Pharmaceutical compositions comprising an antibody binding an ovarian carcinoma protein and uses thereof

TECHNICAL FIELD

The present invention relates generally to ovarian cancer therapy. The invention is more specifically related to polypeptides comprising at least a portion of an ovarian carcinoma protein, and to polynucleotides encoding such polypeptides, as well as antibodies and immune system cells that specifically recognize such polypeptides. Such polypeptides, polynucleotides antibodies and cells may be used in vaccines and pharmaceutical compositions for treatment of ovarian cancer.

It is to be noted that only subject matter embraced in the scope of the claims ¹appended hereto, whether in the manner defined in the claims or in a manner similar thereto and involving the main features as defined in the claims, is intended to be included in the scope of the present invention, while subject matter described and exemplified to provide background and better understanding of the invention, is not intended for inclusions as part of the present invention.

BACKGROUND OF THE INVENTION

Ovarian cancer is a significant health problem for women in the United States and throughout the world. Although advances have been made in detection and * I •1 ' therapy of this cancep no vaccine or other universally successful method for prevention or treatment is ,currently available. Management of the .disease currently relies on a cnrrihinatinn of early diagnosis, and aggressive treatment, which may include one or more of a variety, of treatments such as surgery, radiotherapy, chemotherapy and hormone therapy. .The course.of treatment for a particular cancer is often selected based on a variety of prognostic parameters, including an analysis of specific tumor markers. However, the use of established markers often leads to a result that is difficult to interpret, and. high mortality continues to be observed in many cancer patients.

Immunotherapies have the potential to substantially improve cancer treatment and survival; Suph therapies may involve the generation or enhancement of an immune response-to-,an., ovarian carcinoma antigen. However, :to date, relatively few ovarian carcinoma-antigens are known and the generation of an immune response against such antigens has! not been shown to be therapeutically beneficial.

Accordingly, there is a need in the .art for improved- methods for identifying ovarian tumor- antigens and for using such antigens in the therapy of ovarian cancer. The present invention fulfills these needs and. further provides .other. related advantages.

SUMMARY OF THE INVENTION

Briefly stated, this invention provides a pharmaceutical composition comprising:

an antibody or antigen binding fragment thereof, which specifically binds to an ovarian carcinoma protein, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence set forth in SEQ. ID NO:391 and a physiologically acceptable carrier for use in the manufacture of a medicament for treating ovarian cancer.

Within other aspects, the present invention provides pharmaceutical compositions and vaccines.

In some embodiments, the antibody or antigen binding fragment is conjugated to a toxin and in some embodiments, the toxin is selected from the group consisting of a ricin toxin, abrin toxin, diptheria toxin, cholera toxin, gelonin toxin, Pseudomonas exotoxin, Shigella toxin, and pokeweed antiviral protein.

In some embodiments, the antibody or antigen binding fragment is conjugated to a radionuclide and in some embodiments, the radionuclide is selected from the group consisting of ⁹״Y, ¹²³I, ¹²⁵I, ‘³¹I, ¹⁸⁶Re, '⁸⁸Re, ²¹¹At and ²¹׳Bi.

The present invention also provides, within other aspects, for the use of an isolated antibody, or antigen binding fragment as herein described, in the manufacture of a medicament for killing or inhibiting the growth of a tumor cell which expresses a polypeptide encoded by SEQ ID NO: 391, comprising contacting the tumor cell with said isolated antibody, or antigen binding fragment in an amount sufficient to kill or inhibit the growth of the tumor cell.

In other embodiments, the invention provides for the use of an isolated antibody, or antigen binding fragment as herein described, in the manufacture of a medicament for treating ovarian cancer in a patient, wherein the cancer expresses a polypeptide encoded by SEQ ID NO: 391, comprising administering a therapeutically effective amount of said isolated antibody, or antigen binding fragment in an amount sufficient to treat ovarian cancer.

In other embodiments, the invention provides for the use of a polypeptide as herein described, in the manufacture of a medicament for use in preventing the development of ovarian cancer or for the treatment of ovarian cancer.

. 5 .

Thesq and other aspects of the present invention will^ become apparent upon reference to die following detailed description and attached drawings. All references disclosed herein, are hereby incorporated by reference in their entirety as if each was incorporated individually

BRIEF DESCRIPTION OF THE DRAWINGS

Figures 1A-1S (SEQ ID NOs:l-71) depict partial sequences of polynucleotides encoding representative secreted ovarian carcinoma antigens.

Figures 2A-2C depict full insert sequences for three of the clones of Figure 1. Figure 2A shows the sequence designated O7E (11731; SEQ ID NO:72) 10 Figure 2B shows the sequence designated O9E (11785; SEQ ID NO:73) and Figure 2C shows the sequence designated O8E (13695; SEQ ID NO:74).

Figure .3 presents regylts of microarray expression analysis of the ovarian carcinoma sequence designated O8E.

Figure 4 presents a partial sequence of a polynucleotide (designated 3 g;

SEQ ID NO:75) encoding ;an ovarian carcinoma sequence that is a splice fusion between the human T-cell leukemia virus type I oncoprotein. TAX and osteonectin.

Figure 5 presents the ovanan carcinoma polynucleotide designated 3f (SEQ ID NO:76),

Figure 6 .presents the ovanan carcinoma polynucleotide designated 6b (SEQID NO:77). .: . .

Figures .;7Ai:a1jd 7B present the ovarian carcinoma polynucleotides designated 8e (SEQ ID N:O;78) and 8h (SEQ ID NO:79).

Figure.8.presents the ovarian carcinoma polynucleotide designated 12c (SEQ ID NO:80).

Figure 9, presents the ovarian carcinoma polynucleotide designated 12h (SEQ ID NO:81),

Figure !(). depicts results of microarray expression analysis of the ovarian carcinoma sequence designated 3f.

Figure 11 depicts results of microarray expression analysis of the ovarian carcinoma sequence designated 6b.

Figure 12 depicts results of microarray expression analysis of the ovarian carcinoma sequence designated 8e.

Figure 13 depicts results of microarray expression analysis of the ovarian carcinoma sequence designated 12c.

Figure 14 depicts results of microarray expression analysis of the ovarian carcinoma sequence designated 12h.

Figure 15A-15EEE depicts partial sequences of additional polynucleotides encoding representative secreted ovarian carcinoma antigens (SEQ ID NOs:82310־).

Figure 16 is a diagram illustrating the location of various partial O8E sequences within the full sequence.

DETAILED DESCRIPTION OF THE INVENTION

As noted above, the present invention is generally directed to compositions and use thereof for the treatment of cancer, such as ovarian cancer. The compositions described herein may include immunogenic polypeptides, polynucleotides encoding such polypeptides, binding agents such as antibodies that bind to a polypeptide, antigen presenting cells (APCs) and/or immune system cells (e.g., T cells).

Polypeptides of the present invention generally comprise at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof. Certain ovarian carcinoma proteins have been identified using an immunoassay technique, and are referred to herein as ovarian carcinoma antigens. An “ovarian carcinoma antigen” is a protein that is expressed by ovarian tumor cells (preferably human cells) at a level that is at least two fold higher than the level in normal ovarian cells. Certain ovarian carcinoma antigens react detectably (within an immunoassay, such as an ELISA or Western blot) with antisera generated against serum from an immunodeficient animal implanted with a human ovarian tumor. Such ovarian carcinoma antigens are shed or secreted from an ovarian tumor into the sera of the immunodeficient animal. Accordingly, certain ovarian carcinoma antigens provided herein are secreted antigens. Certain nucleic acid sequences of the subject invention generally comprise a DNA or

RNA sequence that encodes all or a portion of such a polypeptide, or that is complementary to such a sequence.

The present invention further provides ovarian carcinoma sequences that are identified using techniques to evaluate altered expression within an ovarian tumor.

Such sequences may be. polynucleotide or protein sequences. Ovarian carcinoma sequences are generally expressed in an ovarian tumor at a level that is at least two fold, and preferably at least five fold, greater than the level of expression in normal ovarian tissue, as determined using a representative assay provided herein. Certain partial ovarian carcinoma polynucleotide sequences are presented herein. Proteins encoded by >0 genes comprising such polynucleotide sequences (or complements thereof) are also considered ovarian carcinoma proteins. . ‘

Antibodies are generally immune system proteins, or antigen-binding fragments thereof, that . are- capable of binding to at least a- portion of an ovarian carcinoma polypeptide.as!,described herein. T cells that may . be employed, within the 15 compositions provided herein are generally T cells (e.g., CD4־ and/or CD8’) that are specific for such a polypeptide. Certain methods described herein further employ antigen-presenting cells (such as dendritic cells or macrophages) that express an ovarian carcinoma polypeptide as provided herein.

Ovarian Carcinoma Polynucleotides

Any polynucleotide that encodes an ovarian carcinoma protein or a portion or other variant thereof as described herein is encompassed by the present invention. Preferred .polynucleotides comprise at least 15 consecutive nucleotides, preferably at least 30.consecutive nucleotides, and more preferably at least 45 25 consecutive nucleotides, that encode a portion of an ovarian carcinoma protein. More preferably, a polynucleotide encodes an immunogenic portion of an ovarian carcinoma protein, such as an ovarian carcinoma antigen. Polynucleotides complementary to any such sequences are also encompassed by the present invention. Polynucleotides may be single-stranded (coding or antisense) or double-stranded, and may be DNA (genomic, cDNA or synthetic) orRNA molecules. Additional coding or non-coding sequences may, but need not, be, present within a polynucleotide of the present invention, and a polynucleotide may, but need not, be linked to other mofettes and/or support materials.

Polynucleotides may comprise a native sequence(/.?., an endogenous sequence that encodes an ovarian carcinoma protein or. a portion thereof) or may 5 comprise a variant of such a sequence. Polynucleotide variants may contain one or more substitutions, additions, deletions and/or insertions such that the immunogenicity of the encoded polypeptide is not diminished, relative to a native ovarian carcinoma protein. The effect on the immunogenicity of the encoded polypeptide may generally be assessed as described herein. Variants preferably exhibit at least about 70% identity, 10 more preferably at least about 80% identity and most preferably at least about 90% identity to a polynucleotide sequence that encodes a-native ovarian carcinoma protein or a portion thereof.

The percent, identity for two polynucleotide or polypeptide sequences may be readily determined by comparing sequences using computer algorithms well 15 known to those of ordinary, skill in the art, such as Megalign, using default parameters.

Comparisons between: .two sequences are typically performed by comparing the sequences over a comparison window to identify and compare local regions of sequence similarity. A comparison window׳’ as used herein, refers to a segment of at least about 20 contiguous positions, usually 30 to about 75, or 40 to about 50, in which a sequence 20 may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. Optimal alignment of sequences for comparison may be conducted, for example, using the Megalign program in the Lasergene suite of bioinformatics software (DNASTAR, Inc., Madison, WI), using default parameters; Preferably, the percentage of sequence identity is determined by 25 comparing two optimally aligned sequences over a window of comparison of at least 20 positions, wherein the portion of the polynucleotide or polypeptide sequence in the window may comprise additions or deletions (i.e., gaps) of 20 % or less, usually 5 to 15 /0, or 10 to 12/0, relative:to,.the reference sequence (which does not contain additions or deletions). The percent., identity may be calculated by determining the number of 30 positions at which the identical nucleic acid bases or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the reference sequence (i.e., the window size) and multiplying the results by 100 to yield the percentage of sequence identity.

Vanants , may also, or alternatively, be substantially homologous to a native gene, or a portion or complement thereof. Such polynucleotide variants are 5 capable of hybridizing.under moderately stringent conditions to a naturally occurring DNA sequence encoding a native ovarian carcinoma protein (or a complementary sequence). Suitable moderately stringent conditions include prewashing in a solution of 5 X SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0); hybridizing at 50°C-65°C, 5 X SSC, overnight; followed by washing twice at 65°C for 20 minutes with each of 2X, 0.5X and 10 0.2X SSC containing 0.1 % SDS.

It will be appreciated by those of ordinary skill in the art that, as a'result of the degeneracy of the; genetic code, there are many nucleotide sequences that encode a polypeptide as described herein. Some of these polynucleotides bear minimal homology to the nucleotide sequence of any native gene. Nonetheless, polynucleotides 15 that vary due to differences in codon usage are specifically contemplated by the present invention. Further, alleles, of the genes comprising the polynucleotide sequences provided herein are within the scope of the present invention. Alleles are endogenous genes that are altered as a result of one or more mutations, such as deletions, additions and/or substitutions of nucleotides. The resulting mRNA and protein may, but need 20 not, have an altered structure or function. Alleles may be identified using standard techniques (such as hybridization, amplification and/or database sequence comparison).

Polynucleotides may be prepared using any of a variety of techniques. For example, an ovarian carcinoma polynucleotide may be identified, as described in more detail below, .by ;screening a late passage ovarian tumor expression library with 25 antisera generated against sera of immunocompetent mice after injection of such mice with sera from SCID mice implanted with late passage ovarian tumors. Ovarian carcinoma polynucleotides may also be identified using any of a variety of techniques designed to evaluate, differential gene expression. Alternatively, polynucleotides may be amplified from cDNA prepared from ovarian tumor cells. Such polynucleotides may 30 be amplified via polymerase chain reaction (PCR). For this approach, sequence-specific

Primers may be designed based on the sequences provided here,״. _Md _{may b־}purchased or synthesized. ⁷

An amplified portion may be used io isolate a Ml _{leng4 gene fom ־}su. a ־ library (e.g, an ovarian carcinoma cDNA library) using w־U known _tectoiנ Within such techniques, a. library (cDNA or genomic) is screened using one or more polynucleotide prob־־ or primers suitable for amplification. P_ref־rably, a library is ־»־-selected to .״elude larger molecules. Random primed libraries may also be preferred for identifying 5' _{ups־reM regions of}preferred for obtaining introns and extending 5׳ sequences.

” For hybridization techniques, a partial sequence may be labeled (e ־ by mck-translation or end-labeling with ־־P) using w־H known techniques. A bacterial or bactenophage hbrary .is then screened by hybridizing filters containing denatured bactenai colon־־ (or lawns containing phag־ _plaq־״s) with the labeled probe (see Sambrook et al., M^rr/tm cloning: A Laboraiory Manual. Cold Spring Harbor >5 Laboratories, Cold Spring Harbor, NY, 1₉₈₉). Hybridizing colonies or plaques are selected and expanded, and the DNA is isolated for further analysis. cDNA don־־ may be analyzed to determine the amount of additional sequence by, for example, PCR using a primer from the partial sequence and a primer from the vector. Restriction maps and paraal sequences may !־־.generated to identify one or more overlapping clones The complete sequence may then be determined using standard techniques, which may mvoive generating a series of deletion clones. The resulting overlapping sequences are then assembled into a single contiguous sequence. A full length cDNA molecule can be generated by ligating suitable fragments, using well known techniques.

Alternatively, there are numerous amplification techniques for obtaining 25 a fill! length coding sequence from a partial cDNA sequence, within such techniques, amplification is generally, performed via PCR. Any of a variety of commercially available kits may be used to perform the amplification step. Primers may be designed using, for example, software we״ known in the art. Primers are-preferably 22-30 nucleotides in !״־gth. have, a GC content of at least 50־/״ and anneal to the target 0נ sequence at temperatures of about 68״C to 72״C, The amplified region may be sequenced as described above, and overlapping sequences assembled־ into a contiguous sequence.

One such amplification technique is inverse PCR (see Triglia et al, Nucl. Acids Res. 16:8186, 1988), which uses restriction enzymes to generate a fragment in the 5 known region of the.gene. The fragment is then circularized by intramolecular ligation and used as a template for PCR with divergent primers derived from the known region. Within an alternative approach, sequences adjacent to a partial sequence may be retrieved by amplification with a primer to a linker sequence and a primer specific to a known region. The amplified sequences are typically subjected to a second round of 10 amplification with the same linker primer and a second primer specific to the known region. A variation on this procedure, which employs two primers that' initiate extension in opposite directions from the known sequence, is described in WO 96/38591. Additional techniques include capture PCR (Lagerstrom et al. PCR Methods Applic. 7:111199 ,19־!).and walking PCR (Parker et al, Nucl. Acids. Res. /9:3055-60, 15 1991). Other methods empioying amplification may also be employed to obtain a full length cDNA sequence.

In certain. instances, it is possible to obtain a full length cDNA sequence by analysis of sequences provided in an expressed sequence tag .(EST) database, such as that available from GenBank. Searches for overlapping ESTs may generally be 20 performed using well known, programs (e.g., NCBI BLAST searches), and such ESTs may be used to generate a contiguous full length sequence.

Certain nucleic acid sequences of cDNA molecules encoding portions of ovarian carcinoma antigens are provided in Figures 1A-1S (SEQ ID NOS:1 to 71) and Figures 15A to 15EEE (SEQ ID NOs:82 to 310). The sequences provided in Figures 25 1A-1S appear to be novel־. For sequences in Figures 15A-I5EEE, database searches revealed matches having substantial identity. These polynucleotides were isolated by serological screening of an ovarian tumor cDNA expression library, using a technique designed to identify secreted tumor antigens. Briefly, a late passage ovarian tumor expression library was prepared from a SCID-derived human ovarian tumor (OV9334) j0 in the vector λ-screen, (Novagen). The sera used for screening were obtained by injecting immunocompetent mice with sera from SCID mice implanted with one late ¹ V« 1/νο77/^υώΓν passage cva^ tumors. _{technique Λ־} that encode immunogenic, portions of secreted tumor antigens.

The polynucleotides recited herein, _{מ wfl ω M Iength p0)vnucleotides}comprising such sequences, other portions of such Ml length polynucleotides and 5 sequences complementary to all or a portion of such Ml iength modes’ are specifically encompassed, by the present invention. It will be apparent to those of o״tay skill in the art that this technique can al״־ be applied to the identification of antigens that are secreted from other types of tumors.

Other nucleic acid sequences of cDNA molecules encoding portions of !0 ovarian carcinoma proteins ate provided in Figures 4-9 (SEQ ID NOs:75-81), as well as SEQ ID NOs:313-384. These sequences were identified by screening a microarray of cDNAs for tumor-associated expression (I.־., expression that is at least five fold greater tn an ovarian tumor than, in normal ovarian tissue, as determined using a representative assay provided herein),,Such screens were performed using a Synteni microarray (Palo 15 Alto, CA) according to,the manufacturer's instructions (and essentially as described by Schenaet al., Proc. Nall. Acad. Sci. USA 53:10614-10619. 1996 and Heller et al., Proc. Natl. Acad. Sci. USA 94:2150-2155, 1997). SEQ ID NOs:311 and 391 provide Ml length sequences incorporating certain of these nucleic acid sequences.

Any of a variety of well known techniques may be used to evaluate 20 tumor-associated expression of a cDNA. For example, hybridization techniques using labeled polynucleotide probes may be employed. Alternatively, or in addition, amplification techniques such as real-time PCR may be used (see Gibson et al. Genome Research ¢:995-1001,:1996; Heid et al. Genome Research ¢:986-994, 1996). Realtime PCR is a technique that evaluates the level of PCR product accumulation during 2־ amplification. Thisdechnique permits quantitative evaluation of mRNA levels in multiple samples. Briefly, mRNA is extracted fiom tumor and nonnal tissue and cDNA s prepared using standard techniques. Real-time PCR may be performed, for example, using a Perkin Elmer Applied Biosystems (Foster City, CA) 7700-Prism instrument Matching primers and fluorescent probes may be designed for genes of interest using, 30 for example, the primer express program provided by Perkin Elmer/Applied Biosystems (Foster City, CA). Optimal concentrations of primers and probes may be initially determined by those of ordinary skill in the art, and control (e.g_{x t?}ctin) pnmers and probes may be obtained commercially from, for example, Perkin Elmer/Appiied

Biosystems (Foster City/eA). To quantitate the amount of specific RNA in a «mpl, _a standard curve is generated alongside using a plasmid containing the gene of interest

Standard curves may be generated using the Ct values detennined in the real-time PCR, which are related to the initial cDNA concentration used in the assay. Standard dilutions ranging from 10-10־ copies of the gene of interest are generally sufficient. In addition, a standard curve is generated for the control sequence. This permits standardization of initial RNA content of a tissue sample to the amount of control for comparison purposes.

Polynucleotide variants may generally be prepared by any method known m the art,, ״including chemical synthesis by,. for example, solid phase phosphoramidite chemical synthesis. Modifications in a polynucleotide sequence may also be introduced using; standard mutagenesis techniques, such as oligonucleotide15 directed site-specific .- mutagenesis (see Adelman et al., DNA 2:183, 1983) Alternatively, RNA molecules may be generated by in vitro or in vivo transcription of DNA sequences encoding an ovarian carcinoma antigen, or portion thereof, provided that the DNA is incorporated into a vector with a suitable RNA polymerase promoter (such as T7 or SP6). Certain portions may be used to prepare an encoded polypeptide.

as described herein; In addition, or alternatively, a portion may be administered to a patient such that the encoded polypeptide is generated in vivo.

A portion of :a sequence complementary to a coding sequence (i.e., an antisense polynucleotide) may also be used as a probe or to modulate gene expression. cDNA constructs that, can be transcribed into antisense RNA may also be introduced 25 into cells or tissues to; facilitate the production of antisense RNA. An antisense polynucleotide may be used, as described herein, to inhibit expression of an ovarian carcinoma protein. Antisense technology can be used to control gene expression through triple-helix formation, which compromises the ability of the double helix to open sufficiently for. the; binding of polymerases, transcription factors or regulatory molecules (see Gee et al. In Huber and Carr, Molecular and Immunologic Approaches, Futura Publishing Co; (Mt. Kisco, NY; 1994). Alternatively, an antisense molecule may 0־ designed to hybridize with a eontroi region of a gene p_rom0Kr. _enhanc־r or transcription initiation site), and block _transc״_{pIwn of Qr} translation by inhibiting binding of a transcript to ribosomes.

Any polynucleotide may be further modified to increase stability i״ vi״ 5 Possible modifications, include, but are not limited to, the addition of flanking sequences at the 5 and/or 3' ends; the use of phosphorothioate or 2' 0-methyl rather than phosphodiesterase linkages in the backbone; and/or the inclusion of nontraditional bases such as inosine, queosine and wybutosine, as well as acetyl- methyl-, thio- and other modified forms of adenine, cytidine, guanine, thymine and uridine.

Nucleotide sequences as described herein may be joined to a variety of other nucleotide sequences, using established recombinant DNA techniques ' For example, a polynucleotide may be cloned into any of a variety of cloning vectors, including plasmids, phagemids, lambda phage derivatives and cosmids. Vectors of particular interest include, expression vectors, replication vectors, probe generation IS vectors and sequencing vectors. In general, a vector will contain an origin of replication functional in at least one organism, convenient restriction endonuclease sites and one or more selectable markers. Other elements will depend upon the desired use, and will be apparent to those of ordinary skill in the art.

Within certain embodiments, polynucleotides may be formulated so as to 20 permit entry into a cell of a mammal, and expression therein. Such formulations are particularly useful for therapeutic purposes, as described below. Those of ordinary skill in the art will appreciate that there are many ways to achieve expression of a polynucleotide in a target cell, and any suitable method may be employed. For example, a polynucleotide may be incorporated into a viral vector such as, but not 25 limited to, adenovirus, adeno-associated virus, retrovirus, or vaccinia or other pox virus (e.g., avian pox virus). .Techniques for incorporating DNA into such vectors are well known to those of ordinary skill in the art. A retroviral vector may additionally transfer or incorporate a gene for- a- selectable marker (to aid in the identification or selection of transduced cells) and/or. *,targeting moiety, such as a gene that encodes a ligand for a 0־ receptor on a specific target cell, to render the vector target specific. Targeting may also be accomplished using an antibody, by methods known to those of ordinary skill in the art.

Other, formulations for therapeutic purposes include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, microspheres, beads, and 5 lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. A preferred colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (i.e״ an artificial membrane vesicle). The preparation and use of such systems is well known in the art.

Ovarian Carcinoma Polypeptides

Within the context of the present invention, polypeptides may comprise at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof, as described herein״ As noted above, certain ovarian carcinoma proteins are ovarian carcinoma antigens., that are expressed by ovarian tumor cells and react detectably 15 within an immunoassay (such as an ELISA) with antisera generated against serum from an immunodeficient .animal implanted with an ovarian tumor. Other ovarian carcinoma proteins are encoded by ovarian carcinoma polynucleotides recited herein. Polypeptides as described herein may be of any length. Additional sequences derived from the native protein and/or heterologous sequences may be present, and such sequences may (but 20 need not) possess further immunogenic or antigenic properties.

An immunogenic portion. ’ as used herein is a portion of an antigen that is recognized (i.e., specifically bound) by a B-cell and/or T-cell surface antigen receptor. Such immunogenic portions generally comprise at least 5 amino acid residues, more preferably ,.at least 10, and still more preferably at least 20 aminn acid 25 residues of an ovarian carcinoma protein or a variant thereof. Preferred immunogenic portions are encoded by cDNA molecules isolated as described herein. Further immunogenic portions may generally be identified using well known techniques, such as those summarized in Paul, Fundamental Immunology, 3rd ed., 243-247 (Raven Press,

1993) and references cited therein. Such techniques include screening polypeptides for 0ג the ability to react with ovarian carcinoma protein-specific antibodies, antisera and/or T-cell lines or clones. As used herein, antisera and antibodies are ovarian carcinoma protein-specific״ if they specifically bind to an ovarian carcinoma_protein (i.e., they react with the ovarian carcinoma protein in an ELISA or other immunoassay, and do not react detectably with unrelated proteins). Such antisera, antibodies and T cells may be prepared as described herein, and using well known techniques. An immunogenic 5 portion of a native ovarinmcarcinoma protein is a portion, that reacts with such antisera, antibodies and/or T־eclls. at ajevel that is not substantially less than the reactivity of the full length polypeptide (e.g., in an ELISA and/or T-cell reactivity assay). Such immunogenic portions may react within such assays at a level that is similar to or greater than the reactivity of the full length protein. Such screens may generally be 10 performed using methods well known to those of ordinary skill in the art, such as those described in Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring־ Harbor Laboratory, 1988. For.example, a polypeptide may be immobilized on a solid support and contacted with patient sera to allow binding of antibodies within the sera to the immobilized polypeptide,.: Unbound sera may then be removed and bound antibodies 15 detected using, for example,: ¹²⁵!-labeled Protein A.

As . noted above, a composition may comprise a variant of a native ovarian carcinoma protein. A polypeptide “variant,” as used herein, is a polypeptide that differs from a native ovarian carcinoma protein in one or more substitutions, deletions, additions and/or insertions, such that the immunogenicity of the polypeptide 20 is not substantially diminished. In other words, the ability of a variant to react with ovarian carcinoma protein-specific antisera may be enhanced or unchanged, relative to the native ovarian carcinoma protein, or may be diminished by less than 50%, and preferably less than 20%, relative to the native ovarian carcinoma protein. Such variants may generally, be identified by modifying one of the above polypeptide 25 sequences and evaluating the reactivity of the modified polypeptide with ovarian carcinoma protein-specific antibodies or antisera as described herein. Preferred variants include those in which: one or more portions, such as an N-terminal leader sequence or transmembrane domain, have been removed. Other preferred variants include variants in which a small portion (e.g., 1-30 amino acids, preferably 5-15 amino acids) has been 30 removed from the N- and/or C-terminal of the mature protein.

Polypeptide variants preferably exhibit at leas£ ־about 70%, more preferably at least about 90% and most preferably at least about 95% identity to the native polypeptide. Preferably, a variant contains conservative substitutions. A conservative substitution״ is one in which an amino acid is substituted for another 5 amino acid that has similar properties, such that one skilled in the art of peptide chemistry would expect the secondary structure and hydropathic _of the polypeptide to be substantially unchanged. Amino acid substitutions may generally be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity and/or the amphipathic nature of the residues. For example, negatively 10 charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and arginine; and amino acids with uncharged polar head groups having similar hydrophilicity values include leucine, isoleucine and valine; glycine and alanine, asparagine and glutamine; and serine, threonine, phenylalanine and tyrosine. Other groups of amino י acids that may represent conservative changes include: (1) ala, 15 pro, gly, glu, asp, gin, asn, ser, thr; (2) cys, ser, tyr, thr; (3) val, ile, leu, met, ala, phe;

(4) lys, arg, his, and (5.) phe, tyr, trp, his. A variant may also, or alternatively, contain nonconservative changes. Variants may also (or alternatively) be modified by, for example, the deletion or addition of amino acids that have minimal influence on the immunogenicity, secondary structure and hydropathic nature of the polypeptide.

^{20 As noted} above, polypeptides may comprise a signal (or leader) sequence at the N-terminal־'end of the protein which co-translationallv or posttranslationally directs: :transfer of the protein. The polypeptide: may also be conjugated to a linker or other sequence for ease of synthesis, purification or identification of the polypeptide (e.g., polyrfljs), or to enhance binding, of the polypeptide to a solid support.

For example, a polypeptide may be conjugated to an immunoglobulin Fc region.

Polypeptides may be prepared using any of a variety of well known techniques. Recombinant polypeptides encoded by DNA sequences as described above may be readily prepared from the DNA sequences using any of a variety of expression vectors known to those of ordinary skill in the art. Expression may be achieved in any 30 appropriate host cell that has been transformed or transfected with an expression vector containing a DNA molecule that encodes a recombinant polypeptide. Suitable host cells include prokaryotes, yeast and higher eukaryotic cells. Preferably, the host cells employed are £ W yeast or a mammalian cell line _such as COS or CHO. Supernatants from Suitable host/vector systems which secrete recombinant protein or polypeptide into culture media may be first concentrated using acommercially available צ filter. Following Sohdentration, the concentrate may be applied to a suitable purification matrix such as an affinity matrix or an ion exchange resin. Finally, one or more reverse phase HPLC steps can be employed to further purify a recombine polypeptide.

Portions and other variants having fewer than about 100 amino acids, 10 and generally fewer than about 50 amino acids, may also be generated by synthetic means, using techniques well known to those of ordinary skill in the art. For example, such polypeptides may be synthesized using any of the commercially available solidphase techniques, such as the Merrifield solid-phase synthesis, method, where amino acids are sequentially-added to a growing amino acid chain. See Merrifield, J. Am.

Chem. Soc. 85:2149-2146,4963. Equipment for automated synthesis of polypeptides is commercially available from suppliers such as Applied BioSystems, Inc. (Foster City, CA), and may be operated according to the manufacturer’s instructions.

Within certain specific embodiments, a polypeptide may be a fusion protein that comprises , multiple polypeptides as described herein, or that comprises one 20 polypeptide as described herein and a known tumor antigen; such as an ovarian carcinoma protein or-.-a variant of such a protein. A fusion partner may, for example, assist m providing. T-helper: epitopes (an immunological fusion partner), preferably T helper epitopes recognized by humans, or may assist in expressing the protein (an expression enhancer). at .higher yields than the native recombinant protein. Certain 25 preferred fusion partners, are both immunological and expression enhancing fusion partners. Other fusion, partners may be selected so as to increase the solubility of the protein or to enable-the protein to be targeted to desired intracellular compartments. Still further fusion partners include affinity tags, which facilitate purification of the protein.

⁵⁰ Fusion, proteins may generally be prepared using standard techniques, including chemical conjugation. Preferably, a fusion protein is expressed as a recombinant protein, allowing the production of increased levels, relative to a non-ftsed protein, in an expression.system. Briefly, DNA sequences encoding the polypeptide components may.be.a־s־mbl־d separately, and ligated into an appropriate expression vector. The 3' end. of the DNA sequence encoding one polypeptide component is 5 ligated, with or without a .peptide linker, to the 5’ end of a DNA sequence encoding the second polypeptide component so that the reading flames of the. sequences are in phase. This permits translation into a single fusion protein that retains the biological activity of both component polypeptides.

A peptide linker sequence may be employed to separate the first and the 10 second polypeptide components by a distance sufficient to ensure that each polypeptide folds into its secondary and tertiary structures. -Such a peptide linker sequence is incorporated into. the :fusion protein using standard techniques well known in the art. Suitable peptide linker, sequences may be chosen, based on the following factors: (1) their ability to adopt a flexible extended conformation; (2) their, inability to adopt a 15 secondary structure thaUcould interact with functional epitopes on the first and second polypeptides; and (3) the,lack of hydrophobic or charged residues that might react with the polypeptide functional epitopes. Preferred peptide linker sequences contain Gly, Asn and Ser residues. Other near neutral amino acids, such as Thr and Ala may also be used m the linker sequence. Amino acid sequences which may be usefully employed as 20 linkers include those disclosed in Maratea etal., Gene 40-.39-46. 1985; Murphy etal., Proc. Natl. Acad. Sci; USA 53:8258-8262, 1986; U.S. Patent No. 4,935,233 and U.S. Patent No. 4,751,18Q. The linker sequence may generally be from 1 to about 50 amino acids in length. Linker sequences are not required when the first and second polypeptides have non-essential N-terminal amino acid regions that can be used to 25 separate the functional .domains and prevent steric interference.

The ligated DNA sequences are operably linked to suitable transcriptional or translational regulatory elements. The regulatory elements responsible for expression of DNA are located only 5׳ to the DNA sequence encoding the first polypeptides.: Similarly, stop codons required to end translation and 30 transcription termination,signals are only present 3׳ to the DNA sequence encoding the second polypeptide.

Fusion proteins are also provided that comprise_a_pplypeptide of the present invention together with an unrelated immunogenic protein. Preferably the immunogenic protein is capable of eliciting a recall response. Examples of such proteins include tetanus, tuberculosis and hepatitis proteins (see, for example, Stoute et al. New Engl. J.Med., 336:8691,1997־).

Within, preferred embodiments, an immunological fusion partner is derived from protein D, a surface protein of the gram-negative bacterium Haemophilus influenza B (WO 91/18926). Preferably, a protein D derivative comprises approximately the first third of the protein (e.g., the first N-terminal 100-110 amino 10 acids), and a protein D derivative may be lipidated. Within certain preferred embodiments, the first 109 residues of a Lipoprotein D fusion partner is included bn the N-terminus to provide.the.poiypeptide with additional exogenous T-cell epitopes and to increase the expression-level in E. coli (thus functioning as an expression enhancer). The lipid tail ensures- optimal presentation of the antigen to antigen present cells. Other 15 fusion partners include־ the non-structural protein from influenzae virus, NS1 (hemaglutinin). Typically, the N-terminal 81 amino acids are used, although different fragments that include T-helper epitopes may be used.

In another embodiment, the immunological fusion partner is the protein known as LYTA, or a portion thereof (preferably a C-terminal portion). LYTA is 20 derived from Streptococcus pneumoniae, which synthesizes an N-acetyl-L-alanine amidase known as amidase LYTA (encoded by the LytA gene; Gene 73:265-292. 1986). LYTA is an; autolysin that specifically degrades certain bonds in the peptidoglycan backbone., The C-terminal domain of the LYTA protein is responsible for the affinity to. the choline or to some choline analogues such as DEAE. This 25 property has been exploited for the development of E. coli C-LYTA expressing plasmids useful for expression of fusion proteins. Purification of hybrid proteins containing the C-LYTA fragment at the amino terminus has been described (see Biotechnology /0:795-798, 1992). Within a preferred embodiment, a repeat portion of LYTA may be incorporated into a fusion protein. A repeat portion is found in the C30 terminal region starting at residue 178. A particularly preferred repeat portion incorporates residues 188-305.

In general; polypeptides (including fusion proteinsj and polynucleotides as described herein are.isolated. An ״isolated״ polypeptide or polynucleotide is one that is removed from its original environment. For example, a naturally-occurring protein is isolated if it is separated? from some or all of the coexisting materials in the natural 5 system. Preferably, , such polypeptides are at least about 90% pure, more preferably at least about 95% pure and most preferably at least about 99% pure. A polynucleotide is considered to be isolated if, for example, it is cloned into a vector that is not a part of the natural environment.

־־s

Binding Agents

The present invention further provides agents, such as antibodies and antigen-binding fragments, ,thereof, that specifically bind to an ovarian carcinoma protein. As used herein; an: antibody, or antigen-binding fragment thereof, is said to specifically bind to!.an ovarian carcinoma protein if it reacts at a detectable level 15 (within, for example, an^-ELISA) with an ovarian carcinoma protein, and does not react detectably with unrelated proteins under similar conditions. As used herein, binding refers to a noncovalent association between two separate molecules such that a complex is formed!:. The ability to bind may be evaluated by, for example, determining a binding constant for the formation of the complex. The binding constant 20 is the value obtained when the concentration of the complex is divided by the product of the component concentrations. In general, two compounds are said to bind, in the context of the present- invention, when the binding constant for complex formation exceeds about 10 LZmol. ;The binding constant maybe determined using methods well known in the art. , , . .

²⁵ Binding., agents may be further capable of. differentiating between patients with and without .a cancer, such as ovarian cancer, using the representative assays provided herein.:;.!!! other words, antibodies or other binding agents that bind to a ovarian carcinoma antigen; will generate a signal indicating the presence of a cancer in at least about 20% of patients with the disease, and will generate a negative signal 30 indicating the absence of the disease in at least about 90% of individuals without the cancer. To determine: whether a binding agent satisfies this requirement, biological samples (e.g., blood, sera, leukophoresis, urine and/or tumor biopsies) from patients with and without a cancer (as determined using standard clinical tests) may be assayed as described herein for the presence of polypeptides that bind to the binding agent It will be apparent that a statistically significant number of samples with and without the disease should be assayed.? Each binding agent should satisfy the above criteria; however, those of ordinary. skill in the art will recognize that binding agents may be used in combination to improve sensitivity.

Any agent that satisfies the above requirements may be a binding agent For example, a binding agent may be a ribosome, with or without a peptide component, an RNA molecule or a polypeptide. In a preferred embodiment a binding agent is an antibody or an antigen-binding fragment thereof. Antibodies may be prepared־ by any of a variety of techniques known to those of ordinary skill in the art. See, e.g., Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988. In general, antibodies can be. :produced by cell culture techniques, including the generation of monoclonal antibodies-as described herein, or via transfection of antibody genes into suitable bacterial or mammalian cell hosts, in order to allow for the production of recombinant antibodies. In one technique, an immunogen comprising the polypeptide is initially injected into any of a wide variety of mammals (e.g., mice, rats, rabbits, sheep or goats). In this step, the polypeptides of this invention may serve as the immnnogpin without modification. Alternatively, particularly for relatively short polypeptides, a superior immune response may be elicited if the polypeptide is joined to a carrier protein, such as bovine serum albumin or keyhole limpet hemocyanin. The immunogen is injected into the animal , host, preferably according to a predetermined schedule incorporating one or more.booster immunizations, and the animals are bled periodically. Polyclonal antibodies; specific for the polypeptide may then be purified from such antisera by, for example;; affinity chromatography using the polypeptide coupled to a suitable solid support.

Monoclonal antibodies specific for an antigenic polypeptide of interest may be prepared, for example, using the technique of Kohler and Milstein, Eur. J. Immunol. <5:511-519, 1976; and improvements thereto. Briefly, these methods involve the preparation of immortal cell lines capable of producing antibodies having the desired specificity (/. e״ reactivity with the polypeptide of interest). Such cell lines may be produced, for example, from spleen cells obtained from an animal immunized as described above. The.spleen Cells are then immortalized by, for example, fusion with a myeloma cell fusion־ partiler, preferably one that is syngeneic with the immunized animal. A variety of fusion techniques may be employed. For example, the spleen cells and myeloma cells may־ be combined with a nonionic detergent for a few minutes and then plated at low density on a selective medium that supports the growth of hybrid cells, but not myeloma cells. A preferred selection technique uses HAT (hypoxanthine, aminopterin, thymidine) selection. After a sufficient time, usually about 1 to 2 weeks, colonies of hybrids are observed. Single colonies are selected and their culture supernatants tested for binding activity against the polypeptide. Hybridomas having high reactivity and-specificity are preferred.

Monoclonal, antibodies may be isolated from the supernatants of growing hybridoma colonies. In־.addition, various techniques may be employed to enhance the yield, such as injection: of the hybridoma cell line into the peritoneal cavity of a suitable vertebrate host, such as a mouse. Monoclonal antibodies may then be harvested from the ascites fluid or the . blood. Contaminants may be removed from the antibodies by conventional techniques,, such as chromatography, gel filtration, precipitation, and extraction. The polypeptides of this invention may be used in the purification process in, for example, an affinity chromatography step.

Within certain embodiments, the use of antigen-binding fragments of antibodies may be preferred. Such fragments include Fab fragments, which may be prepared using standard- ׳techniques. Briefly, immunoglobulins may- be purified from rabbit serum by affinity chromatography on Protein A bead columns (Harlow and Lane, Antibodies. A Laboratory.Manual, Cold Spring Harbor Laboratory, 1988) and digested by papain to yield Fab and . Fc fragments. The Fab and Fc fragments may be separated by affinity chromatography on protein A bead columns.

Monoclonal antibodies of the present invention may be coupled to one or more therapeutic agents.: Suitable agents in this regard include radionuclides, differentiation inducers:, drugs, toxins, and derivatives thereof. Preferred radionuclides include Y, I, I,_; . :1:, ^ls6Re, ¹⁸⁸Re, ²¹¹At, and ²¹²Bi. Preferred drugs include methotrexate, and pyrimidine and purine analogs. Preferred differentiation inducers include phorbol ester^and butyric acid. Preferred toxins include ricin, abrin, diptheria toxin, cholera toxin, ; gelonin, Pseudomonas exotoxin, Shigella toxin, and pokeweed antiviral protein.

A therapeutic agent may be coupled (־.g״ covalently bonded) to a suitable monoclonal antibody either directly or indirectly (e.g., via a linker group). A direct reaction between an agent and an antibody is possible when each a substituent capable of reacting with the other. For example, a nucleophilic group, such as an amino or sulfhydryl group, on one may be capable of reacting with a carbonyl10 containing group, such as, an anhydride or an acid halide, or with an alkyl group containing a good leaving group-(e.g., _a halide) on־the other.

Alternatively, it may be desirable to couple a therapeutic agent and an antibody via a linker group., A linker group can function as a spacer to distance an antibody from an agent in order to avoid interference with binding capabilities. A 15 linker group can also serve to increase the chemical reactivity of a substituent on an agent or an antibody, and thus increase the coupling efficiency. An increase in chemical reactivity may also -facilitate the use of agents, or functional groups on agents, which otherwise would not be possible.

It will be evident to those skilled in the art that a variety of bifunctional 20 or polyfunctional reagents, both homo- and hetero-functional (such as those described in the catalog of the. Pierce Chemical Co., Rockford, IL), may be employed as the linker group. Couphngmay be,effected, for example, through amino groups, carboxyl groups, sulfhydryl groups or oxidized carbohydrate residues. There are numerous references describing such methodology e.g., U.S. Patent No. 4,671,958, to Rodwell et al.

Wh^ere. a therapeutic agent is more potent when free from the antibody portion of the immunoconjugates of the present invention, it may be desirable to use a linker group which is cleavable during or upon internalization into a cell. A number of different cleavabie linker, groups have been described. The mechanisms for the intracellular release of an agent from these linker groups include cleavage by reduction 30 of a disulfide bond (e.g:, U.S. Patent No. 4,489,71.0, to Spitler), by in-adiation of a photolabiie bond (e.g.,.U.S., Patent No. 4,625,014, to Senter etal.), by hydrolysis of derivatized amino acid side chains (e.g., U.S. Patent No. 4,638,045^0 Kohn et al.), by serum complement-mediated hydrolysis (e.g., U.S. Patent No. 4,671,958, to Rodwell et al.), and acid-catalyzed hydrolysis (e.g., U.S. Patent No. 4,569,789, to Blattler et al.).

It may be desirable to couple more than one agent to an antibody. In one 5 embodiment, multiple molecules of an agent are coupled to one antibody molecule. In another embodiment, more than one type of agent may be coupled to one antibody. Regardless of the particular embodiment, immunoconjugates with more than one agent may be prepared in a variety of ways. For example, more than one agent may be coupled directly to an antibody molecule, or linkers which provide multiple sites for 10 attachment can be used. Alternatively, a carrier can be used.

A earner may bear the agents in a״ vanety of ways, including covalent bonding either directly or via a linker group. Suitable earners include proteins such as albumins (e.g., U.S. Patent No. 4,507,234, to Kato et al.), peptides and polysaccharides such as aminodextran; (e.g., U.S. Patent No. 4,699,784, to Shih et al.). A carrier may 15 also bear an agent by noncovalent bonding or by encapsulation, such as within a liposome vesicle (e.g.<U.S. Patent Nos. 4,429,008 and 4,873,088). Carriers specific for radionuclide agents include radiohalogenated small molecules and chelating compounds. For example, U.S. Patent No. 4,735,792 discloses representative radiohalogenated small molecules and their synthesis. A radionuclide chelate may be 20 formed from chelating compounds that include those containing nitrogen and sulfur atoms as the donor atoms for binding the metal, or metal oxide, radionuclide. For example, U.S. Patent No; 4,673,562, to Davison et al. discloses representative chelating compounds and their synthesis.

A variety of routes of administration for the antibodies and 25 immunoconjugates may be used. Typically, administration will be intravenous, intramuscular, subcutaneous or in the bed of a resected tumor. It will be evident that the precise dose of the antibody/immunoconjugate will vary depending upon the antibody used, the antigen density on the tumor, and the rate of clearance of the antibody.

Also provided herein are anti-idiotypic antibodies that mimic an 30 immunogenic portion of an ovarian carcinoma protein. Such antibodies may be raised against an antibody, or, antigen-binding fragment thereof, that specifically binds to an immunogenic portion, of an ovarian carcinoma protein, using well_known techniques.

Anti-idiotypic antibodies that mimic an immunogenic portion of an ovarian carcinoma protein are those antibodies that bind to an antibody, or antigen-binding fragment thereof, that specifically binds to an immunogenic portion of an ovarian carcinoma protein, as described herein.

T Cells

Immunotherapeutic compositions may also, or alternatively, comprise T cells specific for an ovarian carcinoma protein. Such cells may generally be prepared in vitro or ex vivo, using standard procedures. For example, T cells may be present within (or isolated from) bone marrow, peripheral blood or a fraction of bone marrow or peripheral blood of a mammal, such as a patient, using a commercially available cell separation system, such as the CEPRATE™ system, available from CellPro Inc, Bothell WA (see also U.S. Patent No. 5,240,856; U.S. Patent No. 5,215,926; WO 89/06280; WO 91/16146 and WO 92/07243). Alternatively, T cells may be derived from related or unrelated humans, non-human animals, cell lines or cultures.

T cells may be stimulated with an ovarian carcinoma polypeptide, polynucleotide encoding-an ovarian carcinoma polypeptide and/or an antigen presenting cell (APC) that expresses such a polypeptide. Such stimulation is performed under conditions and for a time sufficient to permit the generation of T cells that are specific for the polypeptide. Preferably, an ovarian carcinoma polypeptide or polynucleotide is present within a delivery vehicle, such as a microsphere, to facilitate the generation of specific T cells.

T cells are considered to be specific for an ovarian carcinoma polypeptide if the T cells kill target cells coated with an ovarian carcinoma polypeptide or expressing a gene encoding such a polypeptide. T cell specificity may be evaluated using any of a variety of standard techniques. For example, within a chromium release assay or proliferation assay, a stimulation index of more than two fold increase in lysis and/or proliferation, compared to negative controls, indicates T cell specificity. Such assays may be performed, for example, as described in Chen et al. Cancer Res. 54:1065-1070, 1994. Alternatively, detection of the proliferation of T cells may be accomplished by a variety of known techniques. For example, TceU proliferation can be detected by measuring an increased rate ofDNA synthesis (e.g., by pulse-labeling cultures of T cells with tritiated thymidine and measuring the amount of tritiated thymidine incorporated into DNA). Contact with an ovarian carcinoma polypeptide 5 (200 ng/ml - 100 pg/mi, preferably 100 ng/ml - 25 gg/ml) for 3 - 7 days should result in at least a two fold increase in proliferation of the T cells and/or contact as described above for 2-3 hours should result in activation of the T cells, as measured using standard cytokine assays in which a two fold increase in the level of cytokine release (e.g., TNF or IFN-γ) is indicative of T cell activation (see Coligan et al., Current 10 Protocols in Immunology, vol. 1, Wiley Interscience (Greene 1998). T cells that have been activated m response to an ovarian carcinoma polypeptide, polynucleotide or ovarian carcinoma polypeptide-expressing APC may be CD4⁺ and/or CD8⁺. Ovarian carcinoma polypeptide-specific T cells may be expanded using standard techniques. Within preferred embodiments, the T cells are derived from a patient or a related or 15 unrelated donor and :are administered to the patient following stimulation and expansion.

For therapeutic purposes, CD4⁺ or CD8+ T cells that proliferate in response to an ovarian carcinoma polypeptide, polynucleotide or APC can be expanded in number either in vitro or in vivo. Proliferation of such T cells in vitro may be 20 accomplished in a variety of ways. For example, the T cells can be re-exposed to an ovarian carcinoma polypeptide, with or without the addition of T cell growth factors, such as interleukin-2, and/or stimulator cells that synthesize an ovarian carcinoma polypeptide. Alternatively, one or more T ceils that proliferate in the presence of an ovarian carcinoma polypeptide can be expanded in number by cloning. Methods for 25 cloning cells are well known in the art, and include limiting dilution. Following expansion, the cells may be administered back to the patient as described, for example, by Chang et al., Grit. Rev. Oncol. Hematol. 22:213, 1996.

Pharmaceutical Compositions and Vaccines ³⁰ Within certain aspects, polypeptides, polynucleotides, binding agents and/or immune system cells as described herein may be incorporated into pharmaceutical compositions or vaccines. Pharmaceutical compositions comprise one or more such compounds or cells and a physiologically acceptable earner. Vaccines may comprise one or more such compounds or cells and a non-specific immune response enhancer. A non-specific immune response enhancer may be any substance that enhances an immune response to an exogenous antigen. Examples of non-specific immune response enhancers include adjuvants, biodegradable microspheres (e.g., polylactic galactide) and liposomes (into which the compound is incorporated; see e.g., Fullerton, U.S. Patent No. 4,235,877). Vaccine preparation is generally described in^ for example, M.F. Powell and M.J. Newman, eds., ״Vaccine Design (the subunit and adjuvant approach),״ Plenum Press (NY, 1995). Pharmaceutical compositions and vaccines within the scope of the present invention-may also contain other compounds, which may be biologically active or inactive. For example, one or more immunogenic portions of other tumor-antigens may be present, either incorporated into a fusion polypeptide or as a separate compound within the composition or vaccine.

^{15 A} Pharmaceutical composition or vaccine may contain DNA encoding one or more of the. polypeptides as described above, such that the polypeptide is generated in situ. As noted above, the DNA may be present within any of a variety of delivery systems known to those of ordinary skill in the art, including nucleic acid expression systems, bacteria and viral expression systems. Appropriate nucleic acid expression systems contain die necessary DNA sequences for expression in the patient (such as a suitable promoter and terminating signal). Bacterial delivery systems involve the administration of a bacterium (such as Bacillus-Calmette-Guerrin) that expresses an immunogenic portion of the polypeptide on its cell surface. In a preferred embodiment, the DNA may be introduced using a viral expression system (e.g., vaccinia or other pox virus, retrovirus, or adenovirus), which may involve the use of a non-pathogenic (defective), replication competent virus. Suitable systems are disclosed, for example, in Fisher-Hoch et al., PNAS 86:317-321, 1989; Flexner et al., Ann. N.Y. Acad. Sci. 569:86-103, 1989; Flexner et al., Vaccine 8:17-21, 1990; U.S. Patent Nos. 4,603,112, 4,769,2530, and 5,017,487; WO 89/01973; U.S. Patent No. 4,777,127; GB 2.200,651;

EP 0,345,242; WO 91/02805; Berkner, Biotechniques 6:616-627, 1988; Rosenfeld et al., Science 252:431 -434,. 1991; Kolls et al., PNAS 92:215-219, 1994; Kass-Eisler et al.,

PNAS 90:11498-11502, 1993; Guzman et al., Circulation 55:283_8-2848, 1993; and Guzman et al., Cir. Res. 73:1202-1207, 1993. Techniques for incorporating DNA into such expression systems are well known to those of ordinary skill in the art. The DNA may also be naked, as described, for example, in Ulmer et al., Science 259:1745-1749, 5 1993 and reviewed by Cohen, Science 259:1691-1692, 1993. The uptake of naked DNA may be increased by coating the DNA onto biodegradable beads, which are efficiently transported into the cells.

While any suitable carrier known to those of ordinary skill in the art may be employed in the pharmaceutical compositions of this invention, the type of carrier 10 will vary depending on the mode of administration. Compositions of the present invention may be formulated for any appropriate manner of administration, including for example, topical, .oral, nasal, intravenous, intracranial, intraperitoneal, subcutaneous or intramuscular administration. For parenteral administration, such as subcutaneous injection, the carrier preferably comprises water, saline, alcohol, a fat, a wax or a buffer. 15 For oral administration, any of the above earners or a solid carrier, such as mannitol _נlactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, glucose, sucrose, and magnesium carbonate, may be employed. Biodegradable microspheres k^e-S-> polylactate polyglycolate) may also be employed as carriers for the pharmaceutical compositions of this invention. Suitable biodegradable microspheres 20 are disclosed, for example, in U.S. Patent Nos. 4,897,268 and 5,075,109.

