA IAACGGGG

1232 CUUGACGC A GCUGCACU AGUGCAGC CUGAUGAG X CGAA ICGUCAAG

1235 GACGCAGC U GCACUCCU AGGAGUGC CUGAUGAG X CGAA ICUGCGUC

1238 GCAGCUGC A CUCCUGCU AGCAGGAG CUGAUGAG X CGAA ICAGCUGC Table 63

1240 AGCUGCAC U CCUGCUUC GAAGCAGG CUGAUGAG X CGAA IUGCAGCU

1242 CUGCACUC C UGCUUCCA UGGAAGCA CUGAUGAG X CGAA IAGUGCAG

1243 UGCACUCC U GCUUCCAG CUGGAAGC CUGAUGAG X CGAA IGAGUGCA

1246 ACUCCUGC U UCCAGACA UGUCUGGA CUGAUGAG X CGAA ICAGGAGU

1249 CCUGCUUC C AGACAGUG CACUGUCU CUGAUGAG X CGAA IAAGCAGG

1250 CUGCUUCC A GACAGUGG CCACUGUC CUGAUGAG X CGAA IGAAGCAG

1254 UUCCAGAC A GUGGAUCG CGAUCCAC CUGAUGAG X CGAA IUCUGGAA

1265 GGAUCGGC U GUACUUCG CGAAGUAC CUGAUGAG X CGAA ICCGAUCC

1270 GGCUGUAC U UCGUCAUG CAUGACGA CUGAUGAG X CGAA IUACAGCC

1276 ACUUCGUC A UGGAAUAU AUAUUCCA CUGAUGAG X CGAA IACGAAGU

1288 AAUAUGUC A ACGGUGGG CCCACCGU CUGAUGAG X CGAA IACAUAUU

1300 GUGGGGAC C UCAUGUAC GUACAUGA CUGAUGAG X CGAA IUCCCCAC

1301 UGGGGACC U CAUGUACC GGUACAUG CUGAUGAG X CGAA IGUCCCCA

1303 GGGACCUC A UGUACCAC GUGGUACA CUGAUGAG X CGAA IAGGUCCC

1309 UCAUGUAC C ACAUUCAG CUGAAUGU CUGAUGAG X CGAA IUACAUGA

1310 CAUGUACC A CAUUCAGC GCUGAAUG CUGAUGAG X CGAA IGUACAUG

1312 UGUACCAC A UUCAGCAA UUGCUGAA CUGAUGAG X CGAA lUGGUACA

1316 CCACAUUC A GCAAGUAG CUACUUGC CUGAUGAG X CGAA IAAUGUGG

1319 CAUUCAGC A AGUAGGAA UUCCUACU CUGAUGAG X CGAA ICUGAAUG

1340 UAAGGAAC C ACAAGCAG CUGCUUGU CUGAUGAG X CGAA IUUCCUUA

1341 AAGGAACC A CAAGCAGU ACUGCUUG CUGAUGAG X CGAA IGUUCCUU

1343 GGAACCAC A AGCAGUAU AUACUGCU CUGAUGAG X CGAA IUGGUUCC

1347 CCACAAGC A GUAUUCUA UAGAAUAC CUGAUGAG X CGAA ICUUGUGG

1354 CAGUAUUC U AUGCGGCA UGCCGCAU CUGAUGAG X CGAA IAAUACUG

1362 UAUGCGGC A GAGAUUUC GAAAUCUC CUGAUGAG X CGAA ICCGCAUA

1371 GAGAUUUC C AUCGGAUU AAUCCGAU CUGAUGAG X CGAA IAAAUCUC

1372 AGAUUUCC A UCGGAUUG CAAUCCGA CUGAUGAG X CGAA IGAAAUCU

1384 GAUUGUUC U UUCUUCAU AUGAAGAA CUGAUGAG X CGAA IAACAAUC

1388 GUUCUUUC U UCAUAAAA UUUUAUGA CUGAUGAG X CGAA IAAAGAAC

1391 CUUUCUUC A UAAAAGAG CUCUUUUA CUGAUGAG X CGAA IAAGAAAG

1405 GAGGAAUC A UUUAUAGG CCUAUAAA CUGAUGAG X CGAA IAUUCCUC

1418 UAGGGAUC U GAAGUUAG CUAACUUC CUGAUGAG X CGAA IAUCCCUA

1435 AUAACGUC A UGUUGGAU AUCCAACA CUGAUGAG X CGAA IACGUUAU

1446 UUGGAUUC A GAAGGACA UGUCCUUC CUGAUGAG X CGAA IAAUCCAA

1454 AGAAGGAC A UAUCAAAA UUUUGAUA CUGAUGAG X CGAA IUCCUUCU

1459 GACAUAUC A AAAUUGCU AGCAAUUU CUGAUGAG X CGAA IAUAUGUC

1467 AAAAUUGC U GACUUUGG CCAAAGUC CUGAUGAG X CGAA ICAAUUUU

1471 UUGCUGAC U UUGGGAUG CAUCCCAA CUGAUGAG X CGAA IUCAGCAA

1483 GGAUGUGC A AGGAACAC GUGUUCCU CUGAUGAG X CGAA ICACAUCC

1490 CAAGGAAC A CAUGAUGG CCAUCAUG CUGAUGAG X CGAA IUUCCUUG

1492 AGGAACAC A UGAUGGAU AUCCAUCA CUGAUGAG X CGAA lUGUUCCU

1507 AUGGAGUC A CGACCAGG CCUGGUCG CUGAUGAG X CGAA IACUCCAU

1512 GUCACGAC C AGGACCUU AAGGUCCU CUGAUGAG X CGAA IUCGUGAC

1513 UCACGACC A GGACCUUC GAAGGUCC CUGAUGAG X CGAA IGUCGUGA

1518 ACCAGGAC C UUCUGUGG CCACAGAA CUGAUGAG X CGAA IUCCUGGU

1519 CCAGGACC U UCUGUGGG CCCACAGA CUGAUGAG X CGAA IGUCCUGG

1522 GGACCUUC U GUGGGACU AGUCCCAC CUGAUGAG X CGAA IAAGGUCC

1530 UGUGGGAC U CCAGAUUA UAAUCUGG CUGAUGAG x- CGAA IUCCCACA

1532 UGGGACUC C AGAUUAUA UAUAAUCU CUGAUGAG X CGAA IAGUCCCA

1533 GGGACUCC A GAUUAUAU AUAUAAUC CUGAUGAG X CGAA IGAGUCCC

1545 UAUAUCGC C CCAGAGAU AUCUCUGG CUGAUGAG X CGAA ICGAUAUA Table 63

1546 AUAUCGCC C CAGAGAUA UAUCUCUG CUGAUGAG X CGAA IGCGAUAU

1547 UAUCGCCC C AGAGAUAA UUAUCUCU CUGAUGAG X CGAA IGGCGAUA

1548 AUCGCCCC A GAGAUAAU AUUAUCUC CUGAUGAG X CGAA IGGGCGAU

1560 AUAAUCGC U UAUCAGCC GGCUGAUA CUGAUGAG X CGAA ICGAUUAU

1565 CGCUUAUC A GCCGUAUG CAUACGGC CUGAUGAG X CGAA IAUAAGCG

1568 UUAUCAGC C GUAUGGAA UUCCAUAC CUGAUGAG X CGAA ICUGAUAA

1581 GGAAAAUC U GUGGACUG CAGUCCAC CUGAUGAG X CGAA IAUUUUCC

1588 CUGUGGAC U GGUGGGCC GGCCCACC CUGAUGAG X CGAA IUCCACAG

1596 UGGUGGGC C UAUGGCGU ACGCCAUA CUGAUGAG X CGAA ICCCACCA

1597 GGUGGGCC U AUGGCGUC GACGCCAU CUGAUGAG X CGAA IGCCCACC

1606 AUGGCGUC C UGUUGUAU AUACAACA CUGAUGAG X CGAA IACGCCAU

1607 UGGCGUCC U GUUGUAUG CAUACAAC CUGAUGAG X CGAA IGACGCCA

1622 UGAAAUGC u UGCCGGGC GCCCGGCA CUGAUGAG X CGAA ICAUUUCA

1626 AUGCUUGC c GGGCAGCC GGCUGCCC CUGAUGAG X CGAA ICAAGCAU

1631 UGCCGGGC A GCCUCCAU AUGGAGGC CUGAUGAG X CGAA ICCCGGCA

1634 CGGGCAGC C UCCAUUUG CAAAUGGA CUGAUGAG X CGAA ICUGCCCG

1635 GGGCAGCC U CCAUUUGA UCAAAUGG CUGAUGAG X CGAA IGCUGCCC

1637 GCAGCCUC C AUUUGAUG CAUCAAAU CUGAUGAG X CGAA IAGGCUGC

1638 CAGCCUCC A UUUGAUGG CCAUCAAA CUGAUGAG X CGAA IGAGGCUG

1664 AGACGAGC U AUUUCAGU ACUGAAAU CUGAUGAG X CGAA ICUCGUCU

1670 GCUAUUUC A GUCUAUCA UGAUAGAC CUGAUGAG X CGAA IAAAUAGC

1674 UUUCAGUC U AUCAUGGA UCCAUGAU CUGAUGAG X CGAA lACUGAAA

1678 AGUCUAUC A UGGAGCAC GUGCUCCA CUGAUGAG X CGAA IAUAGACU

1685 CAUGGAGC A CAACGUUU AAACGUUG CUGAUGAG X CGAA ICUCCAUG

1687 UGGAGCAC A ACGUUUCC GGAAACGU CUGAUGAG X CGAA IUGCUCCA

1695 AACGUUUC C UAUCCAAA UUUGGAUA CUGAUGAG X CGAA IAAACGUU

