WO1993000353A1 - Sequences characteristic of human gene transcription product - Google Patents

Sequences characteristic of human gene transcription product Download PDF

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Publication number
WO1993000353A1
WO1993000353A1 PCT/US1992/005222 US9205222W WO9300353A1 WO 1993000353 A1 WO1993000353 A1 WO 1993000353A1 US 9205222 W US9205222 W US 9205222W WO 9300353 A1 WO9300353 A1 WO 9300353A1
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seq
sequence
sequences
length
strandedness
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PCT/US1992/005222
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French (fr)
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J. Craig Venter
Mark D. Adams
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The United States Of America, As Represented By The Secretary, Department Of Health And Human Services
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Priority to EP92914421A priority Critical patent/EP0593580A4/en
Publication of WO1993000353A1 publication Critical patent/WO1993000353A1/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1096—Processes for the isolation, preparation or purification of DNA or RNA cDNA Synthesis; Subtracted cDNA library construction, e.g. RT, RT-PCR
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers

Definitions

  • the present invention relates to newly identified polynucleotide sequences corresponding to transcription products of human genes, and to complete gene sequences associated therewith.
  • This invention relates to human genes. Identification and sequencing of human genes is a major goal of modern scientific research. The sequence of human genes is more than just a scientific curiosity. For example, by identifying genes and determining their sequences, scientists have been able to make large quantities of valuable human "gene products.” These include human insulin, interferon, Factor VIII, tumor necrosis factor, human growth hormone, tissue plas inogen activator, and numerous other compounds. Additionally, knowledge of gene sequences can provide the key to treatment or cure of genetic diseases (such as muscular dystrophy and cystic fibrosis) . The present invention represents a quantum leap forward in civilization's knowledge of human gene sequences. There are several basic concepts of molecular biology which figure prominently in the invention. A brief explanation of those concepts follows.
  • the present invention is based on identification and characterization of gene segments.
  • Genes are the basic units of inheritance. Each gene is a string of connected bases called nucleotides. Most genes are formed of deoxyribonucleic acid, DNA. (Some viruses contain genes of ribonucleic acid, RNA.) The genetic information resides in the particular sequence in which the bases are arranged. A short sequence of nucleotides is often called a polynucleotide or an oligonucleotide.
  • polypeptides are built from long strings of individual units. These units are amino acids.
  • the nucleotide sequence of a gene tells the cell the sequence in which to arrange the amino acids to make the polypeptide encoded by that gene.
  • chains of up to about 200 amino acids are called polypeptides, while proteins are larger molecules made up of polypeptide subunits; both types of molecules are referred to generally herein as polypeptides.
  • a triplet of nucleotides (codon) in DNA codes for each amino acid or signals the beginning or end of the message (anticodon) .
  • the term codon is also used for the corresponding (and complementary) sequences of three nucleotides in the mRNA into which the original DNA sequence is transcribed.
  • RNA messenger RNA
  • mRNA messenger RNA
  • the mRNA in turn, can be translated into a polypeptide by the cell. This entire process is called gene expression, and the polypeptide is the gene product encoded by the gene.
  • cDNA complementary DNA
  • the various types of genes include those which code for polypeptides, those which are transcribed into RNA but are not translated into polypeptides, and those whose functional significance does not demand that they be transcribed at all. Most genes are found on large molecules of DNA located in chromosomes.
  • Double stranded cDNA carries all the information of a gene. Each base of the first strand is joined to a complementary base (hybridized) in the second strand.
  • the linear DNA molecules in chromosomes have thousands of genes distributed along their length. Chromosomes include both coding regions (coding for polypeptides) and noncoding regions; the coding regions represent only about three percent of the total chromosome sequence.
  • An individual gene has regulatory regions that include a promoter which directs expression of the gene, a coding region which can code for a polypeptide, and a termination signal.
  • the regulatory DNA sequence is usually a noncoding region that determines if, where, when, and at what level a particular gene is expressed.
  • the coding regions of many genes are discontinuous, with coding sequences (exons) alternating with noncoding regions (introns) .
  • the final mRNA copy of the gene does not include these introns (which can be much longer than the coding region itself) , although it does contain certain untranslated regions that usually do not code for the polypeptide gene product.
  • Untranslated sequences at the beginning and end of the mRNA are known as 5 1 - and 3'-untranslated regions, respectively. This nomenclature reflects the orientation of the nucleotide constituents of the mRNA.
  • a cDNA is a DNA copy of a messenger RNA, which contains all of the exons of a gene.
  • the cDNA can be thought of as having three parts: an untranslated 5* leader, an uninterrupted polypeptide-coding sequence, and a 3' untranslated region.
  • the untranslated leader and trailing sequences are important for initiation of translation, mRNA stability, and other functions.
  • the untranslated leader and trailing sequences are called 5'- and 3 '-untranslated sequences, respectively.
  • the 3' untranslated sequence is usually longer than the 5' untranslated leader, and can be longer than the polypeptide-coding sequence.
  • the untranslated regions typically have many, randomly-distributed stop codons, and do not display the nonrandom base arrangements found in coding sequences.
  • the 5'-untranslated sequence is relatively short, generally between 20 and 200 bases.
  • the 3 1 - untranslated sequence is often many times longer, up to several thousand bases.
  • the translated or coding sequence begins with a translational start codon (AUG or GUG) and ends with a translational stop codon (UAA, UGA, or UAG) .
  • translation begins at the first "start” codon on the mRNA and proceeds to the first "stop” codon.
  • Coding sequences can be distinguished by their nonrandom distribution of bases; numerous computer algorithms have been developed to distinguish coding from noncoding regions in this way.
  • Human DNA differs from person to person. No two persons (except perhaps identical twins) have identical DNA. While the differences, called allelic variations or polymorphisms, are slight on a molecular level, they account for most of the physical and other observable differences between individuals. It has been estimated that approximately 14 million sequence polymorphism differences exist between individuals.
  • PCR polymerase chain reaction
  • Primer extension proceeds inward across the region between the two primers, and the product of DNA synthesis of one primer serves as a template for the other primer. Repeated cycles of DNA denaturation, annealing of primers, and extension result in an exponential increase in the number of copies of the region bounded by the primers.
  • a labeled segment of single-stranded DNA can be hybridized to a longer DNA sequence, such as a chromosome, to mark a specific location on the longer sequence. Segments of DNA 50 bases long or longer that hybridize to a unique DNA location in the human genome are extremely unlikely to hybridize elsewhere in the human genome.
  • the Human Genome Project is an effort to sequence all human DNA (the human genome) .
  • the human genome is estimated to comprise 50,000 - 100,000 genes, up to 30,000 of which might be expressed in the brain (Sutcliffe, Ann. Rev. Neurosci. 11:157 (1988)).
  • Once dedicated human chromosome sequencing begins in three to five years, it was expected that 12-15 years will be required to complete the sequence of the genome (Report of the Ad Hoc Program Advisory Committee on Complex Genomes, Reston, Va. , Feb. 1988, D. Baltimore Ed. (NIH, Bethesda, Md, 1988)).
  • the majority of human genes would remain unknown for at least the next decade.
  • the present invention can greatly accelerate the pace at which human genes can be identified and mapped.
  • GenBank listed the sequences of only a few thousand human genes and less than two hundred human brain mRNAs (GenBank Release 66.0, December, 1990).
  • cDNA sequencing complementary DNA
  • Genomic sequencing proponents have argued the difficulty of finding every mRNA expressed in all tissues, cell types, and developmental states, and that much valuable information from intronic and intergenic regions, including control and regulatory sequences, will be missed by cDNA sequencing. (Report of the Committee on Mapping and Sequencing the Human Genome, National Research Council (National Academy Press, Washington, D.C. 1988)). Further, sequencing of transcribed regions of the genome using cDNA libraries has heretofore been considered impractical or unsatisfactory. Libraries of cDNA were believed to be dominated by repetitive elements, mitochondrial genes, ribosomal RNA genes, and other nuclear genes comprising common or housekeeping sequences.
  • cDNA libraries would provide few sequences corresponding to structural and regulatory polypeptides or peptides. See, for example, Putney, et al.. Nature 302;718- 721 (1983) . Putney, et al. sequenced over 150 clones from a rabbit muscle cDNA library and identified clones for 13 of the 19 known muscle polypeptides, including one new isotype but no unknown coding sequences.
  • Another perceived drawback of cDNA sequencing was that some mRNAs are abundant, and some are rare. The cellular quantities of mRNA from various genes can vary by several orders of magnitude. This led critics to believe that most information obtained from cDNA sequencing would be repetitious and useless.
  • cDNA sequencing now provides a rapid method for obtaining enormous amounts of valuable genetic information and DNA products of great utility for the biotechnology and pharmaceutical industries. Not only can many distinct cDNAs be isolated and sequenced, even partial cDNAs can be used, with conventional, well-understood methods, to isolate entire genes, and to determine the chromosomal locations and biological functions of these genes. As is demonstrated here, fragments of only a few hundred bases are sufficient, in many cases, to identify the probable function of a new human gene if it is similar in structure to a gene from another animal, or from plants or bacteria.
  • fragments of untranslated regions of a cDNA can be used to: i) isolate the coding sequence of the cDNA; ii) isolate the complete gene; iii) determine the position of the gene on a human chromosome, and hence the potential of the gene to cause a human genetic disease; and iv) determine the function of the gene by means of experiments in which the function of the native gene is disrupted by the addition of a short DNA fragment to the cell, e.g., using triple helix or antisense probes. Because coding regions comprise such a small portion of the human genome, identification and mapping of transcribed regions and coding regions of chromosomes is of significant interest.
  • ESTs styled Expressed Sequence Tags
  • STSs random genomic DNA sequence tagged sites
  • aspects of the present invention thus include the individual ESTs, corresponding partial and complete cDNA, genomic DNA, mRNA, antisense strands, triple helix probes, PCR primers, coding regions, and constructs. Also, where one skilled in the art is enabled by this specification to prepare expression vectors and polypeptide expression products, they are also within the scope of the present invention, along with antibodies, especially monoclonal antibodies, to such expression products.
  • ESTs from cDNA Libraries The sequences of the present invention were isolated from commercially available and custom made cDNA libraries using a rapid screening and sequencing technique.
  • the method comprises applying conventional automated DNA sequencing technology to screening clones, advantageously randomly selected clones, from a cDNA library.
  • the library is initially "enriched” through removal of ribosomal sequences and other common sequences prior to clone selection.
  • ESTs are generated from partial DNA sequencing of the selected clones.
  • the ESTs of the present invention were generated using low redundancy of sequencing, typically a single sequencing reaction. While single sequencing reactions may have an accuracy as low as 97%, this nevertheless provides sufficient fidelity for identification of the sequence and design of PCR primers.
  • Exon amplification works by artificially expressing part or all of a gene that is contained in a cloned fragment of genomic DNA such as a cosmid or yeast artificial chromosome
  • YAC YAC
  • MIT that uses control elements from virus genes to express the protein-coding exons of the human gene of interest.
  • Exon trapping shows considerable promise as a general technique for identifying those genes in the human genome that cannot be found by cDNA cloning and EST sequencing.
  • Exon amplification will also be useful for identifying the genes in regions of genomic DNA to which disease genes have been mapped.
  • the exon amplification method can be used directly with the cosmid and
  • ESTs comprise DNA sequences corresponding to a portion of nuclear encoded messenger RNA.
  • An EST is of sufficient length to permit: (1) amplification of the specific sequence from a cDNA library, e.g., by polymerase chain reaction (PCR); (2) use of a synthetic polynucleotide corresponding to a partial or complete sequence of the EST as a hybridization probe of a cDNA library, generally having 30 - 50 base pairs; or (3) unique designation of the pure cDNA clone from which the EST was derived (the EST clone) for use as a hybridization probe of a cDNA library.
  • EST-derived primer pairs and sequences amplify or detectably hybridize to a sequence from a genomic library.
  • the ESTs disclosed herein are generally at least 150 base pairs in length.
  • the length of an EST is determined by the quality of sequencing data and the length of the cloned cDNA.
  • Raw data from the automated sequencers is edited to remove low quality sequence at the end of the sequencing run.
  • High quality sequences (usually a result of sequencing templates without excessive salt contamination) generally give about 400 bp of reliable sequence data; other sequences give fewer bases of reliable data.
  • a 150 bp EST is long enough to be translated into a 50 amino acid peptide sequence. This length is sufficient to observe similarities when they exist in a database search.
  • 150 bp is long enough to design PCR primers from each end of the sequence to amplify the complete EST. Sequences shorter than 150 bp are difficult to purify and use following PCR amplification. Furthermore, a 150 bp polynucleotide is likely to give a very strong signal with low background in a screen of a genomic library. Finally, it is highly unlikely that a sequence of the same 150 bp exists in any genes in the genome besides the one tagged by the EST. Some closely related gene family members have very similar nucleotide sequences, but no examples of pairs of human genes with long segments of identical sequence have been reported to date. For instance, there are three known ⁇ -tubulin genes in humans.
  • ESTs were found that matched one or another of these tubulin genes, but several new members of this gene family were also found and could be clearly distinguished from the three known members. ESTs that match perfectly to several different genes can be detected by hybridizing to chromosomes: if many chromosomal loci are observed, the sequence (or a close variant) is present in more than one gene. This problem can be circumvented by using the 3'-untranslated part of the cDNA alone as a probe for the chromosomal location or for the full-length cDNA or gene. The 3'-untranslated region is more likely to be unique within gene families, since there is no evolutionary pressure to conserve a coding function of this region of the mRNA.
  • ESTs can be used to map the expressed sequence to a particular chromosome.
  • ESTs can be expanded to provide the full coding regions, as detailed below. In this manner, previously unknown genes can be identified.
  • cDNA libraries can be used to obtain ESTs
  • human brain cDNA libraries are exemplified and represent a preferred embodiment.
  • Suitable cDNA libraries can be freshly prepared or obtained commercially, e.g. , as shown in Examples 1 and 9.
  • the cDNA libraries from the desired tissue are preferably preprocessed by conventional techniques to reduce repeated sequencing of high and intermediate abundance. clones and to maximize the chances of finding rare messages from specific cell populations.
  • preprocessing includes the use of defined composition prescreening probes, e.g., cDNA corresponding to mitochondria, abundant sequences, riboso es, actins, myelin basic polypeptides, or any other known high abundance peptide; these prescreening probes used for preprocessing are generally derived from known ESTs.
  • Other useful preprocessing techniques include subtraction, which preferentially reduces the population of certain sequences in the library (e.g., see A. Swaroop et al., Nucl. Acids Res. 19:1954 (1991)), and normalization, which results in all sequences being represented in approximately equal proportions in the library (Patanjali et al, Proc. Natl. Acad. Sci. USA 88:1943 (1991)).
  • the cDNA libraries used in the present method will ideally use directional cloning methods so that either the 5' end of the cDNA (likely to contain coding sequence) or the 3' end (likely to be a non-coding sequence) can be selectively obtained.
  • Libraries of cDNA can also be generated from recombinant expression of genomic DNA. After they are amplified, ESTs can be obtained and sequenced, e.g., as illustrated in Example 9.
  • sequences of the present invention include the specific sequences set forth in the Sequence Listing and designated SEQ ID NO: 1 - SEQ ID NO: 315. In one aspect of this embodiment, the invention relates to those sequences of
  • SEQ ID NOS: 1 - 315 that comprise the cDNA coding sequences for polypeptides having less than 95% identity with known amino acid sequences (see Table 2) and more preferably less than 90% or 85% identity.
  • the invention relates to those sequences of SEQ ID NOS: 1 - 315 that encode polypeptides having no similarity to known amino acid sequences (see Examples that follow) . Precisely because they do not contain coding regions and are therefore more unique in their sequence structures, those sequences which meet neither of the preceding criteria can be most useful and are generally preferred for mapping.
  • the ESTs of the present invention generally represent relatively small coding regions or untranslated regions of human genes. Although most of these sequences do not code for a complete gene product, the ESTs of the present invention are highly specific markers for the corresponding complete coding regions.
  • the ESTs are of sufficient length that they will hybridize, under stringent conditions, only with DNA for that gene to which they correspond.
  • Suitably stringent conditions comprise conditions, for example, where at least 95%, preferably at least 97% or 98% identity (base pairing) , is required for hybridization. This property permits use of the EST to isolate the entire coding region and even the entire sequence. Therefore, only routine laboratory work is necessary to parlay the unique EST sequence into the corresponding unique complete gene sequence.
  • each of the ESTs of the present invention "corresponds" to a particular unique human gene.
  • Knowledge of the EST sequence permits routine isolation and sequencing of the complete coding sequence of the corresponding gene.
  • the complete coding sequence is present in a full-length cDNA clone as well as in the gene carried on genomic clones. Therefore, each EST "corresponds" to a cDNA (from which the EST was derived) , a complete genomic gene sequence, a polypeptide coding region (which can be obtained either from the cDNA or genomic DNA) , and a polypeptide or amino acid sequence encoded by that region.
  • the first step in determining where an EST is located in the cDNA is to analyze the EST for the presence of coding sequence, e.g., as described in Example 12.
  • the CRM program predicts the extent and orientation of the coding region of a sequence. Based on this information, one can infer the presence of start or stop codons within a sequence and whether the sequence is completely coding or completely non-coding. If start or stop codons are present, then the EST can cover both part of the 5•-untranslated or 3'-untranslated part of the mRNA (respectively) as well as part of the coding sequence. If no coding sequence is present, it is likely that the EST is derived from the 3'-untranslated sequence due to its longer length and the fact that most cDNA library construction methods are biased toward the 3• end of the mRNA.
  • Radiolabel the isolated insert DNA e.g., with 32 P labels, preferably by nick translation or random primer labeling.
  • Radiolabel the isolated insert DNA e.g., with 32 P labels, preferably by nick translation or random primer labeling.
  • EST is a specific tag for a messenger RNA molecule.
  • the complete sequence of that messenger RNA, in the form of cDNA can be determined using the EST as a probe to identify a cDNA clone corresponding to a full-length transcript, followed by sequencing of that clone.
  • the EST or the full- length cDNA clone can also be used as a probe to identify a genomic clone or clones that contain the complete gene including regulatory and promoter regions, exons, and introns.
  • ESTs are used as probes to identify the cDNA clones from which an EST was derived.
  • ESTs, or portions thereof can be nick-translated or end-labelled with 32 P using polynucleotide kinase and labelling methods known to those with skill in the art (Basic Methods in Molecular Biology, L.G. Davis, M.D. Dibner, and J.F. Battey, ed. , Elsevier Press, NY, 1986).
  • the lambda library can be directly screened with the labelled ESTs of interest or the library can be converted en masse to pBluescript (Stratagene, La Jolla, California) to facilitate bacterial colony screening. Both methods are well known in the art.
  • filters with bacterial colonies containing the library in pBluescript or bacterial lawns containing lambda plaques are denatured and the DNA is fixed to the filters.
  • the filters are hybridized with the labelled probe using hybridization conditions described by Davis et al.
  • the ESTs, cloned into lambda or pBluescript, can be used as positive controls to assess background binding and to adjust the hybridization and washing stringencies necessary for accurate clone identification.
  • the resulting autoradiograms are compared to duplicate plates of colonies or plaques; each exposed spot corresponds to a positive colony or plaque.
  • the colonies or plaques are selected, expanded and the DNA is isolated from the colonies for further analysis and sequencing.
  • the ESTs can additionally be used to screen Northern blots of mRNA obtained from various tissues or cell cultures, including the tissue of origin of the EST clone. Northern analysis will most often produce one to several positive bands. The bands can be selected for further study based on the predicted size of the mRNA.
  • Positive cDNA clones in phage lambda are analyzed to determine the amount of additional sequence they contain using PCR with one primer from the EST and the other primer from the vector.
  • Clones with a larger vector-insert PCR product than the original EST clone are analyzed by restriction digestion and DNA sequencing to determine whether they contain an insert of the same size or similar as the mRNA size on a Northern blot. Once one or more overlapping cDNA clones are identified, the complete sequence of the clones can be determined.
  • the preferred method is to use exonuclease III digestion (McCombie, W.R, Kirkness, E., Fleming, J.T., Kerlavage, A.R., Iovannisci, D.M. , and Martin-Gallardo, R. , Methods: 3: 33-40, 1991) .
  • A- series of deletion clones is generated, each of which is sequenced.
  • the resulting overlapping sequences are assembled into a single contiguous sequence of high redundancy (usually three to five overlapping sequences at each nucleotide position) , resulting in a highly accurate final sequence.
  • a similar screening and clone selection approach can be applied to obtaining cosmid or lambda clones from a genomic DNA library that contains the complete gene from which the EST was derived (Kirkness, E.F., Kusiak, J.W., Menninger, J. , Gocayne, J.D., Ward, D.C., and Venter, J.C. Genomics 10: 985- 995 (1991) .
  • these genomic clones can also be sequenced in their entirety.
  • a shotgun approach is preferred to sequencing clones with inserts longer than 10 kb (genomic cosmid and lambda clones) .
  • the clone is randomly broken into many small pieces, each of which is partially sequenced. The sequence fragments are then aligned to produce the final contiguous sequence with high redundancy.
  • An intermediate approach is to sequence just the promoter region and the intron-exon boundaries and to estimate the size of the introns by restriction endonuclease digestion (ibid.).
  • the polynucleotides of the present invention can be derived from natural sources or synthesized using known methods. The sequences falling within the scope of the present invention are not limited to the specific sequences described, but include human allelic and species variations thereof and portions thereof of at least 15-18 bases.
  • sequences of at least 15-18 bases can be used, for example, as PCR primers or as DNA probes.
  • the invention includes the entire coding sequence associated with the specific polynucleotide sequence of bases described in the Sequence Listing, as well as portions of the entire coding sequence of at least 15-18 bases and allelic and species variations thereof.
  • the invention includes sequences coding for the same amino acid sequences as do the specific sequences disclosed herein.
  • sequences, constructs, vectors, clones, and other materials comprising the present invention can advantageously be in enriched or isolated form.
  • enriched means that the concentration of the material is at least about 2, 5, 10, 100, or 1000 times its natural concentration (for example) , advantageously 0.01%, by weight, preferably at least about 0.1% by weight. Enriched preparations of about 0.5%, 1%, 5%, 10%, and 20% by weight are also contemplated. Further, removal of clones corresponding to ribosomal RNA and "housekeeping" genes and clones without human cDNA inserts results in a library that is "enriched" in the desired clones.
  • isolated requires that the material be removed from its original environment (e.g., the natural environment if it is naturally occurring) .
  • a naturally- occurring polynucleotide present in a living animal is not isolated, but the same polynucleotide, separated from some or all of the coexisting materials in the natural system, is isolated. It is also advantageous that the sequences be in purified form.
  • purified does not require absolute purity; rather, it is intended as a relative definition. Individual EST clones isolated from a cDNA library have been conventionally purified to electrophoretic homogeneity. The sequences obtained from these clones could not be obtained directly either from the library or from total human DNA.
  • the cDNA clones are not naturally occurring as such, but rather are obtained via manipulation of a partially purified naturally occurring substance (messenger RNA) .
  • the conversion of mRNA into a cDNA library involves the creation of a synthetic substance (cDNA) and pure individual cDNA clones can be isolated from the synthetic library by clonal selection.
  • cDNA synthetic substance
  • purification of starting material or natural material to at least one order of magnitude, preferably two or three orders, and more preferably four or five orders of magnitude is expressly contemplated.
  • a cDNA library there are many species of mRNA represented.
  • Each cDNA clone can be interesting in its own right, but must be isolated from the library before further experimentation can be completed. In order to sequence any specific cDNA, it must be removed and separated (i.e. isolated and purified) from all the other sequences. This can be accomplished by many techniques known to those of skill in the art. These procedures normally involve identification of a bacterial colony containing the cDNA of interest and further amplification of that bacteria. Once a cDNA is separated from the mixed clone library, it can be used as a template for further procedures such as nucleotide sequencing. Although claims to large numbers of ESTs and corresponding sequences are presented herein, the invention is not limited to these particular groupings of sequences.
  • the present invention also includes recombinant constructs comprising one or more of the sequences as broadly described above.
  • the constructs comprise a vector, such as a plasmid or viral vector, into which a sequence of the invention has been inserted, in a sense or antisense orientation.
  • the construct further comprises regulatory sequences, including for example, a promoter, operably linked to the sequence.
  • a promoter operably linked to the sequence.
  • Eukar ⁇ otic pWLneo, pSV2cat, pOG44, pXTl, pSG (Stratagene); pSVK3, pBPV, pMSG, pSVL (Pharmacia).
  • Promoter regions can be selected from any desired gene using CAT (chloramphenicol transferase) vectors or other vectors with selectable markers.
  • Two appropriate vectors are pKK232-8 and pCM7.
  • Particular named bacterial promoters include lad, lacZ, T3, T7, gpt, lambda P R , and trc.
  • Eukaryotic promoters include CMV immediate early, HSV thymidine kinase, early and late SV40, LTRs from retrovirus, and mouse metallothionein-I. Selection of the appropriate vector and promoter is well within the level of ordinary skill in the art.
  • the present invention relates to host cells containing the above-described construct.
  • the host cell can be a higher eukaryotic cell, such as a mammalian cell, or a lower eukaryotic cell, such as a yeast cell, or the host cell can be a procaryotic cell, such as a bacterial cell.
  • Introduction of the construct into the host cell can be effected by calcium phosphate transfection, DEAE dextran mediated transfection, or electroporation (Davis, L. , Dibner, M. , Battey, I., Basic Methods in Molecular Biology, (1986)).
  • the constructs in host cells can be used in a conventional manner to produce the gene product coded by the recombinant sequence.
  • the encoded polypeptide can be synthetically produced by conventional peptide synthesizers.
  • Certain ESTs have already been preliminarily categorized by analogy to related sequences in other organisms (see Table 2) .
  • Table 10 of Example 8 categorizes particular ESTs broadly as metabolic, regulatory, and structural sequences where known. Constructs comprising genes or coding sequences corresponding to each of these categories are, therefore, specifically and individually contemplated.
  • Table 11 more particularly separates 27 new ESTs into 11 categories using a different criteria.
  • Table 11 further identifies the EST by the particular gene product for which it apparently codes. Each of these categories individually comprises a preferred category of EST, and preferred constructs and resulting polypeptide can be prepared from those ESTs or the corresponding complete gene sequence.
  • sequences identified herein can be used in numerous ways as polynucleotide reagents.
  • the sequences can be used as diagnostic probes for the presence of a specific mRNA in a particular cell type.
  • these sequences can be used as diagnostic probes suitable for use in genetic linkage analysis (polymorphisms) .
  • the sequences can be used as probes for locating gene regions associated with genetic disease, as explained in more detail below.
  • the EST and complete gene sequences of the present invention are also valuable for chromosome identification. Each sequence is specifically targeted to and can hybridize with a particular location on an individual human chromosome. Moreover, there is a current need for identifying particular sites on the chromosome. Few chromosome marking reagents based on actual sequence data (repeat polymorphisms) are presently available for marking chromosomal location. The present invention constitutes a major expansion of available chromosome markers.
  • ESTs and their corresponding complete sequences can be mapped to chromosomes.
  • the mapping of ESTs and cDNAs to chromosomes according to the present invention is an important first step in correlating those sequences with genes associated with disease.
  • sequences can be mapped to chromosomes by preparing PCR primers (preferably 15-25 bp) from the ESTs. Computer analysis of the ESTs is used to rapidly select primers that do not span more than one exon in the genomic DNA, thus complicating the amplification process. These primers are then used for PCR screening of somatic cell hybrids containing individual human chromosomes. Only those hybrids .containing the human gene corresponding to the EST will yield an amplified fragment.
  • PCR mapping of somatic cell hybrids is a rapid procedure for assigning a particular EST to a particular chromosome. Three or more clones can be assigned per day using a single thermal cycler. Using the present invention with the same oligonucleotide primers, sublocalization can be achieved with panels of fragments from specific chromosomes or pools of large genomic clones in an analogous manner.
  • Other mapping strategies that can similarly be used to map an EST to its chromosome include in situ hybridization, prescreening with labeled flow-sorted chromosomes, and preselection by hybridization to construct chromosome specific cDNA libraries. Results of mapping ESTs to chromosomal segments are listed in Tables 3 and 4.
  • Fluorescence in situ hybridization (FISH) of a cDNA clone to a metaphase chromosomal spread can be used to provide a precise chromosomal location in one step.
  • This technique can be used with cDNA as short as 500 or 600 bases; however, clones larger than 2,000 bp have a higher likelihood of binding to a unique chromosomal location with sufficient signal intensity for simple detection.
  • FISH requires use of the clone from which the EST was derived, and the longer the better. 2,000 bp is good, 4,000 is better, and more than 4,000 is probably not necessary to get good results a reasonable percentage of the time.
  • Ver a et al. Human Chromosomes: a Manual of Basic Techniques; Pergamon Press, New York (1988) .
  • Reagents for chromosome mapping can be used individually (to mark a single chromosome or a single site on that chromosome) or as panels of reagents (for marking multiple sites and/or multiple chromosomes) . Reagents corresponding to noncoding regions of the genes actually are preferred for mapping purposes. Coding sequences are more likely to be conserved within gene families, thus increasing the chance of cross hybridizations during chromosomal mapping (see Tables 8 and 9) .
  • a cDNA precisely localized to a chromosomal region associated with the disease could be one of between 50 and 500 potential causative genes. (This assumes l megabase mapping resolution and one gene per 20 kb.)
  • Comparison of affected and unaffected individuals generally involves first looking for structural alterations in the chromosomes, such as deletions or translocations that are visible from chromosome spreads or detectable using PCR based on that cDNA sequence. Ultimately, complete sequencing of genes from several individuals is required to confirm the presence of a mutation and to distinguish mutations from polymorphisms.
  • sequences of the invention can be used to control gene expression through triple helix formation or antisense DNA or RNA, both of which methods are based on binding of a polynucleotide sequence to DNA or RNA.
  • Polynucleotides suitable for use in these methods are usually 20 to 40 bases in length and are designed to be complementary to a region of the gene involved in transcription (triple helix - see Lee et al, Nucl. Acids Res. 6: 3073 (1979) ; Cooney et al, Science 241: 456 (1988); and Dervan et al. Science 251: 1360 (1991)) or to the mRNA itself (antisense - Okano, J.
  • the present invention is also a useful tool in gene therapy, which requires isolation of the disease-associated gene in question as a prerequisite to the insertion of a normal gene into an organism to correct a genetic defect.
  • the high specificity of the cDNA probes according to this invention have promise of targeting such gene locations in a highly accurate manner.
  • sequences of the present invention are also useful for identification of individuals from minute biological samples.
  • the United States military for example, is considering the use of restriction fragment length polymorphism (RFLP) for identification of its personnel.
  • RFLP restriction fragment length polymorphism
  • an individual's genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identifying personnel. This method does not suffer from the current 1imitations of "Dog Tags" which can be lost, switched, or stolen, making positive identification difficult.
  • the sequences of the present invention are useful as additional DNA markers for RFLP.
  • RFLP is a pattern based technique, which does not directly focus on the actual DNA sequence of the individual.
  • sequences of the present invention can be used to provide an alternative technique that determines the actual base-by-base DNA sequence of selected portions of an individual's genome. These sequences can be used to prepare PCR primers for amplifying and isolating such selected DNA.
  • Panels of corresponding DNA sequences from individuals can provide unique individual identifications, as each individual will have a unique set of such DNA sequences, due to allelic differences.
  • the sequences of the present invention can be used to particular advantage to obtain such identification sequences from individuals and from tissue, as explained in Examples 10 - 12.
  • the EST sequences from Example 1 and the complete sequences from Example 11 uniquely represent portions of the human genome. Allelic variation occurs to some degree in the coding regions of these sequences, and to a greater degree in the noncoding regions. It is estimated that allelic variation between individual humans occurs with a frequency of about once per each 500 bases.
  • Each of the ESTs or complete coding sequences comprising a part of the present invention can, to some degree, be used as a standard against which DNA from an individual can be compared for identification purposes. Because greater numbers of polymorphisms occur in the noncoding regions, fewer sequences are necessary to differentiate individuals.
  • the noncoding sequences of Table 9 for example, could comfortably provide positive individual identification with a panel of perhaps 100 to 1,000 primers which each yield a noncoding amplified sequence of 100 bp. If predicted coding sequences, such as those from Table 6, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.
  • a panel of reagents from ESTs or complete sequences of this invention is used to generate a unique ID database for an individual, those same reagents can later be used to identify tissue from that individual. Positive identification of that individual, living or dead can be made from extremely small tissue samples.
  • DNA-based identification techniques are in forensic biology.
  • PCR technology can be used to amplify DNA sequences taken from very small biological samples such as tissues, e.g., hair or skin, or body fluids, e.g., blood, saliva, semen, etc.
  • gene sequences are amplified at specific loci known to contain a large number of allelic variations, for example the DQ ⁇ class II HLA gene (Erlich, H. , PCR Technology, Freeman and Co. (1992)) .
  • this specific area of the genome is amplified, it is digested with one or more restriction enzymes to yield an identifying set of bands on a Southern blot probed with DNA corresponding to the DQ ⁇ class II HLA gene.
  • sequences of the present invention can be used to provide polynucleotide reagents specifically targeted to additional loci in the human genome, and can enhance the reliability of DNA-based forensic identifications. Those sequences targeted to noncoding regions (see, e.g.. Tables 8 and 9) are particularly appropriate. As mentioned above, actual base sequence information can be used for identification as an accurate alternative to patterns formed by restriction enzyme generated fragments. Reagents for obtaining such sequence information are within the scope of the present invention. Such reagents can comprise complete
  • reagents capable of identifying the source of a particular tissue. Such need arises, for example, in forensics when presented with tissue of unknown origin.
  • Appropriate reagents can comprise, for example, DNA probes or primers specific to particular tissue prepared from the ESTs or complete sequences of the present invention. Panels of such reagents can identify tissue by species and/or by organ type. In a similar fashion, these reagents can be used to screen tissue culture for contamination.
  • each EST corresponds not only to a coding region, but also to a polypeptide.
  • the coding sequence is known, or the gene is cloned which encodes the polypeptide, conventional techniques in molecular biology can be used to obtain the polypeptide.
  • the amino acid sequence encoded by the polynucleotide sequence can be synthesized using commercially available peptide synthesizers. This is particularly useful in producing small peptides and fragments of larger polypeptides. (Fragments are useful, for example, in generating antibodies against the native polypeptide.)
  • the DNA encoding the desired polypeptide can be inserted into a host organism and expressed.
  • the organism can be a bacterium, yeast, cell line, or multicellular plant or animal.
  • the literature is replete with examples of suitable host organisms and expression techniques.
  • naked polynucleotide DNA or mRNA
  • This methodology can be used to deliver the polypeptide to the animal, or to generate an immune response against a foreign polypeptide (Wolff, et al., Science 247:1465
  • the coding sequence, together with appropriate regulatory regions can be inserted into a vector, which is then used to transfect a cell.
  • the cell which may or may not be part of a larger organism
  • Antibodies generated against the polypeptide corresponding to a sequence of the present invention can be obtained by direct injection of the naked polypeptide into an animal (as above) or by administering the polypeptide to an animal, preferably a nonhuman. The antibody so obtained will then bind the polypeptide itself. In this manner, even a sequence encoding only a fragment of the polypeptide can be used to generate antibodies binding the whole native polypeptide. Such antibodies can then be used to isolate the polypeptide from tissue expressing that polypeptide.
  • a panel of such antibodies specific to a large number of polypeptides, can be used to identify and differentiate such tissue.
  • lambda ZAP libraries were converted en masse to pBluescript plasmids, transfected into E. coli XLl-Blue cells, and plated on X- gal/IPTG/ampicillin plates.
  • a total of 1058 clones were picked at random from three human brain cDNA libraries: fetal brain, two-year-old hippocampus, and two-year-old temporal cortex (Stratagene catalog #936206, 936205, 935, respectively.
  • Stratagene 11099 N. Torrey Pines Rd., La Jolla, CA 92037).
  • sequencing reactions were run on an Applied Biosystems, Inc. (Foster City, CA) 373A automated DNA sequencer.
  • Cycle sequencing was performed in a Perkin Elmer Thermal Cycler for 15 cycles of 95°C, 30 sec; 60°C, 1 sec; 70 ⁇ C, 60 sec and 15 cycles of 95°C, 30 sec; 70 ⁇ C, 60 sec with the Applied Biosystems, Inc. Taq Dye Primer Cycle Sequencing Core Kit protocol
  • Some sequencing reactions were performed on an ABI robotic workstation (Cathcart, Nature 347: 310 (1990) hereby incorporated by reference) .
  • the EST sequences from this Example 1 are identified as SEQ ID NOs 1-315.
  • ESTs including SEQ ID NOs 1-315 were analyzed as follows. Initially, the EST sequences were examined for similarities in the GenBank nucleic acid database (GenBank Release 65.0), Protein Information Resource Release 26.0 (PIR) , and ProSite (MacPattern from the EMBL data library, Fuchs R. Comput. Appl. Biosci. 7: 105 (1990) Release 5.0 were used). BLAST was used to search Genbank and the PIR (both maintained by the National Center for Biotechnology Information) ESTs without exact GenBank matches were translated in all six reading frames and each translation was compared with the protein sequence database PIR and the ProSite protein motif database. Comparisons with the ProSite motif database were done by means of the program MacPattern from the EMBL Data Library.
  • GenBank and PIR searches were conducted with the "basic local alignment search tool" programs for nucleotide (BLASTN) and peptide (BLASTX) comparisons (Altschul et al, J. Mol. Biol. 215: 403 (1990)). PIR searches were run on the National Center for Biotechnology Information BLAST network service.
  • the BLAST programs contain a very rapid database-searching algorithm that searches for local areas of similarity between two sequences and then extends the alignments on the basis of defined match and mismatch criteria. The algorithm does not consider the potential gaps to improve the alignment, thus sacrificing some sensitivity for a 6-80 fold increase in speed over other database-searching programs such as FASTA (Pegarson and Lipman, Proc. Natl. Acad. Sci. USA, 85: 2444 (1988)).
  • ESTs matched previously sequenced human nuclear genes with more than 97% identity.
  • Four of these ESTs are from genes encoding enzymes involved in maintaining metabolic energy, including ADP/ATP translocase, aldolase C, hexokinase, and phosphoglycerate kinase.
  • Human homologs of genes for the bovine mitochondrial ATP synthase F 0 B-subunit and porcine aconitase were also found (Table 2) .
  • Brain- specific cDNAs included synaptophysin, glial fibrillary acidic protein (GFAP) , and neurofilament light chain.
  • GFAP glial fibrillary acidic protein
  • ESTs are from genes encoding proteins involved in signal transduction: 2' ,3'-cyclic nucleotide 3'-phosphodiesterase (2 ESTs), calmodulin, c-erbA- ⁇ -2, G s ⁇ , and Na + /K* ATPase ⁇ -subunit.
  • Other ESTs were matches to genes for ubiquitous structural proteins — actins, tubulins, and fodrin (non-erythroid spectrin) .
  • ESTs also document the presence in the hippocampus cDNA library of the ret proto-oncogene, the ras-related gene rhoB, and one of the chromosome 22 breakpoint cluster region transcripts.
  • ESTs are from genes known to be associated with genetic disorders (Online Mendelian Inheritance in Manl . More than half of the human-matched ESTs from Example 1 have been mapped to chromosomes, indicating the bias of GenBank entries toward well-studied genes and proteins.
  • ESTs without significant GenBank matches were also compared to the ProSite database of recognized protein motifs. Not counting post-translational-modification signatures, fifty-four sequences contained motifs from the database. Some patterns, particularly the "leucine zipper", are found in scores or hundreds of proteins that do not share the functional property implied by the presence of the motif.
  • EST00299 SEQ ID NO:180
  • EST00283 SEQ ID NO:271
  • EST00248 SEQ ID NO:102
  • EST00248 SEQ ID NO:102
  • EST00248 SEQ ID NO:102
  • EST00248 SEQ ID NO:102
  • Similarities with an S. cerevisiae RNA polymerase subunit and Torpedo electromotor neuron- associated protein were also observed.
  • Two ESTs may represent new members of known human gene families: EST00270 matched the three ⁇ -tubulin genes with 88-91% identity and EST00271 (SEQ ID NO:248) matched ⁇ -actinin with 85% identity at the nucleotide level.
  • Enhancer of split protein interacts with a membrane protein that is the product of the Notch gene to convert a developmental signal into an altered pattern of gene expression (id. J. Mol. Biol. 215: 403 (1990)).
  • EST00256 (SEQ ID NO:188) matches near the 5' end of the Enhancer of split coding sequence, away from the mammalian G protein ⁇ subunit- and yeast cdc4-like elements (Hartley et al. Cell 55: 785 (1988); Klambt et al. EMBO J. 8: 203 (1989)).
  • EST00259 Part of the EST00259 (SEQ ID NO:227) match to Notch in the cdclO/SW16 region that is similar to three cell-cycle control genes in yeast and is tightly conserved in the Xenopus Notch homolog, Xotch. In Drosophila, Enhancer of split is absolutely required for formation of epidermal tissue. Notch contains several epidermal growth factor-like repeats and appears to play a general role in cell-cell communication during development (Banerjee and Zipursky, Neuron 4:177 (1990) ) . Seven genes were represented by more than one EST.
  • the program evaluates the likelihood that a given GG or CC dinucleotide represents a former exon-intron boundary. Specifically, every input strand is processed by the INTRON program twice, first evaluating the sense mRNA strand, and then processing the complementary or anti-sense strand. The program evaluates each sequence by finding all GG or CC pairs (possible former splice sites) , searching for STOP codons in all three reading frames, and analyzing the GG or CC pairs surrounded by stop codons. All regions of the EST that are unlikely to contain splice junctions based on CC content, GG content, and stop codon frequency are then marked by the program in uppercase.
  • PCR primers from known sequences is well known to those with skill in the art. For a review of PCR technology see Erlich, H.A. , PCR Technology; Principles and Applications for DNA Amplification. 1992; W.H. Freeman and Co., New York. ESTs were examined for the presence of stop codons in each reading frame and for consensus splice junctions. The presence of stop codons and absence of splice junction sequences are more characteristic of 3' untranslated sequences than of introns. The untranslated sequences are unique to a given gene; thus, primers from these regions are less likely to prime other members of a gene family or pseudogenes.
  • the primers were used in polymerase chain reactions (PCR) to amplify templates from total human genomic DNA.
  • PCR conditions were as follows: 60 ng of genomic DNA was used as a template for PCR with 80 ng of each oligonucleotide primer, 0.6 unit of Tag polymerase, and 1 uCu of a 32 P-labeled deoxycytidine triphosphate.
  • the PCR was performed in a microplate thermocycler (Techne) under the following conditions: 30 cycles of 94°C, 1.4 min; 55°C, 2 min; and 72°C, 2 min; with a final extension at 72°C for 10 min.
  • the amplified products were analyzed on a 6% polyacrylamide sequencing gel and visualized by autoradiography.
  • Somatic Cell Hybrid Mapping Panel Number 1 (NIGMS, Camden, NJ) .
  • PCR was used to screen a series of somatic cell hybrid cell lines containing defined sets of human chromosomes for the presence of a given EST.
  • DNA was isolated from the somatic hybrids and used as starting templates for PCR reactions using the primer pairs from EST sequences selected above. Only those somatic cell hybrids with chromosomes containing the human gene corresponding to the EST will yield an amplified fragment.
  • ESTs were assigned to a chromosome by analysis of the segregation pattern of PCR products from hybrid DNA templates. For a review of techniques and analysis of results from somatic cell gene mapping experiments. (See Ledbetter et al., Genomics 6:475- 481 (1990).) The single human chromosome present in all cell hybrids that give rise to an amplified fragment represents the chromosome containing that EST.
  • Example 3 The procedure of Example 3 is repeated for all of the ESTs from Example l not previously mapped to human chromosomes. Data are generated corresponding to the data in Table 3 for all of the unmapped ESTs. As previously mentioned, virtually all of the ESTs will map to a unique chromosomal location. The inability of any ESTs to localize to a unique location will be readily ascertainable during the mapping process.
  • This technique is used to map an EST to a particular location on a given chromosome.
  • Cell cultures, tissue, or whole blood can be used to obtain chromosomes.
  • 0.5 ml. of whole blood is added to RPMI 1640 and incubated 96 hours in a 5%C0 2 /37 ⁇ C incubator.
  • 0.05 ug/ml colcemide is added to the culture one hour before harvest.
  • Cells are collected and washed in PBS.
  • the suspension is incubated with a hypotonic solution of KC1 added dropwise to reach a final volume of 5 ml.
  • the cells are spun down and fixed by resuspending the cells in methanol and glacial acetic acid (3:1).
  • the cell suspension is dropped onto glass slides and dried. The slides are then treated with RNase A and washed then dehydrated in a series of increasing concentrations of ethanol.
  • the EST to be localized is nick-translated using fluorescently labeled nucleotide (Korenberg, Jr., et al., Cell 53(3) :391-400 (1988)). Following nick translation, unincorporated label is removed by spin dialysis through Sepharose. The probe is further extracted with phenol-chloroform to remove additional protein. The chromosomes are denatured in formamide using techniques known in the art and the denatured probe added to the slides. Following hybridization, the cells are washed. The slides are studied under a fluorescent microscope. In addition, the chromosomes can be stained for G-banding or Q-banding using techniques known in the art.
  • the resulting metaphase chromosomes have fluorescent tags localized to those regions of the chromosome that are homologous to the EST. Thus, a particular EST is localized to a particular region on a given chromosome.
  • Table 4 Precise Chromosomal Localization of ESTs
  • ESTs that match human sequences in GenBank are excellent tools for the analysis of the accuracy of double- strand automated DNA sequencing.
  • EST/GenBank matches from a number of clones were examined for the number of nucleotide mismatches and gaps required to achieve optimal alignment by the Genetics Computer Group (GCG) program BESTFIT (Devereux et al, Nucleic Acids Research 12: 387 (1984)).
  • the number of mismatches, insertions and deletions was counted for each hundred bases of the sequence (Table 5) .
  • the sequence quality was best closest to the primer and decreased rapidly after about 400 bases.
  • the number of deletions and insertions relative to the GenBank reference sequence increased five- to ten-fold beyond 400 bases, while the number of mismatches doubled.
  • the average accuracy rate for individual double-stranded sequencing runs was 97.7% to 400 bases. TABLE 5.
  • the ESTs of the present invention were statistically evaluated using the coding-region prediction program CRM via the GRAIL server (Uberbacher, E. & Mural, R. Proc. Natl. Acad. Sci. USA, 88: 11261-5 (1991)).
  • the CRM program uses a neural network to combine results from several different coding regions by looking at different 6 bp sequences found in coding exons and in introns.
  • the program additionally conducts reading frame searches and assesses randomness at the third position of codons. This protocol categorizes sequences as having an excellent, good, marginal, or poor probability of containing coding regions. The results are reported in Tables 6-9.
  • Example 2 By matching new human ESTs to known sequences from other species, the apparent function of the gene corresponding to the EST can be ascertained.
  • the data generated in Example 2 have been used to categorize 28 of the ESTs of the present invention, and their corresponding genes, into predicted functional groups. (These 28 are ESTs with database matches to sequences from other species for which a function was known.) Two different grouping schemes have been used.
  • the first scheme separates the sequences into three broad categories: metabolic; regulatory; and structural. These groupings are set out in Table 10.
  • the second grouping scheme separates the sequences into 13 specific categories: cell surface proteins; developmental control; energy metabolism; kinases and phosphatases; oncogenes; other metabolism-related polypeptides; peptidases and peptidase inhibitors; receptors; structural and cytoskeletal; signal transduction; transporters; transcription, translation, and subcellular localization; and transcription factors.
  • groupings are set out in Table 11.
  • Lysosomal membrane glycoprotein 1 (LAMP-1)
  • MARCKS myristoylated alanine-rich protein kinase smg p25A GDP dissociation inhibitor
  • RNA polymerase II 6th subunit RPO26
  • CS Cell Surface
  • DC Developmental Control
  • EM Energy Metabolism
  • KP Kinases and Phosphatases
  • OG Oncogenes
  • PI Peptidases and Peptidase Inhibitors
  • RT Receptors
  • SC Structural and Cytoskeletal
  • ST Signal Transduction
  • TT Transcription, Translation
  • TX Transcription Factors.
  • EXAMPLE 9 cDNA Libraries Generated From Specific Genomic DNA by Exon Expression & Amplification
  • Exon amplification is used to express potential exons from genomic DNA in a recombinant vector that contains some of the signals necessary for splicing. If an exon is present in the proper orientation in the vector, that exon will be spliced in a mammalian cell and will become part of the mRNA of that cell.
  • the exon splice-product can be purified from other mRNA in the cell by conversion of the mRNA to cDNA and selective amplification of the recombinant splice-product cDNAs.
  • Cosmid DNA from human chromosome 19ql3.3 is digested with Ba HI or BamHI/Bglll restriction enzymes.
  • RNA transcripts are generated using the SV40 early promoter and a polyadenylation signal derived from SV40 both present in the expression vector.
  • a fragment of genomic DNA contains an entire exon with flanking intron sequence in the sense orientation, the exon should be retained in the mature poly(A)+ cytoplasmic RNA. Therefore, the mRNA is used as template for cDNA synthesis using reverse transcriptase and vector-priming.
  • the cDNAs are amplified by vector-priming using PCR.
  • a fraction of this first PCR product is reamplified using internal vector-primers containing terminal cloning sites. These products are end- repaired with T4 DNA polymerase, digested with the appropriate restriction enzymes, gel purified and cloned into pBluescript vectors.
  • the constructs are transfected into XLl-Blue competent cells and plated on LB/X-gal/IPTG/ampicillin plates. When multiple cosmids or YAC clones are used as the source DNA, a pool of specific expressed exons is obtained as a cDNA library.
  • Computational analyses can be applied to genomic DNA sequences to predict protein coding regions.
  • the coding region prediction program CRM (E. Uberbacher and R. Mural, Proc. Natl. Acad. Sci. USA 88:11261-5 (1991)) finds open reading frames and classifies them according to their probability of being coding regions. These regions are subsequently examined using the GM program (C. Fields and C. Soderlund, Comp. Applic. Biosci. 6: 263, 1990), which predicts intron-exon structure.
  • PCR primers are then designed to amplify the predicted exons and used to test human cDNA libraries (for example, fetal brain or placental libraries) for the presence of these putative exons using a PCR assay.
  • EST clones were digested with the restriction enzymes Sail and Kpnl or Pstl and BamHI (for deletions from the Forward primer and Reverse primer ends of the insert, respectively) .
  • the Kpnl and Pstl enzymes leave 3* sticky ends following digestion, which Exonuclease III is unable to bind. This results in unidirectional deletions into the cDNA insert leaving the vector sequence undisturbed.
  • aliquots of the reaction were removed at defined time intervals and the reaction was stopped to prevent further deletion. SI nuclease and Klenow DNA polymerase were added to create blunt ended fragments suitable for ligation.
  • the reading frame, orientation, and coding regions are determined by computer techniques.
  • the complete coding region is considered to be the largest open reading frame from a methionine to a stop codon.
  • the CRM program on the GRAIL server is used as explained in Example 7 to determine probable coding regions. This information is supplemented by location of start and stop codons.
  • the results of the CRM analysis are validated by comparison of the cDNA sequence to known sequences using database matching, in accordance with Example 2. If a match of 50% (or even less) is found in any particular reading frame and orientation, this serves to verify corresponding CRM results. Alternatively, database matches can be used to determine reading frame and orientation without use of the CRM program.
  • the probable orientation is already known.
  • the EST sequences and the corresponding cDNA sequences and genomic sequences may be used, in accordance with the present invention, to prepare PCR primers for a variety of applications.
  • the PCR primers are preferably at least 15 bases, and more preferably at least 18 bases in length.
  • the procedure of Example 3 is repeated using the desired EST, or using the corresponding cDNA or genomic DNA sequence from Example 11. It is preferred that the primer pairs have approximately the same G/C ratio, so that melting temperatures are approximately the same.
  • introns are of no concern; however, when screening genomic DNA, primers should be selected to avoid reading across introns, which usually are too large to amplify.
  • the PCR primers and amplified DNA of this Example find use in the Examples that follow.
  • DNA samples are isolated from forensic specimens of, for example, hair, semen, blood or skin cells by conventional methods.
  • a panel of PCR primers derived from a number of the sequences of Example 1, 9, 10 and/or 11 is then utilized in accordance with Example 10 to obtain DNA of approximately 100-200 bases in length from the forensic specimen.
  • Corresponding sequences are obtained from a suspect.
  • Each of these identification DNAs is then sequenced, and a simple database comparison determines the differences, if any, between the sequences from the suspect and those from the sample.
  • Statistically significant differences between the suspect's DNA sequences and those from the sample conclusively prove a lack of identity. This lack of identity can be proven, for example, with only one sequence. Identity, on the other hand, should be demonstrated with a large number of sequences, all matching.
  • a minimum of 50 statistically identical sequences of 100 bases in length are used to prove identity between the suspect and the sample.
  • primers are prepared from a large number of sequences from Examples 1, 9, 10 and/or 11. Preferably, 20 to 50 different primers are used. These primers are used to obtain a corresponding number of PCR-generated DNA segments from the individual in question in accordance with Example 13. Each of these DNA segments is sequenced, using the methods set forth in Example 1. The database of sequences generated through this procedure uniquely identifies the individual from whom the sequences were obtained. The same panel of primers may then be used at any later time to absolutely correlate tissue or other biological specimen with that individual.
  • Example 15 The procedure of Example 15 is repeated to obtain a panel of from 10 to 2000 amplified sequences from an individual and a specimen.
  • This PCR-generated DNA is then digested with one or a combination of, preferably, four base specific restriction enzymes.
  • Such enzymes are commercially available and known to those of skill in the art.
  • the resultant gene fragments are size separated in multiple duplicate wells on an agarose gel and transferred to nitrocellulose using Southern blotting techniques well known to those with skill in the art.
  • Southern blotting see Davis et al. (Basic Methods in Molecular Biology. 1986, Elsevier Press, pp 62-65).
  • 1, and/or 11, or fragments thereof of at least 15 bases are radioactively or colorimetrically labeled using end-labeled oligonucleotides derived from the ESTs, nick translated sequences or the like using methods known in the art and hybridized to the Southern blot using techniques known in the art (Davis et al., supra) .
  • at least 5 to 10 of these labeled probes are used, and more preferably at least about 20 or 30 are used to provide a unique pattern.
  • the resultant bands appearing from the hybridization of a large sample of ESTs will be a unique identifier. Since the restriction enzyme cleavage will be different for every individual, the band pattern on the Southern blot will also be unique. Increasing the number of EST probes will provide a statistically higher level of confidence in the identification since there will be an increased number of sets of bands used for identification.
  • Another technique for identifying individuals using the sequences disclosed herein utilizes a dot blot hybridization technique.
  • Genomic DNA is isolated from nuclei of subject to be identified. Oligonucleotide probes of approximately 30 bp in length were synthesized that correspond to sequences from the ESTs. The probes are used to hybridize to the genomic DNA through conditions known to those in the art. The oligonucleotides are end labelled with 32 P using polynucleotide kinase (Pharmacia) . Dot Blots are created by spotting about 50 ng cDNA of preferably at least 10 sequences corresponding to a variety of the Sequence ID NOs provided in Table 7 onto nitrocellulose or the like using a vacuum dot blot manifold
  • EST sequences and the corresponding complete cDNA sequences can be used to create a unique fingerprint for an individual.
  • pools of EST sequences can be used in forensics, paternity suits or the like to differentiate one individual from another.
  • Entire EST sequences . can be used; similarly oligonucleotides can be prepared from EST sequences.
  • 20-mer oligonucleotides are prepared from 200 EST sequences using commercially available oligonucleotide services such as Oligos Etc., Wilsonville, OR.
  • Patient cell samples are processed for DNA using techniques well known to those with skill in the art.
  • the nucleic acid is digested with restriction enzymes EcoRI and Xbal. Following digestion, samples are applied to wells for electrophoresis.
  • the procedure may be modified to accommodate polyacrylamide electrophoresis, however in this example, samples containing 5 ug of DNA are loaded into wells and separated on 0.8% agarose gels. The gels are transferred using Southern blotting techniques onto nitrocellulose. 10 ng of each of the oligos are pooled and end-labeled with 32 P. The nitrocellulose is prehybridized with blocking solution and hybridized with the labeled probes. Following hybridization and washing, the nitrocellulose filter is exposed to X-Omat AR X-ray film. The resulting hybridization pattern will be unique for each individual.