Such compositions may also comprise buffers (e.g., neutral buffered saline or phosphate buffered saline), carbohydrates (e.g., glucose, mannose, sucrose or dextrans), mannitol, proteins, polypeptides or amino acids such as glycine, antioxidants, chelating agents such as. EDTA or glutathione, adjuvants (e.g., aluminum hydroxide) 25 and/or preservatives. Alternatively, compositions of the present invention may be formulated as a lyophilizate. Compounds may also be encapsulated within liposomes using well known technology.

Any of a variety of non-specific immune response enhancers may be employed in the vaccines, of this invention. For example, an adjuvant may be included. 30 Most adjuvants contain a substance designed to protect the antigen from rapid catabolism, such as aluminum hydroxide or mineral oil, and a stimulator of immune responses, such as lipid A, Bortadella _pern1ssis or Mycobaaeriumjuberculosis derived proteins. Suitable adjuvants are commercially available as, for example, Freund's Incomplete Adjuvant and Complete Adjuvant (Difco Laboratories, Detroit, MI), Merck Adjuvant 65 (Merck and Company, Inc., Rahway, Nl), alum, biodegradable 5 microspheres, monophosphoryl lipid A and quil A. Cytokines, such as GM-CSF or interleukin-2, -7, or -12, may also be used as adjuvant.^

Within the vaccines provided herein, the adjuvant composition is preferably designed to induce an immune response predominantly of the Thl type. High levels of Thl-type cytokines (e.g., IFN-γ, IL-2 and IL-12) tend to favor the 10 induction of cell mediated immune responses to an administered antigen. In contrast, high levels of Th2-type cytokines (e.g., IL-4, IL-5, IL-6, IL-10 and INF-β)־trad to favor the induction of humoral immune responses. Following application of a vaccine as provided herein, a patient will support an immune response that includes Thl- and Th2-type responses. Within a preferred embodiment, in which a response is 15 predominantly Thl-type, the level of Thl-type cytokines will increase to a greater extent than the level of Th2-type cytokines. The levels of these cytokines may be readily assessed using standard assays. For a review of the families of cytokines, see Mosmann and Coffman, Jnn. 2?ev. Zr/wnwnoZ. 7:145-173 1989.

Preferred adjuvants for use in eliciting a predominantly Thl-type 20 response include, for example, a combination of monophosphoryl lipid A, preferably 3de-O-acylated monophosphoryl lipid A (3D-MPL), together with an Aluminum _sa!t. MPL adjuvants are available from Ribi ImmunoChem Research Inc. (Hamilton, MT; see US Patent Nos. 4,436,727; 4,877,611; 4,866,034 and 4,912,094). Also preferred is AS-2 (SmithKline Beecham). CpG-containing oligonucleotides (in which the CpG 25 dinucleotide is unmethylated) also induce a predominantly Thl response. Such oligonucleotides are well known and are described, for example, in WO 96/02555. Another preferred adjuvant is a saponin, preferably QS21, which may be used alone or in combination with other adjuvants. For example, an enhanced system involves the combination of a monophosphoryl lipid A and saponin derivative, such as the 30 combination of QS21 and 3D-MPL as described in WO 94/00153, or a less reactogenic composition where the QS21 is quenched with cholesterol, as described in WO

96/33739. Other preferred formulations _compns־s tocopherol. A particularly potent adjuvant fonnulation involving QS21, 3D-MPL and tocopherol m an oil-in-water emulaion is described in WO 95/17210. Any vaccine provided herein may . be prepared using well known methods * combmation of antigen, immune response enhancer and a suitable carrier or excipient

The compositions described herein may be administered as part of a sustamed ״lease fonnulation (i.־. a fo״n״lati״n such as a capsule or _Sp_ong־ that effects a slow release of compound Mowing administration). Such fotmulations may generally be prepared using well known technology and administered by, for example, oral, rectal or subcutaneous implantation, or by implantation at the desired target sit־.’ Sustained-release formulations may contain a polypeptide, polynucleotide or antibody dispersed in a carrier matrix and/or contained within a reservoir surrounded by a mte controlling membrane, Carriers for use within such formulations are biocompatible, and may also be biodegradable; preferably the fonnulation provides a relatively constant level of active component release. The amount of active compound contained wtthm a sustained reiease fonnulation depends upon the site of implantation, the rate and expected duration of release and the nature of the condition to be treated or prevented.

Any of a variety of delivery vehicles may be employed within 20 pharmaceutical compositions and vaccines to facilitate production of an antigen-specific immune response that targets tumor cells. Delivery vehicles include antigen presenting cells (APCs), such as dendritic cells, macrophages, B cells, monocytes and other cells that may be engineered, to be efficient APCs. Such cells may, but need not, be genetically modified to increase the capacity for presenting the antigen, to improve 25 activation and/or maintenance of the T cell response, to have anti-tumor effects per _seand/or to be immunologically compatible with the receiver (i.e., matched HLA haplotype). APCs may generally be isolated from any of a variety of biological fluids and organs, including tumor and peritumotal tissues, and may- be autologous, allogeneic, syngeneic or xenogeneic cells.

¹⁰ certain, preferred embodiments of the present invention use dendritic cells or progenitors thereof as antigen-presenting cells. Dendritic cells are highly potent

APCs (Banchereau and Steinman, Nature 392:245-251. 1998) and have been shown to be effective, as a physiological adjuvant for eliciting prophylactic or therapeutic antitumor immunity (see Timmerman and Levy, Ann Rev. Med. 50:507-529, 1999). In general, dendritic cells may be identified based on their typical shape (stellate in situ, 5 with marked cytoplasmic processes (dendrites) visible in vitro) and based on the lack of differentiation markers ofB cells (CD19 and CD20), T ceils (CD3), monocytes (CD14) and natural killer cells (CD56), as determined using standard assays. Dendritic cells may, of course, be engineered to express specific cell-surface receptors or ligands that are not commonly found on dendritic cells in vivo or ex vivo, and such modified to dendritic cells are contemplated by the present invention. As an alternative to cells, secreted vesicles antigen-loaded dendritic cells (called exosomes) may be used within a vaccine (see Zitvogel et al., Nature Med. 4:594-600, 1998)

Dendritic cells and progenitors may be obtained from peripheral blood, bone marrow, tumor-infiltrating cells, peritumoral tissues-infiltrating cells, lymph 15 nodes, spleen, skin, umbilical cord blood or any other suitable tissue or fluid. For example, dendritic cells may be differentiated ex vivo by adding a combination of cytokines such as GM-CSF, IL-4, IL-13 and/or TNFa to cultures of monocytes harvested from peripheral blood. Alternatively, CD34 positive cells harvested from peripheral blood, umbilical cord blood or bone marrow may be differentiated into 20 dendritic cells by adding to the culture medium combinations of GM-CSF, IL-3, TNFa, CD40 ligand, LPS, flt3 ligand and/or other comppund(s) that induce maturation and proliferation of dendritic cells. .

Dendritic cells are conveniently categorized as immature and mature cells, which allows a simple way to discriminate between two well characterized 25 phenotypes. However, this nomenclature should not be construed to exclude all possible intermediate stages of differentiation. Immature dendritic cells are characterized as APC with a high capacity for antigen uptake and processing, which correlates with the high expression of Fey receptor, mannose receptor and DEC-205 marker. The mature phenotype is typically characterized by a lower expression of these 30 markers, but a high expression of cell surface molecules responsible for T cell activation such as class I and class Π MHf , s 1 ana class U MHC, adhesion molecules (e._& CD54 and CD11) and cosnmulatory molecules (e.g״ CD40, CD80 and CD86).

APCs may generally be transfected with a polynucleotide encoding a ovarian carcinoma antigen (or portion or other variant thereof) such that the antigen, or 5 an immunogenic portion thereof, is expressed on the ״־־ surface. _Suchmay take place ex viva, and a composition or vaccine comprising such transfected cells may then be used for therapeutic pmposes, as described herein. Alternatively, a gene ifehvery vehicle that targets a dendritic or other antigen presenting ceil may be administered to a patient, resulting in transfection that occurs in vivo. In vivo and ex .0 vivo transfection of dendritic cells, for example, may generally be performed using any methods known in the art, such as those described in WO 97/24447, or the gene gun approach described by Mahvi et al. Immunology and cell Biology 75:456-160 1997 Antigen loading of dendritic cells may be achieved by incubating dendritic cells or progenitor cells with the polypeptide, DNA (naked or within a plasmid vector) or RNA >5 or with antigen-expressing recombinant bacterium or viruses (e.g. vaccinia, fowlpox,’ adenovirus or lentivirus vectors). Prior to loading, the polypeptide may be covalently conjugated to an immunological partner that provides T cell help (e.g״ a earner molecule). Alternatively, a dendritic cell may be pulsed with a non-conjugated immunological partner, separately or in the presence ofthe polypeptide.

Cancer Therapy

In further aspects of the present invention, the compositions described herein may be used for immunotherapy of cancer, such as ovarian cancer. Within such methods, pharmaceutical, compositions and vaccines are typically administered to a 25 patient. As used herein, a “patient״ refers to any wann-biooded animal, preferably a human. A patient may or may not be afflicted with cancer. Accordingly, the above pharmaceutical compositions and vaccines may be used to prevent the development of a cancer or to treat a patient afflicted with a cancer. Within certain prefered embodiments, a patient is. afflicted with ovarian cancer. Such cancer may be diagnosed 30 usmg criteria generally accepted in .he an, including the presence of a malignant tumor. Pharmaceutical compositions and vaccines may be administered either prior to or following surgical removal of primary tumors and/or treatment such a־ administration of radiotherapy or conventional chemotherapeutic drugs.

Within certain embodiments, immunotherapy may be active immunotherapy, m which treatment relies on the in vivo stimulation of the endogenous 5 host immune system to react against tumors with the administration of immuno response-modifying agents־ (such as tumor vaccines, bacterial adjuvants and/or cytokines).

Within other embodiments, immunotherapy may be passive immunotherapy, m which treatment involves the delivery of agents with established 10 tumor-immune reactivity (such as effector cells or antibodies) that can directly or indirectly mediate antitumor effects and does not necessarily depend on an intact host immune system. Examples of effector cells include T lymphocytes (such as CD8* cytotoxic T lymphocytes- and CD4⁺ T-helper tumor-infiltrating lymphocytes), killer cells (such as Natural Killer cells and lymphokine-activated killer ceils), B cells and 15 antigen-presenting cells (such as dendritic cells and macrophages) expressing a polypeptide provided herein. T cell receptors and antibody receptors specific for the polypeptides recited herein may be cloned, expressed and transferred into other vectors or effector cells for adoptive immunotherapy. The polypeptides provided herein may also be used to generate, antibodies or anti-idiotypic antibodies (as described above and in U.S. Patent No. 4,918,164) for passive immunotherapy.

Effector cells may generally be obtained in sufficient quantities for adoptive immunotherapy-by growth in vitro, as described herein. Culture conditions for expanding single antigen-specific effector cells to several billion in number with retention of antigen recognition in vivo are well known in the art. Such in vitro culture 25 conditions typically use intermittent stimulation with antigen, often in the presence of cytokines (such as IL-2) and non-dividing feeder cells. As noted above, immunoreactive polypeptides as provided herein may be used to rapidly expand antigen-specific T cell cultures in order to generate a sufficient number of cells for immunotherapy. In particular, antigen-presenting cells, such as dendritic, macrophage 30 or B cells, may be pulsed with immunoreactive polypeptides or transfected with one or more polynucleotides using standard techniques well known in the art. For example, antigen-presenting cells can be transfected with a polynucleotide having a promoter appropriate for increasing expression in a recombinant virus or other expression system. Cultured effector cells for use in therapy must be able to grow and distribute widely, and to survive long term in vivo. Studies have shown that cultured effector cells can be 5 induced to grow in vivo and to survive long tenn in substantial numbers by repeated stimulation with antigen supplemented with IL-2 (see, for example, Cheever et al., Immunological Reviews 157:177, 1997).

Alternatively, a vector expressing a polypeptide recited herein may be introduced into stem cells taken from a patient and clonally propagated in vitro for 10 autologous transplant back into the same patient.

Routes and frequency of administration, as well as dosage, wiH’ vary from individual to individual, and may be readily established using standard techniques. In general, the pharmaceutical compositions and vaccines may be administered by injection (e.g., intracutaneous, intramuscular, intravenous or subcutaneous), intranasally 15 (e.g., by aspiration), orally or in the bed of a resected tumor. Preferably, between 1 and 10 doses may be administered over a 52 week period. Preferably, 6 doses are administered, at intervals of 1 month, and booster vaccinations may be given periodically thereafter. Alternate protocols may be appropriate for individual patients. A suitable dose is an amount of a compound that, when administered as described 20 above, is capable of promoting an anti-tumor immune response, and is at least 10-50% above the basal (i.e. untreated) level. Such response can be monitored by measuring the anti-tumor antibodies in a patient or by vaccine-dependent generation of cytolytic effector cells capable of killing the patient’s tumor cells in vitro. Such vaccines should also be capable of causing an immune response that leads to an improved clinical outcome (e.g., more frequent remissions, complete or partial or longer disease-free survival) m vaccinated patients as compared to non-vaccinated patients. In general, for pharmaceutical compositions and vaccines comprising one or more polypeptides, the amount of each polypeptide present in a dose ranges from about 100 μg to 5 mg per kg of host. Suitable dose sizes will vary with the size of the patient, but will typically range from about 0.1 mL to about 5 mL.

In general, an appropriate dosage and treatment regimen provides the active compound(s) in an amount sufficient to provide therapeutic and/or prophylactic benefit. Such a. response can be monitored by establishing an improved clinical outcome (e.g., more frequent remissions, complete or partial, or longer disease-free 5 survival) in treated patients as compared to non-treated patients. Increases in preexisting immune responses to an ovarian carcinoma antigen generally correlate with an improved clinical outcome. Such immune responses may generally be evaluated using standard proliferation, cytotoxicity or cytokine assays, which may be performed using samples obtained from a patient before and .after treatment.

Screens for Identifying Secreted Ovarian Carcinoma Antigens -- ־

The present invention provides methods for identifying secreted tumor antigens. Within such methods, tumors are implanted into immunodeficient animals such as SCID mice and maintained for a time sufficient to permit secretion of tumor 15 antigens into serum. In general, tumors may be implanted subcutaneously or within the gonadal fat pad of an immunodeficient animal and maintained for 1-9 months^ preferably 1-4 months. Implantation may generally be performed as described in WO 97/18300. The serum containing secreted antigens is then used to prepare antisera in immunocompetent mice, using standard techniques and as described herein. Briefly, 20 50-100 pL of sera (pooled from three sets of immunodeficient mice, each set bearing a different SCID-derived human ovarian tumor) may be mixed 1:1 (vokvol) with an appropriate adjuvant, such as RIBI-MPL or MPL + TDM (Sigma Chemical Co., St. Louis, MO) and injected intraperitoneally into syngeneic immunocompetent animals at monthly intervals for a total of 5 months. Antisera from animals immunized in such a 25 manner may be obtained by drawing blood after the third, fourth and fifth immunizations. The resulting antiserum is generally pre-cleared of E. coli and phage antigens and used (generally following dilution, such as 1:200) in a serological expression screen.

The library is typically an expression library containing cDNAs from one 30 or more tumors of the type that was implanted into SCID mice. This expression library may be prepared in any suitable vector, such as λ-screen (Novagen). cDNAs that encode a polypeptide that reacts with the antiserum may be identified using standard techniques, and, sequenced. Such cDNA molecules may be father characterized to evaluate expression in tumor and normal tissue, and to evaluate antigen secretion in patients.

The methods provided herein have advantages over other methods for tumor antigen discovery. In particular, all antigens identified by such methods should be secreted or released through necrosis of the tumor cells. Such antigens may be present on the surface of tumor cells for an amount of time sufficient to permit targeting and killing by the immune system, following vaccination.

Methods for Detecting Cancer In general, a cancer may be detected in a patient based on the presence of one or more ovarian carcinoma proteins and/or polynucleotides encoding such proteins in a biological sample (such as blood, sera, urine and/or tumor biopsies) obtained from 15 the patient. In other words, such proteins may be used as markers to indicate the presence or absence of a cancer such as ovarian cancer. In addition, such proteins may be useful for the detection of other cancers. The binding agents provided herein generally permit detection of the level of protein that binds to the agent in the biological sample. Polynucleotide primers and probes may be used to detect the level of mRNA 20 encoding a tumor protein, which is also indicative of the presence or absence of a cancer. In general, an ovarian carcinoma-associated sequence should be present at a level that is at least three fold higher in tumor tissue than in normal tissue

There are a-yariety of assay formats known to those of ordinary skill in the art for using a binding agent to detect polypeptide markers in a sample. See, e.g., 25 Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988. In general, the presence or absence of a cancer in a patient may be determined by (a) contacting a biological sample obtained from a patient with a binding agent; (b) detecting in the sample a level of polypeptide that binds to the binding agent; and (c) comparing the level of polypeptide with a predetermined cut-off value.

^{30 a} P^ref^erred embodiment, the assay involves the use of binding agent immobilized on a solid support to bind to and remove the polypeptide from the r־ma,״d־_r of the sample. _bound * ־tecnon reagent that contains a reporter group and specifically binds to the binding agent/polypeptide complex. _Such detection ״ * btndtng agent that specifically binds to the poiypepttde or an antibody or other agent 5 that specifically binds to the binding agent, such as an anti-immunoglobulin, protein G protein A or a lectm. Alternatively, a competitive assay may be utilized, in which a polypeptide s labeled with a reporter group and allowed to bind to the immobilized bmdmg agent after incubation of the binding agent with the sample. The extent to which components of the sample inhibit the binding of the !abated polypeptide to the bmdmg agent is indicative of the reactivity of the sample with the immobilized binding agent. Suitable polypeptides for use within such assays include full length־ ovarian carcinoma proteins and portions thereof to which the binding agent binds, as described above.

The solid support may be any material known to those of ordinary skill in the art to which the tumor protein may be attached. For exampie, the solid support may be a test well in a microliter plate or a nitrocellulose or other suitable membrane. Alternatively, the support may be a bead or disc, such as glass, fiberglass, latex or a plastic material such as .polystyrene or polyvinylchloride. The support may also be a magnetic particle or a fiber optic sensor, such as those disclosed, for example, in U S Patent No. 5,359,681. ,The binding agent may be immobiiized on the solid support using a variety of techniques known to those of skill in the an. which are amply described in the patent and scientific literature. In the context of the present invention the term ״immobilization״ refers to both ״״ncovtdent association, such as adsorption and covalent attachment, (which may be a direct linkage between the agent and fimctional groups on the support or may be a linkage by way of a cross-linking agent). Immobilization by adsorption to a well in a microtiter plate or to a membrane is preferred. In such cases, adsorption may be achieved by contacting the binding agent m a suitable buffer, with the soiid support for a suitable amount of time. The contact time varies with temperature, but is typicaily between about I hour and about 1 day In general, contacting a well of a plastic microtiter piate (such as polystyrene or polyvinylchloride) with an amount of binding agent ranging from about 10 ng to about gg, and preferably about 100 ng to about i qg, _is sufficient.!» immobilize an adequate amount of binding agent.

Covalent attachment of binding agent to a solid support may generally be achieved by firat reacting the support with a biftmotional reagent that wiil react with 5 both the support and a functional group, such as a hydroxyl or amino group, on the binding agent. For example, the binding agent may be covalently attached to supports having an appropriate polymer coating using benzoquinone or by condensation of an aldehyde group on the support with an amine and an active hydrogen on the binding partner (see, e.g., Pierce Immunotechnology Catalog and Handbook, 1991, at 10 A12-A13).

In certain embodiments, the assayis a two-antibody sandwich assay. This assay may be performed by first contacting an antibody that has been immobilized on a solid support, commonly the well of a microliter plate,, with the sample, such that polypeptides within the sample are allowed to bind to the immobilized antibody.

Unbound sample is :then- removed from the immobilized polypeptide-antibody complexes and a detection reagent (preferably a second antibody capable of binding to a different site on the polypeptide) containing a reporter group is added. The amount of detection reagent that remains bound to the solid support is then determined using a method appropriate for the specific reporter group.

^{20 M0re s}P^ecificaIly, once the antibody is immobilized on the support as described above, the remaining protein binding sites on the support are typically blocked. Any suitable , blocking agent known to those of ordinary skill in the art, such as bovine serum albumimor Tween 20™ (Sigma Chemical Co., St. Louis, MO). The immobilized antibody is then incubated with the sample, and polypeptide is allowed to bind to the antibody. The sample may be diluted with a suitable diluent, such as phosphate-buffered saline (PBS) prior to incubation. In general, an appropriate contact time (i.e., incubation time) is a period of time that is sufficient to detect the presence of polypeptide within a sample obtained from an individual with ovarian cancer. Preferably, the contact time is sufficient to achieve a level of binding that is at least 30 about 95% of that achieved at equilibrium between bound and unbound polypeptide.

Those of ordinary skill in the art will recognize that the time necessary to achieve equilibrium may be readily determined by assaying the level of binding that occurs over a period of time. At room temperature, an incubation time of about 30 minutes is generally sufficient.

Unbound sample may then be removed by washing the solid support 5 with an appropriate buffer, such as PBS containing 0.1% Tween 20™. _־,ת second antibody, which contains a reporter group, may then be added to the solid support. Preferred reporter groups include those groups recited above.

The detection reagent is then incubated with the immobilized antibodypolypeptide complex for an amount of time sufficient to detect the bound polypeptide.

An appropriate amount of time may generally be determined by assaying the level of binding that occurs over a period of time. Unbound detection reagent is theri removed and bound detection reagent is detected using the reporter group. The method employed for detecting. the reporter group depends upon the nature of the reporter group. For radioactive groups, scintillation counting or autoradiographic methods are 15 generally appropriate. Spectroscopic methods may be used to detect dyes, luminescent groups and fluorescent groups. Biotin may be detected using avidin, coupled to a different reporter group (commonly a radioactive or fluorescent group or an enzyme). Enzyme reporter groups may generally be detected by the addition of substrate (generally for a specific period of time), followed by spectroscopic or other analysis of 20 the reaction products.

To determine the presence or absence of a cancer, such as ovarian cancer, the signal detected from the reporter group that remains bound to the solid support is generally compared to a signal that corresponds to a predetermined cut-off value. In one preferred embodiment, the cut-off value for the detection of a cancer is 25 the average mean signal obtained when the immobilized antibody is incubated with samples from patients without the cancer. In general, a sample generating a signal that is three standard deviations above the predetermined cut-off value is considered positive for the cancer. In an alternate preferred embodiment, the cut-off value is determined using a Receiver Operator Curve, according to the method of Sackett et al., Clinical 30 Epidemiology: A Basic Science for Clinical Medicine, Little Brown and Co., 1985, p- 106-7. Briefly, in this embodiment, the cut-off value may be determined from a plot of pairs oftrue positive rates (i e sensitivity ״«־λ λ,ι ^υ ־’ ^ns1tIW) and false positjve rates fl00%-specificity) that ״־_{mspond to} ־^ _c״t._{off va|uc for} value ״״ die plot that is the ״!־seat t־ _{the upper left}._tad ה מב τ ה^is “״^{most accurate} “^{d a} ־ g־al that« higher than the cut-off value determined by this method may be considered positive. Alternat־,״!,, the cut-off value may be shifted to the iefl a!_{ong a־ piot> tQ}mint».« the false positive rate, or to the right, to minimize the false negative rate In general, a sample generating a signal that is higher than the cut-off value determined by this method is considered positive for a cancer.

1־ a related embodiment, the assay is perforated in a flow-through or Stnp test format, wherein the binding agent is immobilized on a membra־״, such as nitrocellulose. In the flow-through test, polypeptides within the sample bind to the immobilized binding agent as the sample passes through the membrane. A second labeled bmdmg agent then binds to the binding agent-polypeptide complex as a solution containing the second binding agent flows through the membrane. The detection of bound second binding agent may then be performed as described above. In the strip test format, one end of the membrane to which binding agent is bound is immersed in a solution containing the sample. The sample migrates along the membrane through a region contammg second binding agent and to the area of immobilized binding agent. Concentration of second binding agent at the area of immobilized antibody indicates the presence of a cancer. Typically, th־ concentration of second binding agent at that site generates a pattern, such as a line, that can be read visually. The absence of such a pattern tndteates a negative result. In general, the amount of binding agent immobilized membrane is selected to generate a visually discernible pattern when the biological sample contains a !eve! of polypeptide that would be sufficient to generate a positive signal in the two-antibody sandwich assay, in the format discussed above. Preferred binding agents for use in such assays are antibodies and antigen-binding fragments thereof. Preferably, the amount of antibody immobilized-־־ the membrane ranges flora about 25 ng to about l_Mg, and more preferably from about 50 ng to about 500 ng. Such tests can typically be nerformpH ^y penormea with a very small amount of biological sample.

Of course, numerous other assay protocols exist that are suitable for use with the tumor proteins or binding agents of the present invention. The above descriptions are intended to be exemplary only. For example, it will be apparent to those of ordinary skill in the art that the above protocols may be readily modified to use 5 ovarian carcinoma polypeptides to detect antibodies that bind to such polypeptides in a biological sample. The detection of such ovarian carcinoma protein specific antibodies may correlate with the presence of a cancer.

A cancer may also, or alternatively, be detected based on the presence of T cells that specifically react with an ovarian carcinoma protein in a biological sample.

Within certain methods, a biological sample comprising CD4⁺ and/or CD8* T cells isolated from a patient is incubated with an ovarian carcinoma protein, a polynucleotide encoding such a polypeptide and/or an APC that expresses at least an immunogenic portion of such a polypeptide, and the presence or absence of specific activation of the T cells is detected. Suitable biological samples include, but are not limited to, isolated 15 T cells. For example, T cells may be isolated from a patient by routine techniques (such as by Ficoll/Hypaque density gradient centrifugation of peripheral blood lymphocytes). T cells may be incubated in vitro for 2-9 days (typically 4 days) at 37°C with an ovarian carcinoma protein (e.g., 5 - 25 pg/ml). It may be desirable to incubate another aliquot of a T cell sample in the absence of ovarian carcinoma protein to serve as a control. For

CD4⁺ T cells, activation is preferably detected by evaluating proliferation of the T cells. For CD8 T cells, activation is preferably detected by evaluating cytolytic activity. A level of proliferation that is at least two fold greater and/or a level of cytolytic activity that is at least 20% greater than in disease-free patients indicates the presence of a cancer in the patient.

³³ As noted above, a cancer may also, or alternatively, be detected based on the level of mRNA encoding an ovarian carcinoma protein in a biological sample. For example, at least two oligonucleotide primers may be employed in a polymerase chain reaction (PCR) based assay to amplify a portion of an ovarian carcinoma protein cDNA derived from a biological sample, wherein at least one ofthe oligonucleotide primers is 30 specific for (i.e., hybridizes to) a polynucleotide encoding the ovarian carcinoma protein. The amplified cDNA is then separated and detected using techniques well known m die art, such as gel electrophoresis. Similarly, oligonucleotide probes that specifically hybridize to a polynucleotide encoding an ovarian carcinoma pmtein may be used in a hybridization assay to detect the presence of polynucleotide encoding the tumor protein in a biological sample.

To permit hybridization under assay conditions, oligonucleotide primers and probes should comprise an oligonucleotide sequence that has at least about 60%, preferably at least about 75% and more preferably at least about 90%, identity to a portion of a polynucleotide encoding an ovarian carcinoma protein that is at least 10 nucleotides, and preferably at least 20 nucleotides, in length. Preferably, 10 oligonucleotide primers and/or probes hybridize to a polynucleotide encoding a polypeptide described herein under moderately stringent conditions, as defined above. Oligonucleotide primers and/or probes which may be usefully employed in the diagnostic methods described herein preferably are at least 10-40 nucleotides in length. In a preferred embodiment, the oligonucleotide primers comprise at least 10 contiguous 15 nucleotides, more preferably at least 15 contiguous nucleotides, of a DNA molecule having a sequence provided herein. Techniques for both PCR based assays and hybridization assays are well known in the art (see, for example, Mullis et al. Cold Spring Harbor Symp. Quant. Biol., 57:263, 1987; Erlich ed., PCR Technology, Stockton Press, NY, 1989).

^{20 One} P^referred assay employs RT-PCR, in which PCR is applied in conjunction with reverse transcription. Typically, RNA is extracted from a biological sample such as a biopsy tissue and is reverse transcribed to produce cDNA molecules. PCR amplification using at least one specific primer generates a cDNA molecule, which may be separated and visualized using, for example, gel electrophoresis. Amplification 25 may be performed on biological samples taken from a test patient and from an individual who is not afflicted with a cancer. The amplification reaction may be performed on several dilutions of cDNA spanning two orders of magnitude. A two-fold or greater increase in expression in several dilutions of the test patient sample as compared to the same dilutions of the non-cancerous sample is typically considered 30 positive.

In another embodiment, ovarian carcinoma proteinsaid polynucleotides encoding such proteins may be used as markers for monitoring the progression of ־־ncer. In this embodiment, assays as described above for the diagnosis of a cancer may be performed over time, and the change in the level of reactive polypeptide(־) 5 evaluated. For example, the assays may be performed every 24-72 hours for a period of 6 months to 1 year, and thereafter perfotmed as needed. In general, a cancer is progressing in those patients in whom the level of polypeptide detected by the binding agent increases over time. In contrast, the cancer is not progressing when the level of reactive polypeptide either remains constant or decreases with time.

Certain in vivo diagnostic assays may be performed directly on a tumor.

One such assay involves contacting tumor cells-with a binding agent. The bound binding agent may then be detected directly or indirectly via a reporter group. Such binding agents may also be used in histological applications. Alternatively, polynucleotide probes may be used within such applications.

As noted above, to improve sensitivity, multiple ovarian carcinoma protein markers may be assayed within a given sample. It will be apparent that binding agents specific for different proteins provided herein may be combined within a single assay. Further, multiple primers or probes may be used concurrently. The selection of tumor protein markers may be based on routine experiments to determine combinations 20 that results in optimal sensitivity. In addition, or alternatively, assays for tumor proteins provided herein may be combined with assays for other known tumor antigens.

Diagnostic Kits

The present invention further provides kits for use within any of the 25 above diagnostic methods. Such kits typically comprise two or more components necessary for performing a diagnostic assay. Components may be compounds, reagents, containers and/or equipment. For exampie, one container within a kit may contain a monoclonal antibody or fragment thereof that specifically binds to an ovarian carcinoma protein. Such antibodies or fragments may be provided attached to a support □0 material, as described above. One or more additional containers may enclose elements, such as reagents or buffers, to be used in the assay. Such kits may also, or alternatively, contain a detection reagent as described above that direct or indirect detection of antibody binding.

Alternatively, a kit _{w be d־signed t0 detect fte} encodmg an ovarian carcinoma protein in a biological sample. Such kits generally 5 comprise at least one oligonucleotide probe or primer, as described above that hybridizes to a polynucleotide ״־״־ding an ovarian carcinoma pmtein. Such an oligonucleotide may be used, for example, within a PCR or hybridization assay Addinonal components that may be present within such kits include a second oligonucleotide and/or a diagnostic reagent or container to facilitate the detection of a polynucleotide encoding an ovarian carcinoma protein.

The following Examples are offered by way of illustration and riot by way of limitation.

contains a reporter jeroup suitable for

EXAMPLES —— —— Λ

Example

Identification of Representative Ovarian Carcinoma Protein cDNAs

This Example illustrates the identification of cDNA molecules encoding ovarian carcinoma proteins.

Anti-SCID mouse sera (generated against sera from SCID mice carrying late passage ovarian carcinoma) was pre-cleared of E. coli and phage antigens and used 10 at a 1:200 dilution in a serological expression screen. The library screened was made from a SCID-derived human ovarian tumor (OV9334) using a directional RH oligo(dT) priming cDNA library construction kit and the !Screen vector (Novagen). A bacteriophage lambda screen was employed. Approximately 400,000 pfu of the amplified OV9334 library were screened.

196 positive clones were isolated. Certain sequences that appear to be novel are provided in Figures 1A-1S and SEQ ID NOs:l to 71. Three complete insert sequences are shown in Figures 2A-2C (SEQ ID NOs:72 to 74). Other clones having known sequences are presented in Figures' 15A-15EEE (SEQ ID NOs:82 to 310). Database searches identified the following sequences that were substantially identical to 20 the sequences presented in Figures 15 A-15EEE.

These clones were further characterized using microarray technology to determine mRNA expression levels in a variety of tumor and normal tissues. Such analyses were performed using a Synteni (Palo Alto, CA) microarray, according to the manufacturer's instructions. PCR amplification products were arrayed on slides, with 25 each product occupying a unique location in the array. mRNA was extracted from the tissue sample to be tested, reverse transcribed and fluorescent-labeled cDNA probes were generated. The microarrays were probed with the labeled cDNA probes and the slides were scanned to measure fluorescence intensity. Data was analyzed using Synteni s provided GEMtools software. The results for one clone (13695, also referred 30 to as O8E) are shown in Figure 3.

Example

Identification of Ovarian Carcinoma cDNAs using Microamtv TX-hnnl,^

This Example illustrates the identification of ovarian carcinoma polynucleotides by PCR subtraction and microarray analysis. Microarrays of cDNAs were analyzed for ovarian tumor-specific expression using a Synteni (Palo Alto, CA) microarray, according to the manufacturer's instructions (and essentially as described by 10 Schena et al., Proc. Natl. Acad. Sci. USA 93:10614-10619, 1996 and Heller et al., Proc.

Natl. Acad. Sci. USA 94:2150-2155,1997).

A PCR subtraction was performed using a tester comprising cDNA of four ovarian tumors (three of which were metastatic tumors) and a driver of cDNA form five normal tissues (adrenal gland, lung, pancreas, spleen and brain). cDNA fragments 15 recovered from this subtraction were subjected to DNA microarray analysis where the fragments were PCR amplified, adhered to chips and hybridized with fluorescently labeled probes derived from mRNAs of human ovarian tumors and a variety of normal human tissues. In this analysis, the slides were scanned and the fluorescence intensity was measured, and the data were analyzed using Synteni's GEMtools software. In 20 general, sequences showing at least a 5-fold increase in expression in tumor cells (relative to normal cells) were considered ovarian tumor antigens. The fluorescent results were analyzed and clones that displayed increased expression in ovarian tumors were further characterized by DNA sequencing and database searches to deteimine the novelty of the sequences.

²⁵ Using such assays, an ovarian tumor antigen was identified that is a splice fusion between the human T-cell leukemia virus type I oncoprotein TAX (see Jin et al., Cell 93:81-91, 1998) and an extracellular matrix protein called osteonectin. A splice junction sequence exists at the fusion point. The sequence of this clone is presented in Figure 4 and SEQ ID NO:75. Osteonectin, unspliced and unaltered, was 30 also identified from such assays independently.

Further clones identified by this method are referredto herein as 3f, 6b, 8e, 8h, 12c and 12h. Sequences of these clones are shown in Figures 5 to 9 and SEQ ID NOs:76 to 81. Microarray analyses were performed as described above, and are presented in Figures 10 to 14. A fid! length sequence encontpassing clones 3f, 6b, 8־ 5 and 12h was obtained by screening an ovarian tumor (SCID-derived) cDNA library. This 2996 base pair sequence (designated O772P) is presented in SEQ ID NO:311, and the encoded 914 amino acid protein sequence is shown in SEQ ID NO:312. PSORT analysis indicates a Type 1 a transmembrane protein localized to the plasma membrane.

In addition to certain of the sequences described above, this screen identified the following sequences:

<td> Sequence</td><td> Comments</td>

<td> OV4vGll (SEQ ID NO:313)</td><td> human clone 1119D9 on chromosome 20pl2</td>

<td> OV4vBU (SEQ ID NO:314)</td><td> human UWCrC:yl4cO94 from chromosome 6p21</td>

<td> OV4vD9 (SEQ ID NO:315)</td><td> human clone 1U49G16 chromosome 20ql2-13.2</td>

<td> OV4vD5 (SEQ ID NO:316)</td><td> human KIAA0014 gene</td>

<td> OV4vC2 (SEQ ID NO:317)</td><td> human KIAA0084 gene</td>

<td> OV4vF3 (SEQ ID NO:318)</td><td> human chromosome 19 cosmid R31167</td>

<td> OV4VC1 (SEQ ID NO:319)</td><td> novel</td>

<td> OV4vH3 (SEQ ID NO:320)</td><td> novel</td>

<td> OV4vD2 (SEQ ID NO:321)</td><td> novel</td>

<td> O815P (SEQ ID NO:322)</td><td> novel</td>

<td> OV4vC12 (SEQ ID NO:323)</td><td> novel</td>

<td> OV4vA4 (SEQ ID NO:324)</td><td> novel</td>

<td> OV4vA3 (SEQ ID NO:325)</td><td> novel</td>

<td> OV4v2A5 (SEQ ID NO:326)</td><td> novel</td>

<td> 0819P (SEQ ID NO:327)</td><td> lovel</td>

<td> O818P (SEQIDNO:328) !</td><td> tovel</td>

<td> O817P(SEQIDNO:329) _r O816P (SEQ IDNO:330) _r</td><td> lovel lovel</td>

<td> Ov4vC5 (SEQ ID NO:331) _n</td><td> lovel</td>

<td> Sequence</td><td> Comments__</td>

<td> 21/21 (SEQID NO.-332)</td><td> human iumican</td>

<td> 21719 (SEQ IDNO:333)</td><td> human icLiiioic acid-binding protein II</td>

<td> 21/17 (SEQ ID NO:334)</td><td> humau26S piulcasome A1 Base subunit</td>

<td> 21654 (SEQ ID NO:335)</td><td> human copine I</td>

<td> 21627 (SEQ ID NO:336)</td><td> human neuron specific gamma-2 enolase</td>

<td> 21623 (SEQ ID NO:337)</td><td> human geranylgeranyl transferase II</td>

<td> 21621 (SEQ IDNO:338)</td><td> human cyclin-dependent protein kinase</td>

<td> 21616 (SEQ ID NO1339)</td><td> human prepro-megakaryocyte potentiating factor</td>

<td> 21612 (SEQ ID NO:340)</td><td> human UPH1</td>

<td> 21558 (SEQ ID NO.341־)</td><td> human RalGDS-like 2 (RGL2)</td>

<td> 21555 (SEQ ID NO:342)</td><td> human autoantigen P542</td>

<td> 21548 (SEQ ID NO.-343)</td><td> human actin-related protein (ARP2)</td>

<td> 21462 (SEQ ID NO:344)</td><td> human huntingtin interacting protein</td>

<td> 21441 (SEQ IDNO:345)</td><td> human 9UK product (tumor associated antigen)</td>

<td> 21439 (SEQ ID NO:346)</td><td> human guanine nucleotide regulator protein (timl)</td>

<td> 21438 (SEQ ID NO:347)</td><td> human Ku autoimmune (p70/p80) antigen</td>

<td> 21237 (SEQ ID NO:348)</td><td> human S-laminin</td>

<td> 21436 (SEQ ID NO:349)</td><td> human ribophorin I</td>

<td> 21435 (SEQ ID NO:350)</td><td> human cytoplasmic chaperonin hTRiC5</td>

<td> 21425 (SEQIDNO:35I)</td><td> 1umanEMX2</td>

<td> 21423 (SEQ ID NO:352) I</td><td> luman p87/p89 gene</td>

<td> 21419 (SEQ ID NO.-353) 1</td><td> mman HPBRH-7</td>

<td> 21252 (SEQ ID N0:354) I</td><td> luman T1-227H</td>

<td> 21251 (SEQ ID NO:355) ־ h</td><td> Luman cullin I</td>

<td> 21247 (SEQ ID NO:356) k</td><td> unitz type protease inhibitor (KOP)</td>

<td> 21244-1 (SEQ ID NO:357) h c</td><td> uman protein tyrosine phosphatase receptor F PTPRF)</td>

<td> 21718 (SEQ ID NO:358) h</td><td> uman LTR repeat</td>

<td> OV2-90 (SEQ ID NO:359) _n</td><td> ovel</td>

Sequence

Comments

<td> Human zinc finger (SEQ ID NO:2</td><td> 60) ’ ' :----------^:-------------</td>

<td colspan="2"> Human polyA binding protein (SEQ ID NO:361) --------</td>

<td colspan="2"> Human pleitrophin (SEQ ID NO:362) ---------—</td>

<td colspan="2"> Human PAC clone 278C19 (SEQ ID NO:363) -----—--</td>

<td colspan="2"> Human LLRep3 (SEQ ID NO:364) ' ־------------------</td>

<td colspan="2"> Human Kunitz type protease inhib (SEQ ID NO:365)</td>

<td colspan="2"> Human KIAA0106 gene (SEQ ID NO:366) ----</td>

<td colspan="2"> Human keratin (SEQ ID NO:367) ---־-------</td>

<td colspan="2"> Human HIV-1 TAR (SEQ ID NO:368) ~ ----------—</td>

<td colspan="2"> Human glia derived nexin (SEQ־ID NO:369) ^: ‘--------־~^:l- ־-----</td>

<td colspan="2"> Human fibronectin (SEQ ID NO:370) ^י —---------</td>

<td colspan="2"> Human ECMproBM40 (SEQ ID NO:371)</td>

<td colspan="2"> Human collagen (SEQ ID NO:372)</td>

<td colspan="2"> Human alpha enolase (SEQ ID NO:373)</td>

<td colspan="2"> Human aldolase (SEQ ID NO:374)</td>

<td colspan="2"> Human transf growth factor BIG H3 (SEQ ID NO:375)</td>

<td colspan="2"> Human SPARC osteonectin (SEQ ID NO :376)</td>

<td colspan="2"> Human SLP1 leucocyte protease (SEQ ID NO:377)</td>

<td colspan="2"> Human mitochondrial ATP synth (SEQ ID NO:378)</td>

<td colspan="2"> Human DNA seq clone 461P17 (SEQ ID NO:379)</td>

<td colspan="2"> Human dbpB pro Y box (SEQ ID NO:380)</td>

<td colspan="2"> Human 40 kDa keratin (SEQ ID NO:381)</td>

<td colspan="2"> Human arginosuccmate synth (SEQ ID NO:382)</td>

<td colspan="2"> Human acidic ribosomal phosphoprotein (SEQ ID NO.-383)</td>

<td colspan="2"> Human colon carcinoma laminin binding pro (SEQ ID NO:384)</td>

This screen further identified multiple forms of the clone O772P, referred to herein as 21013, 21003 and 21008. PSORT analysis indicates that 21003 (SEQ ID NO:386; translated as SEQ ID NO:389) and 21008 (SEQ ID NO:387;

translated as SEQ ID NO:390) represent Type la transmembrane protein forms of

O772P. 21013 (SEQ ID NO:385; translated as SEQ ID NO:388) appears to be a truncated form of the protein and is predicted by PSORT analysis to be a secreted protein.

Additional sequence analysis resulted in a full length clone for O8E 5 (2627 bp, which agrees with the message size observed by Northern analysis; SEQ ID NO:391). This nucleotide sequence was obtained as follows: the original O8E sequence (OrigO8Econs) was found to overlap by 33 nucleotides with a sequence from an EST clone (IMAGE# 1 987589). This clone provided 1042 additional nucleotides upstream of the original O8E sequence. The link between the EST and O8E was confirmed by 10 sequencing multiple PCR fragments generated from an ovary primary tumor library using primers to the unique EST- and the O8E sequence (ESTxO8EPCR). Full length status was further indicated when anchored PCR from the ovary tumor library gave several clones (AnchoredPCR cons) that all terminated upstream of the putative start methionine, but failed to yield any additional sequence information. Figure 16 presents 15 a diagram that illustrates the location of each partial sequence within the full length O8E sequence.

Two protein sequences may be translated from the full length O8E. For ’a (SEQ ID NO:393) begins with a putative start methionine. A second form b” (SEQ ID NO:392) includes 27 additional upstream residues to the 5' end of the nucleotide 20 sequence.

From the foregoing it will be appreciated that, although specific embodiments of the invention have been described herein for puiposes of illustration, various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims. 25

SUMMARY OF SEQUENCE LISTING

SEQ ID NOs:l-71 are ovarian carcinoma antigen polynucleotides shown in Figures I A-IS.

SEQ ID NOs.72-74 are ovarian carcinoma antigen polynucleotides 30 shown in Figures 2A-2C.

SEQ ID NO:75 is the ovarian carcinoma polynucleotide 3g (Figure 4).

SEQ ID NO:76 is the ovarian carcinoma polynucleotide 3f (Figure 5). SEQ ID NO:77 is the ovarian carcinoma polynucleotide 6b (Figure 6). SEQ ID NO:78 is the ovarian carcinoma polynucleotide 8e (Figure 7A). SEQ ID NO:79 is the ovarian carcinoma polynucleotide 8h (Figure 7B).

SEQ ID NO:80 is the ovarian carcinoma polynucleotide 12e (Figure 8).

SEQ ID NO:81 is the ovarian carcinoma polynucleotide 12h (Figure 9). SEQ ID NOs:82-310 are ovarian carcinoma antigen polynucleotides shown in Figures 15A-15EEE.

SEQ ID NO1311 is a full length sequence of ovarian carcinoma 10 polynucleotide O772P.

SEQ ID NO:312 is the O772P amino acid sequence. ־ ־־ SEQ ID NOs:313-384 are ovarian carcinoma antigen polynucleotides. SEQ ID NOs:3 85-390 present sequences of O772P forms.

SEQ ID NO:391 is a full length sequence of ovarian carcinoma 15 polynucleotide O8E.

SEQ ID NOs:392-393 are protein sequences encoded by O8E.

SEQUENCE LISTING <110> Corixa Corporation <120> COMPOSITIONS AND METHODS FOR THE THERAPY AND DIAGNOSIS OF OVARIAN CANCER <130> 210121.462PC <140> PCT <141> 1999-12-17 <160> 393 <170> FastSEQ for Windows Version 3.0 <210> 1 <211> 461 <212> DNA <213> Homo sapien <400> 1 ttagagaggc acagaaggaa gaagagttaa aagcagcaaa gccgggtttt tttgttttgt60 tttgttttgt tttgttttga gatggagtct cactctgttg cccaagctgg agtacaacgg120 catgatctca gctcgctgca acccccgcct cccacgttca agtgattctc ctgcctcagc180 ctcccaagta gctgggatta caggcgcccg ccaccacgct cagctaattt tttttgtatt240 tttagtagag acagggtttc accaggttgg ccaggctgct cttgaactcc tgacctcagg300 tgatccaccc gcctcggcct cccaaagtgc tgggattaca ggcgtgagcc accacgcccg360 ־ gcccccaaag ctgtttcttt tgtctttagc gtaaagctct cctgccatgc agtatctaca420 taactgacgt gactgccagc aagctcagtc actccgtggt c461 <210> 2 <211> 540 <212כ> DNA <213> Homo sapien <400> 2 taggatgtgt tggaccctct gtgtcaaaaa aaacctcaca aagaatcccc tgctcattac60 agaagaagat gcatttaaaa tatgggttat tttcaacttt ttatctgagg acaagtatcc120 attaattatt gtgtcagaag agattgaata cctgcttaag aagcttacag aagctatggg180 ^a99aggttgg cagcaagaac aatttgaaca ttataaaatc aactttgatg acagtaaaaa240 tggcctttct gcatgggaac ttattgagct tattggaaat ggacagttta gcaaaggcat300 ggaccggcag actgtgtcta tggcaattaa tgaagtcttt aatgaactta tattagatgt360 gttaaagcag ggttacatga tgaaaaaggg ccacagacgg aaaaactgga ctgaaagatg *420 gtttgtacta aaacccaaca taatttctta ctatgtgagt gaggatctga aggataagaa480 aggagacatt ctcttggatg aaaattgctg tgtagagtcc ttgcctgaca aagatggaaa540 <210> 3 <211> 461 <212> DNA <213> Homo sapien <400> 3 ttagagaggc acagaaggaa gaagagttaa aagcagcaaa gccgggtttt tttgttttgt tttgttttgt tttgttttga gatggagtct cactctgttg cccaagctgg agtacaacgg catgatctca gctcgctgca acctccgcct cccacgttca agtgattctc ctgcctcagc ctcccaagta gctgggatta caggcgcccg ccaccacgct cagctaattt tttttgtatt tttagtagag acagggtttc accaggttgg ccaggctgct cttgaactcc tgacctcagg tgatccaccc gcctcggcct cccaaagtgc tgggattaca ggcgtgagcc accacgcccg gcccccaaag ctgtttcttt tgtctttagc gtaaagctct cctgccatgc agtatctaca taactgacgt gactgccagc aagctcagtc actccgtggt c <210> 4 <211> 531 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(531) <223> n = A,T,C or G <400> 4 tctttttctt tcgatttcct tcaatttgtc acgtttgatt ttatgaagtt gttcaagggc taactgctgt gtattatagc tttctctgag ttccttcagc tgattgttaa atgaatccat ttctgagagc ttagatgcag tttctttttc aagagcatct aattgttctt taagtctttg gcataattct tccttttctg atgacttttt atgaagtaaa ctgatccctg aatcaggtgt gttactgagc tgcatgtttt taattctttc gtttaatagc tgcttctcag ggaccagata gataagctta ttttgatatt ccttaagctc ttgttgaagt tgtttgattt ccataatttc caggtcacac tgtttatcca aaacttctag ctcagtcttt tgtgtttgct ttctgatttg gacatcttgt agtctgcctg agatctgctg atgntttcca ttcactgctt ccagttccag gtggagactt tnctttctgg agctcagcct gacaatgcct tcttgntccc t <210> 5 <211> 531 <212> DNA <213> Homo sapien <400> 5 agccagatgg ctgagagctg caagaagaag tcaggatcat gatggctcag tttcccacag cgatgaatgg agggccaaat atgtgggcta ttacatctga agaacgtact aagcatgata aacagtttga taacctcaaa ccttcaggag gttacataac aggtgatcaa gcccgtactt ttttcctaca gtcaggtctg ccggccccgg ttttagctga aatatgggcc ttatcagatc tgaacaagga tgggaagatg gaccagcaag agttctctat agctatgaaa ctcatcaagt taaagttgca gggccaacag ctgcctgtag tcctccctcc tatcatgaaa caacccccta tgttctctcc actaatctct gctcgttttg ggatgggaag catgcccaat ctgtccattc atcagccatt gcctccagtt gcacctatag caacaccctt gtcttctgct acttcaggga ccagtattcc tcccctaatg atgcctgctc ccctagtgcc ttctgttagt a

120 180 240 300 360 420 461

120 180 240 300 360 420 480 531 <210> 6 <211> 531 <212> DNA <213> Homo sapien <400> 6 aatagattta atgcagagtg tcaacttcaa gttgagtagg tttctgagga tgcaccctgg tatctaaaat ctcacttgta ggagaaacca ttgattgata gtggctgcct agagtgctgt cttgaagaga aagactggca ggattaacaa caggcaccag agctgccact ggtgctggca ccagctccac caaggccagc gaagagccca aatgtgagag tggcggtcag gctggcacca gcactgaagc caccactggt gctggcactg gcactggcac tgttattggt actggtactg gcaccagtgc tggcactgcc actctcttgg gctttggctt tagcttctgc tcccgcctgg atccgggctt tggcccaggg tccgatatca gcttcgtccc agttgcaggg cccggcagca ttctccgagc cgagcccaat gcccattcga gctctaatct cggccctagc cttggcttca gctgcagcct cagctgcagc cttcaaatcc gcttccatcg cctctcggta c ר <210>

<211> 531 <212> DNA <213> Homo sapien <400> 7 gccaagaaag cccgaaaggt gaagcatctg gatggggaag aggatggcag cagtgatcag agtcaggctt.ctggaaccac aggtggccga agggtctcaa aggccctaat ggcctcaatg gcccgcaggg cttcaagggg tcccatagcc ttttgggccc gcagggcatc aaggactcgg ttggctgctt gggcccggag agccttgctc tccctgagat cacctaaagc ccgtaggggc aaggctcgcc gtagagctgc oaagctccag tcatcccaag agcctgaagc accaccacct cgggatgtgg cccttttgca agggagggca aatgatttgg tgaagtacct tttggctaaa gaccaaacga agattcccat caagcgctcg gacatgctga aggacatcat caaagaatac actgatgtgt accccgaaat cattgaacga gcaggctatt ccttggagaa agtatttggg attcaattga aggaaattga taagaatgac cacttgtaca ttcttcrcag c <210> 8 <211> 531 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1). . (531) <223> n = A,T,C or G <400> 8 gaggtctcac tatgttgccc aggctgttct tgaactcctg ggatcaagca atccacccat gtrggtctcc aaaagtgctg ggatcatagg cgtgagccac ctcacccagc caccaatrrt caatcaggaa gactttttcc rtcttcaaga agtgaagggt ttccagagta tagccacact attgcttgcc tgagggtgac racaaaattg cttgctaaaa ggttaggatg ggtaaagaat tagattttct gaatgcaaaa ataaaatgtg aactaatgaa ctttaggtaa tacatattca taaaataatt attcacatat ttcctgattt atcacagaaa taatgtatga aatgctttga gtttcttgga gtaaactcca ttactcatcc caagaaacca tattataagt atcactgata ataagaacaa caggaccttg tcataaattc tggataagag aaatagtctc tgggtgtttg ntcttaattg ataaaattta cttgtccatc ttttagttca gaatcacaaa a <210> 9 <211> 531 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(531) <223> n = A,T,C or G

240 300 360 420

480 531

120 180 240 300 360 420 480 531

120 180 240 300 360 420 480 531 <400> 9 aagcggaaat gagaaaggag ggaaaatcat gtggtartga gcggaaaact gctggatgac 60 agggctcagt cctgttggag aactctgggt ggtgctgtag aacagggcca ctcacagtgg 120 ggtgcacaga ccagcacggc tctgtgacct gtttgttaca ggtccatgat gaggtaaaca 180 atacactgag tataagggtt ggtttagaaa ctcttacagc aatttgacaa agtaatcttc 240 tgtgcagtga atctaagaaa aaaattgggg ctgtatttgt atgttccttt ttttcatttc 300 atgttctgag ttacctattt ttattgcatt ttacaaaagc atccttccat gaaggaccgg360 aagttaaaaa caaagcaggt cctttatcac agcactgtcg tagaacacag ttcagagtta420 tccacccaag gagccaggga gctgggctaa accaaagaat tttgcttttg gttaatcatc480 aggtacttga gttggaattg ttttaatccc atcattacca ggctggangt g531 <210> 10 <211> 861 <212> DNA <213> Homo sapien <400> 10 ccgcggctcc tgtccagacc ctgaccctcc ctcccaaggc tcaaccgtcc cccaacaacc60 gccagccttg tactgatgtc ggctgcgaga gcctgtgctt aagtaagaat caggccttat120 tggagacatt caagcaaagg ttggacaact acttttccag aacagaaagg aaactcatgc180 atcagaaaag grgactaata aaggtaccag aagaatargg crgcacaaat accagaatct240 gatcagataa aacagtttaa ggaatttctg gggacctaca ataaacttac agagacctgc300 tttttggact gtgttagaga cttcacaaca agagaagtaa aacctgaaga gaccacctgt360 tcagaacatt gcttacagaa atatttaaaa atgacacaaa gaatatccat gagatttcag420 gaatatcata ttcagcagaa tgaagccctg gcagccaaag caggactcct tggccaacca480 cgatagagaa gtcctgatgg atgaactttt gatgaaagat tgccaacagc tgctttattg540 gaaatgagga ctcatctgat agaatcccct gaaagcagta gccaccatgt tcaaccatct600 gtcatgactg tttggcaaat ggaaaccgct ggagaaacaa aattgctatt taccaggaat660 aatcacaata gaaggtctta ttgttcagtg aaataataag atgcaacatt tgttgaggcc720 ttatgattca gcagcttggt cacttgatta gaaaaataaa ccattgtttc ttcaattgtg780 actgttaatt ttaaagcaac ttatgtgttc gatcatgtat gagatagaaa aatttttatt840 actcaaagta aaataaatgg a gg!