1696 ACGUUUCC U AUCCAAAA UUUUGGAU CUGAUGAG X CGAA IGAAACGU

1700 UUCCUAUC C AAAAUCCU AGGAUUUU CUGAUGAG X CGAA IAUAGGAA

1701 UCCUAUCC A AAAUCCUU AAGGAUUU CUGAUGAG X CGAA IGAUAGGA

1707 CCAAAAUC C UUGUCCAA UUGGACAA CUGAUGAG X CGAA IAUUUUGG

1708 CAAAAUCC U UGUCCAAG CUUGGACA CUGAUGAG X CGAA IGAUUUUG

1713 UCCUUGUC C AAGGAGGC GCCUCCUU CUGAUGAG X CGAA IACAAGGA

1714 CCUUGUCC A AGGAGGCU AGCCUCCU CUGAUGAG X CGAA IGACAAGG

1722 AAGGAGGC U GUUUCUAU AUAGAAAC CUGAUGAG X CGAA ICCUCCUU

1728 GCUGUUUC U AUCUGCAA UUGCAGAU CUGAUGAG X CGAA IAAACAGC

1732 UUUCUAUC U GCAAAGGA UCCUUUGC CUGAUGAG X CGAA lAUAGAAA

1735 CUAUCUGC A AAGGACUG CAGUCCUU CUGAUGAG X CGAA ICAGAUAG

1742 CAAAGGAC U GAUGACCA UGGUCAUC CUGAUGAG X CGAA IUCCUUUG

1749 CUGAUGAC C AAACACCC GGGUGUUU CUGAUGAG X CGAA IUCAUCAG

1750 UGAUGACC A AACACCCA UGGGUGUU CUGAUGAG X CGAA IGUCAUCA

1754 GACCAAAC A CCCAGCCA UGGCUGGG CUGAUGAG X CGAA IUUUGGUC

1756 CCAAACAC C CAGCCAAG CUUGGCUG CUGAUGAG X CGAA IUGUUUGG

1757 CAAACACC C AGCCAAGC GCUUGGCU CUGAUGAG X CGAA IGUGUUUG

1758 AAACACCC A GCCAAGCG CGCUUGGC CUGAUGAG X CGAA IGGUGUUU

1761 CACCCAGC C AAGCGGCU AGCCGCUU CUGAUGAG X CGAA ICUGGGUG

1762 ACCCAGCC A AGCGGCUG CAGCCGCU CUGAUGAG X CGAA IGCUGGGU

1769 CAAGCGGC U GGGCUGUG CACAGCCC CUGAUGAG X CGAA ICCGCUUG

1774 GGCUGGGC U GUGGGCCU AGGCCCAC CUGAUGAG X CGAA ICCCAGCC

1781 CUGUGGGC C UGAGGGGG CCCCCUCA CUGAUGAG X CGAA ICCCACAG

1782 UGUGGGCC U GAGGGGGA UCCCCCUC CUGAUGAG X CGAA IGCCCACA

1808 GAGAGAGC A UGCCUUCU AGAAGGCA CUGAUGAG X CGAA ICUCUCUC Table 63

1812 GAGCAUGC C UUCUUCCG CGGAAGAA CUGAUGAG X CGAA ICAUGCUC

1813 AGCAUGCC U UCUUCCGG CCGGAAGA CUGAUGAG X CGAA IGCAUGCU

1816 AUGCCUUC U UCCGGAGG CCUCCGGA CUGAUGAG X CGAA IAAGGCAU

1819 CCUUCUUC C GGAGGAUC GAUCCUCC CUGAUGAG X CGAA IAAGAAGG

1831 GGAUCGAC U GGGAAAAA UUUUUCCC CUGAUGAG X CGAA IUCGAUCC

1841 GGAAAAAC U GGAGAACA UGUUCUCC CUGAUGAG X CGAA IUUUUUCC

1849 UGGAGAAC A GGGAGAUC GAUCUCCC CUGAUGAG X CGAA lUUCUCCA

1858 GGGAGAUC C AGCCACCA UGGUGGCU CUGAUGAG X CGAA IAUCUCCC

1859 GGAGAUCC A GCCACCAU AUGGUGGC CUGAUGAG X CGAA IGAUCUCC

1862 GAUCCAGC C ACCAUUCA UGAAUGGU CUGAUGAG X CGAA ICUGGAUC

1863 AUCCAGCC A CCAUUCAA UUGAAUGG CUGAUGAG X CGAA IGCUGGAU

1865 CCAGCCAC C AUUCAAGC GCUUGAAU CUGAUGAG X CGAA IUGGCUGG

1866 CAGCCACC A UUCAAGCC GGCUUGAA CUGAUGAG X CGAA IGUGGCUG

1870 CACCAUUC A AGCCCAAA UUUGGGCU CUGAUGAG X CGAA IAAUGGUG

1874 AUUCAAGC C CAAAGUGU ACACUUUG CUGAUGAG X CGAA ICUUGAAU

1875 UUCAAGCC C AAAGUGUG CACACUUU CUGAUGAG X CGAA IGCUUGAA

1876 UCAAGCCC A AAGUGUGU ACACACUU CUGAUGAG X CGAA IGGCUUGA

1888 UGUGUGGC A AAGGAGCA UGCUCCUU CUGAUGAG X CGAA ICCACACA

1896 AAAGGAGC A GAGAACUU AAGUUCUC CUGAUGAG X CGAA ICUCCUUU

1903 CAGAGAAC U UUGACAAG CUUGUCAA CUGAUGAG X CGAA IUUCUCUG

1909 ACUUUGAC A AGUUCUUC GAAGAACU CUGAUGAG X CGAA IUCAAAGU

1915 ACAAGUUC U UCACACGA UCGUGUGA CUGAUGAG X CGAA IAACUUGU

1918 AGUUCUUC A CACGAGGA UCCUCGUG CUGAUGAG X CGAA IAAGAACU

1920 UUCUUCAC A CGAGGACA UGUCCUCG CUGAUGAG X CGAA IUGAAGAA

1928 ACGAGGAC A GCCCGUCU AGACGGGC CUGAUGAG X CGAA IUCCUCGU

1931 AGGACAGC C CGUCUUAA UUAAGACG CUGAUGAG X CGAA ICUGUCCU

1932 GGACAGCC C GUCUUAAC GUUAAGAC CUGAUGAG X CGAA IGCUGUCC

1936 AGCCCGUC U UAACACCA UGGUGUUA CUGAUGAG X CGAA IACGGGCU

1941 GUCUUAAC A CCACCUGA UCAGGUGG CUGAUGAG X CGAA IUUAAGAC

1943 CUUAACAC C ACCUGAUC GAUCAGGU CUGAUGAG X CGAA IUGUUAAG

1944 UUAACACC A CCUGAUCA UGAUCAGG CUGAUGAG X CGAA IGUGUUAA

1946 AACACCAC C UGAUCAGC GCUGAUCA CUGAUGAG X CGAA IUGGUGUU

1947 ACACCACC U GAUCAGCU AGCUGAUC CUGAUGAG X CGAA IGUGGUGU

1952 ACCUGAUC A GCUGGUUA UAACCAGC CUGAUGAG X CGAA IAUCAGGU

1955 UGAUCAGC U GGUUAUUG CAAUAACC CUGAUGAG X CGAA ICUGAUCA

1965 GUUAUUGC U AACAUAGA UCUAUGUU CUGAUGAG X CGAA ICAAUAAC

1969 UUGCUAAC A UAGACCAG CUGGUCUA CUGAUGAG X CGAA IUUAGCAA

1975 ACAUAGAC C AGUCUGAU AUCAGACU CUGAUGAG X CGAA IUCUAUGU

1976 CAUAGACC A GUCUGAUU AAUCAGAC CUGAUGAG X CGAA IGUCUAUG

1980 GACCAGUC U GAUUUUGA UCAAAAUC CUGAUGAG X CGAA IACUGGUC

1996 AAGGGUUC U CGUAUGUC GACAUACG CUGAUGAG X CGAA IAACCCUU

2005 CGUAUGUC A ACCCCCAG CUGGGGGU CUGAUGAG X CGAA IACAUACG

2008 AUGUCAAC C CCCAGUUU AAACUGGG CUGAUGAG X CGAA IUUGACAU

2009 UGUCAACC C CCAGUUUG CAAACUGG CUGAUGAG X CGAA IGUUGACA

2010 GUCAACCC C CAGUUUGU ACAAACUG CUGAUGAG X CGAA IGGUUGAC

2011 UCAACCCC C AGUUUGUG CACAAACU CUGAUGAG X CGAA IGGGUUGA

2012 CAACCCCC A GUUUGUGC GCACAAAC CUGAUGAG X CGAA IGGGGUUG

2021 GUUUGUGC A CCCCAUCU AGAUGGGG CUGAUGAG X CGAA ICACAAAC

2023 UUGUGCAC C CCAUCUUA UAAGAUGG CUGAUGAG X CGAA IUGCACAA

2024 UGUGCACC C CAUCUUAC GUAAGAUG CUGAUGAG X CGAA IGUGCACA

2025 GUGCACCC C AUCUUACA UGUAAGAU CUGAUGAG X CGAA IGGUGCAC Table 63

2026 UGCACCCC A UCUUACAG CUGUAAGA CUGAUGAG X CGAA IGGGUGCA

2029 ACCCCAUC U UACAGAGU ACUCUGUA CUGAUGAG X CGAA IAUGGGGU

2033 CAUCUUAC A GAGUGCAG CUGCACUC CUGAUGAG X CGAA IUAAGAUG

2040 CAGAGUGC A GUAUGAAA UUUCAUAC CUGAUGAG X CGAA ICACUCUG

2050 UAUGAAAC U CACCAGCG CGCUGGUG CUGAUGAG X CGAA IUUUCAUA