  • This example illustrates an approach useful for the association of EST sequences with particular phenotypic characteristics.
  • a particular EST is used as a test probe to associate that EST with a particular phenotypic characteristic.
  • ESTs from patients with these diseases are isolated and expanded in culture. PCR primers from the EST sequences are used to screen genomic DNA and RNA or cDNA from the patients. ESTs that are not amplified in the patients can be positively associated with a particular disease by further analysis.
  • Angelman's disease is characterized by deletions on the long arm of chromosome 15 (15qllql3) (Williams et al. Am. J. Med. Genet. 32:339-345 (1989) hereby incorporated by reference) .
  • the symptoms of the disease include developmental delay, seizures, inappropriate laughter and ataxic movements. These symptoms suggest that the disorder is a neurologic deficiency.
  • This prophetic example illustrates how ESTs, preferably obtained from a cDNA library from human brain, may be used in identifying the defective gene or genes associated with Angelman's Disease.
  • EST sequences may generally be used for identifying gene sequences associated with an inherited disease that is mapped to a chromosome location.
  • ESTs are screened using techniques described in Example 3 and Example 5 to identify those ESTs that localize to the long arm of chromosome 15 and preferably localize to chromosome 15 bands 15qllql3 from normal patients.
  • ESTs that bind to the long arm of chromosome 15 are hybridized to chromosome 15 from AD patients. These studies are preferrably performed using either fluorescence in situ hybridization or using somatic cell hybrids that contain fragments from the long arm of chromosome 15 from AD patients.
  • Those chromosome 15-specific ESTs that do not map to chromosome 15 from AD patients are useful as markers for Angelman's Disease and can be incorporated into diagnostics for genetic screening.
  • These ESTs are associated with chromosome deletions present in Angelman's disease. Identification of the gene associated with these AD negative ESTs and an analysis of the polypeptides encoded by the genes from normal patients is essential for providing gene or other therapies for AD patients.
  • RFLP Restriction fragment length polymorphism
  • cDNA libraries are prepared from the somatic cell hybrids from AD patients. Libraries are prepared using Lambda Zap II Library Kits (Stratagene, La Jolla, California) or other commercially available library kits. The ESTs of interest are used as probes to identify those bacterial colonies carrying genes corresponding to the EST probes.
  • Positive clones are sequenced and the sequences are compared to homologous gene sequences derived from normal patients. Alterations, including deletions and substitutions, within gene sequences, associated with bands 15qllql3, are thus positively identified and associated with AD disease. Wagstaff et al. were able to identify deletions and substitutions in sequences encoding the GABA A receptor protein subunit from patients with Angelman's disease (Am. J. Hum. Genet. 49:330-337, (1991)). It is likely that other genes will additionally be associated with the disease.
  • Antisense RNA molecules are known to be useful for regulating translation within the cell. Antisense RNA molecules can be produced from EST sequences or from the corresponding gene sequences. These antisense molecules can be used as diagnostic probes to determine whether or not a particular gene is expressed in a cell. Similarly, the antisense molecules can be used as a therapeutic to regulate gene expression once the EST is associated with a particular disease (see Example 20) .
  • the antisense molecules are obtained from a nucleotide sequence by reversing the orientation of the coding region with regard to the promoter.
  • the antisense RNA is complementary to the corresponding mRNA.
  • the antisense sequences can contain modified sugar phosphate backbones to increase stability and make them less sensitive to RNase activity. Examples of the modifications are described by Rossi et al., Pharmacol. Ther. 50(2) :245-254, (1991) .
  • Antisense molecules are introduced into cells "that express the gene corresponding to the EST of interest in culture.
  • the polypeptide encoded by the gene is first identified, so that the effectiveness of antisense inhibition on translation can be monitored using techniques that include but are not limited to antibody-mediated tests such as RIAs and ELISA, functional assays, or radiolabelling.
  • the antisense molecule is introduced into the cells by diffusion or by transfection procedures known in the art.
  • the molecules are introduced onto cell samples at a number of different concentrations preferably between lxlO " 0 M to lxlO "4 M. Once the minimum concentration that can adequately control translation is identified, the optimized dose is translated into a dosage suitable for use in vivo.
  • an inhibiting concentration in culture of lxlO "7 translates into a dose of approximately 0.6 mg/kg bodyweight.
  • levels of oligonucleotide approaching 100 mg/kg bodyweight or higher may be possible after testing the toxicity of the oligonucleotide in laboratory animals.
  • the antisense can be introduced into the body as a bare or naked oligonucleotide, oligonucleotide encapsulated in lipid, oligonucleotide sequence encapsidated by viral protein, or as oligonucleotide contained in an expression vector such as those described in Example 23.
  • the antisense oligonucleotide is preferably introduced into the vertebrate by injection. It is additionally contemplated that cells from the vertebrate are removed, treated with the antisense oligonucleotide, and reintroduced into the vertebrate.
  • the antisense oligonucleotide sequence is incorporated into a ribozyme sequence to enable the antisense to bind and cleave its target.
  • ribozyme and antisense oligonucleotides see Rossi et al.
  • Triple helix oligonucleotides are used to inhibit transcription from a genome. They are particularly useful for studying alterations in cell activity as it is associated with a particular gene.
  • the EST sequences or complete sequences of the present invention or, more preferably, a portion of those sequences, can be used to inhibit gene expression in individuals having diseases associated with a particular gene.
  • a portion of the EST or corresponding gene sequence can be used to study the effect of inhibiting transcription of a particular gene within a cell.
  • homopurine sequences were considered the most useful.
  • homopyrimidine sequences can also inhibit gene expression. Thus, both types of sequences from either the EST or from the gene corresponding to the EST are contemplated within the scope of this invention.
  • Homopyrimidine oligonucleotides bind to the major groove at homopurine:homopyrimidine sequences.
  • 10-mer to 20-mer homopyrimidine sequences from the ESTs can be used to inhibit expression from homopurine sequences.
  • SEQ ID NOs such as 282 and 240 contain homopyrimidine 15-mers.
  • the natural (beta) anomers of the oligonucleotide units can be replaced with alpha anomers to render the oligonucleotide more resistant to nucleases.
  • an intercalating agent such as ethidium bromide, or the like, can be attached to the 3' end of the alpha oligonucleotide to stabilize the triple helix.
  • the oligonucleotides may be prepared on an oligonucleotide synthesizer or they may be purchased commercially from a company specializing in custom oligonucleotide synthesis.
  • the sequences are introduced into cells in culture using techniques known in the art that include but are not limited to calcium phosphate precipitation, DEAE-Dextran, electroporation, liposo e- mediated transfection or native uptake. Treated cells are monitored for altered cell function.
  • These cell functions are predicted based upon the homologies of the gene, corresponding to the EST from which the oligonucleotide was derived, with known genes sequences that have been associated with a particular function.
  • the cell functions can also be predicted based on the presence of abnormal physiologies within cells derived from individuals with a particular inherited disease, particularly when the EST is associated with the disease using techniques described in Example 20.
  • a gene sequence of the present invention coding for all or part of a human gene product is introduced into an expression vector using conventional technology.
  • Techniques to transfer cloned sequences into expression vectors that direct protein translation in mammalian, yeast, insect or bacterial expression systems are well known in the art.
  • Commercially available vectors and expression systems are available from a variety of suppliers including Stratagene (La Jolla, California) , Promega (Madison, Wisconsin) , and Invitrogen (San Diego, California) .
  • Stratagene La Jolla, California
  • Promega Micromega
  • Invitrogen San Diego, California
  • the codon context and codon pairing of the sequence may be optimized for the particular expression organism, as explained by Hatfield, et al., U.S. Patent No. 5,082,767, incorporated herein by this reference.
  • the following is provided as one exemplary method to generate polypeptide from cloned cDNA sequences.
  • the cDNA from the EST of interest is sequenced to identify the methionine initiation codon for the gene and the poly A sequence. If the cDNA lacks a poly A sequence, this sequence can be added to the construct by, for example, splicing out the Poly A sequence from pSG5 (Stratagene) using Bgll and Sail restriction endonuclease enzymes and incorporating it into the mammalian expression vector pXTl (Stratagene) .
  • pXTl contains the LTRs and a portion of the gag gene from Moloney Murine Leukemia Virus.
  • the position of the LTRs in the construct allow efficient stable transfection.
  • the vector includes the Herpes Simplex Thymidine Kinase promoter and the selectable neomycin gene.
  • the cDNA is obtained by PCR from the bacterial vector using oligonucleotide primers complementary to the cDNA and containing restriction endonuclease sequences for Pst I incorporated into the 5'primer and Bglll at the 5' end of the corresponding cDNA 3' primer, taking care to ensure that the cDNA is positioned inframe with the poly A sequence.
  • the purified fragment obtained from the resulting PCR reaction is digested with Pstl, blunt ended with an exonuclease, digested with Bgl II, purified and ligated to pXTl, now containing a poly A sequence and digested Bglll.
  • the ligated product is transfected into mouse NIH 3T3 cells using Lipofectin (Life Technologies, Inc. , Grand Island, New York) under conditions outlined in the product specification. Positive transfectants are selected after growing the transfected cells in 600ug/ml G418 (Sigma, St. Louis, Missouri) .
  • the protein is preferrably released into the supernatant. However if the protein has membrane binding domains, the protein may additionally be retained within the cell or expression may be restricted to the cell surface.
  • the cDNA sequence is additionally incorporated into eukaryotic expression vectors and expressed as a chimeric with, for example, ⁇ - globin.
  • Antibody to -globin is used to purify the chimeric.
  • Corresponding protease cleavage sites engineered between the -globin gene and the cDNA are then used to separate the two polypeptide fragments from one another after translation.
  • One useful expression vector for generating 0-globin chimerics is pSG5 (Stratagene) . This vector encodes rabbit ⁇ -globin. Intron II of the rabbit ⁇ -globin gene facilitates splicing of the expressed transcript, and the polyadenylation signal incorporated into the construct increases the level of expression.
  • Polypeptide may additionally be produced from either construct using in vitro translation systems such as In vitro ExpressTM Translation Kit (Stratagene) .
  • Substantially pure protein or polypeptide is isolated from the transfected or transformed cells as described in Example 23. Concentration of protein in the final preparation is adjusted, for example, by concentration on an Amicon filter device, to the level of a few micrograms/ml. Monoclonal or polyclonal antibody to the protein can then be prepared as follows: A. Monoclonal Antibody Production by Hybridoma Fusion
  • Monoclonal antibody to epitopes of any of the peptides identified and isolated as described can be prepared from murine hybridomas according to the classical method of Kohler, G. and Milstein, C. , Nature 256:495 (1975) or derivative methods thereof. Briefly, a mouse is repetitively inoculated with a few micrograms of the selected protein over a period of a few weeks. The mouse is then sacrificed, and the antibody producing cells of the spleen isolated. The spleen cells are fused by means of polyethylene glycol with mouse myeloma cells, and the excess unfused cells destroyed by growth of the system on selective media comprising aminopterin (HAT media) .
  • HAT media aminopterin
  • the successfully fused cells are diluted and aliquots of the dilution placed in wells of a microtiter plate where growth of the culture is continued.
  • Antibody-producing clones are identified by detection of antibody in the supernatant fluid of the wells by i munoassay procedures, such as Elisa, as originally described by Engvall, E., Meth. Enzymol. 70:419 (1980) , and derivative methods thereof. Selected positive clones can be expanded and their monoclonal antibody product harvested for use. Detailed procedures for monoclonal antibody production are described in Davis, L. et al. Basic Methods in Molecular Biology Elsevier, New York. Section 21-2. B. Polyclonal Antibody Production by Immunization
  • Polyclonal antiserum containing antibodies to heterogenous epitopes of a single protein can be prepared by immunizing suitable animals with the expressed protein described above, which can be unmodified or modified to enhance immunogenicity.
  • Effective polyclonal antibody production is affected by many factors related both to the antigen and the host species. For example, small molecules tend to be less immunogenic than other and may require the use of carriers and adjuvant.
  • host animals vary in response to site of inoculations and dose, with both inadequate or excessive doses of antigen resulting in low titer antisera. Small doses (ng level) of antigen administered at multiple intradermal sites appears to be most reliable.
  • An effective immunization protocol for rabbits can be found in Vaitukaitis,
  • Booster injections can be given at regular intervals, and antiserum.harvested when antibody titer thereof, as determined semi-quantitatively, for example, by double immunodiffusion in agar against known concentrations of the antigen, begins to fall. See, for example, Ouchterlony, 0. et al., Chap. 19 in: Handbook of Experimental Immunology D. Wier (ed) Blackwell (1973) . Plateau concentration of antibody is usually in the range of 0.1 to 0.2 mg/ml of serum (about 12 ⁇ M) . Affinity of the antisera for the antigen is determined by preparing competitive binding curves, as described, for example, by Fisher, D. , Chap. 42 in: Manual of Clinical Immunology, 2d Ed.
  • Antibody preparations prepared according to either protocol are useful in quantitative immunoassays which determine concentrations of antigen-bearing substances in biological samples; they are also used semi-quantitatively or qualitatively to identify the presence of antigen in a biological sample.
  • tissue specific antigens by means of antibody preparations according to Example 24 which are conjugated, directly or indirectly to a detectable marker.
  • Selected labeled antibody species bind to their specific antigen binding partner in tissue sections, cell suspensions, or in extracts of soluble proteins from a tissue sample to provide a pattern for qualitative or semi-qualitative interpretation.
  • Antisera for these procedures must have a potency exceeding that of the native preparation, and for that reason, antibodies are concentrated to a mg/ml level by isolation of the gamma globulin fraction, for example, by ion-exchange chromatography or by ammonium sulfate fractionation.
  • unwanted antibodies for example to common proteins, must be removed from the gamma globulin fraction, for example by means of insoluble immunoabsorbents, before the antibodies are labeled with the marker.
  • Either monoclonal or heterologous antisera is suitable for either procedure.
  • a fluorescent marker either fluorescein or rhodamine
  • antibodies can also be labeled with an enzyme that supports a color producing reaction with a substrate, such as horseradish peroxidase. Markers can be added to tissue-bound antibody in a second step, as described below.
  • the specific antitissue antibodies can be labeled with ferritin or other electron dense particles, and localization of the ferritin coupled antigen-antibody complexes achieved by means of an electron microscope.
  • the antibodies are radiolabeled, with, for example 125 I, and detected by overlaying the antibody treated preparation with photographic emulsion.
  • Preparations to carry out the procedures can comprise monoclonal or polyclonal antibodies to a single gene copy or protein, identified as specific to a tissue type, for example, brain tissue, or antibody preparations to several antigenically distinct tissue specific antigens can be used in panels, independently or in mixtures, as required.
  • Tissue sections and cell suspensions are prepared for immunohistochemical examination according to common histological techniques. Multiple cryostat sections (about 4 ⁇ , unfixed) of the unknown tissue and known control, are mounted and each slide covered with different dilutions of the antibody preparation. Sections of known and unknown tissues should also be treated with preparations to provide a positive control, a negative control, for example, pre-immune sera, and a control for non-specific staining, for example, buffer.
  • Treated sections are incubated in a humid chamber for 30 min at room temperature, rinsed, then washed in buffer for 30- 45 min. Excess fluid is blotted away, and the marker developed.
  • tissue specific antibody was not labeled in the first incubation, it can be labeled at this time in a second antibody-antibody reaction, for example, by adding fluorescein- or enzyme-conjugated antibody against the immunoglobulin class of the antiserum-producing species, for example, fluorescein labeled antibody to mouse IgG.
  • fluorescein- or enzyme-conjugated antibody against the immunoglobulin class of the antiserum-producing species for example, fluorescein labeled antibody to mouse IgG.
  • the antigen found in the tissues by the above procedure can be quantified by measuring the intensity of color or fluorescence on the tissue section, and calibrating that signal using appropriate standards.
  • tissue specific proteins and identification of unknown tissues from that procedure is carried out using the labeled antibody reagents and detection strategy as described for immunohistochemistry; however the sample is prepared according to an electrophoretic technique to distribute the proteins extracted from the tissue in an orderly array on the basis of molecular weight for detection.
  • a tissue sample is homogenized using a Virtis apparatus; cell suspensions are disrupted by Dounce homogenization or osmotic lysis, using detergents in either case as required to disrupt cell membranes, as is the practice in the art.
  • Insoluble cell components such as nuclei, microsomes, and membrane fragments are removed by ultracentrifugation, and the soluble protein-containing fraction concentrated if necessary and reserved for analysis.
  • a sample of the soluble protein solution is resolved into individual protein species by conventional SDS polyacrylamide electrophoresis as described, for example, by Davis, L. et al., Section 19-2 in: Basic Methods in Molecular Biology (P. Leder, ed) , Elsevier, New York (1986) , using a range of amounts of polyacrylamide in a set of gels to resolve the entire molecular weight range of proteins to be detected in the sample.
  • a size marker is run in parallel for purposes of estimating molecular weights of the constituent proteins.
  • Sample size for analysis is a convenient volume of from 5-50 ⁇ l, and containing from about 1 to 100 ⁇ g protein.
  • a detectable label can be attached to the primary tissue antigen-primary antibody complex according to various strategies and permutations thereof.
  • the primary specific antibody can be labeled; alternatively, the unlabeled complex can be bound by a labeled secondary anti-IgG antibody.
  • either the primary or secondary antibody is conjugated to a biotin molecule, which can, in a subsequent step, bind an avidin conjugated marker.
  • enzyme labeled or radioactive protein A which has the property of binding to any IgG, is bound in a final step to either the primary or secondary antibody.
  • tissue specific antigen binding at levels above those seen in control tissues to one or more tissue specific antibodies, prepared from the gene sequences identified from EST sequences, can identify tissues of unknown origin, for example, forensic samples, or differentiated tumor tissue that has metastasized to foreign bodily sites.
  • the EST sequences of the present invention are identified herein by SEQ ID NO, and are identified in the GenBank database by a different number, are identified in the inventors' lab (and upcoming publications) by EST number, and clones have been submitted to the American Type Culture Collection (Rockville, Maryland USA) under clone names. Table 12 cross references those different numbers for the ESTs from CDNA, SEQ ID NOS 1-315.
  • CTGCAGCCAC CATATGGGGC ACTCCTGGCT GGTGTACAGG GTGGGCATTG CCCAGGTCTT 360
  • ATCCTCACAC CAGCATTTTG TGTGTAAGGA AACTGGCCGA GAGTGGTTAA GAAATATATC 240
  • CTAGGCACCC GTTCAGTGTG AGGAGGGGGA AGTGGCCTTG CCAAGGGGCC AGTGAGCTCA 420
  • AAATCATTGC TCAAAAGAAR AACCTGGCAA TGCATGATTA CGAAATGCAA AAGAMGATAC 120
  • AGTGTCCCAT CAGAGGTTTA TACAAAGAGA GAATGACTGA ACTATATGAT TATCCCANGT 120
  • CTCCCTTCGC CACCTGCTGG ACGCGAGGGG CTACTACGAT GCCATGGGTG TCCTGRTTTT 60
  • TTATTTCTCA GACAGGACTG CTCTGTATNT GTCTTTGGAT TCTACGTAGA TTTATATTTG 120
  • CCCCCTCCTC TTCCGTCCTG ATTAAGCCCA AGGGTTGGTG GACTTAACTT TCAGCCCATC 120
  • CTTCTAATGA GGTCACTACT GAACATAATT GTTCCCTCTT CTGTTAAATA GAATAGGTTT 300
  • GTCCTTACAT GRCAAAGAGA TGGAAGGGCC AAAAAGATGG TGACCTATTG TGAGGCCTTT 360
  • GAGATTGTKC AGCAGCCACT GCCTCCTTGT CACCTTCGCC TGTGGTCATT CTCCCCACAT 180
  • CAMGAAAACC CAGGACACCA GGGCAGGGGG GCTGCACAAG GTCGGGTAGG TCACAGTGGG 180
  • ACTCAMCTTC TCATTCAATC TGGGGCAGTG GATAACCTTT CTGAATAGAC CCACTTGTTC 120

Abstract

Partial and complete human cDNA and genomic sequences corresponding to particular expressed sequence tags (ESTs). The ESTs are cDNA sequences that are generally between 150 and 500 base pairs in length, are derived from human brain cDNA libraries, correspond to genes transcribed in human brain, and have base sequences identified herein as SEQ ID NOS: 1-315.

Description

SEQUENCES CHARACTERISTIC OF HUMAN GENE TRANSCRIPTION PRODUCT
Technical Field The present invention relates to newly identified polynucleotide sequences corresponding to transcription products of human genes, and to complete gene sequences associated therewith.
Background
This invention relates to human genes. Identification and sequencing of human genes is a major goal of modern scientific research. The sequence of human genes is more than just a scientific curiosity. For example, by identifying genes and determining their sequences, scientists have been able to make large quantities of valuable human "gene products." These include human insulin, interferon, Factor VIII, tumor necrosis factor, human growth hormone, tissue plas inogen activator, and numerous other compounds. Additionally, knowledge of gene sequences can provide the key to treatment or cure of genetic diseases (such as muscular dystrophy and cystic fibrosis) . The present invention represents a quantum leap forward in mankind's knowledge of human gene sequences. There are several basic concepts of molecular biology which figure prominently in the invention. A brief explanation of those concepts follows. Additional background information and definitions for scientific terms can be found in the literature. See, for example, "Glossary of Genetics, Classical and Molecular" by R. Rieger, A. Michaelis, and M.M. Green (Fifth Edition, Springer-Verlag, New York (1991)). The contents of this and other publications cited in the specification are incorporated by reference herein.
At an initial level, the present invention is based on identification and characterization of gene segments. Genes are the basic units of inheritance. Each gene is a string of connected bases called nucleotides. Most genes are formed of deoxyribonucleic acid, DNA. (Some viruses contain genes of ribonucleic acid, RNA.) The genetic information resides in the particular sequence in which the bases are arranged. A short sequence of nucleotides is often called a polynucleotide or an oligonucleotide.
Like genes, polypeptides are built from long strings of individual units. These units are amino acids. The nucleotide sequence of a gene tells the cell the sequence in which to arrange the amino acids to make the polypeptide encoded by that gene. In general, chains of up to about 200 amino acids are called polypeptides, while proteins are larger molecules made up of polypeptide subunits; both types of molecules are referred to generally herein as polypeptides. A triplet of nucleotides (codon) in DNA codes for each amino acid or signals the beginning or end of the message (anticodon) . The term codon is also used for the corresponding (and complementary) sequences of three nucleotides in the mRNA into which the original DNA sequence is transcribed. Generally, enzymes in the cell transcribe the permanent DNA of the gene into a temporary RNA copy, called messenger RNA or mRNA. The mRNA, in turn, can be translated into a polypeptide by the cell. This entire process is called gene expression, and the polypeptide is the gene product encoded by the gene.
Scientists have previously discovered how to reverse the transcription process and copy mRNA back into DNA using an enzyme called reverse transcriptase. The resulting is called complementary DNA, or cDNA. This is schematically shown in the single Figure. When substantially all of the mRNA from one cell or tissue is converted to cDNA at once and cloned into multiple copies of a recombinant vector to allow replication and manipulation in the -laboratory, -the result is called a cDNA library. The various types of genes include those which code for polypeptides, those which are transcribed into RNA but are not translated into polypeptides, and those whose functional significance does not demand that they be transcribed at all. Most genes are found on large molecules of DNA located in chromosomes. Double stranded cDNA carries all the information of a gene. Each base of the first strand is joined to a complementary base (hybridized) in the second strand. The linear DNA molecules in chromosomes have thousands of genes distributed along their length. Chromosomes include both coding regions (coding for polypeptides) and noncoding regions; the coding regions represent only about three percent of the total chromosome sequence.
An individual gene has regulatory regions that include a promoter which directs expression of the gene, a coding region which can code for a polypeptide, and a termination signal. The regulatory DNA sequence is usually a noncoding region that determines if, where, when, and at what level a particular gene is expressed.
The coding regions of many genes are discontinuous, with coding sequences (exons) alternating with noncoding regions (introns) . The final mRNA copy of the gene does not include these introns (which can be much longer than the coding region itself) , although it does contain certain untranslated regions that usually do not code for the polypeptide gene product. Untranslated sequences at the beginning and end of the mRNA are known as 51- and 3'-untranslated regions, respectively. This nomenclature reflects the orientation of the nucleotide constituents of the mRNA.
A cDNA is a DNA copy of a messenger RNA, which contains all of the exons of a gene. The cDNA can be thought of as having three parts: an untranslated 5* leader, an uninterrupted polypeptide-coding sequence, and a 3' untranslated region. The untranslated leader and trailing sequences are important for initiation of translation, mRNA stability, and other functions. The untranslated leader and trailing sequences are called 5'- and 3 '-untranslated sequences, respectively. The 3' untranslated sequence is usually longer than the 5' untranslated leader, and can be longer than the polypeptide-coding sequence. The untranslated regions typically have many, randomly-distributed stop codons, and do not display the nonrandom base arrangements found in coding sequences. The 5'-untranslated sequence is relatively short, generally between 20 and 200 bases. The 31- untranslated sequence is often many times longer, up to several thousand bases.
The translated or coding sequence begins with a translational start codon (AUG or GUG) and ends with a translational stop codon (UAA, UGA, or UAG) . Generally, translation begins at the first "start" codon on the mRNA and proceeds to the first "stop" codon. Coding sequences can be distinguished by their nonrandom distribution of bases; numerous computer algorithms have been developed to distinguish coding from noncoding regions in this way. Human DNA differs from person to person. No two persons (except perhaps identical twins) have identical DNA. While the differences, called allelic variations or polymorphisms, are slight on a molecular level, they account for most of the physical and other observable differences between individuals. It has been estimated that approximately 14 million sequence polymorphism differences exist between individuals.
The ability of one strand of DNA to attach or hybridize to a complementary strand has already been exploited for several purposes. For example, small pieces of DNA (15 to 25 base pairs long) can be made which will hybridize to longer strands of DNA which have a complementary sequence. These short "primers" can be selected such that they hybridize to a specific, unique location on the longer strand. Once the primers have hybridized to their target on the DNA, the polymerase chain reaction (PCR) can be employed to generate millions of copies of (or amplify) the particular segment of DNA between the locations to which two primers are bound. Briefly, this technique allows amplification of a DNA region situated between two convergent primers, using oligonucleotide primers that hybridize to opposite strands. Primer extension proceeds inward across the region between the two primers, and the product of DNA synthesis of one primer serves as a template for the other primer. Repeated cycles of DNA denaturation, annealing of primers, and extension result in an exponential increase in the number of copies of the region bounded by the primers. Similarly, a labeled segment of single-stranded DNA can be hybridized to a longer DNA sequence, such as a chromosome, to mark a specific location on the longer sequence. Segments of DNA 50 bases long or longer that hybridize to a unique DNA location in the human genome are extremely unlikely to hybridize elsewhere in the human genome.
The Human Genome Project is an effort to sequence all human DNA (the human genome) . The human genome is estimated to comprise 50,000 - 100,000 genes, up to 30,000 of which might be expressed in the brain (Sutcliffe, Ann. Rev. Neurosci. 11:157 (1988)). Once dedicated human chromosome sequencing begins in three to five years, it was expected that 12-15 years will be required to complete the sequence of the genome (Report of the Ad Hoc Program Advisory Committee on Complex Genomes, Reston, Va. , Feb. 1988, D. Baltimore Ed. (NIH, Bethesda, Md, 1988)). At that rate, the majority of human genes would remain unknown for at least the next decade. The present invention can greatly accelerate the pace at which human genes can be identified and mapped. Most gene researchers, in conjunction with publication of their results in this field, submit sequence data to the GenBank database. Prior to the present invention, GenBank listed the sequences of only a few thousand human genes and less than two hundred human brain mRNAs (GenBank Release 66.0, December, 1990).
The role of sequencing complementary DNA (cDNA) , reverse transcribed from mRNA, as a part of the human genome project has been vigorously debated since the idea of determining the complete nucleotide sequence of humans first surfaced. The coding sequence of all human genes represents most of the information content of the genome, but only 3-5% of the total DNA. In contrast, cDNA (which is only made from the transcription product of active genes) is one-half to three- fourths (the remainder being 5'- and 3'-untranslated sequence) meaningful genetic information. Thus, some have argued that cDNA sequencing should take precedence over genomic sequencing (Brenner, CIBA Found. Sy p. 149:6 (1990)). However, until now, such arguments have not been heeded. Genomic sequencing proponents have argued the difficulty of finding every mRNA expressed in all tissues, cell types, and developmental states, and that much valuable information from intronic and intergenic regions, including control and regulatory sequences, will be missed by cDNA sequencing. (Report of the Committee on Mapping and Sequencing the Human Genome, National Research Council (National Academy Press, Washington, D.C. 1988)). Further, sequencing of transcribed regions of the genome using cDNA libraries has heretofore been considered impractical or unsatisfactory. Libraries of cDNA were believed to be dominated by repetitive elements, mitochondrial genes, ribosomal RNA genes, and other nuclear genes comprising common or housekeeping sequences. It was believed that cDNA libraries would provide few sequences corresponding to structural and regulatory polypeptides or peptides. See, for example, Putney, et al.. Nature 302;718- 721 (1983) . Putney, et al. sequenced over 150 clones from a rabbit muscle cDNA library and identified clones for 13 of the 19 known muscle polypeptides, including one new isotype but no unknown coding sequences. Another perceived drawback of cDNA sequencing was that some mRNAs are abundant, and some are rare. The cellular quantities of mRNA from various genes can vary by several orders of magnitude. This led critics to believe that most information obtained from cDNA sequencing would be repetitious and useless.
The present invention demonstrates that, despite such skepticism, cDNA sequencing now provides a rapid method for obtaining enormous amounts of valuable genetic information and DNA products of great utility for the biotechnology and pharmaceutical industries. Not only can many distinct cDNAs be isolated and sequenced, even partial cDNAs can be used, with conventional, well-understood methods, to isolate entire genes, and to determine the chromosomal locations and biological functions of these genes. As is demonstrated here, fragments of only a few hundred bases are sufficient, in many cases, to identify the probable function of a new human gene if it is similar in structure to a gene from another animal, or from plants or bacteria. Similarly, even fragments of untranslated regions of a cDNA can be used to: i) isolate the coding sequence of the cDNA; ii) isolate the complete gene; iii) determine the position of the gene on a human chromosome, and hence the potential of the gene to cause a human genetic disease; and iv) determine the function of the gene by means of experiments in which the function of the native gene is disrupted by the addition of a short DNA fragment to the cell, e.g., using triple helix or antisense probes. Because coding regions comprise such a small portion of the human genome, identification and mapping of transcribed regions and coding regions of chromosomes is of significant interest. There is a corresponding need for reagents for identifying and marking coding regions and transcribed regions of chromosomes. Furthermore, such human sequences are valuable for chromosome mapping, human identification, identification of tissue type and origin, forensic identification, and locating disease-associated genes (i.e., genes that are associated with an inherited human disease, whether through mutation, deletion, or faulty gene expression) on the chromosome.
SUMMARY OF THE INVENTION
Contrary to the expectations of the scientific community, cDNA screening and sequencing techniques have now been used to discover a large number of heretofore unknown human genes. Disclosed herein are over 300 new human polynucleotide sequences. The novelty of these sequences has been established through comparison to both nucleotide sequence databases and amino acid sequence databases. Surprisingly, approximately 80% of the sequences generated were unrelated to any sequences previously described in the literature. The sequences of the present invention were ascertained using a fast approach to cDNA characterization. This approach could facilitate the tagging of most expressed human genes within a few years at a fraction of the cost of complete genomic sequencing, provide new genetic markers, provide new DNA-based therapeutics and diagnostics, and provide other valuable nucleotide reagents.
The sequences disclosed herein, styled Expressed Sequence Tags ("ESTs") , are markers for human genes actually transcribed in vivo . Techniques are disclosed for using these ESTs to obtain the full coding region of the corresponding gene. The use of ESTs, complete coding sequences, or fragments thereof for marking chromosomes, for mapping locations of expressed genes on chromosomes, for individual or forensic identification, for mapping locations of disease- associated genes, for identification of tissue type, and for preparation of antisense sequences, probes, and constructs is discussed in detail below. Unlike the random genomic DNA sequence tagged sites (STSs) (Olson et al.. Science 245:1434 (1989)), ESTs point directly to expressed genes.
Various aspects of the present invention thus include the individual ESTs, corresponding partial and complete cDNA, genomic DNA, mRNA, antisense strands, triple helix probes, PCR primers, coding regions, and constructs. Also, where one skilled in the art is enabled by this specification to prepare expression vectors and polypeptide expression products, they are also within the scope of the present invention, along with antibodies, especially monoclonal antibodies, to such expression products.
BRIEF DESCRIPTION OF THE DRAWING The single drawing Figure schematically illustrates the progression from chromosome to gene to mRNA to cDNA.
DETAILED DESCRIPTION OF THE INVENTION The detailed description that follows provides not only the actual sequence of each new EST, but also explains how the ESTs were obtained, how to obtain the corresponding complete cDNA sequence and the corresponding genomic DNA sequence, how to make DNA constructs from the ESTs and corresponding sequences, how to use those sequences as reagents in molecular biology and other fields, how to produce gene products from the ESTs and corresponding sequences and antibodies to those gene products, and the functional categories of many ESTs and corresponding genes. Furthermore, numerous actual working examples and predictive examples are provided to demonstrate and exemplify numerous aspects of the invention.
I. ESTs from cDNA Libraries The sequences of the present invention were isolated from commercially available and custom made cDNA libraries using a rapid screening and sequencing technique. In general, the method comprises applying conventional automated DNA sequencing technology to screening clones, advantageously randomly selected clones, from a cDNA library. Preferably, the library is initially "enriched" through removal of ribosomal sequences and other common sequences prior to clone selection. According to the present method, ESTs are generated from partial DNA sequencing of the selected clones. The ESTs of the present invention were generated using low redundancy of sequencing, typically a single sequencing reaction. While single sequencing reactions may have an accuracy as low as 97%, this nevertheless provides sufficient fidelity for identification of the sequence and design of PCR primers.
Most human genes can be identified by EST sequencing from libraries of cDNA copies of messenger RNAs. However, some genes are expressed only at specific times during embryonic development, or only in small amounts in a few specific cell types. Other genes have mRNAs that are degraded very quickly by the cell in which they are expressed. If any of these are the case, transcripts of the gene will not be represented in cDNA libraries so the gene will not be identifiable by EST sequencing. A new method called "exon amplification", however, can be used to isolate and identify transcripts of such genes. Exon amplification works by artificially expressing part or all of a gene that is contained in a cloned fragment of genomic DNA such as a cosmid or yeast artificial chromosome
(YAC) . The gene is cloned into a special vector, designed at
MIT, that uses control elements from virus genes to express the protein-coding exons of the human gene of interest. Exon trapping shows considerable promise as a general technique for identifying those genes in the human genome that cannot be found by cDNA cloning and EST sequencing. Exon amplification will also be useful for identifying the genes in regions of genomic DNA to which disease genes have been mapped. The exon amplification method can be used directly with the cosmid and
YAC clones from human chromosomes that are being obtained by both NIH and DOE supported human genome centers.
ESTs comprise DNA sequences corresponding to a portion of nuclear encoded messenger RNA. An EST is of sufficient length to permit: (1) amplification of the specific sequence from a cDNA library, e.g., by polymerase chain reaction (PCR); (2) use of a synthetic polynucleotide corresponding to a partial or complete sequence of the EST as a hybridization probe of a cDNA library, generally having 30 - 50 base pairs; or (3) unique designation of the pure cDNA clone from which the EST was derived (the EST clone) for use as a hybridization probe of a cDNA library. Preferably, EST-derived primer pairs and sequences amplify or detectably hybridize to a sequence from a genomic library.
It has been found that sufficient information is contained in the 150-400 base ESTs from one sequencing run to effect preliminary identification and exact chromosome mapping. Accordingly, the ESTs disclosed herein are generally at least 150 base pairs in length. The length of an EST is determined by the quality of sequencing data and the length of the cloned cDNA. Raw data from the automated sequencers is edited to remove low quality sequence at the end of the sequencing run. High quality sequences (usually a result of sequencing templates without excessive salt contamination) generally give about 400 bp of reliable sequence data; other sequences give fewer bases of reliable data. A 150 bp EST is long enough to be translated into a 50 amino acid peptide sequence. This length is sufficient to observe similarities when they exist in a database search. Furthermore, 150 bp is long enough to design PCR primers from each end of the sequence to amplify the complete EST. Sequences shorter than 150 bp are difficult to purify and use following PCR amplification. Furthermore, a 150 bp polynucleotide is likely to give a very strong signal with low background in a screen of a genomic library. Finally, it is highly unlikely that a sequence of the same 150 bp exists in any genes in the genome besides the one tagged by the EST. Some closely related gene family members have very similar nucleotide sequences, but no examples of pairs of human genes with long segments of identical sequence have been reported to date. For instance, there are three known ^-tubulin genes in humans. Several ESTs were found that matched one or another of these tubulin genes, but several new members of this gene family were also found and could be clearly distinguished from the three known members. ESTs that match perfectly to several different genes can be detected by hybridizing to chromosomes: if many chromosomal loci are observed, the sequence (or a close variant) is present in more than one gene. This problem can be circumvented by using the 3'-untranslated part of the cDNA alone as a probe for the chromosomal location or for the full-length cDNA or gene. The 3'-untranslated region is more likely to be unique within gene families, since there is no evolutionary pressure to conserve a coding function of this region of the mRNA.
As demonstrated in the Examples that follow, ESTs can be used to map the expressed sequence to a particular chromosome. In addition, ESTs can be expanded to provide the full coding regions, as detailed below. In this manner, previously unknown genes can be identified.
While a variety of cDNA libraries can be used to obtain ESTs, human brain cDNA libraries are exemplified and represent a preferred embodiment. Suitable cDNA libraries can be freshly prepared or obtained commercially, e.g. , as shown in Examples 1 and 9. The cDNA libraries from the desired tissue are preferably preprocessed by conventional techniques to reduce repeated sequencing of high and intermediate abundance. clones and to maximize the chances of finding rare messages from specific cell populations. Preferably, preprocessing includes the use of defined composition prescreening probes, e.g., cDNA corresponding to mitochondria, abundant sequences, riboso es, actins, myelin basic polypeptides, or any other known high abundance peptide; these prescreening probes used for preprocessing are generally derived from known ESTs. Other useful preprocessing techniques include subtraction, which preferentially reduces the population of certain sequences in the library (e.g., see A. Swaroop et al., Nucl. Acids Res. 19:1954 (1991)), and normalization, which results in all sequences being represented in approximately equal proportions in the library (Patanjali et al, Proc. Natl. Acad. Sci. USA 88:1943 (1991)).
The cDNA libraries used in the present method will ideally use directional cloning methods so that either the 5' end of the cDNA (likely to contain coding sequence) or the 3' end (likely to be a non-coding sequence) can be selectively obtained.
Libraries of cDNA can also be generated from recombinant expression of genomic DNA. After they are amplified, ESTs can be obtained and sequenced, e.g., as illustrated in Example 9.
The sequences of the present invention include the specific sequences set forth in the Sequence Listing and designated SEQ ID NO: 1 - SEQ ID NO: 315. In one aspect of this embodiment, the invention relates to those sequences of
SEQ ID NOS: 1 - 315 that comprise the cDNA coding sequences for polypeptides having less than 95% identity with known amino acid sequences (see Table 2) and more preferably less than 90% or 85% identity. In a second aspect, the invention relates to those sequences of SEQ ID NOS: 1 - 315 that encode polypeptides having no similarity to known amino acid sequences (see Examples that follow) . Precisely because they do not contain coding regions and are therefore more unique in their sequence structures, those sequences which meet neither of the preceding criteria can be most useful and are generally preferred for mapping. Consistent with the NIH mission and its responsibilities to disseminate knowledge and share the tangible fruits of its research, the present inventors have taken a number of steps to facilitate sequence data and clone availability. All EST sequences have been submitted to GenBank. The corresponding cDNA clones have been submitted to the American Type Culture Collection and information on clones and sequences has been submitted to the Genome Data Base (Pearson, P. Nucl. Acids Res. 19 (Suppl.): 2237-9 (1991)).
II. Complete Coding Sequences from ESTs
The ESTs of the present invention generally represent relatively small coding regions or untranslated regions of human genes. Although most of these sequences do not code for a complete gene product, the ESTs of the present invention are highly specific markers for the corresponding complete coding regions. The ESTs are of sufficient length that they will hybridize, under stringent conditions, only with DNA for that gene to which they correspond. Suitably stringent conditions comprise conditions, for example, where at least 95%, preferably at least 97% or 98% identity (base pairing) , is required for hybridization. This property permits use of the EST to isolate the entire coding region and even the entire sequence. Therefore, only routine laboratory work is necessary to parlay the unique EST sequence into the corresponding unique complete gene sequence.
Thus, each of the ESTs of the present invention "corresponds" to a particular unique human gene. Knowledge of the EST sequence permits routine isolation and sequencing of the complete coding sequence of the corresponding gene. The complete coding sequence is present in a full-length cDNA clone as well as in the gene carried on genomic clones. Therefore, each EST "corresponds" to a cDNA (from which the EST was derived) , a complete genomic gene sequence, a polypeptide coding region (which can be obtained either from the cDNA or genomic DNA) , and a polypeptide or amino acid sequence encoded by that region. The first step in determining where an EST is located in the cDNA is to analyze the EST for the presence of coding sequence, e.g., as described in Example 12. The CRM program predicts the extent and orientation of the coding region of a sequence. Based on this information, one can infer the presence of start or stop codons within a sequence and whether the sequence is completely coding or completely non-coding. If start or stop codons are present, then the EST can cover both part of the 5•-untranslated or 3'-untranslated part of the mRNA (respectively) as well as part of the coding sequence. If no coding sequence is present, it is likely that the EST is derived from the 3'-untranslated sequence due to its longer length and the fact that most cDNA library construction methods are biased toward the 3• end of the mRNA.
One general procedure for obtaining complete sequences from ESTs is as follows:
1. Purify selected human DNA from an EST clone (the cDNA clone that was sequenced to give the EST), e.g., by endonuclease digestion using ECOR1, gel electrophoresis, and isolation of the aforementioned clone by removal from low- melting agarose gel.
2. Radiolabel the isolated insert DNA, e.g., with 32P labels, preferably by nick translation or random primer labeling. 3. Use the labeled EST insert as a probe to screen a lambda phage cDNA library or a plasmid cDNA library.
4. Identify colonies containing clones related to the probe cDNA and purify them by known purification methods.
5. Nucleotide sequence the ends of the newly purified clones to identify full length sequences.
6. Perform complete sequencing of full length clones by Exonuclease III digestion or primer walking. Northern blots of the mRNA from various tissues using at least part of the EST clone as a probe can optionally be performed to check the size of the mRNA against that of the purported full length cDNA. An EST is a specific tag for a messenger RNA molecule. The complete sequence of that messenger RNA, in the form of cDNA, can be determined using the EST as a probe to identify a cDNA clone corresponding to a full-length transcript, followed by sequencing of that clone. The EST or the full- length cDNA clone can also be used as a probe to identify a genomic clone or clones that contain the complete gene including regulatory and promoter regions, exons, and introns.
ESTs are used as probes to identify the cDNA clones from which an EST was derived. ESTs, or portions thereof, can be nick-translated or end-labelled with 32P using polynucleotide kinase and labelling methods known to those with skill in the art (Basic Methods in Molecular Biology, L.G. Davis, M.D. Dibner, and J.F. Battey, ed. , Elsevier Press, NY, 1986). The lambda library can be directly screened with the labelled ESTs of interest or the library can be converted en masse to pBluescript (Stratagene, La Jolla, California) to facilitate bacterial colony screening. Both methods are well known in the art.
Briefly, filters with bacterial colonies containing the library in pBluescript or bacterial lawns containing lambda plaques are denatured and the DNA is fixed to the filters. The filters are hybridized with the labelled probe using hybridization conditions described by Davis et al. The ESTs, cloned into lambda or pBluescript, can be used as positive controls to assess background binding and to adjust the hybridization and washing stringencies necessary for accurate clone identification. The resulting autoradiograms are compared to duplicate plates of colonies or plaques; each exposed spot corresponds to a positive colony or plaque. The colonies or plaques are selected, expanded and the DNA is isolated from the colonies for further analysis and sequencing.
The ESTs can additionally be used to screen Northern blots of mRNA obtained from various tissues or cell cultures, including the tissue of origin of the EST clone. Northern analysis will most often produce one to several positive bands. The bands can be selected for further study based on the predicted size of the mRNA.
Positive cDNA clones in phage lambda are analyzed to determine the amount of additional sequence they contain using PCR with one primer from the EST and the other primer from the vector. Clones with a larger vector-insert PCR product than the original EST clone are analyzed by restriction digestion and DNA sequencing to determine whether they contain an insert of the same size or similar as the mRNA size on a Northern blot. Once one or more overlapping cDNA clones are identified, the complete sequence of the clones can be determined. The preferred method is to use exonuclease III digestion (McCombie, W.R, Kirkness, E., Fleming, J.T., Kerlavage, A.R., Iovannisci, D.M. , and Martin-Gallardo, R. , Methods: 3: 33-40, 1991) . A- series of deletion clones is generated, each of which is sequenced. The resulting overlapping sequences are assembled into a single contiguous sequence of high redundancy (usually three to five overlapping sequences at each nucleotide position) , resulting in a highly accurate final sequence.
A similar screening and clone selection approach can be applied to obtaining cosmid or lambda clones from a genomic DNA library that contains the complete gene from which the EST was derived (Kirkness, E.F., Kusiak, J.W., Menninger, J. , Gocayne, J.D., Ward, D.C., and Venter, J.C. Genomics 10: 985- 995 (1991) . Although the process is much more laborious, these genomic clones can also be sequenced in their entirety. A shotgun approach is preferred to sequencing clones with inserts longer than 10 kb (genomic cosmid and lambda clones) . In shotgun sequencing, the clone is randomly broken into many small pieces, each of which is partially sequenced. The sequence fragments are then aligned to produce the final contiguous sequence with high redundancy. An intermediate approach is to sequence just the promoter region and the intron-exon boundaries and to estimate the size of the introns by restriction endonuclease digestion (ibid.). Using the sequence information provided herein, the polynucleotides of the present invention can be derived from natural sources or synthesized using known methods. The sequences falling within the scope of the present invention are not limited to the specific sequences described, but include human allelic and species variations thereof and portions thereof of at least 15-18 bases. (Sequences of at least 15-18 bases can be used, for example, as PCR primers or as DNA probes.) In addition, the invention includes the entire coding sequence associated with the specific polynucleotide sequence of bases described in the Sequence Listing, as well as portions of the entire coding sequence of at least 15-18 bases and allelic and species variations thereof. Furthermore, to accommodate codon variability, the invention includes sequences coding for the same amino acid sequences as do the specific sequences disclosed herein. Finally, although the error rate in the automated sequencing used in the present invention is small, there remains some chance of error. Therefore, claims to particular sequences should not be so narrowly construed as to require inclusion of erroneously identified bases or to exclude corrections.
Any specific sequence disclosed herein can be readily screened for errors by resequencing each EST in both directions (i.e., sequence both strands of cDNA) .
The sequences, constructs, vectors, clones, and other materials comprising the present invention can advantageously be in enriched or isolated form. As used herein, "enriched" means that the concentration of the material is at least about 2, 5, 10, 100, or 1000 times its natural concentration (for example) , advantageously 0.01%, by weight, preferably at least about 0.1% by weight. Enriched preparations of about 0.5%, 1%, 5%, 10%, and 20% by weight are also contemplated. Further, removal of clones corresponding to ribosomal RNA and "housekeeping" genes and clones without human cDNA inserts results in a library that is "enriched" in the desired clones. The term "isolated" requires that the material be removed from its original environment (e.g., the natural environment if it is naturally occurring) . For example, a naturally- occurring polynucleotide present in a living animal is not isolated, but the same polynucleotide, separated from some or all of the coexisting materials in the natural system, is isolated. It is also advantageous that the sequences be in purified form. The term "purified" does not require absolute purity; rather, it is intended as a relative definition. Individual EST clones isolated from a cDNA library have been conventionally purified to electrophoretic homogeneity. The sequences obtained from these clones could not be obtained directly either from the library or from total human DNA. The cDNA clones are not naturally occurring as such, but rather are obtained via manipulation of a partially purified naturally occurring substance (messenger RNA) . The conversion of mRNA into a cDNA library involves the creation of a synthetic substance (cDNA) and pure individual cDNA clones can be isolated from the synthetic library by clonal selection. Thus, creating a cDNA library from messenger RNA and subsequently isolating individual clones from that library results in an approximately 106-fold purification of the native message. Purification of starting material or natural material to at least one order of magnitude, preferably two or three orders, and more preferably four or five orders of magnitude is expressly contemplated. In a cDNA library there are many species of mRNA represented. Each cDNA clone can be interesting in its own right, but must be isolated from the library before further experimentation can be completed. In order to sequence any specific cDNA, it must be removed and separated (i.e. isolated and purified) from all the other sequences. This can be accomplished by many techniques known to those of skill in the art. These procedures normally involve identification of a bacterial colony containing the cDNA of interest and further amplification of that bacteria. Once a cDNA is separated from the mixed clone library, it can be used as a template for further procedures such as nucleotide sequencing. Although claims to large numbers of ESTs and corresponding sequences are presented herein, the invention is not limited to these particular groupings of sequences. Thus, individual sequences are considered as applicants' discoveries or inventions, as are subgroupings of sequences. All of the functional subgroupings set forth in the tables define groupings for which separate claims are contemplated as being within the scope of this invention. Moreover, in addition to claims to individual clones, it is intended that the present disclosure also support claims to numerical subgroupings. Thus, subgroupings of 50 ESTs (and corresponding sequences) are contemplated (e.g., SEQ ID NOS 1-50, 51-100, 101-150, etc.) as being within the scope of this invention, as are subgroupings of 5, 10, 25, 100, 200, and 300 ESTs and corresponding sequences.
III. DNA Constructs
The present invention also includes recombinant constructs comprising one or more of the sequences as broadly described above. The constructs comprise a vector, such as a plasmid or viral vector, into which a sequence of the invention has been inserted, in a sense or antisense orientation. In a preferred aspect of this embodiment, the construct further comprises regulatory sequences, including for example, a promoter, operably linked to the sequence. Large numbers of suitable vectors and promoters are known to those of skill in the art, and are commercially available. The following vectors are provided by way of example. Bacterial; pBs, phagescript, ΦX174, pBluescript SK, pBs KS, pNH8a, pNH16a, pNH18a, pNH46a (Stratagene); pTrc99A, pKK223-3, pKK233-3, pDR540, pRIT5 (Pharmacia).
Eukarγotic: pWLneo, pSV2cat, pOG44, pXTl, pSG (Stratagene); pSVK3, pBPV, pMSG, pSVL (Pharmacia).
Promoter regions can be selected from any desired gene using CAT (chloramphenicol transferase) vectors or other vectors with selectable markers. Two appropriate vectors are pKK232-8 and pCM7. Particular named bacterial promoters include lad, lacZ, T3, T7, gpt, lambda PR, and trc. Eukaryotic promoters include CMV immediate early, HSV thymidine kinase, early and late SV40, LTRs from retrovirus, and mouse metallothionein-I. Selection of the appropriate vector and promoter is well within the level of ordinary skill in the art.
In a further embodiment, the present invention relates to host cells containing the above-described construct. The host cell can be a higher eukaryotic cell, such as a mammalian cell, or a lower eukaryotic cell, such as a yeast cell, or the host cell can be a procaryotic cell, such as a bacterial cell. Introduction of the construct into the host cell can be effected by calcium phosphate transfection, DEAE dextran mediated transfection, or electroporation (Davis, L. , Dibner, M. , Battey, I., Basic Methods in Molecular Biology, (1986)). The constructs in host cells can be used in a conventional manner to produce the gene product coded by the recombinant sequence. Alternatively, the encoded polypeptide can be synthetically produced by conventional peptide synthesizers. Certain ESTs have already been preliminarily categorized by analogy to related sequences in other organisms (see Table 2) . Table 10 of Example 8 categorizes particular ESTs broadly as metabolic, regulatory, and structural sequences where known. Constructs comprising genes or coding sequences corresponding to each of these categories are, therefore, specifically and individually contemplated. Table 11 more particularly separates 27 new ESTs into 11 categories using a different criteria. These are genes related to cell surface; developmental control; energy metabolism; kinase and phosphatase; oncogenes; peptidases and peptidase inhibitors; receptors; structural and cytoskeletal; signal transduction; transcription, translation, and subcellular localization; and transcription factors. Table 11 further identifies the EST by the particular gene product for which it apparently codes. Each of these categories individually comprises a preferred category of EST, and preferred constructs and resulting polypeptide can be prepared from those ESTs or the corresponding complete gene sequence.
IV. ESTs and corresponding Sequences as Reagents Each of the cDNA sequences identified herein (and the corresponding complete gene sequences) can be used in numerous ways as polynucleotide reagents. The sequences can be used as diagnostic probes for the presence of a specific mRNA in a particular cell type. In addition, these sequences can be used as diagnostic probes suitable for use in genetic linkage analysis (polymorphisms) . Further, the sequences can be used as probes for locating gene regions associated with genetic disease, as explained in more detail below.
The EST and complete gene sequences of the present invention are also valuable for chromosome identification. Each sequence is specifically targeted to and can hybridize with a particular location on an individual human chromosome. Moreover, there is a current need for identifying particular sites on the chromosome. Few chromosome marking reagents based on actual sequence data (repeat polymorphisms) are presently available for marking chromosomal location. The present invention constitutes a major expansion of available chromosome markers.
Using the techniques described in Example 3 or 4, ESTs and their corresponding complete sequences can be mapped to chromosomes. The mapping of ESTs and cDNAs to chromosomes according to the present invention is an important first step in correlating those sequences with genes associated with disease.
Briefly, sequences can be mapped to chromosomes by preparing PCR primers (preferably 15-25 bp) from the ESTs. Computer analysis of the ESTs is used to rapidly select primers that do not span more than one exon in the genomic DNA, thus complicating the amplification process. These primers are then used for PCR screening of somatic cell hybrids containing individual human chromosomes. Only those hybrids .containing the human gene corresponding to the EST will yield an amplified fragment.
PCR mapping of somatic cell hybrids is a rapid procedure for assigning a particular EST to a particular chromosome. Three or more clones can be assigned per day using a single thermal cycler. Using the present invention with the same oligonucleotide primers, sublocalization can be achieved with panels of fragments from specific chromosomes or pools of large genomic clones in an analogous manner. Other mapping strategies that can similarly be used to map an EST to its chromosome include in situ hybridization, prescreening with labeled flow-sorted chromosomes, and preselection by hybridization to construct chromosome specific cDNA libraries. Results of mapping ESTs to chromosomal segments are listed in Tables 3 and 4. Fluorescence in situ hybridization (FISH) of a cDNA clone to a metaphase chromosomal spread can be used to provide a precise chromosomal location in one step. This technique can be used with cDNA as short as 500 or 600 bases; however, clones larger than 2,000 bp have a higher likelihood of binding to a unique chromosomal location with sufficient signal intensity for simple detection. FISH requires use of the clone from which the EST was derived, and the longer the better. 2,000 bp is good, 4,000 is better, and more than 4,000 is probably not necessary to get good results a reasonable percentage of the time. For a review of this technique, see Ver a et al. , Human Chromosomes: a Manual of Basic Techniques; Pergamon Press, New York (1988) .
Reagents for chromosome mapping can be used individually (to mark a single chromosome or a single site on that chromosome) or as panels of reagents (for marking multiple sites and/or multiple chromosomes) . Reagents corresponding to noncoding regions of the genes actually are preferred for mapping purposes. Coding sequences are more likely to be conserved within gene families, thus increasing the chance of cross hybridizations during chromosomal mapping (see Tables 8 and 9) .
Once a sequence has been mapped to a precise chromosomal location, the physical position of the sequence on the chromosome can be correlated with genetic map data. (Such data are found, for example, in V. McKusick, Mendelian Inheritance in Man (available on-line through Johns Hopkins University Welch Medical Library) . The relationship between genes and diseases that have been mapped to the same chromosomal region are then identified through linkage analysis (coinheritance of physically adjacent genes) . Next, it is necessary to determine the differences in the cDNA or genomic sequence between affected and unaffected individuals. If a mutation is observed in some or all of the affected individuals but not in any normal individuals, then the mutation is likely to be the causative agent of the disease.
With current resolution of physical mapping and genetic mapping techniques, a cDNA precisely localized to a chromosomal region associated with the disease could be one of between 50 and 500 potential causative genes. (This assumes l megabase mapping resolution and one gene per 20 kb.)