<210> 11 <211> 541 <212> DNA <213> Homo sapien <400> 11 gaaaaaaaat ataaaacaca cttttgcgaa aacggtggcc ctaaaagagg aaaagaattt 60 caccaatata aatccaattt tatgaaaact gacaatttaa tccaagaatc acttttgtaa120 atgaagctag caagtgatga tatgataaaa taaacgtgga ggaaataaaa acacaagact180 tggcataaga tatatccact tttgatatta aacttgtgaa gcatattctt cgacaaattg240 tgaaagcgtt cctgatcttg cttgttctcc atttcaaata aggaggcata tcacatccca300 agagtaacag aaaaagaaaa aagacatttt tgcattttga gatgaaccaa agacacaaaa360 caaaacgaac aaagtgtcat gtctaattct agcctctgaa ataaaccttg aacatctccc420 acaaggcacc gtgatttttg taattctaac ctgaagaaat gtgatgactt ttgtggacat480 gaaaatcaga tgagaaaact gtggtctttc caaagcctga actcccctga aaacctttac540 ^a541 <210> 12 <211> 541 <212> DNA <213> Homo sapien <400> 12 ctgggatcat ttcicttgat gtcataaaag actcttcttc ttcctcttca tcctcttctt catcctcttc tgtacagtgc tgccgggtac aacggctatc tttgtcttta tcctgagatg aagatgatgc ttctgtttct cctaccataa ctgaagaaat ttcgctggaa gtcgtttgac tggctgtttc tctgacttca ccttctttgt caaacctgag tctttttacc tcatgcccct cagcttccac agcatcttca tctggatgtt tatttttcaa agggctcact gaggaaactt ctgattcaga ggtcgaagag tcactgtgat ttttctcctc attttgctgc aaatttgcct ctttgctgtc tgtgctctca ggcaacccat ttgttgtcat gggggctgac aaagaaacct ttggtcgatt aagtggcctg ggtgtcccag gcccatttat attagacctc tcagtatagc ttggtgaatt tccaggaaac ataacaccat tcattcgatt taaactattg gaattggttt <210> 13 <211> 441 <212> DNA <213> Homo sapien <400> 13 gagggttggt ggtagcggct tggggaggtg ctcgctctgt cggtcttgct ctctcgcacg cttcccccgg ctcccttcgt ttcccccccc cggtcgcctg cgtgccggag tgtgtgcgag ggagggggag ggcgtcgggg gggtgggggg aggcgttccg gtccccaaga gacccgcgga gggaggcgga ggctgtgagg gactccggga agccatggac gtcgagaggc tccaggaggc gctgaaagat tttgagaaga gggggaaaaa ggaagtttgt cctgtcctgg atcagtttct ttgtcatgta gccaagactg gagaaacaat gattcagtgg tcccaattta aaggctattt tattttcaaa ctggagaaag tgatggatga tttcagaact tcagctcctg agccaagagg tcctcccaac cctaatgtcg a <210> 14 <211> 131 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1).. (131) <223> n = A,T,C or G <400> 14 aagcaggcgg ctcccgcgct cgcagggccg tgccacctgc ccgcccgccc gctcgctcgc tcgcccgccg cgccgcgctg ccgaccgcca gcatgctgcc gagagtgggc tgccccgcgc tgccgntgcc g <210> 15 <211> 692 <212> DNA <213> Homo sapien <400> 15 atctcttgta tgccaaatat ttaatataaa tctttgaaac aagttcagat gaaataaaaa tcaaagtttg caaaaacgtg aagattaact taattgtcaa atattcctca ttgccccaaa tcagtatttt ttttatttct atgcaaaagt atgccttcaa actgcttaaa tgatatatga tatgatacac aaaccagttt tcaaatagta aagccagtca tcttgcaatt gtaagaaata ggtaaaagat tataagacac cttacacaca cacacacaca cacacacgtg tgcacgccaa tgacaaaaaa caatttggcc tctcctaaaa taagaacatg aagaccctta attgctgcca ggagggaaca ctgtgtcacc cctccctaca atccaggtag tttcctttaa tccaatagca aatctgggca tatttgagag gagtgattct gacagccacg ttgaaatcct gtggggaacc

120 180 240 300 360 420 480 540 541

120 180 240 300

360 420 441

120 180 240 300 360 420 480 attcatgtcc acccactggt gccctgaaaa ctgctgtctc ttccacatcc tcacatagac gcattgctgg tagagcaagt cataggtctc attgcctggt cggtcattgt cataaccaga aatgccaata atttttcgct cccacttctg cccagacccg ctggcccctg gctgggcatc g^ctttgacg tcacagaagc gatacaccaa ga <210> 16 <211> 728 <212> DNA <213> Homo sapien <400> 16 cagacggggt ttcactatgt tggctaggct ggtcttgaac tcctgacttc aggtgatctg cctgccttgg cctcccaaag tgctgggatt acaggcataa gccactgcgc ccggctgatc tgatggtttc ataaggcttt tccccctttt gctcagcact tctccttcct gccgccatgt gaagaaggac atgtttgctt ccccttccac cacgattgta agttgtttcc tgaggcctcc ccggccatgc tgaactgtga gtcaattaaa cctctttcct ttataaatta tccagttttg ggtatgtctt tattagtaga atgagaacag actaatacaa cccttaaagg agactgacgg agaggattct tcctggatcc cagcacttcc tctgaatgct actgacattc ttcttgagga ctttaaactg ggagatagaa aacagattcc atggctcagc agcctgagag cagggaggga gccaagctat agatgacatg ggcaacctcc cctgaggcca ggtgtggccg aacctgggca gtgctgccac ccaccccacc agggccaagt ccrgtocttg gagagccaag cctcaatcac tgctagccrc aagtgtcccc aagccacagt ggctaggggg actcagggaa cagttcccag tctgccctac ttctcttacc tttacccctc ataccrccaa agtagaccat gttcatgagg tccaaagg <210> 17 <211> 531 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) .. (531) <223> n ־ A,T,C or G <400> 17 aagcgaggaa gccactgcgg ctcctggctg aaaagcgacg c&aggctcgg gaacagaagg aacgcgaaga acaggagcgg aagctgcagg ctgaaaggga caagcgaatg cgagaggagc agctggcccg ggaggctgaa gcccgggctg aacgtgaggc cgaggcgcgg agacgggagg agcaggaggc tcgagagaag gcgcaggctg agcaggagga gcaggagcga ctgcagaagc agaaagagga agccgaagcc cggtcccggg aagaagctga gcgccagcgc caggagcggg aaaagcactt tcagaaggag gaacaggaga gacaagagcg aagaaagcgg ctggaggaga taatgaagag gactcggaaa tcagaagccg ccgaaaccaa gaagcaggat gcaaaggaga ccgcagctaa caattccggc ccagaocctt gtgaaagctg tagagactcg gccctctggg cttccagaaa ggattctatt gcagaaagga aggagcrngg ccccccangg a <210> 18 <211> 1041 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1).. (1041) <223> n = A,T,C or G

120 180 240 300 360 420 480 540 600 660 720 728

120 180 240 300 360 420

480 531 <4Ό0> 18 ctctgtggaa aactgatgag gaatgaattt accattaccc atgttctcat ccccaagcaa 60 agtgctgggt ctgattactg caacacagag aacgaagaag aacttttcct catacaggat120 cagcagggcc tcatcacact gggctggatt catactcacc ccacacagac cgcgtttctc180 tccagtgtcg acctacacac tcactgctct taccagatga tgttgccaga gtcagtagcc240 attgtttgct cccccaagtt ccaggaaact ggattcttta aactaactga ccatggacta300 gaggagattt cttcctgtcg ccagaaagga tttcatccac acagcaagga tccacctctg360 ttctgtagct gcagccacgt gactgttgtg gacagagcag tgaccatcac agaccttcga420 tgagcgtttg agtccaacac cttccaagaa caacaaaacc atatcagtgt actgtagccc480 cttaatttaa gctttctaga aagctttgga agtttttgta gatagtagaa aggggggcat540 cacntgagaa agagctgatt ttgtatttca ggtttgaaaa gaaataactg aacatatttt600 ttaggcaagt cagaaagaga acatggtcac ccaaaagcaa ctgtaactca gaaattaagt660 tactcagaaa ttaagtagct cagaaattaa gaaagaatgg tataatgaac ccccatatac720 ccttccttct ggattcacca attgttaaca tttttttcct ctcagctatc cttctaattt780 ctctctaatt tcaatttgtt tatatttacc tctgggctca ataagggcat ctgtgcagaa840 atttggaagc catttagaaa atcttttgga ttttcctgtg gtttatggca atatgaatgg900 agcttattac tggggtgagg gacagcttac tccatttgac cagattgttt ggctaacaca960 tcccgaagaa tgattttgtc aggaattatt gttatttaat aaatatttca ggatattttt1020 cctctacaat aaagtaacaa t1041 <210> 19 <211> 1043 <212> DNA <213> Homo sapien <400> 19 ctctgtggaa aactgatgag gaatgaattt accattaccc atgttctcat ccccaagcaa60 agtgctgggt ctgattactg caacacagag aacgaagaag aacttttcct catacaggat120 cagcagggcc tcatcacact gggctggatt catactcacc ccacacagac cgcgtttctc180 tccagtgtcg acctacacac tcactgctct taccagatga tgttgccaga gtcagtagcc240 cccccaagtt ccaggaaact ggattcttta aactaactga ccatggacta 300 gaggagattt cttcctgtcg ccagaaagga tttcatccac acagcaagga tccacctctg360 ttctgtagct gcagccacgt gactgttgtg gacagagcag tgaccatcac agaccttcga420 tgagcgtttg agtccaacac cttccaagaa caacaaaacc atatcagtgt actgtaaccc480 cttaatttaa gctttctaga aagctttgga agtttttgta gatagtagaa aggggggcat540 cacctgagaa agagctgatt ttgtatttca ggtttgaaaa gaaataactg aacatatttt600 ttaggcaagt cagaaagaga acatggtcac ccaaaagcaa ctgtaactca gaaattaagt660 tactcagaaa ttaagtagct cagaaattaa gaaagaatgg tataatgaac ccccatatac720 ccttccttct ggattcacca attgttaaca tttttttcct ctcagctatc cttctaattt780 ctctctaatt tcaatttgtt tatatttacc tctgggctca ataagggcat ctgtgcagaa840 atttggaagc catttagaaa atcttttgga ttttcctgtg gtttatggca atatgaatgg900 agcttattac tggggtgagg gacagcttac tccatttgac cagattgttt ggctaacaca960 tcccgaagaa tgattttgtc aggaattatt gttatttaat aaatatttca ggatattttt1020 cctctacaat aaagtaacaa tta ’1043 <210> 20 <211> 448 <212> DNA <213> Homo sapien <400> 20 ggacgacaag gccatggcga tatcggatcc gaattcaagc ctttggaatt aaataaacct60 ggaacaggga aggtgaaagt tggagtgaga tgtcttccat atctatacct ttgtgcacag120 ttgaatggga actgtttggg tttagggcat cttagagttg attgatggaa aaagcagaca180 ggaactggtg ggaggtcaag tggggaagtt ggtgaatgtg gaataactta cctttgtgct ccacttaaac cagatgtgtt gcagctttcc tgacatgcaa ggatctactt taattccaca ctctcattaa taaattgaat aaaagggaat gttttggcac ctgatataat ctgccaggct atgtgacagt aggaaggaat ggtttcccct aacaagccca atgcactggt ctgactttat aaattattta ataaaatgaa ctattatc <210> 21 <211> 411 <212> DNA <213> Homo sapien <400> 21 ggcagtgaca ttcaccatca tgggaaccac cttccctttt cttcaggatt ctctgtagtg gaagagagca cccagtgttg ggctgaaaac atctgaaagt agggagaaga acctaaaata atcagtatct cagagggctc taaggtgcca agaagtctca ctggacattt aagtgccaac aaaggcatac tttcggaatc gccaagtcaa aactttctaa cttctgtctc tctcagagac aagtgagact caagagtcta ctgctttagt ggcaactaca gaaaactggt gttacccaga aaaacaggag caattagaaa tggttccaat atttcaaagc tccgcaaaca ggatgtgctt tcctttgccc atttagggtt tcttctcttt cctttctctt tattaaccac t <210> 22 <211> 896 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(896) <223> n = A,T,C or G <400> 22 tgcgctgaaa acaacggcct cctttactgt taaaatgcag ccacaggtgc ttagccgtgg gcatctcaac caccagcctc tgtggggggc aggtgggcgt ccctgtgggc ctctgggccc acgtccagcc tctgtcctct gccttccgtt cttcgacagr gttcccggca tccctggtca cttggtactt ggcgtgggcc tcctgtgctg crccagcagc tcctccaggn ggtcggcccg cttcaccgca gcctcatgtt gtgtccggag gctgctcacg gcctcctcct tcctcgcgag ggctgtcttc accctccggn gcacctcctc cagctccagc tgctggcggg ccrgcagcgt ggccagctcg gccttggcct gccgcgtctc ctcctcarag gctgccagcc ggtcctcgaa ctcctggcgg atcacctggg ccaggttgct gcgctcgcta gaaagctgct cgttcaccgc ctgcgcatcc tccagcgccc gctccttctg ccgcacaagg ccctgcagac gcagattctc gccctcggcc tccccaagct ggcccttcag ctccgagcac cgctcctgaa gcttccgctc cgactgctcc agctcggaga gctcggcctc gtacttgtcc cgtaagcgct tgatgcggct ctcggcagcc ttctcactct cctccttggc cagcgccatg tcggcctcca gccggtgaat gaccagctca atctccttgt cccggccttt ccggatttct tccctcagct cctgttcccg gttcagcagc cacgcctcct ccttcctggt gcggccggcc tcccacgcct gcctctccag ctccagctgc tgcttcaggg tattcagctc catctggcgg gcctgcagcg tggcca <210> 23 <211> 111 <212> DNA <213> Homo sapien <400> 23 caacttatta cttgaaatta taatatagcc tgtccgtttg ctgtttccag gctgtgatat attttcctag tggtttgact ttaaaaataa ataaggttta attttctccc c

240 3Q0 360 420 448

120 180 240 300 360 411

120 180 240 300 360 420 480 540 600 660 720 780 840 896 <210> 24 <211> 531 <212> DNA <213> Homo sapien.

<220>

<221> misc_feature <222> (1).. (531) <223> η = A,T,C or G <400> 24 tgcaagtcac gggagtttat ttatttaatt tttttcccca gatggagact ctgtcgccca ggctggagtg caatggtgtg atcttggctc actgcaacct ccacctcctg ggttcaagcg attctcctgc cacagcctcc cgagtagctg ggattacagg tgcccgccac cacacccagc taatttttat atttttagta aagacagggt ttccccatgt tggccaggct ggtcttgaac ttctgacctc aggtgatcca cctgcctcgg cctcccaaag tgttgggatt acaggcgtga gctacccgtg cctggccagc cactggagtt taaaggacag tcatgttggc tccagcctaa ggcggcattt tcccccatca gaaagcccgc ggctcctata cctcaaaata gggcacctgt aaagtcagtc agtgaagtct ctgctctaac tggccacccg gggccattgg cntctgacac agccttgcca ggangcctgc atctgcaaaa gaaaagttca cttccrttcc 0 <210> 25 <211> 471 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (471) <223> n = A,T,C or G <400> 25 cagagaatct kagaaagata rcgcgttttc ttttaargaa tgagagaagc ccatttgtat ccctgaatca ttgagaaaag gcggcggtgg cgacagcggc gacctaggga tcgatctgga gggacttggg gagcgtgcag agacctctag ctcgagcgcg agggacctcc cgccgggatg cctggggagc agatggaccc tactggaagt cagttggatt cagatttctc tcagcaagat actccttgcc tgataattga agattctcag cctgaaagcc aggttctaga ggatgattct ggttctcact tcagtatgct atctcgacac cttcctaatc tccagacgca caaagaaaat cctgtgttgg atgttgngtc caatccttga acaaacagct ggagaagaac gaggagaccg gtaatagtgg gttcaatgaa catttgaaag aaaaccaggt tgcagaccct g <210> 26 <211> 541 <212> DNA <213> Homo sapien <400> 26 gactgtcctg aacaagggac ctctgaccag agagctgcag gagatgcaga gtggtggcag gagtggaagc caaagaacac ccaccttcct cccttgaagg agtagagcaa ccatcagaag atactgtttt attgctctgg tcaaacaagt cttcctgagt tgacaaaacc tcaggctctg gtgacttctg aatctgcagt ccactttcca taagttcttg tgcagacaac tgttcttttg cttccatagc agcaacagat gctttggggc taaaaggcat gtcctctgac cttgcaggtg gtggattttg ctcttttaca acatgtacat ccttactggg ctgtgctgtc acagggatgt ccttgctgga ctgttctgct atggggatat cttcgttgga ctgttcttca tgcttaattg

6Q 120 180 240 300 360 420 480 531

120 180 240 300 360 420 471 cagtattagc atccacatca gacagcctgg tataaccaga gttggtggtt actgattgta gctgctcttt gtccacttca tatggcacaa gtattttcct caacatcctg gctctgggaa g <210> 27 <211> 461 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(461) <223> n = A,T,C or G <400> 27 gaaatgtata tttaatcatt ctcttgaacg atcagaactc traaatcagt tttctataac arcatgtaat acagtcaccg tggctccaag gtccaggaag gcagtggtta acacatgaag agtgtgggaa gggggctgga aacaaagtat tcttttcctt caaagcttca ttcctcaagg cctcaattca agcagtcatt gtccttgctt tcaaaagtct g.tgtgtgctt catggaaggt atatgtttgt tgccttaatt tgaattgtgg ccaggaaggg tctggagatc taaattcaga gtaagaaaac ctgagctaga actcaggcat ttctcttaca gaacttggct tgcagggtag aatgaangga aagaaactta gaagctcaac aagctgaaga taatcccatc aggcatttcc cataggcctt gcaactctgt tcactgagag atgttatcct g <210> 28 <211> 541 <212> DNA <213> Homo sapien <400> 28 agtctggagt gagcaaacaa gagcaagaaa caarragaag ccaaaagcag aaggctccaa tatgaacaag ataaatctat cttcaaagac atattagaag ttgggaaaat aattcatgrg aactagacaa gtgtgttaag agtgataagt aaaatgcacg tggagacaag tgcatcccca gatctcaggg acctccccct gcctgtcacc tggggagtga gaggacagga tagtgcatgt tctttgtctc tgaattttta gttatatgtg ctgtaatgtt gctctgagga agccccraga aagrctatcc caacatatcc acarcttata ttccacaaat taagctgtag tatgtaccct aagacgctgc taattgactg ccacttcgca actcaggggc ggctgcattt tagtaatggg tcaaatgatt cactttttat gatgcttccc aaggtgcctt ggcttctctt cccaactgac aaatgcccaa gttgagaaaa atgatcataa ttttagcata aaccgagcaa tcggcgaccc c <210> 29 <211> 411 <212> DNA <213> Homo sapien <400> 29 tagctgtctt cctcactctt atggcaatga ccccatatct taatggatta agataatgaa agtgtatttc ttacactctg tatctatcac cagaagctga ggtgatagcc cgcttgtcat tgtcatccat attctgggac tcaggcggga actttctgga atattgccag ggagcatggc agaggggcac agtgcattct gggggaatgc acattggctc agcctgggta atgagtgata tacattacct ctgttcacaa ctcattgccc agcaccagtc acaaggcccc accaaatacc agagcccaag aaatgtagtc ctgttgatat ggttttgctg tgtcccaacc caaatctcat cttgaattgt aagctcccat aattcccatg tgttgtggga gggacctggt g

120 180 240 300 360 420 461

120 180 240 300 360 420 480 540 541

120 180 240 300 360 411 <210> 30 <211> 511 <212> DNA <213> Homo sapien <400> 30 atcatgagga tgttaccaaa gggatggtac taaaccattt gtattcgtct gttttcacac60 tgctttgaag atactacctg agactgggta atttataaac aaaagagatt taattgactc120 acagttctgc atggctgaag aggcctcagg aaacttacag tcatggtgga aggcaaagga180 ggagcaaggc atgtcttaca tgtcagtagg agagagagcg agagcaggag aacctgccac240 ttataaacca ttcagatctc ataactccct atcatgagaa aaacatggag gaaaccaccc300 tcatgatcca atcacctccc gccaggtccc tccctcgaca cgtggggatt ataattcagg360' attagaggga cacagagaca aaccatatca tcattcatga gaaatccacc ctcatagtcc420 aatcagctcc taccaggccc cacctccaac actggggatt gcaattcaac atgagatttg480 gatggggaca cagattcaaa ccatatcata c <210> 31 <211> 827 <212> DNA <213> Homo sapien <400> 31 catggccttt ctccttagag gccagaggtg ctgccctggc tgggagtgaa gctccaggca60 ctaccagctt tcctgatttt cccgtttggt ccatgtgaag agctaccacg agccccagcc120 tcacagtgtc cactcaaggg cagcttggtc ctcttgtcct gcagaggcag gctggtgtga180 ccctgggaac ttgacccggg aacaacaggt ggcccagagt gagtgtggcc tggcccctca240 acctagtgtc cgtcctcctc tctcctggag ccagtcttga gtttaaaggc attaagtgtt300 agatacaagc tccttgtggc tggaaaaaca cccctctgct gataaagctc agggggcact360 gaggaagcag aggccccttg ggggtgccct cctgaagaga gcgtcaggcc atcagctctg420 uccctctggt gctcccacgt ctgttcctca ccctccatct ctgggagcag ctgcacctga480 ctggccacgc gggggcaatg gaggcacagg ctcagggtgg ccgggctacc tggcacccta540 tggcttacaa agtagagttg gcccagtttc cttccacctg aggggagcac tctgactcct600 aacagtcttc cttgccctgc catcatctgg ggtggctggc tgtcaagaaa ggccgggcat660 gctttctaaa cacagccaca ggaggcttgt agggcatctt ccaggtgggg aaacagtctt720 agataagtaa ggtgacttgc ctaaggcctc ccagcaccct tgatcttgga gtctcacagc780 agactgcata tsaacaactg gaaccgaaaa catgcctcaa tataaaa827 <210> 32 <211> 291, <212> DNA <213> Homo sapien <400> 32 . ccagaacctc cttctctttg gagaatgggg aggcctcttg gagacacaga gggtttcacc60 ttggatgacc tctagagaaa ttgcccaaga agcccacctt ctggtcccaa cctgcagacc120 ccacagcagt cagttggtca ggccctgctg tagaaggtca cttggctcca ttgcctgctt180 ccaaccaatg ggcaggagag aaggccttta tttctcgccc acccattctc ctgtaccagc240 acctccgttt tcagtcagyg ttgtccagca acggtaccgt ttacacagtc a291 <210> 33 <211> 491 <212> DNA <213> Homo sapien <400> 33 tgcatgtagt tttatttatg tgttttsgtc tggaaaacca agtgtcccag cagcatgact 60 gaacatcact cacttcccct acttgatcta caaggccaac gccgagagcc cagaccagga 120 ttccaaacac actgcacgag aatattgtgg atccgctgtc aggtaagtgt ccgtcactga 180 cccaracgct gttacgtggc acatgactgt acagtgccac gtaacagcac tgtacttttc 240 tcccatgaac agttacctgc catgtatcta catgattcag aacattttga acagttaatt 300 ctgacacttg aataatccca tcaaaaaccg taaaatcact ttgatgtttg taacgacaac 360 atagcatcac tttacgacag aatcatctgg aaaaacagaa caacgaatac atacatctta 420 aaaaatgctg gggtgggcca ggcacagctt cacgcctgta atcccagcac tttgggaggc 480 ttaagcgggt g ₄₉₁ <210> 34 <211> 521 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(521) <223> n = A,T,C or- G <400> 34 tggg9^cgg^aa agaagccaag gccaaggagc tggtgcggca gctgcagctg gaggccgagg 60 agcagaggaa gcagaagaag cggcagagtg tgtcgggcct gcacagatac cttcacttgc 120 tggatggaaa tgaaaattac ccgtgtcttg tggatgcaga cggtgatgtg atttccttcc 180 caccaataac caacagtgag aagacaaagg ttaagaaaac gacttctgat ttgtttttgg 240 aagtaacaag tgccaccagt ctgcagattt gcaaggatgt catggatgcc ctcattctga 300 aaatggcaag aaatgaaaaa gtacacttta gaaaataaag aggaaggatc actctcagat 360 actgaagccg atgcagtcrc tggacaactt ccagatccca caacgaatcc cagtgctgga 420 aaggacgggc ccttccttct ggtggtggaa cangtcccgg tggtggatct tggaanggaa 480 cctgaangtg gtgtaccccg tccaaggccg accttggcca c 521 <210> 35 <211> 161 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (161) <223> n = A,T,C or G <400> 35 tcccgcgctc gcagggcncg tgccacctgc cygtccgccc gctcgctcgc tcgcccgccg60 cgccgcgctg ccgaccgyca gcatgctgcc gagagtgggc tgccccgcgc tgccgctgcc120 gccgccgccg ctgctgccgc tgctgccgct gctgctgctg c161 <210> 36 <211> 341 <212> DNA <213> Homo sapien <400> 36 ggcgggtagg catggaactg agaagaacga agaagctttc agactacgtg gggaagaatg60 aaaaaaccaa aattatcgcc aagattcagc aaaggggaca gggagctcca gcccgagagc120 ctattattag cagtgaggag cagaagcagc tgatgctgta ctatcacaga agacaagagg180 agctcaagag attggaagaa aatgatgatg atgcctattt aaactcacca cgggcqaata acactgcttt gaaaagacat tttcatggag tgaaagacat aaagtggaga ccaagatgaa gttcaccagc tgatgacact tccaaagaga ttagctcacc t <210> 37 <211> 521 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (521) <223> n = A,T,C or G <400> 37 tctgaaggtt aaatgtttca tctaaatagg gataatgrta aacacctata gcatagagtt gtttgagatt aaatgagata atacatgtaa aattatgtgc ctggcataca gcaagattgt tgttgttgtt gatgatgatg atgatgatga taatattttt ctatccccag tgcacaactg cttgaaccta ttagataatc aatacatgtt tcttgaactg agatcaattt ccccatgttg tctgactgat gaagcccrac attttcttct agaggagatg acatttgagc aagatcttaa agaaaatcag atgccttcac ctgaccactg cttggtgatc ccatggcact ttgtacatct ctccattagc tctcatctca ccagcccatc attattgtat gtgctgcctt ctgaagcttg cagctggcta ccatcmggra gaataaaaat catcctttca taaaatagtg accctccttt tttatttgca tttcccaaag ccaagcaccg tggganggta g <210> 38 <211> 461 <212> DNA <213> Homo sapien <400> 38 tatgaagaag ggaaaagaag ataatttgtg aaagaaatgg gtccagttac tagtctttga aaagggtcag tctgtagctc ttcttaatga gaataggcag ctttcagttg ctcagggtca gatttcctta gtggtgtatc taatcacagg aaacatctgt ggttccctcc agtctctttc tgggggactt gggcccactt ctcatttcat ttaattagag gaaatagaac tcaaagtaca atttactgtt gtttaacaat gccacaaaga catggttggg agctatttct tgatttgtgt aaaatgctgt ttttgtgtgc tcataatggt tccaaaaatt gggtgctggc caaagagaga tactgttaca gaagccagca agaagacctc tgttcattca cacccccggg gatatcagga attgactcca gtgtgtgcaa atccagtttg gcctatcttc t <210> 39 <211> 769 <212> DNA <213> Homo sapien <400> 39 tgagggactg attggtttgc tctctgctat tcaattcccc aagcccactt gttcctgcag cgtcctcctt ctcattccct ttagttgtac cctctctttc atctgagacc tttccttctt gatgtcgcct tttcttcttc ttgctttttc tgatgttctg ctcagcatgt tctgggtgct tctcatctgc atcattcctt tcagatgctg tagcttcttc ctcctctttc tgcctccttt tctttttctt ttttttgggg ggcttgctct ctgactgcag ttgaggggcc ccagggtcct ggcctttgag acgagccagg aaggcctgct cctgggcctc taggcgagca agcttggcct tcattgtgat cccaagacgg gcagccttgt gtgctgttcg cccctcacag gcttggagca gcatctcatc agtcagaatc tttggggact tggacccctg gttgtcgtca tcactgcagc tctccaagtc tttgtttggc ttctctccac ctgaagtcaa tgtagccatc ttcacaaact

120 180 240 300 360 420 480 521

120 180 240 300 360 420 4 61

120 180 240 300 360 420

480 540 tctgatacag caagttgggc ttatctgtac tccatcctgc gctcattcca ccagtggttt cttgcttcag ygtcaccctg ttgggatgat tataacgggt ccagtttcca ctaccaagtt gtgaactcct tggcagggtc agagcctgag tgataccatt ggtctcctta gaaaggctcc ggccgcagtc ttgttgaaga atgtcctacc ccatgagtgr ctccttccg <210> 40 <211> 292 <212> DNA <213> Homo sapien <400> 40 gacaacatga aataaatcct agaggacaaa attaaactca atagagtgta gtctagttaa aaactcgaaa aatgagcaag tctggtggga gtggaggaag ggctatacta taaatccaag tgggcctcct gatcttaaca agccatgctc attatacaca tctctgaact ggacatacca cctttacgca ggaaacaggg cttggaactt ctaagggaaa ttaacatgca ccacccacat ctaacctacc tgccgggtag gtaccatccc tgcttcgctg aaatcagtgc tc <210> 41 <211> 406 <212> DNA <213> Homo sapien <400> 41 ttggaattaa ataaacctgg aacagggaag gtgaaagttg gagtgagatg tcttccatat ctataccttt gtgcacagtt gaatgggaac tgtttgggtt tagggcatct tagagttgat tgatggaaaa agcagacagg aactggtggg aggtcaagtg gggaagttgg tgaatgtgga ataacttacc tttgtgctcc acttaaacca gatgtgttgc agctttcctg acatgcaagg atctacttta attccacact ctcattaata aattgaataa aaaggaatgt tttggcacct gatataatct gccaggctat gtgacagtag gaaggaatgg tttcccctaa caagcccaat gcactggtct gactttataa attatttaat aaaatgaact attatc <210> 42 <211> 381 <212> DNA <213> Homo sapien <400> 42 aaactggacc tgcaacaggg acatgaattt actgcarggt ctgagcaagc tcagcccctc tacctcaggg ccccacagcc atgactacct cccccaggag cgggagggtg aagggggcct gtctctgcaa gtggagccag agtggaggaa tgagctctga agacacagca cccagccttc tcgcaccagc caagccttaa ctgcctgcct gaccctgaac cagaacccag ctgaactgcc cctccaaggg acaggaaggc tgggggaggg agtttacaac ccaagccatt ccaccccctc ccctgctggg gagaatgaca catcaagctg ctaacaattg ggggaagggg aaggaagaaa actctgaaaa caaaatcttg t <210> 43 <211> 451 <212> DNA <213> Homo sapien <400> 43 catgcgtttc accactgttg gccaggctgg tctcgaactc ctggcctcaa gcaatccacc cgcctcagcc tccaaaagtg ctgggattac agatgtgagc catggcacca tgccaaaagg ctatattcct ggctctgtgt ttccgagact gcttttaatc ccaacttctc tacatttaga ttaaaaaata ttttattcat ggtcaatctg gaacataatt actgcatctt aagtttccac

120 180 240 300 360 406

120 180 240 300 360 381.

tgatgtatat aaaatcatta aatcctgata aaggcgcata agaaggctaa attactttca ggttctttat atgagaatac aggcacaatt acttaataac tttttcaaaa cccaaactgg tttatcaaat taattgacat tatatttgcc a ctagtagagt tcctcaaaag atgggatgct aaccaaacat agctgttttc aatttgcaat

420 451 <210> 44 <211> 521 <212> DNA <213> Homo sapien <400 gttggacccc gttccttttt agccgtatca gatgaattag cagaccataa ataataggag ttttgacatg atggtatctc ggtactggtg > 44 cagggactgg attatgcttc gaaatctttt attctgttgg atcaacttct ccacaaactt caagttacag aataaaataa gcttttccgg aaagacactt tggatccgaa tagggaagca tgggaagaga tgctgaaatg cccagaggca ttccaaggcc agtttgatca aagcagagtt cttgcccgag tttgatgaga aaggcgaatg attgaatctc gatggtttta ttagataatg agatgtaaaa atcccgttga gggagaatct ctgtggcggg tgtttgtggg ctccttgtgt caatgcatcc aacccaatga ccttaatacc ggtcgaacag tccagaaatt t agaagctgat tgtgggagcc tatatttatt atattcaagg aggagttatc gtcctggtcg aaattttgaa atagcctcga

120 180 240 300 360 420 480 521 <210> 45 <211> 585 <212> DNA <213> Homo sapien <400> 45 gcctacaaca tccagaaaga gtctaccctg cacctggtgc tscgtctcag aggtgggatg cagatcttcg tgaagaccct gactggtaag accatcactc tcgaagtgga gccgagtgac accatygaga acgtcaaagc aaagatccar gacaaggaag gcrtycctcc tgaccagcag aggttgatct ttgccggaaa gcagctggaa gatggdcgca ccctgtctga ctacaacatc cagaaagagt cyaccctgca cctggtgctc cgtctcagag gtgggatgca ratcttcgtg aagaccctga ctggtaagac catcaccctc gaggtggagc ccagtgacac catcgagaat gtcaaggcaa agatccaaga taaggaaggc atccctcctg atcagcagag gttgatcttt gctgggaaac agctggaaga tggacgcacc ctgtctgact acaacatcca gaaagaatcc actctgcact tggtcctgcg cttgaggggg ggtgtctaag tttccccttt taaggtttcm acaaatttca ttgcactttc ctttcaataa agttgttgca ttccc <210> 46 <211> 481 <212> DNA <213> Homo sapien <400> 46 gaactgggcc ctgagcccaa gtcatgcctt gtgtccgcat ctgccgtgtc acctctgtkc ctgcccctca cccctccctc ctggtcttct gagccagcac catctccaaa tagcctattc cttcctgcaa atcacacaca catgcgggcc acacatacct gctgccctgg agatggggaa gtaggagaga tgaatagagg cccatacatt gtacagaagg aggggcaggt gcagataaaa gcagcagacc cagcggcagc tgaggtgcat ggagcacggt tggggccggc attgggctga gcacctgatg ggcctcatct cgtgaatcct cgaggcagcg ccacagcaga ggagttaagt ggcacctggg ccgagcagag caggagactg agggtcagag tggaggctaa gctgccctgg aactcctcaa tcttgcctgc cccctagtat gaagccccct tcctgcccct acaattcctg

120 180 240 300 360 420 480 540 585

120 180 240 300 360 420 480 481 <210> 47 <211> 461 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1),.(461) <223> n = A,T,C or G <400> 47 atggatctta ctttgccacc caggttggag tgcagtgctg caatcttggc tcactgcagc60 cttaacctcc caggctcaag ctatcctcct gccaaagcct tccacatagc tgggactaca120 ggtacacngc caccacaccc agctaaaatt tttgtat.ttt ttgtagagac gggatctcgc180 cacgttgccc aggctggtcc catcctgacc tcaagcagat ctgcccacct cagcccccca240 acgtgctagg attacaggcg tgagccaccg cacccagcct ttgttttgct tttaatggaa300 tcaccagttc ccctccgtgt ctcagcagca gctgtgagaa atgctttgca tctgtgacct360 ttatgaaggg gaacttccat gctgaatgag ggtaggatta catgctcctg tttcccgggg420 gtcaagaaag cctcagactc cagcatgara agcagggtga g461 <210> 48 <211> 571 <212> DNA <213> Homo sapien <400> 48 ataggggctt taaggaggga attcaggttc aatgaggtcg taaggccagg gctcttatcc60 agtaagactg gggtccttag atgagaaaga gacacccgag gtccttctct ctgccgtgtg120 aggatgcatc aagaaggcgg ccgtctgcaa gcgaaggaga ggccgcacca gaaaccgaca180 ccttcatctt ggacttgcag cctctagaac tgagaaaata actgtctgtt ggttaagcca240 cccagtttgt agtattctct tatggcttcc taagcagact aacaaacaaa cacccaaaat300 taactgatgg cttcgctgtc ttctgtaaaa attgctatga gagaactttt cactcactgt360 tttgcagttt ctccctcagt ccctggttct ttcttctcac ataatcccaa tttcaattta420 tagttcatgg cccaggcaga gtcattcatc acggcatctc ctgagctaaa ccagcacctg480 ctctgctcac ttcttgacrg gctgotcatc atcagccctc ttgcagagat ttcatttcct540 cccgtgccag gtacttcacg caccaagctc a571 <210> 49 <211> 511 <212> DNA <213> Homo sapien <400> 49 ggataatgaa gttgttttat ttagcttgga caaaaaggca tattcctcta ttttcttata60 caacaaatat ccccaaaata aagcaagcat atatatcttg aatgtgtaat aatccagtga120 taaacaagag cagtacttta aaagaaaaaa aaatatgtat ttctgtcagg ttaaaatgag180 aatcaaaacc atttactctg ctaactcatt attttttgct ttctttttgg ttaagagagg240 caatgcaata cactgaaaaa ggtttttatc ttatctggca ttggaattag acatattcaa300 accccagccc ccatttccaa act.ttaagac cacaaacaag taatttactt ttctgaacat360 tggttttttc tggaaaargg gaattataaa atagactttg cagactctta tgagattaaa420 taagataatg tatgaaattc tttcttcttt tttacttctt tttccttttt gagatggagt480 ctcaccccgt cacccaggct ggagtacagt g51!

<210> 50 <211> 561 <212> DNA <213> Homo sapien <400? 50 ccactgcact ccagcctggg tgacggagtg agactctgtc tcaaaaaaac aaacaaacaa60 acaaacaaaa aactgaaaag gaaatagagt tcctctttcc tcatatatga atatattatt120 tcaacagatt gttgatcacc taccatatgc ttggtattgt tctaattgct ggggatacag180 caagaggttc tgcagaactt catggagcat gaaagtaaat aaacaaagtt aatttcaagg240 ccaggcatgg ttgctcacac ctttagtccc agcactttgg gaggctgagg caggtggatc300 acttgggccc aggagttcaa ggctgcagtg agccaagatt gtgccactac tctccaggct360 gggcaacaga gcaagaccct gtctcagggg gaacaaaaag ttaatttcag attttgttaa420 gtgctgtaaa ggaagtaaat aggttgatat tcaagagagc acctgaaggc caggcgtggt480 ggctcacgcc tgtggtctaa cgctttggga agcccgagcg ggcggatcac aaggtcagga540 gaattttggc caggcatggt g561 <210? 51 <211? 451 <212? DNA <213? Homo sapien <400? 51 agaatccatt tattgggttt raaactagtt acacaactga aatcagtttg gcactacttt60 atacagggat tacgcctgtg tatgccgaca cttaaatact gtaccaggac cactgctgtg120 cttaggtctg tattcagtca ttcagcatgt agatactaaa aatatactgt agtgttcctt180 taaggaagac tgtacagggt gtgttgcaag atgacattca ccaatttgtg aattatttca240 acccagaaga tacctttcac tctataaact tgtcataggc aaacatgtgg tgttagcatt300 gagagatgca cacaaaaatg ttacataaaa gttcagacat tctaatgata agtgaactga360 aaaaaaaaaa aaccccacat ctcaattttt gtaacaagat aaagaaaata atttaaaaac420 acaaaaaatg gcattcagtg ggtacaaagc c45!

&lt;210? 52 &lt;211? 682 &lt;212? DNA &lt;213? Homo sapien &lt;400? 52 caaatattta atacaaarct ttgaaacaag ttcagakgaa ataaaaatca aagtttgcaa60 aaacgtgaag attaacttaa ttgtcaaata ttcctcattg coccaaatca gtattttttt120 tatttctatg caaaagtatg ccttcaaact gcttaaatga tatatgatat gatacacaaa180 ccagttttca aatagtaaag ccagtcatct tgcaattgta agaaataggt aaaagattat240 aagacacctt acacacacac acacacacac acacacacgt gtgcaccgcc aatgacaaaa300 aacaatttgg cctctcctaa aataagaaca tgaagaccct taattgctgc caggagggaa360 cactgtgtca cccctcccta caatccaggt agtttccttt aatccaatag caaatctggg420 catatttgag aggagtgatt ctgacagcca csgttgaaat cctgtgggga accattcatg480 tccacccact ggtgccctga aaaaatgcca ataatttttc gctcccactt ctgctgctgt540 ctcttccaca tcctcacata gaccccagac ccgctggccc ctggctgggc atcgcattgc600 tggtagagca agtcataggt ctcgtctttg acgtcacaga agcgatacac caaattgcct660 ggtcggtcat tgtcataacc ag θθ2 &lt;210? 53 &lt;211? 311 &lt;212? DNA &lt;213? Homo sapien &lt;220?

<221? misc feature <222> (1)..(311) <223> n = A,T,C or G <400> 53 tttgacttta gtaggggtct gaactattta ttttactttg ccmgtaatat ttaraccyta60 tatatctttc attatgccat cttatcttct aatgbcaagg gaacagwtgc taamctggct120 tctgcattwa tcacattaaa aatggctttc ttggaaaatc ttcttgatat gaataaagga180 tcttttavag ccatcattta aagcmggntt ctctccaaca cgagtctgct sasggggggk240 gagctgtgaa ctctggctga aggctttccc atacacactg caatgaantg gtttctgacc 300 agbgtgagtt a <210> 54 <211> 561 <212> DNA <213> Homo sapien <400> 54 agagaagccc cataaatgca atcagtgtgg gaaggccttc agtcagagct caagcctttt60 cctccatcat cgggttcata ctggagagaa accctatgta tgtaatgaat gcggcagagc120 ctttggtttt aactctcatc ttactgaaca cgtaaggatt cacacaggag aaaaacccta180 tgtttgtaat gagtgcggca aagcctttcg tcggagtrcc actcttgttc agcatcgaag240 agttcacact ggggagaagc cctaccagtg cgttgaatgt gggaaagctt tcagccagag300 ctcccagctc accctacatc agccgagttc acactggaga gaagccctat gactgtggtg360 actgtgggaa ggccttcagc cggaggtcaa ccctcattca gcatcagaaa gttcacagcg420 gagagactcg taagtgcaga aaacatggtc cagcctttgt tcatggctcc agcctcacag480 cagatggaca gattcccact ggagagaagc acggcaaaac ctttaaccat ggtgcaaatc540 tcattctgcg ctggacagtt c5g!

<210> 55 <211> 811 <212> DNA <213> Homo sapien <400> 55 gagacagggt ctcactttgt cacccaggct ggaatgcagt ggtgcgatct tacgtagctc60 actgcaaccc tgacctcctg gactcaaaca attctcctgc ctcagccctg caagtaacrg120 ggactgtggg tgcatgccac catgcctggc taacttttgt agtttttgta aagatggggt180 tttgccatgt tgcacatgct ggtcttgaac tcctgagctc aaacgatctg cccacctcgg240 cctcccagaa tgttgggatt acaggggtaa accaccacgc ctggccccat tagggtattc300 ttagcatcca cttgctcact gagattaatc ataagagatg ataagcactg gaagaaaaaa360 atttttacta ggctttggat atttttttcc tttttcagct ttatacagag gattggatct420 ttagttttcc tttaactga.t aataaaacat tgaaaggaaa taagtttacc tgagattcac480 agagataacc ggcatcactc ccttgctcaa ttccagtctt taccacatca attattttca540 gaggtgcagg ataaaggcct ttagtctgct ttcgcacttt ttcttccact tttttgtaaa600 cctgttgcct gacaaatgga attgacagcg tatgccatga ctattccatt tgtcaggcat660 acgctgtcaa tttttccacc aatcccttgt ctctctttgg agagatcttc ttatcagcta720 gtcctttggc aaaagtaatt gcaacttctt ctaggtattc tattgtccgt tccactggtg780 gaacccctgg gaccaggact aaaacctcca g. g!!

<210> 56 <211> 591 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(591) <223> n = A,T,C or G <400> 56 atctcatata tatatttctt- cctgacttta tttgcttgct tctgncacgc atttaaaata tcacagagac caaaatagag cggctttctg gtggaacgca tggcag’tcac aggacaaaat acaaaactag ggggctctgt cttctcatac atcatacaat tttcaagtat tttttttatg tacaaagagc tactctatct gaaaaaaaat taaaaaataa atgagacaag atagtttatg catcctagga agaaagaatg ggaagaaaga acggggcagt tgggtacaga ttcctgtccc ctgttcccag ggaccactac cttcctgcca ctgagttccc ccacagcctc acccatcatg tcacagggca agtgccaggg taggtgggga ccagtggaga caggaaccag caacatactt tggcctggaa gataaggaga aagtctcaga aacacactgg tgggaagcaa tcccacnggc cgtgccccan gagcttccca cctgctgctg gctccctggg tggctttggg aacagcttgg gcaggccctt ttgggtgggg nccaactggg cctttgggcc cgtgtggaaa g <210> 57 <211> 481 <212> DNA <213> Homo sapien <400> 57 aaacattgag atggaatgat agggtttccc agaatcaggt ccatatttta actaaatgaa aattatgatt tatagccttc tcaaatacct gccatacttg atatctcaac cagagctaat tttacctctt tacaaattaa ataagcaagt aactggatcc acaatttata atacctgtca attttttctg tattaaacct ctatcatagt ttaagcctat tagggtactt aatccttaca aataaacagg tttaaaatca cctcaatagg caactgccct tctggttttc ttctttgact aaacaatctg aatgcttaag attttccact ttgggtgcta gcagtacaca gtgttacact ctgtattcca gacttcttaa attatagaaa aaggaatgta cactttttgt attctttctg agcagggccg ggaggcaaca tcatctacca tggtagggac ttgtatgcat ggactacttt a /

<210> 58 <211> 141 <212> DNA <213> Homo sapien <400> 58 actctgtcgc ccaggctgga gcccabtggm gcgatctcga ctccctgcaa gctmcgcctc acaggwtcat gccattctcc tgcctcagca tctggagtag ctgggactac aggcgccagc caccatgccc agctaatttt t <210> 59 <211> 191 <212> DNA <213> Homo sapien <400> 59 accttaaaga cataggagaa tttatactgg gagagaaagc ttacaaatgt aaggtttctg acaagacttg ggagtgattc acacctggaa caacatactg gacttcacac tggabagaaa ccttacaagt gtaatgagtg tggcaaagcc tttggcaagc agtcaacact tattcaccat caggcaattc a

120 180 240 300 360 420 480 540 591

120 180 240 300 360 420 480 481 <210> 60 <211> 480 <212> DNA <213> Homo sapien <400> 60 agtcaggatc atgatggctc a-gtttcccac agcgatgaat ggagggccaa atatgtgggc60 tattacatct gaagaacgta ctaagcatga taaacagttt gataacctca aaccttcagg120 aggttacata acaggtgatc aagcccgtac ttttttccta cagtcaggtc tgccggcccc180 ggttttagct gaaatatggg ccttatcaga tctgaacaag gatgggaaga tggaccagca240 agagttctct atagctatga aactcatcaa gttaaagttg cagggccaac agctgcctgt300 agtcctccct cctatcatga aacaaccccc tatgttctct ccactaatct ctgctcgttt360 tgggatggga agcatgccca atctgtccat tcatcagcca ttgcctccag ttgcacctat420 agcaacaccc ttgtcttctg ctacttcagg gaccagtatt cctccctaat gatgcctgct480 <210> 61 <211> 381 <212> DNA <213> Homo sapien <400> 61 ctttcgattt ccttcaattt gtcacgtttg attttatgaa gttgttcaag ggctaactac60 tgtgtattat agctttctct gagttccttc agctgattgt taaatgaatc catttctgaa120 agcttagatg cagtttcttt ttcaagagca tctaattgtt ctttaagtct ttggcataat180 tcttcctttt ctgatgactt totatgaagt aaactgatcc ctgaatcagg tgtgttactg240 agctgcatgt ttttaattct ttcgtttaat agctgcttct cagggaccag atagataaqc300 ttattttgat attccttaag ctcttggtga agttgttcga tttccataat ttccaggtca360 cactggttat cccaaacttc t <210> 62 <211> 906 <212> DNA <213> Homo sapien <400> 62 gtggaggtga aacggaggca agaaaggggg ctacctcagg agcgagggac aaagggggcg60 tgaggcacct aggccgcggc accccggcga caggaagccg tcctgaaccg ggctaccggg120 taggggaagg gcccgcgtag tcctcgcagg gccccagagc tggagtcggc tccacaaccc180 cgggccgtcg gcttctcact tcctggacct ccccggcgcc cgggcctgag gactggcncg240 gcggagggag aagaggaaac agacttgagc agctccccgt tgtctcgcaa ctccactgcc300 gaggaactct catt.tcttcc ctcgctcctt caccccccac ctcatgtaga aaggtgctga360 agcgtccgga gggaagaaga acctgggcta ccgtcctggc cttcccmccc ccttcccggg420 gcgctttggt gggcgtggag ttggggttgg gggggtgggt gggggttctt ttttggagtg480 ctggggaact tttttccctt cttcaggtca ggggaaaggg aatgcccaat tcagagagac540 atgggggcaa gaaggacggg agtggaggag cttctggaac tttgcagccg tcatcgggag600 gcggcagctc taacagcaga gagcgtcacc gcttggtatc gaagcacaag cggcataagt660 ccaaacactc caaagacatg gggttggtga cccccgaagc agcatccctg ggcacagnta720 tcaaaccttt ggtggagtat gatgatatca gctctgattc cgacaccttc tccgatgaca780 tggccttcaa actagaccga agggagaacg acgaacgtcg tggatcagat cggagcgacc840 gcctgcacfia acatcgtcac caccagcaca ggcgttcccg ggacttacta aaagctaaac900 agaccg ggg <210> 63 <211> 491 <212> DNA <213> Homo sapien <400> 63 gacatgtttg cctgcagggg accagagaca atgggattag ccagtgctca ctgttcttta tgcttccaga gaggatgggg acagctctca ggtcagaatc caggctgaga aggccatgct ggttgggggc ccccggaagc acggtccgga tcctccctgg catcagcgta gacccgctgc tcaggcttgg ggtaccaaac tcatgctctg tactgttttg gccccatgcg gtgagaggaa aacctagaaa aagattggtc gtgctaagga atcagctgcc ccctcatcct ccgcatccaa tgctggtgac aacatattcc ctctcccagg acacagactc ggtgactcca cactgggctg agtggcctct ggaggctcgt ggcctaaggc agggctccgt aaggctgatc ggctgaactg ggtggggtga gggtttctga cccttcgctt cccatcccat aaccgctgtc aatgagctca cactgtggtc a <210> 64 <211> 511 <212> DNA <213> Homo sapien <400> 64 gatggcatgg tcgttgctaa tgtgcctgct gggatggagc acttcctcct gtgagcccag gggacccgcc tgtccctgga gcttggggca aggagggaag agtgatacca ggaaggtggg gctgcagcca ggggccag'ag tcagttcagg gagtggtcct cggccctcaa agctcctccg gggactgctc aggagtgatg grgccctgga gtttgcccca actrccctgg ccaccctgga aggtgcctgg ctgctccagg cctctaggct gggctgatgg gtttctccag gacacaagta tcattaaagc caccctctcc tcagcttgtc aggccgcaca tgtgggacag gctgtgctca caaccccctc gcctgccctg ccetccatca ggaggagcca gtggaacctt cggaaagctc ccagcatctc agcagccctc aaaagtcgtc ctggggcaag ctctggttct cctgactgga ggtcatctgg gcttggcctg'ctctctctcg c <210> 65 <211> 394 <212> DNA <213> Homo sapien <400> 65 taaaaaagtg taacaaaggt ttatttagac tttcttcatg cccccagatc caggatgtct atgtaaaccg ttatcttaca aagaaagcac aatatttggt ataaactaag tcagtgactt gcttaactga aatagcgtcc atccaaaagr gggtttaagg taaaactacc tgacgatatt ggcggggatc ctgcagtttg gactgcttgc cgggtttgtc cagggttccg ggtctgttct tggcactcat ggggacaggc atcctgctcg tctgtggggc cccgctggag cccttacgtg aagctgaagg tatcgaccst agggggctct agggcagtgg gaccttcatc cggaactaac aagggtcggg gagaggcctc ttgggctatg tggg

120 180 240 300 360 420 480 491

120 180 240 300

360 420 480 511

120 1.80 240 300 360 394 <210> 66 <211> 359 <212> DNA <213> Homo sapien <400> 66 caagcgttcc tttatggatg tcacgttwaa gacactaggt atttttccat gaagatgtac attccaaaag gttaccacag aatggagaat agtatttctg gaaggaaaat tccatatcca taaattcaaa cagtcatgct cgggcgccac agtgccaccc ggaaatctga tgttgaatat gggctgtaag acctagtgac atgcatcaag a’acatcagaa atatgagttt actcagagac gagccatccc gggctgacag aaggagaaga agaatttgga gaaaatggcc cccaaatgga cctcctaagt gggaaagagg tataaaactg agatcataat agtagaaact attcccagg

120 180 240 300 359 <210> 67 <211> 450 <212> DNA.