2052 UGAAACUC A CCAGCGAG CUCGCUGG CUGAUGAG X CGAA IAGUUUCA

2054 AAACUCAC C AGCGAGAA UUCUCGCU CUGAUGAG X CGAA IUGAGUUU

2055 AACUCACC A GCGAGAAC GUUCUCGC CUGAUGAG X CGAA IGUGAGUU

2064 GCGAGAAC A AACACCUC GAGGUGUU CUGAUGAG X CGAA IUUCUCGC

2068 GAACAAAC A CCUCCCCA UGGGGAGG CUGAUGAG X CGAA IUUUGUUC

2070 ACAAACAC C UCCCCAGC GCUGGGGA CUGAUGAG X CGAA IUGUUUGU

2071 CAAACACC U CCCCAGCC GGCUGGGG CUGAUGAG X CGAA IGUGUUUG

2073 AACACCUC C CCAGCCCC GGGGCUGG CUGAUGAG X CGAA IAGGUGUU

2074 ACACCUCC C CAGCCCCC GGGGGCUG CUGAUGAG X CGAA IGAGGUGU

2075 CACCUCCC C AGCCCCCA UGGGGGCU CUGAUGAG X CGAA IGGAGGUG

2076 ACCUCCCC A GCCCCCAG CUGGGGGC CUGAUGAG X CGAA IGGGAGGU

2079 UCCCCAGC C CCCAGCCC GGGCUGGG CUGAUGAG X CGAA ICUGGGGA

2080 CCCCAGCC C CCAGCCCU AGGGCUGG CUGAUGAG X CGAA IGCUGGGG

2081 CCCAGCCC C CAGCCCUC GAGGGCUG CUGAUGAG X CGAA IGGCUGGG

2082 CCAGCCCC C AGCCCUCC GGAGGGCU CUGAUGAG X CGAA IGGGCUGG

2083 CAGCCCCC A GCCCUCCC GGGAGGGC CUGAUGAG X CGAA IGGGGCUG

2086 CCCCCAGC C CUCCCCGC GCGGGGAG CUGAUGAG X CGAA ICUGGGGG

2087 CCCCAGCC C UCCCCGCA UGCGGGGA CUGAUGAG X CGAA IGCUGGGG

2088 CCCAGCCC U CCCCGCAG CUGCGGGG CUGAUGAG X CGAA IGGCUGGG

2090 CAGCCCUC C CCGCAGUG CACUGCGG CUGAUGAG X CGAA IAGGGCUG

2091 AGCCCUCC C CGCAGUGG CCACUGCG CUGAUGAG X CGAA IGAGGGCU

2092 GCCCUCCC C GCAGUGGA UCCACUGC CUGAUGAG X CGAA IGGAGGGC

2095 CUCCCCGC A GUGGAAGU ACUUCCAC CUGAUGAG X CGAA ICGGGGAG

2109 AGUGAAUC C UUAACCCU AGGGUUAA CUGAUGAG X CGAA IAUUCACU

2110 GUGAAUCC U UAACCCUA UAGGGUUA CUGAUGAG X CGAA IGAUUCAC

2115 UCCUUAAC C CUAAAAUU AAUUUUAG CUGAUGAG X CGAA lUUAAGGA

2116 CCUUAACC C UAAAAUUU AAAUUUUA CUGAUGAG X CGAA IGUUAAGG

2117 CUUAACCC U AAAAUUUU AAAAUUUU CUGAUGAG X CGAA IGGUUAAG

2131 UUUAAGGC C ACGGCUUG CAAGCCGU CUGAUGAG X CGAA ICCUUAAA

2132 UUAAGGCC A CGGCUUGU ACAAGCCG CUGAUGAG X CGAA IGCCUUAA

2137 GCCACGGC U UGUGUCUG CAGACACA CUGAUGAG X CGAA ICCGUGGC

2144 CUUGUGUC U GAUUCCAU AUGGAAUC CUGAUGAG X CGAA IACACAAG

2150 UCUGAUUC C AUAUGGAG CUCCAUAU CUGAUGAG X CGAA IAAUCAGA

2151 CUGAUUCC A UAUGGAGG CCUCCAUA CUGAUGAG X CGAA IGAAUCAG

2161 AUGGAGGC C UGAAAAUU AAUUUUCA CUGAUGAG X CGAA ICCUCCAU

2162 UGGAGGCC U GAAAAUUG CAAUUUUC CUGAUGAG X CGAA IGCCUCCA

2185 UAUUAGUC C AAAUGUGA UCACAUUU CUGAUGAG X CGAA IACUAAUA

2186 AUUAGUCC A AAUGUGAU AUCACAUU CUGAUGAG X CGAA IGACUAAU

2196 AUGUGAUC A ACUGUUCA UGAACAGU CUGAUGAG X CGAA IAUCACAU

2199 UGAUCAAC U GUUCAGGG CCCUGAAC CUGAUGAG X CGAA IUUGAUCA

2204 AACUGUUC A GGGUCUCU AGAGACCC CUGAUGAG X CGAA IAACAGUU

2210 UCAGGGUC U CUCUCUUA UAAGAGAG CUGAUGAG X CGAA lACCCUGA

2212 AGGGUCUC U CUCUUACA UGUAAGAG CUGAUGAG X CGAA IAGACCCU

2214 GGUCUCUC U CUUACAAC GUUGUAAG CUGAUGAG X CGAA IAGAGACC

2216 UCUCUCUC U UACAACCA UGGUUGUA CUGAUGAG X CGAA IAGAGAGA

2220 UCUCUUAC A ACCAAGAA UUCUUGGU CUGAUGAG X CGAA IUAAGAGA Table 63

Input Sequence = PRKCA. Cut Site = CH/ .

Stem Length = 8 . Core Sequence = CUGAUGAG X CGAA (X = GCCGUUAGGC or other stem II)

PRKCA (Homo sapiens protein kinase C, alpha (PRKCA) mRNA. ; 2245 bp)

Table 64

Table 64: Activity of ribozyme core substituted analogues

B

Comparison of single turnover cleavage rates for GCH and GUH substrates with 1-15.1 and A-15.1 ribozymes and ribozyme analogs. Conditions: Single turnover (250 nM substrate, 2.5 μM ribozyme) pH 6.0, 37 C, 10 mM Mg⁺⁺

Claims

Claims:We claim:

1. An enzymatic nucleic acid molecule having formula 4 namely:

wherein each X, Y, and Z represents independently a nucleotide which may be the same or different; 1 is an integer greater than or equal to 3; m is an integer greater than 1 ; n is an integer greater than 1; 0 is an integer greater than or equal to 3; Z' is a nucleotide complementary to Z; Y' is a nucleotide complementary to Y; each X(l) and X(o) are oligonucleotides which are of sufficient length to stably interact independently with a target nucleic acid sequence; W is a linker of > 2 nucleotides; A, U, G, and C represent nucleotides; C is 2'-amino; and represents a chemical linkage.

2. An enzymatic nucleic acid molecule having formula 5 namely:

5" (X)o

wherein each X, Y, and Z represents independently a nucleotide which may be the same or different; 1 is an integer greater than or equal to 3; n is an integer greater than 1; 0 is an integer greater than or equal to 3; Z' is a nucleotide complementary to Z; each XQ and X(₀) are oligonucleotides which are of sufficient length to stably interact independently with a target nucleic acid sequence; W is a linker of > 2 nucleotides in length or may be a non-nucleotide linker; A, U, G, and C represent nucleotides; C is 2'-amino; and represents a chemical linkage.

3. The enzymatic nucleic acid molecule of claims 1 or 2, wherein 1 is selected from the group consisting of 4, 5, 6, 7, 8, 9, 10, 11, 12, and 15.

4. The enzymatic nucleic acid molecule of claim 1, wherein m is selected from the group consisting of 2, 3, 4, 5, 6, and 7.