Comparison of affected and unaffected individuals generally involves first looking for structural alterations in the chromosomes, such as deletions or translocations that are visible from chromosome spreads or detectable using PCR based on that cDNA sequence. Ultimately, complete sequencing of genes from several individuals is required to confirm the presence of a mutation and to distinguish mutations from polymorphisms.
In addition to the foregoing, the sequences of the invention, as broadly described, can be used to control gene expression through triple helix formation or antisense DNA or RNA, both of which methods are based on binding of a polynucleotide sequence to DNA or RNA. Polynucleotides suitable for use in these methods are usually 20 to 40 bases in length and are designed to be complementary to a region of the gene involved in transcription (triple helix - see Lee et al, Nucl. Acids Res. 6: 3073 (1979) ; Cooney et al, Science 241: 456 (1988); and Dervan et al. Science 251: 1360 (1991)) or to the mRNA itself (antisense - Okano, J. Neuroche . 56: 560 (1991) ; Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, FL (1988)). Triple helix formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. Both techniques have been demonstrated to be efficient in model systems. Information contained in the sequences of the present invention is necessary for the design of an antisense or triple helix oligonucleotide.
The present invention is also a useful tool in gene therapy, which requires isolation of the disease-associated gene in question as a prerequisite to the insertion of a normal gene into an organism to correct a genetic defect. The high specificity of the cDNA probes according to this invention have promise of targeting such gene locations in a highly accurate manner.
The sequences of the present invention, as broadly defined, are also useful for identification of individuals from minute biological samples. The United States military, for example, is considering the use of restriction fragment length polymorphism (RFLP) for identification of its personnel. In this technique, an individual's genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identifying personnel. This method does not suffer from the current 1imitations of "Dog Tags" which can be lost, switched, or stolen, making positive identification difficult. The sequences of the present invention are useful as additional DNA markers for RFLP. However, RFLP is a pattern based technique, which does not directly focus on the actual DNA sequence of the individual. The sequences of the present invention can be used to provide an alternative technique that determines the actual base-by-base DNA sequence of selected portions of an individual's genome. These sequences can be used to prepare PCR primers for amplifying and isolating such selected DNA. One can, for example, take an EST of the invention and prepare two PCR primers from the 5' and 3' ends of the EST. These are used to amplify an individual's DNA, corresponding to the EST. The amplified DNA is sequenced.
Panels of corresponding DNA sequences from individuals, made this way, can provide unique individual identifications, as each individual will have a unique set of such DNA sequences, due to allelic differences. The sequences of the present invention can be used to particular advantage to obtain such identification sequences from individuals and from tissue, as explained in Examples 10 - 12. The EST sequences from Example 1 and the complete sequences from Example 11 uniquely represent portions of the human genome. Allelic variation occurs to some degree in the coding regions of these sequences, and to a greater degree in the noncoding regions. It is estimated that allelic variation between individual humans occurs with a frequency of about once per each 500 bases. Each of the ESTs or complete coding sequences comprising a part of the present invention can, to some degree, be used as a standard against which DNA from an individual can be compared for identification purposes. Because greater numbers of polymorphisms occur in the noncoding regions, fewer sequences are necessary to differentiate individuals. The noncoding sequences of Table 9 for example, could comfortably provide positive individual identification with a panel of perhaps 100 to 1,000 primers which each yield a noncoding amplified sequence of 100 bp. If predicted coding sequences, such as those from Table 6, are used, a more appropriate number of primers for positive individual identification would be 500-2,000. If a panel of reagents from ESTs or complete sequences of this invention is used to generate a unique ID database for an individual, those same reagents can later be used to identify tissue from that individual. Positive identification of that individual, living or dead can be made from extremely small tissue samples.
Another use for DNA-based identification techniques is in forensic biology. PCR technology can be used to amplify DNA sequences taken from very small biological samples such as tissues, e.g., hair or skin, or body fluids, e.g., blood, saliva, semen, etc. In one prior art technique, gene sequences are amplified at specific loci known to contain a large number of allelic variations, for example the DQα class II HLA gene (Erlich, H. , PCR Technology, Freeman and Co. (1992)) . Once this specific area of the genome is amplified, it is digested with one or more restriction enzymes to yield an identifying set of bands on a Southern blot probed with DNA corresponding to the DQα class II HLA gene.
The sequences of the present invention can be used to provide polynucleotide reagents specifically targeted to additional loci in the human genome, and can enhance the reliability of DNA-based forensic identifications. Those sequences targeted to noncoding regions (see, e.g.. Tables 8 and 9) are particularly appropriate. As mentioned above, actual base sequence information can be used for identification as an accurate alternative to patterns formed by restriction enzyme generated fragments. Reagents for obtaining such sequence information are within the scope of the present invention. Such reagents can comprise complete
ESTs or corresponding coding regions, or fragments of either of at least 15 bp, preferably at least 18 bp.
There is also a need for reagents capable of identifying the source of a particular tissue. Such need arises, for example, in forensics when presented with tissue of unknown origin. Appropriate reagents can comprise, for example, DNA probes or primers specific to particular tissue prepared from the ESTs or complete sequences of the present invention. Panels of such reagents can identify tissue by species and/or by organ type. In a similar fashion, these reagents can be used to screen tissue culture for contamination.
V. Production of Polypeptide Corresponding to ESTs
As previously explained, each EST corresponds not only to a coding region, but also to a polypeptide. Once the coding sequence is known, or the gene is cloned which encodes the polypeptide, conventional techniques in molecular biology can be used to obtain the polypeptide.
At the simplest level, the amino acid sequence encoded by the polynucleotide sequence can be synthesized using commercially available peptide synthesizers. This is particularly useful in producing small peptides and fragments of larger polypeptides. (Fragments are useful, for example, in generating antibodies against the native polypeptide.)
Alternatively, the DNA encoding the desired polypeptide can be inserted into a host organism and expressed. The organism can be a bacterium, yeast, cell line, or multicellular plant or animal. The literature is replete with examples of suitable host organisms and expression techniques. For example, naked polynucleotide (DNA or mRNA) can be injected directly into muscle tissue of mammals, where it is expressed. This methodology can be used to deliver the polypeptide to the animal, or to generate an immune response against a foreign polypeptide (Wolff, et al., Science 247:1465
(1990); Feigner, et al., Nature 349:351 (1991).
Alternatively, the coding sequence, together with appropriate regulatory regions (i.e., a construct), can be inserted into a vector, which is then used to transfect a cell. The cell (which may or may not be part of a larger organism) then expresses the polypeptide. (See Example 23.) Antibodies generated against the polypeptide corresponding to a sequence of the present invention can be obtained by direct injection of the naked polypeptide into an animal (as above) or by administering the polypeptide to an animal, preferably a nonhuman. The antibody so obtained will then bind the polypeptide itself. In this manner, even a sequence encoding only a fragment of the polypeptide can be used to generate antibodies binding the whole native polypeptide. Such antibodies can then be used to isolate the polypeptide from tissue expressing that polypeptide.
Moreover, a panel of such antibodies, specific to a large number of polypeptides, can be used to identify and differentiate such tissue.
VI. Examples
Certain aspects of the present invention are described in greater detail in the non-limiting Examples that follow.
EXAMPLE 1 cDNA Sequences Determined by Random Clone Selection: First set
METHODOLOGY:
With reference to the data presented in Table 1, lambda ZAP libraries were converted en masse to pBluescript plasmids, transfected into E. coli XLl-Blue cells, and plated on X- gal/IPTG/ampicillin plates. A total of 1058 clones were picked at random from three human brain cDNA libraries: fetal brain, two-year-old hippocampus, and two-year-old temporal cortex (Stratagene catalog #936206, 936205, 935, respectively. Stratagene, 11099 N. Torrey Pines Rd., La Jolla, CA 92037). An analysis of these clones is summarized in Table I (see below) In addition, clones selected from the hippocampus library were also analyzed after subtractive hybridization with the fibroblast library. These results are listed in the "Hippocampus Subtracted" column of Table 1. Templates for DNA sequencing were PCR products or plasmids prepared by the alkaline lysis method. About half of the templates prepared by PCR failed to yield an amplified fragment suitable for sequencing. This was primarily due to use of PCR conditions that minimized the need for further purification of the product but also selected against amplification of long inserts (5 μl fresh or frozen overnight culture of E. coli carrying the pBluescript plasmid, 7.5 μM each dNTP, and 0.1 μ each primer for 35 cycles: 94°C, 40 sec; 55°C, 40 sec; 72°C, 90 sec) . A further percentage of the PCR-generated templates failed to sequence, largely due to primer-dimer or other amplification artifacts. QiagenN columns improved the percentage of plasmid templates, increasing the yields of usable sequence from about 60% with a standard alkaline lysis protocol to over 90%. Overall, 117 PCR-generated templates and 497 plasmid templates resulted in usable sequence. Dideoxy chain termination sequencing reactions were performed with fluorescent dye-labeled M13 universal or reverse primers. After a cycle sequencing protocol, carried out in a Perkin- Elmer thermal cycler, sequencing reactions were run on an Applied Biosystems, Inc. (Foster City, CA) 373A automated DNA sequencer. (Cycle sequencing was performed in a Perkin Elmer Thermal Cycler for 15 cycles of 95°C, 30 sec; 60°C, 1 sec; 70βC, 60 sec and 15 cycles of 95°C, 30 sec; 70βC, 60 sec with the Applied Biosystems, Inc. Taq Dye Primer Cycle Sequencing Core Kit protocol) . Some sequencing reactions were performed on an ABI robotic workstation (Cathcart, Nature 347: 310 (1990) hereby incorporated by reference) .
RESULTS:
Singe-run DNA sequence data were obtained from 609 randomly chosen cDNA clones. The number of clones sequenced from each library is summarized in Table 1. Double-stranded cDNA clones in the pBluescript vector were sequenced by a cycle sequencing protocol with dye-labeled primers and Applied Biosystems, Inc. 373A DNA Sequences. The average length of usable sequence was 397 bases with a standard deviation of 99 bases.
Subtractive hybridization has been used successfully to reduce the population of highly represented sequences in a cDNA library by selectively removing sequences shared by another library. (Schmid and Girou, Neurochem. 48: 307 (1987); Fargnoli et al, Anal. Biochem. 187: 364 (1990); Duguid and Dinauer, Nucl. Acids. Res. 18: 2789 (1990); Schweinfest, et al, Genet. Anal. Techn. Appl. 7: 64 (1990); Travis and Sutcliffe, Proc. Natl. Acad. Sci. USA 85: 1696 (1988); Kato, Eur. J. Neurosci. 2: 704 (1990)). Subtractive hybridization was therefore tested as a way of enhancing the number of brain-specific clones in the hippocampus library by hybridizing the hippocampus library with a WI38 human lung fibroblast cell line cDNA library and removing the common sequences (Schweinfest et al. Genet. Anal. Techn. Appl. 7: 64 (1990); Sive and St. John, Nucl. Acids Res. 16: 10937 (1988)). Clones from this subtraction are listed in the column "Hippocampus Subtracted" in Table 1.
The EST sequences from this Example 1 are identified as SEQ ID NOs 1-315.
TABLE 1. cDNA Library Composition Determined By Random Clone Sequencing
Figure imgf000034_0001
EXAMPLE 2
EST Characterization: First Set
ESTs including SEQ ID NOs 1-315 were analyzed as follows. Initially, the EST sequences were examined for similarities in the GenBank nucleic acid database (GenBank Release 65.0), Protein Information Resource Release 26.0 (PIR) , and ProSite (MacPattern from the EMBL data library, Fuchs R. Comput. Appl. Biosci. 7: 105 (1990) Release 5.0 were used). BLAST was used to search Genbank and the PIR (both maintained by the National Center for Biotechnology Information) ESTs without exact GenBank matches were translated in all six reading frames and each translation was compared with the protein sequence database PIR and the ProSite protein motif database. Comparisons with the ProSite motif database were done by means of the program MacPattern from the EMBL Data Library. GenBank and PIR searches were conducted with the "basic local alignment search tool" programs for nucleotide (BLASTN) and peptide (BLASTX) comparisons (Altschul et al, J. Mol. Biol. 215: 403 (1990)). PIR searches were run on the National Center for Biotechnology Information BLAST network service. The BLAST programs contain a very rapid database-searching algorithm that searches for local areas of similarity between two sequences and then extends the alignments on the basis of defined match and mismatch criteria. The algorithm does not consider the potential gaps to improve the alignment, thus sacrificing some sensitivity for a 6-80 fold increase in speed over other database-searching programs such as FASTA (Pegarson and Lipman, Proc. Natl. Acad. Sci. USA, 85: 2444 (1988)).
Sequence similarities identified by the BLAST programs were considered statistically significant with a Poisson P- value than 0.01. The Poisson P-value less than the probability of as high a score occurring by chance given the number of residues in the query sequence and the database. After the BLASTN search, 30 unmatched ESTs were compared against GenBank by FASTA to determine if significant matches were missed due to the use of BLASTN for the database search. No additional statistically significant matches were found. Statistical significance does not necessarily mean functional similarity; some of the reported matches may indicate the presence of a conserved domain or motif or simply a common protein structure pattern. Those ESTs identified as fully corresponding to known human genes or proteins are not included in this disclosure. Statistically significant matches are reported in Table 2, together with the length and percent identity or similarity of each alignment.
On the basis of database searches, 609 EST sequences were classified into eight groups as shown in Table 1 (see Example 1 above) . Four groups, with 197 or 32% of the sequences, consist of matches to human sequences: repetitive elements, mitochondrial genes, ribosomal RNA genes, and other nuclear genes. Forty-eight (8%) of the sequences matched non-human entries in GenBank or PIR while 230 (38%) had no significant matches. The remaining 134 (22%) sequences contained no insert or consisted entirely of polyA between the EcoRI cloning sites.
Thirty-six ESTs matched previously sequenced human nuclear genes with more than 97% identity. Four of these ESTs are from genes encoding enzymes involved in maintaining metabolic energy, including ADP/ATP translocase, aldolase C, hexokinase, and phosphoglycerate kinase. Human homologs of genes for the bovine mitochondrial ATP synthase F0B-subunit and porcine aconitase were also found (Table 2) . Brain- specific cDNAs included synaptophysin, glial fibrillary acidic protein (GFAP) , and neurofilament light chain. At least six ESTs are from genes encoding proteins involved in signal transduction: 2' ,3'-cyclic nucleotide 3'-phosphodiesterase (2 ESTs), calmodulin, c-erbA-α-2, Gsα, and Na+/K* ATPase α-subunit. Other ESTs were matches to genes for ubiquitous structural proteins — actins, tubulins, and fodrin (non-erythroid spectrin) . ESTs also document the presence in the hippocampus cDNA library of the ret proto-oncogene, the ras-related gene rhoB, and one of the chromosome 22 breakpoint cluster region transcripts. Eight ESTs are from genes known to be associated with genetic disorders (Online Mendelian Inheritance in Manl . More than half of the human-matched ESTs from Example 1 have been mapped to chromosomes, indicating the bias of GenBank entries toward well-studied genes and proteins.
ESTs without significant GenBank matches were also compared to the ProSite database of recognized protein motifs. Not counting post-translational-modification signatures, fifty-four sequences contained motifs from the database. Some patterns, particularly the "leucine zipper", are found in scores or hundreds of proteins that do not share the functional property implied by the presence of the motif.
Similarities to sequences from other organisms were also detected in the BLAST searches of GenBank and PIR (Table 2) . Several ESTs displayed similarity to "housekeeping" genes, including the ribosomal proteins S10 and L30 (rat) and the above glycolytic enzymes. EST00257 (SEQ ID NO:77) shows strong nucleotide sequence similarity to the squid (67%) and Drosophila (70.4%) kinesin heavy chain. Kinesin was first described as a microtubule-associated motor protein involved in organelle transport in the squid giant axon (Vale et al, Cell 42: 39 (1985)). Six oncogene-related sequences were also among the cDNA clones sequenced. EST00299 (SEQ ID NO:180) and EST00283 (SEQ ID NO:271) show similarity to several ras- related genes and EST00248 (SEQ ID NO:102) matched the 3' untranslated region of the bovine substrate of botulinum toxin ADP-ribosyltransferase. Similarities with an S. cerevisiae RNA polymerase subunit and Torpedo electromotor neuron- associated protein were also observed. Two ESTs may represent new members of known human gene families: EST00270 matched the three β-tubulin genes with 88-91% identity and EST00271 (SEQ ID NO:248) matched α-actinin with 85% identity at the nucleotide level. Among the most interesting of the primary sequence relationships was the similarity of ESTs to the Drosophila genes Notch and Enhancer of split. Nucleotide and peptide alignments of EST00256 (SEQ ID NO:188) and EST00259 (SEQ ID NO:227) with the Drosophila genes have been demonstrated. Both genes are part of a signal cascade encoded by the "neurogenic" genes that are involved in the differentiation of neuronal and epidermal cell lineages in the neuroectoderm of the developing Drosophila embryo (Campos-Ortega, Trends in Neuro. Sci. 11: 400 (1988)) . It has been proposed that the Enhancer of split protein interacts with a membrane protein that is the product of the Notch gene to convert a developmental signal into an altered pattern of gene expression (id. J. Mol. Biol. 215: 403 (1990)). EST00256 (SEQ ID NO:188) matches near the 5' end of the Enhancer of split coding sequence, away from the mammalian G protein β subunit- and yeast cdc4-like elements (Hartley et al. Cell 55: 785 (1988); Klambt et al. EMBO J. 8: 203 (1989)). Part of the EST00259 (SEQ ID NO:227) match to Notch in the cdclO/SW16 region that is similar to three cell-cycle control genes in yeast and is tightly conserved in the Xenopus Notch homolog, Xotch. In Drosophila, Enhancer of split is absolutely required for formation of epidermal tissue. Notch contains several epidermal growth factor-like repeats and appears to play a general role in cell-cell communication during development (Banerjee and Zipursky, Neuron 4:177 (1990) ) . Seven genes were represented by more than one EST. Comparisons of all the ESTs against one another revealed two overlaps of unknown ESTs: EST00233 (SEQ ID NO:32) and EST00234 (SEQ ID NO:8) match in opposite orientations and EST00235 (SEQ ID NO:204) and EST00236 (SEQ ID NO-.148) match in the same orientation beginning at the same nucleotide. Five human genes were represented by more than one EST: β-actin (3) , λ-actin (2) , α-tubulin (2) , α-2-macroglobulin (2) , and 2'3'-cyclic-nucleotide-3'-phosphodiesterase (2). Those few instances where two or more ESTs represent different portions of a single cDNA can be readily ascertained when the sequence of the full cDNA insert is determined in accordance with Example 11.
Table 2: ESTs Identified by Database Hatches
Figure imgf000040_0001
There is little redundancy in EST sequencing according to the present invention. Of the nuclear-encoded messenger RNAs, the most common ESTs were to the -actin (approximately 0.6% of the EST clones) and myelin basic protein genes (MBP, approximately 0.5% of the clones). MBP, a highly expressed structural component of nerve tissue (Kamholtz, J. , de Ferra, F. , Puckett, C. , & Lazzarini, R. Proc. Natl. Acad. Sci., USA 83: 4962-4966 (1986)), displays four alternate splicing forms, of which it is believed at least two are present among the ESTs reported here. Other common ESTs were Gs-alpha gamma-actin and both a- and alpha- tubulin.
By matching ESTs to known database sequences, a phenotypic characterization of the tissue begins to emerge. Protein superfamilies matched by ESTs were grouped into three broad functional categories to assess the biological spectrum represented by these randomly selected cDNA clones. Structural and metabolic classes comprised about 30% of the' ESTs with database matches. Twenty-five percent were involved in regulatory pathways and the remainder were not classifiable. In addition, it is believed that several genes not previously known to be expressed in the brain were matched, including spermine/spermidine acetyltransferase (Casero, R. , Celano, P, Ervin, S., Applegren, N. , Wiest, L. & Pegg, A. J. Biol. Chem. 266: 810-814 (1991)) and osteopontin (Young, M. , Kerr, J., Termine, J., Wewer, U. , Wang, M. , McBride, W. & Fisher, L. Genomics 7:491-502 (1990) ) .
EXAMPLE 3
Mapping of ESTs to Human Chromosomes
Randomly selected ESTs corresponding to Sequence Identification numbers were assigned to chromosomes via PCR (see Table 3) . Oligonucleotide primer pairs were designed from EST sequences to minimize the chance of amplifying through an intron. The oligonucleotides were 18-23 bp in length and designed for PCR amplification using the computer program INTRON (National Institutes of Mental Health, Bethesda, MD) . The program is based on the assumptions that: 1) introns are genomic sequences that interrupt the coding and noncoding sequences of genes (Smith, J. Mol. Evol. 27:45-55 (1988)); 2) there are consensus sequences for splice junctions (Shapiro, et al., Nucl. Acids Res. 15:7155-7174 (1987)); and 3) that 90% of the human genes studied have 3' untranslated regions of mRNA not interrupted by introns in the genomic DNA (Hawkins, Nucl. Acids Res. 16:9893-9908 (1988)).
The program evaluates the likelihood that a given GG or CC dinucleotide represents a former exon-intron boundary. Specifically, every input strand is processed by the INTRON program twice, first evaluating the sense mRNA strand, and then processing the complementary or anti-sense strand. The program evaluates each sequence by finding all GG or CC pairs (possible former splice sites) , searching for STOP codons in all three reading frames, and analyzing the GG or CC pairs surrounded by stop codons. All regions of the EST that are unlikely to contain splice junctions based on CC content, GG content, and stop codon frequency are then marked by the program in uppercase. The creation of PCR primers from known sequences is well known to those with skill in the art. For a review of PCR technology see Erlich, H.A. , PCR Technology; Principles and Applications for DNA Amplification. 1992; W.H. Freeman and Co., New York. ESTs were examined for the presence of stop codons in each reading frame and for consensus splice junctions. The presence of stop codons and absence of splice junction sequences are more characteristic of 3' untranslated sequences than of introns. The untranslated sequences are unique to a given gene; thus, primers from these regions are less likely to prime other members of a gene family or pseudogenes.
The primers were used in polymerase chain reactions (PCR) to amplify templates from total human genomic DNA. PCR conditions were as follows: 60 ng of genomic DNA was used as a template for PCR with 80 ng of each oligonucleotide primer, 0.6 unit of Tag polymerase, and 1 uCu of a 32P-labeled deoxycytidine triphosphate. The PCR was performed in a microplate thermocycler (Techne) under the following conditions: 30 cycles of 94°C, 1.4 min; 55°C, 2 min; and 72°C, 2 min; with a final extension at 72°C for 10 min. The amplified products were analyzed on a 6% polyacrylamide sequencing gel and visualized by autoradiography. If the size of the resulting product was equivalent to the EST from which the primers are derived, then the PCR reaction was repeated with DNA templates from two panels of human-rodent somatic cell hybrids; BIOS PCRable DNA (BIOS Corporation) and NIGMS Human-Rodent
Somatic Cell Hybrid Mapping Panel Number 1 (NIGMS, Camden, NJ) .
PCR was used to screen a series of somatic cell hybrid cell lines containing defined sets of human chromosomes for the presence of a given EST. DNA was isolated from the somatic hybrids and used as starting templates for PCR reactions using the primer pairs from EST sequences selected above. Only those somatic cell hybrids with chromosomes containing the human gene corresponding to the EST will yield an amplified fragment. ESTs were assigned to a chromosome by analysis of the segregation pattern of PCR products from hybrid DNA templates. For a review of techniques and analysis of results from somatic cell gene mapping experiments. (See Ledbetter et al., Genomics 6:475- 481 (1990).) The single human chromosome present in all cell hybrids that give rise to an amplified fragment represents the chromosome containing that EST.
The assignment of 81 ESTs and corresponding genes to chromosomes by PCR is shown in Table 3. Table 3: Assignment of ESTs to Chromosomes by PCR
Figure imgf000044_0001
SE D # Chr PRIMER #1 PRIMER #2
9 TCTGGGCTTCTGTGGTTCAA CTGGCTGCTCAGCAACTCAT
10 AGCTGTTCCTGAGAGATGCA CCTTGTGAAGAAAGACTTTC 10 TCAGCAACAGGTCACTTTGG CTAAGCATCTGCATGTCCAG 10 TACTAGCATTTCTTACTCTC TATGCTGATTGTTTGCACTC
10 GGTGATTAGAGAGTCTGTTG GAACTCTGTAGTGTTCTAAA
11 GGAAATTAGGCTTAGCTCAC GTGCAGAATACTTAGAGTCC 11 GTTTGAAGGAAGTGATTTCC TAGGGCCACCTCCAGTTCAT 11 GTCTTTGGATTCTACGTAGA CGATAATGACATTTCTTCTGG
11 AL2-CTAACCACAACCCACACATTG CCTCAGCACAAGAGAAGAATGG
12 AACTTGCAACATAAATACTAG GAGCAATGATTTCTAACAGT
13 TTGTGTACTGTCTGATAGAC TAAGCCATGGGCATCTATAA
14 GGTGCTTAAGGCCACTTTTG CTTAGAGGATCATAGGTCTG 14 CCAGGAGAGTAAGAAGATCA GCAGAGTTGAATATGAACCT 14 GTGCCAAGATGGCTCATGTA GTATAGCTTTAAGCCAGTTC 14 AATGCATTATGCCTGGTCTT GGAAAAGTCTAGAACTTAGT
14 AAGCTGGCTGGGAAATGTTC GTCATGCTAGTAAACTTACAC
15 GTGACAGACCATGTCTATTG AAGTGAGCGATTGCACCTTC
15 AGGATGACCTGAGTGAGCTG CCATGGCAGCAAGGAACTCT
16 TGTGTGAAAGGGAGTCTTGT CCATTTTGACTGTTCCATAG 16 TGGCTAGGGCAGGCCTTAAA GAGAAGAATATCAAATGGGG
16 CCATCTGTGTCCCAATTAAGC AGGGAAGAAGTCTAGAGCGA
17 CAAAGACGGGAGACGAATGA AGTGGAACGCGTGGCCTATG 19 AGAGATGTCAGTCCATTATC CTATTCCACCTTACTCAAGG
19 CATCATGTCGGAGACGCATT TGGATGACCTGAGTCTGCAG
20 AGTTCTGGAGGCTAGGAGTT ATGTAAGGACCCCTAGATGG 20 TGTCAACTTCCCTTTGGCCT GAAGCTTGCTCATTCAGGAA
20 AL2-TCGGAGAAGTTGCAGTTTCTG GTTAAAAGCTGTTAGACGGGGC
22 CACTGACTGACTCCTCTTTA GGAACCGTAACTCTCCATAG
X ATTGACCTTCAATGTAATAA TTGGATTGGGCAAAATAG
Figure imgf000045_0001
X ATGTGAGCATCTATACCTGC AATGAAGGCATGAGAATAGG
Abbreviation: AL2 : Amino-Link-2 Fluorescent Tag, Chr.: Chromosome.
T The foregoing techniques have been used to further localize 6 ESTs and their associated genes to precise locations onto chromosome 6 or chromosome X, as reflected in Table 4 (in Example 5 below) , using sublocalization techniques that employ somatic cell hybrids. ESTs were used as hybridization probes and mapped to other chromosomes using techniques disclosed in Example 5. Somatic cell hybrids were prepared that contained defined subsets of chromosomes 6 and X. Methods for preparing and selecting somatic cell hybrids are known in the art. For a review of an exemplary procedure to generate somatic cell hybrids containing the short arm of human chromosome 6, see Zoghbi, et al., Genomics 9(4):713-720 (1991). For a general review of somatic cell hybridization see Ledbetter et al. (supra) . The hybrids were processed to obtain DNA and analyzed by PCR and by fluorescence in situ hybridization. SEQ ID NOs 19, 22, 1, 224, 288 mapped to chromosome 6, while SEQ ID NO 162 mapped to chromosome X using somatic cell hybrids.
EXAMPLE 4 Mapping of All ESTs to Human Chromosomes
The procedure of Example 3 is repeated for all of the ESTs from Example l not previously mapped to human chromosomes. Data are generated corresponding to the data in Table 3 for all of the unmapped ESTs. As previously mentioned, virtually all of the ESTs will map to a unique chromosomal location. The inability of any ESTs to localize to a unique location will be readily ascertainable during the mapping process.
EXAMPLE 5
Alternative Technigue for Mapping to Chromosomes Mapping of ESTs to chromosomes using fluorescence in situ hybridization
This technique is used to map an EST to a particular location on a given chromosome. Cell cultures, tissue, or whole blood can be used to obtain chromosomes.
0.5 ml. of whole blood is added to RPMI 1640 and incubated 96 hours in a 5%C02/37βC incubator. 0.05 ug/ml colcemide is added to the culture one hour before harvest. Cells are collected and washed in PBS. The suspension is incubated with a hypotonic solution of KC1 added dropwise to reach a final volume of 5 ml. The cells are spun down and fixed by resuspending the cells in methanol and glacial acetic acid (3:1). The cell suspension is dropped onto glass slides and dried. The slides are then treated with RNase A and washed then dehydrated in a series of increasing concentrations of ethanol.
The EST to be localized is nick-translated using fluorescently labeled nucleotide (Korenberg, Jr., et al., Cell 53(3) :391-400 (1988)). Following nick translation, unincorporated label is removed by spin dialysis through Sepharose. The probe is further extracted with phenol-chloroform to remove additional protein. The chromosomes are denatured in formamide using techniques known in the art and the denatured probe added to the slides. Following hybridization, the cells are washed. The slides are studied under a fluorescent microscope. In addition, the chromosomes can be stained for G-banding or Q-banding using techniques known in the art.
The resulting metaphase chromosomes have fluorescent tags localized to those regions of the chromosome that are homologous to the EST. Thus, a particular EST is localized to a particular region on a given chromosome. For a review of the technique, see Verma et al., Human Chromosomes: A Manual of Basic Techniques. Pergamon Press, NY (1988) , which is hereby incorporated by reference. Table 4: Precise Chromosomal Localization of ESTs
Figure imgf000048_0001
EXAMPLE 6 Automated DNA Sequencing Accuracy
ESTs that match human sequences in GenBank are excellent tools for the analysis of the accuracy of double- strand automated DNA sequencing. EST/GenBank matches from a number of clones were examined for the number of nucleotide mismatches and gaps required to achieve optimal alignment by the Genetics Computer Group (GCG) program BESTFIT (Devereux et al, Nucleic Acids Research 12: 387 (1984)). The number of mismatches, insertions and deletions was counted for each hundred bases of the sequence (Table 5) . As expected, the sequence quality was best closest to the primer and decreased rapidly after about 400 bases. The number of deletions and insertions relative to the GenBank reference sequence increased five- to ten-fold beyond 400 bases, while the number of mismatches doubled. The average accuracy rate for individual double-stranded sequencing runs was 97.7% to 400 bases. TABLE 5. Accuracy Of Single-Run Double-Stranded Automated Sequencing
Figure imgf000049_0001
ESTs statistically identical to known human sequences and those matching mitochondrial and ribosomal genes were aligned with sequenced from GenBank using the GCG program BESTFIT. The first 85 nucleotides was polylinker sequence which was not aligned with the pBluescript SK reference sequence. Tabulation of errors began 15 bases into the BESTFIT alignment and thus is reported beginning with bases 101-200. Error rates are reported as number of mismatches, insertions, or deletions per hundred aligned bases. "Mismatches" includes ambiguous base calls.
EXAMPLE 7
Probability of ESTs Containing Coding Sequences
The ESTs of the present invention were statistically evaluated using the coding-region prediction program CRM via the GRAIL server (Uberbacher, E. & Mural, R. Proc. Natl. Acad. Sci. USA, 88: 11261-5 (1991)). The CRM program uses a neural network to combine results from several different coding regions by looking at different 6 bp sequences found in coding exons and in introns. The program additionally conducts reading frame searches and assesses randomness at the third position of codons. This protocol categorizes sequences as having an excellent, good, marginal, or poor probability of containing coding regions. The results are reported in Tables 6-9. There were 32 ESTs categorized as "excellent" (Table 6) ; 14 categorized as "good" (Table 7) ; 13 categorized as "marginal" (Table 8) ; and 213 categorized as "poor" (Table 9) . These results indicate that most ESTs of the present invention comprise noncoding regions.
Table 6: ESTs with Excellent Probability of Containing Coding Sequence
Figure imgf000051_0001
Table 7: ESTs with Good Probability of Containing Coding Sequence
Figure imgf000052_0001
Table 8 : ESTs with Marginal Probability of Containing Coding Sequence
Figure imgf000053_0001
Table 9: ESTs with Poor Coding Probability
Figure imgf000054_0001
EXAMPLE 8 Functional Groupings of ESTs and Corresponding Genes
By matching new human ESTs to known sequences from other species, the apparent function of the gene corresponding to the EST can be ascertained. The data generated in Example 2 have been used to categorize 28 of the ESTs of the present invention, and their corresponding genes, into predicted functional groups. (These 28 are ESTs with database matches to sequences from other species for which a function was known.) Two different grouping schemes have been used.
The first scheme separates the sequences into three broad categories: metabolic; regulatory; and structural. These groupings are set out in Table 10.
The second grouping scheme separates the sequences into 13 specific categories: cell surface proteins; developmental control; energy metabolism; kinases and phosphatases; oncogenes; other metabolism-related polypeptides; peptidases and peptidase inhibitors; receptors; structural and cytoskeletal; signal transduction; transporters; transcription, translation, and subcellular localization; and transcription factors. These groupings are set out in Table 11.
Table 10: Three-Class Functional Groupings of ESTs
Figure imgf000056_0001
Table 11: Thirteen-Class Functional Groupings of ESTs
SEO ID ST Gro Putative Identification
60K filarial antigen
Lysosomal membrane glycoprotein 1 (LAMP-1)
Enhancer of split
Maternal G10 protein
Notch/Xotch
Aconitase
Fo ATPase beta subunit, mitochondrial
Protein-tyrosine phosphatase LRP
Transforming protein (dbl) ras p21-like small GTP-binding protein (smg GDS) rho H12/ ARH12
Prolyl endopeptidase trkB
Actin, other
Agrin
Kinesin
Kinesin
Microtubule-associated protein IB
Tubulin, beta
MARCKS (myristoylated alanine-rich protein kinase smg p25A GDP dissociation inhibitor
Processing enhancing protein
RNA polymerase II 6th subunit (RPO26)
Ribosomal protein L30
Ribosomal protein S10
Wilm's tumor-related protein
Figure imgf000057_0001
Zinc Finger Proteins
Group Key: CS: Cell Surface, DC: Developmental Control, EM: Energy Metabolism, KP: Kinases and Phosphatases, OG: Oncogenes, PI: Peptidases and Peptidase Inhibitors, RT: Receptors, SC: Structural and Cytoskeletal, ST: Signal Transduction, TT: Transcription, Translation, and Subcellular Localization, TX: Transcription Factors. EXAMPLE 9 cDNA Libraries Generated From Specific Genomic DNA by Exon Expression & Amplification
Exon amplification is used to express potential exons from genomic DNA in a recombinant vector that contains some of the signals necessary for splicing. If an exon is present in the proper orientation in the vector, that exon will be spliced in a mammalian cell and will become part of the mRNA of that cell. The exon splice-product can be purified from other mRNA in the cell by conversion of the mRNA to cDNA and selective amplification of the recombinant splice-product cDNAs. Cosmid DNA from human chromosome 19ql3.3 is digested with Ba HI or BamHI/Bglll restriction enzymes. The fragments generated are collected and size specifically cloned into an expression vector (Buckler, et al. Proc. Nat'l. Acad. Sci. USA, 88:4005-4009 (1991)). After transfection by electroporation of these constructs into COS cells, RNA transcripts are generated using the SV40 early promoter and a polyadenylation signal derived from SV40 both present in the expression vector. When a fragment of genomic DNA contains an entire exon with flanking intron sequence in the sense orientation, the exon should be retained in the mature poly(A)+ cytoplasmic RNA. Therefore, the mRNA is used as template for cDNA synthesis using reverse transcriptase and vector-priming. Subsequently, the cDNAs are amplified by vector-priming using PCR. A fraction of this first PCR product is reamplified using internal vector-primers containing terminal cloning sites. These products are end- repaired with T4 DNA polymerase, digested with the appropriate restriction enzymes, gel purified and cloned into pBluescript vectors. The constructs are transfected into XLl-Blue competent cells and plated on LB/X-gal/IPTG/ampicillin plates. When multiple cosmids or YAC clones are used as the source DNA, a pool of specific expressed exons is obtained as a cDNA library.
EXAMPLE 10 PCR Amplification from Predicted Exons
Computational analyses can be applied to genomic DNA sequences to predict protein coding regions. The coding region prediction program CRM (E. Uberbacher and R. Mural, Proc. Natl. Acad. Sci. USA 88:11261-5 (1991)) finds open reading frames and classifies them according to their probability of being coding regions. These regions are subsequently examined using the GM program (C. Fields and C. Soderlund, Comp. Applic. Biosci. 6: 263, 1990), which predicts intron-exon structure. PCR primers are then designed to amplify the predicted exons and used to test human cDNA libraries (for example, fetal brain or placental libraries) for the presence of these putative exons using a PCR assay.
This strategy has been successfully applied in two large scale genomic sequencing projects, the Huntington's locus of human chromosome 4pl6.3 (McCombie, et al., submitted) and human chromosome locus 19ql3.3 (Martin-Gallardo, et al., submitted) .
EXAMPLE 11
Complete Sequence of EST Clone Inserts
There are a number of methods known to those with skill in the art of molecular biology, to obtain sequence information from the cDNAs corresponding to the EST sequences. Procedures for these methods are provided in Basic Methods in Molecular Biology (David et al. supra) . One way to acquire more information about the cDNA from which an EST was derived is to sequence the remainder of the cDNA clone. The complete sequence of the inserts of four EST clones (representing SEQ ID NOs 188, 189, 223, and 227) was determined using Exonuclease III deletions. Briefly, EST clones were digested with the restriction enzymes Sail and Kpnl or Pstl and BamHI (for deletions from the Forward primer and Reverse primer ends of the insert, respectively) . The Kpnl and Pstl enzymes leave 3* sticky ends following digestion, which Exonuclease III is unable to bind. This results in unidirectional deletions into the cDNA insert leaving the vector sequence undisturbed. After addition of Exonuclease III to the Forward and Reverse deletion reactions, aliquots of the reaction were removed at defined time intervals and the reaction was stopped to prevent further deletion. SI nuclease and Klenow DNA polymerase were added to create blunt ended fragments suitable for ligation.
Samples for each time point was purified by electrophoresis through an agarose gel and religated. Two to four representative clones from each time point in each direction were sequenced to give between 200 and 400 base pairs of sequence data. Careful selection of deletion conditions and time points allow a deletion series of approximately 100-200 base pairs difference in length at each consecutive time point. Sequence fragments were reassembled into a redundant contiguous sequence using the INHERIT software from Applied Biosystems, Inc. (Foster City, CA) . In this way, the complete insert from these four cDNA clones was sequenced on both strands to an average redundancy between three and four (each base was sequenced between three and four times, on average) . EXAMPLE 12
Determining Re ding Frame, Orientation, Coding Regions: ESTs and Complete cDNA Sequences
Once the complete cDNA sequence has been determined in accordance with Example 11, the reading frame, orientation, and coding regions are determined by computer techniques. (The complete coding region is considered to be the largest open reading frame from a methionine to a stop codon.) Specifically, the CRM program on the GRAIL server is used as explained in Example 7 to determine probable coding regions. This information is supplemented by location of start and stop codons. Where possible, the results of the CRM analysis are validated by comparison of the cDNA sequence to known sequences using database matching, in accordance with Example 2. If a match of 50% (or even less) is found in any particular reading frame and orientation, this serves to verify corresponding CRM results. Alternatively, database matches can be used to determine reading frame and orientation without use of the CRM program. Of course, if the cDNA is derived from a directional library, the probable orientation is already known.
EXAMPLE 15 Preparation of PCR Primers and Amplification of DNA
The EST sequences and the corresponding cDNA sequences and genomic sequences may be used, in accordance with the present invention, to prepare PCR primers for a variety of applications. The PCR primers are preferably at least 15 bases, and more preferably at least 18 bases in length. The procedure of Example 3 is repeated using the desired EST, or using the corresponding cDNA or genomic DNA sequence from Example 11. It is preferred that the primer pairs have approximately the same G/C ratio, so that melting temperatures are approximately the same. When screening cDNA, introns are of no concern; however, when screening genomic DNA, primers should be selected to avoid reading across introns, which usually are too large to amplify. The PCR primers and amplified DNA of this Example find use in the Examples that follow.
EXAMPLE 14
Forensic Matching bv DNA Sequencing
In one exemplary method, DNA samples are isolated from forensic specimens of, for example, hair, semen, blood or skin cells by conventional methods. A panel of PCR primers derived from a number of the sequences of Example 1, 9, 10 and/or 11 is then utilized in accordance with Example 10 to obtain DNA of approximately 100-200 bases in length from the forensic specimen. Corresponding sequences are obtained from a suspect. Each of these identification DNAs is then sequenced, and a simple database comparison determines the differences, if any, between the sequences from the suspect and those from the sample. Statistically significant differences between the suspect's DNA sequences and those from the sample conclusively prove a lack of identity. This lack of identity can be proven, for example, with only one sequence. Identity, on the other hand, should be demonstrated with a large number of sequences, all matching. Preferably, a minimum of 50 statistically identical sequences of 100 bases in length are used to prove identity between the suspect and the sample.
EXAMPLE 15 Positive Identification by DNA Sequencing
The technique outlined in the previous example may also be used on a larger scale to provide a unique fingerprint-type identification of any individual. In this technique, primers are prepared from a large number of sequences from Examples 1, 9, 10 and/or 11. Preferably, 20 to 50 different primers are used. These primers are used to obtain a corresponding number of PCR-generated DNA segments from the individual in question in accordance with Example 13. Each of these DNA segments is sequenced, using the methods set forth in Example 1. The database of sequences generated through this procedure uniquely identifies the individual from whom the sequences were obtained. The same panel of primers may then be used at any later time to absolutely correlate tissue or other biological specimen with that individual.
EXAMPLE 16
Southern Blot Forensic Identification
The procedure of Example 15 is repeated to obtain a panel of from 10 to 2000 amplified sequences from an individual and a specimen. This PCR-generated DNA is then digested with one or a combination of, preferably, four base specific restriction enzymes. Such enzymes are commercially available and known to those of skill in the art. After digestion, the resultant gene fragments are size separated in multiple duplicate wells on an agarose gel and transferred to nitrocellulose using Southern blotting techniques well known to those with skill in the art. For a review of Southern blotting see Davis et al. (Basic Methods in Molecular Biology. 1986, Elsevier Press, pp 62-65). A panel of ESTs or complete cDNA sequences from Examples
1, and/or 11, or fragments thereof of at least 15 bases, are radioactively or colorimetrically labeled using end-labeled oligonucleotides derived from the ESTs, nick translated sequences or the like using methods known in the art and hybridized to the Southern blot using techniques known in the art (Davis et al., supra) . Preferably, at least 5 to 10 of these labeled probes are used, and more preferably at least about 20 or 30 are used to provide a unique pattern. The resultant bands appearing from the hybridization of a large sample of ESTs will be a unique identifier. Since the restriction enzyme cleavage will be different for every individual, the band pattern on the Southern blot will also be unique. Increasing the number of EST probes will provide a statistically higher level of confidence in the identification since there will be an increased number of sets of bands used for identification.
EXAMPLE 17 Dot Blot Identification Procedure
Another technique for identifying individuals using the sequences disclosed herein utilizes a dot blot hybridization technique.
Genomic DNA is isolated from nuclei of subject to be identified. Oligonucleotide probes of approximately 30 bp in length were synthesized that correspond to sequences from the ESTs. The probes are used to hybridize to the genomic DNA through conditions known to those in the art. The oligonucleotides are end labelled with 32P using polynucleotide kinase (Pharmacia) . Dot Blots are created by spotting about 50 ng cDNA of preferably at least 10 sequences corresponding to a variety of the Sequence ID NOs provided in Table 7 onto nitrocellulose or the like using a vacuum dot blot manifold
(BioRad, Richmond California) . The nitrocellulose filter containing the EST clone sequences is baked or UV linked to the filter, prehybridized and hybridized with labeled probe using techniques known in the art (Davis et al. supra) . The 32P labeled DNA fragments are sequentially hybridized with successively stringent conditions to detect minimal differences between the 30 bp sequence and the DNA. Tetramethyl mmonium chloride is useful for identifying clones containing small numbers of nucleotide mismatches (Wood et al., Proc. Natl. Acad. Sci. USA 82(6) :1585-1588 (1985) which is hereby incorporated by reference. A unique pattern of dots distinguishes one individual from another individuals.
EXAMPLE 18 Alternative "Fingerprint" Identification Technique
EST sequences and the corresponding complete cDNA sequences can be used to create a unique fingerprint for an individual. Thus pools of EST sequences can be used in forensics, paternity suits or the like to differentiate one individual from another. Entire EST sequences . can be used; similarly oligonucleotides can be prepared from EST sequences. In this example, 20-mer oligonucleotides are prepared from 200 EST sequences using commercially available oligonucleotide services such as Oligos Etc., Wilsonville, OR. Patient cell samples are processed for DNA using techniques well known to those with skill in the art. The nucleic acid is digested with restriction enzymes EcoRI and Xbal. Following digestion, samples are applied to wells for electrophoresis. The procedure, as known in the art, may be modified to accommodate polyacrylamide electrophoresis, however in this example, samples containing 5 ug of DNA are loaded into wells and separated on 0.8% agarose gels. The gels are transferred using Southern blotting techniques onto nitrocellulose. 10 ng of each of the oligos are pooled and end-labeled with 32P. The nitrocellulose is prehybridized with blocking solution and hybridized with the labeled probes. Following hybridization and washing, the nitrocellulose filter is exposed to X-Omat AR X-ray film. The resulting hybridization pattern will be unique for each individual.
It is additionally contemplated within this example that the representative number of EST sequences can be varied for additional accuracy or clarity.
EXAMPLE 19
Identification of genes associated with hereditary diseases
This example illustrates an approach useful for the association of EST sequences with particular phenotypic characteristics. In this example, a particular EST is used as a test probe to associate that EST with a particular phenotypic characteristic.
A search of Mendelian Inheritance in Man (supra) revealed 6p21 to be a very gene rich region of the genome containing several known genes and several diseases for which genes have not been identified. Any cDNA encoded by an EST located in this region would thus becomes an immediate candidate for each of these genetic diseases.
Cells from patients with these diseases are isolated and expanded in culture. PCR primers from the EST sequences are used to screen genomic DNA and RNA or cDNA from the patients. ESTs that are not amplified in the patients can be positively associated with a particular disease by further analysis.
EXAMPLE 20 Identification of a gene associated with
Angel an's disease
Angelman's disease (AD) is characterized by deletions on the long arm of chromosome 15 (15qllql3) (Williams et al. Am. J. Med. Genet. 32:339-345 (1989) hereby incorporated by reference) . The symptoms of the disease include developmental delay, seizures, inappropriate laughter and ataxic movements. These symptoms suggest that the disorder is a neurologic deficiency. This prophetic example illustrates how ESTs, preferably obtained from a cDNA library from human brain, may be used in identifying the defective gene or genes associated with Angelman's Disease. (The example is based on analogous work with genomic DNA, rather than cDNA and ESTs, in identifying the genetic defect associated with Angelman's Disease.) This example also illustrates how EST sequences may generally be used for identifying gene sequences associated with an inherited disease that is mapped to a chromosome location.
ESTs are screened using techniques described in Example 3 and Example 5 to identify those ESTs that localize to the long arm of chromosome 15 and preferably localize to chromosome 15 bands 15qllql3 from normal patients. ESTs that bind to the long arm of chromosome 15 are hybridized to chromosome 15 from AD patients. These studies are preferrably performed using either fluorescence in situ hybridization or using somatic cell hybrids that contain fragments from the long arm of chromosome 15 from AD patients. Those chromosome 15-specific ESTs that do not map to chromosome 15 from AD patients are useful as markers for Angelman's Disease and can be incorporated into diagnostics for genetic screening. These ESTs are associated with chromosome deletions present in Angelman's disease. Identification of the gene associated with these AD negative ESTs and an analysis of the polypeptides encoded by the genes from normal patients is essential for providing gene or other therapies for AD patients.
Genetic diseases are not always accompanied by gene deletions. Therefore, it is also important to use the ESTs that bind to bands 15qllql3 from AD patients as tools to identify the polymorphisms present within the disease population. Restriction fragment length polymorphism (RFLP) analysis can be performed on patient cells from AD disease or from somatic cell hybrids created using the long arm of chromosome 15. For a review of RFLP techniques see Donis- Keller et al. (Cell 51:319-337 (1987) hereby incorporated by reference) . DNA is isolated from the somatic cell lines or from cells from AD patients. The DNA is digested with one or more restriction enzymes according to techniques of Donis- Keller et al. The resulting fragments are separated by gel electrophoresis, denatured, transferred to nitrocellulose and hybridized with the selected radio-labeled ESTs that localize to the region of interest. The autoradiographic pattern is compared both to a number of AD patients and to normal patients. Common patterns of EST hybridization in AD patients that are not present in normal patients indicates that the genes associated with these ESTs are candidate genes affected by AD. cDNA libraries are prepared from the somatic cell hybrids from AD patients. Libraries are prepared using Lambda Zap II Library Kits (Stratagene, La Jolla, California) or other commercially available library kits. The ESTs of interest are used as probes to identify those bacterial colonies carrying genes corresponding to the EST probes. Positive clones are sequenced and the sequences are compared to homologous gene sequences derived from normal patients. Alterations, including deletions and substitutions, within gene sequences, associated with bands 15qllql3, are thus positively identified and associated with AD disease. Wagstaff et al. were able to identify deletions and substitutions in sequences encoding the GABAA receptor protein subunit from patients with Angelman's disease (Am. J. Hum. Genet. 49:330-337, (1991)). It is likely that other genes will additionally be associated with the disease.
EXAMPLE 21
Preparation and Use of Antisense Oligonucleotides
Antisense RNA molecules are known to be useful for regulating translation within the cell. Antisense RNA molecules can be produced from EST sequences or from the corresponding gene sequences. These antisense molecules can be used as diagnostic probes to determine whether or not a particular gene is expressed in a cell. Similarly, the antisense molecules can be used as a therapeutic to regulate gene expression once the EST is associated with a particular disease (see Example 20) .
The antisense molecules are obtained from a nucleotide sequence by reversing the orientation of the coding region with regard to the promoter. Thus, the antisense RNA is complementary to the corresponding mRNA. For a review of antisense design see Green et al., Ann. Rev. Biochem. 55:569- 597 (1986) , which is hereby incorporated by reference. The antisense sequences can contain modified sugar phosphate backbones to increase stability and make them less sensitive to RNase activity. Examples of the modifications are described by Rossi et al., Pharmacol. Ther. 50(2) :245-254, (1991) .
Antisense molecules are introduced into cells "that express the gene corresponding to the EST of interest in culture. In a preferred application of this invention, the polypeptide encoded by the gene is first identified, so that the effectiveness of antisense inhibition on translation can be monitored using techniques that include but are not limited to antibody-mediated tests such as RIAs and ELISA, functional assays, or radiolabelling. The antisense molecule is introduced into the cells by diffusion or by transfection procedures known in the art. The molecules are introduced onto cell samples at a number of different concentrations preferably between lxlO" 0M to lxlO"4M. Once the minimum concentration that can adequately control translation is identified, the optimized dose is translated into a dosage suitable for use in vivo. For example, an inhibiting concentration in culture of lxlO"7 translates into a dose of approximately 0.6 mg/kg bodyweight. Levels of oligonucleotide approaching 100 mg/kg bodyweight or higher may be possible after testing the toxicity of the oligonucleotide in laboratory animals.
The antisense can be introduced into the body as a bare or naked oligonucleotide, oligonucleotide encapsulated in lipid, oligonucleotide sequence encapsidated by viral protein, or as oligonucleotide contained in an expression vector such as those described in Example 23. The antisense oligonucleotide is preferably introduced into the vertebrate by injection. It is additionally contemplated that cells from the vertebrate are removed, treated with the antisense oligonucleotide, and reintroduced into the vertebrate. It is further contemplated that the antisense oligonucleotide sequence is incorporated into a ribozyme sequence to enable the antisense to bind and cleave its target. For technical applications of ribozyme and antisense oligonucleotides see Rossi et al.
EXAMPLE 22 Preparation and use of Triple Ηelix Probes
Triple helix oligonucleotides are used to inhibit transcription from a genome. They are particularly useful for studying alterations in cell activity as it is associated with a particular gene. The EST sequences or complete sequences of the present invention or, more preferably, a portion of those sequences, can be used to inhibit gene expression in individuals having diseases associated with a particular gene. Similarly, a portion of the EST or corresponding gene sequence can be used to study the effect of inhibiting transcription of a particular gene within a cell. Traditionally, homopurine sequences were considered the most useful. However, homopyrimidine sequences can also inhibit gene expression. Thus, both types of sequences from either the EST or from the gene corresponding to the EST are contemplated within the scope of this invention. Homopyrimidine oligonucleotides bind to the major groove at homopurine:homopyrimidine sequences. As an example, 10-mer to 20-mer homopyrimidine sequences from the ESTs can be used to inhibit expression from homopurine sequences. SEQ ID NOs such as 282 and 240 contain homopyrimidine 15-mers. Moreover the natural (beta) anomers of the oligonucleotide units can be replaced with alpha anomers to render the oligonucleotide more resistant to nucleases. Further, an intercalating agent such as ethidium bromide, or the like, can be attached to the 3' end of the alpha oligonucleotide to stabilize the triple helix. For information on the generation of oligonucleotides suitable for triple helix formation see Griffin et al. (Science 245:967-971 (1989) , which is hereby incorporated by this reference) .
The oligonucleotides may be prepared on an oligonucleotide synthesizer or they may be purchased commercially from a company specializing in custom oligonucleotide synthesis. The sequences are introduced into cells in culture using techniques known in the art that include but are not limited to calcium phosphate precipitation, DEAE-Dextran, electroporation, liposo e- mediated transfection or native uptake. Treated cells are monitored for altered cell function. These cell functions are predicted based upon the homologies of the gene, corresponding to the EST from which the oligonucleotide was derived, with known genes sequences that have been associated with a particular function. The cell functions can also be predicted based on the presence of abnormal physiologies within cells derived from individuals with a particular inherited disease, particularly when the EST is associated with the disease using techniques described in Example 20.
EXAMPLE 23 Gene expression from DNA Sequences Corresponding to ESTs
A gene sequence of the present invention coding for all or part of a human gene product is introduced into an expression vector using conventional technology. (Techniques to transfer cloned sequences into expression vectors that direct protein translation in mammalian, yeast, insect or bacterial expression systems are well known in the art.) Commercially available vectors and expression systems are available from a variety of suppliers including Stratagene (La Jolla, California) , Promega (Madison, Wisconsin) , and Invitrogen (San Diego, California) . If desired, to enhance expression and facilitate proper protein folding, the codon context and codon pairing of the sequence may be optimized for the particular expression organism, as explained by Hatfield, et al., U.S. Patent No. 5,082,767, incorporated herein by this reference.
The following is provided as one exemplary method to generate polypeptide from cloned cDNA sequences. The cDNA from the EST of interest is sequenced to identify the methionine initiation codon for the gene and the poly A sequence. If the cDNA lacks a poly A sequence, this sequence can be added to the construct by, for example, splicing out the Poly A sequence from pSG5 (Stratagene) using Bgll and Sail restriction endonuclease enzymes and incorporating it into the mammalian expression vector pXTl (Stratagene) . pXTl contains the LTRs and a portion of the gag gene from Moloney Murine Leukemia Virus. The position of the LTRs in the construct allow efficient stable transfection. The vector includes the Herpes Simplex Thymidine Kinase promoter and the selectable neomycin gene. The cDNA is obtained by PCR from the bacterial vector using oligonucleotide primers complementary to the cDNA and containing restriction endonuclease sequences for Pst I incorporated into the 5'primer and Bglll at the 5' end of the corresponding cDNA 3' primer, taking care to ensure that the cDNA is positioned inframe with the poly A sequence. The purified fragment obtained from the resulting PCR reaction is digested with Pstl, blunt ended with an exonuclease, digested with Bgl II, purified and ligated to pXTl, now containing a poly A sequence and digested Bglll.