<213> Homo sapien <220>

<221> misc_feature <222> (1)..(450) <223> n = A,T,C or G <400> 67 taggaataac taatgcccct agtggaggag cttatagagt cagctccaga atacct.gctt accctaagca actgnctttt aaatgtttat tcctctcctt gacacaggac ggaggaggca tggccacgtg tgggatgaga cagtgcaagc ggatgctctc tcagaaatgg ctgcacagga tagcccacca aacaggtccc gttgcagctg gggaggataa agtgagcccc ttgggccacg ataagtaata gacacagatg ccttctcttc ctcaatgtac gactcaatga agccatgcag cggctcccag cataatcacc ggtaacatag ccggtctccc cagatggtca aactctgtga ggaggatatt tacctgaaaa cttcatctct aggcatggga aagatgactg cctatagcac caaccagaag taccatccct accaaggcct

120 180 240 300 360 420 <210> 68 <211> 511 <212> DNA <213> Homo sapien <400> 68 aagcctcctg ccctggaaat ctggagcccc ttggagctga gctggacggg gcagggaggg 60 gctgagaggc aagaccgtct ccctcctgct gcagctgctt ccccagcagc cactgctggg 120 cacagcagaa acgccagcag agaaaatggg agccgagagt ccttagccct ggagctgagg 180 ctgcctctgg gctgacccgc tggctgtacg tggccagaac tggggttggc atctggcatc 240 catttgaggc cagggtggag gaaagggagg ccaacagagg aaaacctatt cctgctgtga 300 caacacagcc cttgtcccac gcagcctaag tgcagggagc gtgatgaagt caggcagcca 360 gtcggggagg acgaggtaac tcagcagcaa tgtcaccttg tagcctatgc gctcaatggc 420 ccggaggggc agcaaccccc cgcacacgtc agccaacagc agtgcctctg caggcaccaa 480 gagagcgatg atggacttga gcgccgtgtt c ₅₁₁ <210> 69 <211> 511 <212> DNA <213> Homo sapien <400> 69 gtttggcaga agacatgttt aataacattt tcatatttaa aaaatacagc aacaattctc 60 tatctgtcca ccatcttgcc ttgcccttcc tggggctgag gcagacaaag gaaaggtaat 120 gaggttaggg cccccaggcg ggotaagtgc tattggcctg ctcctgctca aagagagcca 180 tagccagctg ggcacggccc cctagcccct ccaggttgct gaggcggcag cggtggtaga 240 gttcttcact gagccgtggg ctgcagtctc gcagggagaa cttctgcacc agccctggct 300 ctacggcccg aaagaggtgg agccctgaga accggaggaa aacatccatc acctccagcc 360 cctccagggc ttcctcctct tcctggcctg ccagttcacc tgccagccgg gctcgggccg 420 ccaggtagtc agcgttgtag aagcagccct ccgcagaagc ctgccggtca aatctccccg 480 ctataggagc cccccgggag gggtcagcac c י <210> 70 <211> 511 <212> DNA <213> Homo sapien <400> 70 caagttgaac gtcaggcttg gcagaggtgg agtgtagatg aaaacaaagg tgtgattatg60 aagaggatgt gagtcctttg ggtgtaggag agaaaggctg ttgagcttct atttcaagat120 acttttacct gtgcaaaaag cacattttcc acctccttct catggcattt gtgtaaggtg180 agtatgattc ctattccatc tgcattttag aggtgaagaa taacgtacaa gggattcagt240 gattagcaag ggacccctca ctaagtgttg atggagttag gacagagctc agctgtttga300 atctcagagc ccaggcagct ggagctgggt aggatcctgg agctggcact aatgtgaggt360 gcattccctc caacccaggc tcagatccgg aacctgaccg tgctgacccc cgaaggggag420 gcagggctga gctggcccgt tgggctccct gctcctttca caccacactc tcgctttgag480 gtgctgggct gggactactt cacagagcag c <210> 71 <211> 511 <212> DNA <213> Homo sapien <400> 71 tggcctgggc aggattggga gagaggtagc tacccggatg cagtcctttg ggatgaagac60 tatagggtat gaccccatca tttccccaga ggtctcggcc tcctttggtg ttcagcagct120 gcccctggag gagatctggc ctctctgrga tttcatcact gtgcacactc ctctcctgcc180 ctccacgaca ggcttgctga atgacaacac ctttgcccag tgcaagaagg gggtgcgtgt240 ggtgaactgt gcccgtggag ggatcgtgga cgaaggcgcc ctgctccggg ccctgcagtc300 tggccagtgt gccggggctg cactggacgt gtttacggaa gagccgccac gggaccgggc360 cttggtggac catgagaatg tcatcagctg tccccacctg ggtgccagca ccaaggaggc420 tcagagccgc tgtggggagg aaattgctgt tcagttcgtg gacatggtga agaggaaatc480 tctcacgggg gttgtgaatg cccaggccct t ”5!!

<210> 72 <211> 2017 <212> DNA <213> Homo sapien <400> 72 agccagatgg ctgagagctg caagaagaag tcaggatcat gatggctcag tttcccacag60 cgatgaatgg agggccaaat atgtgggcta ttacatctga agaacgtact aagcatgata120 aacagtttga taacctcaaa ccttcaggag gttacataac aggtgatcaa gcccgtactt180 ttttcctaca gtcaggtctg ccggccccgg ttttagctga aatatgggcc ttatcagatc240 tgaacaagga tgggaagatg gaccagcaag agttctctat agctatgaaa ctcatcaagt300 taaagttgca gggccaacag ctgcctgtag tcctccctcc tatcatgaaa caacccccta360 tgttctctcc actaatctct gctcgttttg ggatgggaag catgcccaat ctgtccattc420 atcagccatt gcctccagtt gcacctatag caacaccctt gtcttctgct acttcaggga480 ccagtattcc tcccctaatg atgcctgctc ccctagtgcc ttctgttagt acatcctcat540 taccaaatgg aactgccagt ctcattcagc ctttatccat tccttattct tcttcaacat600 tgcctcatgc atcatcttac agcctgatga tgggaggatt tggtggtgct agtatccaga660 aggcccagtc tctgattgat ttaggatcta gtagctcaac ttcctcaact gcttccctct720 cagggaactc acctaagaca gggacctcag agtgggcagt tcctcagcct tcaagattaa780 agtatcggca aaaatttaat agtctagaca aaggcatgag cggatacctc tcaggttttc840 aagctagaaa tgcccttctt cagtcaaatc tctctcaaac tcagctagct actatttgga900 ctctggctga catcgatggt gacggacagt tgaaagcrga agaatttatt ctggcgatgc960 acctcactga catggccaaa gctggacagc cactaccact gacgttgcct cccgagcttg1020 tccctccatc tttcagaggg ggaaagcaag ttgattctgt taatggaact ctgccttcat1080 atcagaaaac acaagaagaa gagcctcaga agaaactgcc agttactttt gaggacaaac1140 ggaaagccaa ctatgaacga ggaaacatgg agctggagaa gcgacgccaa gtgttgatgg1200 agcagcagca gagggaggct gaacgcaaag cccagaaaga gaaggaagag tgggagcgga1260 aacagagaga actgcaagag caagaatgga agaagcagct ggagttggag aaacgcttgg1320 agaaacagag gagaggcagc ggcaggagct gaaagaaaag gcagactaca ataaacagtg atcaaaataa acatgcagct aaaaggaaga catctaagct ataatacaca aaatcgaaag agagctggag aaaacaggag gctcagtcag tctccacctg agatgtccaa tgacctggaa gcttatctat cagtaacaca attatgccaa ctcagaaatg gcagttagcc aaaaagatta agacagcggg cttgagagac aagaccaggg gaactggaag atcagaaagc attatggaaa ctggtccctg cctgattcag agacttaaag gattcattta cttgaacaac gagcaaaaaa aggaagagag aacgccgttt aacaagaaga cagtgaatgg aaacacaaaa tcaaacaact agaagcagct ggatcagttt aacaattaga acaatcagct ttcataaaat gagaaaggag agaatgggaa cattgtcagg aaaacatcag gactgagcta tcaacaagag attaaacgaa acttcataaa tgctcttgaa gaaggaactc caaacgtgac atagaaagac agactccgtc ctgagctcca cagatctcag gaagttttgg cttaaggaat agaattaaaa aagtcatcag aaagaaactg agagaaagct aaattgaagg

1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2017 <210> 73 <211> 414 <212> DNA .

<213> Homo sapien <400> 73 atggcagtga cattcaccat catgggaacc accttccctt ttcttcagga ttctctgtag60 tggaagagag cacccagtgt tgggctgaaa acatctgaaa gtagggagaa gaacctaaaa120 taatcagtat ctcagagggc tctaaggtgc caagaagtct cactggacat ttaagtgcca180 acaaaggcat actttcggaa tcgccaagtc aaaactttct aacttctgtc tctctcagag240 acaagtgaga ctcaagagtc tactgcttta gtggcaacta cagaaaactg gtgttaccca300 gaaaaacagg agcaattaga aatggttcca atatttcaaa gctccgcaaa caggatgtgo360 tttcctttgc ccatttaggg tttcttctct ttcctttctc tttattaacc acta414 <210> 74 <211> 1567 <212> DNA <213> Homo sapien <400> 74 atatctagaa gtctggagtg agcaaacaag agcaagaaac aaaaagaagc caaaagcaga 60 aggctccaat atgaacaaga taaatctatc ttcaaagaca tattagaagt tgggaaaata120 attcatgtga actagacaag tgtgttaaga gtgataagta aaatgcacgt ggagacaagt180 gcatccccag atctcaggga cctccccctg cctgtcacct ggggagtgag aggacaggat240 agtgcatgtt ctttgtctct gaatttttag ttatatgtgc tgtaatgttg ctctgaggaa300 gcccctggaa agtctatccc aacatatcca catcttatat tccacaaatt aagctgtagt360 atgtacccta agacgctgct aattgactgc cacttcgcaa ctcaggggcg gctgcatttt420 agtaatgggt caaatgattc actttttatg atgcttccaa aggtgccttg gcttctcttc480 ccaactgaca aatgccaaag ttgagaaaaa tgatcataat tttagcataa acagagcagt540 cggcgacacc gattttataa ataaactgag caccttcttt ttaaacaaac aaatgcgggt600 ttatttctca gatgatgttc atccgtgaat ggtccaggga aggacctttc accttgacta660 tatggcatta tgtcatcaca agctctgagg cttctccttt ccatcctgcg tggacagcta720 agacctcagt tttcaatagc atctagagca gtgggactca gctggggtga tttcgccccc780 catctccggg ggaatgtctg aagacaattt tgttacctca atgagggagt ggaggaggat840 acagtgctac taccaactag tggataaagg ccagggatgc tgctcaacct cctaccatgt900 acaggacgtc tccccattac aactacccaa tccgaagtgt caactgtgtc aggactaaga960 aaccctggtt ttgagtagaa aagggcctgg aaagagggga gccaacaaat ctgtctgctt1020 cctcacatta gtcattggca aataagcatt ctgtctcttt ggctgctgcc tcagcacaga1080 gagccagaac tctatcgggc accaggataa catctctcag tgaacagagt tgacaaggcc1140 tatgggaaat gcctgatggg attatcttca gcttgttgag cttctaagtt tctttccctt1200 cattctaccc tgcaagccaa gttctgtaag agaaatgcct gagttctagc tcaggttttc1260 ttactctgaa tttagatctc cagacccttc ctggccacaa ttcaaattaa ggcaacaaac1320 atataccttc catgaagcac acacagactt ttgaaagcaa ggacaatgac tgcttgaatt gaggccttga ggaatgaagc tttgaaggaa aagaatactt tgtttccagc ccccttccca cactcttcat gtgttaacca ctgccttcct ggaccttgga gccacggtga crgtattaca tgttgttata gaaaactgat tttagagttc tgatcgttca agagaatgat taaatataca tttccta . .

<210> 75 <211> 240 <212> DNA <213> Homo sapien <400> 75 tcgagcggcc gcccgggcag gtccttcaga cttggactgt gtcacactgc caggcttcca gggctccaac ttgcagacgg cctgttgtgg gacagtctct gtaatcgcga aagcaaccat ggaagacctg ggggaaaaca ccatggtttt atccaccctg agatctttga acaacttcat ctctcagcgt gcggagggag gctctggact ggatatttct acctcggccg cgaccacgct <210> 76 <211> 330 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (330} <223> n = A,T,C or G <400> 76 tagcgyggtc gcggccgagg yctgcttytc tgtccagccc agggcctgtg gggtcagggc ggtgggtgca gatggcatcc actccggtgg cttccccatc tttctctggc ctgagcaagg tcagcctgca gccagagtac agagggccaa cactggtgtt cttgaacaag ggccttagca ggccctgaag grccctctct gtagtgttga acttcctgga gccaggccac atgttctcct cataccgcag gytagygatg gtgaagttga gggtgaaata gtattmangr agatggctgg caracctgcc cgggcggccg ctcsaaatcc <210> 77 <211> 361 <212> DNA <213> Homo sapien <400> 77 agcgtggtcg cggccgaggt gtccttcagg gtctgcttat gcccttgttc aagaacacca gtgtcagctc tctgtactct ggttgcagac tgaccttgct caggcctgag aaggatgggg cagccaccag agtggatgct gtctgcaccc atcgtcctga ccccaaaagc cctggactgg acagagagcg gctgtactgg aagctgagcc agctgaccca cggcatcact gagctgggcc cctacaccct ggacagggac agtctctatg tcaatggttt cacccatcgg agctctgtac ccaccaccag caccggggtg gtcagcgagg agccattcaa cctgcccggg cggccgctcg

1380

1440

1500

1560

1567

120 180 240 300 330

120 180 240 300 360 361 <210> 78 <211> 356 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (356) <223> n = A,T,C or G <400> 78 ttggggnttt mgagcggccg cccgggcagg taccggggtg gtcagcgagg agccattcac actgaacttc accatcaaca acctgcggta tgaggagaac atgcagcacc ctggctccag gaagttcaac accacggaga gggtccttca gggcctgctc aggtccctgt tcaagagcac cagtgttggc cctctgtact ctggctgcag actgactttg ctcagacttg agaaacatgg ggcagccact ggagtggacg ccatctgcac cctccgcctt gatcccactg gtcctggact ggacagagag cggctatact gggagctgag ccagtcctct ggcggngacn ccnctt <210> 79 <211> 226 <212> DNA <213> Homo sapien <400> 79 agcgtggtcg cggccgaggt ccagtcgcag catgctcttt ctcctgccca ctggcacagt gaggaagatc tctgctgtca gtgagaaggc tgtcatccac tgagatggca gtcaaaagtg catttaatac acctaacgta tcgaacatca tagcttggcc caggttatct catatgtgct cagaacactt acaatagcct gcagacctgc ccgggcggcc gctcga <210> 80 <211> 444 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) .. (444) <223> n = A,T,C or G <400> 80 tgtggtgttg aacttcctgg agncagggtg acccatgtcc tccccatact gcaggttggt gatggtgaag ttgagggtga atggtaccag gagagggcca gcagccataa ttgtsgrgck gsmgmssgag gmwggwgtyy cwgaggttcy rarrtccact gtggaggtcc caggagtgct ggtggtgggc acagagstcy gatgggtgaa accattgaca tagagactgt tcctgtccag ggtgtagggg cccagctctt yratgycatt ggycagttkg ctyagctccc agtacagccr ctctckgyyg mgwccagsgc ttttggggtc aagatgatgg atgcagatgg catccactcc agtggctgct ccatccttct cggacctgag agaggtcagt ctgcagccag agtacagagg gccaacactg gtgttctttg aata <210> 81 <211> 310 <212> DNA <213> Homo sapien <400> 81 tcgagcggcc gcccgggcag gtcaggaagc acattggtct tagagccact gcctcctgga ttccacctgt gctgcggaca tctccaggga gtgcagaagg gaagcaggtc aaactgctca gatcagtcag actggctgtt ctcagttctc acctgagcaa ggtcagtctg cagccagagt acagagggcc aacactggtg ttcttgaaca agggcttgag cagaccctgc agaaccctcttccgtggtgt tgaacttcct ggaaaccagg gtgttgcatg tttttcctca taatgcaagg ttggtgatgg

120 180 240 300 356

120 180 240 300 360 420 444

120 180 240 300 310 <210> 82 <211> 571 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(571) <223> n = A,T,C or G <400> 82 acggtttcaa tggacacttt tattgtttac ttaatggatc atcaattttg tctcactacc tacaaatgga atttcatctt gtttccatgc tgagtagtga aacagtgaca aagctaatca taataaccta catcaaaaga gaactaagct aacactgctc actttctttt taacaggcaa aatataaata tatgcactct anaatgcaca atggtttagt cactaaaaaa ttcaaatggg atcttgaaga atgtatgcaa atccagggtg cagtgaagat gagctgagat gctgtgcaac tgtttaaggg ttcctggcac tgcatctctt ggccactagc tgaatcttga catggaaggt tttagctaat gccaagtgga gatgcagaaa atgctaagtt gacttagggg ctgtgcacag gaactaaaag gcaggaaagt actaaatatt gctgagagca tccaccccag gaaggacttt accttccagg agctccaaac tggcaccacc cccagtgctc acatggctga ctttatcctc cgtgttccat ttggcacagc aagtggcagt g <210> 83 <211> 551 <212> DNA <213> Homo sapien

(־ <400> 83 aaggctggtg ggtttttgat cctgctggag aacctccgct ttcatgtgga ggaagaaggg aagggaaaag atgcttctgg gaacaaggtt aaagccgagc cagccaaaat agaagctttc cgagcttcac tttccaagct aggggatgtc tatgtcaatg atgcttttgg cactgctcac agagcccaca gctccatggt aggagtcaat ctgccacaga aggctggtgg gtttttgatg aagaaggagc tgaactactt tgcaaaggcc ttggagagcc cagagcgacc cttcctggcc atcctgggcg gagctaaagt tgcagacaag atccagctca tcaataatat gctggacaaa gtcaatgaga tgattattgg tggtggaatg gcttttacct tccttaaggt gctcaacaac atggagattg gcacttctct gtttgatgaa gagggagcca agattgtcaa agacctaatg tccaaagctg agaagaatgg tgtgaagatt accttgcctg ttgactttgt cactgctgac aagtttgatg a <210> 84 <211> 571 <212> DNA <213> Homo sapien.

<400> 84 tttgttcctt acatttttct aaagagttac ttaaatcagt caactggtct ttgagactct taagttctga ttccaactta gctaattcat tctgagaact gtggtatagg tggcgtgtct cttctagctg ggacaaaagt tctttgtttt ccccctgtag agtatcacag accttctgct gaagctggac ctctgtctgg gccttggact cccaaatctg cttgtcatgt tcaagcctgg aaatgttaat ctttaattct tccatatgga tggacatctg tctaagttga tcctttagaa cactgcaatt atcttctttg agtctaattt cttcttcttt gctttgaatc gcatcactaa acttcctctc ccatttctta gcttcatcta tcaccctgtc acgatcatcc tggagggaag acatgctctt agtaaaggct gcaagctggg tcacagtact gtccaagttt tcctgaagtt gctgaacttc cttgtctttc ttgttcaaag taacctgaat ctctccaatt gtctcttcca

120 180 240 300 360 420 480 540 571

120 180 240 300 360 420 480 540 551

120 180 240 300 360 420 480 540 agtggacttt ttct.ctgcgc aaagcatcca g <210> 85 <211> 561 .

<212> DNA <213> Homo sapien <400> 85 tcattgcctg tgatggcatc tggaatgtga tgagcagcca ggaagttgta gatttcattc 60 aatcaaagga ttcagcatgt ggtggaagct gtgaggcaag agaaacaaga actgtatggc 120 aagttaagaa gcacagaggc aaacaagaag gagacagaaa agcagttgca ggaagctgag 180 caagaaatgg aggaaatgaa agaaaagatg agaaagtttg ctaaatctaa acagcagaaa 240 atcctagagc tggaagaaga gaatgaccgg cttagggcag aggtgcaccc tgcaggagat 300 acagctaaag agtgtatgga aacacttctt tcttccaatg ccagcatgaa ggaagaactt 360 gaaagggtca aaatggagta tgaaaccctt tctaagaagt ttcagtcttt aatgtctgag 420 aaagactctc taagtgaaga ggttcaagat ttaaagcatc agatagaagg taatgtatct 480 aaacaagcta acctagaggc caccgagaaa catgataacc aaacgaatgt cactgaagag 540 ggaacacagt ctataccagg t 561 <210> 86 <211> 795 <212> DNA <213> Homo sapien <400> 86 aagccaataa tcaccattta ttacttaata tatgccaacc actgtacttg gcagttcaca 60 aattctcacc gttacaacaa ccccatgagg tatttattcc cattctatag atagggaaac 120 cacagctcaa gtaagttagg aaactgagcc aagtatacac agaatacgaa gtggcaaaac 180 tagaaggaaa gactgacact gctatctgct ggcctccagt gtcctggctc ttttcacacg 240 ggttcaatgt ctccagcgct gctgctgctg ctgcattacc atgccctcat tgtttttctt 300 cctctggtgt tcaactgcat ccttcaaaga atctaactca ttccagagac cacttatttc 360 tttctctctt tctgaaatta cttttaataa ttcttcatga gggggaaaag aagatgcctg 420 ttggtagttt tgttgtttaa gctgctcaat ttgggactta aacaatttgt tttcatcttg 480 tacatcctgt aacagctgtg ttttgctaga aagatcactc tccctctctt ttagcatggc 540 ttctaacctc ttcaattcat tttccttttc tttcaacaca atctcaagtt cttcaaactg 600 tgatgcagaa gaggcctctt tcaagntatg ttgtgctact tcctgaacat gtgcttttaa 660 agattcattt tcttcttgaa gatcctgtaa ccacttccct gtattggcta ggtctttctc 720 tttctcttcc aaaacagcct tcatggtatt catctgttcc tcttttcctt ttaataagtt 780, caggagcttc agaac ' 795 <210> 87 <211> 594 <212> DNA <213> Homo sapien <400> 87 caagcttttt tttttttttt aaaaagtgtt agcattaatg ttttattgtc acgcagatgg 60 caactgggtt tatgtcttca tattttatat ttttgtaaat taaaaaaatt acaagtttta 120 aatagccaat ggctggttat attttcagaa aacatgatta gactaattca ttaatggtgg 180 cttcaagctt ttccttattg gctccagaaa attcacccac cttttgtccc ttcttaaaaa 240 actggaatgt tggcatgcat ttgacttcac actctgaagc aacatcctga cagtcatcca 300 catctacttc aaggaatatc acgttggaat acttttcaga gagggaatga aagaaaggct 360 tgatcatttt gcaaggccca caccacgtgg ctgagaagtc aactactaca agtttatcac 420 ctgcagcgtc caaggcttcc tgaaaagcag tcttgctctc gatctgcttc accatcttgg 480 ctgctggagt ctgacgagcg gctgtaagga ccgatggaaa tggatccaaa gcaccaaaca 540 gagcttcaag act.cgctgct tggcttgaat tcggatccga tatcgccatg gcct <210> 88 <211> 557 <212> DNA <213> Homo sapien <400> 88 aagtgttagc attaatgttt tattgtcacg cagatggcaa ctgggtttat gtcttcatat tttatatttt tgtaaattaa aaaaattmca agttttaaat agccaatggc tggttatatt ttcagaaaac atgattagac taattcatta atggtggctt caagcttttc cttattggct ccagaaaatt cacccacctt ttgtcccttc ttaaaaaact ggaatgttgg catgcatttg acttcacact ctgaagcaac atcctgacag tcatccacat ctacttcaag gaatatcacg ttggaatact tttcagagag ggaatgaaag aaaggcttga tcattttgca aggcccacac cacgtggctg agaagtcaac tactacaagt ttatcacctg cagcgtccaa ggcttcctga aaagcagtct tgctctcgat ctgcttcacc atcttggctg ctggagtctg acgagcggct gtaaggaccg atggaaatgg atccaaagca ccaaacagag cttcaagact cgctgcttgg catgaattcg gatccga <210> 89 <211> 561 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(561) <223> n = A,T,C or G <400> 89 tacaaacttt attgaaacgc acacgcgcac acacacaaac acccctgtgg atagggaaaa gcacctggcc acagggtcca ctgaaacggg gaggggatgg cagcttgtaa tgtggctttt gc.cacaaccc ccttctgaca gggaaggcct tagattgagg ccccacctcc catggtgatg gggagctcag aatggggtcc agggagaatt tggttagggg gaggtgctag ggaggcatga gcagagggca ccctccgagt ggggtcccga gggctgcaga gtcttcagta ctgtccctca cagcagcrgt ctcaaggctg ggtccctcaa aggggcgtcc cagcgcgggg cctccctgcg caaacacttg gtacccctgg ctgcgcagcg gaagccagca ggacagcagt ggcgccgatc agcacaacag acgccctggc ggtagggaca gcaggcccag ccctgtcggt tgtctcggca gcaggtctgg ttatcatggc agaagtgtcc ttcccacact tcacgtcctt cacacccacg tganggctac nggccaggaa g <210> 90 <211> 561 <212> DNA <213> Homo sapien <400> 90 cccgtgggtg ccatccacgg agttgttacc tgatctttgg aagcaggatc gcccgtctgc actgcagtgg aagccccgtg ggcagcagtg atggccatcc ccgcatgcca cggcctctgg gaaggggcag caactggaag tccctgagac ggtaaagatg caggagtggc cggcagagca gtgggcatca acctggcagg ggccacccag atgcctgctc agtgttgtgg gccatttgtc cagaagggga cggcagcagc tgtagctggc tcctccgggg tccaggcagc aggccacagg gcagaactga ccatctgggc accgcgttcc agccaccagc cctgctgtta aggccaccca gctcaccagg gtccacatgg tctgcctgcg tccgactccg cggtccttgg gccctgatgg ttctacctgc tgtgagctgc ccagtgggaa gtatggctgc tgccaatgcc caacgccacc •60 120 180 240 300 360 420 480 540 557

120 180 240 300 360 420 480 tgctgctccg atcacctgca ctgctgcccc aagacactgt gtgtgacctg atccagagta agtgcctctc caaggagaac g <210> 91 <211> 541 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (541) <223> n = A, T,C or G <400> 91 gaatcacctt tctggtttag ctagtacttt gtacagaaca atgaggtttc ccacagcgga gtctccctgg gctctgtttg gctctcggta aggcaggcct acaccttttc ctctcctcta tggagagggg aatatgcatt aaggtgaaaa gtcaccttcc aaaagtgaga aagggattcg attgctgctt caggactgtg gaattatttg gaatgtttta caaatggttg ctacaaaaca acaaaaaagg taattacaaa atgtgtacat cacaacatgc tttttaaaaa cattatgcat tgtgctcaca ttcccttaaa tgttgtttcc aaaggtgctc agcctctagc ccagctggat tctccgggaa gaggcagaga cagtttggcg aaaaagacac agggaaggag ggggtggtga aaggagaaag cagccttcca gttaaagatc agccatcagt taaaggtcag cttcccgcan gctggcctca ngcggagtct gggtcagagg gaggagcagc agcagggtgg gactggggcg t <210> 92 <211> 551 <212> DNA <213> Homo sapien <400> 92 aaccggagcg cgagcagtag ctgggtgggc accatggctg ggatcaccac catcgaggcg gtgaagcgca agatccaggt tctgcagcag caggcagatg atgcagagga gcgagctgag cgcctccagc gagaagttga gggagaaagg cgggcccggg aacaggctga ggctgaggtg gcctccttga accgtaggat ccagctggtt gaagaagagc tggaccgtgc tcaggagcgc ctggccactg ccctgcaaaa gctggaagaa gctgaaaaag ctgctgatga gagtgaaaga ggtatgaagg ttattgaaaa ccgggcctta aaagatgaag aaaagatgga actccaggaa atccaactca aagaagctaa gcacattgca gaagaggcag ataggaagta tgaagaggtg gctcgtaagt tggtgatcat tgaaggagac ttggaacgca cagaggaacg agctgagctg gcagagtccc gttgccgaga gatggatgag cagattagac tgatggacca gaacctgaag tgtctgagtg c <210> 93 <211> 531 <212> DNA <213> Homo sapien <400> 93 gagaacttgg cctttattgt gggcccagga gggcacaaag gtcaggaggc ccaagggagg gatctggttt tctggatagc caggtcatag catgggtatc agtaggaatc cgctgtagct gcacaggcct cacttgctgc agttccgggg agaacacctg cactgcatgg cgttgatgac ctcgtggtac acgacagagc ca.ttggtgca gtgcaagggc acgcgcatgg gctccgtcct cgagggcagg. cagcaggagc attg.ctcctg cacatcctcg atgtcaatgg agtacacagc tttgctggca cactttccct ggcagtaatg aatgtccact tcctcttggg acttacaatc tcccactttg atgtactgca ccttggctgt gatgtctttg caatcaggct cctcacatg־t

120 180 240 300 360 420 480 540 541

120 180 240 300 360 420 480 540 551 gtcacagcag gtgcctggaa ttttcacgat tttgcctcct tcagccagac acttgtgttc 480 atcaaatggt gggcagcccg tgaccctctt ctcccagatg tactctcctc t 531 <210> 94 <211> 531 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(531) <223> n = A,T,C or G <400> 94 gcctggacct tgccggatca gtgccacaca gtgacttgct tggcaaatgg ccagaccttg 60 ctgcagagtc atcgtgt.caa ttgtgaccat ggaccccggc cttcatgtgc caacagccag 120 tctcctgttc gggtggagga gacgtgtggc tgccgctgga cctgcccttg tgtgtgcacg 180 ggcagttcca ctcggcacat cgtcaccttc gatgggcaga atttcaagct tactggtagc 240 tgctcctatg tcatctttca aaacaaggag caggacctgg aagtgctcct ccacaatggg 300 gcctgcagcc ccggggcaaa acaagcctgc atgaagtcca ttgagattaa gcatgctggc 360 gtctctgctg agctgcacag taacatggag atggcagtgg atgggagact ggtccttgcc 420 ccgtacgttg gtgaaaacat ggaagtcagc atctacggcg ctatcatgta tgaagtcagg 480 tttacccatc ttggccacat cctcaoatac accgccncaa aacaacgagt t 531 <210> 95 <211> 605 <212> DNA <213> Homo sapien <400> 95 agatcaacct ctgctggtca ggaggaatgc cttccttgtc ttggatcttt gctttgacgt 60’ tctcgatagt rwcaactkkr ytsramskma agkgyratgr wmttksywgw rasyktmwwm 120 rsgraraytt agacaycccm cctcwgagac gsagkaccar gtgcagaggt ggactctttc 180 tggatgttgt agtcagacag ggtgcgtcca tcttccagct gtttcccagc aaagatcaac 240 ctctgctgat caggagggat gccttcctta tcttggatct ttgccttgac attctcgatg 300 gtgtcactgg gctccacctc gaaggtgatg gtcttaccag tcagggtctt cacgaagaty 360 tgcatcccac ctctgagacg gagcaccagg tgcagggtrg actctttctg gatgttgtag 420 tcagacaggg tgcgyccatc ttccagctgc tttccsagca aagatcaacc tctgctggtc 480 aggaggratg ccttccttgt cytggatctt tgcyttgacr ttctcratgg tgtcactcgg 540 ctccacttcg agagtgatgg tcttaccagt cagggtcttc acgaagatct gcatcccacc 600 tctaa 605 <210> 96 <211> 531 <212> DNA <213> Homo sapien <400> 96 aagtcacaaa cagacaaaga ttattaccag ctgcaagcta tattagaagc tgaacgaaga 60 gacagaggtc atgattctga gatgattgga gaccttcaag ctcgaattac atctttacaa 120 gaggaggtga agcatctcaa acataatctc gaaaaagtgg aaggagaaag aaaagaggct 180 caagacatgc.ttaatcactc agaaaaggaa aagaataatt tagagataga tttaaactac 240 aaacttaaat cattacaaca acggttagaa caagaggtaa atgaacacaa agtaaccaaa 300 gctcgtttaa ctgacaaaca tcaatctatt gaagaggcaa agtctgtggc aatgtgtgag 360 atggaaaaaa agctgaaaga agaaagagaa gctcgagaga aggctgaaaa tcgggttgtt 420 cagattgaga aacagtgttc catgctagac gttgatctga agcaatctca gcagaaacta gaacatttga ctggaaataa agaaaggatg gaggatgaag ttaagaatct a <210> 97 <211> 1017 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(1017) <223> n = A,T,C or G <400> 97 cgcctccacc atgtccatca gggtgaccca gaagtcctac aaggtgtcca cctctggccc ccgggccttc agcagccgct cctacacgag tgggcccggt tcccgcatca gctcctcgag cttctcccga gtgggcagca gcaactttcg cggtggcctg ggcggcggct atggtggggc cagcggcatg ggaggcatca ccgcagttac ggtcaaccag agcctgctga gcccccttgt cctggaggtg gaccccaaca tccaggccgt gcgcacccag gagaaggagc agatcaagac cctcaacaac aagtttgcct ccttcataga caaggtacgg ttcctggagc agcagaacaa gatgctggag accaagtgga gcctcctgca gcagcagaag acggctcgaa gcaacatgga caacatgttc gagagctaca tcaacarcct taggcggcag ctggagactc tgggccagga gaagctgaag ctggaggcgg agcttggcaa catgcagggg ctggtggagg acttcaagaa caagtatgag gatgagatca ataagcgtac agagatggag aacgaatttg tcctcatcaa gaaggatgtg gatgaagctt acatgaacaa ggtagagctg gagtctcgcc tggaagggct gaccgacgag atcaacttcc tcaggcagct gtatgaagag gagatccggg agctgcagtc ccagatctcg gacacatctg tggtgctgtc catggacaac agccgctccc tggacatgga cagcatcatt gctgaggtca aggcacagta cgaggatatt gccaaccgca gccgggctga ggctgagagc atgtaccagg tcaagtatga ggagctgcag agcctggctg ggaagcacgg ggatgacctg cggcgcacaa agactgagat ctctgagatg aacccggaac atcagcccgg ctncaggctg agattgaggg cctcaaaggc caganggctt ncctggangn ccgccat <210> 98 <211> 561 <212> DNA <213> Homo sapien <400> 98 cccggagcca gccaacgagc ggaaaatggc agacaatttt tcgctccatg atgcgttatc tgggtctgga aacccaaacc ctcaaggatg gcctggcgca tgggggaacc agcctgctgg ggcagggggc tacccagggg cttcctatcc tggggcctac cccgggcagg cacccccagg ggcttatcct ggacaggcac ctqcaggcgc ctaccctgga gcacctggag cttatcccgg agcacctgca cctggagtct acccagggcc acccagcggc cctggggcct acccatcttc tggacagcca agtgccaccg gagcctaccc tgccactggc ccctatggcg cccctgctgg gccactgatt gtgccttata acctgccttt gcctggggga gtggtgcctc gcatgctgat aacaattctg ggcacggtga agcccaatgc aaacagaatt gctttagatt tccaaagagg gaatgatgtt gccttccact ttaacccacg cttcaatgag aacaacagga gagtcattgg ttgcaataca aagctggata a

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1017

120 180 24 0 300 360 420 480 540 561 <210> 99 <211> 636 <212> DNA <213> Homo sapien <400> 99 gggaatgcaa ggaaacttag tgttgtagtc gctgatcagg cactgggctc tcccacctct acagggtgcg ggratgcctt acttcgagag agacggagca tccatcttcc caactttatt acaccccccc agacagggtr aggratgcct cacctcgagg gagacggagc yccatcttcc ccttgtcytg tgatggtctt ccaggtgcag agctgtttcc gaaaggaaag tcragcgmag cgwccatctt tccttatctt gtgatggtct accaggtgca agctgctttc gatctttgcy accagtcagg ggtggactct cagcaaagat tgcaatgaaa kaccargtgc ccagctgttt ggatctttgc taccagtcag gggtrgactc csagcaaaga ttgacrttct gtcttcacga ttctggatgg caacct tttgttgaaa araggtggac yccrgcaaag cttgacattc ggtcttcacg tttctggatg tcaacctctg caatggtgtc agatctgcat ttgtagtcag ccttaaaagg tctttctgga atcaacctct tcgatggtgt aagatytgca ttgtagtcag ctggtcagga actcggctcc cccacctcta acagggtgcg

120 180 240 300 360 420' 480 540 600 636 <210> 100 <211> 697 <212> DNA <213> Homo sapien <400 aggttgatct ccagaaagag - gaagaccctg ygtcaargca tgctsggaaa cyaccctgca ctggtaagac agatccaaga agctggaaga ytggtmctbc atcamcmwtg aaggaaggca ► 100 ttgctgggaa tccaccctgc actggtaaga aagatccarg gcagctggaa cctggtgctc catcaccctc taaggaaggc tggacgcacc gtctyagagg akktcgakys ttcctcctga acagctggaa accrggtgct ccatcactct acaaggaagg gatggrcgca cgtctcagag gaggtggagc atccctcctg ctgtctgact kgggrtgcaa castkwcact ccagcagagg gatggacgca ccgtcttaga cgaagtggag catycctcct ccctgtctga gtgggatgca ccagtgacac atcagcagag acaacatcca atctwmgtkw wtcrakaamg ttgatct ccctgtctga ggtgggatgc ccgagtgaca gaccagcaga ctacaacatc ratcttcgtg catcgagaat gttgatcttt gaaagagtcc agacactcac tyrwwgcawa ctacaaccat agatcttcgt ccattgagaa ggttgatctt cagaaagagt aagaccctga gtcaaggcaa gctgggaaac acctytgcac tkkyaagryy gatccmagac

120 180 240 300 360 420 480 540 600 660 697 <210> 101 <211> 451 <212> DNA <213> Homo sapien <400> 101 atggagtctc tctccacttc aggcaggcgt gggctggtct tacaggcgaa aagaacatca atgactattt gagagtggag actctgtcga ctgggttcaa caccataatt cgaactcctg agccaacgct catcaaggat cccaagcatt aagggccagg ccaggctgga gcgatcctcc tttgtatttt acctcaagtg cccggqcagg caattaatta ctacgttgac attcttaggt gcgctgtggt tgcctcagcc tagtagagac atctgtcctg gaacaacttt ccatctatta tgcttgagaa t gcgatatcgg tcccgagtag atggtttcgc gcctcccaaa agaatgaagg attactatat gatgtttgtc ctcactgcag ctgggactac catgttggct gtgttgggat aaatatgcaa gtgggtaatt ctgcatggtg

120 180 240 300 360 420 451 <210> 102 <211> 571 <212> DNA <213> Homo sapien <400> 102 agcgcggtct tccggcgcga gaaagctgaa cagctcgttg aggaggagtt ggacagggct ctggaggagg cagaaaaagc tgcagatgag ggtgatgtgg caggaacgac agtgagagag ccgccctcaa tggccacggc gaatgaaggt ccgacgcatc cctgcagaag gatagaaaac cgggccatga agga.tgagga gaagatggag attcaggaga tgcagctcaa agaggccaag 240 cacattgcgg aagaggctga ccgcaaatac gaggaggtag ctcgtaagct ggtcatcctg 300 gagggtgagc tggagagggc agaggagcgt gcggaggtgt ctgaactaaa atgtggtgac 360 ctggaagaag aactcaagaa tgttactaac aatctgaaat ctctggaggc tgcatctgaa 420 aagtattctg aaaaggagga caaatatgaa gaagaaatta aacttctgtc tgacaaactg 480 aaagaggctg agacccgtgc tgaatttgca gagagaacgg ttgcaaaact ggaaaagaca 540 attgatgacc tggaagagaa acttgcccag c 57!

<210> 103 <211> 451 <212> DNA <213> Homo sapien <400> 103 gtgcacaggt cccatttatt gtagaaaata ataataatta cagtgatgaa tagctcttct 60 taaattacaa aacagaaacc acaaagaagg aagaggaaaa accccaggac ttccaagggt 120 gaagctgtcc cctcctccct gccaccctcc caggctcatt agtgtccttg gaaggggcag 180 aggactcaga ggggatcagt ctccaggggc cctgggctga agcgggtgag gcagagagtc 240 ctgaggccac agagctgggc aacctgagcc gcctctctgg ccccctcccc caccactgcc 300 caaacctgtt tacagcacct tcgcccctcc cctctaaacc cgtccatcca ctctgcactt 360 cccaggcagg tgggtgggcc aggcctcagc catactcctg ggcgcgggtt tcggtgagca 420 aggcacagtc ccagaggtga tatcaaggcc t 451 <210> 104 <211> 441 <212> DNA <213> Homo sapien <400> 104 gcaaggaact ggtctgctca cacttgctgg cttgcgcatc aggactggct ttatctcctg 60 actcacggtg caaaggtgca ctctgcgaac gttaagtccg tccccagcgc ttggaatccr 120 acggccccca cagccggatc ccctcagcct tccaggtcct caactcccgt ggacgctgaa 180 caatggcctc catggggcta caggtaatgg gcatcgcgct ggccgtcctg ggctggcrgg 240 ccgtcatgct gtgctgcgcg ctgcccatgt ggcgcgtgac ggccttcatc ggcagcaaca 300 ttgtcacctc gcagaccatc tgggagggcc tatggatgaa ctgcgtggtg cagagcaccg 360 gccagatgca gtgcaaggtg tacgactcgc tgctggcact gccgcaggac ctgcaggcag 420 cccgcgccct cgtcatcatc a 44!

<210> 105 <211> 509 <212> DNA <213> Homo sapien.

<220>

<221> misc_feature <222> (1) . . . (509) <223> n = A, T,C or G <400> 105 tgcaaaaggg acacaggggt tcaaaaataa aaatttctct tccccctccc caaacctgta 60 ccccagctcc ccgaccacaa cccccttcct cccccgggga aagcaagaag gagcaggtgt 120 ggcatctgca gctgggaaga gagaggccgg ggaggtgccg agctcggtgc tggtctcttt 180 ccaaatataa atacntgtgt cagaactgga aaatcctcca gcacccacca cccaagcact 240 ctccgttttc tgccggtgtt tggagagggg cggggggcag gggcgccagg caccggctgg 300 ctgcggtcta ctgcatccgc tgggtgtgca ccccgcgagc ctcctgctgc tcattgtaga 360 agagatgaca ctcggggtcc ccccggatgg tgggggctcc ctggatcagc ttcccggtgt tggggttcac acaccagcac tccccacgct gcccgttcag agacatcttg cactgtttga ggttgtacag gccatgcttg tcacagttg <210> 106 <211> 571 <212> DNA <213> Homo sapien ' <400> 106 gggttggagg gactggttct ttatttcaaa aagacacttg tcaatattca gtatcaaaac agttgcacta ttgatttctc tttctcccaa tcggccccaa agagaccaca taaaaggaga gtacatttta agccaataag ctgcaggatg tacacctaac agacctccta gaaaccttac cagaaaatgg ggactgggta gggaaggaaa cttaaaagat caacaaactg ccagcccacg gactgcagag gctgtcacag ccagatgggg tggccagggt gccacaaacc caaagcaaag tttcaaaata atataaaatt taaaaagttt tgtacataag ctattcaaga tttctccagc actgactgat acaaagcaca attgagatgg cacttctaga gacagcagct tcaaacccag aaaagggtga tgagatgagt ttcacatggc taaatcagtg gcaaaaacac agtcttcttt ctttctttct ttcaaggagg caggaaagca attaagtggt cacctcaaca taagggggac atgatccatt ctgtaagcag ttgtgaaggg g <210> 107 <211> 555 <212> DNA <213> Homo sapien <400> 107 caggaaccgg agcgcgagca gtagctgggt gggcaccatg gctgggatca ccaccatcga ggcggtgaag cgcaagatcc aggttctgca gcagcaggca gatgatgcag aggagcgagc tgagcgcctc cagcgagaag ttgagggaga aaggcgggcc cgggaacagg ctgaggctga ggtggcctcc ttgaaccgta ggatccagct ggttgaagaa gagctggacc gtgctcagga gcgcctggcc actgccctgc aaaagctgga agaagctgaa aaagctgctg atgagagtga gagaggtatg aaggttattg aaaaccgggc cttaaaagat gaagaaaaga tggaactcca ggaaatccaa ctcaaagaag ctaagcacat tgcagaagag gcagatagga agtatgaaga ggtggctcgt aagttggtga tcattgaagg agacttggaa cgcacagagg aacgagctga gctggcagag tcccgttgcc gagagatgga tgagcagatt agactgatgg accagaacct gaagtgtctg agtgc <210> 108 <211> 541 <212> DNA <213> Homo sapien <400> 108 atctacgtca tcaatcaggc tggagacacc atgttcaatc gagctaagct gctcaatatt ggctttcaag aggccttgaa ggactatgat tacaactgct ttgtgttcag tgatgtggac ctcattccga tggacgaccg taatgcctac aggtgttttt cgcagccacg gcacatttct gttgcaatgg acaagttcgg gtttagcctg ccatatgttc agtattttgg aggtgtctct gctctcagta aacaacagtt tcttgccatc aatggattcc ctaataatta ttggggttgg ggaggagaag atgacgacat ttttaacaga ttagttcata aaggcatgtc tatatcacgt ccaaatgctg tagtagggag gtgtcgaatg atccggcatt caagagacaa gaaaaatgag cccaatcctc agaggtttga ccggatcgca catacaaagg aaacgatgcg cttcgatggt ttgaactcac ttacctacaa ggtgttggat gtcagagata cccgttatat acccaaatca c

120 180 240 300 360 420 480 540 571

120 180 240 300 360 420 480 540 555

120 180 240 300 360 420 480 540 541 <210> 109 <211> 411 <212> DNA <213> Homo sapien <400> 109 ctagacctct aabtaaaagg cacaatcatg ctggagaatg aacagtctga ccccgagggc cacagcgaat tttagggaag gaggcaaaga ggtgagaagg gaaaggaaag aaggaaggaa ggagaacaat aagaactgga gacgttgggt gggtcaggga gtgtggtgga ggctcggaga gatggtaaac aaacctgact gctatgagtt ttcaacccca tagtctaggg ccatgagggc gtcagttctt ggtggctgag ggtccttcca cccagcccac ctgggggagt ggagtgggga gttctgccag gtaagcagat gttgtctccc aagttcctga cccagatgtc tggcaggata acgctgacct gttccctcaa caagggacct gaaagtaatt ttgctcttta 0 <210> 110 <211> 451 <212> DNA <213> Homo sapien <400> 110 ccgaattcaa gcgtcaacga tccytccctt accatcaaat caattggcca ccaatggtactgaacctacg agtacaccga ctacgggcgg actaatcttc aactcctaca tacttccccc attattccta gaaccaggcg acctgcgact ccttgacgtt gacaatcgag tagtactccc gattgaagcc cccattcgta taataattac atcacaagac gtcttgcact catgagctgt ccccacatta ggcttaaaaa cagatgcaat tcccggacgt ctaagccaaa ccactttcac cgctacacga ccgggggtat actacggtca atgctctgaa atctgtggag caaaccacag tttcatgccc atcgtcctag aattaattcc cctaaaaatc tttgaaatag ggcccgtatt taccctatag caccccctct accccctcta g <210> 111 <211> 541 <212> DNA <213> Homo sapien <400> 111 gcrcttcaca cttttattgt taattctctt cacatggcag atacagagct gtcgtcttga agaccaccac tgaccaggaa atgccacttt tacaaaatca tccccccttt tcatgattgg aacagttttc ctgaccgtct gggagcgttg aagggtgacc agcacatttg cacatgcaaa aaaggagtga ccccaaggcc tcaaccacac ttcccagagc tcaccatggg ctgcaggtga cttgccaggt ttggggttcg tgagctttcc ttgctgctgc ggtggggagg ccctcaagaa ctgagaggcc ggggtatgct tcatgagtgt taacatttac gggacaaaag cgcatcatta ggataaggaa cagccacagc acttcatgct tgtgagggtt agctgtagga gcgggtgaaa ggattccagt ttatgaaaat ttaaagcaaa caacggtttt tagctgggtg ggaaacagga aaactgtgat gtcggccaat gaccaccatt tttctgccca tgtgaaggtc cccatgaaac c

120 180 240 300 360 420 451

120 180 240 300 360 420

480 540 541 <210> 112 <211> 521 <212> DNA <213> Homo sapien <400> 112 caagcgcttg gcgtttggac ccagttcagt tttggtttga cccaggggtc agccttagga cagtaccacc cctctctccc cactttccct gaggttcttg ggttttgtgc ctttggggat aggtcttcag gaggaggccg agttcccctt ctcccggcaa catctctggg aatcaacagc atattgacac gttggagccg agcctgaaca tgcccctcgg ccccagcaca ccttccttgc ctaaggtgtc tgagtttctg gctcttgagg catttccaga tcatcagtcc attgctcttg agtctttgca gagaacctca gatcaggtgc aagactttgt ccccacttac agatctatct cctcccttgg gaagggcagg ggtgtatgga ggggaaggga tctcctgcgc ccttcattgc cacacttggt acatctttag tgtctgagct tctcaaatta ctgcaatagg a <210> 113 <211> 568 <212> DNA <213> Homo sapien <400> 113 agcgtcaaat cagaatggaa aagactcaaa accatcatca acaccaagat agratccttc aagaaacagg aaaaaactcc taaaacacca aaaggaccta agacattaaa gcaaaaatgc aagcaagtat agaaaaaggt ggttctcttc agccaaattc atcaattatg tgaagaattg cttccggatg actgaccaag agatctctgg cagtggagga agtctcttta agaaaatagt ttaaacaatt ttttccgtct tatttcattt ctgtaacagt tgatatctgg ctgtcctttt agtgagaact ttccctaccg tgtttgataa atgttgtcca ggttctattg gttgtccaaa atgcctgttt agtttttaaa gatggaactc caccctttgc gtatgtatgg aatgttatga taggacatag tagtagcggt ggtcagacat ggsmgacaaa aatatacatg tgaaataa <210> 114 <211> 483 <212> DNA <213> Homo sapien <400> 114 tccgaattcc aagcgaatta tggacaaacg attcctttta gaggattact tttttcaatt60 tcggttttag taatctaggc tttgcctgta aagaatacaa cgatggattt taaatactgt120 ttgtggaatg tgtttaaagg attgattcta gaacctttgt atatttgata gtatttctaa180 ctttcatttc tttactgttt gcagttaatg ttcatgttct gctatgcaat cgtttatatg240 cacgtttctt taattttttt agattttcct ggatgtatag tttaaacaac aaaaagtcta300 tttaaaactg tagcagtagt ttacagttct agcaaagagg aaagttgtgg ggttaaactt360 tgtattttct ttcttataga ggcttctaaa aaggtatttt tatatgttct ttttaacaaa420 tattgtgtac aacctttaaa acatcaatgt ttggatcaaa acaagaccca gcttattttc480 tgc483 tggaaaaccc240 cttgaaattc300 acctgggaga360 gaatggggac420 gggaccatga480 caaaaggaca 60 gttctgtaga 120 ccaaagtgga 180 aggctattca 240 tgttaaaaaa 300 tataatgcag 360 ccaagaatgt 420 ttggttttaa 480 ggaaatggtg 540 <210> 115 <211> 521 <212> DNA <213> Homo sapien <400> 115 tgtggtggcg ggcccccggc gctgaatgaa aggaaatgtg tctgtgcttg tgcttcaaat aaaagtcact gaccgacgga ttcgcccttg cgggctgagg agcgccggcc attgtcggga cccaacatca gcccgggccc gacaggggca cttcccaaag gcccagcaag cttgtaatgc tggaggccca actacgaact atgaagacac tcattgcggg tgctgggccc ttgacgttgt gccgacataa ccttgaggag ttcggataag ggactctgac gccgtgggtt cgtgagcagg ccctccagga agcactcaaa gaggaataaa gatcatcatt aaccatggaa atcatcgagc cctgcccctg gaaaaatata ctagaggtct accggcaaga gatgccatgt attaaaatgt ctggatgaag atctactcta c

ccttcagcaa ggccagtaaa ttgcaaggga ccacaagcat tggaactcaa ttgctcaaca cagacagcat aaaccactcg

120 180 240 300 360 420 480 521 <210> 115 <211> 501 <212> DNA <213> Homo sapien <400> 116 ctttgcaaag cttttatttc atgtctgcgg catggaatcc acctgcacat ggcatcttaq. ctgtgaagga gaaagcagtg cacgagaagg aatgagtggg cggaaccaac ggcctccaca agctgccttc cagcagcctg ccaaggccat ggcagagaga gactgcaaac aaacacaaqc aaacagagtc tcttcacagc tggagtctga aagctcatag tggcatgtgt gaatctgaca aaattaaaag tgtgcatagt ccattacatg cataaaacac taataataat cctgtttaca cgtgactgca gcaggcaggt ccagctcoac cactgccctc ctgccacatc acatcaaatg ccatggttta gagggttttt catatgtaat tcttttattc tgtaaaaggt aacaaaatat acagaacaaa actttccctt tttaaaacta atgttacaaa tctgtattat cacttgaata taaatagtat ataagctgat c <210> 117 <211> 451 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(451) <223> n = A,T,C or G <400> 117 caagggatat atgttgaggg tacrgrgtga cactgaacag atcacaaagc acgagaaaca ttagttctct ccctccccag cgtctccttc gtctccctgg ttttccgatg tccacagaat gagattgtcc ctaagtaact gcatgatcag agtgctgkct ttataagact cttcattcag cgtatccaat tcagcaattg cttcatcaaa tgccgttttt gccaggctac aggccttttc aggagagttt agaatctcat agtaaaagac tgagaaattt agtgccagac caagacgaat tgggtgtgta ggctgcattn ctttcttact aatttcaaat gcttcctggt aagcctgctg ggagttcgac acaagtggtt tgtttgttgc tccagatgcc acttcagaaa gatacctaaa ataatctcct ttcattttca aagtagaaca c <210> 118 <211> 501 <212> DNA <213> Homo sapien <400> 11a tccggagccg gggtagtcgc cgccgccgcc gccggtgcag ccactgcagg caccgctgcc gccgcctgag tagtgggctt aggaaggaag aggtcatctc gctcggagct tcgctcggaa gggtctttgt tccctgcagc cctcccacgg gaatgacaat ggataaaagt gagctggtac agaaagccaa actcgctgag caggctgagc gatatgatga tatggctgca gccatgaagg cagtcacaga acaggggcat gaactctcca acgaagagag aaatctgctc tctgttgcct acaagaatgt ggtaaggccg cccgccgctc ttcctggcgt gtcatctcca gcattgagca gaaaacagag aggaatgaga agaagcagca gatgggcaaa gagtaccgtg agaagataga ggcagaactg caggacatct gcaatgatgt tctggagctt gttggacaaa tatcttattc caatgctaca caacccagaa a <210> 119 <211> 391

120 180 240 300 360 420 480 501

120 180 240 300 360 420 451

120 180 240 300 360 420 480 501 <212> DNA <213> Homo sapien <400> 119 aaaaagcagc argttcaaca caaaata.gaa atctcaaatg taggatagaa caaaaccaag6C tgtgtgaggg gggaagcaac agcaaaagga agaaatgaga tgttgcaaaa aagatggagg12C agggttcccc tctcctctgg ggactgactc aaacactgat gtggcagtat acaccattcc18C agagtcaggg gtgttcattc ttttttggga gtaagaaaag gtggggatta agaagacgtt24C tctggaggct tagggaccaa ggctggtctc tttcccccct cccaaccccc ttgatccctt30C tctctgatca ggggaaagga gctcgaatga gggaggtaga gttggaaagg gaaaggattc36C cacttgacag aatgggacag actccttccc a <210> 120 <211> 421 <212> DNA <213> Homo sapien <220> <221> misc_feature <222> (1)..(421) <223> n = A,T,C or G <400> 120 tggcaatagc acagccatcc aggagctctt cargcgcatc tcggagcagt tcactgccat60 gttccgccgg aaggccttcc tocactggta cacaggcgag ggcatggacg agatggagtt120 caccgaggct gagagcaaca tgaacgacct cgtctctgag tatcaagcag taccaggatg180 ccaccgcaga agaggaggag gatttcggtg aggaggccga agaggaggcc taaggcagag240 cccccatcac ctcaggcttc tcagttccct tagccgtctt actcaactgc ccctttcctc300 tccctcagaa tttgtgtttg ctgcctctat cttgtttttt gttttttctt ctgggggggt360 ctagaacagt gcctggcaca tagtaggcgc tcaataaata cttggttgnt gaatgtctcc420 <210> 121 <211> 206 <212> DNA <213> Homo sapien <400> 121 agctggcgct agggctcggt tgtgaaatac agcgtrgtca gcccttgcgc tcagtgtaga60 aacccacgcc tgtaaggtcg gtcttcgtcc atctgctttt ttctgaaata cactaagagc120 agccacaaaa ctgtaacctc aaggaaacca taaagcttgg agtgccttaa tttttaacca180 gtttccaata aaacggttta ctacct206 <210> 122 <211> 131 <212> DNA <213> Homo sapien <400> 122 ggagatgaag atgaggaagc tgagtcagct acgggcargc gggcagctga agatgatgag 60 gatgacgatg tcgataccaa gaagcagaag accgacgagg atgactagac agcaaaaaag 120 gaaaagttaa a <210> 123 <211> 231 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(231) <223> n = A,T,C or G <400> 123 gatgaaaatt aaatacttaa attaatcaaa aggcactacg ataccaccta aaacctactg 60 cctcagtggc agtakgctaa kgaagatcaa gctacagsac atyatctaat atgaatgtta 120 gcaattacat akcargaagc atgtttgctt tccagaagac tatggnacaa tggtcattwg 180 ggcccaagag gatatttggc cnggaaagga tcaagataga tnaangtaaa g 231 <210> 124 <211> 521 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (521) <223> n = A,T,C or G <400> 124 gagtagcaac gcaaagcgct tggtattgag tctgtgggsg acttcggttc cggtctctgc 60 agcagccgtg atcgcttagt ggagtgctta gggtagttgg ccaggatgcc gaatatcaaa 120 atcttcagca ggcagctccc accaggactt atctcasaaa attgctgacc gcctgggcct 180 ggagctaggc aaggtggtga ctaagaaatt cagcaaccag gagacctgtg tggaaattgg 240 tgaaagtgta ccgtggagag gatgtctaca ttgttcagag tggntgtggc gaaatcaatg 300 acaatttaat ggagcttttg atcatgatta atgcctgcaa gattgcttca gccagccggg 360 ttactgcagt catcccatgc ttcccttatg ccccggcagg ataagaaaga tnagagccgg 420 gccgccaatc tcagccaagc ttggtgcaaa tatgctatct gtagcagtgc agatcatatt 480 atcaccatgg acctacatgc ttctcaaatt canggctttt t 521 <210> 125 <211> 341 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) .. (341) <223> n = A,T,C or G <400> 125 atgcaaaagg ggacacaggg ggttcaaaaa taaaaatttc tcttccccct ccccaaacct 60 gtaccccagc tccccgacca caaccccctt cctcccccgg ggaaagcaag aaggagcagg 120 tgtggcatct gcagctggga agagagaggc cggggaggtg ccgagctcgg tgctggtctc 180 tttccaaata taaatacgtg tgtcagaact ggaaaatcct ccagcaccca ccacccaagc 240 actctccgtt ttctgccggt gtttggagag gggcggnggg caggggcgcc aggcaccggc 300 tggctgcggt ctactgcatc cgctgggtgt gcaccccgcg a 341 <210> 126 <211> 521 <212> DNA.