5. The enzymatic nucleic acid molecule of claims 1 or 2, wherein n is selected from the group consisting of 2, 3, 4, 5, 6, and 7.

6. The enzymatic nucleic acid molecule of claims 1 or 2, wherein o is selected from the group consisting of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 15.

7. The enzymatic nucleic acid molecule of claims 1 or 2, wherein 1 and o are of the same length.

8. The enzymatic nucleic acid molecule of claims 1 or 2, wherein 1 and o are of different length.

9. The enzymatic nucleic acid molecule of claims 1 or 2, wherein the target nucleic acid sequence is selected from the group consisting of an RNA, DNA and RNA/DNA mixed polymer.

10. The enzymatic nucleic acid molecule of claims 1 or 2, wherein said chemical linkage is selected from the group consisting of phosphate ester linkage, amide linkage, phosphorothioate, and phosphorodithioate.

11. The enzymatic nucleic acid molecule of claims 1 or 2, wherein said COS selected from the group consisting of 2 '-deoxy-2 '-NH₂ and 2' -deoxy-2 '-O-NH₂.

12. A method for inhibiting expression of a gene in a cell, comprising the step of administering to said cell the enzymatic nucleic acid molecule of claims 1 or 2 under conditions suitable for said inhibition.

13. A method of cleaving a separate RNA molecule comprising, contacting the enzymatic nucleic acid molecule of claims 1 or 2 with said separate RNA molecule under conditions suitable for the cleavage of said separate RNA molecule.

14. The method of claim 13, wherein said cleavage is carried out in the presence of a divalent cation.

15. The method of claim 14, wherein said divalent cation is Mg2+.

16. The enzymatic nucleic acid molecule of claims 1 or 2, wherein said enzymatic nucleic acid molecule is chemically synthesized.

17. The enzymatic nucleic acid molecule of claims 1 or 2, wherein said enzymatic nucleic acid molecule comprises at least one ribonucleotide.

18. The enzymatic nucleic acid molecule of claims 1 or 2, wherein said enzymatic nucleic acid molecule comprises no ribonucleotide residues.

19. The enzymatic nucleic acid molecule of claims 1 or 2, wherein said enzymatic nucleic acid molecule comprises at least one 2-amino modification.

20. The enzymatic nucleic acid molecule of claims 1 or 2, wherein said enzymatic nucleic acid molecule comprises at least three phosphorothioate modifications.

21. The enzymatic nucleic acid molecule of claim 20, wherein said phosphorothioate modification is at the 5 '-end of said enzymatic nucleic acid molecule.

22. The enzymatic nucleic acid molecule of claims 1 or 2, wherein said enzymatic nucleic acid molecule comprises a 5 '-cap or a 3 '-cap or both a 5 '-cap and a 3 '-cap.

23. The enzymatic nucleic acid molecule of claim 22, wherein said 5-cap is phosphorothioate modification.

24. The enzymatic nucleic acid molecule of claim 22, wherein said 3 '-cap is an inverted abasic moiety.

25. A compound having the formula 3:

wherein R is independently any nucleoside selected from the group consisting of 2'-O- methyl-2,6-diaminopurine riboside; 2'-deoxy-2'amino-2,6-diaminopurine riboside; 2'- (N-alanyl) amino-2 '-deoxy-uridine; 2'-(N-phenylalanyl)amino-2'-deoxy-uridine; 2'- deoxy -2'-(N-β-alanyl) amino ; 2'-deoxy-2'-(lysiyl) amino uridine; 2'-C-allyl uridine; 2'-O-amino-uridine; 2'-O-methylthiomethyl adenosine; 2'-O-methylthiomethyl cytidine ; 2'-O-methylthiomethyl guanosine; 2'-O-methylthiomethyl-uridine; 2'- deoxy-2'-(N-histidyl) amino uridine; 2'-deoxy-2'-amino-5-methyl cytidine; 2'-(N-β- carboxamidine-β-alanyl)amino-2'-deoxy-uridine; 2'-deoxy-2'-(Ν-β-alanyl)-guanosine; 2'-O-amino-adenosine; 2'-(N-lysyl)amino-2'-deoxy-cytidine; 2'-Deoxy -2'-(L- histidine) amino Cytidine; 5-lmidazoleacetic acid 2'-deoxy uridine, 5-[3-(Ν-4- imidazoleacetyl)aminopropynyl]-2'-O-methyl uridine, 5-(3-aminopropynyl)-2'-O- methyl uridine, 5-(3-aminopropyl)-2'-O-methyl uridine, 5-[3-(N-4- imidazoleacetyl)aminopropyl]-2'-O-methyl uridine, 5-(3-aminopropyl)-2'-deoxy-2- fluoro uridine, 2'-Deoxy-2'-(β-alanyl-L-histidyl)amino uridine, 2'-deoxy-2'-β- alaninamido-uridine, 3-(2'-deoxy-2'-fluoro-β-D-ribofuranosyl)piperazino[2,3-

D]pyrimidine-2-one, 5-[3-(N-4-imidazoleacetyl)aminopropyl]-2'-deoxy-2'-fluoro uridine, 5-[3-(N-4-imidazoleacetyl)aminopropynyl]-2'-deoxy-2'-fluoro uridine, 5-E- (2-carboxyvinyl-2 ' -deoxy-2 ' -fluoro uridine, 5 -[3 -(N-4-aspartyl)aminopropynyl-2 ' - fluoro uridine, 5-(3-aminopropyl)-2'-deoxy-2-fluoro cytidine, and 5-[3-(N-4- succynyl)aminopropyl-2'-deoxy-2-fluoro cytidine.

26. A process for incoφoration of the compounds of claim 25 into an oligonucleotide comprising the step of contacting said compound with a mixture comprising a nucleic acid template, an RNA polymerase enzyme, and an enhancer of modified nucleotide triphosphate incoφoration, under conditions suitable for the incoφoration of said compound into said oligonucleotide.

27. The process of claim 26, wherein said RNA polymerase is a T7 RNA polymerase.

28. The process of claim 26, wherein said RNA polymerase is a mutant T7 RNA polymerase.

29. The process of claim 26, wherein said RNA polymerase is a SP6 RNA polymerase.

30. The process of claim 26, wherein said RNA polymerase is a mutant SP6 RNA polymerase.

31. The process of claim 26, wherein said RNA polymerase is a T3 RNA polymerase.

32. The process of claim 26, wherein said RNA polymerase is a mutant T3 RNA polymerase.

33. The process of claim 26, wherein said enhancer of modified nucleotide triphosphate incoφoration is selected from the group consisting of LiCl, methanol, polyethylene glycol, diethyl ether, propanol, methylamine, and ethanol.

34. A process for the synthesis of a pyrimidine nucleotide triphosphate comprising the steps of:

a. monophosphorylation, wherein a pyrimidine nucleoside is contacted with a mixture comprising a phosphorylating reagent, a trialkyl phosphate and dimethylaminopyridine, under conditions suitable for the formation of a pyrimidine nucleotide monophosphate; and

b. pyrophosphorylation, wherein said pyrimidine monophosphate from step (a) is contacted with a pyrophosphorylating reagent under conditions suitable for the formation of said pyrimidine nucleotide triphosphate.

35. The process of claim 34, wherein said pyrimidine nucleoside triphosphate is uridine triphosphate.

36. The process of claim 34, wherein said uridine triphosphate has a 2'-sugar modification.

37. The process of claim 36, wherein said uridine triphosphate is 2'-O- methylthiomethyl uridine triphosphate.

38. The process of claim 34, wherein said phosphorylating agent is selected from the group consisting of phosphorus oxychloride, phospho-tris-triazolides and phospho- tris-triimidazolides.

39. The process of claim 34, wherein said trialkylphosphate is triethyl phosphate.

40. The process of claim 34, wherein said pyrophosphorylating reagent is tributyl ammonium pyrophosphate.

41. The process of claim 26, wherein said oligonucleotide is RNA.

42. The process of claim 26, wherein said oligonucleotide is an enzymatic nucleic acid molecule.

43. The process of claim 26, wherein said oligonucleotide is an aptamer.

44. A kit for synthesis of an oligonucleotide comprising an RNA polymerase, an enhancer of modified nucleotide triphosphate incoφoration and at least one compound of claim 25.

45. A kit for synthesis of an oligonucleotide comprising a DNA polymerase, an enhancer of modified nucleotide triphosphate incoφoration and at least one compound of claim 25.

46. The kit of claim 44, wherein said RNA polymerase is a bacteriophage T7 RNA polymerase.

47. The kit of claim 44, wherein said RNA polymerase is a bacteriophage SP6 RNA polymerase.

48. The kit of claim 44, wherein said RNA polymerase is a bacteriophage T3 RNA polymerase.

49. The kit of claim 44, wherein said RNA polymerase is a mutant T7 RNA polymerase.

50. The kit of claim 44 or 45, wherein said kit comprises at least two different compounds of claim 25.

51. A nucleic acid catalyst comprising a histidyl modification, wherein said nucleic acid catalyst is able to catalyze an endonuclease reaction in the absence of a metal ion co-factor.