The ligated product is transfected into mouse NIH 3T3 cells using Lipofectin (Life Technologies, Inc. , Grand Island, New York) under conditions outlined in the product specification. Positive transfectants are selected after growing the transfected cells in 600ug/ml G418 (Sigma, St. Louis, Missouri) . The protein is preferrably released into the supernatant. However if the protein has membrane binding domains, the protein may additionally be retained within the cell or expression may be restricted to the cell surface.
Since it may be necessary to purify and locate the transfected product, synthetic 15-mer peptides synthesized from the predicted cDNA sequence are injected into mice to generate antibody to the polypeptide encoded by the cDNA.
If antibody production is not possible, the cDNA sequence is additionally incorporated into eukaryotic expression vectors and expressed as a chimeric with, for example, β- globin. Antibody to -globin is used to purify the chimeric. Corresponding protease cleavage sites engineered between the -globin gene and the cDNA are then used to separate the two polypeptide fragments from one another after translation. One useful expression vector for generating 0-globin chimerics is pSG5 (Stratagene) . This vector encodes rabbit ø-globin. Intron II of the rabbit β-globin gene facilitates splicing of the expressed transcript, and the polyadenylation signal incorporated into the construct increases the level of expression. These techniques as described are well known to those skilled in the art of molecular biology. Standard methods are published in methods texts such as Davis et al. and many of the methods are available from the technical assistance representatives from Stratagene, Life Technologies, Inc., or Promega. Polypeptide may additionally be produced from either construct using in vitro translation systems such as In vitro Express™ Translation Kit (Stratagene) .
EXAMPLE 24 Production of an Antibody to a Human Protein
Substantially pure protein or polypeptide is isolated from the transfected or transformed cells as described in Example 23. Concentration of protein in the final preparation is adjusted, for example, by concentration on an Amicon filter device, to the level of a few micrograms/ml. Monoclonal or polyclonal antibody to the protein can then be prepared as follows: A. Monoclonal Antibody Production by Hybridoma Fusion
Monoclonal antibody to epitopes of any of the peptides identified and isolated as described can be prepared from murine hybridomas according to the classical method of Kohler, G. and Milstein, C. , Nature 256:495 (1975) or derivative methods thereof. Briefly, a mouse is repetitively inoculated with a few micrograms of the selected protein over a period of a few weeks. The mouse is then sacrificed, and the antibody producing cells of the spleen isolated. The spleen cells are fused by means of polyethylene glycol with mouse myeloma cells, and the excess unfused cells destroyed by growth of the system on selective media comprising aminopterin (HAT media) . The successfully fused cells are diluted and aliquots of the dilution placed in wells of a microtiter plate where growth of the culture is continued. Antibody-producing clones are identified by detection of antibody in the supernatant fluid of the wells by i munoassay procedures, such as Elisa, as originally described by Engvall, E., Meth. Enzymol. 70:419 (1980) , and derivative methods thereof. Selected positive clones can be expanded and their monoclonal antibody product harvested for use. Detailed procedures for monoclonal antibody production are described in Davis, L. et al. Basic Methods in Molecular Biology Elsevier, New York. Section 21-2. B. Polyclonal Antibody Production by Immunization
Polyclonal antiserum containing antibodies to heterogenous epitopes of a single protein can be prepared by immunizing suitable animals with the expressed protein described above, which can be unmodified or modified to enhance immunogenicity. Effective polyclonal antibody production is affected by many factors related both to the antigen and the host species. For example, small molecules tend to be less immunogenic than other and may require the use of carriers and adjuvant. Also, host animals vary in response to site of inoculations and dose, with both inadequate or excessive doses of antigen resulting in low titer antisera. Small doses (ng level) of antigen administered at multiple intradermal sites appears to be most reliable. An effective immunization protocol for rabbits can be found in Vaitukaitis,
J. et al. J. Clin. Endocrinol. Metab. 33:988-991 (1971).
Booster injections can be given at regular intervals, and antiserum.harvested when antibody titer thereof, as determined semi-quantitatively, for example, by double immunodiffusion in agar against known concentrations of the antigen, begins to fall. See, for example, Ouchterlony, 0. et al., Chap. 19 in: Handbook of Experimental Immunology D. Wier (ed) Blackwell (1973) . Plateau concentration of antibody is usually in the range of 0.1 to 0.2 mg/ml of serum (about 12 μM) . Affinity of the antisera for the antigen is determined by preparing competitive binding curves, as described, for example, by Fisher, D. , Chap. 42 in: Manual of Clinical Immunology, 2d Ed. (Rose and Friedman, eds.) Amer. Soc. For Microbiol., Washington, D.C. (1980). Antibody preparations prepared according to either protocol are useful in quantitative immunoassays which determine concentrations of antigen-bearing substances in biological samples; they are also used semi-quantitatively or qualitatively to identify the presence of antigen in a biological sample.
EXAMPLE 25
Identification of Tissue Types or Cell Species bv Means of Labeled Tissue Specific Antibodies
Identification of specific tissues is accomplished by the visualization of tissue specific antigens by means of antibody preparations according to Example 24 which are conjugated, directly or indirectly to a detectable marker. Selected labeled antibody species bind to their specific antigen binding partner in tissue sections, cell suspensions, or in extracts of soluble proteins from a tissue sample to provide a pattern for qualitative or semi-qualitative interpretation. Antisera for these procedures must have a potency exceeding that of the native preparation, and for that reason, antibodies are concentrated to a mg/ml level by isolation of the gamma globulin fraction, for example, by ion-exchange chromatography or by ammonium sulfate fractionation. Also, to provide the most specific antisera, unwanted antibodies, for example to common proteins, must be removed from the gamma globulin fraction, for example by means of insoluble immunoabsorbents, before the antibodies are labeled with the marker. Either monoclonal or heterologous antisera is suitable for either procedure.
A. Immunohistochemical Techniques
Purified, high-titer antibodies, prepared as described above, are conjugated to a detectable marker, as described, for example, by Fudenberg, H. , Chap. 26 in: Basic * Clinical immunology, 3rd Ed. Lange, Los Altos, California (1980) or Rose, N. et al., Chap. 12 in: Methods in Immunodiagnosis, 2d Ed. John Wiley & Sons, New York (1980).
A fluorescent marker, either fluorescein or rhodamine, is preferred, but antibodies can also be labeled with an enzyme that supports a color producing reaction with a substrate, such as horseradish peroxidase. Markers can be added to tissue-bound antibody in a second step, as described below. Alternatively, the specific antitissue antibodies can be labeled with ferritin or other electron dense particles, and localization of the ferritin coupled antigen-antibody complexes achieved by means of an electron microscope. In yet another approach, the antibodies are radiolabeled, with, for example 125I, and detected by overlaying the antibody treated preparation with photographic emulsion.
Preparations to carry out the procedures can comprise monoclonal or polyclonal antibodies to a single gene copy or protein, identified as specific to a tissue type, for example, brain tissue, or antibody preparations to several antigenically distinct tissue specific antigens can be used in panels, independently or in mixtures, as required.
Tissue sections and cell suspensions are prepared for immunohistochemical examination according to common histological techniques. Multiple cryostat sections (about 4 μ , unfixed) of the unknown tissue and known control, are mounted and each slide covered with different dilutions of the antibody preparation. Sections of known and unknown tissues should also be treated with preparations to provide a positive control, a negative control, for example, pre-immune sera, and a control for non-specific staining, for example, buffer.
Treated sections are incubated in a humid chamber for 30 min at room temperature, rinsed, then washed in buffer for 30- 45 min. Excess fluid is blotted away, and the marker developed.
If the tissue specific antibody was not labeled in the first incubation, it can be labeled at this time in a second antibody-antibody reaction, for example, by adding fluorescein- or enzyme-conjugated antibody against the immunoglobulin class of the antiserum-producing species, for example, fluorescein labeled antibody to mouse IgG. Such labeled sera are commercially available. The antigen found in the tissues by the above procedure can be quantified by measuring the intensity of color or fluorescence on the tissue section, and calibrating that signal using appropriate standards. B. Identification of Tissue Specific Soluble Proteins
The visualization of tissue specific proteins and identification of unknown tissues from that procedure is carried out using the labeled antibody reagents and detection strategy as described for immunohistochemistry; however the sample is prepared according to an electrophoretic technique to distribute the proteins extracted from the tissue in an orderly array on the basis of molecular weight for detection.
A tissue sample is homogenized using a Virtis apparatus; cell suspensions are disrupted by Dounce homogenization or osmotic lysis, using detergents in either case as required to disrupt cell membranes, as is the practice in the art. Insoluble cell components such as nuclei, microsomes, and membrane fragments are removed by ultracentrifugation, and the soluble protein-containing fraction concentrated if necessary and reserved for analysis.
A sample of the soluble protein solution is resolved into individual protein species by conventional SDS polyacrylamide electrophoresis as described, for example, by Davis, L. et al., Section 19-2 in: Basic Methods in Molecular Biology (P. Leder, ed) , Elsevier, New York (1986) , using a range of amounts of polyacrylamide in a set of gels to resolve the entire molecular weight range of proteins to be detected in the sample. A size marker is run in parallel for purposes of estimating molecular weights of the constituent proteins. Sample size for analysis is a convenient volume of from 5-50 μl, and containing from about 1 to 100 μg protein. An aliquot of each of the resolved proteins is transferred by blotting to a nitrocellulose filter paper, a process that maintains the pattern of resolution. Multiple copies are prepared. The procedure, known as Western Blot Analysis, is well described in Davis, L. et al., (above) Section 19-3. One set of nitrocellulose blots is stained with Coomassie Blue dye to visualize the entire set of proteins for comparison with the antibody bound proteins. The remaining nitrocellulose filters are then incubated with a solution of one or more specific antisera to tissue specific proteins prepared as described in Example 24. In this procedure, as in procedure A above, appropriate positive and negative sample and reagent controls are run.
In either procedure A or B, a detectable label can be attached to the primary tissue antigen-primary antibody complex according to various strategies and permutations thereof. In a straightforward approach, the primary specific antibody can be labeled; alternatively, the unlabeled complex can be bound by a labeled secondary anti-IgG antibody. In other approaches, either the primary or secondary antibody is conjugated to a biotin molecule, which can, in a subsequent step, bind an avidin conjugated marker. According to yet another strategy, enzyme labeled or radioactive protein A, which has the property of binding to any IgG, is bound in a final step to either the primary or secondary antibody.
The visualization of tissue specific antigen binding at levels above those seen in control tissues to one or more tissue specific antibodies, prepared from the gene sequences identified from EST sequences, can identify tissues of unknown origin, for example, forensic samples, or differentiated tumor tissue that has metastasized to foreign bodily sites.
The entire contents of all references cited above are hereby incorporated by reference.
While the present invention has been described in some detail for purposes of clarity and understanding, one skilled in the art will appreciate that various changes in form and detail can be made without departing from the true scope of the invention.
VII. Correlation of EST and Clone Identifiers
The EST sequences of the present invention are identified herein by SEQ ID NO, and are identified in the GenBank database by a different number, are identified in the inventors' lab (and upcoming publications) by EST number, and clones have been submitted to the American Type Culture Collection (Rockville, Maryland USA) under clone names. Table 12 cross references those different numbers for the ESTs from CDNA, SEQ ID NOS 1-315.
Table 12. SEQ ID NO Cross References
Figure imgf000080_0001
I
Figure imgf000081_0001
NOTE REGARDING SEQUENCE LISTINGS: The listings of SEQ ID NOS:
1-315 are in numerical order. However, an occasional number
(for example, SEQ ID NO: 44) is not found in this list. In all, 7 SEQ ID NOS are not used. Nevertheless, the convention
"1-315" is used, for example, to refer to all the SEQ ID NOS in the following list.
SEQUENCE LISTING
(1) GENERAL INFORMATION:
(i) APPLICANT: Venter, J. Craig Adams, Mark D. Moreno, Ruben F.
(ii) TITLE OF INVENTION: Sequences Characteristic of Human Gene Transcription Product
(iii) NUMBER OF SEQUENCES: 308 (1-315, with 7 SEQ ID NOS unused. )
(iv) CORRESPONDENCE ADDRESS:
(A) ADDRESSEE: Knobbe, Martens, Olson, and Bear
(B) STREET: 620 Newport Center Dr. Sixteenth Floor
(C) CITY: Newport Beach
(D) STATE: CA
(E) COUNTRY: USA
(F) ZIP: 92660
(V) COMPUTER READABLE FORM:
(A) MEDIUM TYPE: Floppy disk
(B) COMPUTER: IBM PC compatible
(C) OPERATING SYSTEM: PC-DOS/MS-DOS
(D) SOFTWARE: Patentln Release #1.0, Version #1.25
(vii) PRIOR APPLICATION DATA:
(A) APPLICATION NUMBER: US 07/716,831
(B) FILING DATE: 20-JUN-1991
(viii) ATTORNEY/AGENT INFORMATION:
(A) NAME: Israelsen, Ned A.
(B) REGISTRATION NUMBER: 29,655
(C) REFERENCE/DOCKET NUMBER: NIH004.004CP1
(ix) TELECOMMUNICATION INFORMATION:
(A) TELEPHONE: 619-235-8550
(B) TELEFAX: 619-235-0176
(2) INFORMATION FOR SEQ ID N0:1:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 362 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID N0:1: CTTCCCTTTT GTTCCCCTCA GTGTCCCTTT TAATTGCTTC CCTCCATTTT CCTTAGCAGC 60 ATCCTAGTTG ATGGTCTGGG TTATCAGAGG AGCAAAAACA TTTAAGTGTC AAATAATGCT 120
CATTGTCTCC CTGGGATTTC TAAACAGAAA AAATGAAGAA AGAGGCAGAG AAGAGCTTCA 180
CAAGGTGTGT GCCAGCTCTG CATCATTTCC AGCTGCTCAA CCACCATTTC TCCCATTTTA 240
GGTCCCCAAA AGTAGGAGGT GGGGCCTCAC AGAGCTGCTG TGGGCTTTGG GTATCAAAAG 300
CTGCAGCCAC CATATGGGGC ACTCCTGGCT GGTGTACAGG GTGGGCATTG CCCAGGTCTT 360
TT 362 (2) INFORMATION FOR SEQ ID NO:2:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 214 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID N0:2:
GTTTTNCTTT TTTCTTAGCT TCATTTCTCT TAAAAAACAA GGAACAAGAA AACATTGCAC 60
CAGCGTTCTA AGCCTCAAAC AAAANACAAA ACAAATCCCC CTGCGAAGAA CAATAAACTT 120
TACATCTCTT TGGCAACAAT AACTTAAAAT CACCCAACTT CCATTCGCTC CAACCACAGC 180
AGTTAGTTAG TTACAAAAAT ATTCCNTGTG CTGC 214
(2) INFORMATION FOR SEQ ID NO:3:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 344 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:3:
ATTAATAGGA AAGATGATTG TATAGATGGT GGGCTATTAA CTCAGATCAG GATGAGAATC 60
GGGAGTGCCT TTACATGTGT GGTACCCAAA TGGGTGGTTG GATATAAGAG TAACAAAAGG 120
ACTGAAAGGG TTAAAAAAGA AAGAAAAAAA AAAAACTCCC TGGTTGGGAG GGTGTTAAGT 180
ATCGAGTGTT TTTCCAAACC ATTCCTCCTC TGCTCACCTA CCCCTAGGTG ATTAAAGGAG 240
ATAACTTTTA AAAAAGAAAG AATTGGCTCA AAGGTACTGT AAATTCTAGG ATTATATACC 300
TTTATATAGG TTCATTCCCT GATCCCTGTA TTATCAAGGC ACAG 344 (2) INFORMATION FOR SEQ ID N0:4:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 352 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:4:
GGACACTCAT CTGTGCCCCA CGTCCAGATC CCTGGAGGCA GCTGACCAAT GATGGGCGGT 60
GACCCGGTAA CCGAGGCGGC AAGGAGGCCA GGTAGTCCCG GCACCTCTCA CTCTGCAGAG 120
ACCAGCGGCT TCGTGGGAGG CCTGTGGGTC ACACGTAGGG GCTAGAGCCA GCCTGCATCC 180
TGCCCACCGG GCTCCACTTG GAGATCAGCA GGAGGGCCAG TGTGGGACCC CTGCTGCCAC 240
CTCTCCTGGG CCTGT TCCT TTCTGGAAAT TAAGAAGGTG TGCTCCAGAG CCAAGAGGAG 300
CAATAAGAAA CCTCGTGTGC CAGCTTCTTA AGGGTKGCAG TGCAAGACCC CA 352
(2) INFORMATION FOR SEQ ID NO:5:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 562 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:5:
ATACCCTTAC ATATATATTC ACAGAAAATC ATATTGCATA TACTCTTTCT CCACATCATA 60
AAAATGGGTG TTGGGCTCTC TAGGACACAA GGGAAGCAGG CCAAATTTCT CATATTTTCA 120
GGAATAAACT GAGTGCCCCG AAGGTGTAAT AGGAACCTTT TACTAACCTC ATCTGACTTC 180
ATCCTCACAC CAGCATTTTG TGTGTAAGGA AACTGGCCGA GAGTGGTTAA GAAATATATC 240
CAAAGACGTA TAGTTCCAAA TGGAACACGG ATCTTTTTAT TTAAATTCCA ATCATCTTTC 300
CATTATATCA GCCAATGATG GAGCAGAAAG CTGGTCCAGG CAATCCCAGA ATAGATCTTT 360
CTAGGCACCC GTTCAGTGTG AGGAGGGGGA AGTGGCCTTG CCAAGGGGCC AGTGAGCTCA 420
ATTAGGGTTA ACGCTGCTTC TTAGCCTACC CCAGGGGNCA CCGCACTTAG GTTGTTTTGT 480
GCCCAGCTTT GGCAGGAAGC ATTCCTCCTT TCAAAGATTN NAGCCTTGCG GTCATATATC 540
GGGTGTAATA GGGTTCTTTT TT 562 (2) INFORMATION FOR SEQ ID NO:6:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 359 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:6:
ACATGTTCTC CCTCTTTCAA TTTTAGCAGT AATGTGATCC TCAAAAATGC ATTAATACTA 60
GTTGAAGTAA ATAAACGGAA GAGCTCCAAA ATGCCTGCAT TAAATGCATT TTTCCACACT 120
AATGCCAATC ATCCAAAGCT ATTTTCAACA AGTCAGGTAT TCAAAGCTAT TCACACCACT 180 TGAAAGAGTA ATTACCATTT ACTGAAGCAC TTATCTGTCC TACACTGATG GGAGTAAATG 240 CTTCTCATAG GTTATCTCAT GTACATTATG CCACTTTNAC TTAAAATGAT CACAATTNAG 300 TGCTATAGGT TTTTGGGTTA ATGTTTTCCC NGGGGGAGTT GTTAAAAACA TGGCATTTC 359 (2) INFORMATION FOR SEQ ID NO:7:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 218 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:7:
AACTTGCAAC ATAAATACTA GAAAAAGAGA AAATATCATC AAAATACAAA TAACTGTTAG 60
AAATCATTGC TCAAAAGAAR AACCTGGCAA TGCATGATTA CGAAATGCAA AAGAMGATAC 120
AGTTGCTCTC TGTATATGCG CTTTCCACAT CCACAGATTC AAACAACTGT GGATAAAAAA 180
GGATTTTTCA ATGCCATTAA ACAVCAATGC AACAGTAA 218 (2) INFORMATION FOR SEQ ID NO:8:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 345 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:8:
CTACAATAGA AGGCAAACTA TGTCCCTCCT TTGCTCAGAA ACTTTTAATA TCTKCCTATT 60
TCCCCATGTA AAAGCCAATC CTCAACCACA GTGTAGAAGG GCTATCCATT TCTAGCTACA 120
CATCTCCTCA GTCACTGCCC CCAGCCCCAG TACTTGGGGA CTTTGCCCTT GCAGTTCCCT 180
GTGCCAGCAA ACTCTTCCTC CAGATGTCCA CATGACTCAC CCNNCTCCTT CAGGGGTCTT 240
CTCAAATGTC ACTTTACCAG AGGTGGCTTC CCTGACCATC CTGTATAAAT AGCATCACCC 300
TACCTCCTAT CTCTCTCTCT AATGTCTCAG GAATTCGATA TCAAG 345 (2) INFORMATION FOR SEQ ID NO:9:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 189 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
• (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9:
GTGAACAGAC TAAGGCCTTT NTGGAGGCCC AGAATAAGAT TACTGTGCCA TTTCTTGAGC 60
AGTGTCCCAT CAGAGGTTTA TACAAAGAGA GAATGACTGA ACTATATGAT TATCCCANGT 120
ATAGTTGCCA CTTCAAGAAA GGAGAACGGT GTTTTTATTT TTACAATACA GGNTTTNAGA 180 ACCACCGGG 189
(2) INFORMATION FOR SEQ ID NO:10:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 267 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:10:
CTCCCTTCGC CACCTGCTGG ACGCGAGGGG CTACTACGAT GCCATGGGTG TCCTGRTTTT 60
TTATTTCTCA GACAGGACTG CTCTGTATNT GTCTTTGGAT TCTACGTAGA TTTATATTTG 120
TAAAATATTA CATTTGTCAT GACCAGAAGA AATGTCATTA TCGTAAAATT TAGATTCTGG 180
NGTCTATATA TGNAAGNAAT ACTAACTACT AACTGTTATA ACA CAAAAT GTGGGNTGTA 240
TATCTACARG CCNGAGCCGA CTTGTCA 267 (2) INFORMATION FOR SEQ ID NO:11:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 247 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:
CTCATAAAGC CAGGGTGATA AAAWTGGTAG TTTCATGTTA TCTACAAGRC TAAGKTCAAA 60
ATTCCATGCA TGTGCTGRTA AAAGACCCAT NATGGKCCTM ACTGTACTTA CTCCCCATTT 120
ATTAGCATTC ATTCTGGTCA CCAGCTCTAG TTCCTCTGCT TAGCGAATCT CGCTTGTCTT 180
CAAGATGTCA TTCAAATGTC ACATTTTGTG GGAAGCCTTG CCTTTTTTGA CACGGTCTCC 240
CTGCCAC 247 (2) INFORMATION FOR SEQ ID NO:12:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 280 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:12"
AAGGCGAGAG GCTTCTGGAG AAACCCACCC CACCAACGTC TTGATCTTGG ACTTTTAVCC 60
TCCAGAGCTA TGAGAAAACA AVTTTCTGTV VATVGVGGCC ACTCAGCCTG TGGATACTGG 120
CAGCCCTAGC AAACTCATAC ACACATACAT TTTAAACTCG GTTTAATCCT GTGRCCATTC 180
ACTTATGGTT CAGTTTTTAA ATAGTCCTAG TCTTATGVCC ACTGTTAAAG TTCACCAGGA 240
CATAGGSCAT TGGGGAAAGG GGCCTGTAAC TCTTGGATTA 280 (2) INFORMATION FOR SEQ ID NO:13:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 339 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:13:
VCTVTCTVCC AACTTCATTC AGATATTGAC TCTGGTGATG GGAACATTAA ATACATTCTC 60
TCAGGGGAAG GAGCTGGAAC CATTTTTVTR ATTGATGACA AATCAGGGAA CATTCATGCC 120
ACCAAGACGT TGGATCGAGA AGAGAGAGCC CAGTACACGT TGATGGCTCA GGCGGTGGAC 180
AGGGACACCA ATCGGCCACT GGAGCCACCG TCGGAATTCA TTKTCAAGGK CCAGGACATT 240
AATGACAGTC CTCCGGAGGT TTCCTGCACG AGACCTATCA TGCCAACTGT GCCSTGTARA 300
GGTCCAATKT TGGGTGSTGT ACGGTAGTGG GGAGGCCTG 339 (2) INFORMATION FOR SEQ ID NO:14:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 342 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:14:
GGGVGCAAAG TAGCAGATTC TAGTAAAGGA CCAGATGAGG CAAAAATTAA GGCACTCTTG 60
GAAAGAACAG GCTACACACT TGATGTGACC ACTGGACAGA GGAAGTATGG AGGACCACCT 120
CCAGATTCCG TTTATYCAGG TCAGCAGCCT TCTGTTGGCA CTGAGATATT TGTGGGAAAG 180
ATCCCAAGAG ATCTATTTTG AGGATGAACT TGTTCCATTA TTTGAGAAAG CTTGGACCTA 240
TATGGGATCC TTCGTCTAAT GATGGATCCA CTCACTGGTC TCAATAGAGG TTAATGCGTT 300
TGTCACTTTT TTGTACAAAA GGAGCARGCT CAAGGAGGGC TG 342 (2) INFORMATION FOR SEQ ID NO:15:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 354 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:15:
ATGTTGATGC TGAAATTVAA GATCCACCAA TTCCAGAAAA ACCATGGAAG GTTCATGTGA 60
AATGGATTTT GGACACTGAT ATTTTCAATG AATGGATGAA TGAGGAGGAT TATRAGGTGG 120
ATGAAAATAG GAAGCCTGTR AGTTTYCGTC AGCGGATTTC AACCAAGAAT GAAGAGCCAG 180
TCAGAAGTCC AGAAAGAAGA GATAGAAAAG CATCASCTAA TGCTCGAAAG AGGAAACATT 240 CGCCTTCGCC TCCCCCTCCG ACACCAACAG AWTCACGGGA AGAAGAGTGG GAAGAAAGGC 300 CAAGCTAGCC TTTTATGGGG AAGCCGCAAG AAGTCCAGAA AGAGGGW GG TTGA 354
(2) INFORMATION FOR SEQ ID NO:16:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 348 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:16:
CAGGCAAGTT TCTTCCAGGA TGAGAAATCA GTGGAAAGTG AGGGCCAGCC AACAGCCACC 60
ACCAACCACC CAACACGCGA GCGAGACCAT CTTAAAAGAG CCCCAGCCAA GCTGACCATG 120
GGTCTGACCC CAAACTGAAG AAATGCCCAG CCCAGCCAAA CCCAAATTGC TAACTTGTAT 180
TATAAGCAAG TACAATGGTC CTTACCTTAA GCCACTAAGT TTTGGGATGC TTTGTTACAC 240
AGCTATAGAT AAGCTGATAC AGGGAATGTC AGAWTCCATG ATGAGAGACC GAGCCTTTCA 300
KTCTGTCAGA GGYACCTTVG GTTGGCAAAA CTTCAAAAAG AGGGACCT 348 (2) INFORMATION FOR SEQ ID NO:17:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 415 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:17:
AGCAYGGGCT GGGGGGCCGG GAGTTAGGGC TGGGGCTTGT TTTACGCTCT GCCCCCCACA 60
CCCCCTCCTC TTCCGTCCTG ATTAAGCCCA AGGGTTGGTG GACTTAACTT TCAGCCCATC 120
TCTAAGGGTT TCACAGACTG GATCTTTCTA AACTTTATTG GGTACCTGCT TCCCCTTTTC 180
CCTGGTAGTT TTCATCTACA AAAAGTCAAA ACCTGATCGA AATAGAAATA AGATCATCAA 240
ATTGGACCAT TCTCTTAGCG TTCGAGTGTG CCGGCCAGAC TGGCATTCAG TACACGCTGA 300
GATCCAACCA CATCACACTG GCCTCAGGTC ACCAACTCGC CACTCAGGGC ACAAGGCCTG 360
CCCTTGTGGT CACAAGGCTT TCCTTAATGT CGTCGGTGCC CAGGTGAACC ACAAG 415 (2) INFORMATION FOR SEQ ID NO:18:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 356 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: GTATGTATGT CTGTAGGTAT TTCTATACTT AACCATCTGT GTCCCAATTA AGCTAAACAT 60 GATTCATTCT GATGCCAACC CCCATCCATC ATGCCATGGA TCGCTCTAGA CTTCTTCCCT 120
TGTAACCTCC CACTCAAACA GTGAGAAACC TTTGCCCAGT ATGTTTTGGA GTAACCTCAC 180
TGGGAGTTTG CAGTCCCACT AGATGAATGC CAACCCATTT GTTCATTTAA AAGGACTTTT 240
GGAACCATAG AGCAATGGCT GGGCTGGGTC TVGCACGTTC ATCTTGACTG AAACAATTGG 300
CCATGAAGGC ACTTGCCAAG GAAACTCTAG GGGCCACAAG GGTCCTGGGT GCTTGC 356 (2) INFORMATION FOR SEQ ID NO:19:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 339 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:19:
CATGCTTCCA TTTTTTTTAG TTTTAAACCA CCAAACCAAT ATTTTYCCTT TAAATTTTAA 60
TCTTATAATA TAGAAATCTT ATGTAAATGA AATTTTGTCA TGTTTCAAAT AAAGAGAACT 120
GAAGTAGAAA ATAGAAATGC CAGTAAACAA CATAATGTTT AATTTACAAC TTACATTAGG 180
GGTTTGGGGG VATGCTAATT ATATATTGAG AATATACATT AGAACTCTTC AAAATGGGCT 240
CTTCTAATGA GGTCACTACT GAACATAATT GTTCCCTCTT CTGTTAAATA GAATAGGTTT 300
AAATGACTAG TCCAAATGGA ATTATTGCCT TCTKGTTAA 339 (2) INFORMATION FOR SEQ ID NO:20:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 437 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:20:
AGAACAAGGG AACTCAGCAG CCCCTCCCTT CCCATCAGCT GTTCCTGAGA GATGCAATAT 60
AGTAGTCATC GACATCATCC TTATCAACAG CATCATCACT CAGACAGTGG TGAAAGTCTT 120
TCTTCACAAG GAAAAACAAA GATAAAGAAA TACATGAGCA TTAATCAGAA ATTTTCAAAG 180
CTTGGATTCT AATGATATGC ATTATCATTA GACATTCAAA TGCTATACAT CTTCTGATGA 240
AGCCTCCTTG ACAGCAGCTA CACTTATTTC ACATTAGAAT GCCTAGAGAA ATCCTGACTG 300
CCCAGCTTGG TCATGGGACC TTCCCCACTC TCCTCTTGGA GGAATGAAAA GATGTGGCGG 360
CTTTCTACTT TTGCTACTGA GCTGGGGTAT ATGGCTAGGT CCACTTTCTA AGGGGCTTGG 420
AAGGGTTATT CCATCTG 437 (2) INFORMATION FOR SEQ ID NO:21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 385 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:21:
GTTTGATTTG CTTTTTTTTT AGAGTTTTAC ATCAGTGTTT TTCAGGAATA TTGGTCTTTC 60
ATTTTCTTTT CTTGGAATAT TTTCTAGTTT TACTTTGTCA GAGTAAATTC TGGCTTCACA 120
GAATTATTTG TAGTCTCTCC TGTCTTGGTT TATTCATGCT GCTATAACAA AATACCACAG 180
ACAAGGTGGT AATAAATAAC ACAAATTTAT TTTTCCCAGT TCTGGAGGCT AGGAGTTCAA 240
GAAGCTGGCA AGTTCAATGT CTGGTGAGAC CCATTCCTTC ATAGGTGGCA CCATCTAGGG 300
GTCCTTACAT GRCAAAGAGA TGGAAGGGCC AAAAAGATGG TGACCTATTG TGAGGCCTTT 360
TTTAAAGGGC CTTVAAATCC CAGTC 385 (2) INFORMATION FOR SEQ ID NO:22:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 374 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:22:
ACCTTCATGG TCATGAAGGC CATGCAGTCT CTCAAGTCCC GAGGCTACGT GAAGGAACAG 60
TTTGCCTGGA GACATTTCTA CTGGTACCTT ACCAATGAGG GTATCCAGTA TCTCCGTGAT 120
TACCTTCATC TGCCCCCGGA GATTGTGCCT GCCACCCTAC GCCGTAGCCG TCCAGAGACT 180
GGCAGGCCTC GGCCTAAAGG TCTGGGAGGG TGAGCGACCT GCGAGACTCA CAAGAGGGGA 240
AGCTGACAAG AGATACCTAC AAGACGGGAG TRCCTGTGCC ACCTGGTGCC GACAAGAAAG 300
CCGAGGCTTG GGTCTGGGTC AGCAACCGAA TTCCAGTTTA GAGGCGGATT TVGGTCGTKG 360
ACGGTGTCAG CCAC 374 (2) INFORMATION FOR SEQ ID NO:23:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 322 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:23:
CAAAACGTGA TCACCACAGC TCCGTTCCTG CAGTGACACT TAACATACTC AGCATCTTCA 60
TGAATTCTGA ATAATTTACT GATCGTAAAG TCTAAAAGTA TCAATTTCAG GTGAGCAGTT 120
TTAAATCAGA AAATAGTCAA TAGTTAATCA TGACTCTTCA GGGTATTTCC TTCACGTCCT 180 CTGAAGAGTT TCCCAGAACA TTCTTGTGAA AAGGAATGCC TCCCAACAAT GGAGAGCAAC 240 AATAGCAACA GGCATCTGAA TCAGCCTGGC CTCTGAAAAC AGACCANAGA GGAGTTTATC 300 TGTTTCTTCC AGTGGAGGAA GG 322
(2) INFORMATION FOR SEQ ID NO:24:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 113 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: CCTGAAATCG GAGTCTTTTG GACTGACTCC AAATTCAATG GGTGGCACAG GCAGCACGGA 60 GTCCACGTGA ATCTCCACCC CGTTAACAGG CGGGACGACA GCCCCTTGCA GCC 113
(2) INFORMATION FOR SEQ ID NO:25:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 399 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:25:
GGAAAGAATG AAGGAAAAAC AAGACAAAAT CTACTTCATG GCTGGGTCCA GCAGAAAAGA 60
GCAGACGCTG GCCTCAGACA CAGACAGCAG TCTTGATGCC TCGACGGGAC CCCTTGAAGG 120
CTGTCGATGA TAGGTTAGAA ATAGCAAACC TGTCAGCATT GAAGGAACTC TCACCTCCGT 180
GGGCCTGAAA TGCTTGGGAG TTGATGGAAC CAAATAGAAA AACTCCATGT TCTGCATGTA 240
AGAAACACAA TGCCTTGCCC TACTCAGACC TGATAGGATT GCCTGCTTAG ATGATAAAAT 300
GAGGCAGAAT ATGTCTTGAA GAAAAAANTT GCAAGCCACA CTTCTNGAGA TTTTGTTCAA 360
GATCCATTTC AGGGTGAGCA GTTAGAGTAG GTTGAATTT 399 (2) INFORMATION FOR SEQ ID NO:26:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 355 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:26:
GATTGGTATA CGGGCAACAA TGGATTGATA GCCTTAATAT AGAAATAGTT CCAGCAGGCC 60
AGATGCAGTG GCTCAATTCT GTAAACCCAG TGCTCTGCAC AGCTAGGAAG GAAGATCACT 120
TGGGCCCAGG AGTTCAAGGC TCCAGTGAGC CATGATCACG CCACTKCCTC CAGCCTGGGT 180 GACAGAGTNA GGCCCTGTCT CTAAAAAATG AAATAGCTCC ATCAAGTCAA TAATTAAAAG 240 TTCAACAGCC CAACAGANCA AAAATTGTAA ATGANCACAA ATTAGAAAAT GTACAAATTA 300 AATATTAATG ACCCATAACC CTATAAGGGA AAGTTTAACC TCTCTAGTAT TTTTT 355
(2) INFORMATION FOR SEQ ID NO:27:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 322 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:27:
AAAACGTGAT CACCACAGCT CCGTTCCTGC AGTGACACTT AACATACTCA GCATCTTCAT 60
GAATTCTGAA TAATTTACTG ATCGTAAAGT CTAAAAGTAT CAATTTCAGG TGAGCAGTTT 120
TAAATCAGAA AATAGTCAAT AGTTAATCAT GACTCTTCAG GGTATTTCCT TCACGTCCTC 180
TGAAGAGTTT CCCAGAACAT TCTTGTGAAA AGGAATGCCT CCCAACAATG GAGGAGCAAC 240
AATAGCAACA GGCATCTGAA TCAGCCTGGG CTCTGAAAAC AGACCAAAGA GGNGTTTTTC 300
TGCTTTCTTC CAGTGAGGAA GG 322 (2) INFORMATION FOR SEQ ID NO:28:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 287 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:28:
TATTTTTATT AAAGGACCAC CCTGGCTGTM GTGAGATGAA TGGATTCAAA CAGGGCAAGA 60
GTGGATACAG MGAGATAAGT TAGGAAGCTG GTATAGAAAT CTGGATGAGA TATGGTGGCT 120
TGGATGATAC TAGCAGTGAG TATGGGAAGT AGGTGGATTA CTTTACACTT TTTTAGATCA 180
GTCKATTCTT GATGTCTTGA AGACAAATTA ATCTCATATA TAACTCTAAA CAACATATTT 240
ATATTTCATG TAAATAAGGA TAATGCTGAC CAAATATTAG CACCTTT 287 (2) INFORMATION FOR SEQ ID NO:29:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 282 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: CAGGGCAGGG AAGCCTGGAA GCAAAGGAGG ACCTGGCTCC TGACTCTCAG AGAGGATAGG 60 CTGGGATCCC TGGGGCAGGC CTGTTCCTTG GCTGGCCAAT TTAGTCTTTC AATTGTCTAA 120 GGGCTCTCCA TTGCCTGCCC TTGCCTCTTT CTAGCCTGTT ATTTCTAGGC TCCTCTGAAT 180 AAATCTCAGG TTTCCTACTG TCATGCCTTT AGTTCAAAAA TGAGAATCTG CCCTACAGTG 240 CTGGCCTCCT TCCGGCCTGA AAGCCAGCAC CTTKCGACCC GG 282
(2) INFORMATION FOR SEQ ID NO:30:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 345 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:30:
GAAGCTGGTG AATACATTTC AAGACACAAC ATGGCACCTG TGTCTAGCTC TATGGTACAA 60
CATGGTACTA TGACACATAT AATGGGTTGC CAGATGGGGA AGGCAGCTTC TCTGCAACTG 120
AGCTGAGATC TCAAAATAGA CAATGTCAAG ATGGAATGAG AAGGGAAAAA CAGCATGTGT 180
AGACAGGTAG TGACAAAAGG CTAATTAAGG ACTGAAAGAA ACCAGTGGCC AACAAGGGAA 240
TCTACGGGTG ATAAAGATAA GACGGTGAGA GAGATAAGGC TAGATTGTAT AAGGCTTGAC 300
AGACCATAGC AAGATAAGCA AGGACCTGTG TCCTGTTAAC CATTT 345
(2) INFORMATION FOR SEQ ID NO:31:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 343 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:31:
ATAAAATTGG TCTGGGTACC CTAAGGTGTT TGCKTTGATA GAAAATTGAC ACCCCAAACT 60
AAGTGTTCTA CTTAGCTTCT ACAATAGTTA TTCCTAGACC TTAGATTAGT CATTACATTT 120
TTATTTAAGG TACTATGTTA CTTTCATGAC TACAAAATGA GGCACTCGTA CAAAACAGGA 180
ATGAAAACAT ACATATACTG TCTTGTCTTT ATGTCGTATT AATGCCAAAG ATATTGTCAG 240
GGATTATTTT AAAGAAGCCC TTACTCATGA TGGCTATTTT TAAAAATGGC ACAGGACAGT 300
AACAGGCTGA AAAGAAACAC CTGGTTTGAG GGGCCAAATT AAG 343 (2) INFORMATION FOR SEQ ID NO:32:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 153 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: ACAGGATGGT CAGGACAAGC CACCTCTGGT AAAGTGACAT TTGAGANGAC CCCTGAAGGN 60
GGGGGGTTGA GTCATGTGGA CATCTTGAGG AAGAGTTTAC TGGCACAGGG AACTGCAAGG 120
KCAAAGTCCC CAAGTACTAG GGCTGGGGGC AGT 153 (2) INFORMATION FOR SEQ ID NO:33:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 257 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:33:
TCAGTCAGCT TATCGCAGGT GCAGCCAAAC ACAAAGCTTC AGGACAAATT GTACAAACTT 60
TACAATGTGG GATTTAAATT TAAAATATGA TACATAAAAA TCTACACAAA ACTGATAAAA 120
ATCAAGCACA GNTACCAGGA TTGAAACTTA TAATAATCCA TGTGTGAAAG GGAGTCTTGT 180
TTCCTTTCAA GTGCTTTTAT TCTGCTATGG AACAGTCAAA ATGGAAGNTG TAAAGCTTTG 240
TGGTTAGTTT AAATTAT 257 (2) INFORMATION FOR SEQ ID NO:34:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 307 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:34:
CTCCCACCCA TATCTAATCC AACAAGTCCA GCTGCCTCTC TCTNAAMAAT ACCNARGATC 60
AGGCCCCTTC TCAGCACCCC CACAGCTGCT GCCCCAAAGG AAGCCACGTC ATCTCTCACG 120
GAGATTGTKC AGCAGCCACT GCCTCCTTGT CACCTTCGCC TGTGGTCATT CTCCCCACAT 180
GGCCAGGGAA TGCGTCCTGT TAAAGTCTGC TAGGTCACGG TCCTTCCTAC TCAAAATGCT 240
CCCYTGGCTC CCACTGCCCC CAGAGTAAAA AGCCCAGACC TTCAAATGAC ACAAAGGCCT 300
ACAACGA 307
(2) INFORMATION FOR SEQ ID NO:35:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 266 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:35: TCCACAGGTC ATCAGATRCC TGCTNGATAA TATATAAACA GTAAAAACAA CTTTCACTTC 60 TTCCTATTNT AATCGTGTGC CATGGATCTG ATCTGTACCA TGACCCTACA TAAGGCTGGA 120
TGGACCTCAG GCTGAGGGCC CAATGTATGT KTGGCTGTGG GTGTGGTTGG GAGTGTGTCT 180
GCKGAGTAAG AACACGNTTT TCAAGATTCT AAAGCTCAAT TMAAGTGGCA CATTAATRAT 240
AAACTCAGAT CTGNTCAAAA GTCCGG 266 (2) INFORMATION FOR SEQ ID NO:36:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 388 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:36:
CAGCTTTGGA AAGACTTTGA CCTCTGAACA AAAAGCCAGA AGGCTGCTTA AAGAAATAGT 60
AAGGGTTTCA CTTGCCCTGG ATAGTCACAA ATCTAGGAGT ACTGGTTCAC TGCCTTGGGT 120
TACCAGGTAT CAGCTCTTTC ACAATCTCTC CTCTTCCCAT GCTTCCCCTT AAAGTCCAGT 180
TGACAAATGA AAAAGAAAAA AAGGCCTTGA TTTATAGTAT TGCCAAACAA CCTCATAAGA 240
ATGGGTAAAA TTACATACAC ACATACATAG AGAAGGGAGG TAATGCTGTG AATCTACTTG 300
AGCTGGATTG CATGCTCCCT AGGGACCACG GTGCCCAACC TGTAATTTTA TTTCTAACTT 360
TTATAAATAT ACTCCTTTTT CACGGATG 388 (2) INFORMATION FOR SEQ ID NO:37:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 342 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:37:
GAATGTCTAC ACAAGGAAGT ACAGGATTTG GCTTTTCTAG ATGTCATATC CAAACTTCGC 60
AGTCATGAGA ACAAAAGTGT TGCCCAGCAG GCCTCTCTCA CAGAGCAGAG ACTTACTGTG 120
GAAAGCTGAG AACTGCCCGA TACACGGCAT CATCCCATCT CTAATTTCCC CTCTGTCCTC 180
CATCCAGCGG CTTCTTCCGC TTCATTCTCT ACCATACCAC TTGTGCATGC ATGTRATGTT 240
CTAATACCAA TTGAAGAACC GCTGTAGGTA CCTCCCTAAT AAGGATTTCT AAACCTATAG 300
TTAGTGTGAT CATGACTTTG GTCAAAGGCA AGTYTCCCAC CC 342 (2> INFORMATION FOR SEQ ID NO:38:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 355 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38:
GATGACTTGG AGAATGCCGA AGAGGAAGGC CAGGAGAATG TCGAGATCCT CCCCTCTGGG 60
GAGCGACCGC AGCCAACCAG AAGCGAATCA CCACACCATA CATGACCAAG TACGAGCGAG 120
CCCGCGTGCT GGGCACCCGA GCGCTCCAGA TTGCGATGTG TGCCCCTGTG ATGGTGGAGC 180
TGGAGGGGGA GACAGATCCT CTGCTCATTG CCATGAAGGA ACTCAAGGCC CGAAAGATCC 240
CCATCATCAT TCGCCGTTAC CTGCCAGATG GGAGCTATGA AGACTGGGGG GGTKGACGAG 300
CTCATCATCA CCGACTTGAG CTGGAGTCAT CTTTCCTGMC CTTTGCCCCA TGCCC 355 (2) INFORMATION FOR SEQ ID NO:39:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 303 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:39:
GCCAAAAACA NYTCTGAACC CGTTTTGGGA AATAATGGGA TTCCTTGATC ACGGGACAAC 60
GAATCACCCT GAAGTTTTTC TCCAGTTTAC TCAGTCACAT AAGCCACCAG AGGCTAACCA 120
CACTGACAAC AAAAGCAAGT CCCAGGATTC CGGGGGCTAA TACCATGCTA GGCATTACTT 180
GGGAAGTTAT GAGTTGGTAT ACATCTGTGA ATTTGGTGGG AGGAGAAAAC TAACAGTAAA 240
TTTATCAAAG CCAGTGGTAC GTTCAGCGTT ATAAAAATTA CAAGGATCTG CTTCTCGGCG 300
ACT 303 (2) INFORMATION FOR SEQ ID NO:40:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 178 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:40: GGTGTCGGGG GCTAGAGATA CACATGCCAG TNCTATACAT TTCTCAGCAC TGTGCTGTCG 60 ATTCACAGCA GTTCAATTGT TCATGCGATA TAAGCCAGTC ATGTGGCCCA AGTTATTCTG 120 TCGGCTGTGT TCTCTGCAGG AATCTGATGC AAGAAGGCCT GAAGGATGCA TGGCTTTT 178 (2) INFORMATION FOR SEQ ID NO:41:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 322 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:41: TGCCTTTCTT TAGAAATTTA GGGCAGTGTG ATGCTTCCAG AGGTCTGTAC AAACACCAGC 60
TTTCATTGTG CTTGGGAGTT TCCATGCCTC TYCCTTCTCT TCGCTTAGTG CACGTTTCTG 120
CTTTTTATCA GTTTGACTGC CTGAGACTGA KTCCAACAAC CCAAACTGAA CGCTCAGCTC 180
CTCCKTTTCA AAGGAGGATG ACTTNTCTNA ACAACTATTT AGGTGAATTA TTKCKACAGT 240
TTATTAAAGC AATGGCTCTA AACAAATTCC ACTGGGGGTG ACAAAGTACA ATACAAAAGG 300
CGTACTCTGA GGGCTTGGGG GT 322 (2) INFORMATION FOR SEQ ID NO:42:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 278 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:42:
AAACTTTGGC ATTTTTATTC AGACACGTAT AAAAACAAAA CAAAAAACTT CAGTGATACA 60
ACAGACGTTT TCCCTTAGTT CCCCATCCAA GGGGACAGAG GTGTGCAGCT GAAGCTGGAY 120
CTTTTTTCTG TCCTACCTGG AAGCTGTCTC ACTGCTGGAT GAGAATGGCT TCTAAAAGTG 180
GATCTTGGGG ATCCTTGTGA ATTTGCCCTC GGATAAGGAG TGAAGWTCAT TTACGGCACA 240
TGTGGATTAT GGTTTACACA AAGATGTCCA GTTATTTT 278 (2) INFORMATION FOR SEQ ID NO:43:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 225 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:43:
AGATCAAAAG ATGAGAGAAG CTGAAACAGA ACCGCATGAG GGAAAGAGGA AAGTGGAATC 60
TCTGTGGCCC ATCTTCAGGA TCCACCACCA GAAAACCCGT TACATCTTCG CCTCTTTTAC 120
AAGCGGAAAG CCAGCAGCAG GATCTCTAGG AATATTAGTA TTAAAGAAGG CTATGCAGCA 180