<213> Homo sapien <220>

<221> misc_feature <222> (1).,.(521) <223> n = A,T,C or G <400> 126 aggttggaga aggtcatgca ggtgcagatt gtccaggskc agccacaggg tcaagcccaa6C caggcccaga gtggcactgg acagaccatg caggtgatgc agcagatcat cactaacaca120 ggagagatcc agcagatccc ggtgcagctg aatgccggcc agctgcagta tatccgctta180 gcccagcctg tatcaggcac tcaagttgtg cagggacaga tccagacact tgccaccaat240 gctcaacaga ttacacagac agaggtccag caaggacagc agcagttcaa gccagttcac300 aagatggaca gcagctctac cagatccagc aagtcaccat gcctgcgggc cangacctcg360 ccagcccatg ttcatccagt caagccaacc agcccttcna cgggcaggcc ccccaggtga420 ccggcgactg aagggcctga gctggcaagg ccaangacac ccaacacaat ttttgccata480 cagcccccag gcaatgggca cagcctttct tcccagagga c <210> 127 <211> 351 <212> DNA <213> Homo sapien <400> 127 tgagatttat tgcatttcat gcagcttgaa gtccatgcaa aggrgactag cacagttttt60 aatgcattta aaaaataaaa gggaggtggg cagcaaacac acaaagtcct agtttcctgg120 gtccctggga gaaaagagtg tggcaatgaa tccacccact ctccacaggg aataaatctg180 tctcttaaat gcaaagaatg tttccatggc ctctggatgc aaatacacag agctctgggg 240 tcagagcaag ggatggggag aggaccacga gtgaaaaagc agctacacac attcacctaa300 ttccatctga gggcaagaac aacgtggcaa gtcttggggg tagcagctgt t351 <210> 128 <211> 521 <212> DNA <213> Homo sapien <400> 128 tccagacatg ctcctgtcct aggcggggag caggaaccag acctgctatg ggaagcagaa60 agagttaagg gaaggtttcc tttcattcct gttccttctc ttttgctttt gaacagtttt120 taaatatact aatagctaag tcatttgcca gccaggtccc ggtgaacagt agagaacaag180 gagcttgcta agaattaatt ttgctgtttt tcaccccatt caaacagagc tgccctgttc240 cctgatggag ttccattcct gccagggcac ggctgagtaa cacgaagcca ttcaagaaag300 gcgggtgtga aatcactgcc accccatgga cagacccctc actcttcctt cttagccgca360 gcgctactta ataaatatat ttatactttg aaattatgat aaccgatttt tcccatgcgg420 catcctaagg gcacttgcca gctcttatcc ggacagtcaa gcactgttgt tggacaacag480 ataaaggaaa agaaaaagaa gaaaacaacc gcaacttctg t521 <210> 129 <211> 521 <212> DNA <213> Homo sapien <400> 129 tgagacggac cactggcctg gtcccccctc atktgctgtc gtaggacctg acatgaaacg 60 cagatctagt ggcagaaagg aagatgatga ggaacttctg agacgtcggc agcttcaaga agagcaatta atgaagctta actcaggcct gggacagttg atcttgaaag aagagatgga gaaagagagc cgggaaaggt catctctgtt agccagtcgc tacgattctc ccatcaactc agcttcacat attccatcat ctaaaactgc atctctccct ggctatggaa gaaatgggct tcaccggcct gtttctaccg acttcgctca gtataacagc tatggggatg tcagcggggg agtgcgagat taccagacac ttccagatgg ccacatgcct gcaatgagaa tggaccgagg agtgtctatg cccaacatgt tggaaccaaa gatatttcca tatgaaatgc tcatggtgac caacagaggg ccgaaaccaa atctcagaga ggtggacaga a <210> 130 <211> 270 <212> DNA <213> Homo sapien <400> 130 tcactttatt tttcttgtat aaaaacccta tgttgtagcc acagctggag cctgagtccg ctgcacggag actctggtgt gggtcttgac gaggtggtca gtgaactcct gatagggaga cttggtgaat acagtctcct tccagaggtc gggggtcagg tagctgtagg tcttagaaat ggcatcaaag gtggccttgg cgaagttgcc cagggtggca gtgcagcccc gggctgaggt gtagcagtca tcgataccag ccatcargag <210> 131 <211> 341 <212> DNA <213> Homo sapien <400> 131 ctggaatata gacccgtgat cgacaaaact ttgaacgagg ctgactgtgc caccgtcccg ccagccattc gctcctactg atgagacaag atgtggtgat gacagaatca gcttttgtaa ttatgtataa tagctcatgc atgtgtccat gtcataactg tcttcatacg cttctgcacr ctggggaaga aggagtacat tgaagggaga ttggcaccta gtggctggga gcttgccagg aacccagtgg ccagggagcg tggcacttac ctttgtccct tgcttcattc ttgtgagatg ataaaactgg gcacagctct taaataaaat ataaatgaac a <210> 132 <211> 844 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(844) <223> n = A, T, C or G <400> 132 tgaatgggga ggagctgacc caggaaatgg agcttgngga gaccaggcct acaggggatg gaaccttcca gaagtgggca tctgtggtgg tgcctcttgg gaaggagcag aagtacacat gccatgtgga acatgagggg ctgcctgagc ccctcaccct gagatggggc aaggaggagc ctccttcatc caccaagact aacacagtaa tcattgctgt tccggttgtc cttggagctg tggtcatcct tggagctgtg atggcttttg tgatgaagag gaggagaaac acaggtggaa aaggagggga ctatgctctg gctccaggct cccagagctc tgatatgtct crcccagatt gtaaagtgtg aagacagctg cctggtgtgg acttggtgac agacaatgtc ttcacacatc tcctgtgaca tccagagacc tcagttctct ttagtcaagt gtctgatgtt ccctgtgagt ctgcgggctc aaagtgaaga actgtggagc ccagtccacc cctgcacacc aggaccctat ccctgcactg ccctgtgttc ccttccacag ccaaccttgc tgctccagcc aaacattggt

120 180 240 300 360

420 480 521

120 180 240

300 360 420 480

540 600 ggacatctgc agcctgtcag ctccatgcta ccctgacctt caactcctca cttccacact gagaataata atttgaatgt gggtggctgg agagatggct cagcgctgac tgctcttcca aaggtcctga gttcaaatcc. cagcaaccac atggtggctc acaaccatct gtaatgggat ctaataccct cttctgcagt gtctgaagac asctacagtg tacttacata taataataaa taag <210> 133 <211> 601 <212> DNA <213> Homo sapien <400> 133 ggccgggcgc gcgcgccccc gccacacgca cgccgggcgt gccagtttat aaagggagag agcaagcagc gagtcttgaa gctctgtttg gt.gctttgga tccatttcca tcggtcctta cagccgctcg tcagactcca gcagccaaga tggtgaagca gatcgagagc aagactgctt ttcaggaagc cttggacgct gcaggtgata aacttgtagt agttgacttc tcagccacgt ggtgtgggcc ttgcaaaatg atcaagcctt tctttcattc cctctctgaa aagtattcca acgtgatatt ccttgaagta gatgtggatg actgtcagga tgttgcttca gagtgtgaag tcaaatgcat gccaacattc cagtttttta agaagggaca aaaggtgggt gaattttctg gagccaataa ggaaaagctt gaagccacca ttaatgaatt agtctaatca tgttttctaa aaatataacc agccattggc tatttaaaac ttgtaatttt tttaatttac aaaaatataa aatatgaaga cataaacccm gttgccatct gcgtgacaat aaaacattaa tgctaacact t <210> 134 <211> 421 <212> DNA <213> Homo sapien <400> 134 tcacataaga aatttaagca agttacrcta tcttaaaaaa cacaacgaat gcattttaat agagaaaccc ttccctccct ccacctccct cccccaccct cctcatgaat taagaatcta agagaagaag taaccataaa accaagtttt gtggaatcca tcatccagag tgcttacata gtgattaggt taatattgcc ttcttacaaa atttctattt taaaaaaaat tataacctta attgcttatt acaaaaaaat tcagtacaaa agttcaatat attgaaaaat gcctttcccc tccctcacag caccgtttta taratagcag agaataarga agagattgcc agtctagata gggcaatctt caaattacac caagacgcac agtggtttat ttaccccccc cttctcaraa g

120 180 240 300 360 420 480 540 600 601

120 180 240 300 360 420 421 <210> 135 <211> 511 <212> DNA <213> Homo sapien <400 ggaaaggatt gctgacagac tgactatgaa gaaactctta gacagtatcc gggttgatgt accactggaa gaacacttct gacacatcag • 135 caagaattag aaagagagag cagcttcttg gaaggcgaag cgagcatcct ggaagaatca atgtttgcat gaacaggatc tcagttataa aggacttgct agatggcgga atgtaaagtt aagagaggtt caagtcgtag gaggcgaagt cgaagaaatt aaccaatggg atatacctca tgctrragaa aataagggat agccctggac gaagctgtct tgtaccgtac agtagtgtta gatgttgatg aaggcttggg a aaagacaact caaatgcagc atggaaatca ccaagccctt aactagagga gcatctctca ggaaatttat agatgatcag ctcgtcgcat aacagctgaa gtgcttacag cttcccgtgr aagcggaaga ttccgcctca cccgcttgaa aaaaattgga

120 180 240 300 360 420 480 511 <210> 136.

<211> 341 <212> DNA <213> Homo sapien <400> 136 catgggtttc accaggttgg ccaggctgct cttgaactsc tgacctcagg tgatccaccc 60 gcctcggcct cccaaagtgc tgggattaca ggcgtgagcc accacgcccg gcccccaaag 120 ctgtttcttt tgtctttagc gtaaagctct cctgccatgc agtatctaca taactgacgt 180 gactgccagc aagctcagtc actccgtggt ctttttctct ttccagttct tctctctctc 240 ttcaagttct gcctcagtga aagctgcagg tccccagtta agtgatcagg tgagggttct 300 ttgaacctgg ttctatcagt cgaartaatc cttcatgatg g 34!

<210> 137 <211> 551 <212> DNA <213> Homo sapien <400> 137 gatgtgttgg accctctgtg tcaaaaaaaa cctcacaaag aatcccorgc toattacaga 60 agaagatgca tttaaaatac gggttatttt caacttttta tctgaggaca agtatccarr 120 aartattgtg tcagaagaga ttgaatacct gcttaagaag cttacagaag cratgggagg . 180 aggttggcag caagaacaat ttgaacatta taaaatcaac tttgatgaca gtaaaaacgg 240 cctttctgca tgggaactta ttgagcttat tggaaatgga cagtttagca aaggcatgga 300 ccggcagact gtgtctatgg caattaatga agtctttaat gaacttatat tagatgtgtt 360 aaagcagggt tacatgatga aaaagggcca cagacggaaa aactggactg aaagatggtt 420 tgtactaaaa cccaacataa tttcttacta tgtgagtgag gatctgaagg ataagaaagg 480 agacattctc ttggatgaaa attgctgtgt agaagtcctt gcctgacaaa ag'atggaaag 540 aaatgccttt t 551 <210> 138 <211> 531 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (531) <223> n = A,T,C or G <400> 138 gactggttct tt.atttcaaa aagacacttg tcaatattca gtrtcaaaac agttgcacta 60 ttgatttctc tttctcccaa tcggccccaa agagaccaca taaaaggaga gtacatttta 120 agccaataag ctgcaggatg tacacctaac agacctccta gaaaccttac cagaaaatgg 180 ggactgggta gggaaggaaa cttaaaagat caacaaactg ccagcccacg gactgcagag 240 gctgtcacag ccagatgggg tggccagggt gccacaaacc caaagcaaag tttcaaaata 300 atataaaatt taaaaagttt tgtacataag ctattcaaga tttctccagc actgactgat 360 acaaagcaca attgagatgg cacttctaga gacagcagct tcaaacccag aaaagggtaa 420 tgagatgaag tttcacatgg ctaaatcagt ggcaaaaaca cagtcttctt tctttctttc 480 tttcaaggan gcaggaaagc aattaagtgg tcaccttaac ataaggggga c 531 <210> 139 <211> 521 <212> DNA <213> Homo sapien <220>

<221> misc_featdre <222> (1)..(521) <223> η = A,T,C or G <400> 139 tgggtgggca ccatggctgg gatcaccacc atcgaggcgg tgaagcgcaa gatccaggtt ctgcagcagc aggcagatga tgcagaggag cgagctgagc gcctccagcg agaagttgag ggagaaaggc gggcccggga acaggctgag gctgaggtgg cctccttgaa ccgtaggatc cagctggttg aagaagagct ggaccgtgct caggagcgcc tggccactgc cctgcaaaag ctggaagaag ctgaaaaagc tgctgatgag agtgagagag gtatgaaggt tattgaaaac cgggccttaa aagatgaaga aaagatggaa ctccaggaaa tccaactcaa agaagctaag cacattgcag aagaggcaga taggaagtat gaagaggtgg ctcgtaagtt ggtgatcatt gaaggagact tggaaccgca cagaaggaac gagcttgagc ttggcaaaag tcccgttgcc cagagatggg atgaaccaga ttagactgat ggaccanaac c <210> 140 <211> 571 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1). . (571) <223> n = A,T,C or G <400> 140 ^aggg9^cng^cg ggTgcgtggg ccactgggtg accgacttag cctggccaga ctctcagcac ctggaagcgc cccgagagtg acagcgtgag gctgggaggg aggacttggc ttgagcttgt taaactctgc tctgagcctc cttgtcgcct gcatttagat ggctcccgca aagaagggtg gcgagaagaa aaagggccgt tctgccatca acgaagtggt aacccgagaa tacaccatca acattcacaa gcgcatccat ggagtgggct tcaagaagcg tgcacctcgg gcactcaaag agattcggaa atttgccatg aaggagatgg gaactccaga tgtgcgcatt gacaccaggc tcaacaaagc tgtctgggcc aaaggaataa ggaatgtgcc araccgaatc cggtgtacgg ctgtccagaa aacgtaatga ggatgaaqat tcaccaaata agctatatac tttggttacc tatgtacctg ttaccacttt caaaaaccta caaacagtca atgtgaatga gaactaatcg ctgatcgtca gatcaaataa agttataaaa t <210> 141 <211> 531 <212> DNA <213> Homo sapien <400> 141 tcgggagcca cacttggccc tcttcctctc caaagsgcca gaacctcctt ctctttggag aatggggagg cctcttggag acacagaggg tttcaccttg gatgacctct agagaaattg cccaagaagc ccaccttctg gtcccaacct gcagacccca cagcagtcag ttggtcaggc cctgctgtag aaggtcactt ggctccattg cctgcttcca accaatgggc aggagagaag gcctttattt ctcgcccacc cattcctcct gtaccagcac ctccgttttc agtcagtgtt gtccagcaac ggtaccgttt acacagtcac ctcagacaca ccatttcacc tcccttgcca agctgttagc cttagagtga ttgcagtgaa cactgtttac acaccgtgaa tccattccca tcagtccatt ccagttggca ccagcctgaa ccatttggta cctggtgtta actggagtcc tgtttacaag gtggagtcgg ggcttgctga cttctcttca tttgagggca c

120 180 240 300 360 420 480 521

120 180 240 300 3 60 420 480 540 571

120 180 240 300 360 420 480 531 <210> 142 <211> 491 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(491) <223> n = A,T,C or G <400> 142 acctagacag aaggtgggtg agggaggact ggtaggaggc tgaggcaatt ccrtggtagt 60 ttgtcctgaa accctactgg agaagtcagc atgaggcacc tactgagaga agtgcccaga 120 aactgctgac tgcatctgtt aagagttaac agtaaagagg tagaagtgtg tttctgaatc 180 agagtggaag cgtctcaagg gtcccacagt ggaggtccct gagctacctc ccttccgtga 240 gtgggaagag tgaagcccat gaagaactga gatgaagcaa ggatggggtt cctgggctcc 300 aggcaagggc tgtgctctct gcagcaggga gccccacgag tcagaagaaa agaactaatc 360 atttgttgca agaaaccttg cccggatact agcggaaaac tggaggcggn ggtgggggca 420 caggaaagtg gaagtgattt gatggagagc agagaagcct atgcacagtg gccgagtcca 480 cttgraaagt g 49!

<210> 143 <211> 515 <212> DNA <213> Homo sapien <400> 143 ttcaagcaat tgtaacaagt atatgtagat tagagtgagc aaaatcatat acaattttca 60 tttccagttg ctattttcca aattgttctg taatgtcgrt aaaattactt aaaaartaac 120 aaagccaaaa attatattta tgacaagaaa gccatcccta cattaatctt acttttccac 180 tcaccggccc atctccttcc tctttttcct aactatgcca ttaaaactgt tctactgggc 240 cgggcgtgtg gctcatgcct gtaatcccag cattttggga ggccaaggca ggcggatcat 300 gaggtcaaga gattgagacc atcctggcca acatggtgaa accccgcctc gactaagaat 360 acaaaaatta gctgggcatg gtggcgcatg cctgtagtct cagctactcg ggaggctgag 420 gcagaagaat cgcttgaacc cgggaggcag aggatgcagt gagccccgat cacgccactg 480 cactctagcc tgggcgacag actgagactc tgctc 515 <210> 144 <211> 340 <212> DNA <213> Homo sapien <400> 144 tgtgccagtc tacaggccta tcagcagcga ctccttcagc aacagatggg gtcccctgtt 60 cagcccaacc ccatgagccc ccagcagcat atgctcccaa atcaggccca gtccccacac 120 ctacaaggcc agcagatccc taattctctc tccaatcaag tgcgctctcc ccagcctgtc 180 ccttctccac ggccacagtc ccagcccccc cactccagtc cttccccaag gatgcagcct 240 cagccttctc cacaccacgt ttccccacag acaagttccc cacatcctgg actggtagtt 300 gcccaggcca accccatgga acaagggcat tttgccagcc 340 <210> 145 <211> 630 <212> DNA <213> Homo sapien <400> 145 tgtaaaaact tgtttttaat tttgtataaa ataaaggtgg tccatgccca cgggggctgt aggaaatcca agcagaccag ctggggtggg gggatgtagc ctacctcggg ggactgtctg tcctcaaaac gggctgagaa ggcccgtcag gggcccaggt cccacagaga ggcctgggat actcccccaa cccgaggggc agactgggca gtggggagcc cccatcgtgc cccagaggtg gccacaggct gaaggagggg cctgaggcac cgcagcctgc aacccccagg gctgcagtcc actaactttt tacagaataa aaggaacatg gggatgggga aaaaagcacc aggtcaggca gggcccgagg gccccagatc ccaggagggc caggactcag gatgccagca ccaccctagc agctcccaca gctcctggca caggaggccg ccacggattg gcacaggccg ctgctggcca tcacgccaca tttggagaac ttgtcccgac agaggtcagc tcggaggagc tcctcgtggg cacacactgt acgaacacag atctccttgt taatgacgta cacacggcgg aggctgcggg gacagggcac gggaggtctc agccccactt

120 180 240 300 360 420 480 540 600 630 <210> 145 <211> 521 <212> DNA <213> Homo sapien <400> 146 atggctgctg ccttgggtct atgacctgat acagactgga agaaatctga aaaaaccctg aaattattat taatttattt aggcrtaata gatttaggtg ggagagccat ggattgctcg gtttttggtg ttgttgtgtg actggctgtt acttcaccta tattctctct tttaattgat gtaatagggg gaaaagggaa accaagacac ctgaatagag tattcaatgt ttttccctgt aatggaagac cctttttatt ttgrttaata ctgtgggcca ggaaaagagg agaagtgaag ccagttgcta gtgattttaa attctttaca tgctgtgttt ttgcctgcag tgtatataaa taaatctgaa gcaagtcctg tctgtgtctg aaaaattggg aaataaacag actatttttt gtggaaattt aatccgttga gccttgagaa aacctaacca tgcacttccc ggtttggtga caacaacaat gaccctctga tgtaattttt aagactaata <210> 147 <211> 562 <212> DNA ! <213> Homo sapien <400> 147 ggcatgcgag cgcacccggc agacgcaagg gcggcgggga gcacacggag cactgcaagc gccgggttgg gacagcgtct tcgctgctgc tggatagtcg rgttttcggg gatcgaggat actcaccaga aaccgaaaat gccgaaacca atcaatgtcc gagttaccac catggatgca gagctggagt ttgcaatcca gccaaataca actggaaaac agctttttga tcaggtggta aagactatcg gcctccggga agtgtggtac tttggcctcc actatgtgga taataaagga tttcctacct ggctgaagct ggataagaag gtgtctgccc aggaggtcag gaaggagaat cccctccagt tcaagttccg ggccaaagtt ctaccctgaa gatgtggctg aggagctcat ccaggacatc acccagaaac ttttcttcct tcaagtgaag gaaggaatcc ttagcgatga gatctactgc cccccttgar actgccgtgc tcttggggtc ctacgcttgt gcatgccaag tttggggact accaccaaga ag <210> 148 <211> 820 <212> DNA <213> Homo sapien <400> 148 gaaggagtcg ggatactcag cattgatgca ccccaatttc aaagcggcat tcttcggcag gtctctggga caatctctag ggtcactacc tggaaactcg ttagggtaca actgaatgct gaaaggaaag aacacctgca gaaccggaca gaaattcacc ccggcgatca gctgattgat

120 180 240 300 360 420 480 540 562 ctcggtcgac tcgaagtgag caccagctcc gttcagctgg accgccggga gaggggtggt ggggcgaggg gcggccacca tccagggccg cggcttcgtc tcccaaccgc cagaagtcat tccagcagca cggggggccc tacaccaggg ccagggaagc ccccaccgcg cctcgttctt cgagcgtcag ggagcgcagc tccgtoctet accctagctt ggetaaagat gtctgaggta aggtgccagc accggtaccg cgccgacacg gccgccggca cctttgtcgc gattagcacc tacagctcga ccattcagca cgttacctgc gacgaggacg ttcgggccgg cttatctaca cagcgtcagg ttggagaccc ccccgcgcgg ccattgctgc ttccgtttgt gcgtcggcgc ccacgggtcc gcctcgcttg ttgtcaattc ttatgcacct ttcctcaggg ttgtccgctc tgeggatgee gtteggegte tccagaggac agatgeggaa cgccgctagg eggaaaaage cctgggcttt ggaccaccag tctgatcaaa gggctggggg cacagccaca cagcaacggt gaagccgcag cctcatggtc agccgcggct tcagccscgg

240 300 360 420 480 540 600 660 720

780 820 <210> 149 <211> 501 <212> DNA <213> Homo sapien <400> 149 cagattttta tttgeagteg tcactggggc cgtttcttgc tgcttatttg tctgctagcc tgctcttcca getgeatgge caggcgcaag geettgarga catctcgcag ggctgagaaa tgcttggctt gctgggccag agcagattcc gctttgttca caaaggtctc caggtcatag tetggetget cggtcatctc agagagetea agccagtctg gtccttgctg tatgatctcc ttgagetett ccatagcctt ctcctccagc tccctgatct gagteatgge ttcgttaaag ctggacatct gggaagacag ttcctcctct teettggata aattgcctgg aatcagcgcc ccgttagagc aggcttccat ctcttctgtt tccatttgaa tcaactgctc tccactgggc ccactgtggg ggctcagctc cttgaccctg etgeatatet taagggtgtt taaaggatat tcacaggaac ttatgcctgg t

120 180 240

300 360 420 480 <210> 150 <211> 511 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (511) <223> n = A,T,C or G <400> 150 ctcctcttgg racatgaacc caagttgaaa gtggacttaa caaagtatct ggagaaccaa gcattctgct ttgactttgc atttgatgaa acagcttcga atgaagttgt ctacaggttc acagcaaggc cactggtaca gacaatcttt gaaggtggaa aagcaacttg ttttgcatat ggccagacag gaagtggcaa gacacatact atgggcggag acctctctgg gaaagcccag aatgcatcca aagggatcta tgccatggcc ttccgggacg tettettetg aagaatcaac cctgctaccg gaagttgggc etggaagtet atgtgacatt ettegagate tacaatggga agctgtttga cctgctcaac aagaaggcca agettgegeg tgctggaaga cggcaagcaa caggtgcaag tggtgggggc ttgcaggaac atetggntaa ctctgcttga tgatggcant caagatgatc gacatgggca gcgcctgcag a

120 180 240 300 360 420 480 511 <210> 151 <211> 566 <212> DNA <213> Homo sapien <400> 151 tcccgaattc caaatctttt ttcacaatca gtagaagaga aaagagagga tgggtggcgg cacctctagg ccatgagtgg cggggcctgt gtagagggag aagcgacaaa gcgccaagat agaaatgcag ggaagagatg aagttacagc aggagcaatg aggtggtggt ttccatgatg gggtggacag agaagagtac ttggawagtg ctgatgagac aaacgtaaag atgattcgtc cgaatgggct aacatgggag ggcataggtt ggaagtgaca ggtcctagag gaaggc aaatggaaga gacaggaaga aaatgcaatt aacgtgagat acatggatcc atccctatgg atgaagctaa tgcgtactga gaatggggcc cgcctatcat attaagacgc gaggcaagag ggaagaacaa acgggaaaga ttcaggaggc tcctggcgtt gcgctttggg tggaactcca gaacatcagg atggaagaac gaggaacgac atgaggcgcc gacatgcgaa cagaaatttc ccaccagcaa cagggaggtg gcaggatatg

120 180 240 300 360 420 480 540 566 <210> 152 <211> 518 <212> DNA <213> Homo sapien <400> 152 ttcgtgaaga ccctgactgg taagaccatc actctcgaag tggagcccga gtgacaccat60 tgagaatgtc aaggcaaaga tccaagacaa ggaaggcatc cctccrgacc agcakaggtt120 gatctttgct gggaaacagc tggaagatgg acgcaccctg rctgactaca acatccagaa180 agagtccacc ctgcacctgg tgctccgtct cagaggtggg atgcaaatct tcgtgaagac240 cctgactggt aagaccatca ccctcgaggt ggagcccagt gacaccatcg agaatgtcaa300 ggcaaagatc caagataagg aaggcatccc tcctgatcag cagaggttga tctttgctgg360 gaaacagctg gaagatggac gcaccctgtc tgactacaac atccaaaaag agtccactct420 gcacttggtc ctgcgcttga gggggggtgt ctaagtttcc ccttttaagg tttcaacaaa480 tttcattgca ctttcctttc aataaagttg ttgcattc518 <210> 153 <211> 542 <212> DNA <213> Homo sapien <400> 153 gcgcgggtgc gtgggccact gggtgaccga cttagccrgg ccagactctc agcacctgga60 agcgccccga gagtgacagc gtgaggctgg gagggaggac ttggcrtgag cttgttaaac120 tcrgctctga gccrccttgt cgcctgcatt ragatggct.c ccgcaaagaa gggrggcgag180 aagaaaaagg gccgttctgc catcaacgaa gtggtaaccc gagaatacac catcaacatt240 cacaagcgca tccatggagt gggcttcaag aagcgtgcac ctcgggcact caaagagatt300 cggaaatttg ccatgaagga gatgggaact ccagatgtgc gcattgacac caggctcaac360 aaagctgtct gggccaaagg aataaggaat gtgccatacc gaatccgtgt gcggctgtcc420 agaaaacgta atgaggatga agattcacca aataagctat atactttggt tacctatgta480 cctgttacca ctttcaaaaa tctacagaca gtcaatgtgg atgagaacta atcgctgatc540 gt54 2 <210> 154 <211> 411 <212> DNA <213> Homo sapien <400> 154 aattctttat ttaaatcaac aaactcatct tcctcaagcc ccagaccatg gtaggcagcc 60 ctccctctcc atcccctcac cccacccctt agccacagtg aagggaatgg aaaatgagaa 120 gccacgaggg cccctgccag ggaaggctgc cccagatgtg tggtgagcac agtcagtgca 180 gctgtggctg gggcagcagc tgccacaggc tcctccctat aaattaagtt cctgcagcca 240 cagctgtggg agaagcatac ttgtagaagc aaggccagtc cagcatcaga aggcagaggc 300 agcatcagtg actcccagcc atggaatgaa cggaggacac agagctcaga gacagaacag 360 gccaggggga agaaggagag acagaatagg ccagggcatg gcggtgaggg a 411 <210> 155 <211> 421 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(421) <223> n = A, T, C or G <400> 155 tgatgaatct gggtgggctg gcagtagccc gagatgatgg gctcttctct ggggatccca 60 actggttccc taagaaatcc aaggagaatc ctcggaactt ctcggataac cagctgcaag 120 agggcaagaa cgtgatcggg ttacagatgg gcaccaaccg cggggcgtct cangcaggca 180 tgactagcta cgggatgcca cgccagatcc tctgatccca ccccaggcct tgcccctgcc 240 ctcccacgaa tggttaatat atatgtagat atatatttta gcagtgacat tcccagagag 300 ccccagagct ctcaagctcc tttctgtcag ggtggggggt tcaagcctgt cctgtcacct 360 ctgaagtgcc tgctggcatc ctctccccca tgcrtactaa tacattccct tccccatagc 420 a 421 <210> 156 <211> 670 <212> DNA <213> Homo sapien <400> 156 agcggagctc cctcccctgg tggctacaac ccacacacgc caggctcagg catcgagcag 60 aactccagcg actgggtaac cactgacatt caggtgaagg tgcgggacac ctacctggat 120 acacaggtgg tgggacagac aggtgtcatc cgcagtgtca cggggggcat gtgctctgtg 180 tacctgaagg acagtgagaa ggttgtcagc atttccagtg agcacctgga gcctatcacc 240 cccaccaaga acaacaaggt gaaagtgatc ctgggcgagg atcgggaagc cacgggcgtc 300 ctactgagca ttgatggtga ggatggcatt gtccgtatgg accttgatga gcagctcaag 360 atcctcaacc rccgcttcct ggggaagctc ctggaagcct gaagcaggca gggccggtgg 420 acttcgtcgg atgaagagtg atcctccttc cttccctggc ccttggctgt gacacaagat 480 cctcctgcag ggctaggcgg attgttctgg atttcctttt gtttttcctt ttaggtttcc 540 atcttttccc tccctggtgc tcattggaat ctgagtagag tctgggggag ggtccccacc 600 ttcctgtacc tcctccccac agcttgcttt tgttgtaccg tctttcaata aaaagaagct 660 gtttggtcta 670 <210> 157 <211> 421 <212> DNA <213> Homo sapien <400> 157 ggttcacagc actgctgctt gtgtgttgcc ggccaggaat tccaggctca caaggctatc 60 ttagcagctc gttctccggt ttttagtgcc atgtttgaac atgaaatgga ggagagcaaa 120 aagaatcgag ttgaaatcaa tgatgtggag cctgaagttt ttaaggaaat gatgtgcttc 180 atttacacgg ggaaggctcc aaacctcgac aaaatggctg atgatttgct ggcagctgct 240 gacaagtatg ccctggagcg cttaaaggtc atgtgtgagg atgccctctg cagtaacctg 300 tccgtggaga acgctgcaga aattctcatc ctggccgacc tccacagtgc agatcagttg 360 aaaactcagg cagtggattt catcaactat catgcttcgg atgtcttgga gacctcttgg 420 g

<210> 158 <211> 321 <212> DNA <213> Homo sapien <400> 158 tcgtagccat ttttctgctt ctttggagaa tgacgccaca ctgactgctc attgtcgttg gttccatgcc aattggtgaa atagaacctc atccggtagt ggagccggag ggacatcttg tcatcaacgg tgatggtgcg atttggagca taccagagct tggtgttctc gccatacagg gcaaagaggt tgtgacaaag aggagagata cggcatgcct gtgcagccct gatgcacagt tcctctgctg tgtactctcc actgcccagc cggaggggct ccctgtccga cagatagaag atcacttcca cccctggctt g <210> 159 <211> 596 <212> DNA <213> Homo sapien <400> 159 tggcacactg ctcttaagaa actatgawga tctgagattt ttttgtgtat gtttttgact cttttgagtg gtaatcatat grgtctttat agatgtacat acctccttgc acaaatggag gggaattcat tttcatcact gggagtgtcc ttagtgtata aaaaccatgc tggtatatgg cttcaagttg taaaaatgaa agtgacttta aaagaaaata ggggatggtc caggatctcc actgataaga ctgtttttaa gtaacttaag gacctttggg tctacaagta tatgtgaaaa aaatgagact tactgggtga ggaaattcat tgtttaaaga tggtcgtgtg tgtgtgtgtg tgtgtgtgtg ttgtgttgtg ttttgttttt taagggaggg aatttattat ttaccgttgc ttgaaattac tgkgtaaata tatgtytgat aatgatttgc tytttgvcma craaaattag gvctgtataa gtwctaratg cmtccctggg kgttgatytt ccmagatatt gatgatamcc cttaaaattg taaccygcct ttttcccttt gctytcmatt aaagtctatt cmaaag <210> 160 <211> 515 <212> DNA <213> Homo sapien <400> 160 gggggtaggc tctttattag acggttartg ctgtactaca gggtcagagt gcagtgtaag cagtgtcaga ggcccgcgtt cagcccaaga atgtggattt tctctcccta ttgatcacag tgggtgggtt tcttcagaaa agccccagag gcagggacca gtgagctcca aggttagaag tggaactgga aggcttcagt cacatgctgc ttccacgctt ccaggctggg cagcaaggag gagatgccca tgacgtgcca ggtctcccca tctgacacca gtgaagtctg gtaggacagc agccgcacgc ctgcctctgc caggaggcca atcatggtag gcagcattgc agggtcagag gtctgagtcc ggaataggag caggggcagg tccctgcgga gaggcacttc tggcctgaag acagctccat tgagcccctg cagtacaggy gtagtgcctt ggaccaagcc cacagcctgg taaggggcgc ctgccagggc cacggccagg aggca <210> 161 <211> 936 <212> DNA <213> Homo sapien <400> 161 taatttctta gtcgtttgga atccttaagc atgcaaaagc tttgaacaga agggttcaca

120 180 240 300 360 420 480 540 596

120 180 240 300 360

420 480 515 aaggaaccag ggttgtctta tggcatccag ttaagccaga gctgggaatg cctctgggtc 120 atccacatca ggagcagaag cacttgactt gtcggtcctg ctgccacggt ttgggcgccc 180 accacgccca cgtccacctc gtcctcccct gccgccacgt cctgggcggc caaggtctcc 240 aaaattgatc tccagctgag acgttatatc atttgctggc ttccggaaat gatggtccat 300 aaccgaatct tcagcatgag cctcttcact ctttgattta tgaagaacaa atcccttctt 360 ccactgccca tcagcacctt catttggttt tcggatatta aattctactt ttgcccggtc 420 cttattttga atagccttcc actcatccaa agtcatctct tttggaccct cctcttttac 480 ctcttcaact tcattctcct tattttcagt gtctgccact ggatgatgtt cttcaccttc 540 aggtgtttcc tcagtcacat ttgattgatc caagtcagtt aattcgtctt tgacagttcc 600 ccagttgtga gatccgctac ctccacgttt gtcctcgtgc ttcaggccag atctatcact 660 tccactatgc ctatcaaatt cacgtttgcc acgagaatca aatccatctc ctcggcccat 720 tccacgtcca cggccccctc gacctcttcc aagaccacca cgacctcgaa taggtcggtc 780 aataatcggt ctatcaactg aaaattcgcc tccttcaccc ttttcttcaa gtggcttttc 840 gaatcttcgt tcacgaggtg gtcgcctttc tggtcttcta tcaattattt tcccttcacc 900 ctgaagttgt tgatcaggtc ttcttccaac tcgtgc 936 <210> 162 <211> 950 <212> DNA <213> Homo sapien <400> 162 aagcggatgg acctgagtca gccgaatcct agccccttcc cttgggcctg ctgtggtgct 60 cgacatcagt gacagacgga agcagcagac catcaaggct acgggaggcc cggggcgctt 120 gcgaagatga agtttggctg cctctccttc cggcagcctt atgctggctt tgtcttaaat 180 ggaatcaaga ctgtggagac gcgctggcgt cctctgctga gcagccagcg gaactgtacc 240 atcgccgtcc acattgctca cagggactgg gaaggcgatg cctgtcggga gctgctggtg 300 gagagactcg ggatgactcc tgctcagatt caggccttgc tcaggaaagg ggaaaagttt 360 ggtcgaggag tgatagcggg actcgttgac attggggaaa ctttgcaatg ccccgaagac 420 ttaactcccg atgaggttgt ggaactagaa aatcaagctg cactgaccaa cctgaagcag 4.80 aagtacctga ctgtgatttc aaaccccagg tggttactgg agcccatacc taggaaagga 540 ggcaaggatg tattccaggt agacatccca gagcacctga rccctttggg gcatgaagtg 600 tgacaagtgt gggctcctga aaggaatgtt ccrgagaaac cagctaaatc atggcacctt 660 caatttgcca tcgtgacgca gacctgtata aattaggtta aagatgaatt tccactgctt 720 tggagagtcc cacccactaa gcactgtgca tgtaaacagg ttcctttgct cagatgaagg 780 aagtaggggg tggggctttc cttgtgtgat gcctccttag gcacacaggc aatgtctcaa 840 gtactttgac cttagggtag aaggcaaagc tgccagtaaa tgtctcagca ttgctgctaa 900 ttttggtcct gctagtttct ggattgtaca aataaatgtg ttgtagatga 950 <210> 163 <211> 475 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(475) <223> n = A,T,C or G <400> 163 tcgagcggcc gcccgggcag gtgtcggagt ccagcacggg aggcgtggtc ttgtagttgt 60 tctccggctg cccattgctc tcccactcca cggcgatgtc gctgggatag aagcctttga 120 ccaggcaggt. caggctgacc tggttcttgg tcatctcctc ccgggatggg ggcagggtgt 180 acacctgtgg ttctcggggc tgccctttgg ctttggagat ggttttctcg atgggggctg 240 ggagggcttt gttggagacc ttgcacttgt actccttgcc attcaaccag tcctggtgca 300 ngacggtgag gacgctnacc tcttggcatt atgcacctcc cgtggctcac gtccaccacc acacggtacg ngctggtgta acgccgtcca cgtaccaatt acgcatgtaa cctcaaanct ctgctcctcc gaacttgacc cggncgcgan cgcggctttg tcagggtctt cacgc <210> 164 <211> 476 <212> DNA <213> Homo sapien agcgtggtcg ccctgaggtc gccgcgggag ccaggactgg ccccatcgag cctgccccca aggcttctat actacaagac cggccgaggt aagttcaact gagcagtaca ctgaatggca aaaaccatct tcccgggagg cccagcgaca cacgcctccc ctgaggttac ggtacgtgga acagcacgta aggagtacaa ccaaagccaa agatgaccaa tcgcccgtgg gtgctggact atgcgtggtg cggcgtggag ccgtgtggtc gtgcaaggtc agggcagccc gaaccaggtc agtgggagag ccgacacctg gtggacgtga gtgcataatg agcgtcctca tccaacaaag cgagaaccac agcctgacct caatgggcag ccgggcggcc gccacgaaga ccaagacaaa ccgtcctgca ccctcccagc aggtgtacac gcctggtcaa ccggagaaca gctcga

120 180 240 300

360 420 476 <210>

<211>

<212>

<213>

DNA

Homo sapien <220>

<221>

<222>

<223>

misc_feature (1). -(256) or G n = A,T,C <400> agcgtggttn gcaacatgga actggtacat ccgatggatt ccgggcggnc

165 cggccgaggt gactggtgag cagcaagaac ccagttcgag gctcga cccaaccaag acctgcgtgt cccaaggaca tatggcggcc gctgcancct accccactca agaggcatgt agggctccga ggatgccatc gcccagtgtg ctggttcggc ccctgccgat aaagtcttct gcccagaaga gagagcatga gtggacctgc

120 .180 240 256 <210>

<211>

<212>

<213>

DNA

Homo sapien <400> agcgtggtcg ! cactctgact gccatcaaag ׳ agtgtggccc ttcggcgaga gccgatgtgg

166 cggccgaggt ggaagagtgg tcttctgcaa agaagaactg gcatgaccga acctgcccgg caagaacccc agagtactgg catggagact gtacatcagc tggattccag gcggccgctc gcccgcacct attgacccca ggtgagacct aagaacccca ttcgagtatg ga gccgtgacct accaaggctg gcgtgtaccc aggacaagag gcggccaggg caagatgtgc caacctggat cactcagccc gcatgtctgg ctccgaccct <210>

<211>

<212>

<213>

DNA

Homo sapien <220>

<221> misc_feature <222> (1)..(332) <223> n = A, T,C or G <400> 167 tcgagcggtc gcccgggcag gtccacatcg gcagggtcgg agccctggcc gccatactcg aactggaatc catcggncat gctctcgccg aaccagacat gcctcttgnc cttggggttc ttgctgatgt accagntctt ctgggccaca ctgggctgag tggggtacac gcaggtctca ccantctcca tgttgcanaa gactttgatg gcatccaggt tgcagccttg gttggggtca atccagtact ctccactctt ccagacagag tggcacatct tgaggtcacg gcaggtgcgg gcggggttct tgacctcggt cgcgaccacg ct

120 180 240 300 332

168 ־<210>

<211> 276 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(276) <223> n = A,T,C or G <400> 168 tcgagcggcc gcccgggcag gtcctcctca gagcggtagc tgttcttatt gccccggcag cctccataga tnaagttatt gcangagttc ctctccacgt caaagtacca gcgtgggaag gatgcacggc aaggcccagt gactgcgttg gcggtgcagt attcttcata gttgaacata tcgctggagt ggacttcaga atcctgcctt ctgggagcac ttgggacaga ggaatccgct gcattcctgc tggtggacct cggccgcgac cacgct <210> 169 <211> 276 <212> DNA <213> Homo sapien <400> 169 agcgtggtcg tcccagaagg caccgccaac ggagaggaac ccgctctgag cggccgaggt caggattctg gcagtcactg tcctgcaata gaggacctgc ccaccagcag aagaccactc ggccttgccg acttcatcta ccgggcggcc gaatgcagcg cagcgatatg tgcatccttc tggaggctgc gctcga gattcctctg ttcaactatg ccacgctggt cggggcaata tcccaagtgc aagaatactg actttgacgt agaacagcta <210> 170 <211> 332 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1).. (332) <223> n = A,T,C or G <400> 170 tcgagcggcc. gcccgggcag gtccacatcg aactggaatc catcggtcat gctctcgccg ttgctgatgt accagttctt ctgggccaca gcagggtcgg agccctggcc gccatactcg aaccagacat gcctcttgtc cttggggttc ctgggctgag tggggtacac gcaggtctca

<td colspan="2" rowspan="2"> ccagtctcca tgttgcagaa atccagtact ctccactctt gcggggttct tgacctcggc</td><td colspan="3"> gactttgatg gcatccaggt tgcagccttg</td><td rowspan="2"> gttggggtca gcangtgcgg</td>

<td> ccagccagaa cgcgaccacg</td><td> tggcacatct ct</td><td> tgaggtcacg</td>

<td> &lt;210&gt; &lt;211&gt; &lt;212&gt; &lt;213&gt; &lt;400&gt; agcgtggtcg</td><td colspan="2"> 171 333 DNA Homo sapien 171 cggccgaggt caagaaaccc</td><td> cgcccgcacc</td><td> tgccgtgacc</td><td> tcaagatgtg</td>

<td> ccactctggc</td><td> tggaagagtg</td><td> gagagtactg</td><td> gattgacccc</td><td> aaccaaggct</td><td> gcaacctgga</td>

<td> tgccatcaaa</td><td> gtcttctgca</td><td> acatggagac</td><td> tggtgagacc</td><td> tgcgtgtacc</td><td> ccactcagcc</td>

<td> cagtgtggcc</td><td> cagaagaact</td><td> ggtacatcag</td><td> caagaacccc</td><td> aaggacaaga</td><td> ggcatgtctg</td>

<td> gctcggcgag</td><td> agcatgaccg</td><td> atggattcca</td><td> gttcgagtat</td><td> ggcggccagg</td><td> gctccgaccc</td>

<td> tgccgatgtg &lt;210&gt; &lt;211&gt; &lt;212&gt; &lt;213&gt; &lt;220&gt; &lt;221&gt; &lt;222&gt; &lt;223&gt; &lt;400&gt; agcgtggtcg</td><td colspan="2"> gacctgcccg ggcggccgct 172 527 DNA Homo sapien misc_feature (1). .(527) n = A,T,C or G 172 cggccgaggt cctgtcagag</td><td> ega tggcactggt</td><td> agaagntcca</td><td> ggaaccctga</td>

<td> actgtaaggg</td><td> ttcttcatca</td><td> gtgccaacag</td><td> gatgacatga</td><td> aatgatgtac</td><td> tcagaagtgt</td>

<td> cctgnaatgg</td><td> ggcccatgan</td><td> atggttgnct</td><td> gagagagagc</td><td> ttcttgtcct</td><td> acattcggcg</td>

<td> ggtatggtct</td><td> tggcctatgc</td><td> cttatggggg</td><td> tggccgttgn</td><td> gggcggtgng</td><td> gtccgcctaa</td>

<td> aaccatgttc</td><td> ctcaaagatc</td><td> atttgttgcc</td><td> caacactggg</td><td> ttgctgacca</td><td> naagtgccag</td>

<td> gaagctgaat</td><td> accatttcca</td><td> gtgtcatacc</td><td> cagggtgggt</td><td> gaegaaaggg</td><td> gtcttttaaa</td>

<td> ctgtggaagg</td><td> aacatccaag</td><td> atctctgntc</td><td> catgaagatt</td><td> ggggtgtgga</td><td> agggttacca</td>

<td> gttggggaag</td><td> ctcgctgtct</td><td> ttttccttcc</td><td> aatcangggc</td><td> tcgctcttct</td><td> gaatattett</td>

<td> cagggcaatg</td><td> acataaattg</td><td> tatattcggt</td><td> tcccggttcc</td><td> aggccag</td><td></td>