52. The nucleic acid catalyst of claim 51, wherein said catalyst is able to cleave a separate nucleic acid molecule.

53. The nucleic acid catalyst of claim 52, wherein said separate nucleic acid molecule is an RNA molecule.

54. The nucleic acid catalyst of claim 52, wherein said separate nucleic acid molecule is a DNA molecule.

55. The nucleic acid catalyst of claim 51, wherein said nucleic acid catalyst comprises at least one ribonucleotide.

56. The enzymatic nucleic acid molecule of claim 2, wherein said nucleic acid molecule has an endonuclease activity to cleave RNA of HER2 gene.

57. The enzymatic nucleic acid molecule of claim 56, wherein said nucleic acid molecule comprises sequences complementary to any of substrate sequences defined as Target sequence in Tables 58, 59 and 62.

58. The enzymatic nucleic acid molecule of claim 56, wherein said nucleic acid molecule comprises any of ribozyme sequences defined as Ribozyme sequence in Tables 58, 59 and 62.

59. A method for treating cancer using the enzymatic nucleic acid molecule of claim 56.

60. The method of claim 59, wherein said cancer is breast cancer.

61. A method for treating conditions associated with the level of HER2 gene using the enzymatic nucleic acid molecule of claim 56.

62. The enzymatic nucleic acid molecule of claim 56, wherein said enzymatic nucleic acid molecule comprises a substrate binding region which has between 5 and 30 nucleotides complementary to the RNA.

63. The enzymatic nucleic acid molecule of claim 56, wherein said enzymatic nucleic acid molecule comprises a substrate binding region which has between 7 and 12 nucleotides complementary to the RNA.

64. A mammalian cell including the enzymatic nucleic acid molecule of claim 56.

65. The mammalian cell of claim 64, wherein said mammalian cell is a human cell.

66. A mammalian cell including the enzymatic nucleic acid molecule of claims 1 or 2.

67. The mammalian cell of claim 66, wherein said mammalian cell is a human cell.

68. A method for inhibiting expression of HER2 gene in a cell, comprising the step of administering to said cell the enzymatic nucleic acid molecule of claim 56 under conditions suitable for said inhibition.

69. A method of cleaving RNA derived from HER2 gene comprising, contacting the enzymatic nucleic acid molecule of claim 56 with said RNA molecule under conditions suitable for the cleavage of said RNA molecule.

70. A pharmaceutical composition comprising the enzymatic nucleic acid molecule of any of claims 1 or 2.

71. A pharmaceutical composition comprising the enzymatic nucleic acid molecule of claim 56.

72. A method of treatment of a patient having a condition associated with the level of HER2, wherein said patient is administered the enzymatic nucleic acid molecule of claim 56 under conditions suitable for said treatment.

73. The method of claim 72, wherein said method is performed in conjunction with one or more other therapies.

74. The method of claim 59, wherein said enzymatic nucleic acid molecule is used in conjunction with one or more other therapies.

75. The enzymatic nucleic acid molecule of claim 56, wherein said enzymatic nucleic acid molecule comprises at least one sugar modification.

76. The enzymatic nucleic acid molecule of claim 56, wherein said enzymatic nucleic acid molecule comprises at least one nucleic acid base modification.

77. The enzymatic nucleic acid molecule of claim 56, wherein said enzymatic nucleic acid molecule comprises at least one phosphate backbone modification.

78. The enzymatic nucleic acid molecule of claim 56, wherein said phosphate backbone modification is selected from the group consisting of phosphorothioate, phosphorodithioate and amide.

79. An enzymatic nucleic acid molecule which down regulates expression of genes selected from the group consisting of beta site APP-cleaving enzyme (BACE) and telomerase reverse transciptase (TERT) genes.

80. The enzymatic nucleic acid molecule of claim 79, wherein said gene is the beta site APP-cleaving enzyme (BACE).

81. The enzymatic nucleic acid molecule of claim 79, wherein said gene is the telomerase reverse transcriptase (TERT).

82. A nucleic acid molecule which down regulates expression of genes selected from the group consisting of protein-tyrosine phosphatase- IB (PTP-IB), methionine aminopeptidase (MetAP-2), hepatitis B virus (HBV), phospholamban (PLN), and presenilin (ps-2) genes.

83. The nucleic acid molecule of claim 82, wherein said nucleic acid molecule is an enzymatic nucleic acid molecule.

84. The nucleic acid molecule of claim 82, wherein said nucleic acid molecule is an antisense nucleic acid molecule.

85. The nucleic acid molecule of any of claims 82-84, wherein said gene is the protein- tyrosine phosphatase- IB (PTP-IB).

86. The nucleic acid molecule of any of claims 82-84, wherein said gene is the methionine aminopeptidase (MetAP-2).

87. The nucleic acid molecule of any of claims 82-84, wherein said gene is the hepatitis B virus (HBV).

88. The nucleic acid molecule of any of claims 82-84, wherein said gene is the phospholamban (PLN).

89. The nucleic acid molecule of any of claims 82-84, wherein said gene is the presenilin (ps-2).

90. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid molecule is adapted for use to treat diseases and conditions related to the expression of genes selected from the group consisting of beta site APP-cleaving enzyme (BACE), telomerase reverse transciptase (TERT), protein- tyrosine phosphatase- IB (PTP-IB), methionine aminopeptidase (MetAP-2), hepatitis B virus (HBV), phospholamban (PLN), and presenilin (ps-2) genes.

91. The nucleic acid molecule of claim 82, wherein said nucleic acid molecule is adapted for use to treat diseases and conditions related to the expression of genes selected from the group consisting of protein-tyrosine phosphatase- IB (PTP-IB), methionine aminopeptidase (MetAP-2), hepatitis B virus (HBV), phospholamban (PLN), and presenilin (ps-2) genes.

92. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid molecule has an endonuclease activity to cleave RNA encoded by said beta site APP-cleaving enzyme (BACE), telomerase reverse transciptase (TERT), protein-tyrosine phosphatase- IB (PTP-IB), methionine aminopeptidase (MetAP-2), hepatitis B virus (HBV), phospholamban (PLN), and presenilin (ps-2) genes.

93. The enzymatic nucleic acid of any of claims 79 or 83, wherein a binding arm of said enzymatic nucleic acid molecule comprise sequences complementary to any of the sequences defined as Target or Substrate sequence in Tables 3-30, and 36- 43.

94. The enzymatic nucleic acid molecule of any of claims 79 or 83 wherein said enzymatic nucleic acid molecule comprises any of the sequences defined as Ribozyme or DNAzyme sequence in Tables 3-29, and 37-43.

95. The nucleic acid molecule of claim 84, wherein said antisense nucleic acid molecule comprises sequence complementary to any of the sequences defined as

Target or Substrate sequence in Tables 3-12, 24-30, and 36-43.

96. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid molecule is in a hammerhead (HH) motif.

97. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid molecule is in a zinzyme (Class II) motif.

98. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid molecule is in a amberzyme (Class 1) motif.

99. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid molecule is in a haiφin, hepatitis Delta virus, group I intron, VS nucleic acid, or RNAse P nucleic acid motif.

100. The enzymatic nucleic acid molecule of claim 97, wherein said zinzyme motif comprises sequences complementary to any of the substrate sequences shown in Tables 21, 27 and 40.

101. The enzymatic nucleic acid molecule of claim 98, wherein said amberzyme motif comprises sequences complementary to any of the substrate sequences shown in Tables 23, 29, and 42.

102. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid molecule is in a NCH motif.

103. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid molecule is in a G-cleaver motif.

104. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid molecule is a DNAzyme.

105. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid molecule comprises between 12 and 100 bases complementary to the RNA of genes selected from the group consisting of beta site ^" APP-cleaving enzyme (BACE), telomerase reverse transciptase (TERT), protein- tyrosine phosphatase- IB (PTP-IB), methionine aminopeptidase (MetAP-2), hepatitis B virus (HBV), phospholamban (PLN), and presenilin (ps-2) genes.

106. The enzymatic nucleic acid of any of claims 79 or 83, wherein said enzymatic nucleic acid molecule comprises between 14 and 24 bases complementary to the RNA of genes selected from the group consisting of beta site APP-cleaving enzyme (BACE), telomerase reverse transciptase (TERT), protein-tyrosine phosphatase- IB (PTP-IB), methionine aminopeptidase (MetAP-2), hepatitis B virus (HBV), phospholamban (PLN), and presenilin (ps-2) genes.

107. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid is chemically synthesized.

108. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid comprises at least one 2 '-sugar modification.

109. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid comprises at least one nucleic acid base modification.

110. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid comprises at least one phosphate backbone modification.

111. A mammalian cell including the enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said mammalian cell is not a living human.

112. The mammalian cell of claim 111, wherein said mammalian cell is a human cell.

113. The antisense nucleic acid molecule of claim 84, wherein said antisense nucleic acid is chemically synthesized.

114. The antisense nucleic acid molecule of claim 84, wherein said antisense nucleic acid comprises at least one 2 '-sugar modification.

115. The antisense nucleic acid molecule of claim 84, wherein said antisense nucleic acid comprises at least one nucleic acid base modification.

116. The antisense nucleic acid molecule of claim 84, wherein said antisense nucleic acid comprises at least one phosphate backbone modification.