TAAACCTGAT TTCAAAATGG TAAAAGCAAG GTTATGTGTA CTTGT 225 (2) INFORMATION FOR SEQ ID NO:45:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 305 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:45: GGATTGCCAG GAGCTGTTCC AGGTTGGGGA GAGGCAGAGT GGACTATTTG AAATCCAGCC 60 TCAGGGGTCT CCGCCATTTT TGGTGAACTG CAAGATGACC TCAGATGGAG GCTGGACAGT 120
AATTCAGAGG CGCCACGATG GCTCAGTGGA CTTCAACCGG CCCTKGGTAG CCTACAAGGC 180
GGTGGTTTTG GGGGATCCCC ACGGCGAGTT CTGGCTTGGG TCTTGGAGAA AGGKGCATAG 240
CATCACGGGG GGACCGGAAC AGCCGMCTGG CCGTGCAAMC TGCGGGGACT GGGATGGGCA 300
AACGC 305
(2) INFORMATION FOR SEQ ID NO:46:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 264 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:46:
ATGAAATAGC ATATCTNNGC CTAATTAAAA GATTCCATTA CATTTACTTT TATCATTTAT 60
ACTGCCAAGG ATCAGTCACA AAAAATTCAA ATTATACATA TTATTCATGC TTTAATTTCA 120
TAAATAAGTA AATTAAAGCA AGCCAATATG TCTCTCTTCA TAACATAGGG AAAAATTACT 180
GTTTAGCATA ACAGNGTAAT AGGCAAAGTC TAGCCATACA GCAGCAGTTC ACGGTGTTGT 240
CAAGTTGGKA CAGGTTCCAT CGAT 264 (2) INFORMATION FOR SEQ ID NO:47:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 175 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:47: GATCTCTTCC AGCGTCAATG TACTGGGACA GCAAACACTC ACATTTGAAG TTCCTTCTGG 60 CCACCGGCTT CCCAGTACAT TGACGCTGGA AGAGATCATC TCAAATGGTT CTCCAGTGTC 120 AGGCTGGAGA TCTCCAGAAA TGGAGTCTAC TCCTGGGGTG GCTTGTATGG GAGCC 175
(2) INFORMATION FOR SEQ ID NO:48:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 270 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:48: GTCTGTCAGA GCNACCGGGC AGCTCAMRCC CACAGCGGCT CCTCATCCTC TGTGGTGGCA 60 TCCTCATTCC ACTCTCATCT GCCACCTKCT CAGGCGGGCC TCTAGCTTTC TCATGTACTC 120 TAGCAATTCC TGTTTCTCCT GCTGTAACTG CTCCTTTTCC TTCTGGAGCA CACGCAGGGC 180 TGACCGCAGC TGTGTCAGCT TCCGCTTACT TTMTGACAAC TGTACCAGGC TAGAATCCTT 240 TCTGCCTGGG TCAGCTTCAG TCTTTGAACA 270
(2) INFORMATION FOR SEQ ID NO:49:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 359 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:49:
CCCTGAAGAG TGGGTGGGAC AACCAGATGG GTGTAACCCC TTGTGGGGGA AAAGGAGTGA 60
GTTTACTTGG TAAAATAATA ATGGTAATGT CAGCAGCGTG GCTGGGGGAC TCAGTATGGT 120
CCCGGGAAAA GAGTTGGGGC AGTGAACTTC CCAGGCCGAC TGGCCTTGGG CTGGCAGCAG 180
GGAGGCTGCA GGGCGCCTAC CTMCTCTGCC ACGTCCCTGC CTAGGAAACC TATCCCAGGA 240
CACCCTGCTT TGGCCTGGAT AGCAGCCTAG GGATGAGCAT TTCTTTGAAA GCAATTAGGT 300
TATTCACCTG GTATTAAAAC TATTTACTGT TAAAAAATCT GTGACTTCAT GGARGTGGG 359 (2) INFORMATION FOR SEQ ID NO:50:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 271 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:50:
CCAGGAAGGA CAGGAAGTGT CCTCTAATAC GCATAAGATC CAGTACAGGA GAGATGGGAA 60
GMGAGKCTCC AGGATGAAGG GGAAAARAGG CCGCATGCCA GTCACCTGGC ATCTNCCAGA 120
GAGGGYCAGY CTNCCCACTG AGACTGGGGC ACGAGTCCCG TCATCACCAT GCCCTCTGAC 180
TGTCGAACTG TCTTTTTACC TGACAAATAC TACACAGGTA TCGMTCGTGG CCATACTCTG 240
CTATCTAAAC CCAGGAACTG ATTAGATTGT T 271 (2) INFORMATION FOR SEQ ID NO:51:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 226 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:51: CTCCAAGCAG TAAAGACTTG CAAAGCATTG CATTTTGATT AAACCTTGCT GGGCTGAAGG 60 GCAGGCAGAG CTGTGGTGGA CACTGGCAGG ACGCAGCACC CCCCGACTGG CCCTTGGCAG 120 GCTGCACCGG GCGCATGCGG GTGTGGGCCA GGGTTGCTTT AGGAAGCAGG TGGGAGTCTK 180 NCACGTGCAG KCGGTCCAGG AGKGYACCAK GCCTGGCAGG GCACTG 226
(2) INFORMATION FOR SEQ ID NO:52:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 408 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:52:
GGTGGGGCAA GGTGGGGGTG AAGTGCACTC CTGCTGCATG AGTGGCAGGG CAGGGTGCAC 60
ACACACACGT GGGTMCTGGC TGGGTGAGGC AAGCAAAACC TGCCTGCACA TGGCAAAGGG 120
ATGTGGGAAG TATCCATGGG CNCCAGGGGA AGCTGCAGTT TGGGGAGGGA ATGGGTGGCA 180
CTGCTGCGTG TCTGTGGGGG CCACCCCACT GGGGGTCTCC AAGTGGTCAA GTTCCGTCTG 240
CCAGGTTAGA AGCTATGATG GGGGCTTCTA GGACACTNGA GGCTGACCTG AAAGCAAGGT 300
ACTTTTCACA CTGGGACCCT GCAAGAGGCC AACAAGATTA AGGGATGCTT CAGGTCAGAC 360
TTGGCCCTCT TCTTATGGGG CAAGACCTTC CCCGCAGAGT TCAGATCT 408 (2) INFORMATION FOR SEQ ID NO:53:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 314 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:53:
TTCTGTGCAG GAGGACCACA TGGCAGTCCA GCAGACTGCA CATTTTTAAA AACTAGGTCT 60
TCCCAGGTAG TTTGAGGAGC ACCAGGGCAC ACTCAGGGAA GGGACATGTC AGTGTCTGAG 120
AGCTCACGGG AGGAAGGTGT AGTGACAACA TGGACCATGG TGGAGTGACT TTAGACGGCT 180
CTTGGGTNAG GAGAATCATC ATGTAACAAA GCATTAAATC ATTTGGAGAA ATTCAGAAAA 240
NTCGTAGATG TACATTCTAG CCCACTTACC AGGCCTACTA AACGTCAATC AGATATATTT 300
CAATTTGAAT TCGG 314
(2) INFORMATION FOR SEQ ID NO:54:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 310 base pairs (B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:54: AAGCCACCGC ACCTGGCCCA TTACATTTAT AATGTTATAA GGGGGTTGAG GGGTCGTCCA 60 CTGGAGCAGT GGTTCTCAAA CTCGTGTATG CATAGGAATT ACCTGAAGGG CTTGTTAAAA 120
CACAAACTGC AGGGCCCACC CCCAGAGTTT CTGGTTGGGG AGGTGTGGGC TGGGCTTGAG 180
GATGTGAATC TCTCACAAGC TCCCAGGTGA GGCTGCTGGT CTGTGGACCC ACTTCAAAGA 240
CCCAGTGAAT CAGAAGAGTC AGTGAGACTG GACAAATGAA CGCAAGACAG TCTTCAAAGG 300
AGACCAGAGG 310 (2) INFORMATION FOR SEQ ID NO:55:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 252 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:55:
TTTTTTTTTT TYCCGGGGAR GTCAAACATA CTTTTTCAAC ATAGGATKTC TGACAGGAGG 60
CCCTTGGMCA GGGTTCCCTG ACCTCTGYTT CAAACCCCAC TGGAAACAGA GCAAAGTCAT 120
CAMGAAAACC CAGGACACCA GGGCAGGGGG GCTGCACAAG GTCGGGTAGG TCACAGTGGG 180
CCAGCACACA GTGGCCCCGC CCAGGTCCAG CCCAGCCTGG GGGAGGGTGT GAGGGTTCCA 240
KGCAAGCTCA TT 252 (2) INFORMATION FOR SEQ ID NO:56:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 188 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double (D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:56:
GTCAAGTCTA CCATCATTCT AGAAGGAAAA GGCATGGTGG GAATTCAGCA CCTGAACTTG 60
TATTTACACC AGCCTCGGCA TCTGGCAAGG RAATAGCGAT TGTTCATAGT GATGCAGAGA 120
GAGAACAGGA GGAKGAAGAA CAAATACACA CAAACAACTG ATCTAGGGAG ACTCCAARGA 180
TCCAACAG 188
(2) INFORMATION FOR SEQ ID NO:57:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 304 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:57: AATCAGCCTG CAAGCAAAAG ATAGGAATAT TCACCTACAG TGGGCACCTC CTTGAAGAAG 60 CTGATAGCTT TTACACAGTA TTAGATTGAA ATAATGGACA GAAACACATT CTTGTCAAGA 120 AAGGGGGAGA GAAGTCTGTT TGCAAGTTTC AAAGCAAAAA GCAAAAGTGA AATGATTTGA 180
GGATTTCTGT TCTAATTGGA GATGATTCTC TGGTTGTTAG AAATGGCAAA TATTGATGAT 240
TGTGTGCTAT TGATTGGTGC AGGATACTTG GTATACGAGT AAATACTTGA GACTCGTGTC 300
ACTT 304 (2) INFORMATION FOR SEQ ID NO:58:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 261 base pairs
(B) TYPE: nucleic acid (C)- STRANDEDNESS: double (D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:58:
CCAGAAGCTT CTTGCCTTCT CTGTGCTCTC AGTGGTTCCC TTCCCTGAAG TGCCTCCCTT 60
CTCATTAATT ATAGCCTGTG TCTGAACATT GTGAGCTATA AGAACCCTCA TATTAATGGT 120
TAAGGGACTG TTGGAAATGA TGTGATTTTA TTAAAAATGG GGTCTTTGTG GAGGAGTCAG 180
GAATGGTCAA AATGAGCTTC AGGTATGGGG CTTGCTCTRT GCTCCTGATA CCAAGGGTCT 240
GGCAAGCACA AAGGAAGGTG G 261
(2) INFORMATION FOR SEQ ID NO:59:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 470 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:59:
AATACGTATT CTGAAGCCAC TATATCTGCA TATGTATCCC AGATTTGAAC AATTAAGTAA 60
AAAGATGGTG AATGATGAAA GCCAGTTTTC TGTCTGTAGA AGTGAGAGGT GACAGATAAC 120
CAAAGGAAGA AGGCTAGAAT GGATAGAGGA CAGTGCTTAA GTGTAGTTCC TGTTGCCTTT 180
AGTCTTATAG ACTTCATTTC CAAAGTTTCT TAGCACCCCC CTTCCCCCTT TGGTGAGGTT 240
GTTTCACATA TTTTCTAGAC AATTAGATTC TTTTGTCAAA GTCTGTGTTC CATCCGGAGA 300
GCCTCTGATC TCTTAAATGA TTTTTTAAAT TTACATACAT TAAGGTTCAC TCTGCTGTAA 360
AGGTCTGTGG GTTTTAATCC TGTCTCACAG TTTTTGCATA TGTTGGCCTT CTGCCTGGGA 420
ATACTCTCCC AGATATTCCC CATGACTGGC CCCTTATCTT CAATCAGATC 470 (2) INFORMATION FOR SEQ ID NO:60:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 466 base pairs
(B) TYPE: nucleic acid (C) STRANDEDNESS: double
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:60:
GTGTTTCAAG GGAAGGCAAC TMCAAGTTTG TGCAGCTGAA TTTCTGTAAA GTTAAGACAG 60
ACTCAMCTTC TCATTCAATC TGGGGCAGTG GATAACCTTT CTGAATAGAC CCACTTGTTC 120
ACGGACAGGG ATAGAGGTTT GCCTTTCTTC TTTCCTTGAA TTTGGAGTGA GCACTAGGGA 180
GGGGAAGTGC ATGGGTGACA TGAAGAAGGT GAAGATGTAG TAAAAGCATC ATCCAGGTAC 240
ACATTAACGG TGCTGCAGAA TTTTCACAAT ACAACTGAGG GAGTCTGTAG TGGCAAAAGC 300
AATTACTGAG CACAAAAGCC AGTCCTCAAG GGCTGATTCC ACCTTCCCTG TCCAGGGACT 360
TTCTCAGCAA ACTTTGTTCA TGAGCAGTTG TTCGCTTTGA TGGTCTTAGC CAGTTTTTGG 420
TGCAGGGGTG TTCCTCTGGT ACTAGGGCTA GGGCAGCTGT TTAAAG 466
(2) INFORMATION FOR SEQ ID NO:61:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 491 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:61:
GACACCCCTC CTGCCATGAA GAATGCCACT AGCTCTAAGC AGCTCCCACT GGAACCAGAG 60
AGCCCCTCAG GGCAGGTCGG GCCTAGGCCA GCCCCCCCGC AGGAAGAGTC CCCTTCCTCT 120
GAAGCAAAGA GCAGAGGACC CACCCCACCA GCCATGGGCC CACGGGATGC CAGACCTCCT 180
CGAAGGAGCA GCCAGCCATC TCCAACAGCA GTGCCAGCCT CCGACAGCCC TCCCACCAAG 240
CAAGAGGTGA AGAAGGCAGG AGAGAGACAC AAGCTGGCAA AGGAGCGGCG AGAAGAGCGT 300
GCCAAGTACC TGGCGGCCAA GGAAGGCAGT GTGGCTGGGA AGGAGGAGAA AGGCCAAGGT 360
GCTGCGGGAG GAAGCAAGCT CCATGGAGCG CCGCTGCCGG TTTTAGGGAG CAAACGTCTT 420
AAAGCCGAGC AACGCCGTTC AAGCCTTGGA GGAACGGCTA GCGGAAGAAG TTTGTGGAAA 480
ACAAGGGGCG T 491 (2) INFORMATION FOR SEQ ID NO:62:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 478 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:62: ATCATTGAGT ACGCAGAGCT CAAAACAGAC GTGTTCCAGA GCCTGAGGGA AGTGGGCAAT 60 GCATCCTCTT CTGCCTCCTC ATAGAGCAAG CTCTGTCTCA GGAGGAGGTC TGCGATTTGC 120 TCCATGCCGA CCCTTCCAAA ACATCTTGCC TAGAGTCTAC ATCAAAGAGG GGGAGCGCCT 180
GGAGGTCCGG ATGAAACGTC TGGAAGCCAA GTATGCCCCG CTCCACCTGG TCCCTCTGAT 240
CGAGCGGCTG GGGACCCTCA GCAAATCGCC ATTGCTCGCG AGGGTGACCT CCTGACCAAG 300
GAGCGGCTGT CTGTGGCTGT CCATGTTCGA GGTCATCCTG ACCCGATTCG GAGCTACCTT 360
CAGGACCCAT CTGGCGGGGC CACCGCCACC AATGCGTATG ACGTCGATGA GTTTTTGAGT 420
TCACTGCTGT GAGCGCATGA GTCGTGTACT GAATCCTGTG GACAACGGTT AAGTTACA 478 (2) INFORMATION FOR SEQ ID NO:63:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 183 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:63:
CCTGGAAAGT GGGGGTGGGC CAGGGGGCCA GGCCCAGCAT GCACCCCCAT TTTTTTGGGG 60
GCTGATCCCT GCCCCAGCTC TGCTGATACC CGGGGCCACA GCGTCAGGCC GTTGGGGGTG 120
GAGKTAGAGG TGGGAGAGCA GGGGAGAGAG CCTKAGGAGC CACAATTGGG CAGACAGAAG 180
CGG 183 (2) INFORMATION FOR SEQ ID NO:64:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 316 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:64:
GGATATTGCA CCTTACAGAC TTAGGGAGCC TTTACCAGAG ACGCCTAAAA CGCCCCAGGT 60
TCAGCCATTG TGCTGAATAG AGTGGAATAT AGAACCAGGG ACAGAGTATT TCATTTAACG 120
TTGATATATA CTTGCTAAGG AAACACTAAC AATACTGTAA CTTTGTTAAA GGACATAGTA 180
TTGAAATGGG AAATAGAGGT CAGGCTCACA TCATCTTAGT TTAATGCTGG GCAACTTTTT 240
CTGATTTCTG TAGTTCCCTG GAAAATGTGT CCTTCGTACC CATAAAGTGG TACAAATGCA 300
TTTGTAACCA TTTTTG 316 (2) INFORMATION FOR SEQ ID NO:66:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 411 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:66: ATCTGGTCTA GAGAGGCGAC TCCAAGCTCT CTTGCTGGCT CCCAGCTGTG GGAATCCTTT 60
AGGCTTGTTC TCAACCTACA CGTTAAAAAT GCTTCTTGGT GTGTTTGGGG AGGGGGAGAG 120
GGAAACTGAG CTCTCTCTTG ACCTCCTCCA ACACCCTTGA CTTGCTTACC CAGCCATTTT 180
CAGTAGCTAC ACGGGTGGTC ACAGAACACT GGGCGGCACT CGGCACACAA CACAGAACCG 240
GGGCAGTCCA TGCAGGTGCG GGAACACATG TCGGACCCAG GGAGCAAGGA ACACGCCACC 300
CCGAGGAACA TGCAAACGGA GGAAGGATTC CCTTCAGATT CCAAGGATGC CACAACCCCG 360
ACGGGCGGCT TAGGGAGGCA CCGATTATCT AAGGAAAAAG GCCACTGTTT G 411 (2) INFORMATION FOR SEQ ID NO:67:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 413 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ.ID NO:67:
CTGCTCCTTA TGTTTTTATT TCCAAAGTTT AGAATTTCTT TGCTTCATAG TATTATTTTA 60
TTTTACTAAA TTACAGAGTA AGAAAAGCTT TTCATTTTAT CTGATTTTAT TCTTAGAACA 120
AAAATATTAC GATCTTCTAT ATTTTTGTTC TTTTGCCAAA AAGTGTAGGC AATTTTACAT 180
CATCTTTTTT CCCAATCAGT TTGTGATCCA ACTATAAAAA GGAGACATAG AATACTGAAT 240
AAATGAAACA GAAACTCCAA GGCCAAGAAG TGTCCATCTT GAAAGAGTGT TAGTGGCAAG 300
ATATGTGACT GCAGACTAGA TGTAGACAAA CCTGAGAAAA ACCAAGCATG GGGGAAAGGA 360
TYCCTATTTT AATAAATGGT GCTGGGGAAA ACTGGCTAGC CATATGTACT TTA 413 (2) INFORMATION FOR SEQ ID NO:68:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 372 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:68:
GCACGGTTAA AAGACCAACG TGTGTGGNTC AAATATAAAG GCCACACCTT TCAGACCGAA 60
CCTACTCAAA GATCCTTTAC TTTGCAATAA TTTGAACTGG AGAACCAAAG ACGGGAGACG 120
AATGAAAGCA AAGATGCTCA AAGAACCAAA GGAAAGACCT GAAGGAATCC ACCTGCATAG 180
GCCACGCGTT CCACTCTGGG TCAAATGCTT CCACGATGCA GAAACCTTTT TTTAAAAAAG 240
TGCAAGTCTA ATTACCTACC AAGGGTAATA AAAAGCACAG CACAGGAATG ATTACAGCTG 300
ATGGTCAAAA AACAAACCAA AACCATTAAA AAAACAATCA GGCAGAAAAC AGGAGTTAAA 360
TGTTTACATA TG 372 (2) INFORMATION FOR SEQ ID NO:69:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 389 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:69:
TCTAGAACCT GGACCCACCC AGCGCGTCCT TTCTTATCCC CGAGTGGATG GATGGATGGA 60
TGGATGGTAG GGATGTTAAT AATTTTAGTG GAACAAAGCC TGTGAAATGA TTGTACATAG 120
TGTTAATTTA TTGTAACGAA TGGCTAGTTT TTATTCTCGT CAAGGCACAA AACCAGTTCA 180
TGCTTAACCN TTTTTTCCTT TCCTTTCTTT GCTTTTCTTT CTCTCCTCTC ATACTTTCTC 240
TTCTCTCTCT TTTAATTTTC TTGTGAGATA ATATTCTAAG AGGCTCTAGA AACATGAAAT 300
ACTCAGTAGT GGATGGGTTT CCCACTTCTC CTCAATCCGT TGCATGAAAT AATTACTATG 360
GTGCCCTAAT GCACACAAAT AGCTAAGGG 389 (2) INFORMATION FOR SEQ ID NO:71:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 329 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:71:
GAAAAAATGG GAGGGCAGCC ATGTATTAAT TGTACATCCA AGGAAACTGT GCCCCAGGGG 60
TCTTGTGTGT ATTTCTGAGA AGAGGGGTGA GAAAAGGCAC TGTGTCAACA TTTGCTTCTG 120
CCTGAACGTG CACCTCCCAG TGCTCCTCCA TCAATTAGGA GAACTGTCTT GAAGAATGCT 180
GCCTCAGCTT CTGAAGAGAA GACCCCAGGA CATGCATTAA TGAGAGGAGG GGAGTCACAG 240
CTGCAGAAGA ATAAAGCTCT CTGAGGGAGC CTGGGNGCCC CCAGTGGAGG CCTGGAGCTT 300
GTTGACCANN GCAGCAGGAG ACCCCTGCT 329 (2) INFORMATION FOR SEQ ID NO:72:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 418 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:72:
CTGAGTTGCC TGAGGTCATT CACATGCTTC AGCACCAGTT CCCATCTGTT CAGGCAAATG 60
CAGCGGCCTA CCTGCAGCAC CTGTGCTTTG GTGACAACAA AGTGAAGATG GAGGTGTGTA 120
GGTTAGGGGG AATCAAGCAT CTGGTTGACC TTCTGGACCA CAGAGTTTTG GAAGTTCAGA 180 AGAATGCTTG TGGTGCCCTT CGAAACCTCG TTTTTGGCAA GTCTACAGAT GAAAATAAAA 240
TAGCAATGAA GAATGTTGGT GGGGATACCT GCCTTGTTGC GGCTGTTGAG AAAAATCTAT 300
TTGATGCAGA AGTAAGGGAG CTTGTTACAG GAGTCTTTGG AATTATCCCT CATGTGATGC 360
CTGTAAAAAT GACATTCATT CGAGATGCTC TCTCAACCTT AACAAACACT GTGATTGT 418 (2) INFORMATION FOR SEQ ID NO:73:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 336 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:73:
CTGAATTTTT ATATGCTTCA CTTAGGCTTT CATTTGAGTA GACTCTAAAA ATTCTGCCTT 60
GCTTAAGTNC TAACACTGCC TCTCAGATTT CAGTTTTGGA CATTGCACAA CTAAGACCTT 120
TTAAACGCAT TTNCTTGCTA ACTCGGAAGA CACATAGTCT GCAGCAAGAC ATTCCTATAT 180
TGAAGAAATG AGAGAAAATT TTATGCTGCA TCAGGTGGAG AGCAAGGCTC AACGGTGGTT 240
GCATTAGTTC CCTCGGAAGT ATTGAAAAAN CTTTGAAATG GGAAGGAAAA TTTTTTGCAC 300
CTAATGTTCC TGAGGTACCC AGAATGTCTG GGGGTT 336 (2) INFORMATION FOR SEQ ID NO:74:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 402 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:74:
GTGCTCAGTA AATACAAATT GGATGGACTA GAGAGATAGC CCCGAGGACA CTGCCAAATA 60
AATAACAAAT TGTGCAAGCA GCAGGCCGCT GTAATTAGAC CAAGGAGGAC AGTCAGTTAT 120
TAATATCAGA CACGTGGCAG GGTTAACAGC CACTGAGGGT GGGTACAATG AAGAGAGTCA 180
CTTTCTGCAC CCTCAGGGAC TTCCCTTGTG ATGGCCTTCT AAAGAGGGCT GAACAGCACC 240
AAGTGCCCTC GCTGCCTCTG GTTCCTGCTG CCCTCCGCGT GCCTTGGGTG CCCCACAACT 300
AGGGCCCTGG GTCCCTCCCA TGTCCCCCTC CCTCCTACAA CCCCTCAGCC CCTTATCTGG 360
CCAGCCATTA TGATGCCTAT CAGTATGAGG CCAGATGAGA GT 402 (2) INFORMATION FOR SEQ ID NO:75:
(i) SEQUENCE CHARACTERISTICS:"
(A) LENGTH: 454 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear -1Q7-
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:75:
GGACCCCGGG CCCGCGATGT GGCCCAGTAC CTGCTCTCAG ACAGCCTCTT CGTGTGGGTT 60
CTAGTAAATA CCGCTTGCTG TGTTTTGATG TTGGTGGCTA AGCTCATCCA GTGTATTGTG 120
TTTGGCCCTC TTCGAGTGAG TGAGAGACAG CATCTCAAAG ACANATTTTG GAATTTTATT 180
TTCTACAAGT TCATTTTCAT CTTTGGTGTG CTGAATGTCC AGACAGTGGA AGAGGTGGTC 240
ATGTGGTGCC TCTGGTTTGC CGGACTTGTC TTTCTGCACC TGATGGTTCA GCTCTGCAAG 300
GNTCGATTTG AATATCTTTC CTTCTCGNCC ACCACGGCGA TGAGCAGCCA CGGGTCGAGT 360
CCTGTCCCTG TTTGGTTGCC ATGCTGCTTT TCCTGCTGTG GACTTGCGGC CGTTTGCTCA 420
TTACCGGGTA CACCACGGAA TGCACACCTG GCTT 454
(2) INFORMATION FOR SEQ ID NO:76:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 313 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:76:
GCTTTGATAG CTAGTTGTCT AAAAGTGCTG NTTATTAAAT AATCCACCTN TTTCCCCACT 60
TAAAACATCC CTCTTACCAT ATACTAAATT CCNGTAGCCC TGGGTCTGTT TCTGGACTCT 120
CCCGTCTGTC TGACCCCCTC CAGGTCACAC TGAGTGAGGT AATGGTGGCG TGAGAATCCT 180
CTGGGAATCT GGCAGGNTCA CCCCNGAGCA GTCCACCCCN CAACTCATTA NCATCGTTCA 240
GAGTGGNCTG AGTGNTCTCA CACATTCACT CTGCCAAATG CACTTTAGGA ACTGTCAAAT 300
TCCAAAGTTT CAA 313 (2) INFORMATION FOR SEQ ID NO:77:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 446 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:77:
CTCAGCCGTA GCCCTAAGTC GTTTTTCCAA TTTAGGAAGC TCACAACGCA GATCTGCATT 60
GTCACGTACC AGCTGTTTGT GAACCTTTGT AAGCTGTTCC AGGTTGTTCT CAAGAAAGGA 120
AATCTTCTGC TTTTGGGAGT GAATCCCCCC ACTGTCTTCG GGCTCCATTT CTGCACTTTT 180
CTTGACTCGA GTCGTGACGT CTTGAACGAA CAGCTTGCGA AGGTTGTGGC SGGTCTGGAG 240
TTCCCGGGCA ACTGTCTCCT CCAGACCCTT GAGGTCCTGC TTGTGACTGC TCAATGTCGC 300 TCGTACAGAA ATGTCAGCTC CTGCAGCTTT GGTGCTCTTC TCGTGGTTCT TCGCTCTTTC 360
AGCTTTCTCG TAGTCAAGCC TGAAGGCTTC TCTAAGCTCT AACTGGAGCT TCTGATTTAA 420
GGTCTTTTGA GCTCATCAAA TGGTCT 446 (2) INFORMATION FOR SEQ ID NO:78:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 296 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:78:
AGCCGGTGGC GCAATGGAGA GAATGTGCCT GAGACAGAGC GCCTGGCTGG GGAGGAGGCA 60
GCCCTGGGNG CCGAGCTCTG TGAGGAGACC CCTGTGAATG ACAACTCATC CATCGTGGTG 120
CGCATCGCGC CCGAGGAGCG GCAGAAATAC GAGGAGGAGA TCCGCCGTCT CTATAAGCAG 180
CTTNACGACA AGGATGATGA AATCAACCAA CAAAGCCAAC TCATAGAGNA GCTCAAGCAG 240
CAAATNCTGG ACCAGGAAGA GCTGCTGGTG TNCACCCGAG GAGACAACGA GAAGGT 296 (2) INFORMATION FOR SEQ ID NO:79:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 285 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:79:
CCTTTCCTGC CTGGGAAGTG ATGACTCGCA GGTCGGGCTT GCGGCTGGGG GCTCCAAGCT 60
GGGTGCTGTG GGTAGGTGGG GGCGGAGACT TGGCAGGGAT GACCTTGTTT AGGCTGTTGC 120
CATTGGCCAC AGGGAGGAGG CCAGGGGAAG CCCGAGCACT GACGTAGCCA TTCCCAACAG 180
GGCTGGGGCA GGCTCCGTTA GCACTGTTCA GGTCACCNCC CAGCATGGCC CCCGCACTAG 240
CTGGCCGCTG GGGCAGGCCA GGAGACACAC TGTTCCTCTG TAGTG 285 (2) INFORMATION FOR SEQ ID NO:80:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 402 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:80:
ATGATTTCTT GCCTGTNATA ACCTATGCAC TCACAAAGAT GAACTCTCTG AGAGGGATGA 60
GCAAGAGCTT CAGGAAATCC GAAAGTATTT CTCCTTTCCT GTATTCTTTT TCAAAGTGCC 120
GAAACTGGGC TCGGAGATAA TAGACTCCTC AACCAGGAGA ATGGAGAGCG AAAGATCACC 180 GCTTTATCGC CAGCTAATTG ACCTGGGCTA TCTGAGCAGC AGTCACTGGA ACTGTGGGGC 240
TCCTGGCCAG GGATACTAAA GCTCAGAGCA TGTTGGTGGA ACAGAGTGAA AAGCTGAGAC 300
ACTTGAGCAC ATTTTCTCAC CAGGTGTTAC AGACTCGCCT GGTNGATGCA GCCAAGGCCC 360
TGAAACCTGG TGCACTGCCA CTGCCTTGAC ATCTTTTATT AA 402 (2) INFORMATION FOR SEQ ID NO:81:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 246 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:81:
CATTTTTAAT AGAGACGGGG TTTAACCATG TTGGCCAGGC TGGTCTTGAA CTCTTGATCT 60
CAGGTAATCC ACCCACTATG GCCTCCCAAA GTGCTGGGGT TACAGGTTTG AGCCTCTGTN 120
CCCGGCCCGG CCAAAGACTG CCTATTCTAA ACGTTGCTGA GGACGTGGAN CAATCACAGC 180
TCTCCTNTCT TTCCAGTGGG AGTTTAACAT GGCACAACCG CCTGAAAACC GTTTGGNGAT 240
TTCTGT 246 (2) INFORMATION FOR SEQ ID NO:82:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 394 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:82:
GGGAACCCTC AGCAAAATAT AATGGTACCG CTATTATCAG CCTTGTTCGA GGCCCAGGGA 60
TTTTGGGGGA GGTCACAGTG TTCTGGAGGA TATTCCCTCC TTCCGTGGGG GAATTTGCTG 120
AAACATCAGG NAAACTGACA ATGCGAGACG AACAGTCTGC AGTCATTGTA GTAATACAGG 180
CTTTGAACGA TGACATTCCC GAGGAAAAAA GCTTCTATGA GTTTCAGCTC ACTGCAGTCA 240
GTNAGGGAGG AGTTCTGAGT GAATCCAGCA GCACTNCCAA CATCACGGTG GTGGCCAGCG 300
ACTCTCCCTA TGGCCGATTT GCCTTTTNAC ATGAGGCAAC TTCGAGTGTC AGAAGCACAG 360
AGGGNTAACA TCACAATCAT CCGTTCCAGT GGAG 394 (2) INFORMATION FOR SEQ ID NO:83:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 308 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:83: ATAAGACCAT TGGCAAAGGG AGAATTCATG AACTGAAAGA TCTGAAGTAA TTTCCCAGAA 60
TGTAATGTTA AGAAATAAGT TAAAAGGCAG AGCATAATGA GTCTAACATG TGTGATTGAA 120
GTCTTATAAG GMGAGAATTA AGAMCAGGCA ATATTTTAAA GGRATAATGG AGAAAATGGA 180
ATAATTGATG AAATATGTGA ATATATATAG GGACCATATG CATATGAMGG CCGGGGGTTA 240
AATAAAACGA AATCTACTTG TACATACTTT ATGGGATTCC TGCAGCCCGG GGGGATCCAC 300
TAGTTCTT 308 (2) INFORMATION FOR SEQ ID NO:84:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 313 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:84:
CTTTAACTTA ATGGCAATTA AAACTCACTG GCAAAAAAAA TCACTAGAGA TGTCAGTCCA 60
TTATCTTACC AAATAGTGTA TTTTTACCAT CTTTTACCTA CACCCTTGAG TAAGGTGGAA 120
TAGGTTAAAG TTACTGGCAT AATAACACTT CATTGAATTC ATGATAGTAT TTAACATGTT 180
AAAACTGTTT AGTTGAAAAG TTCACATGCA ATTTATAATT TAAAAATATG CTACATATAT 240
TTCATAAAAW TACAATAGGT CATACTARAC TTTGACTAAA ATTAAGAATG TKTTTCTKTC 300
ATAATAATGC AGG 313 (2) INFORMATION FOR SEQ ID NO:85:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 303 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:85:
TGCTCCGTTT ATTGCTCTAT TCAATGACCA CGAGCGAATT ATAAAAAGAC ACCAAATGTC 60
TCTGTCTGCC GTGGGATAAA TATTTAAAGT CAGCAATAAA GTCACGTGGC TCCAAGRTAA 120
TACATGTTGC CAAAGAGTCA TGCATGCCCT CCTGATGGGC TCTCAACACA CGTATGGWCA 180
TGGGAACACA CGCAGAGCAA CACGCAGTAT GAACTTSTGG GAAGGCTTTA CCACAGTGAC 240
ACAGTAAAAT GTCTCACGTA GATCTGRGCT GAGTCCCCAC CCAAACCTTG AGCTCCCCTT 300
CCA 303 (2) INFORMATION FOR SEQ ID NO:86:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 380 base pairs
(B) TYPE: nucleic acid (C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:86:
AAAACAAACC AGCTTTAATA CCAATATAGT TCTCTCTTAA ATACCGTGTT TCCCAGGACA 60
AATGCAGGGG CAGGCTCTTG GCAGAAAGAG TAGAAAGGAA ATGTGGAACA AAATGGAATG 120
GATGGCCCAG GCCCAGGGTC CCTGCCTTGG GCACTAGGGA CTGGGCTGCC TCGGGGATGG 180
GGGAGTGACA GCAGCTCCCC CTGGTCCAGT TATTGCAGAG GCGTCGGGGG CTCCCCTCCC 240
TCCCCAGGCC TGAAACATTT CTCAGGATTA CTTCTGACCT TCAGCCCCAG CAGGGCCAGG 300
GCCTGGGCTC CTCTGGTCTA GGATGGGCCC CTTTGCCCAA AAGGGCCTTC AGCTAAGGCG 360
TTGGGTTGGG CGGGGAGCCC 380 (2) INFORMATION FOR SEQ ID NO:87:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 280 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:87:
GCCTTTGCTG CTTATTCGCA TCGATGGTGA AAGAGATGTC AGGAGCACTT CTCTGCTGAG 60
GTGGCTGAGA CGAAGAGGAC TCTGCTGCCA GCCTTGCCGC ATACCTGGCA ATTAGCCTGT 120
GTTCTTCATC AAGCCGGTTT GAACTCTCAA GCATGCTCCT GGTAATAAAA GGACTTCCTG 180
AGGAGGGAAC AGAGTGNGAG AACAGGGTGT CGTTCATGCT GGTTACAGGT CTGGGAGGCA 240
CGATGTGAGC CAAGTTGAGT GGCTTCTCAG GCTGATCTGG 280 (2) INFORMATION FOR SEQ ID NO:88:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 446 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:88:
CCTGCGTCTC TTACACCCYC TCCCACCCGA GGCTCCCCAG AGATAGCAGA GAATTCGAAG 60
AGGTCGCCGG GGACTGGAAA GAAGTCCCNG NAGGCCGCCT TCGCAGTCTA CACCCCAGCC 120
TGCTTCCCAG CCTACAYCCA GACCCAGCTC AGACCTTCGT GACCACCCCA TCCCTTTCTC 180
CGGCTGGCTG GGTCGGGGGC ATCCCTCTCT GTCGCTGGCT TCCAGAGGCA GGACAGGCCT 240
CCTGGTAAGC CCGCAAAGTT GCTGACCTCC TGACTTCGTC TGCCTTTTAT TAATATCTGT 300
ATTGCTGATA ACCGTGCTCT TGACTATGTG TCCCAGGTCA TGTCCCAGGT CATGGAGAAG 360- CCCGTGCCAC AGTGACCCTT CCCATACTTC TGGGGGGGCT GCTCTCCATC TGGATCGTAG 420 GAGGATATAG GTGTGTTCTG GACCAT 446
(2) INFORMATION FOR SEQ ID NO:89:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 384 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:89:
GTCCCTTCTG GGGACTCTRT TTCCCCATTT ATTGCTGCTG TGTCCCTNAC CAGTTCCTTG 60
CAGGATTCCC TCCTTTTAAA ATGCCCTTAA ATCTAGCTTT GCCTTGGAGA CCCCAGTGGG 120
TGCTGCTCCT GCCGTTTTCT TCCTGCCAAG CCTGAATCAA TGTTTCATCT CCAACCCTCT 180
GCCAGTTTGG CCCCTCAAAG CTTGGTGGCT CAAGACTGTW AGCCTGGCAG AGCCGCGNGG 240
TGAAGGGAGA AGCTCTTGGA GCAGGCAGGA TGCCACCGCT GCTTCAGCTT GCCTCCTCGC 300
CCAGCTACCC TTTGGCCCCA TTGGGCCCTC GTMTGCCTCT CCAGGATTGT ATGTTTCAAG 360
NCTTGTCCTG TGTTCCTTTG TCTG 384
(2) INFORMATION FOR SEQ ID NO:90:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 344 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:90:
TCAAGCTGGA AAGGGCTACT ACCTCATGCT GGAAAGGGCT ACTACCTCAA GCTGGAAAGG 60
GCTACTACCT CAAGCTGGAA AGGGCTACTA CCTCAAGCTG GAAAGGGCTA CTACCTCAAG 120
CTGGAAAGAG CTACTACCTC AAGCTGGAAA GGGCTACTAC CTCATGCTGG AAAGGGCTAC 180
TACCTCAAGC TGGAAAGAGC TACTACCTCA AGCTGGAAAG GGCTACTACC TCAAGCTGGA 240
AAGGGCTACT ACCTCAAGCT GGAAAGAGCT ACTACCTCCA AGCTGGAAAG GGCTACTACC 300
TCATGCTGGG AAAGGGCTAC TACCTCAAGC TGGACAGGGC TACT 344
(2) INFORMATION FOR SEQ ID NO:91:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 364 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:91: GCCCCAGGGT GAGGGCTATG AGGGGTCAGG GGTCAGGTTC CCCAGGACCC TAGTCCTTGT 60
CCCCTTCCCT GGTGCTAAAT AAAAGTGAAT AAATACTAAA TAAATACAAC TGGGGCCCAG 120
GCCCTCCCTG CCTTCCCCCT CCCTCCTGTG ACCCGCAGCA GAGGGGGCAG TTTAGATGGA 180
GGGCTGTCTG TCAGCCCCTT CCATCCACTA ACCCATCACT GCCTCCCAGG GCAGGAAACC 240
AGGGCAGGGC CAGCCTGCGC ATTAGGGCAG AGAGGAGGGG CAGGTCTCAC GCCCACAGCC 300
CCTTCCCACT TGAGTCTTAG CATGAGGCAG CAACAGAAGC TCTCTCTTCC TCCCAGCTAA 360
GTCC 364 (2) INFORMATION FOR SEQ ID NO:92:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 218 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:92:
ATTTAATAGA AAATTAAAAT AATAAATAAT ATGAAACAGA CTGATAACGC TGAGCTGGGC 60
AGGCCCAGGC CAGTCTAGTA CAAAGTTAAG GAGGTAGGGA GGATGGTGGG GAGGAGGGGG 120
CGGACTACCC TGCAGGACGC GGGAGGCTGC TCAGACTGTG GTGATGTCAG GAAGGGCCGC 180
ACACTTTGGC ATGGACGATG CACTAAAAAA AGAGAAAG 218 (2) INFORMATION FOR SEQ ID NO:93:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 364 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:93:
GCTTTCAAGG GAACAAAGAA TCGGCCTGGC AGTGCCCTGG AGAAGGAGGT GGAGAGCATG 60
GGGGCCCATC TTAATGCCTA CAGNACCCGG GAGCACACAG CTTACTACAT CAAGGCGCTG 120
TCCAAGGATC TGCCGAAAGC TGTGGAGCTC CTGGGTGACA TTGTGCAGAA CTGTAGTCTG 180
GAAGACTCAC AGATTGAGAA GGAACGTGAT GTGATCCTGC GGGAGATGCA GGAGAATGAT 240
GCATCTATGC GAGATGTGGT CTTTAACTAC CTGCATGCCA CAGCATTCCA GGGGCACACC 300
TCTAGCCCAG GCTTTGGAGG GGCCCAGTGA GAATGTCAGG AAGCTGTCTC GTGCAGACTT 360
GACC 364 (2) INFORMATION FOR SEQ ID NO:94:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 423 base pairs
(B) TYPE: nucleic acid (C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:94:
CTTCATACTA GAACTGTCTG CCATCTTTAT TTCTTTGTTT TCAGGAAAAT TGGAGAGAAA 60
AGTATTTCTT TTTTAAAAAT GATTATTATA CTTTAAGTTC TGGGATACAT GTGCAGAACG 120
TGCACGTTTG TTACATAAGT ATACACGTGC CATGGTGGTT TGCTGCACCC ATCAACCCGT 180
CATCTACATT AGGTATTTCT CCTAATGCTA TCCCTCCCCT AGCCCCCCAC CCTCCAACAG 240
GCTCCAGTGT GTGATGTTCC CCTCCCTGTG TCCATGTGTT CTCATTGTTC AACTCCCACT 300
TATGAGTGAG GGACATGCAG TGTTTGATTT TCTGTTCCTG TGTTACTTTG CTGAGAATGA 360
TGGCTTCCAG ATTCATCCAT GTCCTTGCAA AGGCATGAAC TCATCCTTTT TATGGCTGCA 420
TAG 423 (2) INFORMATION FOR SEQ ID NO:95:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 405 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:95:
AACAGCCCCC GATCTGCATA GCCTGTGAAA GCCCACGGGG ACATCAGTAA CCTTCTGCAG 60
CCACCATCCA ATGCCATTAC TGTNAAGTGA GACTTGGCCA CTGTAGCCTG GGCCTGCTGC 120
AGGAGCTCTT CAGAAAGGCA CATGAGGACC ACGGTTTGCC TCAGTTTCTG GTAAAACACA 180
AGGTCTGGAG TGCCCCTGCA AAGGGTATTG ATGGACTTCC TGCCAGTGAC AGAGCATGTC 240
TATTGCAAAC AATTCTCTCA GTTACGTTCA GCACTTAAGA ACGGCTAATG NCAATAGGAT 300
CTTTAGCAAC TTTTTCACAT CATAGAAGGT GCAATCGCTC ACTTGGGAAC ACTACTGAGA 360
GTGACTTCTC TTTTAAAATT GAGTAGCAGA TGAAAAATTA AAATT 405 (2) INFORMATION FOR SEQ ID NO:96:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 173 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:96:
GAAGACAATA CTGATGCCAG CTCTTTGTAA TTGTGAAATC TGTACCCAAA CCTCTGGATT 60
AGAATCTCCA GTTGTCTACT GTAAATACTG GAATTACAGC AAAGGATATG GGGACTGGGC 120
TGCTTTTCTG TATTGTACAA GCACTATTCT AGATATTAAA GAAATTTAAC CGC 173 (2) INFORMATION FOR SEQ ID NO:97:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 337 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:97:
ATGGCGCCCT ACAGCCTACT GGTGACTCGG CTGCAGAAAG CTCTGGGTGT GCGGCAGTAC 60
CATGTGGCCT CAGTCCTGTG CCAACGGGCC AAGGTGGCGA TGAGCCANTT TGAGCCCAAC 120
GAGTACATCC ATTATGACCT GCTAGAGAAG AACATTAACA TTGTTCGCAA ACGACTGAAC 180
CGGCCGCTGA CCCTCTCGGA GAAGNTTGTG TATGGACACC TGGATGACCC CGCCAGCCAG 240
GAAATTGAGC GAGGCAAGTC GTACCTGCGG CTGCGGNCGG ACCGTGTGGC CATGCAGGAT 300
GCGACGGSCC AGATTGGCCA TGCTCCAGTT CATCAAG 337 (2) INFORMATION FOR SEQ ID NO:98:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 212 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:98:
TGAAGCCCAA GNAGTNTGTG AAGACAGAGA ATGACCACAT CAACCTGAAG GTGGCCGGGC 60
AGGACGGCTC CGTGGTGCAG TTCAAGATCA AGAGGCACAC GCCGCTGAGC AAGCTGATGA 120
AGGCCTACTG AGAGAGGCAG GGCTTKTCAA KGAGGCAGAT CAGATTCAGK TTCGACGGGC 180
AGCCAATCAG TGAAACTGAC ACTCCAGCAC AG 212
(2) INFORMATION FOR SEQ ID NO:99:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 265 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:99:
CCTTTTAATA ATAATTCTGC TGTCTGCTGT GTACTAGAAC CCATGCCTAC TGCTTGGGGT 60
ATAATGTAGT AAATGTAGTA AAAACAATAT CCGCCGGGCG CGGTGGCTCA CGCCTGTAAT 120
TCCAGCACTT TGGGAGGCCA AGGAGGGCGG ATCACGAGGT CAGGAGAGCG AGACCATCCT 180
GGCTAACATG GTGAAACCCC GTCTCTACTA AAAATACCAA AAATTAGCCA GGCGTGGTGA 240
TGGACGCCTG TAGTCCCAGC TACTC 265 (2) INFORMATION FOR SEQ ID NO:100: (i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 333 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:100:
AAAATGCTCA CAGTGGTCTT CTCTGGCCGG TGAGCCTACA GCTGATCTTG TCAGAGACAA 60
ACGTTAGTTT TACTGAGTCA CCCAGAGCCC TGTGCTGGTG CCTGAGGGTT TGTTCCATGG 120
GACAGTCTCC ACAATTCCTC TGGGGAAGGG CCACAAATCC CACAGTGTGT CCCAAGAGGG 180
CTGGAGTAGG CGGAGTCCCC AGCAGCTGTG GCATGACCAG CCATCTCTCT CAAAACAATT 240
GTTAACAAGC CTTCTGCAAG TTAAGGTTCC ACATGGTAGC CGTGGTACAG AGGCATTTCT 300
CTAGGGTGGG AGAGGCTTGT GCTCTACACC AGG 333
(2) INFORMATION FOR SEQ ID NO:101:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 156 base pairs (B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:101: CTCTGACTTT CCTGTGGNTT TAGAGCCAAG CTCAAGGTAG TAGGCCGTAG GGNCTTATTT 60 TATTTTCAAA CCCCCATCCT CAGAGCGCAG ATACATGCAG AGGCTTCTGC CAGGCTACCA 120 CGGGGCCTTA GTGGGAACAG GTTGAGACCA GCACTT 156
(2) INFORMATION FOR SEQ ID NO:102:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 331 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:102:
CGAAAAGGGG NNNTATGGCC ATCTTTTATC AGAAAAAGTG ACAAAACGGG AATTTAAAAA 60
ATGAATTTTC NNTCTGACTT TATTTNNAAA TACACTTTCT TTTTTNNAAA ACCAATACAC 120
TTTCTTTGAG GATGACAGTA TTAGGAAATC CAATTNNACA AAAAATACTA CATCTAGTCT 180
GGGGTAGATA TATTTATTTT TGGTAACATA CATTAAGTGG CACTAATTAC ACAGTAACTA 240
TAAGGTAACT AACATGAAAC CACAGAACTG TAACTCTGCC ACAGCTGCAT GAACTTGGGC 300
TTTTCTGGTT GAGCCCATTT TCAAAAAACT G 331 (2) INFORMATION FOR SEQ ID NO:103: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 316 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:103:
AGCCACTGCG CCCCACCCCA TTTCGGTGTN ANCTCAGCTC ACTTCAACCT ACCCCTCCCA 60
AGTTCAAGTG ATTCTCCTAC CTCAGCCTCT TGAGTAGCTG GGATTACAGG GGTCTGCCAC 120
CACGCTGGGT GATTTTCCTA TTTTTAGTTG ACACTGCATT TCACCAGGTT GGCCAGGCTG 180
GTGTTGAACT CCTGACCTCA GCTGATCCAC CCGTCTCGGG GTCCCAAAGT GTTGGGATTA 240
CAGGTGTGAG CCACCACACC AGGCCCATAT TTTCTTTTAG ACATGCAGGC AATGTTGGTG 300
GGTTTGTCTG TTAAGA 316 (2) INFORMATION FOR SEQ ID NO:104:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 308 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:104:
GTTTTTCCTG CATCTATTGA GATAATCATG TGGTTTTTGT ATTTGGCTCT GTTTATATGC 60
TGGATTACAT TTATTGATTT GCGTATATTG AACCAGCCTT GCATCCCAGG GATGANGCCC 120
ACTNGATCAT GGTCGATAAG CTTTTTGATG TGCTGCTGGA TTCGTTTTGC CAGTATTTTA 180
TTGAGGATTT TTGCATCAAT GTTCATCAAG GATATTGGNC TAAAAGTGTG CTGTATTCAG 240
GAAACCCATC TCACGTGCAG AGACACACAT AGGCTCAAAA TAAAGGGATG GAGGAAGATC 300
TACCAAGC 308 (2) INFORMATION FOR SEQ ID NO:105:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 355 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:105:
GGCCTTCCTC AATATGTAGG CGCCACTTTT TCTCCCTGTG CCCTCACCTG GTCACCCCTC 60
TGTGCGCGAN ATCCCACTGT CTCTCTGGGT GTCCAAACTT CCTCTTCTTA GGAGGACACA 120
AGTCAGATTG GATTAGGGCC CACCCCAATG GCCTCATTTT AACTTAATCA CCTCCCTTTT 180
GTTTGGGCTT TTTAACTTAA TCACCTCTTT AAAGACCTTA TCTCCAACTA AGGTTTCATT 240
CTGAGGTATA CTGGAGGTTA AGACTTTAAA ACACGAATTT GGAGGGGACG TAATTCAGCC 300 CATAACAATA ACAATAATGA CATCTTACAA CTTACTGCCA CCACCAAGCT TGCTG 355
(2) INFORMATION FOR SEQ ID NO:106:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 355 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:106:
GGATGAGGTC GCCGGGATCG TGGCTGCACG CCACTGCAAG ACCAACATCG TCACAGCTTC 60
CGTGGACGCC ATTAATTTTC ATGACAAGAT CAGAAAAGGC TGCGTCATCA CCATCTCGGG 120
ACGCATGACC TTCACGAGCA ATAAGTCCAT GGAGATCGAG GTGTTGGTGG ACGCCGACCC 180
TGTTGTGGAC AGCTCTCAGA AGCGNTACCG GGCCGCCAGT GCCTTCTTCA CCTACGTGTC 240
GCTGAGCCAG GAAGGCAGGT CGCTGCCTGT GCCCCAGNTG GTGCCCGAGA CCGAGGACGA 300
GAAGAAGCGC TTTTAGGAAG GCAAAGGGCG GTACCTGCAG ATGAAGGCGA GGGAC 355 (2) INFORMATION FOR SEQ ID NO:107:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 273 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:107:
GTGTCTCTTT TAAAGAAAAC ATACTTTATT TTGGTCTAAA TTGTGAAAAT ACCCAAAACA 60
TTTGATAGAA ATTGAACTCT GTCAACAGTG TTATTTATAC TAAGATCAGG ACAGTTCCTT 120
GAGATCATAC TGTTTTATTA CTAAGTTTGG CCTTTGTTTT ACAAATGTAA TGTTCATATT 180
TATTTGAATT TTAAGATTGG TTAAATGTTA ATGAAAAGCA ATCCAATTGT TANTTTTTAG 240
TAGTGCCTTT TCTCTGTATG CCTTAATTTT ATT 273 (2) INFORMATION FOR SEQ ID NO:108:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 359 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:108:
ATTTTATTTC CTTACATCGA AGAAAATGTT AAAGAGTATC TGCAGACACA TTGGGAAGAA 60
GAGGAGTGCC AGCAGGATGT CAGTCTTTTG AGGAAACAGG CTGAAGAGGA CGCCCACCTG 120
GATGGGGCTG TTCCTATCCC TGCAGCATCT GGGAATGGAG TGGATGATCT GCAACAGATG 180 ATCCAGGCCG TGGTAGATAA TGTGTGCTGG CAGATGTCCC TGGNTCGAAA GACCACTGCA 240
CTCAAACAGC TGCAGGGCCA CATGTGGAGG GCGGCATTCA CAGCTGGGCG CATGAAAGCA 300
GAGTTCTTTG CAGATGTAGT TCCAGCAGTC AGGTAAGTGG AGAGAGGCCG GGATGAAGG 359 (2) INFORMATION FOR SEQ ID NO:109:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 360 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:109:
TTTATNAAAG CAGTTAAACT TAGCATTAAA TAACACTCTT TAAATGGTAC ACCTATGAAG 60
CAAGAGTTAA ATATAAACCC AGTCTAATCC TGTACACTTG TGATTAATTG TGACAATCTT 120
AAGTTGCTCA CTTCTTTCCC ATTTACCAAT TCAGAGAAAG CCCGTTTCCT GTTTTCTCCT 180
CACCACTTTG CCTTGGCATC ACACCAACCC TGCCTCGGGC TTCAGCTGCA GATCCTCCCC 240
AGCCCCTCCT CCCAGCTGGG CTGACTCCAG TCCCAGCCCC AGTCTCCACC AACTGAGCAG 300
CGTACGCAGG GTTGTGTCTG GCTTCCAGCA TCTACCAACC CTTCAGAGCA ACTTCCAACA 360
(2) INFORMATION FOR SEQ ID NO:110:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 364 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:110: TCTCAGAGGG GCTCTGGGGG TCATTCAAGG GGGACTTCTA GCTTCTCTCT GGAACCCTTT 60
GTCCAGAGCA AAGCCAGGTT TCCAAGGTCC CCACGGCAAG GCTGTTGGGT GCTGGCAGCA 120
AGAGGTACAC AGCAGTTCTC CCAGCTCACA GCAGTGACCT CAGATCTCCA GCAGCAAGGG 180
CCGCACTCTC GTGCCCACAA GGGCCTTGCA GAAATNCTCC GGTCCCTGGG NCTCCCCCGG 240
CAGGAGGGGC GGGGCTCCTG CCTGCAGTGA GGCCACAGCA CTAAGCGGCT TCAGTCACAT 300
GCTTTTCAGG TGAATCACTC CAAATTCAGT GAGGAGGGCC ACGACAAGGA AGTTCAGGTA 360
GAAG 364 (2) INFORMATION FOR SEQ ID NO:111:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 455 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:111:
TTTTTTTTTT TATATTTTAA ATGGAATTTA TTCTATCAAC TGCCTGAGAG GACACAATGG 60
GGGAGGGGCT TCGGACCACA GCAGGAGCCC CGACTGCCCA CCTGAGGGCA GGGAGAGCCT 120
GACCCCATTG GCCCAGGCCC TGGCTCTGTA ACCATTAACC TCTTCCCCCA ACTAACACCA 180
ATGAAAACAC CATTCCACGT GACTGGGCTG TGTGTTTGCC TCTGTGACAT GGGGACCCCT 240 t
GACCCTAGGG GTCTCGCCTG AGCCAGACCT GAGGGACCCA CCCGCGTAGG ATGGAGGAAG 300
GTTTAGGCCT CCCTTTTGCC AGCCAACGCC GGGGGGTGGG GCAGACCCTG GGAGTGGGCC 360
TTACAGACCA GCCACAGGTA TTTCTTAGGC AATTTGACAC ATTTTATTAC AAAACCAGTC 420
TACATTCATT CCTAAAAGGG TCATTTTCAG TAAAA 455 (2) INFORMATION FOR SEQ ID NO:112:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 398 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:112:
CTGATCTGAC AGGAGGTGTA GGTCAGGCAG TAATGGAAGT SATGGGGAAC AGCTGTAAAT 60
ACAGATAAAG CTTTACTCAC TCGCCCACCC ACTGCTCATC TCCTGCTGTA CTGCCCAGTT 120
CCTAACAGAC AGCAGACAGC TACTGGTCTG TSGCCCAAGG GTTGGGGACC CCTGACATAG 180
ACTAAACAAT TCACAATGTT TATATTAAAC AACTTATTCC AAGTTTCCAT TTTAGACTCT 240
GGAACATCTG ACATGGTGAA TCCACAGGTA GTAAATSGGA AGGGAGATAA CAGACAACTT 300
GACGGCCGTG GAAGACGCAC TGGGCGGGCA CTGGTGACGG GTCTCGGGAC AGACTTCACA 360
TCTCCAGACT GGCACAGTGG GCTCACACCT GCCTCCCA 398 (2) INFORMATION FOR SEQ ID NO:113:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 444 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:113:
ATCAGTGTCA GTGTCTAACA GAAGGGTCTG TTAAGGATGC TTCTGATTTA ACCAAAAGAT 60
TAAGCTTCAG AAACAATCTA ACATACTCAA AGGAGCACCA AATTATCAAC CGGCTACAAG 120
GATGCAAAGG ACCTAAACAA CAGATGTCAA AGGGCTTGTA AAAACTGGAG CCAGCAACCA 180
TTCCACTTGA AGGAATCCAT CTCAGGGAAA TGCTGGAATC CACACACAAA AGCAGGTGTG 240
CAAATAATCA CTGCAGCACG CCTTCTAATA GTGAACAACA GAGGCAATCC AAATATCCTT 300 CAACAGGGAA CTGAGTAAAT ACCAACTATG GGCATATCCA CATAAGGCTC TCTGCAGTCA 360 TTAAAAAGGA TTGCACTTAC ATGCATGTCT GCCATGGAGG TCTTTCAGGC CAATGGTTCC 420 ACTCGGAAGG GCAACCACCA ATTA 444
(2) INFORMATION FOR SEQ ID NO:114:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 472 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:114:
TCGGGCCCCA ACGGAGACCT GGGGATGCCG GTGGAGGCGG GAGCGGAAGG CGAGGAGGAC 60
GGCTTCGGGG AAGCAGAATA CGCTGCCATC AACTCCATGC TGGACCAGAT CAACTCCTGT 120
CTGGACCACC TGGAGGAGAA GAATGACCAC CTCCACGNCC GCCTCCAGGA GCTGCTGGAG 180
TCCAACCGGC AGACACGCCT GGAGTTCCAG CAGCAGCTCG GGGAGGCCCC CAGTGATGCC 240
AGCCCCTAGG CTCCAAGAGC CCCCAACCGG GACCCAACCC TGCCTCCCTG GGGCTAAGCT 300
CTGGCCTGGG GCACTCACCC CCTGGCTTAG ACAACTTCTC AAGGGCTTGG CCTTCAGGGG 360
ACCCTTGTGG GTCTTGCCTT GCTGGGGCCA CCTTTTCTTG CTTGGGGCTT CCCCTTTGGC 420