<td> &lt;210&gt; &lt;211&gt; &lt;212&gt; &lt;213&gt; &lt;220&gt; &lt;221&gt; &lt;222&gt; &lt;223&gt; &lt;400&gt; tcgagcggcc</td><td colspan="2"> 173 635 DNA Homo sapien misc_feature (1)..(635) n = A,T,C or G 173 gcccgggcag gtccaccaca</td><td> cccaattcct</td><td> tgctggtatc</td><td> atggcagccg</td>

<td> ccacgtgcca</td><td> ggattaccgg</td><td> ctacatcatc</td><td> aagtatgaga</td><td> agcctgggtc</td><td> tcctcccaga</td>

<td> gaagtggtcc</td><td> ctcggccccg</td><td> ccctggtgtc</td><td> acagaggcta</td><td> etattaetgg</td><td> cctggaaccg</td>

<td> ggaaccgaat</td><td> atacaattta</td><td> tgtcattgcc</td><td> etgaagaata</td><td> atcagaagag</td><td> cgagcccctg</td>

<td> attggaagga</td><td> aaaagacaga</td><td> cgagcttccc</td><td> caactggtaa</td><td> cccttccaca</td><td> ccccaatctt</td>

<td> catggaccag</td><td> agatcttgga</td><td> tgttccttcc</td><td> acagttcaaa</td><td> agaccccttt</td><td> cgtcacccac</td>

120 180 240 300 360 420 480 527

<td> cctgggtatg acactggaaa gttgggcaac aaatgatctt ggcaccccca taaggcatag tctcanacaa ncatctcatg catcctggtg gcactgataa</td><td> tggtattcag tgangaacat gccaagaaca ggccccattc aaacccttac</td><td> cttcctggca ggntttaggc tacccgncga cangacactt agtta</td><td> cttctggtca ggaccacacc atgtaggaca ctgagtacat</td><td> gcaacccagt ggccacaacg agaagctctn canttcatgg</td><td> 420 480 540 600 635</td>

<td colspan="2"> &lt;210&gt; 174 &lt;211&gt; 572 &lt;212&gt; DNA &lt;213&gt; Homo sapien</td><td></td><td></td><td></td><td></td>

<td colspan="2"> &lt;220&gt; &lt;221&gt; misc_feature &lt;222&gt; (1) . . (572) &lt;223&gt; n = A,T,C or G</td><td></td><td></td><td></td><td></td>

<td> &lt;400&gt; 174 agcgtggtcg cgggcgaggt actgtaaggg ttcttcatca cctggaatgg ggcccatgag ggtatggtct tggcctatgc aaccatgttc ctcaaagatc gaagctgaat accatttcca ctgtggaagg aacatccaag gttggggaag ctcgtctgtc tcagggcaat gacataaatt ctgtgacacc anggcggggc</td><td> cctgtcagag gtgccaacag atggttgtct cttatggggg atttgttgcc gtgtcatacc atctctggtc tttttccttc gtatattcgg cgaagganca</td><td> tggcactggt gatgacatga gagagagagc tggccgttgt caacactggg cagggtgggt catgaagatt caatcanggg ntcccgggtn ct</td><td> agaagttcca aatgatgtac ttcttgtcct gggcggtgtg ttgctgacca gacgaaaggg ggggtgtgga ctcgctcttc cagccaataa</td><td> ggaaccctga tcagaagtgt acattcggcg gtccgcctaa gaagtgccag gtcttttgaa agggttacca tgattattct taataaccct</td><td> 60 120 180 240 300 360 420 480 540 .572</td>

<td colspan="2"> &lt;210&gt; 175 &lt;211&gt; 372 &lt;212&gt; DNA &lt;213&gt; Homo sapien</td><td></td><td></td><td></td><td></td>

<td colspan="2"> &lt;220&gt; &lt;221&gt; misc_feature &lt;222&gt; (1)..(372) &lt;223&gt; n = A, T,C or G</td><td></td><td></td><td></td><td></td>

<td> &lt;400&gt; 175 agcgtggtcg cggccgaggt ctgaaagacc agcagaggca aacgaaggct tgaaccaacc tatgccgttg gagatgagtg tgcttangct ttggaagtgg ggtgtgaact acaagattgg gcggccgctc ga</td><td> cctcaccaga taaggttcgg tacggatgac ggaacgaatg tcatttcaga agagaagtgg</td><td> ggtaccacct gaagaggttg tcgtgctttg tctgaatcag tgtgattcat gaccgtcagg</td><td> acaacatcat ttaccgtggg acccctacac gctttaaact ctagatggtg gagaaaatgg</td><td> agtggaggca caactctgtc agtttcccat gttgtgccag ccatgacaat acctgcccgg</td><td> 60 120 180 240 300 360 372</td>

<210> 175 <211> 372 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(372)

<td> &lt;223&gt;</td><td> n = A,T,C</td><td> or G</td>

<td> &lt;400&gt; tcgagcggcc</td><td> 176 gcccgggcag</td><td> gtccattttc tccctgacgg tcccacttct ctccaatctt 60</td>

<td> gtagttcaca</td><td> ccattgtcat</td><td> ggcaccatct agatgaatca catctgaaat gaccacttcc 120</td>

<td> aaagcctaag</td><td> cactggcaca</td><td> acagtttaaa gcctgattca gacattcgtt cccactcatc 180</td>

<td> tccaacggca</td><td> taatgggaaa</td><td> ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt 240</td>

<td> caagccttcg</td><td> ntgacagagt</td><td> tgcccacggt aacaacctct tcccgaacct tatgcctctg 300</td>

<td> ctggtctttc</td><td> agtgcctcca</td><td> ctatgatgtt gtaggtggta cctctggtga ggacctcggc 360</td>

<td> cgcgaccacg &lt;210&gt; &lt;211&gt; &lt;212&gt; &lt;213&gt; &lt;220&gt; &lt;221&gt; &lt;222&gt; &lt;223&gt; &lt;400&gt; agcgtggccg</td><td colspan="2"> ct 372 177 269 DNA Homo sapien misc_feature (1)..(269) n = A,T,C or G 177 cggccgaggt ccattggctg gaacggcatc aacttggaag ccagtgatcg 60</td>

<td> tctcagcctt</td><td> ggttctccag</td><td> ctaatggtga tggnggtctc agtagcatct gtcacacgag 120</td>

<td> cccttcttgg</td><td> tgggctgaca</td><td> ttctccagag tggtgacaac accctgagct ggtctgcttg 180</td>

<td> tcaaagtgtc</td><td> cttaagagca</td><td> tagacactca cttcatattt ggcgnccacc ataagtcctg 240</td>

<td> atacaaccac &lt;210&gt; &lt;211&gt; &lt;212&gt; &lt;213&gt; &lt;400&gt; tcgagcggcc</td><td colspan="2"> ggaatgacct gtcaggaac 269 178 529 DNA Homo sapien 178 gcccgggcag gtcctcagac cgggttctga gtacacagtc agtgtggttg 60</td>

<td> cctcgcacga</td><td> tgatatggag</td><td> agccagcccc tgattggaac ccagtccaca gctattcctg 120</td>

<td> caccaactga</td><td> cctgaagttc</td><td> actcaggtca cacccacaag cctgagcgcc cagtggacac 180</td>

<td> cacccaatgt</td><td> tcagctcact</td><td> ggatatcgag tgcgggtgac ccccaaggag aagaccggac 240</td>

<td> caatgaaaga</td><td> aatcaacctt</td><td> gctcctgaca gctcatccgt ggttgtatca ggacttatgg 300</td>

<td> cggccaccaa</td><td> atatgaagtg</td><td> agtgtctatg ctcttaagga cactttgaca agcagaccag 360</td>

<td> ctcagggtgt</td><td> tgtcaccact</td><td> ctggagaatg tcagcccacc aagaagggct cgtgtgacag 420</td>

<td> atgctactga</td><td> gaccaccatc</td><td> accattagct ggagaaccaa gactgagacg atcactggct 480</td>

<td> tccaagttga</td><td> tgccgttcca</td><td> gccaatggac ctcggccgcg accacgctt 529</td>

<210> 179 <211> 454 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(454) <223> n = A,T,C or G

79־1 <400>

agcgtggtcg cggccgaggt ctggccgaac tgccagtgta cagggaagat gtacatgtta 60 tagntcttct cgaagtcccg ggccagcagc tccacggggt ggtctcctgc ctccaggcgc 120 ttctcattct catggatctt cttcacccgc agcttctgct tctcagtcag aaggttgttg 180 tcctcatccc tctcatacag ggtgaccagg acgttcttga gccagtcccg catgcgcagg' 240 gggaattcgg tcagctcaga gtccaggcaa ggggggatgt atttgcaagg cccgatgtag 300 tccaagtgga gcttgtggcc cttcttggtg ccctccaagg tgcactttgt ggcaaagaag 360 tggcaggaag agtcgaaggt cttgttgtca ttgctgcaca ccttctcaaa ctcgccaatg 420 ggggctgggc agacctgccc gggcggccgc tcga 454 <210> 180 <211> 454 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (454) <223> n = A, T,C or G <400> 180 tcgagcggcc gcccgggcag gtctgcccag cccccattgg cgagtttgag aaggngtgca 60 gcaatgacaa caagaccttc gactcttcct gccacttctt tgccacaaag tgcaccctgg 120 agggcaccaa gaagggccac aagctccacc tggactacat cgggccttgc aaatacatcc 180 ccccttgcct ggactctgag ctgaccgaat tccccctgcg catgcgggac tggctcaaga 240 acgtcctggt caccctgtat gagagggatg aggacaacaa ccttctgact gagaagcana 300 agctgcgggt gaagaanatc catgagaatg anaagcgcct gnaggcanga gaccaccccg 360 tggagctgct ggcccgggac ttcgagaaga actataacat gtacatcttc cctgtacact 420 ggcagttcgg ccagacctcg gccgcgacca cgct 454 <210> 181 <211> 102 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1). . . (102) <223> n = A,T,C or G <400> 181 agcgtggntg cggacgacgc ccacaaagcc attgtatgta gttttanttc agctgcaaan 60 aataccncca gcatccacct tactaaccag catatgcaga ca 102 <210> 182 <211> 337 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1). . (337) <223> n = A,T,C or G <400> 182 tcgagcggtc gcccgggcag gtctgggcgg atagcaccgg gcatattttg gaatggatga

Ill

Γ\ ggtctggcac cctgagcagc ccagcgagga cttggtctta gttgagcaat ttggctagga ggatagtatg cagcacggtt ctgagtctgt gggatagctg ccatgaagna acctgaagga ggcgctggct ggtangggtt gattacaggg ctgggaacag ctcgtacact tgccattctc tgcatatact ggntagtgag gcgagcctgg cgctcttctt tgcgctgagc taaagctaca tacaatggct ttgnggacct cggccgcgac cacgctt <210> 183

74־3 <211>

<212> DNA <213> Homo sapien <400> 183 tcgagcggcc gcccgggcag gtccattttc tccctgacgg tcccacttct ctccaatctt gtagttcaca ccattgtcat gacaccatct agatgaatca catctgaaat gaccacttcc aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt caagccttcg ttgacagaag ttacccacgg taacaacctc ttcccgaacc ttatgcctct gctggtcttt caagtgcctc cactatgatg ttgtaggtgg cacctctggt gaggacctcg gccgcgacca cgct <210> 184 <211> 375 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1). . (375) <223> n = A,T,C or G <400> 184 agcgtggttt gcggccgagg tcctcaccan aggtgccacc tacaacatca tagtggaggc actgaaagac cagcagaggc ataaggttcg ggaagaggtt gttaccgtgg gcaactctgt caacgaaggc ttgaaccaac cracggatga ctcgtgcrtt gacccctaca cagnttccca ttatgccatt agagataagt gggaacgaat gtcrgaatca ggctttaaac tgttgrgcca gtgcttangc tttggaagtg gtcatttcag atgtgattca tctanatggt gtcatgacaa tggtgngaac tacaagattg gagagaagtg gnaccgtcag ggganaaaat ggacctgccc gggcggcncg ctcga <210> 185 <211> 148 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . - (148) <223> n = A,T,C or G <400> 185 agcgtggtcg cggccgaggt ctggcttnct gctcangtga ttatcctgaa ccatccaggc caaataagcg ccggctatgc ccctgnattg gattgccaca cggctcacat tgcatgcaag tttgctgagc tgaaggaaaa gattgatc

120 180 240

300 337

120 180 240

300 360 374

120 180 240 300

360 375 <210> 186 <211> 397 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(397) <223> n = A,T,C or G <400> 186 tcgagcggcc gcccgggcag gtccaattga aacaaacagt tctgagaccg ttcttccacc actgattaag agtggggngg cgggtattag ggataatatt catttagcct tctgagcttt ctgggcagac ttggtgacct tgccagctcc agcagccttc tggtccactg ctttgatgac acccaccgca actgtctgtc tcatatcacg aacagcaaag cgacccaaag gtggatagtc tgagaagctc tcaacacaca tgggcttgcc aggaaccata tcaacaatgg gcagcatcac cagacttcaa gaatttaagg gccatcttcc agctttttac cagaacggcg atcaatcttt tccttcagct cagcaaactt gcatgcaatg tgagccg <210> 187 <211> 584 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(584) <223> n = A, T,C or G <400> 187 tcgagcggcc gcccgggcag gtccagaggg ctgtgctgaa gtttgctgct gccactggag ccactccaat tgctggccgc ttcactcctg gaaccttcac taaccagatc caggcagcct tccgggagcc acggcttctt gtggntactg accccagggc tgaccaccag cctctcacgg aggcatctta tgttaaccta cctaccattg cgctgtgtaa cacagattct cctctgcgct atgtggacat tgccatccca tgcaacaaca agggagctca ctcagngggg tttgatgtgg tggatgctgg ctcgggaagt tctgcgcatg cgtggcacca tttcccgtga acacccatgg gangncatgc ctgatctgga cttctacaga gatcctgaag agattgaaaa agaagaacag gctgnttgct ganaaagcaa gtgaccaagg angaaatttc ahgggtgaaa nggactgctc ccgctcctga attcactgct actcaacctg angntgcaga ctggtcttga aggngnacan gggccctctg ggcctattta agcancttcg gtcgcgaaca cgnt <210> 188 <211> 579 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1).7.(579) <223> n = A, T, C or G <400> 188 agcgtgngtc gcggccgagg tgctgaatag gcacaaaggg cacctgtaca ccttcagacc agtctgcaac ctcaggctga gtagcagtga actcaggagc gggagcagtc cattcaccct gaaattcctc cttggncact gccttctcag cagcagcctg ctcttctttt tcaatctctt caggatctct gtagaagtac agatcaggca tgacctccca tgggtgttca cgggaaatgg

120 180 240 300 360

120 180 240 300 360

420 480 540 584 tgccacgcat gcgcagaact tcccgagcca gcatccacca catcaaaccc actgagtgag ctcccttgtt gttgcatggg atgggcaatg tccacatagc gcagaggaga atctgtgtta cacagcgcaa tggtaggtag gttaacataa gatgcctccg cgagaagctg gtggtcagcc ctggggtcaa gtaaccacaa gaagccgtgg ctcccggaag gctgcctgga tctggttagt gaaggntcca ggagtgaagc ggccaacaat tggagtggct tcagtggcaa gcagcaaact tcagcacaag ccctctggac ctgcccggcg gccgctcga <210> 189 <211> 374 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)- . (374) <223> n = A, T,C or G <400> 189 tcgagcggcc gcccgggcag gtccattttc tccctgacgg ncccacttct ctccaatctt gtagttcaca ccattgtcat ggcaccatct agatgaarca catctgaaat gaccacttcc aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc. tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt caagccttcg ttgacagagt tgcccacggt aacaacctcn tccccgaacc ttatgcctct gctgggcttt cagngcctcc actatgatgn tgtagggggg cacctctggn gangacctcg gccgcgacca cgct <210> 190 <211> 373 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (373) <223> n = A,T,C or G <400> 190 agcgtggtcg cggccgaggt cctcaccaga ggtgccacct acaacatcat agtggaggca ctgaaagacc agcagaggca taaggctcgg gaagaggttg ttaccgtggg caactctgtc aacgaaggct tgaaccaacc tacggatgac tcgtgctttg acccctacac agtttcccat tatgccgttg gagatgagtg ggaacgaatg tctgaatcag gctttaaact gttgtgccag tgcttangct ttggaagtgg gtcatttcag atgtgattca tctagatggt gccatgacaa tggngngaac tacaagattg gagagaagtg gnaccgncag ggagaaaatg gacctgcccg ggcggccgct cga

300 360 420 4 80

540 579

120 180 240 300 360 374

120 180 240 300 360 373 <210> 191 <211> 354 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . - (354) <223> n = A,T,C or G <400> 191.

agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt gctgatgtac cagttcttct gggccacact gggctgagtg gggtacacgc aggtctcacc agtctccatg ttgcagaaga ctttgatggc atccaggntg caaccttggt tggggtcaat ccagtactct ccactcttcc agccagagtg gcacatcttg aggtcacggc aggtgcggnc gggggntttt gcggctgccc tctggncttc ggntgtnctc natctgctgg ctca <210> 192 <211> 587 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(587) <223> n=A,T,Cor G <400> 192 tcgagcggcc gcccgggcag gtctcgcggt cgcactggtg atgctggtcc tgttggtccc60 cccggccctc ctggacctcc tggcccccct ggtcctccca gcgctggttt cgacttcagc120 ttcctgcccc agccacctca agagaaggct cacgatggtg gccgctacta ccgggctgat180 gatgccaatg tggttcgtga ccgtgacctc gaggtggaca ccaccctcaa gagcctgagc240 cagcagatcg agaacatccg gagcccagag ggcagncgca agaaccccgc ccgcacctgc .300 cgtgacctca agatgtgcca ctctgactgg aagagtggag agtactggat tgaccccaac360 caagctgcaa cctggatgcc atcaaagtct tctgcaacat ggagactggt gagacctgcg420 tgtaccccac tcagcccagt gtggcccaaa agaactggta catcagcaag aaccccaagg480 acaagaagca tgtctggttc ggcgagaaca tgaccgatgg attccagttc gagtatggcg540 ggcagggctc cgaccctgcc gatggggacc ttggccgcga acacgct587 <210> 193 <211> 98 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1).. (98) <223> n = A,T,C or G <400> 193 agcgtggnng cggccgaggt ataaatatcc agnccatatc ctccctccac acgctganag 6C atgaagctgt ncaaagatct cagggtggan aaaaccat <210> 194 <2H> 240 <212> DNA <213> Homo sapien <400> 194 tcgagcggcc gcccgggcag gtccttcaga cttggactgt gtcacactgc caggcttcca6( gggctccaac ttgcagacgg cctgttgtgg gacagtctct gtaatcgcga aagcaaccat12( ggaagacctg ggggaaaaca ccatggtttt atccaccctg agatctttga acaacttcat181 ctctcagcgt gcggagggag gctctggact ggatatttct acctcggccg cgaccacgct241

195 <210> 400 <ע21>

<212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(400) <223> n = A,T,C or G <400> cgagcgggcg aagctacacc gaatgacaat atccaacctg acgtgccagg gnggtccctc aaccgatatc

195 accgggcagg atcacaggtt gctcggagct cgtttcctgg attaccggta ggccccgccc nattttgnca tncagactcc tacaaccagg .cccctgtggt ccaccacacc catcatcnag tgntgtccca ttggccttca aatccanana cactgactac catcgacgcc caattccttg tatganaagc naggntacta acaataatta accatcaagc aaganctacc tccactgcca ctggtatcat ctgggcctcc ttactgngcc cagatgtcag tgcacacctt ttgatgcacc ggcagccgcc tcccagagaa ngcaaccggc

00 <210> 196 <211> 494 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) .. (494) <223> n = A,T,C or G <400> 196 agcgtggttc gcggccgang tcctgtcaga gtggcactgg tagaagttcc aggaaccctg aactgtaagg gttcttcatc agngccaaca ggatgacarg aaatgatgta ctcagaagtg tcctggaatg gggcccatga gatggttgtc tgagagagag cttcttgncc tgtctttttc cttccaatca ggggctcgct cttctgatta ttcttcaggg caatgacata aattgtatat tcgggtcccg gntccaggcc agtaatagta ncctctgtga caccagggcg gngccgaggg accacttctc tgggaggaga cccaggcttc tcaracttga tgatgtaacc ggtaatcctg gcacgtggcg gctgccatga taccagcaag gaattggggt gtggtggcca ggaaacgcag gttggatggn gcatcaatgg cagtggaggc cgtcgatgac cacaggggga gctccgacat tgtcattcaa ggtg <210> 197 <211> 118 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(118) <223> n = A,T,C or G <400> 197 agcgtggncg cggccgaggt gcagcgcggg ctgtgccacc ttctgctctc tgcccaacga taaggagggt ncctgccccc aggagaacat taactntccc cagctcggcc tctgccgg

120 180 240 300 360 420 480 494 <210> 198 <211> 403.

<212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(403) <223> n = A,T,C or G <400> 198 tcgagcggcc gcccgggcag gttttttttg ctgaaagtgg ntactttatt ggntgggaaa gggagaagct gtggtcagcc caagagggaa tacagagncc cgaaaaaggg gagggcaggt gggctggaac cagacgcagg gccaggcaga aactttctct cctcactgct cagcctggtg gtggctggag ctcanaaatt gggagtgaca caggacacct tcccacagcc attgcggcgg catttcatct ggccaggaca ctggctgtcc acctggcact ggtcccgaca gaagcccgag ctggggaaag ttaatgttca cctgggggca ggaaccctcc ttatcattgn gcagagagca gaaggtggca cagcccgcgc tgcacctcgg ccgcgaccac get <210> 199 <211> 167 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1). . (167) <223> n = A,T,C or G <400> 199 tcgagcggcc gcccgggcag gtccaccata agteetgata caaccacgga tgagctgtca ggagcaaggt tgatttcttt cattggtccg gncttctcct tgggggncac ccgcactcga tatccagtga gctgaacatt gggtggcgtc cactgggcgc teagget <210> 200 <211> 252 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(252) <223> n ־ A,T,C or G <400> 200 tegageggtt cgcccgggca ggtccaccac acccaattcc ttgctggtat catggcagcc gccacgtgcc aggattaeeg gctacatcat caagtatgag aagcctgggt ctcctcccag agaageggte cctcggcccc gccctggtgt cacagaggct actattactg gcctggaacc gggaaccgaa tatacaattt atgtcattgn cctgaagaat aatcannaan agcgancccc tgattggaag ga

120 180 240 300 360 403 <210> 201 <211> 91 <212> DNA <213> Homo sapien <400> 201 agcgtggtcg cggccgaggt tgtacaagct tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt t <210> 202 <211> 368 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1). . (368) <223> n = A,T,C or G <400> 202 tcgagcggnc gcccgggcag gtctgccaac accaagattg gcccccgccg catccacaca gtccgtgtgc ggggaggtaa caagaaatac cgtgccctga ggttggacgt ggggaatttc tcctggggct cagagtgttg tactcgtaaa acaaggatca tcgatgttgt ctacaatgca tctaataacg agctggttcg taccaagacc ctggtgaaga attgcatcgt gctcatcgac agcacaccgt accgacagtg gtacgagtcc cactatgcgc tgcccctggg ccgcaagaag ggagccaagc tgactcctga ggaagaagag attttaaaca aaaaacgatc taanaaaaaa aaaacaat <210> 203 <211> 340 <212> DNA <213> Homo sapien <400> 203 agcgtggtcg cggccgaggt gaaatggtat tcagcttcct ggcacttctg gtcagcaacc cagtgttggg caacaaatga tctttgagga acatggtttt aggcggacca caccgcccac aacggccacc cccataaggc ataggccaag accatacccg ccgaatgtag gacaagaagc tctctctcag acaaccatct catgggcccc attccaggac acttctgagt acatcatttc atgtcatcct gttggcactg atgaagaacc cttacagttc agggttcctg gaacttctac cagtgccact ctgacaggac ctgcccgggc ggccgctcga <210> 204 <211> 341 <212> DNA <213> Homo sapien <400> 204 tcgagcggcc gcccgggcag gtcctgtcag agtggcactg gtagaagttc caggaaccct gaactgtaag ggttcttcat cagtgccaac aggatgacat gaaatgatgt actcagaagt gtcctggaat ggggcccatg agatggttgt ctgagagaga gcttcttgtc ctacattcgg cgggtatggt cttggcctat gccttatggg ggtggccgtt gtgggcggtg tggtccgcct aaaaccatgt tcctcaaaga tcatttgttg cccaacactg ggttgctgac cagaagtgcc aggaagctga ataccatttc acctcggccg cgaccacgct a <210> 205

70־7 <211>

<212> DNA <213> Homo sapien

120 180 240 300 360 368 <220>

<221> mis.c_feature (770־) . . . (1) <222>

<223> n = A,T,C or G <400> 205 tcgagcggcc gcccgggcag gtctcccttc ttgcggccca ggggcagcgc atagtgggac tcgtaccact gtcggtacgg tgtgctgtcg atgagcacga tgcaattctt caccagggtc ttggtacgaa ccagctcgtt attagatgca ttgtagacaa catcgatgat ccttgtttta cgagtacaac actctgagcc ccaggagaaa ttccccacgt ccaacctcag ggcacggtat ttcttgttac ctccccgcac acggactgtg tggatgcggc gggggccaag ctgactcctg aggaagaaga gattttaaac aaaaaacgat ctaaaaaaat tcagaagaaa tatgatgaaa ggaaaaagaa tgccaaaatc agcagtctcc tggaggagca gttccagcag ggcaagcttc ttgcgtgcat cgcttcaagg ccgggacagt gtgaccgagc agatggctat gtgctagagg gcaaagaagt ggagttctat cttaagaaaa tcagggccca gaatggtgng tcttcaacta atccaaaggg gagtttcaga ccagtgcaat cagcaaaaac attgatactg ntggccaaat ttattggtgc agggcttgca cantangann ggctgggtct tggggcttgg attggnacaa gctttggcag ccttttcttt ggttttgcca aaaacctttt gntgaagang anacctnggg cggacccctt aaccgattcc acnccnggng gcgttctang gncccncttg <210> 206 <211> 810 <212> DNA <213> Homo sapien

120 180 240 300 360 420 480 540 600' 660 720 770 <220>

<221> misc_feature <222> (1). . . (810) <223> n = A,T,C or G <400> 206 agcgtggtcg cggccgaggt ctgctgcttc agcgaagggt ttctggcata accaatgata aggctgccaa agactgttcc aataccagca ccagaaccag ccactcctac tgttgcagca cctgcaccaa taaatttggc agcagtatca atgtctctgc tgattgcact ggtctgaaac tccctttgga ttagctgaga cacaccattc tgggccctga ttttcctaag atagaactcc aactctttgc cctctagcac atagccatct gctcggtcac actgtcccgg ccttgaagcg atgcacgcaa gaagcttgcc ctgctggaac tgctccrcca ggagactgct gattttggca ttctttttcc tttcatcata tttcttctga atttttttag atcgtttttt gtttaaaatc tcttcttcct caggagtcag cttggccccc gccgcatcca cacagtccgt gtgcggggag gtaacaagaa ataccgtgcc ctgaggttgg acgtggggaa tttctcctgg ggctcagagt ggtgtactcg taaaacaagg atcatcgatg gtgnctacaa tgcatctaat aacgagctgg gtcggaccca aagaacctgg ngaanaaatg gatcgnctca tcgacaggac accgtacccg acaggggnac gantcccact atgcgcttgc ccctgggccg caanaaagga aaactgcccg ggcggccntc gaaagcccaa ttntggaaaa aatccatcac actgggnggc cngtcgagca tgcatntana ggggcccatt ccccctnann <210> 207 <211> 257 <212> DNA <213> Homo sapien <400> 207 tcgagcggcc gcccgggcag gtccccaacc aaggctgcaa cctggatgcc atcaaagtct tctgcaacat ggagactggt gagacctgcg tgtaccccac tcagcccagt gtggcccaga agaactggta catcagcaag aaccccaagg acaagaggca tgtctggttc ggcgagagca tgaccgatgg attccagttc gagtatggcg gccagggctc cgaccctgcc gatgtggacc

120 180 240 300 360 420 480 540 600

660 720 780 810 tcggccgcga ccacgct <210> 208 <211> 257 <212> DNA <213> Homo sapien <400> 208 agcgtggtcg ctggaatcca gctgatgtac agtctccatg cccgggcggc cggccgaggt tcggtcatgc cagttcttct ttgcagaaga cgctcga ccacatcggc tctcgccgaa gggccacact ctttgatggc agggtcggag ccagacatgc gggctgagtg atccaggttg ccctggccgc ctcttgtcct gggtacacgc cagccttggt catactcgaa tggggttctt aggtctcacc tggggacctg <210> 209 <211> 747 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(747) <223> n = A,T,C or G <400> 209 tcgagcggcc gcccgggcag gtccaccaca cccaattcct tgctggtatc atggcagccg ccacgtgcca ggattaccgg ctacatcatc aagtatgaga agcctgggtc tcctcccaga gaagtggtcc ctcggccccg ccctggtgtc acagaggcta ctattactgg cctggaaccg ggaaccgaat atacaattta tgtcattgcc ctgaagaata atcagaagag cgagcccctg attggaagga aaaagacaga cgagcttccc caactggtaa cccttccaca ccccaatctt catggaccag agatcttgga tgttccttcc acagttcaaa agaccccttt cgtcacccac cctgggtatg acactggaaa tggtattcag cttcctggca cttctggtca gcaacccagt gttgggcaac aaatgatctt tgaggaacat ggntttaggc ggaccacacc gcccacaacg gccaccccca taaggcatag gccaagacca tacccgccga atgtaggaca agaagctntn tntcanacac catntnatgg gccccattcc aggacacttc tgagtacatc atttatgnca tctgtggcac ttgatgaaaa cccttacagt tcagggttct ggaactttta ccaggcctnt tacaggactn ggccggacnc cttaagccna ttncacccrg gggcgttcta nggtcccact cgnncactgg ngaaaatggc tactgtn <210> 210 <211> 872 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(872) <223> n ־־ A, T-, C or G <400> 210 agcgtggtcg cggccgaggt ccactagagg tctgtgtgcc attgcccagg cagagtctct gcgttacaaa ctcctaggag ggcttgctgt gcggagggcc tgctatggtg tgctgcggtt catcatggag agtggggcca aaggctgcga ggttgtggtg tctgngaaac tccnaggaca ngagggctaa attccatgaa gtttgtggat ggcctgatga tccacaatcg gagaccctgt taactactac cgtctnaccn cctgctgtnc ncccccnttt ctgctnaana catngggntn

120 180 240 300 360 420 480 540 600 660 720 747 ntncttgncc ntccttgggt ngaanatnna atngcctncc cnttcntanc nctactngnt 360 ccananttgg cctttaaana atccnccttg ccttnnncac tgttcanntn tttnntcgta 420 aaccctatna nttnnattan atnntnnhnn nctcaccccc ctcntcattn anccnatang 480 ctnnnaantc cttnanncct cccncccnnt ncnctcntac tnantncttc tnncccatta 540 cnnagctctt tcntttaana taatgnngcc nngctctnca tntctacnat ntgnnnaatn 600 cccccncccc cnancgnntt tttgacctnn naacctcctt tcctcttccc tncnnaaatt 660 ncnnanttcc ncnttccnnc ntttcggntn ntcccatnct ttccannnct tcantctanc 720 ncnctncaac ttattttcct ntcatccctt nttctttaca nnccccctnn tctactcnnc 780 nnttncatta natttgaaac tnccacnnct anttncctcn ctctacnntt ttattttncg 840 ntcnctctac ntaatanttt aatnanttnt cn 872 <210> 211 <211> 517 <212> DNA <213> Homo. sapien <220>

<221> misc_feature <222> (1). . . (517) <223> n = A,T,C or G <400> 211 tcgagcggcc gcccgggcag gtctgccaag gagaccctgt tatgctgtgg ggactggcrg 60 gggcatggca ggcggctctg gcttcccacc cttctgttct gagatggggg tggtgggcag 120 tatctcatct ttgggttcca caatgctcac gtggtcaggc aggggcttct tagggccaat 180 cttaccagtt gggtcccagg gcagcatgat cttcaccttg atgcccagca caccctgtct 240 gagcaacacg tggcgcacaa gcagtgtcaa cgtagtaagt taacagggtc tccgctgtgg 300 atcatcaggc catccacaaa cttcatggat ttagccctct gtcctcggag tttcccagac 360 accacaacct cgcagccttt ggccccactc tccatgatga accgcagcac accatagcag 420 gccctccgca caagcaagcc ctcctaagaa tttgtaacgc ananactctg ctggcaatgg 480 cacacaaacc tctagtggac ctcggncgcg accacgc 517 <210> 212 <211> 695 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . (695) <223> n = A,T,C or G <400> 212 tcgagcggcc gcccgggcag gtctggtcca ggatagcctg cgagtcctcc tactgctact 60 ccagacttga catcatatga atcatactgg ggagaatagt tctgaggacc agtagggcat 120 gattcacaga ttccaggggg gccaggagaa ccaggggacc ctggttgtcc tggaatacca 180 gggtcaccat ttctcccagg aataccagga gggcctggat ctcccttggg gccttgaggt 240 ccttgaccat taggagggcg agtaggagca gttggaggct gtgggcaaac tgcacaacat 300 tctccaaatg gaatttctgg gttggggcag tctaattctt gatccgtcac atattatgtc 360 atcgcagaga acggatcctg agtcacagac acatatttgg catggttctg gcttccagac 420 atctctatcc gncataggac tgaccaagat gggaacatcc tccttcaaca agcttnctgt 480 tgtgccaaaa ataatagtgg gatgaagcag accgagaagt anccagctcc cctttttgca 540 caaagcntca tcatgtctaa atatcagaca tgagacttct ttgggcaaaa aaggagaaaa 600 agaaaaagca gttcaaagta nccnccatca agttggttcc ttgcccnttc agcacccggg 660 ccccgttata aaacacctng ggccggaccc ccctt 695 <210> 213 <211> 804 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (804) <223> n ־־ A,T,C or G <400> 213 agcgtggtcg cggccgaggt gttttatgac gggcccggtg ctgaagggca gggaacaact tgatggtgct actttgaact gcttttcttt tctccttttt gcacaaagag tctcatgtct gatatttaga catgatgagc tttgtgcaaa aggggagctg gctacttctc gctctgcttc atcccactat tattttggca caacaggaag ctgttgaagg aggatgttcc catcttggtc agtcctatgc ggatagagat gtctggaagc cagaaccatg ccaaatatgt gtctgtgact caggatccgt tctctgcgat gacataatat gtgacgatca agaattagac tgccccaacc cagaaattcc atttggagaa tgttgtgcag tttgcccaca gcctccaact gctcctactc gccctcctaa tggtcaagga cctcaaggcc ccaagggaga tccaggccct cctggtattc ctgggagaaa tggtgaccct ggtattccag gacaaccagg gtcccctggt tctcctggcc cccctggaat cnggngaatc atgccctact ggtcctcaaa ctattctccc anatgattca tatgatgtca agtctgggat agcnagtang ganggactcg caggctattc tggaccanac ctgccggggg ggcgttcgaa agcccgaatc tgcananntn cnttcacact ggcggccgtc gagctgcttt aaaagggcca ttccnccttt agngnggggg antacaatta ctnggcggcg ttttanancg cgngnctggg aaat <210> 214 <211> 594 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(594) <223> n = A, T,C or G <400> 214 agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt gctgatgtac cagttcttct gggccacact gggctgagtg gggtacacgc aggtctcacc agtctccatg ttgcagaaga ctttgatggc atccaggttg cagccttggt tggggtcaat ccagtactct ccactcttcc agtcagagtg gcacatcttg aggtcacggc aggtgcgggc ggggttcttg cggctgccct ctgggctccg gatgttctcg atctgctggc tcaggctctt gagggtggtg tccacctcga ggtcacggtc acgaaccaca ttggcatcat cagcccggta gtagcggcca ccatcgtgag ccttctcttg angtggctgg ggcaggaact gaagtcgaaa ccagcgctgg gaggaccagg gggaccaana ggtccaggaa gggcccgggg gggaccaaca ggaccagcat caccaagtgc gacccgcgag aacctgcccg gccgnccgct cgaa

120 180 240 300 360' 420 480 540 600 660 720 780 804

120 180 240 300 360 420 480 540 594 <210> 215 <211> 590 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(590) <223> n = A,T,C or G <400> 215 tcgagcgnnc gcccgggcag gtctcgcggt cgcactggtg atgctggtcc tgttggtccc 60 cccggccctc ctggacctcc tggtccccct ggtcctccca gcgctggttt cgacttcagc 120 ttcctgcccc agccacctca agagaaggct cacgatggtg gccgctacta ccgggctgat 180 gatgccaatg tggttcgtga ccgtgacctc gaggtggaca ccaccctcaa gagcctgagc 240 cagcagatcg agaacatccg gagcccagag ggcagccgca agaaccccgc ccgcacctgc 300 cgtgacctca agatgtgcca ctctgactgg aagagtggag agtactggat tgaccccaac 360 caaggctgca acctggatgc catcaaagtc ttctgcaaca tggagactgg tgagacctgc 420 gtgtacccca ctcagcccag tgtggcccag aagaactggt acatcagcaa gaaccccaag 480 gacaagaggc atgtctggtt cggcgagagc atgaccgatg gattccagtt cgagtatggc 540 ggccagggct cccaccctgc cgatgtggac ctccggccgc gaccaccctt 590 <210> 216 <211> 801 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(801) <223> n = A,T,C or G <400> 216 tngagcggcc gcccgggcag gntgnnaacg ctggtcctgc tggtcctcct ggcaaggctg 60 gtgaagatgg tcaccctgga aaacccggac gacctggtga gagaggagtt gttggaccac 120 agggtgctcg tggtttccct ggaactcctg gacttcctgg cttcaaaggc attaggggac 180 acaatggtct ggatggattg aagggacagc ccggtgctcc tggtgtgaag ggtgaacctg 240 gtgcccctgg tgaaaatgga actccaggtc aaacaggagc ccgtgggctt cctggtgaga 300 gaggaccgtg ttggtgcccc tggcccanac ctcggccgcg accacgctaa gcccgaattt 360 ccagcacact ggnggccgtt actantggat ccgagctcgg taccaagctt ggcgtaatca 420 tggtcatagc tgtttcctgn gtgaaattgt tatccgctca caatttcaca cancatacga 480 agccggaaag cataaagtgt aaagccttgg ggtgctaatg agtgagctaa ctcncattaa 540 attgcgttgc gctcactgcc cgcttttcca nnngggaaac cntggcntng ccngcttgcn 600 ttaantgaaa tccgccnacc cccggggaaa agncggtttg cngtattggg gcnctttttc 660 cctttcctcg gnttacttga nttantgggc tttggncgnt tcgggttgng gcgancnggt 720 tcaacntcac nccaaaggng gnaanacggt tttcccanaa tccgggggnt ancccaangn 780 aaaacatnng ncnaangggc t 801 <210> 217 <211> 349 <212> DNA <213> Homo sapien <220>

<221> misc_feature>

<222> (1)..(349) <223> n = A,T,C or G <400> 217 agcgtggttn gcggccgagg tctgggccag gggcaccaac acgtcctctc tcaccaggaa60 gcccacgggc tcctgtttga cctggagttc cattttcacc aggggcacca ggttcaccct120 tcacaccagg ctttgaagcc actcctctct ggaggaccag agcaccgggc aggaagtcca caccaggtcg caggaccagc tgtcccttca ggagttccag tccgggtttt gttaccaacc atccatncag ggaaaccacc ccagggtgac tgcccgggcg accattgtgn gagcaccctg catcttcacc gccgctcga cccctaatgc tggtccaaca agccttgcca <210> 218 <211> 372 <212> DNA <213> Homo sapien <400> 218 tcgagcggcc gcccgggcag gtccattttc tccctgacgg tcccacttct ctccaatctt60 gtagttcaca ccattgtcat ggcaccatct agatgaatca catctgaaat gaccacttcc120 aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc180 tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt240 caagccttcg ttgacagagt tgcccacggt aacaacctct tcccgaacct tatgcctctg300 ctggtctttc agtgcctcca ctatgatgtt gtaggtggca cctctggtga ggacctcggc 360 cgcgaccacg ct372 <210> 219 <211> 374 <212> DNA <213> Homo sapien <400> 219 agcgtggtcg cggccgaggt cctcaccaga ggtgccacct acaacatcat agtggaggca60 ctgaaagacc agcagaggca taaggttcgg gaagaggttg ttaccgtggg caactctgtc120 aacgaaggct tgaaccaacc tacggatgac tcgtgctttg acccctacac agtttcccat180 tatgccgttg gagatgagtg ggaacgaatg tctgaatcag gctttaaact gttgtgccag240 tgcttaggct ttggaagtgg tcatttcaag atgtgattca tctagatggt gccatgacaa300 tggtgtgaac tacaagattg gagagaagtg ggaccgtcag ggagaaaatg gacctgcccg 360 ggccggccgc tcga374 <210> 220 <211> 828 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . (828) <223> n = A,T,C or G <400> 220 tcgagcgnnc gcccgggcag gtccagtagt gccttcggga ctgggttcac ccccaggtct 60 gcggcagttg tcacagcgcc agccccgctg gcctccaaag catgtgcagg agcaaatggc 120 accgagatat tccttctgcc actgttctcc tacgtggtat gtcttcccat catcgtaaca 180 cgttgcctca tgagggtcac acttgaattc tccttttccg ttcccaagac atgtgcagct 240 catttggctg gctctatagt ttggggaaag tttgttgaaa ctgtgccact gacctttact . 300 tcctccttct ctactggagc tttcgtacct tccacttctg ctgttggtaa aatggtggat 360 cttctatcaa tttcattgac agtacccact tctcccaaac atccagggaa atagtgattt 420 cagagcgatt aggagaacca aattatgggg cagaaataag gggcttttcc acaggttttc 480 ctttggagga agatttcagt ggtgacttta aaagaatact caacagtgtc ttcatcccca 540 tagcaaaaga agaaacngta aatgatggaa ngcttctgga gatgccnnca tttaagggac 600 ncccagaact tcaccatcta caggacctac ttcagtttac annaagncac atantctgac 660 tcanaaagga cccaagtagc nccatggnca gcactttnag cctttcccct ggggaaaann ttacnttctt aaancctngg ccnngacccc cttaagncca aattntggaa aanttccntn cnnctggggg gcngttcnac atgcntttna agggcccaat tnccccnt <210> 221 <211> 476 <212> DNA <213> Homo sapien <400> 221 tcgagcggcc gcccgggcag gtgtcggagt ccagcacggg aggcgtggtc ttgtagttgt tctccggctg cccattgctc tcccactcca cggcgatgtc gctgggatag aagcctttga ccaggcaggt caggctgacc tggttcttgg tcatctcctc ccgggatggg ggcagggtgt acacctgtgg ttctcggggc tgccctttgg ctttggagat ggttttctcg atgggggctg ggagggcttt gttggagacc ttgcacttgt actccttgcc attcagccag tcctggtgca ggacggtgag gacgctgacc acacggtacg tgctgttgta ctgctcctcc cgcggctttg tcttggcatt atgcacctcc acgccgtcca cgtaccagtt gaacttgacc tcagggtctt cgtggctcac gtccaccacc acgcatgtaa cctcagacct cggccgcgac cacgct <210> 222 <211> 477 <212? DNA <213> Homo sapien <400> 222 agcgtggtcg cggccgaggt ctgaggttac atgcgtggtg gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa gccgcgggag gagcagtaca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag ccctcccagc ccccatcgag aaaaccatct ccaaagccaa agggcaagcc ccgagaacca caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta tcccagcgac atcgccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacgcctccc gtgctggact ccgacacctg cccgggcggc cgctcga <210> 223 <211> 361 <212> DNA <213> Homo sapien <400> 223 tcgagcggcc gcccgggcag gttgaatggc tcctcgctga ccaccccggt gctggtggtg ggtacagagc tccgatgggt gaaaccattg acatagagac tgtccctgtc cagggtgtag gggcccagct cagtgatgcc gtgggtcagc tggctcagct tccagtacag ccgctctctg tccagtccag ggcttttggg gtcaggacga tgggtgcaga cagcatccac tctggtggct gccccatcct tctcaggcct gagcaaggtc agtctgcaac cagagtacag agagctgaca ctggtgttct tgaacaaggg cataagcaga ccctgaagga cacctcggcc gcgaccacgc .t

120 180 240 300 360 420 476

120 180 240

300 360 420 477

120 180 240 300 360 361 <210> 224 <211> 361 <212> DNA <213> Homo sapien <400> 224 agcgtggtcg cggccgaggt gtccttcagg gtctgcttat gcccttgttc aagaacacca gtgtcagctc tctgtactct ggttgcagac tgaccttgct caggcctgag aaggatgggg cagccaccag agtggatgct gtctgcaccc atcgtcctga ccccaaaagc cctggactgg acagagagcg gctgtactgg aagctgagcc agctgaccca cggcatcact gagctgggcc cctacaccct ggacagggac agtctctatg tcaatggttt cacccatcgg agctctgtac ccaccaccag caccggggtg gtcagcgagg agccattcaa cctgcccggg cggccgctcg a <210> 225 <211> 766 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . .(766) <223> n = A,T,C or G <400> 225 agcgtggtcg cggccgaggt cctgtcagag tggcactggt. agaagttcca ggaaccctga actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgrac tcagaagtgt cctggaatgg ggcccatgag atggttgtct gagagagagc ttcrtgtcct acattcggcg ggtatggtct tggcctatgc cttatggggg tggccgttgt gggcggrgtg gtccgcctaa aaccatgttc ctcaaagatc atttgttgcc caacactggg ttgctgacca gaagtgccag gaagctgaat accatttcca gtgtcatacc cagggtgggt gacgaaaggg gtcttttgaa ctgtggaagg aacatccaag atctctggtc catgaagatt ggggtgtgga agggttacca gttggggaag ctcgtctgtc tttttccttc caatcagggg ctcgctcttc tgattattct tcagggcaat gacataaatt gtatattcgg tcccggttcc aggccagtaa tagtagcctc tgtgacacca gggcggggcc gagggaccct tctnttggaa gagaccagct tctcatactt gatgatgagn ccggtaatcc tggcacgtgg nggttgcatg atnccaccaa ggaaatnggn gggggnggac ctgcccggcg gccgttcnaa agcccaattc cacacacttg gnggccgtac tatggatccc actcngtcca acttggngga atatggcata actttt <210> 226 <211> 364 <212> DNA <213> Homo sapien <400> 226 tcgagcggcc gcccgggcag gtccttgacc ttttcagcaa gtgggaaggt gtaatccgtc tccacagaca aggccaggac tcgtttgtac ccgttgatga tagaatgggg tactgatgca. acagttgggt agccaatctg cagacagaca ctggcaacat tgcggacacc ctccaggaag cgagaatgca gagtttcctc tgtgatatca agcacttcag ggttgtagat gctgccattg tcgaacacct gctggatgac cagcccaaag gagaaggggg agatgttgag catgttcagc agcgtggctt cgctggctcc cactttgtct ccagtcttga tcagacctcg gccgcgacca cgct <210> 227 <211> 275 <212> DNA <213> Homo sapien <400> 227 agcgtggtcg cggccgaggt ctgtcctaca gtcctcagga ctctactccc tcagcagcgt ggtgaccgtg ccctccagca acttcggcac ccagacctac acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagagagt tgagcccaaa tcttgtgaca aaactcacac

120 180 240 300 360

120 180 240 300 360 420 480 540 600 660 720

66

120 180 240 300 360 364 atgcccaccg tgcccagcac ctgaactcct ggggggaccg tcagtcttcc tcttcccccg catccccctt ccaaacctgc ccgggcggcc gctcg <210> 228 <211> 275 <212> DNA <213> Homo sapien <400> 228 cgagcggccg cccgggcagg tttggaaggg ggatgcgggg gaagaggaag actgacggtc cccccaggag ttcaggtgct gggcacggtg ggcatgtgtg agttttgtca caagatttgg gctcaactct cttgtccacc ttggtgttgc tgggcttgtg atctacgttg caggtgtagg tctgggtgcc gaagttgctg gagggcacgg tcaccacgct gctgagggag tagagtcctg aggactgtag gacagacctc ggccgcgacc acgct <210> 229 <211> 40 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(40) <223> n = A,T,C or G <400> 229 nggnnggtcc ggncngncag gaccactcnt cttcgaaata <210> 230 <211> 208 <212> DNA <213> Homo sapien <400> 230 agcgrggtcg cggccgaggt cctcacttgc ctcctgcaaa gcaccgatag ctgcgctctg gaagcgcaga tctgttttaa agtcctgagc aatttctcgc accagacgct ggaagggaag tttgcgaatc agaagttcag tggacttctg ataacgtcta atttcacgga gcgccacagt accaggacct gcccgggcgg ccgctcga <210> 231 <211> 208 <212> DNA <213> Hoino sapien <220>

<221> misc_feature <222> (1). - (208) <223> n = A,T,C or G <400> 231 tcgagcggcc gcccgggcag gtcctggtac tgnggcgctc cgtgaaatta gacgttatca gaagtccact gaacttctga ttcgcaaact tcccttccag cgtctggtgc gagaaattgc tcaggacttt aaaacagatc tgcgcttcca gagcgcagct atcggtgctt tgcaggaggc aagtgaggac ctcggccgcg accacgct <210> 232 .