117. A mammalian cell including the antisense nucleic acid molecule of claim 84, wherein said mammalian cell is not a living human.

118. The mammalian cell of claim 117, wherein said mammalian cell is a human cell.

119. A method of reducing BACE activity in a cell, comprising the step of contacting said cell with the enzymatic nucleic acid molecule of claim 80, under conditions suitable for said inhibition.

120. A method of reducing TERT activity in a cell, comprising the step of contacting said cell with the enzymatic nucleic acid molecule of claim 81, under conditions suitable for said inhibition.

121. A method of reducing PTP-IB activity in a cell, comprising the step of contacting said cell with the nucleic acid molecule of claim 85, under conditions suitable for said inhibition.

122. A method of reducing MetAP-2 activity in a cell, comprising the step of contacting said cell with the nucleic acid molecule of claim 86, under conditions suitable for said inhibition.

123. A method of reducing HBV activity in a cell, comprising the step of contacting said cell with the nucleic acid molecule of claim 87, under conditions suitable for said inhibition.

124. A method of reducing phospholamban (PLN) activity in a cell, comprising the step of contacting said cell with the nucleic acid molecule of claim 88, under conditions suitable for said inhibition.

125. A method of reducing presenilin-2 (ps-2) activity in a cell, comprising the step of contacting said cell with the nucleic acid molecule of claim 89, under conditions suitable for said inhibition.

126. A method of treatment of a patient having a condition associated with the level of BACE, comprising contacting cells of said patient with the enzymatic nucleic acid molecule of claim 80, under conditions suitable for said treatment.

127. A method of treatment of a patient having a condition associated with the level of TERT, comprising contacting cells of said patient with the enzymatic nucleic acid molecule of claim 81, under conditions suitable for said treatment.

128. A method of treatment of a patient having a condition associated with the level of PTP-IB, comprising contacting cells of said patient with the nucleic acid molecule of claim 85, under conditions suitable for said treatment.

129. A method of treatment of a patient having a condition associated with the level of MetAP-2, comprising contacting cells of said patient with the nucleic acid molecule of claim 86, under conditions suitable for said treatment.

130. A method of treatment of a patient having a condition associated with the level of HBV, comprising contacting cells of said patient with the nucleic acid molecule of claim 87, under conditions suitable for said treatment.

131. A method of treatment of a patient having a condition associated with the level of phospholamban (PLN), comprising contacting cells of said patient with the nucleic acid molecule of claim 88, under conditions suitable for said treatment.

132. A method of treatment of a patient having a condition associated with the level of presenilin-2 (ps-2), comprising contacting cells of said patient with the nucleic acid molecule of claim 89, under conditions suitable for said treatment.

133. The method of any of claims 126-132 further comprising the use of one or more drug therapies under conditions suitable for said treatment.

134. A method of cleaving RNA of BACE gene, comprising, contacting the enzymatic nucleic acid molecule of claim 80, with said RNA under conditions suitable for the cleavage of said RNA.

135. A method of cleaving RNA of TERT gene, comprising, contacting the enzymatic nucleic acid molecule of claim 81, with said RNA under conditions suitable for the cleavage of said RNA.

136. A method of cleaving RNA of PTP-IB gene, comprising, contacting the enzymatic nucleic acid molecule of claim 85, with said RNA under conditions suitable for the cleavage of said RNA.

137. A method of cleaving RNA of MetAP-2 gene, comprising, contacting the enzymatic nucleic acid molecule of claim 86, with said RNA under conditions suitable for the cleavage of said RNA.

138. A method of cleaving RNA of HBV gene, comprising, contacting the enzymatic nucleic acid molecule of claim 87, with said RNA under conditions suitable for the cleavage of said RNA.

139. A method of cleaving RNA of phospholamban (PLN) gene, comprising, contacting the enzymatic nucleic acid molecule of claim 88, with said RNA under conditions suitable for the cleavage of said RNA.

140. A method of cleaving RNA of presenilin-2 (ps-2) gene, comprising, contacting the enzymatic nucleic acid molecule of claim 89, with said RNA under conditions suitable for the cleavage of said RNA.

141. The method of any of claims 134-140, wherein said cleavage is carried out in the presence of a divalent cation.

142. The method of claim 141, wherein said divalent cation is Mg2+.

143. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid comprises a cap structure, wherein the cap structure is at the 5 '-end or 3 '-end or both the 5 '-end and the 3 '-end.

144. The antisense nucleic acid molecule of claim 84, wherein said antisense nucleic acid comprises a cap structure, wherein the cap structure is at the 5 '-end or 3 '-end or both the 5 '-end and the 3 '-end.

145. The enzymatic nucleic acid molecule of claim 96, wherein said hammerhead motif comprises sequences complementary to any of sequences defined as Target or Substrate sequences in Tables 3, 9, 13, 18, 24, and 37.

146. The enzymatic nucleic acid molecule of claim 102, wherein said NCH motif comprises sequences complementary to any of sequences defined as Target or Substrate sequences in Tables 4, 10, 14, 19, 25, and 38.

147. The enzymatic nucleic acid molecule of claim 103, wherein said G-cleaver motif comprises sequences complementary to any of sequences defined as Target or Substrate sequences in Tables 5, 11, 15, 20, 26, and 39.

148. The enzymatic nucleic acid molecule of claim 104, wherein said DNAzyme comprises sequences complementary to any of sequences defined as Target or Substrate sequences in Tables 6, 16, 22, 28, and 41.

149. The method of any of claims 119-125 or 133, wherein said enzymatic nucleic acid molecule is in a hammerhead motif.

150. The method of any of claims 119-125 or 133, wherein said nucleic acid molecule is a DNAzyme.

151. An expression vector comprising nucleic acid sequence encoding at least one enzymatic nucleic acid molecule of any of claims 79 or 83, in a manner which allows expression of that enzymatic nucleic acid molecule.

152. An expression vector comprising nucleic acid sequence encoding at least one antisense nucleic acid molecule of claim 84, in a manner which allows expression of that antisense nucleic acid molecule.

153. A mammalian cell including an expression vector of any of claims 151 or 152, wherein said mammalian cell is not a living human.

154. The mammalian cell of claim 153, wherein said mammalian cell is a human cell.

155. The expression vector of claim 151, wherein said enzymatic nucleic acid molecule is in a hammerhead motif.

156. The expression vector of claim 151, wherein said expression vector further comprises a sequence for an antisense nucleic acid molecule complementary to the RNA of genes selected from the group consisting of beta site APP-cleaving enzyme (BACE), telomerase reverse transciptase (TERT), protein-tyrosine phosphatase- IB (PTP-IB), methionine aminopeptidase (MetAP-2), hepatitis B virus (HBV), phospholamban (PLN), and presenilin (ps-2) genes.

157. The expression vector of claim 151, wherein said expression vector comprises sequence encoding at least two said enzymatic nucleic acid molecules, which may be same or different.

158. The expression vector of claim 157, wherein one said expression vector further comprises sequence encoding antisense nucleic acid molecule complementary to the RNA of genes selected from the group consisting of beta site APP-cleaving enzyme (BACE), telomerase reverse transciptase (TERT), protein-tyrosine phosphatase- IB (PTP-IB), methionine aminopeptidase (MetAP-2), hepatitis B virus (HBV), phospholamban (PLN), and presenilin (ps-2) genes.

159. A method for treatment of Alzheimer's disease comprising the step of administering to a patient the enzymatic nucleic acid molecule of claim 80 under conditions suitable for said treatment.

160. The method of claim 159, wherein said treatment of Alzheimer's disease is treatment of dementia.

161. A method for treatment of Alzheimer's disease comprising the step of administering to a patient the antisense nucleic acid molecule of claim 89 under conditions suitable for said treatment.

162. A method for treatment of diabetes comprising the step of administering to a patient the nucleic acid molecule of claim 85 under conditions suitable for said treatment.

163. The method of claim 162, wherein said diabetes is type I diabetes.

164. The method of claim 162, wherein said diabetes is type II diabetes.

165. A method for treatment of diabetes comprising the step of administering to a patient the antisense nucleic acid molecule of claim 85 under conditions suitable for said treatment.

166. A method for treatment of obesity comprising the step of administering to a patient the nucleic acid molecule of claim 85 under conditions suitable for said treatment.

167. A method for treatment of obesity comprising the step of administering to a patient the antisense nucleic acid molecule of claim 85 under conditions suitable for said treatment.

168. A method for treatment of heart disease comprising the step of administering to a patient the nucleic acid molecule of claim 88 under conditions suitable for said treatment.

169. The method of claim 168, wherein said heart disease is heart failure.

170. The method of claim 168, wherein said heart disease is congestive heart failure.

171. A method for treatment of pressure overload hypertrophy, or dilated cardiomyopathy, or both, comprising the step of administering to a patient the nucleic acid molecule of claim 88 under conditions suitable for said treatment.

172. A method for treatment of cancer comprising the step of administering to a patient the nucleic acid molecule of claim 86 under conditions suitable for said treatment.

173. A method for treatment of hepatitis comprising the step of administering to a patient the nucleic acid molecule of claim 87 under conditions suitable for said treatment.