CTACCTTGGG GCCAAGCCCC TACCAACTTT GGATTGCCTT CTTGGGGGCC AA 472 (2) INFORMATION FOR SEQ ID NO:115:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 293 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:115:
CTNGGGGCCA TGTGGCTGAT TTCCATCACC TTCCTTCCAT TKGCTACGGC GACATGGTGC 60
CCCACACCTA CTGCGGGAAG GGTGTGTGCC TKCTCACTGG CATCATGAGA GCTGGCTTTA 120
CCGCGCTCGT GGTGGCTGTG GTRGCTCRCA AGCTGGAGCT CACCAAGGCT GAGAAGCACG 180
TGCACAACTT CATGATTGAC ACTCAGCTCA CCAAGCGGGT AAAAAACGAG GCTGCTAACG 240
TTCTCAGGGA GACGTTGGCT CATCTACAAA CATACCAGAG CTGGTGAAAG AAG 293 (2) INFORMATION FOR SEQ ID NO:116:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 448 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:116: TTTGAAAATT TAGAGGATAT TTATTTCTCA GGAAGGTGCA CAACAGCTGG CAGGCACTGC 60
TTTCCCTGCT CTAGGGGATT CCTCTCTCCT TTTCCAAGAA ATCCCCTCTC TTCTTAGAAG 120
TGCCCATGGG AGGCTGGGAT GTGAAAAGAA ACCATACACA ACACTCCAGA GCCTTAAAAA 180
AATAAAGCAA CAACCTCCTC CACACGAATA CACTTACAAA ATAAATAGAC GGATAAAAGA 240
GAGGCCACGT GCCTCCCATC CCGGCTGTAG GGCTGCTTGG GGATAGTGGG GCTGGGTGGC 300
TCGGTCCCAC TTCTCCCAGC CAGGATGATC CAAAGGCTAA ATGGGATGGA AGGGCCCTGG 360
CTTTCAGAGA GAGGGTGGGG CAGGCCTCTC CTGGTACTCA GCAGGGAGGA CACTGGGGCA 420
CGGGTAGGGG TCCAAGGGCC ACTTAATA 448 (2) INFORMATION FOR SEQ ID NO:117:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 551 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:117:
GAGACGGAGG CTCGCTCTGT CCCCCAGGCT GGAGTGCAGT GGCGAGATCT CAGCTCACTG 60
CAAGCTCCGC CTCCCGGGTT CACGCCATTC TCCTGCCTCA GCCTCCCGAG TAGCTGGGAG 120
CCAGCGCGCC CAGCCTAAAA AACTTTTCAA GTCAATATTA CTACGATTTA ACATTAGAGT 180
GTGGACATGT GATTTAATCG CTATAGCTAA AATACGTCAA ATATACGTTG TCATGTGCTT 240
GAACATGATG CTAACCCTGA CAGGATGAAG GAAAGTAATA TTCTTTCAGT GTAGTTCAGG 300
AGAGCATTTG TTTTCTTTTC TACCAATTAA CCCATCATTG CTTTTAAACA ACCATCTGAA 360
GGAGCAGAGA GGCAGGGTAG AAGACAGAAG GGGGTCTATG TGGGTACTAA AGATGTTTCT 420
GTTTTGTAAT ATTGTGTGTG TGTGGGTTTA TGGTTTGCTT AAGGGATCAA AACCTGGAAA 480
AAATGGGATT CCAGGAATGG CTCTGTTATT TTTGCTGGGT TCCAGCTTGT AATGCCTACT 540
GCCTTGGTTC A 551 (2) INFORMATION FOR SEQ ID NO:118:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 426 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:118:
CCCCACCCCA AAATCAAAAC TGAAGGTAGT GTCAGTGTAT ATATGGNGTC CCTTGTGCTG 60
AAAGTCAAAG CAGCTTCATT TTGGGGCCTC AAGAGCTCCA GCTCTGGGCT CTTCACCTCT 120
AAGCCCATGG GCAGTGCCCG CCCAGTGGTG TGTATAGATC GGAGGCTGAG GGCCTCACCC 180 TTAGCTGAGC TGTCGCGTGC TGGGGAGCCT GTGCAGGAGG GTACAAGTAG GAAAGTGCCA 240
TCTGCATGGG AAGAAAAATG CAGCGTCCTT GGTAGTGCGG ATGGGGTCCA GGAGACCCAG 300
GGAGCTTGCC CAGAGGGACC TGAGTGGCAT TCCTGTAGGA AAGCAGCCCA GATCTTGGGG 360
CCGTAACGGA TGTTCTGGAA GTTTTGACTT TGAACCACCA GGTCCCATTG TTAACAAGCT 420
TCTTGA 426 (2) INFORMATION FOR SEQ ID NO:119:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 434 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:119:
TTTTTCGGTT AAAAAGGCCC AAAACTTTAT TTAGTTTTCA GGGAAATATA AGATGCATGT 60
AAACATAAAA TACAAAACAA AACCCAAATC TTACAGTCTA GAAGCATGCC AAGACAGAGC 120
ATTTTCTGCA GACCAAAGAG TCCCGTCAAA GTGATAAAGG ACACCTGGAA AGTGGCAGGC 180
CAAGGGGCTG GTCCCTTCCC CAAGGGCACT GCATTTTTGT GATGAGATTA AAAACAAACC 240
AACTCCACTA TTAAAAATGC TAGAAACATG GGATAGTTTA GCACCACCAT TGATTCTGGC 300
AAATATTTCA GCACTCACAT CGACTGCACT GAGTTTAATG TCCTTTCTCC AGTTTCTCTG 360
CTGAGGAGGG AAGGAGGGAA ACCTGGGCGG AAGGGGCTCC TCCTGACCCC ACAGGGCCAC 420
TAGGAGCTTG GAGG 434 (2) INFORMATION FOR SEQ ID NO:120:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 276 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:120:
AGGAAGTGTT AGCAAATGCT ACCATGTGGA ACACTCAACT TTATTTGCTT TATTTATATA 60
TTTAACAATT CTAAAGTATT TACTTCTTGC TTTGACAAAA AATGAAAAAT ATAGGGGCAC 120
TGACTGACTC CTCTTTAGGA GAAAAGGGTT ATATGTACAG CTATGGAGAG TTACGGTTCC 180
CCCTTTAACA AAGGCAAATA TTAATAAAAA AGGGCTTCAT CGGTCAAAAA AGGGCTAAGA 240
GCTGCAAGCA TTTATTCACA CTGTACATCG GGCCCC 276 (2) INFORMATION FOR SEQ ID NO:121:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 554 base pairs
(B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:121:
ATTTCTTTCC TTAATCATAT CTGATGCTGG GATGTGGGTA ACCCCAAACT GAAGGCAGCT 60
GCTAAATCTC AAATGCTAAA AAAATACTGC AATTTTGACA TCAGTGAGTC AGATCAATAC 120
ATCCTCTGGG GCTGATTTTG CTTCACAGTT AGGATGAGCC ATCTCTTAAG CTGCAGGCTC 180
AAATGGGATT AACTGAACTC TATACCTGGG ATGGGCCATG GACTGAGCTG TCCATGCAGA 240
AGGACCAGGC TGTCCATGCC TTCCCTGCCC TTTTACTCAC CACTGCACAG CAGCCCCAGT 300
GGGCCTACTG CACATGTCTA GGAGAAATCA CTCTAAGAAA ACCAACAGGA ACAGGCTTTA 360
GGCAACAAGA GACGTCTCAC TGCATCTCCT CCCACGTCAG AACTTGAGTA CTGGGTCTTT 420
GCAGCTCAGA GCATTCCTCC CTTCCCTTTC CTGCCCGAAA GGCCTGCCTT TTCCTGAGAC 480
ATATGGCACT CCATGCTGCA AGTTTCAAGC AGATGCAGGT TCTTATGGGG CTTTTTGCTC 540
AAAGAGCTTT GGTT 554
(2) INFORMATION FOR SEQ ID NO:122:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 238 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:122:
CACCTAAGCA GGTAGACATC CGCAAAGTCA GATGCTTTCC AACATGACAC CTGAACATCT 60
TCCTTTATGC AACACCCAAA CATCTTGGCA TCCCCACCCC AGGAAGTGCG GGGAGGAGGT 120
TATGATCCCT GGGCGCTTCG GCAGAATGGA GAGCTGAGGT GTCCCTCCCC TGCTAGTCAC 180
CTACCAGGTG TCTGAGCAGC TGCATGCTCC CTGGCTCAAG TGGGCACTGT ACCTTTTG 238 (2) INFORMATION FOR SEQ ID NO:123:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 244 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:123:
ATCCAGGCTT TCATTTCTAG CCAACCCTCA AACACCACCA ACTACAAAGA AAATTTAAAA 60
GTCTAATTTG TAACCTTCAG ATAAGTATAA ATTAGTTTTT TCTAGGCTTT CATTATTTGG 120
CTTCTTATAC AATCTATCTT GTAAAGTACA TTCCTCTAAA TTTACATTAT CTAAAATTAA 180
GGCTAAGCAT TATTTAAATC ANTTAATCAT ACAATATTTT ATGGCAATAT GCACATATTT 240 -12.5-
ATAA 244
(2) INFORMATION FOR SEQ ID NO:124:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 330 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:124:
CTCAGCGTAT CATAGGCGTG CTCACCCTCC TCCCCACGCT CCCGCCCCGC AGGCAGGTGG 60
TGTAGGATAG AGTGGTGCAT GAAAGGGGGG AAGCCCGAGG GGCCCGCTGG GAAGGGTGCT 120
GCCCCGTAAA GGGCATCCCA CTGGCACTGT GCCTCANCTG CCGCTTTCTG CTTCAGCTCA 180
GCCAGTCGCC GCCGCTGCTC TTCAATCACT TGTTGTCCCT TCTGCTGCAG AGCTAGTTGG 240
CGCTTTGGTC TCGATGTCCT GCAGTGTGGC TGCCAGGTTG CAAGGAAGGC TGCCCGGTGC 300
CATTCTGGGG GTGAGTAGGA GCGCTCTTTT 330 (2) INFORMATION FOR SEQ ID NO:125:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 281 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:125:
CCTCTCTCCC TTCGGTTCTC CATTTACCGA GCCACAGTAT TTCTTAAAGC TCGTTGGCAG 60
CCTGCACCCT GCTTATTCTT GGGAGACACG AGTTTGCATC CTATTACAAC CCATAGTTTT 120
TGCATAACCA TGGTGAGAGG AACCATCCTT CCCAATCCCA ACCTCAACCA AAGCTTAGAA 180
AAAGTGCCAT CNTTAACCTT TCAGAATCAC TCATAAGTAA ATCCTATAGC AGTCTCTGCT 240
AATGCAAATT TCAATGTGTG CCCGCTTATT AGGTGACTTT T 281 (2) INFORMATION FOR SEQ ID NO:126:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 266 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:126:
CTTTTAATGA TGTGGTTCTG GTGGGATTTA TAAAGGGAGA TGGACCCCTG GNAAGATGCT 60
TTCCTMAACC ACAACCCACA CATTGGGTCA CCATTTCCTC TTCCTCCTCC TTCTGTGGGT 120
GGCCGGAGAC CTGTAGGACC TTCCCTCCCT TTAGGGTTCT GTAAGGCCCC TTNTCAGTCC 180
TCAGAGTCCA TTCTTCTCTT GTGCTGAGGG CCTGCAGTGG GGACCATATA CTTCTGGTGC 240 TCTTAGTTTG CTGTCGCGTC TGTTTT 266
(2) INFORMATION FOR SEQ ID NO:127:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 435 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:127:
GTCTGGTTCT ATTCATTTTG TAGTTGCGAG AAAAGGAATG AACCGTGACT ATGGCAATTC 60
ACCGTGACGT GTGATAATTT AGTTTGCTAT GAGTTTTCAC TCTTAGGTAA AACCTAGTTA 120
TCCTAATTAA TAATTAGTTA TGGATGATAT AGTAATTTTT TTTTTTTTTG ACTGCGTCTC 180
ACTGTCATTC GGGCTGGAGT ACAGTGGCTG ATCACAGTTC GGTGCAGCCT CGACCTCCCT 240
GGGCTCAGTG ATTCTCCTGC CTCAGCTTCC CAAGTGGCTG GGGATTATGG GCATGCACCA 300
TCAATGTCTG GCTAATGTTT GGTGTGTTTT TTTATAAAGC CAAGGGTTTT GCCCATGNTT 360
CAAGACCCCG GGGCTGGTCC TTGAACCTCT TTGGGGCTTC AGGCAAGTCC TCCCACCTTC 420
GGGCCTTCCC AAAGT 435 (2) INFORMATION FOR SEQ ID NO:128:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 471 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:128:
TTCCCTTCCC AAGGACTCGA CCTGAGAACC GCCATGTACT CGGAGATCCA GAGGGAGCGG 60
GCAGACATTG GGGGCCTGAT GGCCCGGCCA GAATACAGAG AGTGGAATCC GGAGCTCATC 120
AAGCCCAAGA AGCTGCTGAA CCCCGTGAAG GCCTCTCGGA GTCACCAGGA GCTCCACCGG 180
GAGCTGCTCA TGAACCACAG AAGGGGCCTT GGTGTGGACA GCAAGCCAGA GCTGCAGCGT 240
GTCCTAGAGC ACCGCCGGCG GAACCAGCTC ATCAAGAAGA AGAAGGAGGA GCTGGAAGCC 300
AAAGCGGCTG CAGTGCCCCT TTGAGCAGGA GCTGCTGAGA CGGCAGCAGA GGCTGAACCA 360
GCTGGAAAAA CCACCAGAGA AGGAAGAGGT TCACGCCCCC GAGTTTATTA AGTCAAGGGA 420
AACCTTCGGA GATTTCCACA CTGACCAGCG AGAGAGAGAG CTTTAGGGCC A 471 (2) INFORMATION FOR SEQ ID NO:129:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 186 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:129: GCCTTTAACA TCCTCTGCCA ATRACTGGCC TCAAATCACC AGTGGAACCT TTTCAAAAAA 60 TACACCATTG GCTCTATGTA GTTCTACTGA TCTRAAATAT CCACGTGTGG GCCAGGAGCA 120 CTGGCTCATG CCTGTAATCC CAGCATCTTG GGAGAGCGAG GAAGGAGGAT CATTTRAGCC 180 CAGGAG 186
(2) INFORMATION FOR SEQ ID NO:130:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 307 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:130:
ATAAAATACT TAGGAATATA CCTAACCAAG AAGGTGAAAA ACCTCTCCAA GGAAAACTAT 60
GAAACACTGC TGAAAGAAAT CATAGACTAC ACAAATACAT TTCATGCTCA AGGATGGGTA 120
GAATCAATAT TGTGAAAATG GCCATACTGC CAAAAGGGAT CTWCAAATTC AACGGTATCC 180
CCATYAAATA CCACCATCMT TCTTTACAGG NTTCGGAAAA GGAATTCTAA AATTCATATG 240
GGACCCAAGA CGGGGGCCGC ATAGCCCATG GCCGGCTTAG SAAWAAGGGA CAAATCTGGG 300
AGGCCTT 307 (2) INFORMATION FOR SEQ ID NO:131:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 184 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:131:
CCAGGTTGGA TGGAGTGCAA TGGCACGATC TCGGCTCACT GCAACCTCCC AGGTTCAAGC 60
AATTATCCTG TCTCAGCCTC CTGAGTAGCC GGGATTACAG GCACGTGCCA CCACACCCAG 120
CCAATTTTTG TATTTTTAGT AGAGACGGGG TTTCACCGTG TTAGCCAGGA TGGTCTCAAT 180
CTCC 184 (2) INFORMATION FOR SEQ ID NO:132:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 270 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:132: GCNGGAGGGC GTCGAGGGCC AGGAGCTATT CTACACGCCC GAAATGGCTG ACCCCAAGTC 60 AGAACTMTTC GMGNAGACAG CCAGGAGCAT TGAGAGCACC CTGGACGACC TCTTCCGGAA 120
TTCAGACGTC AAGAAGGATT TCCGGAGTGT CCGCTTGCGG GACCTGGGGC CCGGCAAATC 180
CTTCCGNNNC ATTGTGGATG TCCACTTTAA CCCCACCACA GCCTTCAGGG CACCCGACGT 240
GGCCCGGGCC CTGCTCCGGT AGATCCAGGT 270 (2) INFORMATION FOR SEQ ID NO:133:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 529 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:133:
CTTGCAGTAC ATAGCATTGT TATTACTGAT AGCTTTATAA ATCTGCCAAA TAACATAGAA 60
TGTAGCCTCA AAAGGATGGT CGAGGGTTCG CAATCTTTCT TTCTCCACCC AGTGGTGTGG 120
AGCAACTCTG TGCCTTAAAG AGGGCACCAT GGAAAGAAAC AAAAAGGAAT CTCTTTCAAA 180
ATGCTGGAAA TTAGGCTTAG CTCACTACTT TCAGGATAAA GACAACTGCA TCTAATTAAG 240
TCCACTCCAC ATTTCTTTGG ACTCTAAGTA TTCTGCACCT GAAGGCTAAA TTGAACTGGC 300
TCAGCCCTAT CTTTTTTGCC ACATCTTTAA TTACAAATCT ATTTCTTCTT CCTTTCATTT 360
ACTTCTCTTC TCTTAAGTAA GAAATGTGGG AAATGAGACT GGCAGTTTGG TTTGTTTGCA 420
TGTGGGTGTC CATTAGGCGT CTCATCCTAT GGCCCTTTTT GGAAATGTTG CCTTCCTACT 480
ACACACCTGG GAGGTTTCCC CAAGGCTCAA CCTTTTTGCT TCAGGTAAA 529 (2) INFORMATION FOR SEQ ID NO:134:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 437 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:134:
GACGGTGGCG ACGCGTGCAC CGGGGATGTG TCCTGCCACC AGAGGAGGTG TGCGTGGCGG 60
GGAGCAGAGG GGCTTTGTTT CCCAGGTGAA GGTGCGGCTT CTTCACTCTT AGAGGTGCGT 120
GTGTGGGTGG GGGTGCTTGC TGTTGAGGTT TATGCCTGTA ACTGACAGCT GTCCCCCAAG 180
CCATGCTGGC AGTGTGTAGG TGTCGTGCCG GCCACCGCAG AGGAATCCTC TGGGCTTCTG 240
TGGTTCAAGT GGGGCCCAGC GCAGAGCTCC ATGAGTTGCT GAGCAGCCAG CCCTTCAGCA 300
TCTCCTGGGT TTTGGCAGCA GGAGGCGTCC CCTTGTGCAA TTCAGGGGGC CGTGGGGGCT 360
GGGGGCACTC GTAGCAAGGT AAAGGAGCCC CTGCTCAGGC CCTTGTTTGC TCCCCTTTCT 420
TGCAAGAGGG GTAGACG 437 (2) INFORMATION FOR SEQ ID NO:135:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 534 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:135:
GGCATTGTTC TGGTGGGTGT GTCACGCTCC CAGAAGACTG AATTTATGGT AGGATCACTC 60
GCAAGGCCTT GTGAAGGAGT CTTACCTAAA ACAAAAGAAA TATCAGGGAC TTTTGTTGAC 120
TATTTACAAC TCAGTTTTAC ATTTAAATTC AGGCAGTGTT AATATGCCAA GGTAGGGAAT 180
GTGCCTTTTT CAGAGTTGGC CAGGAGCTCC TGGCTGGGAC ACGGAGAGGC AGGTGTGGCG 240
TAAGGCCTCA CTCCCGGCTG TGAAGGTCTC TGATCACACA GAAGCAGCCC TGCCCAGCCT 300
GGGTCATTTG CTGTCCGCTT TTCTCTGTGA CCACAAGCAG CCCTGAACAA CCAGTATGTG 360
TCTTCTTTCT CCAGATAGTG AAAAAGGGTG TCCAGATAAA CCCACCTAAG TGAAATGGGC 420
CATCCTCTAA ACTGGGGTAC CTCACTGCAC AGGTTCTAGG TAGGCTTTCC ACTTAATCTA 480
ACTTGAGGCC TACAGGTACC CTGTAAAGTT AGTGGGGCTT GTCCTTGATT GTGG 534
(2) INFORMATION FOR SEQ ID NO:136:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 279 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:136:
CAGTTTGGAC AAAGTAGCAT AGTGACTTTN TTCCTACANT GACTTTCGGA GAAGTTNGCA 60
GTTTCTGGCA AAGTGACGCT GGGCTGTTTG AAAAAGGCAA GCTTAGCCTA GGCTGCCATC 120
TTAAAACATT TCGAGGCTGT AGCTTCCTCA GGATCCTTTG CCTGTGGTCT GGTGGCCGGC 180
AGTGCCCCGT CTAACAGCTT TTAACTCTGC ACTTAGTGCC TGAGCACCTA TGGCTGTGAG 240
AGATGCTAGA TACAGAACCC TGTCCTGTAC CACGTGGGG 279 (2) INFORMATION FOR SEQ ID NO:137:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 518 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:137: CAAATATTTA ATGGAGATCT TCCTTGTTGG TCTGTTATAT GTCTATCCGT TTCTGGGTGG 60— TTTAGGAGAA TCTGTACTAT TTCAGCATGT CCTCCTCCAG CAGCAAAATG AAGAGGAGAA 120
CTAAGTTGTC CATTTAAAAG GTTTGGATTG CACTTTCCTT TCTCTAACAA TATGCGAGTG 180
GCCTCAACTT TTCCATACCA GCATGCATAA TGAATGGGTG CCCAGTGGTC ACTATCTAAC 240
TGGTTGACTG AAAATCTTTC ACTGAGAAGA CGGCTTAGTA ATTCTGAATC TCCTTCACAG 300
GCGCTTCGGT GGAGAGGAAA ATCATCTACC CACTGTCGTT CCTTGTCTTC TGTGACACTG 360
CTCATGCTTC TCTGCCAGTT TTTCCTGTTT AGGGTATTTG GATTTTTGAG TAGTCTGGAG 420
CTCCTAGACC CAAGTATGGA TTTATTACCC ACTTATCTAC CCGATTTGTA TACTGAGGAT 480
CCTATCCAAC AAAGGGTGTA AATCCAGGAT CCGCCTTC 518 (2) INFORMATION FOR SEQ ID NO:138:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 266 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:138:
GATTGCAGGC ATGANCCACT GCGCCCAGTC GAGTGGTAAT ATGTTMAAAG GAAACCTTTT 60
TCTGAGCAGG TCTCAAAAGA GAGGTTAAAA TACTGAGTAG ACCATMCTGT AAACAGATGT 120
MCTGTTATYC GGGCTTTCAT ATTCCATTTA TAAAGCACAG GCAGAGCTCA GAGTAGATTT 180
AAYGTAACTC TGAAGGGCAC TAGGATTTTC AGAATGGTAA ATAAGCATTG GCTTCACCTT 240
AAATYCAAAT CTGCATTGGG CTTGTA 266 (2) INFORMATION FOR SEQ ID NO:139:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 341 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:139:
ACCTCGCTCA CCGCTCTGAC CACCGACAGG CAGAGCAAAG GATGCGGGAG TTGCCTCTGC 60
TGCCCATCTA AGGGGACGTA GGCAGAGAAG CAAAGGCCTC TGCTCTCCCT CCATCCATCC 120
CGGTGTGCTG GCCCCAACGG AACAGGAGTC CTTCAACTAT TGCCTGCCAG AGACCCAATT 180
TTAGGGACTG TAGTCTGCAT CTGGATGAGC TGGGCTGTAG ATTGAAGTCT CAGAAGCAGG 240
GAAGGTTGGA AGGGGTAGGG TCCCAGAGCC CATGGAGTTA TTGCTGAGAA GATATGCAGG 300
GGACACATTT CCCAGGGGCA GAGTAGAAGC CCTGGGCCTT G 341 (2) INFORMATION FOR SEQ ID NO:140: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 234 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:140:
GTGAAGGGAG TTGCAGAATC AAATTGCTAC ATAGGCCAAA CAAAAAAGAA GGCTTTTTCA 60
AAAAACATTA AATTCACATG CAGTCTCAGA GACTATTTAG GCAAAGTTCA AGTTAGGAGC 120
TTTTAGGATG TGGGANTAAA ACTTTAATKG GAGGGGAGGG CTTGCTTCTG GAGAAGGAAG 180
AAGCCAGACT TGTTAGACAG TACTCTTAAC TCCTAGCCCA GCCTAGCGTG CCCT 234 (2) INFORMATION FOR SEQ ID NO:141:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 354 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:141:
CAACTCAGGT TAGCAACTGC AGGAAAACTT TCTTCATTTT CACTGAATTT TAAAGAGAGA 60
ATCCTGTCTC TATTTCTCAG AGAAACTTAG GTGAAAAGTA AAAGAGAGGC AAAATCTCTT 120
TCCTTCATGA GATACTTTTA TTTTTATCTC TTTCTCTACT CATGTGCTTA ACTGGTGAAA 180
TGATTCTGTA GAAATAGATC CTTCTGATTC TGCATCTCAT TTCCTTATGG CAACTACAAC 240
AGGAGGAATC CAGCTGGAAA TGCCACTAAC CCCACATCCA GCACCTGAGA GAGGAAGCCA 300
GTCGGAGCGC CGTGCTGGGC TCACTCACTC TGGGCCTGCG CACTGGGGTT GTGG 354 (2) INFORMATION FOR SEQ ID NO:142:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 373 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:142:
GTTTTTGCAA CACTTTTTTT TTAAGTTATT GGGTGCAAAA TCCCAAACCA GGATATGTGT 60
ATGTCTGTGT GTTTATGTTT TTNATTTGAC CCTCCCCTCT TTCAACCTAC CCCCTTTTAT 120
ATCTAATGTA GAAAAAGCGA AATTGAATCT GGAAAGCAAA CTGTTGTATA TAGTTGCGGT 180
AACAATCATG AAGAGAGAGC CGGGCTGTCC AGTTGTTTTT GAGACAGAGT CTCACTCTGT 240
TGCCCAGGCT GGAGTGCAGT AGCATGATCT TGGCTCACTG CAACCTCCCC CTCCCTGGGT 300
TTAGGCGATT CTCCTGCCTC AGCCCTCCCA AAGTAGCTGG GATTACAGAC CCGTACCACC 360
ACAACTGGGC TAA 373 (2) INFORMATION FOR SEQ ID NO:143:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 262 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:143:
CCGCACCTCG GCCAGAGGCG GCTGCAGCAG CTGCTMCCTT TTCCCTGCCG CCGCCTCTCC 60
AGTCCCTTTT TTAATTACCA CTCCAMCTGC TGGGAACGGG CGAGAAAGAG GAGGAGGCGA 120
GAAACTCCCA CCGACCCACA GAGGGAGCAT GATTTCGGCA ACTTCACCTA TCATTCTGAA 180
ATGGGACCCC AAAATTTTGG AAATCCGGAC GCTAACAGTG GAAAGGCTGT TGGAGCCACT 240
TGTTACACAG GTGACTACAC TT 262 (2) INFORMATION FOR SEQ ID NO:144:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 384 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:144:
GGAAAAGCGG GACCCAAACA GTGGTGCTGG GGAAATTTTT CCCTGTCCCC TTTGGAAGGC 60
TGAGTGGGTG ATGCAGCACA GGAACAAGGC TTGGACGTCA GAGGTCTCAT CTTCACTGTN 120
ACAAAGCATA AAGGACTTGG GGTTGAGCGT GTGTNTGGGC TCAAGTGACC ATGCAAGTCC 180
TGTCACCTCC TTCCTAAGAC CCCATCCTTC TCCCAAGTCC TCCACAAGAG CTACCTTCTT 240
CAAAACAATA ACAGAAACAC ATCAAGCTTG GGCGTCACTG AATTCAAGTT CTGATTTCTC 300
CCGTCACCCC AGCAACAGTG CCCAGTTTGA TTGTGACACT TTGACCCAGC ACTTGGTTTT 360
GAATGTTCTT TTCGGCTTGT ACCG 384 (2) INFORMATION FOR SEQ ID NO:145:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 324 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:145:
CTACATGGAA TCATAAGTKT TCCTAAAAAA GGAAGACAGA TTTGAAGACA GAGGAGGAAG 60
GTGATGTGAT GATGGAAACA AGGGGAGAAA ACGCAATGTG ATGTGGCCAC GAACCAAGTA 120
ATGAGGACAG CCTACAGAAG CTGGTCAAGG CAAGGAAACA GATTCTCCTC TAAAGTCCCT 180
GGAGAGGGCC TGGCCATGCT GACACCTTGA TTTTKTCCCA GCAGAAACTC ATTTTGGATT 240 TCTGGCCTCC CAGAAAAGTA AGGGGGTAAT GTGCTGTTTT ATGTCAGGTT TKGGGTAATT 300 TGTTTATTGC AGCCATCGGG AAGG 324
(2) INFORMATION FOR SEQ ID NO:146:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 355 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:146:
TTTGCCTCCT TCCTTCCTTA TCCAAGCAAG GGTGTGGTGA CAATGACCTG ATCGGGGTTT 60
AACGCCGGCT CTGTCTGCTC ACCAGACCTG GGGTGCTGAG CTCTGACCAG CCTGGGCAGC 120
CCAACCCACA GGAACTGCGG TTTCATAGCT GGGTCTTCAG GAAGGGGTGG AGGCTTTGGG 180
AGTGGCAGCT CCCCGCCTCC CACCACCCCA AGCCAGAGAA TGGGGCAAAC TTGTATGCAT 240
GGCTTATCTC TAAATTACTA ATCTGCTTCG GACCAGACTC ATCTCTACAG TATAGAGTTA 300
GAGTTATTGC TTCTATGACA GGTGTTCCAG AAGCCCTGGG TGGCTTTAAA GTCTG 355 (2) INFORMATION FOR SEQ ID NO:147:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 337 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:147:
CAGTTTTCTG AGTTCCCGTG TGCTAGACTG GCCAGAAGAG AGGGTCTGGG GCCTGGTCAC 60
TCGGCCACTC TCTCCTGTTT CTGGCCTCTT CTCCCTTCAC TCCCGTCCAG TCTGGTTTTG 120
AGAGCAGGGG CTGTTCTACA GCACCTCAGG GAAGGGAGGA GAGATACCTG CTGCTTCCAT 180
TGCTTTTCCC TTCCTGGAGT CGATGCCTTT CTAAGGGTTG GAGCTGCTCC TTGCAGGGGC 240
GGGTCAGTTT CCCAGGCCAT GCCGGGGGTG GCCATCTATG CTAGGGCTGG AAGCTGAGGC 300
TGGCCGCCAA CTGTGGGGCT GGGGTGGGGG TGGGTGG 337 (2) INFORMATION FOR SEQ ID NO:148:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 278 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:148: GGAATCAGAT GCTCAGGTGT CCAAGCAGGG ATAAGGACAG GCAAAATAAA TAACCCGCCC 60 AACCCCCATC GTCACTCTGC TGCAACACGA CACAAAGGTT TAAAGATCTG GGCCCAAAGA 120 CTCTGGGACC CTTCAAGCAA GTCAGGTGGA AGAAGGTTTC CCCACCCCCC ACCAGGCCTG 180 TTTGTCCCAG GTTGCCCTAG GATGGAGGCA GTTCAGACCC TGGGTCACTG ATGCTTGATA 240 GGAAGATCTT TGATATCAAT GGCCTAAGCT CTGCTCAT 278
(2) INFORMATION FOR SEQ ID NO:149:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 368 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:149:
TTTTTTTTTT GTTTTCAACA AACTTTACTA AATAACCCTG GAAAGGCAAT GAACGATCTG 60
ACAATTTAAG CTCTAATGAT TTAAAGCTCA GCTAGAAGAA AGTGAGGCAT GACATATACT 120
GTCAACGGAG GGTGAAGGAG GCAGATTTCT GGAAATGCAA TGATCCCACA CATTTGCTTC 180
AAGGAGAAAC CTGCAGACAT ATTTTCAGGT CTTGCTAAGT AACAACTGTT TATTTGTAAT 240
CAATACATTT GGGGAAAGTC TGCTATGTAG CTAAGGTCAC TGTGACCACA GACCAACAGA 300
TGGAAAGGAA AAAGGCACTG GACCAGCAAG GAAAAATACA TCCCCATCCT CAAAAGAATT 360
TTAAGGTG 368 (2) INFORMATION FOR SEQ ID NO:150:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 367 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:150:
TTGTGAAATG GGCCTGGGTA GATAAGGAAA AGAACCTCCA AGAGGTTAAG TGATTTGCGG 60
ATTTGCCTAA ATTATACAGA AGAGTCAGCA CCAGTGCCCA GGCCTTCTGA TTCTTAGTGC 120
AGTAAACACT AAGCACCATC ATTCCATTTC ACCACACTCC TGTCTTGCTG TTGTCCTCAG 180
CTAAGAAAGC CTACCCCTGA GTTACCCTCT TCCATCTTAG AGCCTTCCTG CTCGCTGTCT 240
GCCCCCCTGC GATGGGGACT TCTTTGGCCC TTCTCACCCA GCCCAGCCTC TGCCCGTTTT 300
CCTTCTCCTT TCCACTGCGG CTGAGCTCTT TTCTCCTTCC GAGAAGCCTT TCCTTCATCT 360
TTCCTGG 367
(2) INFORMATION FOR SEQ ID NO:151:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 366 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double -13.5-
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:151:
CCCAGCGGGC CGCCTCCCTC CTCTCTCCTC CATAGGTGGG GGTTGTGGGC CTTCTTTTTT 60
TTTTTGTCTT GGAGGGCAGT TAAACTTCTC CATTTGCCTC TCTCTTCACA CCCAAATGCC 120
AAAGGACACT TTTCCTTTCT TTTGTGGGTA GTTGCAAAAA AAAAAAATTC CTATGGGTTA 180
CTGCCACTTT TAAATACTTT GTAACTTAAA GGCAAAGTAG TATGTCACTG TTTCTTTTCC 240
CTGTAGTTTA CTTTTGAGGT TAAACATCTT TCCATGTCTT TATTGGTCAA ATACAGTTCC 300
TYCTTTTGTA CAATGTTAAT CCTAATATGG ACCATTTTTC CTAATGGGAT TACCGATTTT 360
TTTAAA 366 (2) INFORMATION FOR SEQ ID NO:152:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 269 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:152:
GTTATTCTGG CAAGTGCTTT CAGGGCCCTC CAGGGTTTGG CTGGTCACCA TGGAGGGGGG 60
GTTCAGGTGC TGAATTTAGG GACCCCAGCA TCTCACAGGT TTCCCCTTCC ATCTTTCCCA 120
GTGGCACTGT GTCTGAGCAG GTGTGCCCAG GTGAGGTTGT ATCCACTGTG TCTGAGCAGG 180
TGTGCCCAGG TGAGGTTGTA TCCACTGTGT GTGAGCAGGT GTGGCTGTTG CAGGTGGAAG 240
TGGGGATATN TGGGCACCTG GGTGCCATT 269 (2) INFORMATION FOR SEQ ID NO:153:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 260 base pairs
(B) TYPE: nucleic acid (C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:153: TTTCAGGATT TTATTTAAAA TTTATTGTAA TGGGGTCCGC GCAAAAGGAA GGGGTGGAGG 60 GTGGGGTACA TGCAGGGGAC ACAGGAACAN GATCCACATG GCCAGGGNCA CAACTTCTTC 120 TGTCGTGGGG AAGAGGGATG AAAAGACAAG ACCAGGGCTA NGAGCTGGGG TGGAAGAGGG 180 GAGGGGNAAC ACTGGCTGCA TTCCCCNAAC CCCANGANGC ACCTATAGGC CCTGGACCCA 240 TGGGTCACCC TGGGCCCTAG 260
(2) INFORMATION FOR SEQ ID NO:154: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 405 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:154:
TGGAACTTGT GAGTGGGGAC CCATGATGTA TGGGTCTCAC CTGACTTGAG GTGAATTTTG 60
GAGTGAAGGG CCCTGAGGTC AGCTCCCAGG TCGGTCGTGC TGGGCCAGGC CTGGTTTTCA 120
CAGGGGCTGA AGGATCCCAG TCCACCTGTG TGCATGTCAG GGCTCGGCCG GGAAGAAGCC 180
AGCAAAGTCC CCCGTGTCCC TTGCTGAGTA TTCTGTCACA GACAAGCCTC CATTAAAGCC 240
ACAGCAGTGC TACCCACCAC ACACACCTTG CTGGCCCGGC CACCACTGCT GGCTTCAGCC 300
CCTTNAGCAG CCCATGGNTT AGCAGACCCT CAGATGTAGG TCAGTGGCCT TANCTGTNTC 360
TATCCATGCT GTTAAACTCC CTGCCTCCAA CTGGGGGTCA CCAGT 405
(2) INFORMATION FOR SEQ ID NO:155:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 400 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:155:
CCATGATCTT ATTTATTACA TCTAGTTTTT CTTTATACCT CTAAAAAAAA GTGCCTTTTA 60
GATTTACAGC TTGTGCTTCT AAAGCAAAGG TTAAAACATC ATGCCCCAAA GGAAAACAAG 120
GTAAAAAGGA AGCTGCCATA TAAGCTCTTA AAANTTGTAT GTTAGAAGGT TCTAAAATCT 180
CTTCAGCACT GGTTGGTTGG TAGATTGTAC GACACTGACA TGGTGCTTGG GAGGGTCATT 240
TATCTGATGG TTGGAGCAGC ACCATGGGAA AGCTGCCCAG ATGGTCTACT GAAGTCCTTG 300
GCTGTGCACA GAATGGGCCC AAGGGCCAGN AATTCATGAG TCCGGGGAAC TTTGGNGGTC 360
CTTACTCAAT CTCCTTAGTG CTAAAGNTTC AGAGTCTCAA 400 (2) INFORMATION FOR SEQ ID NO:156:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 443 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:156:
GTCCTCTGGA TTGCTTCGTT GGTTGCGAAC TTTAAGAATG GCAAACTGTG ATTGGNTCCG 60
ATTAAGACAA GCTTTGTAGT TTTCTTCGTG TAAACACCAA ATCCCGCCTG GGCCATGAGG 120
TAGCAGAAGT GGGCCGCATC CAAGAGGCCC CTTGAAGCCA GAGTGTCGCC CATGGTAGCC 180 ATCGTCCTGG ACTCGACGTC CATGTTGTTG TTCAAGTTGG ACAAGACCAT GGCGAGGTGC 240
GGCCTCCAAT CTCCCCATTT CTCGTCTCCA CAGCACGTGG ACGCGGCAGG CATCCGTCCG 300
GACATGAGCT GGTAGACTGT CTTCAGAGGG TCGTTGATTK GGGAGGCTTT TTAGCAAACC 360
TKGGTCATGA CTCGGGCGTG TGTCCGGCTG TTCCATCTTA CTTGCAAGTA GCAGAGCGTG 420
ACCCCACAAG GCCATTCTTA ATT 443 (2) INFORMATION FOR SEQ ID NO:157:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 383 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:157:
ATTGGAAAGG GTTTTAAACG GAGTCGGAAC CTGAGTAGAT TTCCAAATTT TACAGCCAGG 60
ACTACAGAAG TGCATCATTC TAGAATGTGT AGACCTGAGT AGCTTATACA CTACAGAGCA 120
CTTTGCTTAT TTGAAAGTAA TTCAGCAACA GGTCACTTTG GGATATAACC TGAACCTTTT 180
TTTGGAGTGG GGTGGGTAGA CTACAGTAGA CACAAGGGCT GGACATGCAG ATGCTTAGGG 240
GATTAGCGTT TTTCATAATT TGTTCTGTTT GTCAGTTCAT TCCTGTGTGT TCTTACCTCT 300
ACAAAGGTAC ATTACACATT TTARGTTTTT TAGTGACCTT TAACCATGTT ACTTGAAGCA 360
TTTTGGAATA TAAAGCTATT TTA 383 (2) INFORMATION FOR SEQ ID NO:158:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 241 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:158:
TGGTSTGTGG CTCAGCTGCA GCGGCASGTA AGTGGGTSTC CAGGGGAGTG GACAAGCAAT 60
TCTCCTGTCA TTTGCAACTT TCTTCAGGAA CTCAGATAAA GAACACTTGG ATAACGATGA 120
TCCCTGTAGA GGGATTTCAT CTGTACCATC ACACATGGAA GAGGAGTTTC TAGGTCAGGA 180
AAGGCAGCTN CTAAGCTAAA GGTTTCTTGG TCCCTTNGTC CTGGCATGCC TTAAGGAGGG 240
G 241 (2) INFORMATION FOR SEQ ID NO:159:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 224 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:159:
CTGTCAGTAA TGGCTCACTA AAGGGCCAGC AGTTTAAATT ACACAGGTTG CACTAAAAGC 60
TGCAGCTTTG GCCAGGCAAG GTGGATCACG CCTATAATCC CAACACTTTG GGAGGCCGAG 120
GCGGGCAAAT CACCTGAGGT CAGGAGTTCA AGACCAGCCT GGCCAATATG GTGAAACCTA 180
AGCCTCTACT AAAATTACAG AAATTAGCCG GTCGTGGTGG CACA 224 (2) INFORMATION FOR SEQ ID NO:160:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 377 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:160:
GGAGGCTGAG GCGGGCGGAT CACGAGGTTA GGAGATGGAG ACCATCCTGG CTAACACAGT 60
GAAACCCTGT CTGTACTAAA GATACAGAAA ACTGGCCGGG CGTGGTGGTG GGTGCCTGTA 120
GTCCCAGCTA CTTGGGAACT CGGGAGGCTG AGGCAGGAGA ATGACCTGAA CCCGGGAGGC 180
GGAGCTTGCA GTGAGCAGAG ATTGCGCCAT TGCACTCCAG CCTGGGCGAC AGAGTAAGAC 240
TGTCTCCAAA AAAAAAAAAA ATAATAATCA AAGCTCTTGG ATTTATAGTT TGGTCCCCAG 300
CCTTGTTTTG ATCTTTCCTT TATCCTGTTT TATTGCCATT TACCACGTCC TTTTGGAAAC 360
ATCCCTTTCA ACTGCTG 377 (2) INFORMATION FOR SEQ ID NO:161:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 273 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:161:
GCAGCGGCGC CGGGCGAGGA GGCGGCAGGG GCGAGGAGGG GGCGGCGGGT GGCGACCCGC 60
AGGAGGCCAA GCCCCAGGAG GCCGCTGTCG CGCCAGAGAA GCCGCCCGCC AGCGACGAGA 120
CCAAGGCCGC CGAGGAGCCC AGCAAGGTGG AGGAGAAAAA GGCCGAGGAG GCCGTGGCCA 180
GCTCCGCGCT GCTAGGCCCC CTTCGCGCGG GCCCGGCGCG CCCCCGGAGC AAGGAGGCAG 240
CCCCCGCGGA GGAGCCCGCG GNCGCCGCAG ACT 273 (2) INFORMATION FOR SEQ ID NO:162:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 286 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:162: TTTTGGTCAA ATAAATCAGA GTACTACAAT CATCAAACAT CTGATTCATT TAACATGTGA 60 GCATCTATAC CTGCCCATTT GTGTGAATAT TCAGTATATA TCTCATACCT ATTCTCATGC 120 CTTCATTTAT TGTGGTTATG GCTGTAGATA TGGAAAAAAC AGTAGCTGAG ACATTTTTAT 180 TATGAACTAT ATTATACCTT AATCAATCAG TCAGAAAATG CTTAGGAAGA AGAAATGCAT 240 GATTGTAAAT GCATGATTTC AACATGCTAC CCGGCCAACA AAGTTG 286
(2) INFORMATION FOR SEQ ID NO:163:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 342 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:163:
TGCCCAAGGA AGACAGAACA TGGAGAACCG TCAAGGCAGG AACCCCACAG ACTGTCCCTT 60
CCAGCCCACA CTCTGCCACC TCCTGGCCCT GTCCCAATTC TGAGCCAAGG CCTCCCCGAG 120
GCAGAAGTTG CCTGGTCCTC TGTCCCCACA GTGACCTGAC TGGGGGTGAG GGAGAAGGAG 180
GAGAGAGCCC ATGTGTGGTG TGTGTGCCCC TGAGAACTTC GTGGTGACTG CCTTTGGGAG 240
CCCGCAAGTG GCCAGAGGCA GGGGTAGCTG AGTTCCTGGG AGACCCCTTT TTTTCCCCCA 300
RGTTCCCCAG AGGGCAACGC CATCAGTAGC AGTGTGGTGT TT 342 (2) INFORMATION FOR SEQ ID NO:164:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 392 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:164:
ATTACCCGGG CCCCGCCTCC CTAAAACAGA TCTACGGACC TTAACCGACG CCATGCTGAG 60
GCTCATTCCA TCCCTGCRGA CGTATGCAGA GCCGCTCACT GCTGCCATGG TGGAGTTCTA 120
CACCATGTTA GGAGGAATTC ACCCAGGATA CACAACCTCA CTATATCTAT TCACCCCGTG 180
AAATGACTAG GTGGGTGAGA GGCATCTTTG AAGCGCTGAG ACCTCTGGAG ACCCTGCCTG 240
TTGAAGGCCT CCTTCGGATT TGGGCACATG AAGCTCTGCG TCTCTTCCCA GATAGACTCG 300
TAGGGGATGA GGAGAGGCGT TGGGACTGAA TGAGAAGATC GACACGGTTG CTCTTGAAGG 360
CACTTTCCCT AACCTTCGGC AGAGAGGAGG GC 392 (2) INFORMATION FOR SEQ ID NO:165: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 406 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:165:
GTTATAATTA TCTTGTTTTA TTATTTATTG TTTATCTCTT ACTGTGTATA ATGTAGAAAT 60
TAAACTTTAC CATAGGTATA TACATATTGG AAAAAGCATC TTATATACAG GGTTTGTTAC 120
TATCTGTGGT TTCAGGCATC CACTGGGGGT CTTGGAACAT ATCCCTTGCA GATAAGAGGG 180
AACTGCTGTA TCCATAGAAT AAAAACACCC CATCTTGAAG ATAGGAGGTT CTGTAAATTG 240
GGATGGGGTC AGGGAATCTG AATTTTAAAA GTTTCCCATG TGATTTGATG CCCAGCCAAG 300
GGCTGGGGAC CACTGTCTTG AAATATAATG CTGAGGAAGA TACTGTCTTT GGATTTTCCT 360
GGTAATTCCG AGTGCAAATT CTCAGGCTGG AACCTTATGG GCCTTG 406
(2) INFORMATION FOR SEQ ID NO:166:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 453 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:166:
GAAAACTTTG CCATGGGTCA GTTTTATTGG AAGTTCATTT TCCTGAATGT TTGGAAGAAA 60
GTCTAGTGAC TCAGGATAGC ATTTCTAATT TCACAGAGTT ATTTTTCCGT TATGAAACAC 120
AGATTGCCTT TGAGGTCTCC TGTTTCTACT ACTGCCCCTC ACTTTTATGT GGGCCTCCTC 180
TTTCCTTTGT TTCTGGAGAA CCTTTTCCTG TTCAATTCTG TTTTAATTTT CAGCAGTTTT 240
TTTTCTGTGT GAGTGAGGCT GTTTCCTAGC AGGGAGGTCT GGTTGGTCAT TTTCAAGTTC 300
ATCAGGGCTT CATCAGGGCT TGTCCACTTC AACCCTTACG CTATAGGNCC CTNTGCACCA 360
TCTGCANTCT TCAAAATGTG CCCACTGGTT CGTTCCCATG GANGGCTTGT TGGTAATTTG 420
GGCTTTTAGG GGGGGCCATG GAAGGAGCAA ATC 453 (2) INFORMATION FOR SEQ ID N0:167:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 285 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:167: TTTACTCTTA AAACTGTTAC AACAGAATCA TGGACTGACA CAGGTAATGG CTGAGCCATA 60 AGCAAATCGA GAAGTACAGA AATGTCCCAC CCCAAACAGC TGCGGAGTAC ACATCACACA 120 GGGCCTCTGG TCCCGGCCTT CTCAGGTGCT CTGGAGTGGA GGATCCTTTG AGGGAACTCT 180
GACCACTCCT GTTGTCTACC TAGAGAGCAC GCCACTTGGG CCACCTACCC CCAACCTTTG 240
GCCAAAGGAG TGAAAGGACC TGGAACCTGT CGTCAACCTC AGCAT 285 (2) INFORMATION FOR SEQ ID NO:168:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 327 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:168:
CTAGAGGGCA CTCTGTATAC CCGTCAGCTC CTGGAGCCAT TCATTCTATG CTGGGCAGAC 60
AGGCTGTGAG AGGACATGGG GGACGGTGGA AAGGNTCCAA AGACGAAGCT GTNGTTTATC 120
CTTGTTGGTT TTACACAGGG AATGATGAAA CATTGAAGGG GTTTAATAAG CTTTTCCTAA 180
AACATTTTCC CCCTAAACAG GCTGGCACTA TGTCGAAGCT GCCCAAATTT GAGATTGATT 240
TACCAGCTGC GNCTAAGTCA ACTAAACCCA NGCCTTTCCG AAAGAGACAT CGCAANTGGC 300
TTACCCAANG TANTGTCCCG TTTTCAG 327 (2) INFORMATION FOR SEQ ID NO:169:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 346 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:169:
GGTGCTATGG AGAGCCGGCC GTCCTCCAGG GGTGAGCTGG GGAGGCTTCT GCGGTTCTGG 60
AGTCCCGGCG ATGGCGCCAG TTCCCCAGCA AACCCCCTCC AGAGCTGCCC CCGGATGCAC 120
AGACAAGGAG GGGGCTTGGG AGTGACTTGA GGCTGTGACG GGRTCGCCCT CGGTGTGGGC 180
AAGTGAGTCC TCTGTGGCCA AGAGGTCAGA GTCGTCCCTG AGGCTGAGTC GAACACAGAC 240
CCGTGGCCCT CATAAAATTA AACATAAAAG CACAAAAATG GGCGCAACCA GACAGCATTG 300
GCTTTCAGAC AGGCAGGGAC ACGGGGGCCC CTTCGTGTTG ACCTGT 346 (2) INFORMATION FOR SEQ ID NO:170:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 398 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:170: TTGACCTCAA CTTACTGAGC AATGCCGTAG CTATGGAATA GAAGCATTTG TTGCACTCTT 60 TTTGTGAGCC AGGCCCTGTA GGAGGGATTG TGGATGGCAA AACCTCAGGT TCTGCCCAAA 120
TCCTCCCCTT GGGGGCTGGA GGGTCTCTAG TTAATTGGCA TTCCGGTGCT TAAGGCCACT 180
TTTGGGTAGA GGTTTGGCAA GGATGGAGTG TCCAGACCTA TGATCCTCTA AGAACTTTAC 240
CTTTTAAAAA CAGCCACCCA AATGGTGGTG GCGTGGGGAG CAGGTGGTGG TGAAGGGACT 300
GGGGGTGTCT GGCCATKGCC ACGTACCAGA GGAGACTCTG TGAGCCCTCT CCCTGCCTGA 360
GGGACACTTA ACTTTTATAG CACTACATAG GGTCAACG 398 (2) INFORMATION FOR SEQ ID NO:171:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 321 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:171:
AGACAGCATC TGGCTCTGTC ACCCAGGCTG GAGTGCAGTG GCGCAATCTC GGTTCACTGC 60
AACCTCTGCC TTCCAGGTTC AAGTGATTCT CCTGCCTCAG CCTCCCAAAT AGCTGGGATT 120
ACAGGCATGT GCCACCATAC CCAGCTAATT TTTGTATTTT CAGCAGAGAC GGGGTTTCAC 180
CATGTTGGCC AGACTGGTCT CGAACTTCTG ACCTCAAATG ATCTGCCCAT CTAGGCCTCC 240
AAAAGTGCTG GGATTATAGG TGTGAGCCAC TGCGCCTGGC CCTTGGGTAA ACACTTCAAA 300
TGCAMCCAAC CATTAAAGGT A 321
(2) INFORMATION FOR SEQ ID NO:172:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 293 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:172:
GAAACTTATA GTCTTGCCTC CCAACCTTCT GAACACTCCA GTAGAAAAAT CTTCTCGCCT 60
ACCTTTATCA CCCCACGACC TACTAGCATT TCTTACTCTC AAAAAAAATC TTTTCTGAAA 120
AATCAAGACA GAGTGCAAAC AATCAGCATA ATTTTATTAT GACARAACTT TTAAATTTTA 180
TCCCCCTCTC TGAGAGKTCT GCTAGGACTC CTTCAGATAA GTGAAAAAGA AAKTTTTTAA 240
AATTTATTCT CAAATCCGAA TTCCAATCTG TATAAAAAGG GCGATTCTCC CTC 293 (2) INFORMATION FOR SEQ ID NO:173:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 282 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:173:
GCTTGGTCCC GTTCCTCAGG AAAAGGATGG ACCTTCTCTT CTTCTCAGAT GGTCCCTTCC 60
ATTCCCCTGA AACCTGCATG AGAGCTCCTA ACATGTTTCT CCAATGCAAT CAAGCCTAGA 120
CTCCAAATGT CCTCCCAGCT CACCTCCATC TATGCATCTC ATCTCTGGAT TTGGTGATCA 180
GACTCTATAT TGACAGTAGG ATCTCAAACC CTGCATCCAT CCTTCCTCCA GCAAGCCCTG 240
CTAGCCACAT GAGGAACAAG TTTCCGTGTC TTCATGACTT CC 282 (2) INFORMATION FOR SEQ ID NO:174:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 353 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:174:
CAAGAGGTGG GAGAGGTAGG GGGCAACTAC AGCTCCCCAC CAGCCCCACC AGGGGGAATG 60
GACCCCTCCC TGCCTCCTGC CCAAGTGGCT CCCCCTGTAT TATGGGGGGG ACTTTGTGCA 120
AACTCTGCCC CGAGGGGGTG GGGAGGGTGG AGGGTGAGTG TGAAATGGCA GCGGTTGGGG 180
CTGGCAGCTG TGCTACTGGG CACTGGGGGG CTTGTAGGGC TCCAGGAGGA GGGCCGAGAA 240
GGTGTTGACC TTGTCTGCCC CCCGCACCTC ATGGGGTAAC AGCGGCAMTT TCACGATGTG 300
GAAGTTCTTC ATACAGGTCC TCCAATCTGG TCCAGATACT TGGCCTGGGT TCT 353 (2) INFORMATION FOR SEQ ID NO:175:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 394 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:175:
GCCCATGCCC TTGTGTACAT AATCTCTAAT ATTTATATAT ATTGATATAG AATTCTCTCT 60
ATAATATATG TCATAGAATC TCTCTTGGGC CTGGCGTGGG AATGTGACAT TAAGAAAACA 120
TGCTAAGACT GGCCAGAAAA ATGGATATTT CCCAGACCTG GAGGATGGTG TGTGGGATGT 180
ATAGGTGAGG TCGTGGAGAA GATAATAAAC TCATTCCCCA AGATACCCTC TTCAACACAA 240
GGACAAGAAG GAAGGTGTGT GGTGGGGGAG GGGACAATGG AGGGGGAGGA GTGGAAGATT 300
TGGATTTTCA TTTAATAAAG TCAATTGAAA AATGAAAGTG CACCCCCCCT CCAAAAAACA 360
GGAGATTCAT TTAGCAAGAG CCGTTTCATT CACA 394 (2) INFORMATION FOR SEQ ID NO:177: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 381 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:177:
ATTGGGACGG GCCCCCCTCT GAGGCGACGG ATCGATAAGC TTGATATCGA ATTCCTTGAT 60
NTTTTCTAGT GTTATGGTTT TCTCCCACTC CAATAACTWT TCATACCTKT GGTCTKAGTT 120
TTTCCATCTA TAAAATCATG TGCTAAATAA TTAACTATCA TCTCTATCAT TGTCAGACTA 180
CACAAAGCTT CCAGCCTGGG CAACAGGAAC CCTGTCTCTA AAAAAAATAC AAACATTAGC 240
CAGGTGTGGT GGTATGCGCC TGTATTCCCA GCTACTTGGG AGGCTGAGGT GGTAGGACTA 300
CTTGGGCTTT AGAGGTCAAG GCTGCAAGTG AGCTGTGATT GCGCCACTGC ACTCCAGCCT 360
GGGCAACAGG GCAAGACCCT G 381 (2) INFORMATION FOR SEQ ID NO:178:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 443 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:178:
GATTTTATTC AAACACAGGC AAGAACAATG ACCTTCAGAG CTGGGTAAAA ATAATAAGTT 60
AAAAGCATGG TTAGAATTTT AGACAATCAG ATAAAAAGTT TGAAGGAAGT GATTTCCCCT 120
TCCTCTCCTA ATTGATTAAT TCAACACAGC ATAAAAATAA TTTGTATCTA TAAAATATCC 180
TTGTTCCCAC ACAAATGAAC TGGAGGTGGC CCTAGGATTT CCTTGACTAT GCACAATGCA 240
CACAATCTAC ATGTCCCTCC TCCCCAACTT TTAAGGCAAA AATGGTCCTG CATCTTCAGG 300
CAGAGGGTGG GCTCATGCCA GCAGTCAGCT GTGGTCAAGG ACACTGGGGG TGCGTTTYCT 360
CCACCGAAAG ATGCCTGCTT TGGGTCCACT TTGGGCGCGG GATCCCATTT TATTTTCTAG 420
CCTGTGCCTC ACCACAGGGA AAA 443 (2) INFORMATION FOR SEQ ID NO:179:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 325 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:179: TGGGGGACCA GCATTGCTCC CAGCTGAGGG CGCCGTCTTC CTCACCACGT ACCGGGTCAT 60 CTTCACGGGG ATGCCCACGG ACCCCCTGGT TGGGGAGCAG GTGGTGGTCC GCTCCTTCCC 120 GGTGGCTGCG CTGACCAAGG AGAAGCGCAT CAMCKTCCAG ACCCCTGTGG ACCAGCTCTT 180
GCAGGACGGG CTCOAGCTGC GCTCCTGCAC ATTCCAGCTG CTGAAAATGG CCTTTGACGA 240
GGAGGTGGGG TCTTACAGCG CCGAGCTCTT TCCGTAAGCA GCTGCATAAG CTGCGGNTAC 300
CCGCCGGACA ATCATGGCCA ACTTT 325 (2) INFORMATION FOR SEQ ID NO:180:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 213 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:180:
GAGCATGCCC CCGGAGTCCC CAAGATCCTG GTGGGGAACC GCCTGCACCT GGCGTTCAAG 60
CGGCAGGTGC CCACGGAGCA GGCCCAGGCC TACGCCGAGC GCCTGGNCGT GACCTTTTTT 120
TAGGTCAGCC CTCTTTGCAA TTTCAACATC ACAGAGTCGT TCACGGAGCT GGCCAGGTTC 180
GTNCTGCTGC GGCATGGGAT GGACCGGCTC TTG 213
(2) INFORMATION FOR SEQ ID NO:181:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 219 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:181:
AGCTTTATCA CATTATACAC AAACATAGAA AACAGTGTTT CAGAAGAGAA GCAAAGGCCA 60
TTGGCTTCAA ATATTTATGC AACAATGAAA ATGTTCTCAG CCCTTAAATG AGCACTTGTG 120
ACTTGTCCAA CAGTGAGATA ACTAGTCAAT GGAAGAGTTC AACACTAGAG CATGTATCTC 180
AGTCTGTTCT CATATTGCTA TAAAGGGCTS CCTCAGACT 219 (2) INFORMATION FOR SEQ ID NO:182:
(i) SEQUENCE CHARACTERISTIcjs:
(A) LENGTH: 451 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:182:
GTCTTACTCT GTTACCCAGG CTGGAATGCA GTGGTGTGAT CATAGCTCAT TGCAACCTCT 60
GCCCTCTAGG CTCAAGTGAT CCTCCCACCT CAGCCTCCCG AGTAGCTGGG ACTACACGTA 120
CATGCCACCA TGCCCAGCTA ATTTTTGTAT TTTTGGTAGA GACGGGGTTT TGCCATGTTG 180 ACTAGGCTGG TCTTGAACTC GTGAGCTCAA GTGATCTGCC TGCCTCGGCC TCCCAAAGTG 240
CTGGGATTAC AAGCGTGAGT CATGGTGCCT GGCCTAGTTT GCTCTTATTT TTTTTCCATC 300