<211> 332 <212> DNA <213> Homo sapien <400> 232 tcgagcggcc gcccgggcag gtccacatcg gcagggtcgg agccctggcc gccatactcg aactggaatc catcggtcat gctctcgccg aaccagacat gcctcttgtc cttggggttc ttgctgatgt accagttctt ctgggccaca ctgggctgag tggggtacac gcaggtctca ccagtctcca tgttgcagaa gactttgatg gcatccaggt tgcagccttg gttggggtca atccagtact ctccactctt ccagtcagag tggcacatct tgaggtcacg gcaggtgcgg gcggggttct tgacctcggc cgcgaccacg ct <210> 233 <211> 415 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(415) <223> n = A, T,C or G <400> 233 gtgggnttga acccntttna nctccgcttg gtaccgagct cggatccact agtaacggcc gccagtgtgc tggaattcgg cttagcgtgg tcgcggccga ggtcaagaac cccgcccgca cctgccgtga cctcaagatg tgccactctg actggaagag tggagagtac tggattgacc ccaaccaagg ctgcaacctg gatgccatca aagtcttctg caacatggag actggtgaga cctgcgtgta ccccactcag cccagtgtgg cccagaagaa ctggtacatc agcaagaacc ccaaggacaa gaggcatgtc tggttcggcg agagcatgac cgatggattc cagttcgagt atggcggcca gggctccgac cctgccgatg tggacctgcc cgggcggccg ctcga <210> 234 <211> 776 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(776) <223> n = A,T,C or G <400> 234 agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata ttacaggatc acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct gtcactggcc gtggagacag ccccgcaagc agcaagccaa tttccattaa ttaccgaaca gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc aagtggctgc cttcaagttc ccctgttact ggttacagag taaccaccac tcccaaaaat ggaccaggac caacaaaaac taaaactgca ggtccagatc aaacagaaat gactattgaa ggcttgcagc ccacagtgga gtatgtggtt aagtgtctat gctcagaatc caagcggaga gaagtcagcc tctggttcag actgnaagta accaacattg atcgcctaaa ggactggcat tcactgatgn. ggatgccgat tccatcaaaa ttgnttggga aaacccacag gggcaagttt ncangtcnag gnggacctac tcgagccctg aggatggaat ccttgactnt tccttnncct gatggggaaa aaaaaccttn aaaacttgaa ggacctgccc gggcggccgt ncaaaaccca

120 180 240 300 332

120 180 240 300 360 415

120 180 240 300

360 420 480 540 600

660 720 attccacccc cttgggggcg ttctatgggn cccactcgga ccaaacttgg ggtaan <210> 235 <211> 805 <212> DNA <213> Homo sapien <220> <221> misc_feature <222> (1).. (805) <223> n = A,T,C or G <400> 235 tcgagcggcc gcccgggcag gtccttgcag ctctgcagtg tcttcttcac catcaggtgc agggaatagc tcatggattc catcctcagg gctcgagtag gtcaccctgt acctggaaac ttgcccctgt gggctttccc aagcaatttt gatggaatcg gcatccacat cagtgaatgc cagtccttta gggcgatcaa tgttggttac tgcagtctga accagaggct gactctctcc gcttggattc tgagcataga cactaaccac atactccact gtgggctgca agccttcaat agtcatttct gtttgatctg gacctgcagt tttagttttt gttggtcctg gtccattttt gggagtggtg gttactctgt aaccagtaac aggggaactt gaaggcagcc acttgacact aatgctgttg tcctgaacat cggtcacttg catctgggat ggtttgtcaa tttctgttcg gtaattaatg gaaattggct tgctgcttgc ggggcttgtc tccacggcca gtgacagcat acacagtgat ggtataatca actccaggtt taagccgctg atggtagctg aaactttgct ccaggcacaa gtgaactcct gacagggcta tttcctnctg ttctccgtaa gtgatcctgt aatatctcac tgggacagca ggangcattc caaaacttcg ggcgngaccc cctaagccga attntgcaat atncatcaca ctggcgggcg ctcgancatt cattaaaagg cccaatcncc cctataggga gtntantaca attng <210> 236 <211> 262 <212> DNA <213> Homo sapien <400> 236 tcgagcggcc gcccgggcag gtcacttttg gtttttggrc atgrtcggtt ggtcaaagat aaaaactaag tttgagagat gaatgcaaag gaaaaaaata ttttccaaag tccatgtgaa attgtctccc atttttttgg cttttgaggg ggttcagttt gggttgcttg tctgtttccg ggttgggggg aaagttggtt gggtgggagg gagccaggtt gggatggagg gagtttacag gaagcagaca gggccaacgt eg <210> 237 <211> 372 <212> DNA <213> Homo sapien <400> 237 agegtggteg eggeegaggt cctcaccaga ggtgccacct acaacatcat agtggaggca ctgaaagacc agcagaggca taaggttegg gaagaggttg ttaccgtggg caactctgtc aaegaagget tgaaccaacc tacggatgac tcgtgctttg acccctacac agtttcccat tatgccgttg gagatgagtg ggaacgaatg tctgaatcag gctttaaact gttgtgccag tgettagget ttggaagtgg tcatttcaga tgtgattcat ctagatggtg ccatgacaat ggtgtgaact acaagattgg agagaagtgg gaccgtcagg gagaaaatgg acctgcccgg gcggccgctc ga

120 180 240 300 360 420 480 540 600 660 720 780 805 <210> 238 <211> 372 <212> DNA <213> Homo sapien <400> 238 tcgagcggcc gcccgggcag gtccattttc tccctgacgg tcccacttct ctccaatctt60 gtagttcaca ccattgtcat ggcaccatct agatgaatca catctgaaat gaccacttcc120 aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc180 tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt240 caagccttcg ttgacagagt tgcccacggt aacaacctct tcccgaacct tatgcctctg300 ctggtctttc agtgcctcca ctatgatgtt gtaggtggca cctctggtga ggacctcggc 360 cgcgaccacg ct372 <210> 239 <211> .720 , <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(720) <223> n ־־ A, T,C or G <400> 239 tcgagcggcc gcccgggcag gtccaccata agtcctgata caaccacgga tgagctgtca60 ggagcaaggt tgatttcttt cattggtccg gtcttctcct tgggggtcac ccgcactcga120 tatccagtga gctgaacatt gggtggtgtc cactgggcgc tcaggcttgt gggtgtgacc180 tgagtgaact tcaggtcagt tggtgcagga atagtggtta ctgcagtctg aaccagaggc240 tgactctctc cgcttggatt ctgagcatag acactaacca catactccac tgtgggctgc300 aagccttcaa tagtcatttc tgtttgatct ggacctgcag ttttagtttt tgttggtcct360 ggtccatttt tgggagtggt ggttactctg taaccagtaa caggggaact tgaaggcagc420 cacttgacac taatgctgtt gtcctgaaca tcggtcactt gcatctggga tggtttgnca480 atttctgttc ggtaattaat ggaaattggc ttgctgcttg cggggctgtc tccacggcca540 gtgacagcat acacagngat ggnatnatca actccaagtt taaggccctg atggtaactt600 taaacttgct cccagccagn aaacttccgg acagggtatt .tcttctggtt ttccgaaagn660 gancctggaa tnntctcctt ggancagaag gancntccaa aacttgggcc ggaacccctt720 <210> 240 <211> 691 <212> DNA <213> Homo sapien <220> <221> misc_feature <222> (1)..(691) <223> n = A,T,C or G <400> 240 agcgtggtcg cggccgaggt cctgtcagag tggcactggt agaagttcca׳ ggaaccctga60 actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagtgt120 cctggaatgg ggcccatgag atggttgtct gagagagagc ttcttgtcct acattcggcg180 ggtatggtct tggcctatgc cttatggggg tggccgttgt gggcggtgtg gtccgcctaa240 aaccatgttc ctcaaagatc atttgttgcc caacactggg ttgctgacca gaagtgccag300 gaagctgaat accatttcca gtgtcatacc cagggtgggt gacgaaaggg gtcttttgaa360 ctgtggaagg aacatccaag atctctggtc catgaagatt ggggtgtgga agggttacca420 gttggggaag ctcgtctgtc tttttccttc caatcagggg ctcgctcttc tgattattct tcagggcaat gacataaatt gtatattcgg ttcccggttc caggccagta atagtagcct cttgtgacac caggcggggc ccanggacca cttctctggg angagaccca gcttctcata cttgatgatg taacccggta atcctgcacg tggcggctgn catgatacca ncaaggaatt gggtgnggng gacctgcccg gcggccctcn a <210> 241 <211> 808 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(808) <223> n = A,T,C or G <400> 241 agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata ttacaggatc acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct gtcactggcc gtggagacag ccccgcaagc agcaagccaa tttccattaa ttaccgaaca gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc aagtggctgc cttcaagttc ccctgttact ggttacagag taaccaccac tcccaaaaat ggaccaggac caacaaaaac taaaactgca ggtccagatc aaacagaaat gactattgaa ggcttgcagc ccacagtgga gtatgtggtt agtgtctatg ctcagaatcc aagcggagag agtcagcctc tggttcagac tgcagtaacc actattcctg caccaactga cctgaagttc actcaggtca cacccacaag cctgagccgc cagtggacac cacccaatgt tcactcactg gatatcgagt gcgggtgacc cccaaggaga agacccggac ccatgaaaga aatcaacctt gctcctgaca gctcatccgn gggtgtatca ggacttatgg gggactgccc cggcnggccg ntcgaaancg aattntgaaa tttccttcnc actgggnggc gnttcgagct tncttntana nggcccaatt cncctntagn gggtcgtn <210> 242 <211> 26 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(26) <223> n = A,T,C or G <400> 242 agcgtggtcg cggccgaggt cnagga <210> 243 <211> 697 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1).-.(697) <223> n ־ A,T,C or G

120 180 240 300 360 420 480 540 600 660 720 780 808 <400> 243.

tcgagcggcc gcccgggcag gtccaccaca cccaattcct tgctggtatc atggcagccg ccacgtgcca ggattaccgg־ctacatcatc aagtatgaga agcctgggtc tcctcccaga gaagtggtcc ctcggccccg ccctggtgtc acagaggcta ctattactgg cctggaaccg ggaaccgaat atacaattta tgtcattgcc ctgaagaata atcagaagag cgagcccctg attggaagga aaaagacaga cgagcttccc caactggtaa cccttccaca ccccaatctt catggaccag agatcttgga tgttccttcc acagttcaaa agaccccttt cgtcacccac cctgggtatg acactggaaa tggtattcag cttcctggca cttctggtca gcaacccagt gttgggcaac aaatgatctt tgaggaacat ggttttaggc ggaccacacc gcccacaacg ggcaccccca taaggnatag gccaagacca taccccgccg aatgtaggac aagaagctct ntctcaacaa ccatctcatg ggccccattc caggacactt ctgagtacat catttcatgt catcctggtg ggcacttgat gaanaaccct tacagttcag ggttcctgga acttctacca gngccacttc tgacagganc ttgggcgnga ccaccct <210> 244 <211> 373 <212> DNA <213> Homo sapien <400> 244 agcgtggtcg cggccgaggt ccattttctc cctgacggtc ccacttctct ccaatcttgt agttcacacc attgtcatgg caccatctag atgaatcaca tctgaaatga ccacttccaa agcctaagca ctggcacaac agtttaaagc ctgattcaga cattcgttcc cactcatctc caacggcata atgggaaact gtgtaggggt caaagcacga gtcatccgta ggttggttca agccttcgtt gacagagttg cccacggtaa caacctcttc ccgaacctta tgcctctgct ggtctttcag tgcctccact atgatgttgt aggtggcacc tctggtgagg acctgcccgg gcggcccgct ega <210> 245 <211> 307 <212> DNA <213> Homo sapien <400> 245 agcgtggtcg cggccgaggt gtgccccaga ccaggaattc ggcttcgacg ttggccctgt ctgcttcctg taaactccct ccatcccaac ctggctccct cccacccaac caactttccc cccaacccgg aaacagacaa gcaacccaaa ctgaaccccc tcaaaagcca aaaaaatggg agacaatttc acatggactt tggaaaatat ttttttcctt tgcattcatc tctcaaactt agtttttatc tttgaccaac cgaacatgac caaaaaccaa aagtgacctg cccgggcggc egetega <210> 246 <211> 372 <212> DNA <213> Homo sapien <400> 246 tcgagcggcc gcccgggcag gtcctcacca gaggtgccac ctacaacatc atagtggagg cactgaaaga ccagcagagg cataaggttc gggaagaggt tgttaccgtg ggcaactctg teaaegaagg cttgaaccaa cctacggatg actcgtgctt tgacccctac acagtttccc attatgeegt tggagatgag tgggaacgaa tgtetgaate aggctttaaa ctgttgtgcc agtgettagg ctttggaagt ggtcatttca gatgtgattc atetagatgg tgccatgaca atggtgtgaa ctacaagatt ggagagaagt gggaccgtca gggagaaaat ggacctcggc cgcgaccacg ct

120 180 240 300 360 420 480 540 600 660 697

120 180 240 300 360 373

120 180 240 300 307

120 180 240 300

360 372 <210> 247 <211> 348 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1).. (348) <223> n = A,T,C or G <400> 247 tcgagcggcc gcccgggcag gtaccggggt ggtcagcgag gagccattca cactgaactt caccatcaac aacctgcggt atgaggagaa catgcagcac cctggctcca ggaagttcaa caccacggag agggtccttc agggcctgct caggtccctg ttcaagagca ccagtgttgg ccctctgtac tctggctgca gactgacttt gctcagacct gagaaacatg gggcagccac tggagtggac gccatctgca ccctccgcct tgatcccact ggtnctggac tggacanana gcggctatac ttgggagctg anccnaacct ttggcggnga cnccnctt <210> 248 <211> 304 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(304) <223> n = A,T,C or G <400> 248 gaggactggc tcagctccca gtatagccgc tctctgtcca gtccaggacc agtgggatca aggcggaggg tgcagatggc gtccactcca gtggctgccc catgtttctc aagtctgagc aaagncagtc tgcagccaga gtacagaggg ccaacactgg tgctcttgaa cagggacctg agcaggccct gaaggaccct ctccgtggtg ttgaacttcc tggagccagg gtgctgcatg ttctcctcat accgcaggtt gttgatggtg’ aagttcagtg tgaatggctc ctcgctgacc accc <210> 249 <211> 400 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1). . (400) <223> n = A, T,C or G <400> 249 agcgtggtcg cggccgaggt ccaccacacc caattccttg ctggtatcat ggcagccgcc acgtgccagg attaccggct acatcatcaa gtatgagaag cctgggtctc ctcccagaga agtggtccct cggccccgcc ctggtgtcac agaggctact attactggcc tggaaccggg aaccgaatat acaatttatg tcattgccct gaagaataat cagaagagcg agcccctgat tggaaggaaa aagacagacg agcttcccca actggtaacc cttccacacc ccaatcttca tggaccanan ancttggatn gtcctttcac nggttnaaaa aacccttttc gcccccccac cttggggatt aaccttggga aanggggatt tnaccnttcc

120 180 240 300 348 <210> 250 <211> 400 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(400) <223> n=A,T,C or G <400> 250 tcgagcggcc gcccgggcag gtcctgtcag agtggcactg gtagaagttc caggaaccct gaactgtaag ggttcttcat cagtgccaac aggatgacat gaaatgatgt actcagaagt gtcctggaat ggggcccatg agatggttgt ctgagagaga gcttcttgtc ctacattcgg cgggtatggt cttggcctat gccttatggg ggtggccgtt gtgggcggtg tggtccgcct aaaaccatgt tcctcaaaga tcatttgttg cccaacactg ggttgctgac cagaagtgcc aggaagctga ataccatttc cagtgtcata cccagggngg gtgaccaaag ggggtcnttt ngacctggng aaaggaacca tccaaaanct ctgncccatg <210> 251 <211> 514 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . (514) <223> n ־־ A, T,C or G <400> 251 agcgtggncg cggccgaggt ctgaggatgt aaactcttcc caggggaagg ctgaagtgct gaccatggtg ctactgggtc cttctgagtc agatatgtga ctgatgngaa ctgaagtagg tactgtagat ggtgaagtct gggtgtccct aaatgctgca tctccagagc cttccatcat taccgtttct tcttttgcta tgggatgaga cactgttgag tattctctaa agtcaccact gaaatcttcc tccaaaggaa aacctgtgga aaagcccctt atttctgccc cataatttgg ttctcctaat cnctctgaaa tcactatttc cctggaangt ttgggaaaaa nngggcnacc tgncantgga aantggatan aaagatccca ccattttacc caacnagcag aaagtgggaa nggtaccgaa aagctccaag taanaaaaag gagggaagta aaggtcaagt gggcaccagt ttcaaacaaa actttcccca aactatanaa ccca <210> 252 <211> 501 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(501) <223> n = A,T,C or G <400> 252 aagcggccgc ccgggcaggn ncagnagtgc cttcgggact gggntcaccc ccaggtctgc ggcagttgtc acagcgccag ccccgctggc ctccaaagca tgtgcaggag caaatggcac cgagatattc cttctgccac tgttctccta cgtggtatgt cttcccatca tcgtaacacg ttgcctcatg agggtcacac ttgaattctc cttttccgtt cccaagacat gtgcagctca

120 180 240 300

360 4 00

120 180 240 300 360 420 480 514 tttggctggc tctatagttt ggggaaagtt tgttgaaact gtgccactga cctttacttc 300 ctccttctct actggagctt tccgtacctt ccacttctgc tgntggnaaa aagggnggaa 360 cntcttatca atttcattgg acagtanccc nctttctncc caaaacatnc aagggaaaat 420 attgattncn agagcggatt aaggaacaac ccnaattatg ggggccagaa ataaaggaaa 480 cttttccaca ggtnttttcc t 501 <210> 253 <211> 226 <212> DNA <213> Homo sapien <400> 253 tcgagcggcc gcccgggcag gtctgcaggc tattgtaagt gttctgagca catatgagat60 aacctgggcc aagctatgat gttcgatacg ttaggtgtat taaatgcact tttgactgcc120 atctcagtgg atgacagcct tctcactgac agcagagatc ttcctcactg tgccagtggg180 caggagaaag agcatgctgc gactggacct cggccgcgac cacgct226 <210> 254 <211> 226 <212> DNA <213> Homo sapien <400> 254 agcgtggtcg cggccgaggt ccagtcgcag catgctcttt ctcctgccca ctggcacagt60 gaggaagatc tctgctgtca gtgagaaggc tgtcatccac tgagatggca gtcaaaagtg120 catttaatac acctaacgta tcgaacatca tagcttggcc caggttatct catatgtgct180 cagaacactt acaatagcct gcagacctgc ccgggcggcc gctcga226 <210> 255 <211> 427 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(427) <223> n = A,T,C or G <400> 255 cgagcggccg cccgggcagg tccagactcc aatccagaga accaccaagc cagatgtcag60 aagctacacc atcacaggtt tacaaccagg cactgactac aagatctacc tgtacacctt120 gaatgacaat gctcggagct cccctgtggt catcgacgcc tccactgcca ttgatgcacc180 atccaacctg cgtttcctgg ccaccacacc caattccttg ctggtatcat ggcagccgcc240 acgtgccagg attaccggct acatcatcaa gtatgagaag cctgggtctc ctcccagaga300 agtggtccct cggccccgcc ctggtgncac agaagctact attactggcc tggaaccggg360 aaccgaatat acaatttatg tcattgccct gaagaataat canaagagcg agcccctgat420 tggaagg <210> 256 <211> 535 <212> DNA <213> Homo sapien <220>

<221> miso feature <222> (1)..(535) <223> n = A, T,C or G <400> 256 agcgtggtcg cggccgaggt cctgtcagag tggcactggt agaagttcca ggaaccctga actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagtgt cctggaatgg ggcccatgag atggttgtct gagagagagc ttcttgtcct gtctttttcc ttccaatcag gggctcgctc ttctgattat tcttcagggc aatgacataa attgtatatt cggttcccgg ttccaggcca gtaatagtag cctctgtgac accagggcgg ggccgaggga ccacttctct gggaggagac ccaggcttct catacttgat gatgtanccg gtaatcctgg caccgtggcg gctgccatga taccagcaag gaattgggtg tggtggccaa gaaacgcagg ttggatggtg catcaatggc agtggaggcg tcgatnacca caggggagct ccgancattg tcattcaagg tggacaggta gaatcttgta atcaggtgcc tggtttgtaa acctg <210> 257 <211> 544 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (544) <223> n = A,T,C or G <400> 257 tcgagcggcc gcccgggcag gtttcgtgac cgtgacctcg aggtggacac caccctcaag agcctgagcc agcagatcga gaacatccgg agcccagagg gcagccgcaa gaaccccgcc cgcacctgcc gtgacctcaa gatgtgccac tctgactgga agagtggaga gtactggatt gaccccaacc aaggctgcaa cctggatgcc atcaaagtct tctgcaacat ggagactggt gagacctgcg tgtaccccac tcagcccagt gtggcccaga agaactggta catcagcaag aaccccaagg acaagaagca tgtctggttc ggcgaaagca tgaccgatgg attccagttc gagtatggcg gccagggctc cgaccctgcc gatgtggacc tcggccgcga ccacgctaag cccgaattcc agcacactgg cggccgttac tagtgggatc cgagcttcgg taccaagctt ggcgtaatca tgggncatag ctgtttcctg ngtgaaaatg gtattccgct tcacaatttc ccac <210> 258 <211> 418 <212> DNA <213> Homo sapien <400> 258 agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt gctgatgtac cagttcttct gggccacact gggctgagtg gggtacacgc aggtctcacc agtctccatg ttgcagaaga ctttgatggc atccaggttg cagccttggt tggggtcaat ccagtactct ccactcttcc agtcagagtg gcacatcttg aggtcacggc aggtgcgggc ggggttcttg cggctgccct ctgggctccg gatgttctcg atctgctggc tcaagctctt gaagggtggt gtccacctcg aggtcacggt cacgaaacct gcccgggcgg ccgctcga <210> 259 <211> 377 <212> DNA <213> Homo sapien

120 180 240 300 360' 420 480 535

120 180 240

300 360 420 480

540 544 <220>

<221> misc_feature <222> (1)..(377) <223> n = A,T,C or G <400> 259 agcgtggtcg cggccgaggt caagaacccc gcccgcacct gccgtgacct caagatgtgc cactctgact ggaagagtgg agagtactgg attgacccca accaaggctg caacctggat gccatcaaag tcttctgcaa catggagact gg״tgagacct gcgtgtaccc cactcagccc agtgtggccc agaagaactg gtacatcagc aagaacccca aggacaagag gcatgtctgg ttcggcgaga gcatgaccga tggattccag ttcgagtatg gcggccaggg ctccgaccct gccgatgtgg acctgcccgn gccggnccgc tcgaaaagcc cnaatttcca gncacacttg gccggccgtt actactg <210> 260 <211> 332 <212> DNA <213> Homo sapien <400> 260 tcgagcggcc gcccgggcag gtccacatcg gcagggtcgg agccctggcc gccatactcg aactggaatc catcggtcat gctctcgccg aaccagacat gcctcttgtc cttggggttc ttgctgatgt accagttctt ctgggccaca ctgggctgag tggggtacac gcaggtctca ccagtctcca tgttgcagaa gactttgatg gcatccaggt tgcagccttg gttggggtca atccagtact ctccactctt ccagtcagag tggcacatct tgaggtcacg gcaggtgcgg gcggggttct tgacctcggc cgcgaccacg ct <210> 261 <211> 94 <212> DNA <213> Homo sapien <400> 261 cgagcggccg cccgggcagg tcccccccct tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttt <210> 262 <211> 650 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(650) <223> n = A, T,C or G <400> 262 agcgtggtcg cggccgaggt ctggcattcc ttcgacttct ctccagccga gcttcccaga acatcacata tcactgcaaa aatagcattg catacatgga tcaggccagt ggaaatgtaa agaaggccct gaagctgatg gggtcaaatg aaggtgaatt caaggctgaa ggaaatagca aattcaccta cacagttctg gaggatggtt gcacgaaaca cactggggaa tggagcaaaa cagtctttga atatcgaaca cgcaaggctg tgagactacc tattgtagat attgcaccct atgacattgg tggtcctgat caagaatttg gtgtggacgt tggccctgtt tgctttttat aaaccaaact ctatctgaaa tcccaacaaa aaaaatttaa ctccatatgt gntcctcttg ttctaatctt ggcaaccagt gcaagtgacc gacaaaattc cagttattta tttccaaaat

120 180 240 300 360 377

־60

120 180 240 300 360 420 480 gtttggaaac agtataattt gacaaagaaa aaaggatact tctctttttt tggctggtcc accaaataca attcaaaagg ctttttggtt ttattttttt anccaattcc aatttcaaaa tgtctcaatg gngcttataa taaaataaac tttcaccctt nttttntgat <210> 263 <211> 573 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (573) <223> n = A, T,C or G <400> 263 agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata ttacaggatc60׳ acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag120 tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct180 gtcactggcc gtggagacag ccccgcaagc agcaagccaa tttccattaa ttaccgaaca240 gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc300 aagtggctgc cttcaagttc ccctgttact ggttacagaa gtaaccacca ctcccaaaaa360 tggaccagga ccaacaaaaa ctaaaactgc aggtccagat caaacagaaa atggactatt420 gaaggcttgc agcccacagt ggaagtatgt ggntaggngt ctatgctcag aatcccaagc480 cggagaaagt cagccttctg gtttagactg cagtaaccaa cattgatcgc cctaaaggac540 tggncattca cttggatggt ggatgtccaa ttc573 <210> 264 <211> 550 <212> DNA <213> Homo sapien <220> <221> misc_feature <222> (1).. (550) <223> n = A,T,C or G <400> 264 tcgagcggcc gcccgggcag gtccttgcag ctctgcagng tcttcttcac catcaggtgc60 agggaatagc tcatggattc catcctcagg gctcgagtag gtcaccctgt acctggaaac120 ttgcccctgt gggctttccc aagcaatttt gatggaatcg acatccacat cagngaatgc180 cagtccttta gggcgatcaa tgttggttac tgcagtctga accagaggct gactctctcc240 gcttggattc tgagcataga cactaaccac atactccact gtgggctgca agccttcaat300 agtcatttct gtttgatctg gacctgcagt tttaagtttt tggtggtcct gncccatttt360 tgggaagtgg ggggttactc tgtaaccagt aacaggggaa cttgaaggca gccacttgac420 actaatgctg ttgtcctgaa catcggtcac ttgcatctgg ggatggtttt gacaatttct480 ggttcggcaa attaatggaa attggcttgc tgcttggcgg ggctgnctcc acgggccagt540 gacagcatac550 <210> 265 <211> 596 <212> DNA <213> Homo sapien <220>

<221> misc feature catcaggtgc 60 acctggaaac 120 cagtgaatgc 180 gactctctcc 240 agccttcaat 300 gnnccatttt 360 gccacttgac 420 tcaatttctg 480 cggncagtga 540 atggta 596 ttacaggatc 60 tgggagcaag 120 <222> (1).,.(596) <223> n = A,T,C or G <400> 265 tcgagcggcc gcccgggcag gtccttgcag ctctgcagtg tcttcttcac agggaatagc tcatggattc catcctcagg gctcgagtag gtcaccctgt ttgcccctgt gggctttccc aagcaatttt gatggaatcg acatccacat cagtccttta gggcgatcaa tgttggttac tgcagtctga accagaggct gcttggattc tgagcataga cactaaccac atactccact gtgggctgca agtcatttct gtttgatctg gacctgcagt tttaagtttt tgttggncct tggggaaggg gtggttactc ttgtaaccag taacagggga acttgaagca actaatgctg gtggcctgaa catcggtcac ttgcatctgg gatggtttgg ttcggtaatt aatgggaaat tggcttactg gcttgcgggg gctgtctcca caagcataca caggngatgg gtataatcaa ctccaggttt aaggccnctg <210> 266 <211> 506 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (506) <223> n = A,T,C or G <400> 266 agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct180 gtcactggcc gtggagacag ccccgcaagc agtaagccaa tttccattaa ttaccgaaca240 gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc300 aagtggctgc cttcaagttc ccctgttact ggttacagag taaccaccac tcccaaaaat360 gggaccagga ccaacaaaaa actaaaactg canggtccag atcaaacaga aatgactatt420 gaaggcttgc agcccacagt ggagtatgtg ggttagtgtc tatgctcaga atnccaagcg480 gagagagtca gcctctggtt cagact5q5 <210> 267 <211> 548 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1). . . (548) <223> n = A,T,C or G <400> 267 tcgagcggcc gcccgggcag gtcagcgctc tcaggacgtc accaccatgg cctgggctct60 gctcctcctc accctcctca ctcagggcac agggtcctgg gcccagtctg ccctgactca120 gcctccctcc gcgtccgggt ctcctggaca gtcagtcacc atctcctgca ctggaaccag180 cagtgacgtt ggtgcttatg aatttgtctc ctggtaccaa caacacccag gcaaggcccc240 caaactcatg atttctgagg tcactaagcg gccctcaggg gtccctgatc gcttctctgg300 ctccaagtct ggcaacacgg cctccctgac cgtctctggg ctccangctg aggatgangc360 tgattattac tggaagctca tatgcaggca acaacaattg ggtgttcggc ggaagggacc420 aagctgaccg tnctaaggtc aagcccaagg cttgcccccc tcggtcactc tgttcccacc480 ctcctctgaa gaagctttca agccaacaan gncacactgg gtgtgtctca taagtggact LuCuaCCC <210> 268 <211> 584 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (584) <223> n = A,T,C or G <400> 268 agcgtggtcg cggccgaggt ctgtagcttq tgtgggactt ccactgctca ggcqtcaqqc tcaggtagct gctggccgcg tacttgttgt tgctttgntt ggagggtgtg gtggtctcca ctcccgcctt gacggggctg ctatctgcct tccaggccac tgtcacggct cccgggtaga agtcacttat gagacacacc agtgtggcct tgttggcttg aagctcctca gaggagggtg ggaacagagt gaccgagggg gcagccttgg gctgacctag gacggtcagc ttggtccctc cgccgaacac ccaattgttg ttgcctgcat atgagcrgca gtaataatca gcctcatcct cagcctggag cccagagacn gtcaagggag gcccgtgttt gccaagactt ggaagccaga naagcgatca gggacccctg agggccgctt tacngacctc aaaaaatcat gaatttgggg ggcctttgcc tgggngttgg ttggtnacca gnaaaacaaa atttcataaa gcaccaacgt cactgctggt ttccagtgca ngaanatggt gaactgaant gtcc <210> 269 <211> 368 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (368) <223> n = A,T,C or G <400> 269 agcgtggtcg cggccgaggt ccagcatcag gagccccgcc ttgccggctc tggtcatcgc ctttcttttt gtggcctgaa acgatgtcat caattcgcag tagcagaact gccgtctcca ctgctgtctt ataagtctgc agcttcacag ccaatggctc ccatatgccc agttccttca tgtccaccaa agtacccgtc tcaccattta caccccaggt ctcacagttc tcctgggtgt gcttggcccg aagggaggta agtanacgga tggtgctggt cccacagttc tggatcaggg tacgaggaat gacctctagg gcctgggcna caagccctgt atggacctgc ccgggcggqc ccgctcga

120 180 240 300 360 420 480 540 584

120 180 240 300 360 368 <210> 270 <211> 368 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)., (368) <223> n = A, T,C or G <400> 270 tcgagcggcc ttgtaccctg caagcacacc ggacatgaag agcagtggag gaaaggcgat ccacgctt gcccgggcag atccagaact caggagaact gaactgggca acggcagttc gaccanagcc gtccatacag gtgggaccag gtgagacctg tatgggagcc tgctactgcg ggcaaggcgg ggctgttgcc caccatccgt gggtgtaaat attggctgng aattgatgac ggcttcctga caggccctag ctacttacct ggngagacgg aagctgcana atcgtttcag tgctggacct aggncattcc cccttcgggc gtactttggt cttataagac gccacaaaaa cggccgccga

120 180 240 300 360 368 <210> 271 <211> 424 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1).. (424) <223> n = A,T,C or G <400> 271 agcgtggtcg cggccgaggt ccactagagg tctgrgtgcc attgcccagg cagagtctcr gcgttacaaa ctcctaggag ggcttgctgt gcggagggcc tgctatggtg tgctgcggrt catcatggag agtggggcca aaggctgcga ggttgtggtg tctgggaaac tccgaggaca gagggctaaa tccatgaagt ttgtggatgg cctgatgatc cacagcggag accctattaa ctactacgtt gacactgctg tgcgccacgt gttgctcana cagggtgtgc tgggcatcaa ggtgaagatc atgctgccct gggacccanc tggcaaaaat ggcccttaaa aaccccttgc cntgaccacg tgaaccattt gtgngaaccc caagatgaan atacttgccc accacccccc attc

120 180 240 300 360 420 424 <210> 272 <211> 541 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(541) <223> n = A,T,C or G <400 tcgagcggcc gggcatggca tatctcatct cttaccagtt gagcaacacg catcaggcca ccacaacctc ancaaggccc ttgcctgggg t > 272 gcccgggcag ggcggctctg ttgggttcca gggtcccagg tggcgcacag tccacaaact gccagccttt ttccgcacag caaatgggca gtctgccaag gcttcccacc caatgctcac gcagcatgat cagtgtcaac tcatggattt gggccccact gnaagccctt cacagacctn gagaccctgt cttctgttct gtggtcaggc cttcaccttg gtagtagtta agccctctgt tcttcatgaa cctaaggagt tantnggacc tatgctgtgg gagatggggg aggggcttct atgcccagca acagggtctc cctcggagtt tgaaaccgca tttgtaaacg ttggnccgcg ggactggctg tggtgggcag tagggccaat caccctgtct cgctgtggat tcccaaaaca gcacaccatt caaaaaactc aaccaccgct

120 180 240 300 360 420 480 540 541 <210> 273 <211> 579 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(579) <223> n = A, T,C or G <400> 273 agcgtggtcg cggccgaggt ctggccctcc tggcaaggct ggtgaagatg gtcaccctgg aaaacccgga cgacctggtg agagaggagt tgttggacca cagggtgctc gtggtttccc tggaactcct ggacttcctg gcttcaaagg cattagggga cacaatggtc tggatggatt gaagggacag cccggtgctc ctggtgtgaa gggtgaacct ggngcccctg gtgaaaatgg aactccaggt caaacaggag cccgngggct tcctggngag agaggacgtg ttggtgcccc tggcccanac ctgcccgggc ggccgctcna aaagccgaaa tccagnacac tggcggccgn tactantgga atccgaactt cggtaccaaa gcttggccgt aatcatggcc atagcttgtt ccctggggng gaaattggta ttccgctncc aattccacac aacataccga acccggaaag cattaaagtg taaaagccct gggggggcct aaatgangtg agcntaactc ncatttaatt ggcgttgcgc ttcactgccc.cgcttttcca gtccgggna <210> 274 <211> 330 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (330) <223> n = A,T,C or G <400> 274 tcgagcggcc gcccgggcag gtctgggcca ggggcaccaa cacgtcctct ctcaccagga agcccacggg ctcctgtttg acctggagtt ccattttcac caggggcacc aggttcaccc ttcacaccag gagcaccggg ctgtcccttc aatccatcca gaccattgtg ncccctaatg cctttgaagc caggaagtcc aggagttcca gggaaaccac gagcaccctg tggtccaaca actcctctct caccaggtcg tccgggtttt ccagggtgac catcttcacc agccttgcca ggagggccag acctcggccg cgaccacgct <210> 275 <211> 97 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> fl)..(97) <223> n = A,T,C or G <400> 275 ancgtggtcg cggccgaggt cctcaccaga ggtgncacct acaacatcat agtggaggca ctgaaagacc ancagaggca taaggttcgg gaagagg <210> 276 <211> 610 <212> DNA <213> Homo sapien

120 180 240 300 360 420 480 540 579

120 180 240 300 330 <220>

ure <2Z2> (1) . (610) <223> n = A, T,C or G <400> 276 tcgagcggcc gcccgggcag gtccattttc tccctgacgg tcccacttct ctccaatctt gtagttcaca ccattgtcat ggcaccatct agatgaatca catctgaaat gaccacttcc aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt caagccttcg ttgacagagt tgtccacggt aacaacctct tcccgaacct tatgcctctg ctggtctttc agtgcctcca ctatgatgtt gtaggtggca cctctggtga ggacctcngn ccngaacaac gcttaagccc gnattctgca gaataatccc atcacacttg gcggccgctt cgancatgca tcntaaaagg ggccccaatt tcccccttat aagngaancc gtatttncca atttcactgg ncccgccgnt tttacaaacg ncggtgaact ggggaaaaac cctggcggtt acccaacttt aatcgccntt ggcagcacaa tccccccttt tcgnccancn tgggcgtaaa taaccgaaaa <210> 277 <211> 38 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) .. (38) <223> n = A,T,C or G <400> 277 ancgnggtcg cggccgangt nttttttctt nttttttt <210> 278 <211> 443 <212> DNA <213> Homo sapien <220>

<221> tnisc_feature <222> (1)..(443) <223> n = A,T,C or G <400> 278 agcgtggtcg cggccgaggt ctgaggttac atgcgtggtg gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa gccgcgggag gagcagtaca acagcacgta ccgggnggtc agcgtcctca ccgtcctgca ccagaattgg ttgaatggca aggagtacaa gngcaaggtt tccaacaaag ccntcccagc ccccntcgaa aaaaccattt ccaaagccaa agggcagccc cgagaaccac aggtgtacac cctgccccca tcccgggagg aaaagancaa naaccnggtt cagccttaac ttgcttggrc naangctttt tatcccaacg nacttccccc ntggaantgg gaaaaaccaa tgggccaanc cgaaaaacaa ttacaanaac ccc

120 180 240 300 360 420 480 540 600 610

120 180 240 300 360 420 443 <210> 279 <211> 348 <212> DNA <213> Homo sapien <221> misc_feature <222> (1) . . . (348) <223> n=A,T,C or G <400> 279 tcgagcggcc gcccgggcag gtgtcggagt ccagcacggg aggcgtggtc ttgtagttgt tctccggctg cccattgctc tcccactcca cggcgatgtc gctgggatag aagcctttga ccaggcaggt caggctgacc tggttcttgg tcatctcctc ccgggatggg ggcagggtga acacctgggg ttctcggggc ttgccctttg gttttgaana tggttttctc gatgggggct ggaagggctt tgttgnaaac cttgcacttg actccttgcc attcacccag .ncctggngca ggacggngag gacnctnacc acacggaacc gggctggtgg actgctcc <210> 280 <211> 149 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (149) <223> n = A,T,C or G <400> 280 agcgtggtcg cggacgangt cctgtcagag tggnactggt agaagttcca ngaaccctga actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagngn cctggaatgg ggcccatgan atggttgcc <210> 281 <211> 404 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1). . (404) <223> n = A,T,C or G <400> 281 tcgagcggcc gcccgggcag gtccaccaca cccaattcct tgctggtatc atggcagccg ccacgtgcca ggattaccgg ctacatcatc aagtatgaga agcctgggtc tcctcccaga gaagtggtcc ctcggccccg ccctggtgtc acagaggcta ctattactgg cctggaaccg ggaaccgaat atacaattta tgtcattgcc ctgaagaata atcagaagag cgagcccctg attggaagga aaaagacaga cgagcttccc caactggtaa cccttccaca ccccaatctt catggaccag agatcttgga tgttccttcc acagttcaaa agaccccttt cggcaccccc cctgggtatg aacctgggaa aanggnantt aanctttcct ggca <210> 282 <211> 507 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1). . (507)

120 180' 240 300 348 _____ 11 = a, T, C or G <400> 282 agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata ttacaggatc 60 acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag 120 tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatact 180 gtcactggcc gtggagacag ccccgcaagc agcaagccaa tttccattaa ttaccgaaca 240 gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc 300 aagtggctgc cttcaaggtn ccctggtact gggttacaga ntaaccacca ctcccaaaaa 360 tggaccagga accacaaaaa cttaaactgc agggtccaga tcaaaacaga aatgactatt 420 gaangcttgc agcccacagt gggagtatgn gggtagtgnc tatgcttcag aatccaagcg 480 gaaaaangtc aagccttntg ggttcaa 507 <210> 283 <211> 325 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(325) <223> n = A, T,C or G <400> 283 tcgagcggcc gcccgggcag gtccttgcag ctctgcagtg tcttcttcac catcaggtgc 60 agggaatagc tcatggattc catcctcagg gctcgagtag gtcaccctgt acctggaaac 120 ttgcccctgt gggctttccc aagcaatttt gatggaatcg acatccacat cagtgaatgc 180 cagtccttta gggcgatcaa tgttggttac tgcagnctaa accagaggct gactctctcc 240 gcttggattc tgagcataga cactaaccac atactccact gtgggctgca anccttcaat 300 aanncatttc tgtttgatct ggacc 325 <210> 284 <211> 331 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (331) <223> n = A,T,C or G <400> 284 tcgagcggcc gcccgggcag gtctggtggg gtcctggcac acgcacatgg gggngttgnt 60 ctnatccagc tgcccagccc ccattggcga gtttgagaag gtgtgcagca atgacaacaa 120 naccttcgac tcttcctgcc acttctttgc cacaaagtgc accctggagg gcaccaaaaa 180 gggccacaag ctccacctgg actacatcgg gccttgcaaa tacatccccc cttgcctgga 240 ctctgagctg accgaattcc cccttgcgca tgcgggactg gctcaagaac cgtcctggca 300 cccttgtatg anagggatga agacacnacc c 33!

<210> 285 <211> 509 <212> DNA <213> Homo sapien <220>

sx.4 12 m!sc_feature <222> (1)..(509) <223> n = A,T,C or G <400> 285 agcgtggtcg cggccgaggt ctgtcctaca gtcctcagga ctctactccc tcagcagcgt ggtgaccgtg ccctccagca acttcggcac ccagacctac acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagagagt tgagcccaaa tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg tcagtcttcc tcttcccccg catccccctt ccaaacctgc ccgggcggcc gctcgaaagc cgaattccag cacactggcg gccggtacta gtgganccna acttggnanc caacctggng gaantaatgg gcataanctg tttctggggg gaaattggta tccngtttac aattcccnca caacatacga gccggaaaca taaaagngta aaagcctggg ggnggcctan tgaagtgaag ctaaactcac attaattngc gttgccgctc actggcccgc ttttccagc

120 180 240 300 360 420 480 509 <210> 286 <211> 336 .

<212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1). . (336) <223> n = A,T,C or G <400> 286 tcgagcggcc gcccgggcag gtttggaagg gggatgcggg ggaagaggaa gactgacgat60 ccccccagga gttcaggtgc tgggcacggt gggcatgtgt gagttttgtc acaagatttg120 ggctcaactc tcttgtccac cttggtgttg ctgggcttgt gatctacgtt gcaggtg־ag180 gtctgggngc cgaagttgct ggagggcacg gtcaccacgc tgctgaggga gtagagtcc240 ־ gaggactgta ngacagacct cggccgngac cacgctaagc cgaattctgc agatatccat300 cacactggcg gccgctccga gcatgcattt tagagg336 <210> 287 <211> 30 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(30) <223> n = A,T,C or G <400> 287 agcgtggncg cggacganga caacaacccc 30 <210> 288 <211> 316 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(316) <223> n = A,T,C or G <400> 288 tcgagcggcc aactggaatc ttgctgatgn ccagtctcca atccagtact gcggggttct gcccgggcag catcggtcat accagttctt tgttgcagaa ctccactctt tgacct gnccacatcg gctcttgccg ctgggccaca gactttgatg ccagtcagag gcagggtcgg aaccagacat ctgggctgag gcatccaggt tggcacatct agccctggcc gcctcttgtc tggggtacac tgcagccttg tgaggtcacg gccatactcg cttggggtrc gcaggtctca gttggggtca gcaggtgcgg

120 180 240 300 316 <210> 289 <211> 308 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1).. (308) <223> n = A,T,C or־G <400> 289 agcgtggtcg ccaggtatag cctgctggtt ggggctccgg agaggtggag ccacctgg cggccgaggt ctggacctcg tccctggtgc ntganaaagg ctggcccccc ccagcctgga tggtagccct tcctggacag tgaaggaggc tggccccgaa gataanggtg ggtgagagag aatggtgaac cctcctgnat ggaggaaagg aaggtggtgc gtgaaactgg ctggnggtaa tggcaggggc gtgctgctgg ccccggacrt ccctccaaga aggagaaaga cccangactt tcctcctggg <210> 290 <211> 324 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1).,.(324) <223> n = A, T,C or G <400> 290 tcgagcggcc gcccgggcag gtctgggcca ggaggaccaa taggaccagt aggacccctt gggccatctt tccctgggac accatcagca cctggaccgc ctggttcacc cttgtcaccc tttggaccag gacttccaag acctcctctt tctccaggca ttccttgcag accaggagta ccancagcac caggtggccc aggaggacca gcagcaccct ttcctccttc gggaccaggg ggaccagctc cacctctaag tcctggggcc cctgccaatc caggagggcc tccttcacct ttctcacccg gagcccctct ttct

120 180 240 300 324 <210>

<211>

<212>

<213>

<220>

<221>

<222>

<223>

DNA

Homo sapien misc_feature (1) .. (278) n = A,T,C or G tcgagcggcc gcccgggcag gtccaccggg atattcgggg gtctggcagg aatgggaggc atccagaacg agaaggagac catgcaaagc ctgaacgacc gcctggcctc ttacctggac agagtgagga gcctggagac cgacaaccgg aggctggaga gcaaaatccg ggagcacttg gagaagaagg gaccccaggt cagagactgg agccattact tcaagatcat cgaggacctg agggctcana tcttcgcaaa tactgcngac aatgcccg <210> 292 <211> 299 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(299) <223> n = A, T,C or G <400> 292 atacgnggtc gcggccgang accanctctg gctcatactt gactctaaag ncntcaccaa nanctacggn cattgccaat ctacagaacg atgcgggcat tgrccgcant atttgcgaag atctgagccc tcaggncctc gatgatcttg aagtaanggc tccagrctct gacctggggt cccttcttct ccaagtgctc ccggattttg ctctccagcc tccggttctc ggtctccaag ncttctcact ctgtccagga aaagaggcca ggcggncgat cagggctttt gcatggact <210> 293 <211> 101 <212> DNA <213> Homo sapien <400> 293 agcgtggtcg cggccgaggt tgtacaagct tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt t <210> 294 <211> 285 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . .(285) <223> n = A,T,C or G <400> 294 tcgagcggcc gcccgggcag gtctgccaac accaagattg gcccccgccg catccacaca gttngtgtgc ggggaggtaa caagaaatac cgtgccctga ggntggacgn ggggaatttc tcctggggct cagagtgttg tactcgtaaa acaaggatca tcgatgttgt ctacaatgca tctaataacg agctggttcg taccaagacc ctggtgaaga attgcatcgt gctcatngac agcacaccgt accgacagtg ggtaccgaag tcccactatg cncct <210> 295 <211> 216 <212> DNA <213> Homo sapien

120 180 240 278

<td> tcgagcggcc gcccgggcag gtccaccaca ccacgtgcca ggattaccgg ctacatcatc gaagtggtcc ctcggccccg ccctggtgtc ggaaccgaat atacaattta tgtcattgcc</td><td> cccaattcct aagtatgaga acagaggcta ctgaag</td><td> tgctggtatc agcctgggtc ctattactgg</td><td> atggcagccg tcctcccaga cctggaaccg</td><td> 60 120 180 216</td>

<td> &lt;210&gt; 296 &lt;211&gt; 414 &lt;212&gt; DNA &lt;213&gt; Homo sapien</td><td></td><td></td><td></td><td></td>

<td> &lt;220&gt; &lt;221&gt; misc_feature &lt;222&gt; (1). (414) &lt;223&gt; n = A,T,C or G</td><td></td><td></td><td></td><td></td>

<td> &lt;400&gt; 296 agcgtgntcn cggccgagga tggggaagct nnntcttctg attattcttc agggcaanga gnccagtaat agtagcctct gtaacaccag gagacccagg cttctcatac ttgatgatga catgatacca ccaangaatt gggtgtggtg gaattcntgc aagaatatcc atcacacttg gggccccaat ttccccccta ttaggngaag</td><td> cgnctgtctt cataaattgt ggcggggccg agccggtaat gacctgcccg ggcgggccgn ccncatttaa</td><td> tttccttcca atattcggnt agggaccact cctggcacgt ggcgggccgc tcgaaccatg caaattccac</td><td> atcaggggct cccggttcca tctctgggag gggcggctgc tcgaaaancc catcntaaaa ttgg</td><td> 60 120 180 240 300 360 414</td>

<td> &lt;210&gt; 297 &lt;211&gt; 376 &lt;212&gt; DNA &lt;213&gt; Homo sapien</td><td></td><td></td><td></td><td></td>

<td> &lt;220&gt; &lt;221&gt; misc_feature &lt;222&gt; (1).-. (376) &lt;223&gt; n = A,T,C or G</td><td></td><td></td><td></td><td></td>

<td> &lt;400&gt; 297 tcgagcggcc gcccgggcag gtctcgcggt cccggccctc ctggacctcc tggtccccct ttcctgcccc agccacctca agagaaggct gatgccaatg tggttcgtga ccgtgacctc ccagcagaat cgaaaacatt cggaacccaa gcacctggcc gngaacctcc aagaangtgc ntacttggaa ttggac</td><td> cgcactggtg ggtcctccca cacgatggtg gaggtggaca gaagggcaag ccacntcttg</td><td> atgctggtcc gcgctggttt gccgctacta ccaccctcaa cccgcaaaga actgggaaaa</td><td> tgttggtccc cgacttcagc ccgggctgat gagccttgag aaccccgccc aaagggaaaa</td><td> 60 120 180 240 300 360 376</td>

<td> &lt;210&gt;</td><td> 298</td><td></td>

<td> &lt;211&gt;</td><td> 357</td><td></td>

<td> &lt;212&gt;</td><td> DNA</td><td></td>

<td> &lt;213&gt;</td><td> Homo</td><td> sapien</td>

<td> &lt;220&gt;</td><td></td><td></td>

<td> &lt;221&gt;</td><td> mi sc</td><td> _feature</td>

<td> &lt;222&gt;</td><td> (1) .'</td><td> .(357)</td>

<td> &lt;223&gt;</td><td> n =</td><td> A,T,C or G</td>

<400> 298 ctggaatcca gctgatgtac agtctccatg ccagtactct gcggggttct

-.ay'-'-y^ggt tcggtcatgc cagttcttct ttgcagaaga ccactcttcc tgcgggctgc ccacatcggc tctcgccgaa gggccacact ctttgatggc agtcagaagt ccttctgggc agggtcggag ccagacatgc gggctgagtg atccaggttg ggcacatctt tcccggaatg ccctggccgc ctcttgtcct gggtacacgc cagccttggt gaggtcacgg ttctnngaac catactcgaa tggggttctt aggtctcacc tggggtcaat cagggtgcgg ttgctgg

120 180 240 300 357 <210> 299 <211> 307 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (307) <223> n = A,T,C or G <400> agcgtggtcg . gcgrtacaaa catcatggag gagggctaaa ctactacgtt caaggng

299 cggccgaggt ctcctaggag agtggggcca tccatgaagt gacacttgct ccactagagq ggcttgctgt aaggctgcga ttgtggatgg tgtgcgccac tctgtgtgcc gcggagggcc gqttgtggtg cctgatgatc gtgttgctca attgcccagg tgctarggtg tctgggaaac cacagcggag nacangggtg cagagtctct tgctgcggtt tccgaggaca accctgttaa ggctgggcat

120 180 240 300 307 <210> 300 <211> 351 <212> DNA <213> Homo sapien <400> 300 tcgagcggcc gcccgggcag gtctgccaag gagaccctgt tatgctgtgg ggactggctg 60 gggcatggca ggcggctctg gcttcccacc cttctgttct gagatggggg tggtgggcag 120 tatctcatct ttgggttcca caatgctcac gtggtcaggc aggggcttct tagggccaat 180 cttaccagtt gggtcccagg gcagcatgat cttcaccttg atgcccagca caccctgtct 240 gagcaacacg tggcgcacag caagtgtcaa cgtaagtaag ttaacagggt ctccgctgcg 300 gatcatcagg ccatccacaa acttcatgga tttaaccctc tgtcctcgga g 351 <210> 301 <211> 330 <212> DNA <213> Homo sapien <400> 301 tcgagcggcc gcccgggcag gtgtttcaga ggttccaagg tccactgtgg aggtcccagg 60 agtgctggtg gtgggcacag aggtccgatg ggtgaaacca ttgacataga gactgttcct 120 gtccagggtg taggggccca gctctttgat gccattggcc agttggctca gctcccagta 180 cagccgctct ctgttgagtc cagggctttt ggggtcaaga tgatggatgc agatggcatc 240 cactccagtg gctgctccat ccttctcgga cctgagagag gtcagtctgc agccagagta 300 cagagggcca acactggtgt tctttgaata 330 <210> 302 <211> 317 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(317) <223> η = A,T,C or G <400> 302 agcgtggtcg cggccgaggt ctgtactggg agctaagcaa actgaccaat gacattgaag60 agctgggccc ctacaccctg gacaggaaca gtctctatgt caatggtttc acccatcaga120 gctctgtgnc caccaccagc actcctggga cctccacagt ggatttcaga acctcaggga180 ctccatcctc cctctccagc cccacaatta tggctgctgg ccctctcctg gtaccattca240 ccctcaactt caccatcacc aacctgcagt atggggagga catgggtcac cctgnctcca300 ggaagttcaa caccaca <210> 303 <211> 283 <212> DNA <213> Homo sapien <220>

<221> misc_fearure <222> (1)..(283) <223> n = A,T,C or G <400> 303 tcgagcggcc gcccggacag gtctgggcgg atagcaccgg gcatattttg gaatggatga 60 ggtctggcac cctgagcagt ccagcgagga cttggtctta gttgagcaat ttggctagga 120 ggatagtatg cagcacggnt ctgaanctgt gggatagctg ccatgaagta acctgaagga 180 ggtgctggct ggtangggtt gattacaggg ttgggaacag ctcgtacact tgccattctc 240 tgcatatact ggttagtgag gtgagcctgg ccctcttctt ttg 283 <210> 304 <211> 72 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (72) <223> n = A,T,C or G <400> 304 agcgtggtcg cggccgaggt gagccacagg tgaccggggc tgaagctggg gctgctggnc ctgctggtcc tg <210> 305 <211> 245 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(245) <223> n = A,T,C or G <211> 429 <212> DNA <213> Homo sapien <400> 309 agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa 60 ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt 120 gctgatgtac cagttcttct gggccacact gggctgagtg gggtacaccg caggtctcac 180 cagtctccat gttgcagaag actttgatgg catccaggtt gcagccttgg ttggggtcaa 240 tccagtactc tccactcttc cagtcagaag tgggcacatc ttgaggtcac cggcaggtgc 300 cgggccgggg gttcttgcgg cttgccctct gggctccgga tgttctcgat ctgcttggct 360 caggctcttg agggtgggtg tccacctcga ggtcacggto accgaaacct gcccgggcgg 420 cccgctcga 429 <210> 310 <211> 430 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1) . . . (430) <223> n = A, T, C or G <400> 310 tcgagcggtc gcccgggcag gtttcgtgac cgtgacctcg aggtggacac caccctcaag60 agcctgagcc agcagatcga gaacatccgg agcccagaag gcagccgcaa gaaccccgcc120 cgcacctgcc gtgacctcaa gatgtgccac tctgactgga agagtggaga gtactggatt180 gaccccaacc aaggctgcaa cctggatgcc atcaaagtct tctgcaacat ggagactggt240 gagacctgcg tgtaccccac tcagcccagt gtgggcccag aagaaactgg tacatcagca300 aggaacccca aggacaagag gcattgtctt ggttcggcaa anagcatgac ccgatggatt360 ccagtttcga gtattggcgg ccagggcttc ccgaccct־a ccgatgtgga cctcggccgc420 gaccaccgct430 <210> 311 <211> 2996 <212> DNA <213> Homo sapien <400> 311 cagccaccgg agtggatgcc atctgcaccc accgccctga ccccacaggc cctgggctgg 60 acagagagca gctgtatttg gagctgagcc agctgaccca cagcatcact gagctgggcc 120 cctacaccct ggacagggac agtctctatg tcaatggttt cacacagcgg agctctgtgc 180 ccaccactag cattcctggg acccccacag tggacctggg aacatctggg actccagttt 240 ctaaacctgg tccctcggct gccagccctc tcctggtgct attcactctc aacttcacca 300 tcaccaacct gcggtatgag gagaacatgc agcaccctgg ctccaggaag ttcaacacca 360 cggagagggt ccttcagggc ctggtccctg ttcaagagca ccagtgttgg ccctctgtac 420 tctggctgca gactgacttt gctcaggcct gaaaaggatg ggacagccac tggagtggat 480 gccatctgca cccaccaccc tgaccccaaa agccctaggc tggacagaga gcagctgtat 540 tgggagctga gccagctgac ccacaatatc actgagctgg gcccctatgc cctggacaac 600 gacagcctct ttgtcaatgg tttcactcat cggagctctg tgtccaccac cagcactcct 660 gggaccccca cagtgtatct gggagcatct aagactccag cctcgatatt tggcccttca 720 gctgccagcc atctcctgat actattcacc ctcaacttca ccatcactaa cctgcggtat 780 gaggagaaca tgtggcctgg ctccaggaag ttcaacacta cagagagggt ccttcagggc 840 accttgctca cgccctgacc ctgacccaca aatggtttca ccattcacac ggctccctca cagaggagca aagaacggtg ccaggtctgc cggctgggcc ggtccagatg gaagccacaa aatctccagt gtccttcagc ggttgccaac acctgcacct gagctgagtc agcctcttca aatttccaca accctgctga gacacattcc aaggcattgt accctgaatg acagaaatgg ctgaatttca aattaccaga agcatcaaga caccacaccg gttgccatct accctggaca actgggaatt ggactcatca ggagaataca gatctgcaat agaagcttgg ggccagagaa ccacaggccc gcatcactga cccatcggag tgaacttcac agttcaacat gcctgggtgc ctgagacacg ctatcaagca cctactctct agcctcctac cagccatggg attcaccaga acctgctcag tgatctccct accaccctga agctgaccca tcaatggcta ttgtcaactg gggacatcca gcttctgcct tctcctccaa cctcattcca agtcatcagt ccatcaccaa ggaacaaaag gttatttttc gggtggactc atgaggaatt ggagcagtgt ctgaccttcc catgcctgat acgtccagca gactggaact ctggggcaga gaacaccagt agatggggaa tgggctggac gctgggcccc ctctgtaccc catcaacaac cacagacaac acggtacaca ggtggacctc ggtgttccat ggacaaagac aactcccaag gtaccacctg tatgggcaag acccttgttc caggcctgag ccctgtgggc tggtgtcacc tgcaccccag gaacctcagt ggacaaggtc ggtcaccaac tttggacccc ttggctgggc ttatcaacca cctaccatat gaatattgag tgactgtcaa cctgtgtaac tctgcggatg ccttgtggat cttctgggct ctgcggtgtc acagtgccca tgccggtgcc aataaaccat gttggccctc gccaccggag agagagcagc tacacactgg accaccagca ctgcgctaca gtcatgaagc ggctgcaggg ctctgcacct gagctgagcc agcctctacc ccagccacca aagaccctca ggctcagcta cagaagagca aaggatgggg cccgggctgg caactgggct aatttatcaa aatccagacc accacactct ttgacgatgg agcctggtgg tccacctacc acaagcagct tcccaggaca gatgcgctca gtttcaacat ttctcgccac acccggaatg gggtattttc gtcatcctca ctggtgacca ggctactacc tggggtgcct attggtcgga tgtactctgg tggatgccat tgtatttgga acagggacag ccggggtggt tggcggacat acctgctcag tcatcgcact acctgcagcc agcagaccca ttaacggtta cattcctgcc cactcaactt cattcaactc gcatgggccc cagccactgg acatacagca tctatgtcct tccggggcga ccacatcctc acaaaggcag actccgtgtt agcaagtctt agttggtgga ccagcaccca aagcccagcc accaactctt tcaggtctgt tggctcggag gtacccagct ccaacagaaa tcggcttggc cccgccggcg agtcacacct ttcccccagc cacaaaaaaa ctgcaggctg ctgcacccac gctgagccag tctctatgtc cagcgaggag gggccaaccc tcctttgttc aaggtctgtg cctcagcggc tggcatcacc caatgaacct tcctctgtca caccatctcc caccgagggg cttctacttg tgtggacacc gctttactgg ggacagggat gtaccagata agagtacatc tcaactacar ggtcactgtc tctagataag catccatgtg gcacttctac aggcaccacc ccgaaacagc ccccaacagg agtagacaga gcagaacttc tgagccctta aggactcctg gaagaaggaa agacctggag cagggtccaa aaaaaa