174. A method for treatment of hepatocellular carcinoma comprising the step of administering to a patient the nucleic acid molecule of claim 87 under conditions suitable for said treatment.

175. The method of claim 159, wherein said enzymatic nucleic acid molecule is in a hammerhead motif.

176. The method of claim 159, wherein said method further comprises administering to said patient the enzymatic nucleic acid molecule in conjunction with one or more of other therapies.

177. The method of any of claims 162, 165-168, or 171-174, wherein said nucleic acid molecule is an enzymatic nucleic acid molecule.

178. The method of any of claims 162, 166-168, or 171-174, wherein said nucleic acid molecule is an antisense nucleic acid molecule.

179. The method of any of claims 162, 165-168, or 171-174, wherein said method further comprises administering to said patient the nucleic acid molecule in conjunction with one or more of other therapies.

180. The enzymatic nucleic acid molecule of any of claims 79 or 83, wherein said enzymatic nucleic acid molecule comprises at least five ribose residues; at least ten 2'-O-methyl modifications, and a 3'- end modification.

181. The enzymatic nucleic acid molecule of claim 180, wherein said enzymatic nucleic acid molecule further comprises phosphorothioate linkages on at least three ofthe 5' terminal nucleotides.

182. The enzymatic nucleic acid molecule of claim 180, wherein said 3'- end modification is 3 '-3' inverted abasic moiety.

183. The enzymatic nucleic acid molecule of claim 104, wherein said DNAzyme comprises at least ten 2'-O-methyl modifications and a 3 '-end modification.

184. The enzymatic nucleic acid molecule of claim 183, wherein said DNAzyme further comprises phosphorothioate linkages on at least three of the 5' terminal nucleotides.

185. The enzymatic nucleic acid molecule of claim 183, wherein said 3'- end modification is 3 '-3' inverted abasic moiety.

186. An enzymatic nucleic acid molecule having formula 1 :

— G— A — A — I D 3'

(N) n^_ (N)_p— A — G— N — A — G — U 5'

wherein N represents independently a nucleotide or a non-nucleotide linker, which may be same or different; D and E are independently oligonucleotides of length sufficient to stably interact with a target RNA molecule; o and n are integers independently greater than or equal to 1, wherein if (N)o and (N)n are nucleotides, (N)o and (N)n are optionally able to interact by hydrogen bond interaction; • indicates base-paired interaction; L is a linker which may be present or absent, but when present, is a nucleotide linker, a non-nucleotide linker, or a combination of nucleotide and a non-nucleotide linker; p is an integer 0 or 1 ; represents a chemical linkage; and A, U, I, C and G represent adenosine, uridine, inosine, cytidine and guanosine nucleotides, respectively.

187. An enzymatic nucleic acid molecule having formula 2:

wherein N represents independently a nucleotide or a non-nucleotide linker, which may be same or different; D and E are independently oligonucleotides of length sufficient to stably interact with a target RNA molecule; o and n are integers independently greater than or equal to 0, wherein if (N)o and (N)n are nucleotides, (N)o and (N)n are optionally able to interact by hydrogen bond interaction; • indicates base-paired interaction; L is a linker which may be present or absent, but when present, is a nucleotide linker, a non-nucleotide linker, or a combination of nucleotide and a non-nucleotide linker; p is an integer 0 or 1 ; represents a chemical linkage; and A, U, I, C and G represent adenosine, uridine, inosine, cytidine and guanosine nucleotides, respectively.

188. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said D and E are independently of length selected from the group consisting of 3, 4, 5, 6, 7, 8,

9, 10, 11, 12, 13, 14, 15, 17, and 20 nucleotides.

189. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said D and E are ofthe same length.

190. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said D and E are of different length.

191. The enzymatic nucleic acid molecule of claim 186, wherein said o and n are independently integers selected from the group consisting of 2, 3, 4, 5, 6, 7, 8, 9,

10, 15, 20, 25, 30, 35, and 50.

192. The enzymatic nucleic acid molecule of claim 187, wherein said o and n are independently integers selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, and 50.

193. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said (N)o and (N)n comprise nucleotides that are complementary to each other.

194. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said (N)o and (N)n are ofthe same length.

195. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said (N)o and (N)n are of different length.

196. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said L is a nucleotide linker.

197. The enzymatic nucleic acid molecule of claim 196, wherein said nucleotide linker is of length between 3-50 nucleotides.

198. The enzymatic nucleic acid molecule of claim 196, wherein said nucleotide linker is an aptamer.

199. The enzymatic nucleic acid molecule of claim 196 wherein said nucleotide linker is selected from the group consisting of 5'-GAAA-3' and 5'-GUUA-3'.

200. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said L is a non-nucleotide linker.

201. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said chemical linkage is independently or in combination selected from the group consisting of phosphate ester linkage, amide linkage, phosphorothioate, arabino, arabinofluoro, and phosphorodithioate.

202. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said p is 1.

203. The enzymatic nucleic acid molecule of claim 202, wherein said N of (N)p is independently selected from the group consisting of adenosine, uridine, and cytidine.

204. The enzymatic nucleic acid molecule of claims 186 or 187 wherein said enzymatic nucleic acid molecule is chemically synthesized.

205. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said enzymatic nucleic acid molecule comprises at least three ribonucleotide residues.

206. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said enzymatic nucleic acid molecule comprises at least four ribonucleotide residues.

207. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said enzymatic nucleic acid molecule comprises at least five ribonucleotide residues.

208. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said I is selected from the group consisting of ribo-inosine and xylo-inosine.

209. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said enzymatic nucleic acid molecule comprises at least one sugar modification.

210. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said enzymatic nucleic acid molecule comprises at least nucleic acid base modification.

211. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said enzymatic nucleic acid molecule comprises at least one phosphate backbone modification.

212. The enzymatic nucleic acid molecule of claim 209, wherein said sugar modification is selected from the group consisting of 2'-H, 2'-O-methyl, 2'-O- allyl, and 2 '-deoxy-2 '-amino.

213. The enzymatic nucleic acid molecule of claim 211, wherein said phosphate backbone modification is selected from the group consisting of phosphorothioate, phosphorodithioate and amide.

214. The enzymatic nucleic acid molecule of claims 186 or 187 wherein said enzymatic nucleic acid molecule comprises a 5 '-cap or a 3 '-cap or both a 5 '-cap and a 3 '-cap.

215. The enzymatic nucleic acid molecule of claim 214, wherein said 5 '-cap is a phosphorothioate modification of at least one 5 '-terminal nucleotide in said enzymatic nucleic acid molecule.

216. The enzymatic nucleic acid molecule of claim 214, wherein said 5 '-cap is a phosphorothioate modification of at least two 5 '-terminal nucleotide in said enzymatic nucleic acid molecule.

217. The enzymatic nucleic acid molecule of claim 214, wherein said 5'-cap is a phosphorothioate modification of at least three 5 '-terminal nucleotide in said enzymatic nucleic acid molecule.

218. The enzymatic nucleic acid molecule of claim 214, wherein said 3 '-cap is a 3'- 3 ' inverted abasic moiety.

219. The enzymatic nucleic acid molecule of claim 214, wherein said 3'-cap is a 3'- 3' inverted nucleotide moiety.

220. A method for inhibiting expression of a gene in a cell, comprising the step of administering to said cell the enzymatic nucleic acid molecule of claims 186 or 187 under conditions suitable for said inhibition.

221. A method of cleaving a separate RNA molecule comprising, contacting the enzymatic nucleic acid molecule of claims 186 or 187 with said separate RNA molecule under conditions suitable for the cleavage of said separate RNA molecule.

222. The method of claim 221, wherein said cleavage is carried out in the presence of a divalent cation.

223. The method of claim 222, wherein said divalent cation is Mg2+.

224. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said enzymatic nucleic acid molecule has an endonuclease activity to cleave RNA derived from HER2 gene.

225. The enzymatic nucleic acid molecule of claim 224, wherein said enzymatic nucleic acid molecule comprises sequences complementary to any of NCH substrate sequence of Table 34.

226. The enzymatic nucleic acid molecule of claim 224, wherein said enzymatic nucleic acid molecule comprises any of the NCH ribozyme sequences shown in Table 34.

227. The enzymatic nucleic acid molecule of claim 224, wherein said enzymatic nucleic acid molecule is used to treat cancer.

228. The enzymatic nucleic acid molecule of claim 224, wherein said cancer is breast cancer.

229. The enzymatic nucleic acid molecule of claim 224, wherein said enzymatic nucleic acid molecule is used to treat conditions associated with the level of HER2 gene.

230. An enzymatic nucleic acid molecule, wherein said enzymatic nucleic acid molecule comprises any of sequence shown as NCH ribozyme sequence in Table 31.

231. The enzymatic nucleic acid molecule of claim 224, wherein said enzymatic nucleic acid molecule comprises a substrate binding region which has between 5 and 30 nucleotides complementary to the RNA.

232. The enzymatic nucleic acid molecule of claim 224, wherein said enzymatic nucleic acid molecule comprises a substrate binding region which has between 7 and 12 nucleotides complementary to the RNA.