TTTGCAGTTT CTAGGCCACT GGGAACAGGC TGCAGAGCTC AGAGTCCACA GCTGTGAGGC 360
TCCATGTTGC ACCATCAAAA AATAAGGTGA CGAGAGTCCT GGGTTTCCCA GTGTCACGGC 420
AAGAGGGGTT ACTGCTCACG GGTACACACA G 451 (2) INFORMATION FOR SEQ ID NO:183:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 444 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:183:
CCAAGTTGAC CCGCCGAACC ACCGACAGGA AGAGTGAGTT CCTGAAAACT CTGAAGGATG 60
ACCGGAATGG AGACTTCTCA GAGAATAGAG ACTGTGACAA GCTGGAAGAT TTGGAGGACA 120
ACAGCACACC TGAACCAAAG GAAAATGGGG AGGAAGGCTG TCATCAAAAT GGTCTTGCCC 180
TCCCTGTAGT GGAAGAAGGG GAGGTTCTCT CACACTCTCT AGAAGCAGAG CACAGGTTAT 240
TGAAAGCTAT GGGTTGGCAG GAATATCCTG AAAATGATGA GAATTGCCTT CCCCTCACAG 300
AGGATGAGCT CAAAGAGTTC CACATGAAGA CAGAGCAGCT GAGAAGAAAT GGCTTTGGGA 360
AGAATGGCTT CTTGCAGAGC CGCAGTTCCA GTCTGTTCTC CCCTTGGAGA GCACTTGCAA 420
GCAGAGTTTG AGGCTCAGCA CCGA 444 (2) INFORMATION FOR SEQ ID NO:184:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 399 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:184:
GGCAGAAAGA GGAAGGAGAC AGTGCCAGGA GGAAGAAGGA AGGAGTCCCT TAGCTCTCTT 60
CATTGTCCCC TTTACTTCCT GCTATCTTCT TCTCCTCTTC TTCTCTCTCT TGCCTNTATG 120
CCTGTATTTC TGGCAATATG ACAGGCCTGC CTACCCAAGA TCAGAACTCC AAAACCACTC 180
CCACCCCTGA AGGTCGGGAG GGTCTTAGCA GCCCTGGGTG GCTGCCTGTG CTCAGGTCCT 240
CAGCTCCATG GGAAATAAAA ATGGCACCCT GAATCTCTAG GATTTTGTCA CTTTGGAGTC 300
ACAGCAAAGT TCTCTTCCTC TTGTCCCCCC GTTTGCTGCT CCTTGGGTTA TAGGACATGG 360
TAAATATTTA TTACTTTCAG GGAACCAGTA TTTTATTAG 399 (2) INFORMATION FOR SEQ ID NO:185:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 263 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:185:
CAGAGACACT GGCCCAGCTA TTTTCAGCAG GGACAGAGTC GAGGCTCACT GGGGATGGCT 60
TCAGAGGACA CTGAGGCCCC TCTCAGGGAG GGCAAGGCAC AGATACCCCA AATTCCACCC 120
CACGTCCCAA AGGTCTCCCA GCGGGGCTGT CCAGTCCATG TCAGCAGAAG GCTCTTGGGC 180
GTGTGAGGGA GGGTCTTGGA GAACTAAGCG AAGGAGGCAA ACGCCAGGGC CCCTTGCAGG 240
TCAAGGCACC ATGTGCACCA CTT 263 (2) INFORMATION FOR SEQ ID NO:186:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 343 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:186:
GTTCCAATAG CTGGTTTTAT TCTCAGCACA AAAGGGCCCT GTGTAAAAAC CAGAAGGATT 60
TTGTAAAATA TCAAAATGAA TATTTGGCCT GGAGGTTGGA AAGTGAAGCA AGGCTGGACA 120
TAGAAAAAAA CTGATCAGTA GTTATTCAGG ATATTATTTA GGATAAATGA AATAGGAACT 180
TAGGGGCATC TCTTACTTTT CTACAGGTTC TTATCTGGGT CAATGAAGAA ATTGTGTTTA 240
TCTTGCTGCC CTTGCATCAG GTTTTTTGCA CTAATGGAAA AAAGCCGGCC GAAAAACAAA 300
ACCCAATCCT TTCAGTCCTA GCTTTTACAT CTTGCCCTTG CAA 343 (2) INFORMATION FOR SEQ ID NO:187:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 229 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:187:
GGTGCGGCTC CACCCCTTCC ACGTCATCCG CATCAACAAG ATGTTGTCCT GTGCTGGGGC 60
TGACAGGCTN CAAACAGGCA TGCGAGGTGC CTTTGGAAAG CCCCAGGGCA CTGTGGCCAG 120
GGTTCACATT GGCCAAGTTA TCATGTCCAT CCGCACCAAG CTGCAGAACA AGGAGCATGT 180
GATTGAGGCC CTGCGCAGGG CCAAGTTCAA GTTTCCTGGC CGCCAGAAG 229 (2) INFORMATION FOR SEQ ID NO:188: (i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 284 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:188:
CCAGCAACTC AAATTCACCA CCTCGGACTC CTGCGACCGC ATCAAAGACG AATTTCAGCT 60
ACTGCAAGCT CAGTACCACA GCCTCAAGCT CGAWTGTNAC AAGTTGGCCA GTGAGAAGTC 120
AGAGATGCAG CKTCACTATK TGATGTACTA CGAGAKGTCC TACGGCTTGA CCATCGAGAT 180
GCACAAACAG GCTGAGACCG TCAAAAGGCT GACGGGATTT GTGCCCAGGT CCTGCCCTAC 240
CTTTCCCAAG GAGCACCAGC AGCAGGTTTT TGGGGGCCAT TGAG 284 (2) INFORMATION FOR SEQ ID NO:189:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 215 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:189:
GGAAGGATGA GAAACAGATT TCTGCTCACT TCATGGGCTG RCCTRGRATT GACGATGGTR 60
CAAACCCAAG ATTATCCTCA TGTAATTTAT GAAGATTATG GAACTGCAGC GCATGACATC 120
GGGGACACCA CGAACAGAAG TAATGCAATC CCTTCCACAG ACGTCACTGA TACAACCGGT 180
CGGGCACATC TCKCGGCCTA TGCTGCCGGT GGTGC 215 (2) INFORMATION FOR SEQ ID NO:190:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 153 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:190: TTTCATATGG AAAGAGCTAG TACAATCACA TATTTGAAAG GAGAAACAAT AGGTACTGAA 60 CCGGAGGGAA AGGGCGAGGG TGAGTGTGCC AGCACCGGCC TGGTGAATCC ACGATTCGGT 120 TTCCCATCCA AGGGTAAGTT TCCCAAAATA CCG 153
(2) INFORMATION FOR SEQ ID NO:191:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 316 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:191: GTATTTATAC ATTTATTTAT ATATGTATAT TTACTTCAGA NGAAACGAAC ATTTCGGGGA 60
CAGGAAGCAA GCAGGCCCGG GGCTGCTTCC CTCACTGCCC ACCTCAGAGT CAGAGTTGGC 120
ACATGACAAA TACCAAGCTC AGGGTGAAGA ACTGGGAGTT AACTGGGAAG TAGGGKGCGC 180
TCTATGCACA CGCAGGCTTC TAAGGGTGCA CGGTATGGGC AGKKGGTTTG CACTGGGAGG 240
CCCTATGTAC AGCTTGAAAG CTAGGGGTGA GATTAGCCCA GTGACTACAG GAACATACGT 300
CAAAGTTGAG AGAAGA 316 (2) INFORMATION FOR SEQ ID NO:192:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 360 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:192:
GTGGTTTTTG GTTATATGCA GCTTTTGACT AGCATGTATT GTGTCTTTTT CTCCTCTATG 60
AATAATTTTA TATTTCATGC TACTTCTTGA AAGTTTACTC TTTGATGCTC TAAGAGAACA 120
GCCAGATGGT TTATATGAAT AANCTTTATC TGCAGGATGG TGGATTGGTA AATNAGGAGA 180
ATGTTGTTTG AGATATCAAG ATTTATGTCT GGGAACTAAA ATATATAATG CCAAATGTGT 240
TTTTGTCAAT TACTAGAGAA TTCTGTGCAA ACATATCATC TCTTCACATG CTGCACACTT 300
TGCTTTTTGT TAAACAGCAG GTAGTAGACA GACCAATACC AGTTTCGCGT TAAGGCTTTT 360
(2) INFORMATION FOR SEQ ID NO:193:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 397 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:193:
GAAAAGACCA AGGAGATGGT GAAGACAGCA GAAGCCCAGA AGCAGCAACT GAAGGAGGAG 60
CAGGGGAGGT CAGCAAGGAA CGGGAGAGTG GGGATGGAGA GGCTGAGGGA GACCAGAGNA 120
CTGGAGGGTA CTATTTAGAA GAGGACACCC TCTCTGAAGG TTCAGGTGTA GCGTCCCTGG 180
AGGTTGACTG TGCCAAAGAG GGCAATCCTC ACTCTTCTGA GATGGAAGAG GTAGCCCCAC 240
AGCCACCTCA GCCAGAGGAG ATGGAGCCTG AGGGGCAGCC CAGTCCAGAC GGCTGTCTAT 300
GCCCCTKTTC TCTTGGCCTG GGTTGGCGTG GGGCATGCGT CTAGCTTTCA CTCTGGTTCA 360
GGTCCAACAG GGTCCGTTCT GTGCCTTTGG TGCCCCC 397 (2) INFORMATION FOR SEQ ID NO:194: (i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 225 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:194:
GATTATTGGC TTTGCTTTCA TAACATGTAT TTTTAAGTAT TTACTCTCTT AATGGCCCTC 60
GTGTCTATTT TATACATCAT ATCTCTTAAT TCTCTAGATG GAACACTGAA GGACAGGAAT 120
TAAGTAAGTG ACTGGCCATG CAAGGGTTGG AAATTTTACT GTATCCCTTC CTCRGTAGAA 180
GTTATGTTAA ACATTCAAGC AACCACATAT CTAACAGAGG AGTTT 225 (2) INFORMATION FOR SEQ ID NO:195:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 294 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:195:
ATTACTAGAT ATTTGTATGT TAAATTATGT GGGTTTTCAA ATTTGTGGAG AATAAGTAAT 60
AGTGACATTA GTTTAAGGAC AGTGTTTCAT CAGGGCATTA TTTTAATGAA TCTTATATTT 120
AAATGTCTGT TTCAGGAATT CATGTGAATC TTTCTTTTTA TAGAGGACCC ACAGGCATGA 180
NTTATTTACT CCTCCGGTGA TAGGTTCTCA CCCTGATGAA AGCGGAAGCA AATTCCAGGT 240
TAGAACATTA TNCTAGTTAT GTAGGGGGGT ATAAAGTGTG TAAGTTTAAT ATTT 294
(2) INFORMATION FOR SEQ ID NO:196:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 233 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:196:
TTATTTTTCT CTAAATTTTA AAATAGAAGA CTTTAATGGA AAACATTTAG TACCATCATG 60
TCAMCCTGAA TGCCAGCAAT ACCTCGACTT TTACACACGC AGGAAGCCTA GTAAAAGCCC 120
CGTCAGTAGT ACACATTTCT CTATGGTCCT TCAACAGTTT TTCATATACA AAATTTTCTG 180
CTATTTTTGC TTTTGCAAAC AGCAATAACT TTTGGGTTTC CCATATGACC ACC 233 (2) INFORMATION FOR SEQ ID NO:197:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 230 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:197: AAGATATCTA CCTGGAGTAG CTGTGCAGCC CCGCCCTCTG CTTCCCCCAG CCCTCAGGCC 60 AGTGCCAGGA CAGCTGGCTG CTGACAGGAT GTGGCACTGC TTGAGGAGGG GCACCTGCCA 120 CCGCCAGAGG ACAAGGAAGT GGGGGCCGCT GGCCAGGGTA GGGAAGGKTG GGGCAATGGG 180 GAGAGGCAAA TGCAGTTTAT TGTAATATAT GGAATTAGAT TCATCTATGG 230
(2) INFORMATION FOR SEQ ID NO:198:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 118 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:198: TTCTCCTGGG GAAAGGGCTG TTGCTGAAGT GGCCGGTTTT TTTAAGCATC GACATTTGCA 60 TCCAAAGGTT CAAGCAGCCG CCTCAGGTTC CARAGGCTTC CACCTGATGG CTGCACTT 118 (2) INFORMATION FOR SEQ ID NO:199:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 268 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:199:
TAAATGATGG AGTTAAATGA TGTTGTCAGT GCCTATTTAA AAAACTACTC TTCCCCTTCT 60
CTATGAGTTC TACTTTGGTA AATATTAATA TTTAACCAGT TAGTAAAACT AACACCACTA 120
TTTCAATTCT CTTTTGTGCA TAGTAAGTAA ATTTTGCTTT ACTTACTTTA TAAAAAAATA 180
CTTTACATTT TATAAAGCAG GTTTTAGAAA AACGGTTTAC AAGAAAGTTT GCCTCCATTT 240
CACTGCCAAT TTAAGCACAG GGGAAAAT 268 (2) INFORMATION FOR SEQ ID NO:200:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 422 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:200:
CCAGTGAGTT TGTGAAAAGC AACAGGGGTA NGACAGGTTC AAGGAAGGAC ACAGACAGTG 60
CCCTGTTTTA GGTTCCAAAT TTCTTCTTTT TAATGGGTGG TGGGAGCTGA GCAATGATGT 120
CATTTGGAAG GGGCAATGAC TTGTCAATNA TGCAGAACAT GTAGGCATCA TGGAGAAGGA 180 TGTGCATCGG TCTCTTGGGA TGAAAACTGA TGTGTGTGAT AGGAGTATCC CTTTGGAGCC 240
AAAGGTGGTG AAAGCCCTGC TTCTGGACAG TCCGGCTCCA ATCTGTATAC TGTTTGTCTG 300
GGATGCTGTA CTCAAATACC TGCTGGTCCG AATGAGCGAT GACAAGGTTG TTTGGTATTG 360
GGGGCAATAG CCATAGCAGT CACTTGGGAA ATTGTAAGCA GGCACCGTGC AGTGAAGTTT 420
TA 422 (2) INFORMATION FOR SEQ ID NO:201:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 273 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:201:
ACTCCACGCT GATGAACCCG ACGTCCATTT CTCCAAGAAA TTCCTGAACG TCTTCATGAG 60
TGGCCGCTCC CGCTCCTCCA GTGCTGAGTC CTTCGGGCTG TTCTCCTGCA TCATCAACGG 120
GGAGGAGCAG GAGCAGACCC ACCGGGCCAT ATTCAGGTTT GTGCCTCGAC ACGAAGACGA 180
ACTTTGAGCT GGAAGTGGAT GACCCTCTGC TAGTGGAGTC CAGGCCCCCA GACTACTTGT 240
TACGAGGGCT ACAACATGTG CACTGGGTGC CCG 273 (2) INFORMATION FOR SEQ ID NO:202:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 436 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:202:
GGACTCCAAC CCCCCAGGAG GCCGAATGCT GAGCTTGGCA ATGGTGGCCT GGATGGAGCT 60
GATGGGCACA TCCCCACCGA GGACCAGGTC CTGGGAGTCC TGAGGAAGGT GGTTCTTCTG 120
GCTGATGCTT GCACTGGCCA AGGGTTTGCA TGGAGGAGGC ACACCATGGC GCTGCAGGAC 180
CTGCTCCACG TGTCTCACCA CTGCCTCATA GCAGAACCTG AGGTGCAGCT TCTCCTGCAG 240
CATGTGCTTT CTCTGCTGCC GCATGCGCCG CACCAGCTGA GGCAGCTCAG GGATTCCKTT 300
CCCAGCCTCC ACCTCCTGCA CAGCTGCATA GAGCAGTGCA AAGGCTCCCG TGCGGCCCAC 360
ACCAGAGCTG CAGTGCACAA TGATGGGCGT TTGCAGGGGC CGTGATGCAA GGTAATTTGC 420
GTGCACCTCC TGGGTT 436 (2) INFORMATION FOR SEQ ID NO: 03:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 336 base pairs
(B) TYPE: nucleic acid (C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:203:
CTGCATGTNT TGGGGACACT TACGCCAAGG CGCCGCGTTC TCATTAGGAG CTGGGACCAG 60
AAGTGAATAA GCCAGGTTCC TGTCTCAGGG AGCTCCATAG CAGGACTCAG AACCACACAC 120
GGCCCTCTAG GCATTTKTGA AGCTCTGTGC TTCATTTTTT TTGCTTTGCC TCTAGTTTTG 180
CCTTTGCAGT ACCAATGCAG CCAGCCCATG TKTCCCCTCT ATGTGGAATG TTAACGATAT 240
TCCCACTGTT TCTGGTGTCC TTTCTGTAAT CAGAGCTGCC GTGACCATTC CAGTTCAGGC 300
ATCCTGGTGG CCTGGCTTTC TCTGGGGCAT AGAGCT 336 (2) INFORMATION FOR SEQ ID NO:204:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 393 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:204:
GGAATCAGAT GCTCAGGTGT CCAAGCAGGG ATAAGGACAG GCAAAATAAA TAACCCCCCA 60
ACCCCCATCG TCACTCTGCT GCAACACGAC ACAAAGGTTT AAAGATCTGG GCCCAAAGAC 120
TCTGGGTCCC TTCAAGCAAG CTCAGGTGGA AGGAGGTTTC CCCACCCCCC ACCAGGCCTG 180
TTTGCCCCAG GTTGCCCTAG GATGGAGGCA GTTCAGACCC TGGGTCACTG AAGCTGATAG 240
GAAGAACTNC GATATCAATG GCCTAAGCCT GCTGTNTGCC CAAGGGAGCC AAGGGCAAGA 300
GCCAAAGGGC CAATTTAAAG GACGTGGACC TGGGGGGCCA GAGGAGGCAC CACAGCCGAG 360
GGGAGCCACG CCCTGGGCCG GCAGGGCACA TGG 393 (2) INFORMATION FOR SEQ ID NO:205:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 390 base pairs
(B) TYPE: nucleic acid (C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:205:
GAGGAAGAGG ATGACCTGAG TGAGCTGCCA CCGCTGGAGG ACATGGGACA ACCCCCGGCG 60
GAGGAGGCTG AGCAGCCTGG GGCCCTGGCC CGAGAGTTCC TTGCTGCCAT GGAGCCCGAG 120
CCCGCCCCAG CCCCGGCCCC AGAAGAGTGG CTGGACATTC TGGGGAACGG GCTGTTGAGG 180
AAGAAGACGC TGGTCCCAGG GCCGCCAGGT TCGAGCCGCC CGGTCAAGGG CCAGGTGGTC 240
ACCGTACATC TNCAGACGTC GCTGGAGAAT GGCACACGGG TGCAGGAGGA GCCGGAGCTG 300 GTGTTCACTC TGGGTGACTG TNACGTCATC CAGGCCC1GG TTCTCAGTGT CCCACTCATG 360 GACGTNGGGG AGACGGCCAT GGTCACTTCT 390
(2) INFORMATION FOR SEQ ID NO:206:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 172 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:206: CTTTACTGTG GGTGTGGGTG TCACTGTCAC TGCCACAGCC ACTNGGAGGG ACACACAGCT 60 TTAACCCCTR TTTGCTTAGG NGAAGGGTGG GGGCATTCAG GGTTATAAAA CTAACTATAT 120 ACACAGAAGG TCCTAGGKAG AAAGCCACCC TGAGCACACA TGTCTAGGCA CA 172
(2) INFORMATION FOR SEQ ID NO:207:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 215 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:207:
AAGGCAATTA GAAGATTTAT TGAATATTGG TTAAAAGTAG ATTGACAATG ACATTAAAGA 60
ATAAAGTGTA ATTTATTTGG TGCTACTTTG TGAATGCTTC CAAGTACAAA TCATCTCACA 120
ATACCATATA CAACATACTT TCAATCACAA CTCAAATATA AAATAACCTA CAAAATCACA 180
TTGCTATAAT CAATATACAA TAATTGTATT TTTAA 215 (2) INFORMATION FOR SEQ ID NO:208:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 444 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:208:
GGAGTTCTCT TGTCCACGGA GAGCAGTGTT GCAGTGTATG GAATGCTAAA TCTTACCCCA 60
AAGGGCAAGC AGGCTCCAGG TGGCCATGAG CTGAGTTGTG ACTTCTGGGA ACTAATTGGG 120
TTGGCCCCTG CTGGAGGAGC TGACAACCTG ATCAATGAGG AGTCTGACGT TGATGTCCAG 180
CTCAACAACA GACACATGAT GATCCGAGGA GAAAACATGT CCAAAATCCT AAAAGCACGA 240
TCCATGGTCA CCAGGTGCTT TAGAGATCAC TTCTTTGATA GGGGGTACTA TGAAGTTACT 300
CCTCCAACAT TAGTGCAAAC ACAAGTAGAA GGTGGGTGCC ACACTCTTCA AGCTTTGACT 360
ATTTTGGGGG AAGAGGCATT TTGACTCAAT CCTCTCAGTT GTACTTGAGA CCTTCCTCCC 420 AGCCTGGGAG ATGTTTTTTG TATT 444
(2) INFORMATION FOR SEQ ID NO:209:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 338 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:209:
GCAGATCACT TGAGGTCAGG AGTTCGAGAT CAGCCTATAT ATGCAAGTAC ACACACAGGC 60
ACTCGCACGC ATGCATGCTC ATGCAACACA CATGTACACT CTACATGTAC AGCTCACATA 120
TGCATCCATA CACATGTGCA TGCTCACCCA TACACCAGCC ACACACAAGT ACTCATACGC 180
ATACATGGCC ACACACAAAG TACACACACG TACACCATAT GCATATGTAT GCACTCATAC 240
ACTCATACAT ATGTGCCCCC TCAGAGAAGT ACACAAGTGC ATGCGCATCA CACATGCATA 300
CGTGCTCATG CATACACACG GGACATTTCA TACACACG 338 (2) INFORMATION FOR SEQ ID NO:210:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 371 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:210:
GAGGAAGTAG AGCCTNAGGA GGCTGAAGAA GGCATCTCTG AGCAACCCTG CCCAGCTTGA 60
CACAGAGGTG GTGGAAGACT CCTTGAGGCA AGCGTAAAAG TCAGCATGCT GCAAGGGGAC 120
TGTAGATTTA ATGATGCGTT TTCAAGGGTA CACACCAAAA CAATATGTCA ACTTCCCTTT 180
GGCCTGCAGT TTGTACCAAA TCCTTAATTT TTCCTGAATG AGCAAGCTTC TCTTAAAAGA 240
TGCTCTCTAG TCATTTTGGG TCTCATGGCA GTAAGCCTCA TGTTATACTA AGGGGGAGTC 300
TTCCAGGTGT GACAATCAGG TTATTGGAAA AACAAAACGT GGTTTTGGGA TCTGTTTGGG 360
AGACTGGGGA T 371
(2) INFORMATION FOR SEQ ID NO:211:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 295 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:211: CCTCCCAACG TGTTGACATT ACAGGCGTGA GCACACGCAC CCAGCCCATC TAGCATAATG 60 TTTTGCATAG TTGTCAGCAG ATAAATATTG AATGACAAAA CTCAGATGGA GGAAAAAGAA 120
CAAAATAACC TAGTTCTCAG AAAGATTTAA TGAGCAAATG GGAAAATGTC AAAAAGATTT 180
ACAGACAGGG GCATCTTAGA GTCACTGGAA TCACACAGGC CTTCCCTCAG CTTGAGGGGC 240
TGCCTGGAGG TGGGGGTGGG GGTACACCTC CTCAGTGGGG AGAGACTTGC CAAAT 295 (2) INFORMATION FOR SEQ ID NO:212:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 370 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:212:
TGGCCGATAT GAGGGGGGTG GGACTGGGCC CCGCGCTGCC CCCGCCGCCT CCCTATGTCA 60
TTCTCGAGGA GGGGGGGATC CGCGCATACT TCACGCTCGG TGCTGAGTGT CCCGGCTGGG 120
ATTCTACCAT CGAGTCGGGG TATGGGGAGG CGCCCCCGCC ACGGAGAGCC TGGAAGCACT 180
CCCCACTCCT GAGGCCTCGG GGGGGAGCCT GGAAATCGAT TTTCAGGTTG TACAGTCGAG 240
CAGTTTTGGT GGAAGAGGGG GGCCCTAGAA ACCCTGTAGC GCAATGGGGT TGGGCGCCCC 300
AAAGGTTAAG TTTGAACCCG AAGAGCAAAG GAAGAGGCGA TCATCATAAG TGGAGGATTA 360
GGATTAGGAT 370 (2) INFORMATION FOR SEQ ID NO:213:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 302 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:213:
ATCTGTGGAA TAATCTGCGG GCTAACACGG ATAACTCAGT ATAAGAACCA CCCAGTTGAT 60
GTCTATTGTG GCTTTTTAAT AGGAGGAGGA ATTGCACTGT ACTTGGGCTT GTATGCTGTG 120
GGGAATTTCC TGCCCANTGA TGAGAGTATG TTTCAGCACA GAGACGCCCT CAGGTCTCTT 180
GACAGACCTC AATCAAGATC CCAACCGACT TTTTATCTGC TAAAAATGGG TAGCAGCAGT 240
GTATGGGAAT TTTCTCATAC AGAAGGGCAT CCCTCAAACC GGAAACCACA GAGATGCTAG 300
GT 302 (2) INFORMATION FOR SEQ ID NO:214:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 354 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:214:
ATGGATGAGT GGGCACCCCG CACAGGGCTG CAGGGTGGAA AACGCTCGAC GGCCAGGTGG 60
TGACTTGGGG GCAGAGAGCG CAGTGTNGTA GGGGAGGAGA GGTGGTGTCC CTGCTGCCTG 120
GGAGCCAGCC TGCCTGTNCT GTGGGCAGAG CAAGGCACTT TCTGCTGCCG GTGCTTCCAG 180
GGCCTAAGCA GCCGCTGCAC ACTCACCAGC GCAAGGCTCC TCTGCAGGGA ACGAGGGCTG 240
CTACCCATTT CACAGATGAG GGCAAGCAAG GACTTGCCCA GGGTTGCCCA NAGCAAGTGC 300
GTAACAGGCC CTGAGAAGAG NGCCAGTGAG CTCATCCTGA GTTAATTATG GGCT 354 (2) INFORMATION FOR SEQ ID NO:215:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 260 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:215:
TGGTTCAAAG TCTAGGCCCT CTTNAGAGCT GGCTGATTCA GCTTGCCAAC AGTGACATCA 60
GGGTGAGGCT TCCTCTGTCC ACAGCATTAG CTGCGAATAT CCTCATGGTC ACAAGATGGC 120
TGCCAGTGGC CGTCAGGGTG TGTGCTTCCT TGTTCACATC CAGTGGAAGA GTGACAGCCT 180
GCTCCCCTTA GCTCTCTGAC ACCANTGTGA AGGTGCCANG AACTTACTAG CAGGNCTTTC 240
CTCATGACCC ATTCAACAGG 260 (2) INFORMATION FOR SEQ ID NO:216:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 232 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:216:
CTTGGACAAG ATCTGGGATA ATTCTCTGGA TTACCTGGCA GAGACTTTTK TTCTCTTCCC 60
TTACTGTCTC CCAAATAAAC AGTCTCTCAC TCTGTTGTGA GCCACCTGAA GCTGTGATAT 120
TTCCAACGAC TGTAGGAGGA AAAAATTAAG GGGAGAGAGG AAAACAAAAC CAACCAACCC 180
CTAANATCAT TTNTTTATTG TACATAACGA CCTCATTCTC CTGTATATGC GG 232 (2) INFORMATION FOR SEQ ID NO:218:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 219 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:218: CTGCAACCAT CCATACCTTT TNCCCGTGGC TGCTATGGAG TCCCCCAAAC TCCCCAGTGG 60
GGCTTATGAG GGTGGGGCAC TTATTANGTN GTCTGGGAAG CTCATGCTGC TCCAGAAGAT 120
GCTGCGAAGC TGAAAGGAGC AAGGACACCG AGTGCTCAAT NTTCTCGCAG ATGACCAANA 180
TGTTAGCCTT GCTTGAGGGC TTTCTTAGNC TATGAGGCT 219 (2) INFORMATION FOR SEQ ID NO:219:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 390 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:219:
GATAGGTAGC AGAGACCAAG GCGCAGGGTG CTTCAGATGA GCAAGAGAAC CCAGTCGAAC 60
CAGATACCCC AGGTGGGCCG GAGGGACCCC AGACCTTCAG AGGGCTGCCC TGGTGTTCTC 120
CACAGTGCAG TCCCTCTGTA TTCCCAGAGT GGGATCGGGG CTTTCAGCCC ACCCTGATGC 180
CTGCCCTCCA GGATGGCTGG TTTAGTCTGG GTCCATGTCC CAGACCCCTC TATTCTGCTC 240
CAGGACAGCA GGACTTCAGG TCTTTCCTGG GGGTGGATAT AGGAGAAAAT TTCTGCCTGG 300
CACACACCTG GGCTCCAACC ACTTGCCAAG TGATTCACTC TTAGGCCCAG GGGGAACACA 360
ATGACTATCA TTACTGATGC AGACCTGGCT 390 (2) INFORMATION FOR SEQ ID NO:220:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 382 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:220:
TTTTTGTTTT GTTTTAATAT TTTTGATATT CTCTTTGCAT TGAAATGGTA TAAATGAATC 60
CATTTAAAAA GTGGTTAAGG ATTTGTTTAG CTGGTGTGAT AATAATTTTT AAAGTTGCAC 120
ATTGCCCAAG GCTTTTTTTG TGTGTTTTTA TTGTTGTTTG TACATTTGAA AAATATTCTT 180
TGAATAACCT TGCAGTACTA TATTTCAATT TCTTTATAAA TTTAAGTGCA TTTTAACTCA 240
TAATTGTACA CTATAATATA AGCCTAAGTT TTTATTCATA AGTTTTATTG ANGTTCTGAT 300
CGGTCCCCTT CAGAAATCTT TTTATATTAT CCTTCAAGTT ACTTTCTTAT TTATATTGTA 360
TGTGCATTTT ATCCATTAAT GT 382 (2) INFORMATION FOR SEQ ID NO:221:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 314 base pairs
(B) TYPE: nucleic acid (C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:221:
GACTTTGGTT TATTTAAAAA ACAAGCCAAA AAAAAAAAAA AAAAACCCCA ACTTTATATA 60
CAAAGTCAAA CTGAAACCAC GGWTTATGGA AAGAGGCAAG AWTTATGGGT AACAGGGGAG 120
AAGGCTGGGC CAGAGCCAAT ACCACATTCT GAACACAGGA GCCACGGGAA AGAGGTGCTG 180
GTTTCTTCTG GCAAGACCGG GGTGACTGGA ACGCAGTGGT CCTACTGGCA AACCCAGCCC 240
AACACTGAGC TCTTTCTAGC ATGGACTCCA TTCCCGTGAT TGGCCAAGGG AGACCCTTCC 300
CCCAGGAGGC CTGT 314 (2) INFORMATION FOR SEQ ID NO:222:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 342 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:222:
TTCCTTCTCT GCGGCGGCAC GTCGCNAGCA GCCTGCTTCG CCCCGTCGTC AACTTTGAGC 60
TGGAGGAGAA GCAACTTTGG CAGTGGCCGC GGGGTGGGAA TCCCGCTTCT CCTCGGCAGC 120
AGTAGGCTCG CAAGTCGCTG GGGTTAGGTG GGGCAAGAGT TTCGCCGGCG CATCAGCGCT 180
TGCTTCGGAC TGTTTGCAAC GTGTTTCCAG CGAGCTGGGA GCGGGGGTTG TGACTGCGAG 240
TCGTCTGGGG GAGGGGGACT TGTTTTTCTT TTCCTCTAGA GACCTCGGCT TTCAACTGGA 300
TCAAACGTTG TCGAAAGGAT GTAAATAGGC AAGAGCAAAC TG 342 (2) INFORMATION FOR SEQ ID NO:223:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 376 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:223:
GTGATGGCTG CCTTGAGGGG GACCATCATG TCGGAGACGC ATTGGTGCAG GTCTCACCCC 60
ACAGCCCATG CCCAGCCTCC TGCAGACTCA GGTCATCCAG CTGGTCGATG GCTCTTTGCA 120
TACCTGGTGC CTTCTCCTCT CGGGCTTGGC AGGCTTCTCT GGGGGCTTCT CAGATGACTC 180
TTTTGCCTTC TTCTCTGTCT TGGCTAACTC CTTGGCCAGC TCTGAACGTG CCTCCTTGGC 240
TCCCTCTTCT ACCACCTCCT CCCGTTTGGC CAACTTGCTC ACGGCCGTCT TGGTAGTGGC 300
TTTGAGGCTC TCCTTGCTAT CAGCCCGCTG TTTGATTTTG CTGGGCTTGA GGTTGGTAAG 360 GCACAGCCCC AAGAAG 376
(2) INFORMATION FOR SEQ ID NO:224:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 445 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:224:
GTTGATAGAC ATTGGCATTG GGGTTGCTTC CACCTTTTGG CTGTCATGAA TAATATTGCT 60
ATGAACACTA ATGTACAATT CTTTGCCTGA ACGTAAATGT TTTCATTTCT CTTGGGTATT 120
TATCTAGAAA TGAAATTGCT GTATGTTAAC CCTTTGTTTA ACCTCTTGAG GAACTGGCAG 180
ACTTTTCCAA AGCAGCTGCA CCATTTTAAA TTCTAACCAG CAGTGTTTGA GGGTTCCAAT 240
TTCTCTATAT CCTTGGTAAC ACTTGTTATC TGCCCTTTTG GTTAGAGACA TCCTAGTGAG 300
TGTGAAGTGG CATCTCACTG TGGTTTTGAT GTGCATTTCC CTGATAGCTA ATTGTGTGGA 360
TCCCTTTTGC TTTTAGTGGA ATGAAATATC TGGTAGTCTC GTATGCCAAA CTAAAGCTAA 420
AATTAAAATG ACTCTGCATG ATGGA 445 (2) INFORMATION FOR SEQ ID NO:225:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 403 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:225:
TGCTCTCGGG ACAGTTTCCC GGGCAGCTCC TGGCCAGCTT CCAGCCCAGA GTCCTCAAGT 60
CCAGGGCACC TTGGGCCCAG CGCAGGCAGA ATCCGAGGTG GTCCTGGCTC TACCCTGGGC 120
CTCCTACTCC CCAGCACCCC TGGAGGAGGC AGGGGCTCCC CGCCGCCGAG GCTGCCTGCC 180
CTAGGCCCAC CTCTGCATGC TGCTCATGGG GCCACCCTGC CTCCTGGGCC CTCACTCTGC 240
CTAGGGGAGC TGGGCCAGGC ACTAGCCTTT GCCCAGGGAG GTGGGCCTCA GGCTGCCCAG 300
GTGCCTGCAC CCCAGCCGGG CTTCTCTGGG GCCTCCCCGT CGTCAAGCCT ATATCCTGTC 360
TGTCCCCACC CCAGCTGTCC CTTGCCAGGG GACTGGCATA AAA 403
(2) INFORMATION FOR SEQ ID NO:226:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 440 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:226:
GTGCCTTAAG GAGAGAGATT GTGTTCTTCC TCTCTCAGGG GTGATAACTC AGGAAGCCTC 60
TGGGTTGGGA AGACCATCAG TTCTTTTGTC TTAGGTTTCT TTTCCTGTCC CTCTTCCATC 120
CCCAAGATGT GACCCCATAA AAATTTTTCC TGAGTTGGCC AGGCATGGTG GCTCACGCCT 180
GTAATCCCAA CACTTTGGGA GGCTGAGGCG GGCGGATCAC GAGGTCAGGA GTTCGAGACC 240
AGCCTGACCA ACATGGTGAA AACCCCATCT CTACTAAGGA TACAAAAATT AGCCGGGTGT 300
GGTGGCACAC ACCAGTAAGT CCCAGCTGCT CAGGAGGCTG AGGCAGGAGA TTTGCTTGAA 360
CCTGGGAGGC AGAGGTTGCA AGTTAGGCCG GGATTGCGCC GTTTGTACTC CAGCCTGGGC 420
AAGCAGAGCA AGACCATCTA 440 (2) INFORMATION FOR SEQ ID NO:227:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 426 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:227:
GACCAAGAAG TTCCGGTTCG AGGAGCCCGT GGTTCTGCCT GACCTGGACG ACCAGACAGN 60
CCACCGGCAG TGGACTCAGC AGCACCTGGA TGCCGCTGAC CTGCGCATGT YTGCCATGGC 120
CCCCACACCG CCCCAGGGTG AGGTTGACGC CGACTGCATG GACGTCAATG TCCGCGGGCC 180
TGATGGCTTC ACCCCGCTCA TGATCGCCTC CTGCAGCGGG GGCGGCCTGG AGACGGGCAA 240
CAGCGAGGAA GAGGAGGACG CGCCGGCCGT CATCTCCGAC TTCATCTACC AGGGCGCCAC 300
TTGCCACAAC CAGACAGACC GCACGGGCGA GACCGCTTTG CACCTGGCCG CCGTTACTTA 360
CGCTCTGATG CCGCAAGGGC TCTTGAGGCC AGCGAAGATG CCAACATCAG GCAACATGGG 420
CCGAAC 426 (2) INFORMATION FOR SEQ ID NO:228:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 278 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:228:
CAGGACCAGG AGAAGATCCT GGAAGATGCA GTGGATGAGT GGACGGGCTT TAACAACAAG 60
GTTAAAAAGG CCACTGAGAT TGTTTTAGAA AACCAACAGC AAAACACTGA CAAGGTACAT 120
AAATACAGAT TGGACATTTT AGGGTAAATT CACTGTATTT CCTACTTGCT TGTAGGAAAC 180
CGAGTAAAGT GGAAAAGCTG TCCTGATCAT ATGGCATGCA CACCAGACTG CAAAAGGNCG 240 TCCACACTAT TTAACAGGAC TGTGGCAAAA TAGCTTTA 278
(2) INFORMATION FOR SEQ ID NO:229:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 425 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:229:
TTTTTGTTCC CAAGCCTTTG TGACTGACTT TAAATCCTCT CACCTGCAGA ACAGAGATGG 60
CTTCAAAGTG GGGAGTGAGG GAGTGAGCGA GGACCCTGGG CTGAGACCTG TTTTTCTTCC 120
ATTTCTGCTG TGGCTTCCCA CAGCTCCCTG GTTCCACACC AGGCCCTGCT CTGCCGCAGA 180
AAATGGATTC CCAGGCCACA GAGCTGTCAG GCCTTTGACT TTGCAGAGAC CAAGCACCCC 240
AGAGGCTGTG CGACASGGCT AGTCCCTGGT GGGCCGGTCT GGGGCATGGG GGGCAGGGAG 300
ACTKGGAGAT GGGGAGGGCG TTGAGAATCC GGGGGGTCCT GGATACTTGA CAAATTGGCT 360
CAGGTCTTAG CTYTGGYTGC CCCACTGATT GTGTTGCTTG GCAAGGTGCA AGTYTTCGGC 420
TGTTC 425 (2) INFORMATION FOR SEQ ID NO:230:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 382 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:230:
TTGGAGGATG TGCTGCCCCT CCTGCAGCAG GCCGACGAGC TGCACAGGGG TGATGAGCAA 60
GGCAAGCGGG AGGGCTTCCA GCTGCTGCTC AACAACAAGC TGGTGTATGG AAGCCGGCAG 120
GACTTTCTCT GGCGCCTGGC CCGAGCCTAC AGTGACATGT GTGAGCTCAC TGAGGAGGTG 180
AGCCAGAAGA AGTCATATGC CCTAGATGGA AAAGAAGAAG CAGAGGCTGC TCTGGAGAAG 240
GGGGATGAGA GTTCTGACTG TCACCTGTGG TATGCGGTGC TTTGTGGTCA GCTGGCTGAG 300
CATGAGAGCA TCCAGAGGCG CATCCAGAGT KGCTTTAGCT TCAAAGGAGC ATKTTGACAA 360
AGCCATTKCT CTTCAGCCAG GA 382 (2) INFORMATION FOR SEQ ID NO:231:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 398 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:231: GAGGCTGGAG AATCGYTTGA ACCCAGGAGG CGGAGGTTGC AGTGAGCCGA GATGGCGCCA 60
TTGCACTCCA GCCTGGGCCA GAGCAAGGTT CCTTCTCAAA AAACTTGGAA ATCTGTTGGG 120
AAGTAGGGGG AGGGCAAGGT TAAAACCTAT GCAGGTGTGT CAATTAGACT TGTTCCAACT 180
TGAGAACCTG AATTTTGCAT GTAATTGAAA TGTTCCAGAA CAAGTCTGGC AGTTTCATAA 240
GGGAGTTTTT AGATGCCAAT ACATTGCAGA TAACCATATT GGTTACATTA GGGGAATGAG 300
CATGGGATAG GTGCCTCCCA GTTGGTAGGA TAGCATGAGG AGGTTTCAAA AGTAACCSCT 360
TTAAGGGTTA TGTCCAGTAT TTGCTAAGTA ACCAAGGT 398 (2) INFORMATION FOR SEQ ID NO:232:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 272 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:232:
GGGGCTGCAG ACTGAGTTAT TTTATTTCGC TATTTCCAGT TTGAAGCTAC TATCATGGGC 60
GTTTAGAGTT ATACAAATGA CACTTACAAA AAATAAAAGA CCAAGACACC CAGAGTGAGA 120
TGCATGTTGG GGACGGGGGA GGCTGGCAGC AGGGGGGCCC CGGCGGYTCA CCCCAGGGCT 180
CCCGGAGGGG CGACGCCTGG CTTCATCCAC CCGGGAGGCC CAGGGAGCAC CAATCACAGC 240
AGGGGCTCTG GCCCAGGTGT CGGCAGCCCA GG 272 (2) INFORMATION FOR SEQ ID NO:233:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 364 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:233:
ATTTTACAGT TTTATTTTTA AATCATTTAC ACATATTCAT ACAAAGAAAA ATAAATTTCA 60
GGATGGAATC CTGGGGACCA TGGTAGTTTA AAAAAAAAAA TCTCTCTGAT CATTAGCTAC 120
TAAAGACANG GCAAGAGGCT TAGCAGTCAT TTCTGGGGGT TAGTGTATCT CCCCATGCAG 180
GGGACAACTG NGAAGAATCC AAGCTGCTCC CTCATCTTCC TTCGATCTAG ATGGGGGAAG 240
GGGATTTTCC AATGCTCTCC CCTAGAAACA TTTCAAGAAG TACAGCAAAG GCTTATGGTA 300
ACACTGGAAC CTATTTGCTA GAAATCTGGC AAGATTGCAC TTTCTGAACC CAATTTTCCT 360
ATAA 364 (2) INFORMATION FOR SEQ ID NO:234: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 217 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:234:
GGCCAGGAGC CAGAGGGCCC CGGGGCCACC CCTGCCGGGG AACGTGATGA CCAGAGTCCA 60
GACAGTGTCC CAGAGAGGCC GCGGCCCGCA GACCGGAGGC TCTGTCTGCC CTNCGTGGAC 120
GCCTCGCCAC TCCCAGGGAG GACGGCCTGC CCGTCGCTGC AGGAGGCCAC GCGGCTCATC 180
CAGGAGGAAT TTGCCTTCGA TGGCTACCTG GACAATG 217 (2) INFORMATION FOR SEQ ID NO:235:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 221 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:235:
AACTTTAAAG TTAGGATTTT AAAATATTTG TAACTGGCTA AATTTTAAAG TCGTGACAAA 60
TAATTACTTA GGTTCAGAAA TATACACACA CTTACTCTTT AGCCAGTTTC TTTCAAGGTN 120
TTACTGTCCC ATCAGATATC TAGCCATTTK CCTTTGCAAA TTACATACCT TCTTAAGAGT 180
GTATTTTTAA GATTATTACT TATGCTTTAT GATGATATAG T 221 (2) INFORMATION FOR SEQ ID NO:236:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 221 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:236:
ATAAATGGGT TTCTCACTCC TTAGGGACAC GATTGGAAAC AATACATCCC ATGAACACAG 60
GTGAATGTCC CTGGTTATCC CTGAGCTGGG CAGTTTCACA CAATCANTTT TNCTCTGAGG 120
CCAAAGTCTG TGGTTTGATC ATCTTAGCAG CTTCCAGAAC AGAAAGTAGG TTTACTTTGT 180
CTCCAAANTC TNATTCTCGG TGCTCAAAGA AGAATGACCT G 221 (2) INFORMATION FOR SEQ ID NO:237:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 251 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:237: GACATCTTTC TAAGATTCTC TGTGGGAAAA TGACTGTCAA TANAATGCGG GTTTCTGGGC 60
CATTCGTCTT ACTTTCATTT TTTGATTACA AATTTCTCTT GACGCACACA ATTATGTCTG 120
CTAATCCTCT TCTTCCTAGA GAGAGAAACT GTGCTCCTTC AGTGTTGCTG CCATAAAGGG 180
GTTTTGGGAA TCGATTGTAA AAGTCCCAGG TTCTAAATTA ACTAAATGTG TACAGAAATG 240
AACGTGTAAG T 251 (2) INFORMATION FOR SEQ ID NO:238:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 327 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:238:
GTTCGTGGCT GTCACAATAA TGCTGTGATA ATGCTGTGGT TTCCCAGCAG GGAGGTGGGA 60
GCGGGGAGGG GGCTGCAGCC TGATGAGAGC CAGCTGAAGG AAGAGCTGCC TCTCCCTTCC 120
TAAGCCCCTT CCCAAGGTCT GCCCCACCGC CCAAACCAAA GACCACTCCG AACAAAGTGA 180
GGATGTGGAT GCTCTTGCTG GGTCCGCTGT TCCGCAGAGG GAAAGAAAGG GTAGCTGCAC 240
TGACCCCACT GTCCCCATAT ACAAGGGTTK GGGGGCAAGA GCATGTGGCT ACTCCCAGCA 300
AGGGRAAAAT GGGAGGAGCA GTAGAAA 327 (2) INFORMATION FOR SEQ ID NO:239:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 285 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:239:
ATTATTAGTT TATGGTGCTT TAAACCTATC AAAATAGTTG TAAGTAAATG GATTTCTTGT 60
NCTCCCAATA ACAATTCTCT GAGCTAGGAT AGATGTCTTT CTGGCCATTT TACAGGTGAT 120
GACACTGACA TAGGGACTGA GTGGGTAGCT TAAGTNCCAT GGTTACCAGG AGCAGGACCN 180
ACGTTTCCTG NCTCCCAGTC TCATCCTGTT TTCCACTGAC CAGGTTGGTT GCTCCCTTGG 240
AAAGCAGTCC CTGAGAGTTG ACTTAGAAGT TCAGGGNGAA GAGGT 285 (2) INFORMATION FOR SEQ ID NO:240:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 349 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:240: TTTTGCCATG TTGGACAGGC TGATCTCAAA CTCCTGGCCT CAAATRATCT GCCCAGCTTG 60
GMCTCCCAAA GYGCTGGGAT TACAGATRTG AGCCACTGCA CCCAGCCTGA CATGCCATAG 120
TTTCAGCATT TTCTTGGGCA ATGATCCAAG CTGAAGGCTG GTCTGAGGGA TCTSAAGAAG 180
CGTATGAGTT GGAAGAGAGG GACAGAAAGG AAGAAGACAT GTGAAGAGAG AAAAGGAAGG 240
AAGCTAGCAG AGGAATGCCC TCCAATAGAG ACTGCTGCCT GAAGCTCAGC CCCTCTGAAG 300
ATAGGTAGGC CAGGCTGGCT TAGCTGAGGC AGTGGGTTAG ACCAGCCCT 349
(2) INFORMATION FOR SEQ ID NO:241:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 233 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:241:
GTGCAGCGGT CTGCCTTCAT CTTTTAATGG CCGGTGCGGT ACAGTTAGTG GACAGACGGG 60
GGATGGGACA CAGCAGGGGT GAAACAGGGC AGTCACAGCC GGGGCCGGGG ATCTGGAAGC 120
GGGGGCGGTC CTCCCCCTGG AAACACCGTN TCTGGAAGGA CACCCTTAGG ATCCCCTGAC 180
CTCARGGTGC CACCCACACG GGCCTGGTGT TCTGGGAGGC CCGGCTKGAG TGA 233 (2) INFORMATION FOR SEQ ID NO:242:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 372 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:242:
ATATGTACTA CATTTGGTGG AATACGCATG TACAATTCTT CAAAAATAGT AAAGAGCAAA 60
ACAAACAAAA AATAGTAGAA GCACTGGAGA AATACACTAT GGCATAAACT AGTTACGGGT 120
GGGATGTCAC ATGGACCATA TCTACACTCT GTGGCAACCT TCTTACCTGA CTCCAAAGGA 180
TCAGATAATC AAACAGGAAA TTATGGTAGG AAATCAGAAA ATTGAAGTAT GCATTCATAT 240
CCTAAGCATT TTATTTTAGC TCAAAATATA AAAATATTCA TCAGTTAGCC AAGCTTTTGN 300
GATGAGAGAT CATAGCCTCC TCTTTGATAG GGGGTTTCTT GGGTTTCCTT GATTTCATGT 360
TTCAGAGTTT TT 372 (2) INFORMATION FOR SEQ ID NO:243:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 256 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:243: CTCACACATT CATACCCAAG GAAGAGGCAA ACACACTCAA GTCCAGAGTT CCCAGTGGTG 60 CCGCCCAGAC CTACTGTCCC GGGGGTGTTA TGGCTGTCCC TCGGCTTCCC CAGAGCAGCC 120 AGGACAGCCT GCACCGNCTN CCAGACTCTC GCAGGAAGGG GAGCTCTGCC CTGGGGAGGA 180 AACTNACAGG CTGGGAGACA AGACTCCCAT CGCAGGGACA TGCACAGCAG CAGCCACAGC 240 CCCGCGGACG GGGCAT 256
(2) INFORMATION FOR SEQ ID NO:244:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 220 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:244:
CAAATGGCAG TTCTCGAGAA TCGACGAGGA ACTTAAATCT GGACTCAGGG TTTCAGTGCG 60
GTCTCCGACT CCCACCACCC CGCCCCTCCG NCTGTCTCGC CGCCAGGNGT GACCTCCACG 120
CGAAGGAATC TTCTTCGGAT GGGTGCACCT TGCCAANAGG TGTGGCACCT GGNGGACTAG 180
GAGGCGCCTC CANACTAAGG GCGCTCANTG CGGCGTTCTT 220 (2) INFORMATION FOR SEQ ID NO:245:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 239 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:245:
TTCATGCTCA TGTAACCTTC TTAATAGTGC CTTGTCTGCT GGGTTTGTAG CTGTAAGAGT 60
TCTGCAAACT GGCCCTATAA AAATATTGAT GCTGTCCATT AAAATGAATC TCTCTCTCTC 120
ACTCAGTCTC TCTCTCTGTC TGTCTCTCTT TCTTCTCTCT CCTGCCATGT GTGTGTCTCT 180
CTCTACTCCT CTGATTTTGN CCTCTCTCTC TATTCTGCTA CTCTCTCTCC TCTCCTCCG 239 (2) INFORMATION FOR SEQ ID NO:246:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 269 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:246: GGTTTCACCA GCGTTTAATG TGCTCTGATG TTGACCGTCC CTCTNAGTNT TCTGGGGAGG 60 AGGGGGTGGG GCGGAGGGTC AGGAAAGCAG GCTCAGCTTC CAGGGTCAGG GAGTTGTGGG 120
CCCAGAGGGG CTGTCACAGT GGATGCACCC TGCCCCCTCC CTCGCCAGAC CCGAGGGTAG 180
GGCAGAGGCA CCTCCTCGNC AGCCTNTGGG CTGCACCCAC AGGGAATNGA GGGGAGGGGC 240
ACCATTACCA CTGGACCCAC CAAAGACCC 269
(2) INFORMATION FOR SEQ ID NO:247:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 297 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:247:
CTATTCAAAG TTTACTGACC TCCCCAGCCA GGCAGGCCAA CCCTTCCGAG CAGGGGAAAT 60
GTCCATCTAG CTGCCCTCTG CTGGGTTGCA GCCTATGCCA TGAGAGGGTA CTGGAAGCAG 120
GAGGGAGCCC TGGCTAGGGC AGGCCTTAAA CGCAAGGGAA GCTGAGCAGA GATCTGCACA 180
CTCAACCCCA TTTGATATTC TTCTCCTCCT CAGTCATGGC CAGCGTGTTG GTGACTAGAC 240
CGGTGCCAAT AGTCCGGTTG CCATCTCGCA GGGTGAAAAG ATGGCCTTTC TCTTAAG 297 (2) INFORMATION FOR SEQ ID NO:248:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 281 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:248:
ACAACAAGCA CACCAACTAT ACCATGGAGC ACATCCGCGT GGGCTGGGAG CAGCTGCTCA 60
CCACCATTGC CCGCACCATC AACGAGGTGG AGAACCAGAT CCTCACCCGC GACGCCAAGG 120
GCATCAGCCA GGAGCAGATG CAGGAGTTCC GGGCGTCCTT CAACCACTTC GACAAGGATC 180
ATGGCGGGGC GCTGGGGCCC GAGGAGTTCA AGGCCTGCCT CATCAGCCTG GGCTACGACG 240
TGGAGANCGA CCGGCAGGGT GAGGNCGAAG TTCAACCGCA T 281 (2) INFORMATION FOR SEQ ID NO:249:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 383 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:249: AGCGCATCCA CACCGGGGAG CGGCCCTACC CCTGCTCCTA CTGTGGCAGG AGCTTCCGCT 60 ACAAACAGAC ACTCAAGGNC CACCTCCGTT CAGGCCACAA TGGAGGCTGT GGGGGTGATA 120
GTGACCCATC AGGTCAGCCA CCCAACCCAC CAGGTCCCCT CATAACTGGG CTTGAAACTT 180
CTGGCCTGGG TGTCAACACT GAAGGTCTAG AGACCAACCA GTGGTATTGG GGAAGGGAGT 240
CGAGGGGGAG TTTTGTAAAT CCAAATCTCT GTGGNTTCAT GCTTTGTATA TGCTCACAGC 300
AGGGCACAAT AATCCAAGAG AAGGTCTGTG AGCCCCNATC CAACACCCAC AGTAATTATA 360
ATCTTGGCAC ATCAATGGAA TTT 383 (2) INFORMATION FOR SEQ ID NO:250:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 397 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:250:
GTATCCTACG TTACAACAAT AATATCATGG GAGAAATAGA AATAGCCTAG TTTGCTTCCA 60
ATAGAAACTG CTTTTAACAT GGGCTGTATA TAAAAATATT AAAGAGAAAC AAAACTGTAC 120
ATTTCCTCAT TGCTCCGCTA CAGACAACCC ATGTCATAAC CTTGTTGCAA ATATTTTTCT 180
CCTATAGCAG TAAGTACAGC ATTAGAAGGT GATTAGAGAG TCTGTTGATG AAACACAAAT 240
GTATGTTTTT ATTGATTTTT ACTTTAGAAC ACTACAGAGT TCCTGGGACC GGGGTGAANG 300
GCATTTAGCT GGGGTGGTTT GTGTGGGGGT TAAATACCTT CCCACTTGCA AGTGACTTGC 360
CTGTNCCCGC TGCGGGAATC CTGTTNCTTG GGTGGGA 397 (2) INFORMATION FOR SEQ ID NO:251:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 276 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:251:
GGCCATAAAA GAAAGAGCCT GTTACCTATC CATAAACCCC CAAAAGGATG AGACGCTAGA 60
GACAGAGAAA GCTCAGTACT ACCTGCCTGA TGGCAGCACC ATTGAGATTG GTCCTNCCCG 120
ATTCCGGGNC CCTGAGTTGC TCTTCAGGNC NGATTTGATT GGAGAGGNGA GTNAAGGCAT 180
CCACGAGGTC CTGGTGTTCG CCATTCAGAA GTCANGACAT GGACCTGCGG CGCACGCTTT 240
TCTCTAACAT TGTCCTCTCA GGGAGGGNTC TACCCT 276 (2) INFORMATION FOR SEQ ID NO:252:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 314 base pairs
(B) TYPE: nucleic acid (C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:252:
CCTGAACAGT CTGTTTCATT TGACTGTTTG GGGGTCTCCC AGTTTAAGCA AGATATTTAA 60
GCCTTATTTC TCTTGGCATG CTTGGATTCC CCAGTAAAAA AAACTCCTGC CCTGGGCTGA 120
CAATCAAAGT TCTGGGAACT AATATGGATA AGCAAGCTGG AAATGGAGAA GGCTATTCAC 180
TGTGCCTGGG TCCTACTGTT TTCTGGNTGG GAACTGCTTT TCCATTAGGC CTGGTGTGCC 240
CTGGAAGGGA NGAGCCTCTT GCAGAGACTA CAATCTTGGA TGGGTCCTTT GCCAAGTTTG 300
AAGGTAGGAA CCCA 314 (2) INFORMATION FOR SEQ ID NO:253:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 293 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:253:
GAACACTCTG CTCCAGCCAA GGTGGTGAGG GCAGCTGTTC CTAAACAGCG CAAAGGCAGC 60
AAGCCACAGT CCCACAAGCC TCAGCCTACC CGTAAACTGC CACCCAAGAA GGACATGAAG 120
GAACAGGAGA AAGGAGAAGG GAGTGATAGT AAGGAGAGTC CAAAAACCAA ATCAGATGAA 180
TCAGGGGAGG AAAAGAATGG AGATGAGGAT TGCCAGCGAG GCGGGCAGTA GAAGAAAGGA 240
AACAANCACA AGTGGGTTCC ATTACAAATA GACATGAAGC CTGAAGTGCC CAG 293 (2) INFORMATION FOR SEQ ID NO:254:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 413 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:254:
CTTTTTCTTA ATATATTAAT ATTTACCAAG GCAAGACAGT GATTTATGGA CATTTAAATT 60
AGTTTAGCTT TGTTCTGCTG TTCTAAAACA TTGTGTACTG TCTGATAGAC TTTTAAAAAA 120
CAGTGCTTTT CCAGGATGAT TTATGATATG CAGTATTGTT TATAGATGCC CATGGCTTAA 180
CCTTGAAAAG TCAATTAAGT GACACAATTA AGAGAGATAT GAATAGTGGT AGAAAAAGCA 240
TGTACTCTGG ATAAGTGGGG GTAAATCTAG TATTTGTTAT TCCTGTCAGT AATATTGTCA 300
NTAGTATTTT TTAGAAGGTT TAATTTTTTT ATGGGTTATA AATTCATGTC ACTCTTCTGC 360
AATGGGTACC ATCAGTGGGA ATGCNGGAAT TATCCATGCT TTGGGGGTTA AAA 413 (2) INFORMATION FOR SEQ ID NO:255:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 376 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:255:
GGGTCCAGGG GAGAATCAAT ATATCTAGTA TAGTTTATAT TTGTACCTTC TCTCCTTAAG 60