233. A mammalian cell including the enzymatic nucleic acid molecule of claim 224, wherein said mammalian cell is not a living human.

234. The mammalian cell of claim 233, wherein said mammalian cell is a human cell.

235. A mammalian cell including the enzymatic nucleic acid molecule of claims 186 or 187, wherein said mammalian cell is not a living human.

236. The mammalian cell of claim 235, wherein said mammalian cell is a human cell.

237. A method for inhibiting expression of HER2 gene in a cell, comprising the step of administering to said cell the enzymatic nucleic acid molecule of claim 224 under conditions suitable for said inhibition.

238. A method of cleaving RNA derived from HER2 gene comprising, contacting the enzymatic nucleic acid molecule of claim 224 with said RNA molecule under conditions suitable for the cleavage of said RNA molecule.

239. A pharmaceutical composition comprising the enzymatic nucleic acid molecule of any of claims 186 or 187.

240. A pharmaceutical composition comprising the enzymatic nucleic acid molecule of claim 224.

241. A method of treatment of a patient having a condition associated with the level of HER2, wherein said patient is administered the enzymatic nucleic acid molecule of claim 224 under conditions suitable for said treatment.

242. The method of claim 241, wherein said method is performed in conjunction with one or more other therapies.

243. The enzymatic nucleic acid molecule of claim 227, wherein said enzymatic nucleic acid molecule is used in conjunction with one or more other therapies.

244. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said nucleic acid molecule comprises at least five ribose residues; a 2'-C-allyl modification at position No. 4 of said enzymatic nucleic acid; at least ten 2'-O- alkyl modifications, and a 3'- cap structure.

245. The enzymatic nucleic acid molecule of claim 244, wherein said 2'-O-alkyl modifications is selected from the group consisting of 2'-O-methyl and 2'-O-allyl.

246. The enzymatic nucleic acid molecule of claim 244, wherein said 3 '-cap is 3 '-3' inverted abasic moiety.

247. The enzymatic nucleic acid molecule of claim 244, wherein said 3'-cap is 3'-3' inverted nucleotide.

248. The enzymatic nucleic acid molecule of claim 244, wherein said enzymatic nucleic acid comprises phosphorothioate linkages in at least three ofthe 5' terminal nucleotides.

249. The enzymatic nucleic acid molecule of claims 186 or 187, wherein said nucleic acid molecule comprises at least five ribose residues; a 2'-deoxy-2' -amino modification at position Nos. 4 and 7 of said enzymatic nucleic acid; at least ten 2'- O-alkyl modifications, and a 3'- cap structure.

250. The enzymatic nucleic acid molecule of claim 249, wherein said 2'-O-alkyl modifications is selected from the group consisting of 2'-O-methyl and 2'-O-allyl.

251. The enzymatic nucleic acid molecule of claim 249, wherein said 3 '-cap is 3 '-3' inverted abasic moiety.

252. The enzymatic nucleic acid molecule of claim 249, wherein said 3'-cap is 3'-3' inverted nucleotide.

253. The enzymatic nucleic acid molecule of claim 249, wherein said enzymatic nucleic acid comprises phosphorothioate linkages in at least three ofthe 5' terminal nucleotides.

254. The enzymatic nucleic acid molecule of claim 224, wherein said enzymatic nucleic acid molecule comprises at least one sugar modification.

255. The enzymatic nucleic acid molecule of claim 224, wherein said enzymatic nucleic acid molecule comprises at least one nucleic acid base modification.

256. The enzymatic nucleic acid molecule of claim 224, wherein said enzymatic nucleic acid molecule comprises at least one phosphate backbone modification.

257. The enzymatic nucleic acid molecule of claim 224, wherein said phosphate backbone modification is selected from the group consisting of phosphorothioate, phosphorodithioate and amide.

258. The enzymatic nucleic acid molecule of claim 224, wherein said nucleic acid molecule comprises at least five ribose residues; a 2'-C-allyl modification at position No. 4 of said enzymatic nucleic acid; at least ten 2'-O-alkyl modifications, and a 3'- cap structure.

259. The enzymatic nucleic acid molecule of claim 258, wherein said 2'-O-alkyl modifications is selected from the group consisting of 2'-O-methyl and 2'-O-allyl.

260. The enzymatic nucleic acid molecule of claim 258, wherein said 3'-cap is 3'-3' inverted abasic moiety.

261. The enzymatic nucleic acid molecule of claim 258, wherein said 3'-cap is 3'-3' inverted nucleotide.

262. The enzymatic nucleic acid molecule of claim 258, wherein said enzymatic nucleic acid comprises phosphorothioate linkages in at least three ofthe 5' terminal nucleotides.

263. The enzymatic nucleic acid molecule of claim 224, wherein said nucleic acid molecule comprises at least five ribose residues; a 2'-deoxy-2'-amino modification at position Nos. 4 and 7 of said enzymatic nucleic acid; at least ten 2'-O-alkyl modifications, and a 3'- cap structure.

264. The enzymatic nucleic acid molecule of claim 263, wherein said 2'-O-alkyl modifications is selected from the group consisting of 2'-O-methyl and 2'-O-allyl.

265. The enzymatic nucleic acid molecule of claim 263, wherein said 3 '-cap is 3 '-3' inverted abasic moiety.

266. The enzymatic nucleic acid molecule of claim 263, wherein said 3 '-cap is 3 '-3' inverted nucleotide.

267. The enzymatic nucleic acid molecule of claim 263, wherein said enzymatic nucleic acid comprises phosphorothioate linkages in at least three ofthe 5' terminal nucleotides.

268. The enzymatic nucleic acid molecule of claim 186, wherein said enzymatic nucleic acid molecule is capable of down-regulating the expression of protein kinase C alpha (PKC alpha) gene.

269. A method for inhibiting expression of a PKC alpha gene in a cell, comprising the step of administering to said cell the enzymatic nucleic acid molecule of claim

268 under conditions suitable for said inhibition.

270. A method of cleaving a PKC alpha RNA molecule comprising, contacting the enzymatic nucleic acid molecule of claim 268 with said separate PKC alpha RNA molecule under conditions suitable for the cleavage of said PKC alpha RNA molecule.

271. The method of claim 270, wherein said cleavage is carried out in the presence of a divalent cation.

272. The method of claim 271, wherein said divalent cation is Mg2+.

273. The enzymatic nucleic acid molecule of claim 268, wherein said enzymatic nucleic acid molecule has an endonuclease activity to cleave RNA derived from

PKC alpha gene.

274. The enzymatic nucleic acid molecule of claim 273, wherein said enzymatic nucleic acid molecule comprises sequences complementary to any of NCH substrate sequence of Table 63.

275. The enzymatic nucleic acid molecule of claim 273 wherein said enzymatic nucleic acid molecule comprises any of the NCH ribozyme sequences shown in Table 63.

276. The enzymatic nucleic acid molecule of claim 268, wherein said enzymatic nucleic acid molecule is used to treat cancer.

277. The enzymatic nucleic acid molecule of claim 276, wherein said cancer is selected from the group consisting of lung, breast, colon, prostate, bladder, ovary, melanoma, and glioblastoma cancer.

278. The enzymatic nucleic acid molecule of claim 268, wherein said enzymatic nucleic acid molecule is used to treat conditions associated with the level of PKC alpha gene.

279. The enzymatic nucleic acid molecule of claim 268, wherein said D and E independently has between 5 and 30 nucleotides complementary to the RNA.

280. The enzymatic nucleic acid molecule of claim 268, wherein said D and E independently has between 7 and 12 nucleotides complementary to the RNA.

281. A mammalian cell including the enzymatic nucleic acid molecule of claim 268, wherein said mammalian cell is not a living human.

282. The mammalian cell of claim 281, wherein said mammalian cell is a human cell.

283. A pharmaceutical composition comprising the enzymatic nucleic acid molecule of claim 238.

284. A pharmaceutical composition comprising the enzymatic nucleic acid molecule of claim 273.

285. A method of treatment of a patient having a condition associated with the level of PKC alpha, wherein said patient is administered the enzymatic nucleic acid molecule of claim 268 under conditions suitable for said treatment.

286. The method of claim 285, wherein said method is performed in conjunction with one or more other therapies.

287. The enzymatic nucleic acid molecule of claim 286, wherein said enzymatic nucleic acid molecule is used in conjunction with one or more other therapies.

288. An antisense nucleic acid molecule comprising sequence complementary to any of substrate sequence in Tables 13-23.

289. The antisense nucleic acid molecule of claim 288, wherein said enzymatic nucleic acid is chemically synthesized.

290. The antisense nucleic acid molecule of claim 288, wherein said antisense nucleic acid comprises at least one 2'-sugar modification.

291. The antisense nucleic acid molecule of claim 288, wherein said antisense nucleic acid comprises at least one nucleic acid base modification.

292. The antisense nucleic acid molecule of claim 288, wherein said antisense nucleic acid comprises at least one phosphate backbone modification.

293. A mammalian cell including the antisense nucleic acid molecule of claim 288, wherein said mammalian cell is not a living human.

294. The mammalian cell of claim 293, wherein said mammalian cell is a human cell.