AGTTACAGTG AGTGACTCTA CTCCTCAAAT GGAGCACCTC TCTCCAGGAG AGTAAGAAGA 120
TCACATAAAT AGAAAGTGAG CTTTGGACTC TAACAGACAT AGGTTCATAT TCAACTCTGC 180
TACTTAATAT CCATATTGGT TTGAGTTATT TAACCTTGAC AATCCACACT GTAAAATGGG 240
TAAATAATAA ATACCCTCCT CTCAGAAGTG TTACAAAGTT TATATGAAAT AATGTGCTTA 300
AAAAGCTGGG TACATAGTAG GAGCTTAGTC ATTGTTTATT TTCTCCCTCA TACCCATACA 360
TGNTTCATTC CTACTG 376
(2) INFORMATION FOR SEQ ID NO:256:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 241 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:256:
GTAGAGATGG GCTCACTATK TTGCCCAGGC TGGTCCTGAA CTCCTGAGGT AGGAGGATCG 60
CTTGAGCCTG GGAGACAGAG GTTGCAGTGA GCCGAGATCA CGCCACTGCA CTCCTGCCTG 120
GGTGACACAG TGAGACTCTG TCTTAAACAA AACAAAACAA AAAAAGGCCA GGCGCAGGGG 180
CTCACACCTG GTAATCCCAG CACTTTGGGA GGCCAAGGTG GGTGGATCAC CTGAGGTCAG 240
G 241 (2) INFORMATION FOR SEQ ID NO:257:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 406 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:257:
CAAGGGTGTC CTTCGCCAGA TCACTGTTAA TGATTTGCCT GTGGGACGCT CCGTGGATGA 60
GGCTCTGCGG CTGGTCCGAT TAAGAAAACC AAGAGAGGCC GGGCACGGTG ACTCACGCCT 120
GTAATCCCAG CACTTTGGGA GGCCGAGGTG GCGGATCATG AGGTCAGGAG ATTGAGACCA 180 TCCTGGCTAA CACAGTGAAA CCCCGTCTCT ACTAAAAATA CAAAAAAATT AGCTGGGCAT 240
GGTGGCACGC GATTGTAGTC CCAGCTACTA GAGAGGCTAA GGCAGGTGAA TCGCTTGAAT 300
CCAGGAGGTG GGGGTTTCAA TGAGNCCGAG ATCGTACCAC TGCACTCCAG CCTGGGGCAA 360
CAGAGTANGA CTTCGTAACC CCCAACCAAC CCNCCAACCC CCCGCC 406 (2) INFORMATION FOR SEQ ID NO:258:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 157 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:258: GAAAAGAAGG AAGGAAAGAG GGGAGGGAGG GAGGAAAGGA GAGAGGGAGG GAAAGAAGGA 60 GAAAATGCTG GAGCAAAGGA GGTTGGTTAC ATGATTTCTC TAATGGCAAT GAGCTGCTTT 120 CTGGATGAAA TACAGAATCA GAGCGAGACT CCGTCTC 157
(2) INFORMATION FOR SEQ ID NO:259:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 361 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:259:
AAGCAGATAT AAATGGGACC ACTGTGAATC AAAGGGGAAA AATTCCAGGA AAAAAAAATT 60
CCAATAGCTT CACAGTTTAA CTGAGGTTTT GGAAAAACTT AAGTGAATTC AGCTGATGTT 120
TGAAATATCT GTCTACATTT AATTAGATGT GTTGTATTTA CCAAGGAGGC ACAAATATGT 180
AGTTCTGTAG ATTTTAATAC TAACTTTTCC AGTAAGAAAA ATAATACCAG GTGATTTCAA 240
AAAGGGCAGT GATCTATAAA CACTCAAAAT GCATCTTTGA ACAGGGGAGC AGAAATAGCT 300
AATTTAATGA AAACAAACCT TAAGCACTTT ACTTGGCTTC TAATAAGGCA TCCCAAGAAA 360
A 361 (2) INFORMATION FOR SEQ ID NO:260:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 349 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:260: CAATACATGT ATACAGTGTA CACTGATCAA ATAAGAGTAA TTAGCATATT TATCACCTCA 60 TTTCTTTTGT GGTGAGAACA TTTAAAATCC TTTCTTTTTG CTATTTTGAA ATATACAGTA 120 CATTGCTATT AAGTATAGTC ATCTGGCTGT GCAATAAAAC ACCAGNACTT ACCCCTCCTG 180
TCTGTGACTT TGTACCCTGT TCACCACCCC TCCAATCCTC TAGTAACTAC CATTCTACTC 240
TCTACTTCTA TGAGCCTGAC TTTTTAAAAT TCCACATGTA AGTGAGATTA CATGGTATTA 300
TTCTCTCNGT GGCTGGCTTA TTTCACTTTA ACATAATGTC CTCTAAATT 349 (2) INFORMATION FOR SEQ ID NO:261:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 415 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:261:
GGAAGATGAG GATCTAGGTG TGAGCGTGCA GAGCCCTGAG GCTGGGCAGG CAGGGAGCTC 60
TGCCTGCACA ATGATGTAGC CATGTGTGGC CACACCAGCA CTGGGCAGCA CCTCTGGGGA 120
GGGGGGCAGG GCAAGGACAA CTGGAGAGAC AAAGCCAGAT GGGGCCACGT CCTTAGAAGT 180
GTGTGTGCAC GCACATGTGT GTGTGTGTGT GTGTAATACG CAGGGCAGAA ACACACCATG 240
TAGGTCAGGC AGGACAGAAA CACATCATGT AGGCCAGGCG TGGTGGCTCA GGCCTGTAAT 300
GCCAGCACTT AGGNAGGCCA AAGTGGGCGG ATCACCTGAG GTCAGGAGTT CGAGACCAGC 360
CTGGCCAACA TTGCAAAACC TCATCTCTAC TAAAATTCTA AAATTAGCCA GGCGT 415 (2) INFORMATION FOR SEQ ID NO:262:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 382 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:262:
GGCATGGGGT CTGGCTTTAA TGTGTAACTG ACGTGGGTCA CTGAAACTGT TCAGGCTGAT 60
CTTGAACTCC TAGGCTCAAG TGATCCTGCT GCCTTGGCCT CCCAAAGTGC TGGAATTACA 120
GGAATGAGTC ACAGCACCCA GCCGGCTGTG TTTTGTTTTT TGTTTTTTAC CCCGACAGGT 180
NCTCAGTCAG TCGTTAGCTG GAGTGAAGTG GCGTAACACA GCTCACTGCA GCCTTGATCT 240
CCTGGGCTCA AGTGATCCTT CCATTTCTTC CTTCCAGAGT AACTGGTACT GCAGGCCCAC 300
GGCACCACAC ATGGCTAATT TTTAAATTTC GTAGAGACGA GGTCTTGCCA TGTTTGCTCA 360
GGCTCCAGCT GTTGTATTCT TT 382 (2) INFORMATION FOR SEQ ID NO:263:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 447 base pairs
(B) TYPE: nucleic acid (C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:263:
TGTATCAACT CAGAATTTCC AGAGAGCTCT TCCTGGCTGA AAAGATGTCC AAGGATCATC 60
TCCGGAATGG AAGAGGTGAG GCCTGTTAGC TTGTGGGCTG CCCAATCCAT CCAACCCTTG 120
GCATTGGGAT CAATGTTGAT GAGGACAAGA CCTTCAACAG TGTCCGGGTG GTTAAGAGCA 180
TATCTCGCCA GGATGTAGGC TCCAGCTCCA ACACCAACTC CAATTATTGT AGAGAAATTT 240
AGGTACTGCA GGACGCAAGG GATCATGTCT GCAAGCTGGT CCAGAGATGG GTACTGATAT 300
CCCAAAGGGA ACACAGGGGC TCCCTCTTCC ATTCCAGGGG CATCCACATG GACCCGCACA 360
AAGTTCTGAA TGATTTCCTG CATGTCCTCG AACTKGAACA GTGGCTGGAG GAAAGATTTA 420
TAGTTGAGTC CACATCGGGT AGGTAAG 447 (2) INFORMATION FOR SEQ ID NO:264:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 317 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:264:
TTTTCGCTGT CAACAGACAG TTTATTCTAT ATACAAACAC AATTTTGTAC ACTGCAATTA 60
AATAGAATGG AATGAGCGCT CCTCCGCATT CCTCCCCGAG TGACTGGTTT GGCCGCCGGC 120
CACTCCATCC CCGAGTGGGA CTGGACCACG GCCCTGGNTG CTGCCACTGA TGTTGGNGCC 180
TGCACCCCAC GTCCCTATGC CCGAGGCGCA ANTCTGCTCT CCCGGGGACC CCAAGNCTGG 240
NGCACACGCG GGGAGGGCGG GGCCATGGAG AAGGCACTGC AGGGAGCACC AGGCAGAGCC 300
GTGTTGAGGC CGGCCGG _ 317 (2) INFORMATION FOR SEQ ID NO:265:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 270 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:265:
GCAGAGCAGG TGGAAGTGAT CAGGAACCAT AGTTGACAGT TCCAATCAGT AGCTTAAGAA 60
AAAACCGTGT TTGTCTCTTC TGGAATGGTT AGAAGTGAGG GAGTTTGCCC CGTTCTGTTT 120
GTAGAGTCTC ATAGTTGGAC TTTCTAGCAT ATATGTGTCC ATTTCCTTAT GCTGTAAAAG 180
CAAGTCCTGC AACCAAACTC CCATCAGCCC AATCCCTGAT CCCTGATCCC TTCCACCTGC 240 TCTGCTGATG ACCCCCCCAG CTTCACTTCT 270
(2) INFORMATION FOR SEQ ID NO:266:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 297 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:266:
ATGAGGCGAG GCCTGCGAAG TGGCTGGCAT GCAGCAGGTG CTAATGAGTG TTGCAAAGGT 60
GATGTCACGC AGGCAGCTTC CCGTGGCCAG AGAAACATTG CAGAGAAGGG ATAAGTAGGG 120
CTTAGTGACT TTGACGGGTC AATGGAAGAA TGACCCAAAG AAGGCTTCAA GGCCAGGCCT 180
GCAGTTCTCC ACCACAAAGG CCCTCACTGA TAGCACCCAC TCCCCCACAC TCAGCTTTNG 240
GGCCTAGGTC TGGGTCACCC AGCTAGAAGC CACAGGACCC TGAGGCGTCC GAGGGGT 297 (2) INFORMATION FOR SEQ ID NO:267:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 387 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:267:
CTTGTTTTCA TCATGAGCTC GATCAGATGT CTCTCGATCT TCAGACTGGT GGTGTCCTAT 60
AATGTCCTGT GCACGCATTC TTGAGCTTTC CAGGATTTCT GTCTGTTCTC TCTGTTTATC 120
TACAGAAGAA ACTTTCTCCT TGAGTTCCTG TTCTTCGTAG CGCCTTGAAC TCTCTTTCCT 180
TTCTGGTTTA CGATCCTCCT CTTTCCATCT ACCCTGTCTG TCTTCTGTGA GGTGCGAGGG 240
ACTAAGAGAA CGAGATTCTT GAGGTCGTAC AACTTGGCTC AAGAGTCTGT GTTTTTTCAT 300
TTNTNATCAT CTCCACTGTT GTAGGCATCA CTGTCCGGAG AATGTTCACG CCGGCGCTTT 360
CGGGGGACTG TCTAGGGCTG GGACTCC 387 (2) INFORMATION FOR SEQ ID NO:268:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 318 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:268:
CCTGAAGGTT ACCTCTTTGG AGAGAACATG GATCTGAACT TCCTGGGCAG CCGCCCGGTC 60
CAGTTTCCCT ACGTCACTCC TGCCCCCCAC GAGCCCGTGA AGACGCTGCG GAGCTGGTGA 120
ACATCCGCAA AGACTCCCTG CGGCTGGTGA GGTACAAAGA CGATGCCGAC AGCCCCACCG 180 AGGACGGCGA CAAGCCCCGG GTGCTCTACA GCCTGGAGTT CACCTTCGAC GCCGATGCCC 240
GCGTGGCCAT CACCATCTAC TTCCAGGCAT CGGAGGAGTT CCTGAACGGC AGGGCAGTAT 300
ACAGCCCCAA GAGCCCCT 318 (2) INFORMATION FOR SEQ ID NO:269:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 422 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:269:
ACATGTCTAT TCAGGTCTTT TGCCCATTTT GAAATAGCAT TGCTTGTTCT TTTGCTGGAT 60
ATTAACCCCT TGTCAGGTGC ACAGTTTGCA AGTTACCTTT TCTCATCCTA TAGGTTATCT 120
CCTCACTCTT GATTGTTTCT GTTGCTGTGC AGTAGCTTTT AAGTTTGGTG TAATACCATT 180
GTGTTTTCTC TGCTGCCCTT TTAAGTTTCA CTGGGTCAAA AGTTTAAAAT TTGTGAATTC 240
CTATATTTTT AGGGCAATTC TCCTGCCACT GTTGGAATTA TGCCTCAATC TATGCAGTAG 300
AATATTAGTG TGAAATGCTT CTGTACCAAT GGAGATGATG CTGGATGGTC TCTATCATAA 360
ACCCATACCT CATCAACACA AACTGCAATT ACACAAGGGC TCTATATCAT GGATCTCCAT 420
TT 422 (2) INFORMATION FOR SEQ ID NO:270:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 376 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:270:
GAAGAAGAGC CCAGACCTAG GGGAGTATGA TCCACTTACC CAGGCTGACA GTGATGAGAG 60
CGAAGACGAT CTGGTGCTTA ACCTGCAGAA GAATGGAGGG GTCAAAAATG GGAAGAGTCC 120
TTTGGGAGAA GCGCCAGAAC CCGACTCAGA TGCTGAGGTT GCAGAGGCTG CAAAGCACAT 180
CTTTCAGAAG TCACCACGGA GGGCTACCCC TCAGAACCCC TTNGGGGCCT GGAACAGAAG 240
GCGGCCTCCT CCCTGGTGTC ATATGTGCGC ACGTCTGTCT TCCTGCTTGA CTTTGGGGAT 300
CTCGATGATC CTGGTGCTCC TGTGTGCTTT CCTGATCCCC TGTCCTCCCA GAGATCTTGA 360
CAGAACTGGA GCCGCA 376
(2) INFORMATION FOR SEQ ID NO:271: (i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 346 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:271:
TGTTCACGTT CCCTTTCTTT GTCTTTCTTT TTCCTATCTT TATCTATACT TCGACTCCTC 60
TCCTTTTTCC TCTCTTGTTC TTTAGCCTCA CCTTTATGCT TATGACTGTN CCCACTAAGA 120
TTTCCACGTT GATCATCAAT TTTACGNCTA TCTCGACTCC TACTGCGACT GGCACGATTG 180
GTTCGTCTAT CCCTTGAGCG ACTTCTACGA ATGCTTATGA AAAAGAATCA AGTTGGNCAC 240
CAAATGTTTC ATAGCAGTAG GAAATTTCTT TTAGAGACTT CTGATGGGAA ATTTGAAGTG 300
TATGTTGCTA TCAGATCAAG TGCAGGAGAG GTATAAGGCT ACTGGA 346 (2) INFORMATION FOR SEQ ID NO:272:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 394 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:272:
GTTGTTGTTG TTGAGTCGGA GTCTCGCACT GTTGCCTGGG CTGGAGTGCA ATGGTGCAAT 60
CTCGGCTCAC TGTAACCTCC GCCTCCCAGG TTCAAGCCAT TCTCTTGCTT CAGCCTCCTA 120
GTAGCTGGGA TTACAGGCAC CTGCCAGCAC ACCTGGCTAA TTTTTTATAT TTTNAGTACA 180
GACAGGGTTT CACTATGTTG GCCAGGCTGG NCTTGAACTC CTGACCTTGT GATCTGCCCA 240
CCTCAGCCTN CCAAAGTTTT TCAGAATTTT TTAAGGAAAC ACTTTTAACC CTTAAGGCTT 300
TCTTTCAAAC TCAGATCCCC TTACACAATT GATCAGACGT GGCAAAGTTT TGCTTCAAAG 360
TTTTTGGACT GGGTTTCCAC TTTAGGCTTA CTGA 394 (2) INFORMATION FOR SEQ ID NO:273:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 259 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:273:
CAACCTGTAC CCAGGCTGCG AGAACGTRAG TTTRAGGAGC CGCAGCATGA TGTTCGAGCC 60
GGGTCTTACC AAAGGRATGC TGGAGGTGTT TKTGGCCCCG ACCCACCACC CGCACTGCTC 120
GGCCGATGAC CAGTCCACCA AGGSCATCGA CATCCAGAAC GCTTATTTRA ATGGAGTTGG 180
CGATTTCAGC GTGTGGGAGT TCTCTGGAAA TCCTGTGTAT TTCTGCTGTW ATRACTATTT 240 TGCTGCAAAT AATCCCACG 259
(2) INFORMATION FOR SEQ ID NO:274:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 348 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:274:
TCCCAGTTGT CCCGATTGTA ACTCAAAGGG TGGAATATCA AGGTCGTTTT TTTCATTCCA 60
TGTGCCCAGT TAATCTTGCT TTCTTTGTTT GGCTGGGATA GAGGGGTCAA GTTATTAATT 120
TCTTCACACC TACCCTCCTT TTTTTCCCTA TCACTGAAGC TTTTTAGTGC ATTAGTGGGG 180
AGGAGGGTGG GGAGACATAA CCACTGCTTC CATTTAATGG GGTGCACCTG TCCAATAGGC 240
GTAGTATCCG GACAGAGCAC GTTTGCAGAA GGGGGACTCT TCTTCCAGGT AGCTGAAAGG 300
GGGAAGACCT GACGTACTCT GGGTTAGGTT AGGACTTGCC CTCGTGGT ' 348 (2) INFORMATION FOR SEQ ID NO:275:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 396 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:275:
GTTTGGTGAA TTTGGTCTGT GATAAAATTG GAGTTCAAGA AACAAACAGG AAACTACAAG 60
TGCCCCTTCG CCCCCAGGTC ACCCGAGTGG CAGGGCAGTG ACCGCTGCTC TCAGGCTGCC 120
CAGTGTGGAC CTGCCTGTCG GAATGCTCCT CCTCCACGTC CCCTCGCTCC TGTGTCCCAG 180
CCACATGCAC CTTCCCTCTA CCTCTGGGAT CCCTGCACCA GGTCTGCCCC TGTCTTCTCA 240
GGGCTGCTCC TNTTGGNCCA CAGGACCTCA GCTGGAATGT TGCCTCCTCC AAGAGGCCTT 300
CCTGACTATT CAGCTCACAG TGGCCACCCA GCCACAATCT GCCATGTGCT TTGGGGGATT 360
GTCTGTTAAC TGGCAACATA CTGGCAGCCC ATAACT 396 (2) INFORMATION FOR SEQ ID NO:276:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 381 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:276: GGTGTCGGGG AGGCTGCGCA AGGGGGCGAG CCCGGGCAGC CGGCGCAACC CCCGNCCCAG 60 CCGCACCCAC CGCCGCCCCA GCAGCAGCAC AAGGAAGAGA TGGCGGCCGA GGCTGGGGAA 120 GCCGTGGCGT CCCCCATGGA CGACGGGTTT NTGAGCCTGG ACTCGCCCTC CTATGTCCTG 180
TACAGGGACA GAGCAGAATG GGCTGATATA GATCCGGTGC CGCAGAATGA TGGCCCCAAT 240
CCCGTGGTCC AGATCATTTA TAGTGACAAA TTTTAGAGAT GTTTATGATT ACTTCCGAGC 300
TGGTCCTGCA GCGTTGATGA AAGAAGTGAA CGAGCTTTTA AGTTAACCCG GGATTGCTAT 360
TNAGTTAAAT GCAAGCCAAT T 381 (2) INFORMATION FOR SEQ ID NO:277:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 206 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:277:
TTAATACGAC AGGGCTGGCG CCCGAGTAAT TCAAGCCCTT CGGAAGTGTC ACCGGCTGCC 60
AGGCCTCGGA TGCAATCCTG GAGGCGGGAG ATTCGGCCTN AAGACTGGCT CGAGCCGCCC 120
AGGGGCTCCA TGGGAGACTA ACGCGGAAGT YCCAGCCGTC CCAGTGCCGT GACGTCCCCC 180
CTTGGTGGGG CCTGCACCCG ACTACT 206 (2) INFORMATION FOR SEQ ID NO:278:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 260 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:278:
ACCTGTAATC CCNGCACTTT GGGAGGCTGA GGTGGGCAGA TCACGAGGTC AGGAGATAGA 60
GACCATCCTG GCTAACACGG TGAAACCCCA TCTCTACTAG AAAAATACAA AAAATTAGCC 120
GGGCATGGTG GCGGGCGCCT GTAGTCCCAG CTACTCGGGA GGCTGAGGCA GGAGAATGGC 180
GGGAACCCGG GAGGCGGANT TGCAGTGAGC TGAGATGCGC CCGTCTCTCC AGCCTGGGCA 240
ATAGAGTGGG ACTCCATCTC 260 (2) INFORMATION FOR SEQ ID NO:279:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 308 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:279: GTGTCTGGGC TCAGGGTTGG CCAGCTTGCA GAGGAGCAAG CTAGTAGAAA TATTGCAGGG 60 TTCCCAAAAC CAGGTCAAGC AAGATGCCAT GTCACCCCTG AGCATGCCTG TCTTCCCAGG 120 GGTGTACCTC TTGGCTGGCA AAGCCAAGGC CAGTGGGNAC TTGTATAAAT CACATGGGTA 180
TGTTCTTGGT TCAGTGATCT TGGAGTGATG ATGGTAACTN ATGAACAGAG AACTTTYYAG 240
AACTTKGGTC CTGTCTTCCT CCCTGAACCT AGACAAGTTT CACCCCTCCT CCTGTACCCA 300
ACCCCATT 308 (2) INFORMATION FOR SEQ ID NO:280:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 402 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:280:
ATTTTAGCAG CTTTCTTGAA ATTTAAAATA TATGTGTAAG TATCTCATTT ATATGCATTT 60
CTAGTTTCTT TATACAACAG AATAACTTCT TTTACATCAA ATTTCTGAAT TTGACTAAAT 120
TTAGAAATAA TGGAATCTCA TCCATTAAAT ATAGTCATAG AAGGAAGGAA ATATGAAAAT 180
TAGGATTTCA GATGTTTGAA CATAAAAGAT AATTTTAAAC ATTGTCAGTA ATCTATTTCT 240
TTTTTTTTTC GAGACGGAGT TTTGCTCTGT CACCCAGGCT GGAGTGCAGT GGCGCGGTCT 300
TGGCTTACTG CACCCTCTGC CTCCCAGTTC AAGTGGATTC TCCTGCCTCG NCCTCCTGAG 360
TAGCTGGGGT TACAGGGGCA TGCCAACATG CCGGGGCTAA TT 402 (2) INFORMATION FOR SEQ ID NO:281:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 313 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:281:
GAGAATCCGT CTTAAAAAGA AAAAAAGAAA ATTATAGAGG GAGATGAGGT GGGACAGAGT 60
CTGGCAGTTC ATCAGGGGGA CTGAGAAGGT GGCATTTGGA GGAGAGGAGG CAGTGAGCTG 120
TGCAGTGTCC AGGCAGCCAC CCTTCCCAGC GGCCACCATG ACGGTGTCCT CATTGCTTTA 180
ACCATTAGTA ATCATTCATT CATTCATTCA TTTATCCGAC GTCAGCTGGA GGNCCTGCCC 240
GNGGGGCATG CGCTTAGATT TNGGAGGCCT TCCGGGATGC TTGCGCTCCA ACGGGGGAAG 300
GCCGACTTGG GCT 313 (2) INFORMATION FOR SEQ ID NO:282:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 217 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:282:
TGACCTCAGT TGATCCACCC ACCTTGGCCT CCCAAAGTGC TAGTATTATG GGCGTGAACC 60
ACCATGNCCA GCCGAAAAGC TTTTGAGGGG CTGACTTCAA ATCCATGTAG GGAAGTAAAA 120
TGGANGGAAA TTGGGGTGCA TTTTCTAAGG ACCTTTCTAA CANATGGCTA TAATNTAAGG 180
GGTTTAGGGT CCTTTTTTTT TTTTCAGGGA TACATTT 217 (2) INFORMATION FOR SEQ ID NO:283:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 327 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:283:
TAGAGAGCGC TTTACTCCTG GTCCCATGGC GTAAAGATGT GGCTGGGCCT GACAAGGCTC 60
AGCCTCCAGT CTTAAGATGG GCACAGAAGG GCAAGAAGTA AGATGACGAG TCCCAGAATT 120
AGGACAAGCC ATGAGCCAAG GCCTGGTCTG AGCAAGGGCA GCCCCCTGTC CCAGACACAG 180
GCACCCCCAA TCTCACTTTG GACAGAGCCA ACGTGGGGGG ATCCTCCCGG GCCTGGGCCT 240
GTCAAGTCTG CCTGCAGGAC CCTGCCATTG TGCTCAAATC ACAACCATTT TTTGCTTCCA 300
ACATTTTAGG GTGCTTGTGC AGTGAGT 327 (2) INFORMATION FOR SEQ ID NO:284:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 340 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:284:
CTTTGGAAAT GTAAATTGTT ACAAACTTAC TTTAGAGCAA ATTTAGTCAT CCTTCAAAAA 60
TTTAAATGTA TACTTATTTC CTAAGAATTC GTTTGGCTCA CACAATTGTG AAAAGATAGA 120
TGTACACCAG TGTTCATTAC AACAATTATG CAACAAATCT ATTATGTGCC AGACATTATT 180
CGGAACTCTG GGAATACATA AGTGAACAAA GCAGATTCCT GATCTCAGGA CCTGGGGTCA 240
GGGGTCAGGA GAAGCCAAAA AACACGCTNG AGAAATACTT TATGCAGTGT GGGGGGAGTG 300
CTACCAGCAG AGCAGGGGAT GGNGATGTGA AATCTTGTGT 340 (2) INFORMATION FOR SEQ ID NO:285:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 335 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:285:
GACATTCACG GAGGTGGGTT CGACCTCCGG TTCCCCCACC ATGACAATGA GCTGGCACAG 60
TCGGAGGCCT ACTTTGAAAA CGACTGCTGG GTCAGGTACT TCCTGCACAC AGGCCACCTG 120
ACCATTGCAG GCTGCAAAAT GTCAAAGTCA CTAAAAAACT TCATCACCAT TAAAGATGCC 180
TTGAAAAAGC ACTCAGCACG GCAGTTGCGG CTGGCCTTCC TCATGCACTC GTGGAAGGAC 240
ACCCTGGACT ACTCCAGCAA CACCATGGAG TCAGCGCTTC AATATGAGAA GTTCTTGAAT 300
GAGTTTTTCT TTAAATGTGA AAGATATCCT TCGCG 335
(2) INFORMATION FOR SEQ ID NO:286:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 399 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:286:
GCACAATTAT TAAAAAGAGG CCACTTAAAT TCAACTCTCC ATGGATACAG TGTCTGTGGC 60
AATGTTTAAT TAGAGATTAA AATTGAGGAA TTGAATAATT GAGGTTGCTA ATGAATTTGA 120
AAACTCAGCA AAGCAAGGAG AGCTGAGCGT TTTTCCGACT TAGCTTTTCT TTCTCTAACC 180
CTTTTCTCAT TTCCTACTAT TATCACATNT CTGGCCTTGA CTGCTGAGTT TATTACTACC 240
CATAACCCTG GCCTAAGTGG AAACAAAAAA GCTGTAGCCT CTTTGCTGAG CTCCTGGAGA 300
CATTTGGTCT ATTGGATTTA TGACATGTTC AGAAGCTTGC AGTTGCAGGA GGCTGACAAT 360
GATGAAAATG AGATATGNTG GGCCACCACG CTTTTCTGT 399 (2) INFORMATION FOR SEQ ID NO:287:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 294 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:287:
TTCCAGTTGA ATTCACCAGT GGACAAAATG AGGAAAACAG GTGAACAAGC TTTTTCTGTA 60
TTTACATACA AAGTCAGATC AGTTATGGGA CAATAGTATT GAATAGATTT CAGCTTTATG 120
CTGGAGTAAC TGGCATGTGA GCAAACTGTG TTGGCGTGGG GGTGGAGGGG TGAGGTGGGC 180
GCTAAGCTTT TTTTAAGATT TTNCAGGTAC CCCTCACTAA AGGCACCGAA GCTTAAAGTA 240
GGACAACCAT GGAGCCTTCC TGTGGCAGGA GAGACAACAA AGCGCTATTA TCCT 294 (2) INFORMATION FOR SEQ ID NO:288: (i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 391 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:288:
TCTACAGATG AGGAAAGCAA GCCTCAAGCA AGGGGGGCCT GATCCTTTCC CTGTTCCCTG 60
TGTATTCCCT GTCTGTGGCA AAGCCCATTG CCTTGATTCT CTTCTCTTTA CTTTCATGTT 120
GAGAAGTAGT TTCTTTCTGC AGTTTATTTA ATTTACTGGC AAAATGACGT ATTTTTTTTT 180
CAGCAATGTT TCAGCTAGAT ATTTGCTTTA TGCATGTAAT GTCAATGAAG TACTCATAAG 240
TTTTCAAGAA ATGACTGATA TAAATCATGT GTTCCACTAC ATAGTCTAAA TATTTAGTAT 300
TTGGTCATCT ATTTTAATAT GTTCAAATTC TGTTAAACAA GNCATAGTCA CTATGTGAAG 360
ATAAAAATAG NCAAAGTTGC ATTATGACTT T 391 (2) INFORMATION FOR SEQ ID NO:289:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 198 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:289:
CTTATATTCT ACTTTATTTG GTAAAACTCA GAAACTAACA ATTCACATCC TCCCACCTTC 60
TTCTTTCCGA AGAAGGCAGT TTGCAGAGAC AAAAGGGCTG TGGCGTGGGG ATCATCCACC 120
ATCTCCAGGT TTTACACCCA GGCTACCCAT GGCTTGGCAG TCAGGCCTCT AGGCTGATTG 180
CTCTCAGAGG CAATAGAA 198 (2) INFORMATION FOR SEQ ID NO:290:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 353 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:290:
GGTTTTCATC TTCGGTTTAC AAAAGTCCTA CTATTTATTT ATTTTAACTT TAATTTAAAT 60
ATCACCTACC TTAGGTAGAA GTTTTCCTTT GTGTAATATA ATATAAAACC GACATTTCTT 120
GGGGGCATAA TAGTAAAGAT GTTAACATTT TTTGGTTCTT TTTGGATGCT GTATTTGTGC 180
TTCTTCTGAA AGTGATGTGT GCCAAGATGG CTCATGTAAC CCAGTTTTGA CTAGGCTATT 240
GATATTCTGT CTGGTTAATT TATTGAACTG GCTTAAAGCT ATACATATTT CCTTTTAGNT 300
AACTATGTAA GATATTCTAG ATATATTGGT CTACTGATTC ATAATATCAC TGG 353 (2) INFORMATION FOR SEQ ID NO:291:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 163 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:291: CCTGGTAGGC CTGCTACACA GTCTTGCAAC GNCCCTCGTG CTTGGGCTTC TGCGGTGAGG 60 CAGGGGAGTC TGCTTGTCTT AGATGTTGGT GGTGCAGTCC CAGGACCAAG CTTAAGGAGA 120 GGAGAGCATC TGCTCTGAGA CGGATGGAAG GAGAGAGGTT GAG 163
(2) INFORMATION FOR SEQ ID NO:292:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 397 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:292:
ACGGGAAGGT GAGTATGTNA GTATGTNTGC CAGACAATGG TGTTTCCATG TCAATGGAGG 60
TTTCTCAGAG AGAGGTGATC TGGCTGGAGA AAGCTTAATC TGGTGGCAAT GGACAGGTGA 120
CTTTAAGAAG TGGGGAACGA GGGAAGGAGG CCAGTTTGAA AATNATAACA AGGGTCCAGA 180
CTCAGTGATG CAGCAGTGAC CATGAGAACA GAGCAGCTGC AGGTAGAAGA TGGAGACAGA 240
ACTNGGGAGA TCTGGTGGAG GTAAGCCGCG TGGAAAGATG ATGTCAGGTT TATACCTAGA 300
GGACACATGA TCCATTCACA AAGCCAGGGG NAACCTAAAG AGAAAACACT TAGAATTTTN 360
GGAGAANAGG CTAGGGCTGG GCCTTAGACA TGGGCTG 397 (2) INFORMATION FOR SEQ ID NO:293:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 360 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:293:
GAGGTAAAAT TTACATACAG TGAAATCCAA ATCTTAAGTG TACCACTAGA TAAATTTTGA 60
TAAATGCATT ATGCCTGGTC TTCACACACC CTTTTCAATA TATAGAAAAT NTCCAGATAA 120
TTTATTTTGT TGTTTTTTTC ACACACTAAG TTCTAGACTT TTCCAGGTCC GAGGGAACTA 180
TTAGGGGGGA AAGTACTTGT NATAGTAAAA AAGATTTTAG GTGTGTTTGT TTTTAAGGTG 240
CAGAAACACA TCGCAGATTT AAGGTCTGCA ATCTCTGCTT TTTGTTATTG TTCCAGTTTT 300
GATCTCAGTG ACATTACAAG CAAGCAGAAA CACTCAGACA TGAAATGGCC CAGTGCCTGT 360 (2) INFORMATION FOR SEQ ID NO:294:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 321 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:294:
TTTTTTTCAG GNTTCAACCG TTTTATTGGG AGGTTTTGTT TTCTGTGAAA TACACTAGAG 60
GGTGGGGAAG GGGACACATT CACTTTGCAA GATAAGGGTT TCCCACCACT AAAGGAAAGG 120
CATGGGGCAG GGCACACTGG GGTTTGGGTC CGTTTTCCCA CCTCCTTCTG CTTGGCTCAC 180
TTTTCTTTTC TCTCAGCAAG TACCACAGAA CACAAAGACA AGAAACAAAA CAGCAAATCA 240
ACCTCCAACG GGGCCATGCC AAGCCTTCCC CACTCCCCCA GGCTGGGCAA GGGCTGGGAG 300
GGGGCTGGGG CAGCTCACTC G 321 (2) INFORMATION FOR SEQ ID NO:295:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 165 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:295: GACACACAGC GCCTCCGGCC CCGCACAGGG GGCATGTCCA GAGGTGCTGT GTGTCACCAA 60 CTGGTCTTCT AATTTGGAAG GAGTTGGAAA GGCCTTTTTG TTGATGAAAA GTTGGAAACA 120 GTGGCACATA TCTNAGAGGG AGGAACGAGG CAGCGTGGTG AAGCG 165
(2) INFORMATION FOR SEQ ID NO:296:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 315 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:296:
CGAATACAGG TAGTGCCCAG CTGGTTGGGC TGGCCCAGGA AAATNCTGCT GTGTCAAATA 60
CTGCTGGCCA GGATGAAGCC ACAGCTAAGG CTGTGTTGGA GCCCATTCAG AGCACCAGTC 120
TAATTGGGAC TTTAACCAGG ACATCTGACA GTGAGGTTCC AGATGTGGAA TCTCGTGAAG 180
ACTTAATTAA AAATCACTAC ATGGCAAGNA TAGTGGAACT TACGTCTCAG TTGCAGCTGG 240
CTGACAGTAA GTCAGTGCAT TTTTATGCCG AGTGCCGAGC ACTGTCTAAA AGACTNGCCT 300
TGGCTGNAAA GTCTA 315 (2) INFORMATION FOR SEQ ID NO:297:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 244 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:297:
AGTACGGTTN NCGCTNAAGC TTGATNATCG RATTGCCAAT CTNCATATTT GTGTTAGAAT 60
CATTTGTTTT TGTGTCTTCA TGTTTCTATA AGATAGGACC AATATTCTTT ATTGGGCTTT 120
GATTTTATTT TGTAACTTAA ATGTATTAAG GCAATAAATG TAATTTTCCA CTNAAAACTA 180
TCATTATAGA TTTGGTTACT ACCTACTGCT CAGCAATTTT TTTTCTTATC AAAATTCTTC 240
CTGG 244 (2) INFORMATION FOR SEQ ID NO:298:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 152 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID N0:298: CCTGAACAGG TAATGAGAAA AATTTACACA CAAGTGATTT TGAAAACAGA ATGGGTTGCT 60 TACAAATTAC AGGAAATGTT ATAACACAAA CCAGAAGAAT TCAATGGAAG GCAATAAGGG 120 ATTCTGAAAT GAAAATTATA AAAGTATCAN GA 152
(2) INFORMATION FOR SEQ ID NO:299:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 374 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:299:
CGATGTTTTT AATGTCATCA CACGTTGTCT CAAAATGAGT GGTGGCATCΔ TATGTGCGGG 60
AAATAAAGAT CTGGCTTTCT GTTCCCAAGT CTTTTGGTAC CAGGAGGTCA CTGATGCTAA 120
CAAATTTCTG TTCAATTGGT TCCAAGAGCT CCAAAGCTGG TCTGATTTCC TTCTCAGGCT 180
CCTTGGTTTC CACAGTTGTA CTAACTATAG CAATGTACTT CCCTTGTGCT GCTACATTGT 240
GCGCAAAGGA GATCATGCAG ACGTAGATAT CTGACTTTCG ATTGACTTTG GTTCTGTGGA 300
ATAATGATCT GGCAGGAGTT GGCATCATTG GTGTTCTTTG ATGGGGGTGG CTGAGGGATG 360
CAAATAACCT CTTG 374 (2) INFORMATION FOR SEQ ID NO:300: (i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 365 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:300:
GGCTCACCAA GCTCAGCAAG TACGTGTACT TCTTCGAGGC CTGCCGGCTG CTGCAGAAGA 60
TGATTGACAT CTCCCTGGAT GGCTTCCTGC TGACTCCGGT GCAGAAGATC TGCAAGTACC 120
CTCTGCAGCT GGCCGAGCTG CTCAAATACA CGCACCCCCA GCACAGGGAC TTCAAGGATG 180
TTGAAGCCGC CTTGCATGCC ATGAAGAACG TGGCCCAGCT CATCAACGAG CGGAAGGGTA 240
GACTTGAGAA CATCGACAAG ATTGCTCAGT GGCAGAGCTC CATAGAGGAC TGGGAGGGAG 300
AAGGATCTCT TGGTCAGGAG CTCAGAACTC ATCTACTCGG GGGGAGCTGA CCTCGGGTTA 360
CACAG 365
(2) INFORMATION FOR SEQ ID NO:301:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 224 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:301:
GGTATTCAAA CAAATAGCCT GAGAATTTNG GGGGGATCTG AAATAGAGTA CTATGCTATG 60
TTGGCTAAAA CTGGTGTCCA TCACTACAGT GGCAATANTA TTGAACTGGG CACAGCATGC 120
GGAAAATACT ACAGAGTGTG CACACTGGCT ATCATTGATC CAGGTGACTC TGACATCATT 180
AGAAGCATGC CAGANCAGAC TGGTGAAAAG TAAACCTTTT CACG 224 (2) INFORMATION FOR SEQ ID NO:302:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 363 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:302:
AGTTTCACTC TTGTTGCCCA GGCTGGAGTG CAATGGCGTG ATCTCGGCTC ASTGCAATCK 60
GCACCTTCCG GKTTCAAGCG ATTCTCCTGC CTCAGCCTCC CAAGTAGTTG GGATTACAGG 120
CATGCGCCAC CATGCCCGGC CAATTTTKTA TTTTTCGTAC ACACAGGGTT TCTCCATGTT 180
GGTCAGGCTG GTCTCAAACT CCCAACCTCG GTGATCCGTC CACCTCGGCC TCTCAAAGTG 240
CTGGGATTAT AGGCATGAGC CACTGTGTCC GGCCAGCTCA AACAATTTTA ATGCTTCTTT 300 CAAGNCTATT AGAAACCTTT AATTGCTTCT TAAGTTTCTC CCCCAACTAT GGAGGAAGCA 360 TAT - 363
(2) INFORMATION FOR SEQ ID NO:303:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 253 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:303:
ATGCAGGAAS ATCTACCARG CAAATCGAAA ACAAAAAAAG GCAGGGGTTG CAATCCATCT 60
CTCTGATAAA ACAGACTTTA AACCAACAAR RRTCAAAAGA CACAGAGARG GCCATARCAT 120
AATAGTAAAG CGGATCAATT CAACAAGAAG AGCTAACTAT CCTAAATATA TATGCACCCA 180
ATACAGGAGC AACTAGATTC ATAAAGCAAG TCCTGGAGGT GCCTACAGAG GAGGCTTAGG 240
CTCCCACACA TTA • 253 (2) INFORMATION FOR SEQ ID NO:304:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 416 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:304:
TTTTTTTGAG ATGGAGTACT CGCTCTCTTG CCCGGGCTGG AGTGCAGTGG CGCGATCTCG 60
GCTCACCTGC AACCCCTGCC TCCCCAGTTC AAGAGGTTCT CCTGCCTCAG CCTCCCGGGT 120
GGCTGGAATT GCAGGCACAC ACCACCATGC CCAGCTGCTT TCTTGTATTT TTAGTGGAGA 180
CGTGGTTTCA CCATGTTGGC CAGGCTGGTC TTGAGCTCCT GACCTTAAGT GATCCGCCAG 240
CCTTGGCCTC CCAAAGTGCT GGGATTACAG GCGTGAGCAC CGTGCCCAGG CTGTTTTTTA 300
ACTGACTTTG GATTTTACTC CCTTTCTATG CAAATTTATT TTAGAATCTG TTCCTTAACC 360
TTAGGGGGTT GGGTTAGACA AGTTTCAAGG GAGCCTCAAG TGKAAATTGC TTAAGG 416 (2) INFORMATION FOR SEQ ID NO:305:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 223 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:305: CACACCCAGC TAATTTTTGT ATTTTTAGTA GAGACGGGGT TTCACCATGT TGGCTTGGCT 60 GGTCACGAAC TCCTGGCCTT GAGTGATCCC CCTGCCTCAG CCTCCCAAAG TGCTGGGATT 120 ACAGGTGTGA GTCAGCGTGC CCAGCCCAGA TTTTATTGTT TTAATTACAA ATTTTACGTA 180 AGTTGTTTCT GCACATTTAT ATTTGCACAC TTGTGCTAGT GAG 223
(2) INFORMATION FOR SEQ ID NO:306:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 169 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:306: GTTTTGCCAC ATTGGCCAGG CTGGTCTCGA ACTCCCGACC WGTGAGCCA CCTGCCTTGG 60 CCTCTCAAAG TGCTGGGATT ACAGGCGTGA GCACCACGCC CGACCCATAG CTCTTTACAA 120 CTGCCTTGTA AAGAAAGCAT CATTTGGCAC TGTTAGTATT TCTCTTGAA 169
(2) INFORMATION FOR SEQ ID NO:307:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 303 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:307:
GATTTGGTAC AGAGTATGTC AGGAAGACAA CTCAGATTGC CATTTTAAAT AAAGTTGTAC 60
ATGAACAATA ATTGGAATCA TCAGGTAATT TTTTTAAACA AAGGTTCTTC ATTTACTGTT 120
ATGATTGGAA AAAAAATTAG AAAATAAAGT AAGTSCCATA GGCTAATTAA AAAATAAAAC 180
CTTGGCCGGG CGCGGTGGCT TACGCCTATA ATCCCAGCAC TTTGGGAGGC CGAGACGGGC 240
AGATCACGNG GTCAGGAGAT TGAGACCATC CTGGCTAACA CGGTGAAACC CCATCTGTAC 300
TTG 303
(2) INFORMATION FOR SEQ ID NO:308:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 143 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:308:
ATCTAGGAGG CTGAGGTGGG ATCGCCCCAG TACTGGAGGT CAGGGCTGCA GTCAGCCATG 60
ATCATGCCAC TACACTCCAK CCTGGGTGAC AGAGTGAGAC CCTCTSTCAA AAAACCTCAG 120
TCAATVCAAA CATACAGTAT ATT 143
(3) INFORMATION FOR SEQ ID NO:309: (i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 199 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:309:
CCCACCCTCA TAANCCCCAC TGGGGAGTCT GGGGGCCTCT ATTGCCATGT GCCTGGAATN 60
ATNATATGCT CATCACTTTA TGAAGAATAA AATTTGTNTT TCCTGCCTTA AAGTTACATT 120
CGTTCTTCCG CTCAAATCCT GATCTGGTCC ATTAAAGAGT GTTCGCAGAC AAAGTTTCTG 180
AAAGATTAGA GAAGAATCC 199
(2) INFORMATION FOR SEQ ID NO:310:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 426 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:310:
TCCCTGTACC ACCTCTTCCT GAATACGGAG GAAAAGTTCG TTATGGACTG ATCCCTGAGG 60
AATTCTTCCA GTTTCTTTAT CCTAAAACTG GTGTAACAGG ACCCTATGTA CTCGGAACTG 120
GGCTTATCTT GTACGCTTTA TCCAAAGAAA TATATGTGAT TAGCGCAGAG ACCTTCACTG 180
CCCTATCAGT ACTAGGTGTA ATGGTCTATG GAATTAAAAA ATATGGTCCC TTTGTTGCAG 240
ACTTTGCTGA TAAACTCAAT GAGCAAAAAC TTGCCCAACT AGAAGAGGCG AAGAAGTTCT 300
TCCATCCAAC ACATCCAGAA TGCAATTGGA TACGGAGAAG GTCACAACAG GCACTGGTTT 360
CCAGGAAGCG CCATTTACCG TTTTTMATGG GMCAAAGGGA GTTACATTGG CTATGGCTTT 420
TGGAAG 426 (2) INFORMATION FOR SEQ ID NO:311:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 489 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:311:
TCGACTCGGT CCTGGATGTG GTGAGGAAGG AGTCAGAGAG CTGTGACTGT TTCCAGGGCT 60
TCCAGCTGAC CCACTCTCTG GGGGGCGGCA CGGGGTCCGG GATGGGCACC CTGCTCATCA 120
GCAAGATCCG GGAAGAGTAC CCAGACCGCA TCATGAACAC CTTCAGCGTC ATGCCCTCAC 180
CCAAGGTGTC AGACACGGTR GTGGAGCCCT ACAACGCCAC CCTMTCGGTC CACCAGCTGG 240 TGGAAAACAC AGATGAAACC TACTGCATTG ACAACGAGGC CCTGTATGAC ATCTGCTTCC 300
GCACCCTGAA GCTGACCACC CCCACCTACG GGGACCTCAA CCACCTGGTG TCGGCCACCA 360
TGAGCGGGGT AACACCTGCT TGCGCTTYCC GGGCCAGCTG AACGAGACCT GGCAAAGTGG 420
CGGTTGACAT GGTGCCTTTC CTGGCTGAAT TTTTAATGCC CGGTTTGGGC CCTACCAGCC 480
GGGGAAGCA 489 (2) INFORMATION FOR SEQ ID NO:313:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 302 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:313:
CTTCTCATGC CAGTCTAATG ATTGTTTTTA GAAAAGGATA TACATTGACC TTCAATGTAA 60
TAAGAAATGC AACACTTTAC GGTGTCCAAC TGCTAAGATT TATTTCCAAC TTGTCAGACA 120
CAACTATTTT GCCCAATCCA AATCAAAGGG AATCAAGGCT GTGAAATCCA CACAGGACAT 180
CAACGCACAC ATAAATGAAA ACTACAGATG TGTCAGAGGC AACCATATAC ACACAAATAA 240
TGTAACTACT AAATTCCATG AAGTAGCTGT CCAGGGAATA CTTTCCAAAT AACCTTCAGC 300
AG 302 (2) INFORMATION FOR SEQ ID NO:315:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 339 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:315:
CGCGTTATTT AAATTGTGAA AAATAATGAA TATTAATTTG GAGCATAATA TTTAAATACA 60
TGAAAAAAGC TGGCTGGGAA ATGTTGGCAT GACTTTTCCC AGATGTTAGC ACTGCTTCAA 120
CTTTTGAGAG NGCACTCTGA GTGTAAGTTT ACTAGACTGA CATTACTAAA ATCATTGGTG 180
CTATAGAGGC AGGAGAATAC GGGGAATAAG AAAGCCAGTT GCAAGCCAAC AATCCTAAAA 240
CTCCTCCTTT TGCCATGGAC TGACGGCATA TTAAATGAGA TCATGCATTT TAAGGNATTA 300
ACAGTGTACA CCACATGTGC GTGTTCCAAT AAAAGGAAG 339 Note regarding Claims: Certain SEQ ID NOS are excluded from some claims based on their homology to known non-human sequences (See Table 2) .

Claims

WHAT IS CLAIMED IS:
1. An enriched oligonucleotide having a sequence designated as one of: SEQ ID NO: 1 - 315; or having a sequence complementary thereto.
2. An enriched oligonucleotide having a sequence designated as one of:
SEQ ID NO: 1 - 315, except SEQ ID NOS: 22 or 187; or allelic variation or complementary sequence thereto or portion thereof at least 15 nucleotides in length.
3. An isolated oligonucleotide that includes a sequence designated as one of: SEQ ID NO: 1 - 315, except SEQ ID NOS: 22, 187; or allelic variation or complementary sequence thereto or portion thereof at least 15 nucleotides in length.
4. An enriched or isolated oligonucleotide operably coding for a human gene product, which includes a region coding for the same amino acid sequence as the coding region of a gene corresponding to a sequence designated as one of: SEQ ID NO: 1 - 315.
5. The sequence of Claim 4, wherein said SEQ ID NO is listed in Table 6.
6. The sequence of Claim 4, wherein said SEQ ID NO is listed in Table 7.
7. The sequence of Claim 4, wherein said SEQ ID NO is identified in Table 10 in a metabolic functional grouping.
8. The sequence of Claim 4, wherein said SEQ ID NO is identified in Table 10 in a structural functional grouping.
9. The sequence of Claim 4, wherein said SEQ ID NO is identified in Table 11 in a developmental control grouping.
10. An enriched or isolated oligonucleotide coding for a human gene product, which includes a coding region corresponding to the EST identified as: SEQ-ID NO: 1 - 315; or a sequence complementary thereto or comprising an allelic variation thereof.
11. The oligonucleotide of Claim 10, wherein said SEQ ID NO is 1-315.
12. The oligonucleotide of Claim 10, wherein the SEQ ID NO is 1001-1500.
13. The oligonucleotide of Claim 10, wherein the SEQ ID NO is 1501-2000.
14. The oligonucleotide of Claim 10, wherein the SEQ ID NO is 2001-2421.
15. The oligonucleotide of Claim 10, wherein said sequence further includes the entire sequence designated as any one of SEQ ID NOS: 1-315.
16. An enriched or isolated oligonucleotide fragment comprising at least 15 bp of a sequence of Claim 10 and wherein said SEQ ID NO excludes NOS 22 and 187.
17. An enriched or isolated oligonucleotide sequence corresponding to a human gene, which hybridizes to a sequence designated as any one of SEQ ID NOS 1-315, except SEQ ID NOS 22, 187, or to a sequence complementary thereto, under hybridization conditions sufficiently stringent to require at least 97% base pairing.
18. An oligonucleotide according to any one of Claims 1- 17, in substantially purified form.
19. A construct comprising a vector and an oligonucleotide according to any one of Claims 1-17.
20. The construct according to Claim 19, further comprising a promoter operably linked to said oligonucleotide.
21. A panel of at least 100 oligonucleotides according to Claim 3 or Claim 16.
22. An antisense oligonucleotide capable of blocking expression of the gene product of any one of the sequences of Claim 10.
23. A triple helix probe capable of blocking expression of the gene product of any one of the sequences of Claim 10.
PCT/US1992/005222 1991-06-20 1992-06-19 Sequences characteristic of human gene transcription product WO1993000353A1 (en)

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US5869638A (en) * 1992-08-28 1999-02-09 Hoechst Japan Limited Bone-related cadherin-like protein and process for its production
EP0585801A3 (en) * 1992-08-28 1994-06-29 Hoechst Japan Bone-related cadherin-like protein and process for its production
EP0585801A2 (en) * 1992-08-28 1994-03-09 Hoechst Japan Limited Bone-related cadherin-like protein and process for its production
EP0743989A1 (en) * 1994-02-14 1996-11-27 Smithkline Beecham Corporation Differentially expressed genes in healthy and diseased subjects
EP1813684A2 (en) * 1994-02-14 2007-08-01 Smithkline Beecham Corporation Differently expressed genes in healthy and diseased subjects
EP1813684A3 (en) * 1994-02-14 2009-11-18 Smithkline Beecham Corporation Differently expressed genes in healthy and diseased subjects
EP0743989A4 (en) * 1994-02-14 2000-11-08 Smithkline Beecham Corp Differentially expressed genes in healthy and diseased subjects
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US5866330A (en) * 1995-09-12 1999-02-02 The Johns Hopkins University School Of Medicine Method for serial analysis of gene expression
US5695937A (en) * 1995-09-12 1997-12-09 The Johns Hopkins University School Of Medicine Method for serial analysis of gene expression
US6383743B1 (en) 1995-09-12 2002-05-07 The John Hopkins University School Of Medicine Method for serial analysis of gene expression
GB2305241B (en) * 1995-09-12 1999-11-10 Univ Johns Hopkins Med Method for serial analysis of gene expression
GB2305241A (en) * 1995-09-12 1997-04-02 Univ Johns Hopkins Med Oligonucleotide, tagged with nucleotide sequences, for the serial analysis of gene expression (SAGE)
US6746845B2 (en) 1995-09-12 2004-06-08 The Johns Hopkins University Method for serial analysis of gene expression
US6482922B2 (en) 1995-11-02 2002-11-19 Human Genome Sciences, Inc. Mammary transforming protein
US5936078A (en) * 1995-12-12 1999-08-10 Kyowa Hakko Kogyo Co., Ltd. DNA and protein for the diagnosis and treatment of Alzheimer's disease
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US6759210B1 (en) * 1996-02-16 2004-07-06 Millennium Pharmaceuticals, Inc. Compositions and methods for the treatment and diagnosis of cardiovascular disease using fehd545 as a target
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US6890721B1 (en) 1996-05-20 2005-05-10 Human Genome Sciences, Inc. Interleukin-1β converting enzyme like apoptotic protease-6
US7115260B2 (en) 1996-05-20 2006-10-03 Human Genome Sciences, Inc. Interleukin-1β converting enzyme like apoptotic protease-6
US6010878A (en) * 1996-05-20 2000-01-04 Smithkline Beecham Corporation Interleukin-1 β converting enzyme like apoptotic protease-6
US6294169B1 (en) 1996-05-20 2001-09-25 Human Genome Sciences, Inc. Interleukin-1 beta converting enzyme like apoptotic protease-6
WO1999032515A3 (en) * 1997-12-19 1999-09-10 Zymogenetics Inc Angiopoietin homolog, dna encoding it, and method of making it
WO1999032515A2 (en) * 1997-12-19 1999-07-01 Zymogenetics, Inc. Angiopoietin homolog, dna encoding it, and method of making it
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US8563689B1 (en) 2001-06-26 2013-10-22 North Carolina State University Methods for regulating inflammatory mediators and peptides for useful therein
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