900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 2996 <210> 312 <211> 914 <212> PRT <213> Homo sapien <400> 312

Met Ser Met Val Ser His Ser Gly Ala Leu Cys Pro Pro Leu Ala Phe 15 1015

Leu Gly Pro Pro Gin Trp Thr Trp Glu His Leu Gly Leu Gin Phe Leu 20 2530

Asn Leu Val Pro Arg Leu Pro Ala Leu Ser Trp Cys Tyr Ser Leu Ser 35 4045

Thr Ser Pro Ser Pro Thr Cys Gly Met Arg Arg Thr Cys Ser Thr Leu 50 5560

Ala Pro Gly Ser Ser Thr Pro Arg Arg Gly Ser Phe Arg Ala TrpSer

70 7580

Leu Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys ArgLeu

9095

Glu Lys Asp 100

He Cys Thr His His Pro Asp Pro

115120

Gin Leu Tyr Trp Glu Leu Ser Gin

130135

Gly Pro Tyr Ala Leu Asp Asn Asp

145150

His Arg Ser Ser Val Ser Thr Thr 165

Tyr Leu Gly Ala Ser Lys Thr Pro 180

Ala Ser His Leu Leu He Leu Phe

195200

Leu Arg Tyr Glu Glu Asn Met Trp

210215

Thr Glu Arg Val Leu Gin Gly Leu

225230 :

Ser Val Gly Pro Leu Tyr Ser Gly 245

Glu Lys Asp Gly Glu Ala Thr Gly 260

Pro Asp Pro Thr Gly Pro Gly Leu

275280

Leu Ser Gin Leu Thr His Sep He

290295

Asp Arg Asp Ser Leu Tyr Val Asn

305310

Pro Thr Thr Ser Thr Gly Val Val 325

Phe Thr lie Asn Asn Leu Arg Tyr 340

Ser Leu Lys Phe Asn He Thr Asp

355360

Pro Leu Phe Gin Arg Ser Ser Leu

370375

Val He Ala Leu Arg Ser Val Lys

385390

Leu Leu Cys Thr Tyr Leu Gin Pro 405

Lys Gin Val Phe His Glu Leu Ser 420

Leu Gly Pro Tyr Ser Leu Asp Lys

435440

Asn Glu Pro Gly Pro Asp Glu Pro

450455

Thr Phe Leu Pro Pro Leu Ser Glu

465470

Leu Lys Thr Leu Thr Leu Asn Phe 485

Pro Asp Met Gly Lys Gly Ser Ala 500

Leu Gin His Leu Leu Arg Pro Leu

515 520

Phe Tyr Leu Gly Cys Gin Leu lie

Gly Thr Ala Thr Gly Val Asp Ala ¹⁰⁵ HO

Lys Ser Pro Arg Leu Asp Arg Glu 125

Leu Thr His Asn He Thr Glu Leu 140

Ser Leu Phe Val Asn Gly Phe Thr

155160

Ser Thr Pro Gly Thr Pro Thr Val

I⁷⁰175

Ala Ser He Phe Gly Pro Ser Ala

185190

Thr Leu Asn Phe Thr He Thr Asn

Pro Gly Ser Arg Lys Phe Asn Thr 220

Leu Arg Pro Leu Phe Lys Asn Thr

235240

Cys Arg Leu Thr Leu Leu Arg Pro

250255

Val Asp Ala He Cys Thr His Arg

265270

Asp Arg Glu Gin Leu Tyr Leu Glu

Thr Glu Leu Gly Pro Tyr Thr Leu 300

Gly Phe Thr His Arg Ser Ser Val

315320

Glu Glu Pro Phe Thr Leu Asn

330335

Met Ala Asp Met Gly Gin Pro Gly

345350

Asn Val Met Lys His Leu Leu Ser

Gly Ala Arg Tyr Thr Gly Cys Arg 380

Asn Gly Ala Glu Thr Arg Val Asp

395400

Leu Ser Gly Pro Gly Leu Pro He

410415

Gin Gin Thr His Gly He Thr Arg

425430

Asp Ser Leu Tyr Leu Asn Gly Tyr

Pro Thr Thr Pro Lys Pro Ala Thr 460

Ala Thr Thr Ala Met Gly Tyr His

475480

Thr lie Ser Asn Leu Gin Tyr Ser

490495

Thr Phe Asn Ser Thr Glu Gly Val

505510

Phe Gin Lys Ser Ser Met Gly Pro 525

Ser Leu Arg Pro Glu Lys Asp Gly

<td></td><td> 535</td><td> 540</td>

<td> Ala Ala Thr Gly</td><td> ׳ Val Asp Thr Thr</td><td> Cys Thr Tyr His Pro Asp Pro Val</td>

<td> 545</td><td> 550</td><td> 555 560</td>

<td> Gly Pro Gly Leu</td><td> Asp He Gin Gin</td><td> Leu Tyr Trp Glu Leu Ser Gin Leu</td>

<td></td><td> 565</td><td> 570 575</td>

<td> Thr His Gly Val</td><td> Thr Gin Leu Gly</td><td> Phe Tyr Val Leu Asp Arg Asp Ser</td>

<td> 580</td><td></td><td> 585 590</td>

<td> Leu Phe He Asn</td><td> Gly Tyr Ala Pro</td><td> Gin Asn Leu Ser lie Arg Gly Glu</td>

<td> 595</td><td> 600</td><td> 605</td>

<td> Tyr Gin He Asn</td><td> Phe His He Val</td><td> Asn Trp Asn Leu Ser Asn Pro Asp</td>

<td> 610</td><td> 615</td><td> 620</td>

<td> Pro Thr Ser Ser</td><td> Glu Tyr He Thr</td><td> Leu Leu Arg Asp lie Gin'Asp Lys</td>

<td> 625</td><td> 630</td><td> 635 640</td>

<td> Val Thr Thr Leu</td><td> Tyr Lys Gly Ser</td><td> Gin Leu His Asp Thr Phe Arg Phe</td>

<td></td><td> 645</td><td> 650 '655</td>

<td> Cys Leu Val Thr</td><td> Asn Leu Thr Met</td><td> Asp Ser Val Leu Val Thr Val Lys</td>

<td> 660</td><td></td><td> 665 670</td>

<td> Ala Leu Phe Ser</td><td> Ser Asn Leu Asp</td><td> Pro Ser Leu Val Glu Gin Val Phe</td>

<td> 675</td><td> 680</td><td> 685</td>

<td> Leu Asp Lys Thr</td><td> Leu Asn Ala Ser</td><td> Phe His Trp Leu Gly Ser Thr Tvr</td>

<td> 690</td><td> 695</td><td> 700</td>

<td> Gin Leu Val Asp</td><td> He His Val Thr</td><td> Glu Met Glu Ser Ser Val Tyr Gin</td>

<td> 705</td><td> 710</td><td> 715 720.</td>

<td> Pro Thr Ser Ser</td><td> Ser Ser Thr Gin</td><td> His Phe Tyr Leu Asn Phe Thr lie</td>

<td></td><td> 725</td><td> 730 735</td>

<td> Thr Asn Leu Pro</td><td> Tyr Ser Gin Asp</td><td> Lys Ala Gin Pro Gly Thr Thr Asn</td>

<td> 740</td><td></td><td> 745 750</td>

<td> Tyr Gin Arg Asn</td><td> Lys Arg Asn lie</td><td> Glu Asp Ala Leu Asn Gin Leu Phe</td>

<td> 755</td><td> 760</td><td> 765</td>

<td> Arg Asn Ser Ser</td><td> lie Lys Ser Tyr</td><td> Phe Ser Asp Cys Gin Val Ser Thr</td>

<td> 770</td><td> 775</td><td> 780</td>

<td> Phe Arg Ser Val</td><td> Pro Asn Arg His</td><td> His Thr Gly Val Asp Ser Leu Cys</td>

<td> 785</td><td> 790</td><td> 795 800</td>

<td> Asn Phe Ser Pro</td><td> Leu Ala Arg Arg</td><td> Val Asp Arg Val Ala He Tyr Glu</td>

<td></td><td> 805</td><td> 810 815</td>

<td> Glu Phe Leu Arg</td><td> Met Thr Arg Asn</td><td> Gly Thr Gin Leu Gin Asn Phe Thr</td>

<td> 820</td><td></td><td> 825 830</td>

<td> Leu Asp Arg Ser</td><td> Ser Val Leu Val</td><td> Asp Gly Tyr Phe Pro Asn Arg Asn</td>

<td> 835</td><td> 840</td><td> 845</td>

<td> Glu Pro Leu Thr</td><td> Gly Asn Ser Asp</td><td> Leu Pro Phe Trp Ala Val lie Leu</td>

<td> 850</td><td> 855</td><td> 8 60</td>

<td> He Gly Leu Ala</td><td> Gly Leu Leu Gly</td><td> Leu lie Thr Cys Leu He Cys Gly</td>

<td> 865</td><td> • 870</td><td> 875 880</td>

<td> Val Leu Val Thr</td><td> Thr Arg Arg Arg</td><td> Lys Lys Glu Gly Glu Tyr Asn Val</td>

<td></td><td> 885</td><td> 890 895</td>

<td> Gin Gin Gin Cys</td><td> Pro Gly Tyr Tyr</td><td> Gin Ser His Leu Asp Leu Glu Asp</td>

<td> 900</td><td></td><td> 905 910</td>

<td> Leu Gin</td><td></td><td></td>

<210> 313 <211> 656 <212> DNA <213> Homo sapiens acagccagtc ggagctgcaa gtgttctggg tggatcgcgy atatgcactc aaaatgctct 60 ttgtaaagga aagccacaac atgtccaagg gacctgaggc gacttggagg ctgagcaaag 120 tgcagtttgt ctacgactcc tcggagaaaa cccacttcaa agacgcagtc agtgctggga 180 agcacacagc caactcgcac cacctctctg ccttggtcac ccccgctggg aagtcctatg 240 agtgtcaagc tcaacaaacc atttcactgg cctctagtga tccgcagaag acggtcacca 300 tgatcctgtc tgcggtccac atccaacctt ttgacattat ctcagatttt gtcttcagtg360 aagagcataa atgcccagtg gatgagcggg agcaactgga agaaaccttg cccctgattt420 tggggctcat cttgggcctc gtcatcatgg taacactcgc gatttaccac gtccaccaca480 aaatgactgc caaccaggtg cagatccctc gggacagatc ccagtataag cacatgggct540 agaggccgtt aggcaggcac cccctattcc tgctccccca actggatcag gtagaacaac600 aaaagcactt ttccatcttg tacacgagat acaccaacat agctacaatc aaacag656 <210> 314 <211> 519 <212> DNA <213> Homo sapiens <400> 314 ־grgcgtgga ccagtcagct tccgggtgtg actggagcag ggcttgtcgt cttcttcaaa60 gtcactttgc aggggttggt gaagctgctc ccatccatgt acagctccca gtctactgac120 gtttaaggat ggtctcggtg gttaggccca ctagaataaa ctgagtccaa tacctctaca180 cagttatgtt taactgggct ctctgacacc gggaggaagg tggcggggtt taggtgttgc240 aaacttcaat ggttatgcgg ggatgttcac agagcaagct ttggtatcta gctagtctag300 cattcattag ctaatggtgt cctttggtat ttattaaaat caccacagca tagggggact360 ttatgtttag gttttgtcta agagttagct tatctgcttc ttgtgctaac agggctattg420 ctaccaggga ctttggacat gggggccagc gtttggaaac ctcatctagt ttttttgaga480 gataggccac tggccttgga cctcggccgc gaccacgct519 <210> 315 <211> 441 <212> DNA <213> Homo sapiens <400> 315 cacagagcgt ttattgacac caccactcct gaaaattggg atttcttatt aggttcccct60 aaaagttccc atgttgatta cangtaaata gtcacatata tacaatgaag gcagtttctt120 cagaggcaac cagggtttat agtgctaggt aaatgtcatc tcttttgtgc tactgactca180 ttgtcaaacg tctctgcact gttttcagcc tctccacgtt gcctctgtcc tgcttcttag240 ttccttcttt gtgacaaacc aaaagaataa gaggatttag aacaggactg cttttcccct300 atgatttaaa aattccaatg actttcgccc ttgggagaaa tttccaagga aatctctctc360 gctcgctctc tccgttttcc tttgtgagct tctgggggag ggttagtggt gactttttga420 tacgaaaaaa tgcattttgt g441 <210> 316 <211> 247 <212> DNA <213> Homo sapiens <400> 316 tggcgcggct gctggatttc accttcttgc acctgccggt gagcgcctgg ggtctaaagg60 ggcgggatac tccattatgg cccctcgccc tgtagggctg gaatagttag aaaaggcaac120 ccagtctagc ttggtaagaa gagagacatg cccccaacct cggcgccctt tttcctcacg180 atctgctgtc cttacttcag cgactgcagg agcttcacct gcaagaaaac agcattgagc240 tgctgac247 <210> 317 <211> 409 <212> DNA <213> Homo sapiens <400> 317 tgacagggct cctggagttg ttaagtcacc aagtagctgc aggggatgga cactgcccca60 cacgatgtgg gatgaacagc agccttggtt tgtagcccag ggtgtccatg gatttgaccc120 gaatgctccc tggaggccct gtggcgagga caggcactgg atggtccaga ccctctggct180 ggaggagtgg tggagccagg actgggcctt cagecatgag ggetagaata acctgacctc240 ttgeatteta acactgggtc attaatgaca cctttccagt ggatgttgca aaaaccaaca300 ctgtcaggaa cctggccctg ggagggctca ggtgagetea caaggagagg tcaagccaag360 ccaaagggta ggkaacacac aacaccaggg gaaaccagcc cccaaacca409 <210> 318 <211> 320 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1)..(320) <223> ת = A,T,C or G <400> 318 caaggnagat cttaagnggg gtcntatgta agtgtgctcc tggctccagg gttcctggag60 cctcacgagg tcaggggaac ccttgtagaa ctccaccagc agcatcatct cgtgaaggat120 gtcattggtc aggaagetgt cctggacgta ggccatctcc acatccatgg ggatgccata180 gtcactgggc etttgetegg gaggaggcat cacccagaaa ggegagatet tggactcggg240 gcctgggttg ccagaatagt aaggggagca nagcagggcg aggcagggct ggaagccatt300 gctggagccc tgcagccgca320 <210> 319 <211> 212 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1)..(212) <223> n = A,T,C or G <400> 319 tgaagcaata gcgcccccat tttacaggcg gagcatggaa gccagagagg tgggtggggg60 ^a99gg9^tcct tccctggctc aggcagatgg gaagatgagg aagccgctga agaegetgte120 ggcctcagag ccctggtaaa tgtgaccctt tttggggtct ttttcaaccc anacctggtc180 accctgctgc agacctcggc cgcgaccacg et212 <210> 320 <211> 769 <212> DNA <213> Homo sapiens <400> 320 “ל-ס־־. - -- -כ־ד gagatytcag gcaagagtgt cacagcagag ccctaaascc 60 tccaactcac cagtgagaga tgagactgcc cagtactcag ccttcatctc ctgggccacc 120 tggagggcgt ctttctccat cagcgcatac tgagcagggg tactcagatc cttcttggaa 180 cctacaagga agagaagcac actggaaggg tcattctcct tcagggcatc ggccagccac 240 tgcctgccat gggaggtgga aagtaaggga tgagtgagtc tgcagggccc ctcccactga 300 cattcatagg cccaattacc ccctctctgg tcctacatgc attcttcttc ttcctgacca360 cccctctgtt ctgaaccctc tcttcccgga gcctcccatt atattgcagg atgctcactt420 acttggtatg ttccagagat gccacatcat tcaggttgaa gacaatgatg atggcttgga480 agagtggcag aaacagcccc aggttgacag ggaagacact actgctcatt tccccaatcc540 ttccagctcc atatgagaaa gccatgtgca ctctgagacc cacctacccc acttcaccca600 gccccttacc ttgagctcct ctatagtagg ttgatgcaat gcatttgaac ctctcctgcc660 cagcggtatc ccaactggaa ggaaggaaga gtgaagcaca ggtatgtatc ttggggggtg720 tgggtgctgg ggagaaggga tagctggaag gggtgtggaa gcactcaca769 <210> 321 <211> 690 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1)..(690) <223> n = A,T,C or G <400> 321 tgggctgtgg gcggcacctg tgctctgcag gccagacagc gatagaagcc tttgtctgtg60 cctactcccc cggaggcaac tgggaggtca acgggaagac aatcatcccc tataagaagg120 gtgcctggtg ttcgctctgc acagccagtg tctcaggctg cttcaaagcc tgggaccatg180 caggggggct ctgtgaggtc cccaggaatc cttgtcgcat gagctgccag aaccatggac240 gtctcaacat cagcacctgc cactgccact gtccccctgg ctacacgggc agatactgcc300 aagtgaggtg cagcctgcag tgtgtgcacg gccggttccg ggaggaggag tgctcgtgcg360 tctgtgacat cggctacggg ggagcccagt gtgccaccaa ggtgcatttt cccttccaca420 cctgtgacct gaggatcgac ggagactgct tcatggtgtc ttcagaggca gacacctatt480 acagaagcca ggatgaaatg tcaaaggaat ggcggggtgc tggcccagat caagagccag540 aaagtgcagg acatcctcgc cttctatctg ggccgcctgg agaccaccaa cgaggtgact600 gacagtgact ttgagaccag gaacttctgg atngggctca cctacaagac cgccaaggac660 tccrtncgct gggccacagg ggagcaccag690 <210> 322 <211> 104 <212> DNA <213> Homo sapiens <400> 322 gtcgcaagcc ggagcaccac catgtagcct ttcccgaagt accggacctt ctcctcctcc 60 acgcrcacat cacggacatc atggagcagg accaccacct ggtc 104 <210> 323 <211> 118 <212> DNA <213> Homo sapiens <400> 323 gggccctggg cgcttccaaa tgacccagga ggtggtctgc gacgaatgcc ctaatgtcaa 60 actagtgaat gaagaacgaa cactggaagt agaaatagag cctggggtga gagacgga 118 cagcngctcc ctcctctttc tggggccagc cagcaggacc acgct nacggggcct tcctttagca aggaccgacc agcagcccca gngggaccaa ccaggttgac tcaccacgtt gcttcgcccc caacaccgtt cagcagcncc caccagggct ggtcacctgt ttcaccctta ancaggacca tccccgagga ggctcacctc ggccctttgg gcaaatccat ccagcaggac ggccgcgacc <210> 306 <211> 246 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(246) <223> n = A,T,C or G <400> 306 tcgagcggtc gcccgggcag gtccaccggg atagccgggg gtctggcagg aatgggaggc atccagaacg agaaggagac catgcaaagc ctgaacgacc gcctggcctc ttacctggac agagtgagga gcctggagac cganaaccgg aggctggana gcaaaatccg ggagcacttg gagaagaagg gaccccaggt caagagactg gagccattac ttcaagatca tcgagggacc tggagg

120 180 240 246 <210> 307 <211> 333 <212> DNA <213> Homo sapien <220>

<221> misc_feature <222> (1)..(333) <223> n = A,T,C or G <400> 307 agcgnggtcg cggccgaggt ccagctctgt ctcatacttg actctaaagt catcagcagc aagacgggca ttgtcaatct gcagaacgat gcgggcattg tccgcagtat ttgcgaagat ctgagccctc aggtcctcga tgatcttgaa gtaatggctc cagtctctga cctggggtcc cttcttctcc aagtgctccc ggattttgct ctccagcctc cggttctcgg tctccaggct cctcactctg tccaggtaag aaggcccagg cggtcgttca ggctttgcat ggtctccttc tcgttctgga tgcctcccat tcctgccaga ccc <210> 308 <211> 310 <212> DNA <213> Homo sapien <400> 308 tcgagcggcc gcccgggcag gtcaggaagc acattggtct tagagccact gcctcctgga ttccacctgt gctgcggaca tctccaggga gtgcagaagg gaagcaggtc aaactgctca gatcagtcag actggctgtt ctcagttctc acctgagcaa ggtcagtctg cagccagagt acagagggcc aacactggtg ttcttgaaca agggcttgag cagaccctgc agaaccctct tccgtggtgt tgaacttcct ggaaaccagg gtgttgcatg tttttcctca taatgcaagg ttggtgatgg

120 180 240 300 333

120 180 240 300 <210> 324 <211> 354 <212> DNA <213> Homo sapiens <400> 324 tgctctccgg gagcttgaag aagaaactgg ctacaaaggg gacattgccg aatgttctcc60 agcggtctgt atggacccag gcttgtcaaa ctgtactata cacatcgtga cagtcaccat120 taacggagat gatgccgaaa acgcaaggcc gaagccaaag ccaggggatg gagagtttgt180 ggaagtcatt tctttaccca agaatgacct gctgcagaga cttgatgctc tggtagctga240 agaacatctc acagtggacg ccagggtcta ttcctacgct ctagcgctga aacatgcaaa300 tgcaaagcca tttgaagtgc ccttcttgaa attttaagcc caaatatgac actg354 <210> 325 <211> 642 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1)..(642) <223> n = A,T,C or G <400> 325 ncatgcttga atgggctcct ggtgagagat tgccccctgg tggtgaaaca atcgtgtgtg60 cccactgata ccaagaccaa tgaaagagac acagttaagc agcaatccat ctcatttcca120 ggcacttcaa taggtcgctg attggtcctt gcaccagcag tggtagtcgt acctatttca180 gagaggtctg aaattcaggt tcttagtttg ccagggacag gccctacctt atattttttt240 ccatcttcat catccacttc tgcttacagt ttgctgctta caataactta atgatggatt300 gagttatctg ggtggtctct agccatctgg gcagtgtggt tctgtctaac caaagggcat360 tggcctcaaa ccctgcattt ggtttagggg ctaacagagc tcctcagata atcttcacac420 acatgtaact gctggagatc ttattctatt atgaataaga aacgagaagt ttttccaaag480 tgttagtcag gatctgaagg ctgtcattca gataacccag cttttccttt tggcttttag540 cccattcaga ctttgccaga gtcaagccaa ggattgcttt tttgctacag ttttctgcca600 aatggcctag ttcctgagta cctggaaacc agagagaaag ag642 <210> 326 <211> 455 <212> DNA <213> Homo sapiens <400> 326 tccgtgagga tgagcttcga gtccttcacc aggcactgca ggggcacagt cacgtcaatc60 accttcacct tctcgctctt cctgctcttg tcattgacaa acttcccgta ccaggcattg120 acgatgatga ggcccattct ggactcttct gcctcaatta tccttcggac agattcctgc180 atcagccgga cagcggactc cgcctcttgc ttcttctgca gcacatcggt ggcggcgctt240 tccctctgct tctccaattc cttctctttc tgagccctga ggtatggttt gatgatcaga300 cggtgcatgg caaagtagac cactagaggc cccacggtgg catagaacat ggcgctgggc360 agaagctggt ccgtcaagtg aatagggaag aagtatgtct gactggccct gttgagcttg420 actttgagag aaacgccctg tggaactcca acgct455 <210> 327 <211> 321 <212> DNA <400> 327 ttcactgtga actcgcagtc ctcgatgaac tcgcacagat gtgacagccc tgtctccttg 60 ctctctgagt tctcttcaat gatgctgatg argcagtcca cgatagcgcg cttatactca 120 aagccaccct cttcccgcag catggtgaac aggaagttca taaggacggc gtgtttgcga 180 ggatatttct gacacagggc actgatggcc tggacaacca ccaccttgaa ttcatccgag 240 atttctgaca tgaaggagga gatctgcttc atgaggcggt cgatgctgct ctcgctgccc 300 gtcttaagga gggtggtgat g 32!

<210> 328 <211> 476 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1)..(476) <223> n = A,T,C or G <400> 328 tgcaggaggg gccatggggg ctgtgaatgg gatgcagccc catggtgtcc ctgataaatc60 cagtgtgcag tctgatgaag tctgggtggg tgtggtctac gggctggcag ctaccatgat120 ccaagaggta atgcactcct tttcccatct ctccaccatc tgtatcctgg ccmagaaaaa180 cttcccttca aaccaaccaa aatttccttt caaaggcata acccaaatgc catccttggt240 ccggtctaat aaagcctccc ccatttttcc cctggtatgc attcccaggc tccctggcct300 tncagggctt nctgtctgtg ggtcatagtt tatctcctcc cacttgctgg gagctccttg360 aaggcaaaga ctctactgcc tccatctatc cagtggaagt ggctcttcag agggtgccaa420 gttagtatgt atgactgtca tctctcccaa cagggcctga cttggsaggg cttcca476 <210> 329 <211> 340 <212> DNA <213> Homo sapiens <400> 329 cgagggagat tgccagcacc ctgatggaga gtgagatgat ggagatcttg tcagtgctag60 ctaagggtga ccacagccct gtcacaaggg ctgctacagc ctgcctggac aaagcagtgg120 aatatgggct tatccaaccc aaccaagatg gagagtgagg gggttgtccc tgggcccaag180 gctcatgcac acgctaccta ttgtggcacg gagagtaagg acggaagcag ctttggctgg240 tggtggctgg catgcccaat actcttgccc atcctcgctt gctgccctag gatgtcctct300 gttctgagtc agcggccacg ttcagtcaca cagccctgct340 <210> 330 <211> 277 <212> DNA <213> Homo sapiens <400> 330 tgtcaccatc acattggtgc caaataccca gaagacatcg tagatgaaga gtccgcccag60 caggatgcag ccagtgctga cattgttgag gtgcaggagc tctactccat taagggagaa120 ggccaggcca aaaaggttgt tggcaatcca gtgcttcctc agcaggtacc agacgccaac180 gatgctgctc aggcccaggc acaccaggtc cttggtgtca aattcataat tgatgatctc240 ctccttgttt tcccagaacc ctgtgtgaag agcagac277 <211> 136 <212> DNA <213> Homo sapiens <400> 331 ttgcttccca cctcctttct ctgtcctctc ctgaggttct gccttacaat ggggacactg 60 atacaaacca cacacacaat gaggatgaaa acagataaca ggtaaaatga cctcacctgc 120 ccgggcggcc gctcga 136 <210> 332 <211> 184 <212> DNA <213> Homo sapiens <400> 332 ttgtgagata aacgcagata ctgcaatgca ttaaaacgct tgaaatactc atcagggatg60 ttgctgatct tattgttgtc taagtagaga gttagaagag agacagggag accagaaggc120 agtctggcta tctgattgaa gctcaagtca aggtattcga gtgatttaag acctttaaaa180 gcag184 <210> 333 <211> 384 <212> DNA <213> Homo sapiens <400> 333 cggaaaactt cgaggaattg ctcaaagtgc tgggggtgaa tgtgatgctg aggaagattg60 ctgtggctgc agcgtccaag ccagcagtgg agatcaaaca ggagggagac actttctaca120 tcaaaacctc caccaccgtg cgcaccacag agattaactt caaggttggg gaggagtttg180 aggagcagac tgtggatggg aggccctgta agagcctggt gaaatgggag agtgagaata240 aaatggtctg tgagcagaag ctcctgaagg gagagggccc caagacctcg tggaccagag300 aactgaccaa cgatggggaa ctgatcctga ccatgacggc ggatgacgtt gtgtgcacca360 gggtctacgt ccgagagtga gcgg384 <210> 334 <211> 169 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1) . . . (169) <223> n = A,T,C or G <400> 334 cnacaaacag agcagacacc ctggatccgg tcctgctact ggccaggacg gctggaccgt60 aaaattgaat ttccacttcc tgaccgccgc cagaagagat tgattttctc cactatcact120 agcaagatga acctctctga ggaggttgac ttggaagact atgtngccc169 <210> 335 <211> 185 <212> DNA <213> Homo sapiens ccaggtttgc agcccaggct gcacatcagg tgctgactga tggtgctgtg acggatgtgg cgaacctgcc catgtcagtg atcattgtgg agcag <210> 336 <211> 358 <212> DNA <213> Homo sapiens ggactgcctc gcaatacttc atgctgttgc 60 aagccacacg tgaggctgtg gtgcgtgcct 120 gtgtgggtgg tgctgacttt gaggccatgg 180 185 <220>

<221> misc_feature <222> (1)..(358) <223> n = A, T,C or G <400> 336 ctgcccctgc cttacggcgg ccaganacac acccaggatg gcattggccc caaacttgga60 tttgttctca gtcccatcca actccagcat caggttgtcc agtttctctt gctccaccac120 agagagacct gagctgatga gggctggcgc gatggtggag ttgatgtggt ccactgcctt180 caggacacct ttgccraagt aacgctgttt gtctccatcc ctcagctcca gggcctcata240 gatgcccgta gaggctccac tgggcactgc agcccggaaa agacctttgg cagtatagaa300 atccacctcc actgtggggt tcccgcggga gtccaggatc tcccgggccc agatcttc358 <210> 337 <211> 271 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1)..(271) <223> n = A,T,C or G <400> 337 cacaaagcca ccagccnggg aaatcagaat ttacttgatg caactgactt gtaatagcca60 gaaatcctgc ccagcatggg attcagaacc tggtctgcaa ccaaatccac cgtcaaagtt120 catacaggat aaaacaaatt caattgcctt ttccacatta atagcatcaa gcttccccaa180 caaagccaaa gttgccaccg cacaaaaaga gaatcttgtg tcaatttctc cctactttat240 aaaagtagat ttttcacatc ccatgaagca g271 <210> 338 <211> 326 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1). . .(326) <223> n = A,T,C or G <400> 338 ctgtgctccc gactngnnca tctcaggtac caccgactgc actgggcggg gccctctggg60 gggaaaggct ccacggggca gggatacatc tcgaggccag tcatcctctg gaggcagccc120 aatcaggtca aagattttgc ccaactggtc ggcttcagag tttccacaga agagaggctt180 —1 agatacagcc aacactccac atgtccacag gtgttgcata 24 0 tgtggactgc agaagaactt cgggagctcg gtaccagagt gtaacaacca cgggtgtaag 300 tgccatctgg tagctgtaga ttctgg 32g <210> 339 <211> 260 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (1)..(260) <223> n = A,T,C or G <400> 339 ttcacctgag gactcatttc gtgccctttg ttgacttcaa gcaaagncct tcanggtctn 60 caaggacgnc acatttccac ttgcgaatgn nctcanggct catcttgaag aanaagnanc120 ccaagtgctg gatcccagac tcgggggtaa ccttgtgggt aagagctcat ccagtttatg180 ctttaggacg tccanctact cgggggagct ggaagcctgc gtggatgcgg ccctgctgga240 cctcggccgc gaccacgcta260 <210> 340 <211> 220 <212> DNA <213> Homo sapiens <220> <221> misc_feature <222> (1) . . (220) <223> n = A,T,C or G <400> 340 ctggaagccc ggctnggnct ggcagcggaa ggagccaggc aggttcacgc agcggtgctg 60 gcagtagcgg tagcggcact cgtctatgtc cacacactcg ggcccgatct tgcggtaacc120 atcagggcag gtgcactgat aggagccagg caagttatgg cagtcctggc tggggcgaca180 gtcgrgcagg gcctgggcac actcgtccac atccacacag220 <210> 341 <211> 384 <212> DNA <213> Homo sapiens <400> 341 ctgctaccag gggagcgaga gctgactatc ccagcctcgg ctaatgtatt ctacgccatg 60 gatggagctt cacacgattt cctcctgcgg cagcggcgaa ggtcctctac tgctacaccg120 ggcgtcacca gtggcccgtc tgcctcagga actcctccga .gtgagggagg agggggctcc180 tttcccagga tcaaggccac agggaggaag attgcacggg cactgttctg aggaggaagc240 cccgttggct tacagaagtc atggtgttca taccagatgt gggtagccat cctgaatggt300 ggcaattata tcacattgag acagaaattc agaaagggag ccagccaccc tggggcagtg360 aagtgccact ggtttaccag acag384 <210> 342 <211> 245 <212> DNA <213> Homo sapiens <400> 342 ctggctaagc tcatcattgt tactggtggg caccatgtcc ttgaagcttc aggcaagcaa 60 tgtaaccaac aagaatgacc ccaagtccat caactctcga gtcttcattg gaaacctcaa 120 cacagctctg gtgaagaaat cagatgtgga gaccatcttc tctaagtatg gccgtgtggc 180 cggctgttct gtgcacaagg gctatgcctt tgttcagtac tccaatgagc gccatgcccg 240 ggcag 245 <210> 343 <211> 611 <212> DNA <213> Homo sapiens <400> 343 ccaaaaaaat caagatttaa tttttttatt tgcactgaaa aactaatcat aagtgttaat60 tctcagccat ctttgaagct.tgaaagaaga gtctttggta ttttgtaaac gttagcagac120 tttcctgcca gtgtcagaaa atcctattta tgaatcctgt cggtattcct tggtatctga180 aaaaaatacc aaatagtacc atacatgagt tatttctaag tttgaaaaat aaaaagaaat240 tgcatcacac taattacaaa atacaagttc tggaaaaaat atttttcttc attttaaaac300 tttttttaac taataatggc tttgaaagaa gaggcttaat ttgggggtgg taactaaaar360 aaaaagaaat gattgacttg agggtctctg tttggtaaga atacatcatt.agcttaaata420 agcagcagaa ggttagtttt aattatgtag cttctgttaa tattaagtgt tttttgtctg480 ttttacctca atttgaacag ataagtttgc ctgcatgctg gacatgcctc agaaccatga540 atagcccgta ctagatcttg ggaacatgga tcttagagtc ctttggaata agttcttata600 taaatacccc a gjj <210> 344 <211> 311 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1) . . . (311) <223> n = A,T,C or G <400> 344 nctcgaaaaa gcccaagaca gcagaagcag acacctccag tgaactagca aagaaaagca60 aagaagtatt cagaaaagag atgtcccagt tcatcgtcca gtgcctgaac ccttaccgga120 aacctgactg caaagtggga agaattacca caactgaaga ctttaaacat ctggctcgca180 agctgactca cggtgttatg aataaggagc tgaagtactg taagaatcct gaggacctgg240 agtgcaatga gaatgtgaaa cacaaaacca aggantacat taanaagtac atgcannaan300 tttggggctt g <210> 345 <211> 201 <212> DNA <213> Homo sapiens <400> 345 cacacggtca tcccgactgc caacctggag gcccaggccc tgtggaagga gccgggcagc60 aatgtcacca tgagtgtgga tgctgagtgt gtgcccatgg tcagggacct tctcaggtac120 ttctactccc gaaggattga catcaccctg tcgtcagtca agtgcttcca caagctggcc180 tctgcctatg gggccaggca g201 <211> 37U <212> DNA <213> Homo sapiens <400> 346 ctgctccagg tctcttcaga cagaaaggac ctcccggaaa gttggtgaca acatacttgg ggcgctgacg gcgtggtgtg atgttctgga ttgagggaaa ttgctgttgc taaggcaggt aaggagaaga ccttcgtggc gcagcagttt ggcgctggca tattcatcag agacccggcg tattgttctc ctctgcctcc gaggcgggtg gacggggtcg gctctggaag gaagtctggg aaagttctct tccgaggagc atgcgttgga ctctccagct gtgcgttcct gcgtggttca tccaggtctg caggctgtgt agggcagaat tctccaagac gataggtctg ggactacgtc aaaggaacgt <210> 347 <211> 416 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1)..(416) <223> n = A,T,C or G <400> 347 ctgttgtgct gtgtatggac gtgggcttta ccatgagtaa ctccattcct ggtatagaat60 ccccatttga acaagcaaag aaggtgataa ccatgtttgt acagcgacag gtgtttgctg120 agaacaagga tgagattgct ttagtcctgt ttggtacaga tggcactgac aatccccttt180 ctggtgggga tcagtatcag aacatcacag tgcacagaca tctgatgcta ccagattttg240 atttgctgga ggacattgaa agcaaaatcc aaccaggttc tcaacaggct gacttcctgg300 atgcactaat cgtgagcatg gatgtgattc aacatgaaac aataggaaag aagtttggag360 aagaggcata ttgaaatatt cactgacctc aagcagcccg attcagcaaa agtcan416 <210> 348 <211> 351 <212> DNA <213> Homo sapiens <400> 348 gtacaggaga ggatggcagg tgcagagcgg gcactgagct ctgcaggtga aagggctcgg60 cagttggatg ctctcctgga ggctctgaaa ttgaaacggg caggaaatag tctggcagcc120 tctacagcag aagaaacggc aggcagtgcc cagggacgag caggagacag atgccttcct180 cttgtctcaa ctgcaaagag gcgttccttc ctctttcact aatcctcctc agcacagacc240 ctttacgggt gtcaggctgg gggacagtaa ggtctttccc ttcccacaag gccatatctc300 aggctgtctc agtgggggga aaccttggac aatacccggg ctttcttggg c351 <210> 349 <211> 207 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1)..(207) <223> n = A,T,C or G <400> 349 nccgggacat ctccaccctc aacagtggca agaagagcct ggagactgaa cacaaggcct 60 tgaccagtga gattgcactg ctgcagtcca ggctgaagac agagggctct gatctgtgcg 120 acagagtgag cgaaatgcag aagctggatg cacaggtcaa ggagctggtg ctgaagtcgg 180 cggtggaggc tgagcgcctg gtggctg 207 <210> 350 <211> 323 <212> DNA <213> Homo sapiens <400> 350 ccatacaggg ctgttgccca ggccctagag gtcattcctc gtaccctgat ccagaactgt60 ggggccagca ccatccgtct acttacctcc cttcgggcca agcacaccca ggagaactgt120 gagacctggg gtgtaaatgg tgagacgggt actttggtgg acatgaagga actgggcata180 tgggagccat tggctgtgaa gctgcagact tataagacag cagtggagac ggcagttctg240 ctactgcgaa ttgatgacat cgtttcaggc cacgaaaaga aaggcgatga ccagagccgg300 caaggcgggg ctcctgatgc tgg323 <210> 351 <211> 353 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1) . . . (353) <223> n = A,T,C or G <400> 351 cgccgcatcc cntggtccct tccantccct tttcctttnt cngggaacgt gtatgcggtt60 tgtttttgtt ttgtagggtt tttttccttc tccacctctc cctgtctctt ttgctccatg120 ttgtccgttt ctgtggggtt aggtttatgt ttttaatcat ctgaggtcac gtctatttcc180 tccggactcg cctgcttggt ggcgattctc caccggttaa tatggtgcgt cccttttttc240 ttttgttgcg aatctgagcc ttcttcctcc agcttctgcc ttttgaactt tgttcttcgg300 ttctgaaacc atacttttac ctgagtttcc gtgaggctga ggctgtgtgc caa353 <210> 352 <211> 467 <212> DNA <213> Homo sapiens <400> 352 ctgcccacac tgatcacttg cgagatgtcc ttagggtaca agaacaggaa ttgaagtctg60 aatttgagca gaacctgtct gagaaactct ctgaacaaga attacaattt cgtcgtctca120 gtcaagagca agttgacaac tttactctgg atataaatac tgcctatgcc agactcagag180 gaatcgaaca ggctgttcag agccatgcag ttgctgaaga ggaagccaga aaagcccacc240 aactctggct ttcagtggag gcattaaagt acagcatgaa gacctcatct gcagaaacac300 ctactatccc gctgggtagt gcagttgagg ccatcaaagc caactgttct gataatgaat360 tcacccaagc tttaaccgca gctatccctc cagagtccct gacccgtggg gtgtacagtg420 aagagaccct tagagcccgt ttctatgctg ttcaaaaact ggcccga467 <210> 353 <211> 350

ר6\ <213> Homo sapiens <400> 353 ctgctgcagc cacagtagtt cctcccatgg tgggtggccc tcctggtcct gctggcccag60 gaaatctgtc cccaccagga acagcccctg gaaaacggcc ccgtcctcta ccaccttgtg120 gaaatgctgc acgggaactg cctcctggag gaccagcttt accttcccca gacatttgtc180 ctgattgtgt agttttcctg gactgcattt caaattgact caggaactgt ttattgcatg240 gagttacaac aggattctga ccatgaagtt ctcttttagg taacagatcc attaactttt300 ttgaagatgc ttcagatcca acaccaacaa gggcaaaccc ctttgactgg350 <210> 354 <211> 351 <212> DNA <213׳> Homo sapiens <400> 354 atttagatga gatctgaggc atggagacat ggagacagta tacagactcc tagatttaag60 ttttaggttt tttgcttttc taatcaccaa ttcttatata caatgtatat tttagactcg120 agcagatgat catcttcatc ttaagtcatt ccttttgact gagtatggca ggattagagg180 gaatggcagt atagatcaat gtctttttct gtaaagtata ggaaaaacca gagaggaaaa240 aaagagctga caattggaag gtagtagaaa attgacgata atttcttctt aacaaataat300 agttgtatat acaaggaggc tagtcaacca gattttattt gttgagggcg a351 <210> 355 <211> 308 <212> DNA <213> Homo sapiens <400> 355 ttttggcgca agttttacag attttattaa agtcgaagct attggtcttg gaagatgaaa60 atgcaaatgt tgatgaggtg gaattgaagc cagatacctt aataaaatta tatcttggtt120 ataaaaataa gaaattaagg gttaacatca atgtgccaat gaaaaccgaa cagaagcagg180 aacaagaaac cacacacaaa aacatcgagg aagaccgcaa actactgatt caggcggcca240 tcgtgagaat catgaagatg aggaaggttc tgaaacacca gcagttactt ggcgaggtcc300 tcactcag3 <210> 356 <211> 207 <212> DNA <213> Homo sapiens <400> 356 ctgtcccaag tgctcccaga aggcaggatt ctgaagacca ctccagcgat atgttcaact 60 atgaagaata ctgcaccgcc aacgcagtca ctgggccttg ccgtgcatcc ttcccacgct 120 ggtactttga cgtggagagg aactcctgca ataacttcat ctatggaggc tgccggggca 180 ataagaacag ctaccgctct gaggagg 207 <210> 357 <211> 188 <212> DNA <213> Homo sapiens <220>

<221> miso feature <222> (1)..(188) <223> n = A,T,C or G <400> 357 tcgaccacgc cctcgtagcg catgngctnc aggacgatgc tcagagtgat gaacaccccg60 gtgcggccca cgccagcact gcagtgcacc gtgataggcc catcctgtcc aaactgctcc120 ttggtcttat gcacctgccc gatgaagtca atgaatccct cgcctgtctt gggcacgccc180 tgctctgg1g8 <210> 358 <211> 291 <212> DNA <213> Homo sapiens <400> 358 ctgggagcat cggcaagcta ctgccttaaa atccgatctc cccgagtgca caatttctgt60 cccttttaag ggttcacaac actaaagatt tcacatgaaa gggttgtgat tgatttgagc120 aggcaggcgg tacgtgacag gggctgcatg caccggtggt cagagagaaa cagaacaggg180 cagggaattt cacaatgttc ttctatacaa tggctggaat ctatgaataa catcagtttc240 taagttatgg gttgattttt aactactggg tttaggccag gcaggcccag g291 <210> 359 <211> 117 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1) . . . (117) <223> n = A,T,C or G <400> 359 gccaccacac tccagcctgg gcaatacagc aagactgtct caaaaaaaaa aaaaaaaaaa 60 cccaaaaaaa ctcaaaaang taatgaatga tacccaangn gccttttcta gaaaaag 117 <210> 360 <211> 394 <212> DNA <213> Homo sapiens <400> 360 ctgttcctct ggggtggtcc agttctagag tgggagaaag ggagtcaggc gcattgggaa60 tcgtggttcc agtctggttg cagaatctgc acatttgcca agaaattttc cctgtttgga120 aagtttgccc cagctttccc gggcacacca ccttttgtcc caagtgtctg ccggtcgacc180 aatctgcctg ccacacattg accaagccag acccggttca cccagctcga ggatcccagg240 ttgaagagtg gccccttgag gccctggaaa gaccaatcac tggacttctt cccttgagag300 tcagaggtca cccgtgattc tgcctgcacc ttatcattga tctgcagtga tttctgcaaa360 tcaagagaaa ctctgcaggg cactcccctg tttc394 <210> 361 <211> 394 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1)..(394) <223> n ־ A,T,C or G <400> 361 ctgggcggat agcaccgggc atattttntt natggatgag gtctggcacc ctgagcagtc60 cagcgaggac ttggtcttag ttgagcaatt tggctaggag gatagtatgc agcacggttc120 tgagtctgtg ggatagctgc catgaagtaa cctgaaggag gtgctggctg gtaggggttg180 attacagggt tgggaacagc tcgtacactt gccattctct gcatatactg gttagtgagg240 tgagcctggc gctcttcttt gcgctgagct aaagctacat acaatggctt tgtggacctc300 ggccgcgacc acgctaagcc gaattccagc acactggcgg ccgttactag tggatccgag360 ctcggtacca agcttggcgt aatcatggtc atag394 <210> 362 <211> 268 <212> DNA <213> Homo sapiens <400> 362 ctgcgcgtgg accagtcagc ttccgggtgt gactggagca gggcttgtcg tcttcttcag60 agtcactttg caggggttgg tgaagctgct cccatccatg tacagctccc agtctactga120 tgtttaagga tggtctcggt ggttaggccc actagaataa actgagtcca atacctctac180 acagttatgt ttaactgggc tctctgacac cgggaggaag gtggcggggt ttaggtgttg240 caaacttcaa tggttatgcg gggatgtt268 <210> 363 <211> 323 <212> DNA <213> Homo sapiens <400> 363 ccttgacctt ttcagcaagt gggaaggtgt aatccgtctc cacagacaag gccaggactc60 gtttgtaccc gttgatgata gaatggggta ctgatgcaac agttgggtag ccaatctgca120 gacagacact ggcaacattg cggacaccct ccaggaagcg agaatgcaga gtttcctctg180 tgatatcaag cacttcaggg ttgtagatgc tgccattgtc gaacacctgc tggatgacca240 gcccaaagga gaagggggag atgttgagca tgttcagcag cgtggcttcg ctggctccca300

<td> ctttgtctcc</td><td> agtcttgatc aga</td><td> 323</td>

<td> &lt;210&gt; 364 &lt;211&gt; 393 &lt;212&gt; DNA &lt;213&gt; Homo</td><td> sapiens</td><td></td>

<td> &lt;220&gt; &lt;221&gt; misc_</td><td> feature</td><td></td>

<td> &lt;222&gt; (1).7</td><td> ’.(393)</td><td></td>

<223> n = A,T,C or G <400> 364 ccaagctctc catcgtcccc gtgcgcagng gctactgggg gaacaagatc ggcaagcccc60 acactgtccc ttgcaaggtg acaggccgct gcggctctgt gctggtacgc ctcatcactg120 cacccagggg cactggcatc gtctccgcac ctgtgcctaa gaagctgctc atgatggctg180 gcatcgatga.ctgctacacc tcagcccggg gctgcactgc caccctgggc aacttcgcca 240 aggccacctt tgatgccatt tctaagacct acagctacct gacccccgac ctctggaagg300 agactgtatt caccaagtct ccctatcagg agttcactga ccacctcgtc aagacccaca360 ccagagtctc cgtgcagcgg actcaggctc cag 393 <210> 365 <211> 371 <212> DNA <213> Homo sapiens <400> 365 cctcctcaga gcggtagctg ttcttattgc cccggcagcc tccatagatg aagttattgc60 aggagttcct ctccacgtca aagtaccagc gtgggaagga tgcacggcaa ggcccagtga120 ctgcgttggc ggtgcagtat tcttcatagt tgaacatatc gctggagtgg tcttcagaat180 cctgccttct gggagcactt gggacagagg aatccgctgc attcctgctg gtggacctcg240 gccgcgacca cgctaagccg aattccagca cactggcggc cgttactagt ggatccgagc300 tcggtaccaa gcttggcgta atcatggtca tagctgtttc ctgtgtgaaa ttgttatccg360 ctcacaattc c371 <210> 366 <211> 393 <212> DNA <213> Homo sapiens <400> 366 atttcttgcc agatgggagc tctttggtga agactccttt cgggaaaagt tttttggctt60 cttcttcagg gatggttgga aggaccatca cactatcccc atccttccaa tcaactgggg120 tggcaaccct tttttctgct gtcagctgga gagagatgac taccctgaga atctcatcaa180 agttcctgcc agtggtagct gggtagagga tagacagctt cagcttctta tcaggaccaa240 aaacaaacac cacacgagct gccacaggca tgcccttttc atccttctct gctggatcca300 gcatgcccaa caggatggca agctcccgat tcctatcatc gatgatggga aaaggtaact360 tttctgtggg ctcttcacaa ttgtaagcat tga393 <210> 367 <211> 327 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1)..(327) <223> n = A,T,C or G <400> 367 ccagctctgt ctcatacttg actctaaagt cttnagcagc aagacgggca ttgnnaatct60 gcagaacgat gcgggcattg tccacagtat ttgcgaagat ctgagccctc aggtcctcga120 tgatcttgaa gtaatggctc cagtctctga cctggggtcc cttcttctcc aagtgctccc180 ggattttgct ctccagcctc cggttctcgg tctccaggct cctcactctg tccaggtaag240 aggccaggcg gtcgttcagg ctttgcatgg tctccttctc gttctggatg cctcccattc300

<td> ctgccagacc</td><td> cccggctatc ccggtgg</td><td> 327</td>

<td> &lt;210&gt; 368</td><td></td><td></td>

<td> &lt;211&gt; 306</td><td></td><td></td>

<td> &lt;212? DNA</td><td></td><td></td>

<td> &lt;213&gt; Homo</td><td> sapiens</td><td></td>

<220>

<221> misc feature <222> (1)..(306) <223> n = A,T,C or G <400> 368 ctggagaagg acttcagcag tttnaagaag tactgccaag tcatccgtgt cattgcccac60 acccagatgc gcctgcttcc tctgcgccag aagaaggccc acctgatgga gatccaggtg120 aacggaggca ctgtggccga gaagctggac tgggcccgcg agaggcttga gcagcaggta180 cctgtgaacc aagtgtttgg gcaggatgag atgatcgacg tcatcggggt gaccaagggc240 aaaggctaca aaggggtcac cagtcgttgg cacaccaaga agctgccccg caagacccac300 cgagga <210> 369 <211> 394 <212> DNA <213> Homo sapiens <400> 369 tcgacccaca ccggaacacg gagagctggg ccagcattgg cacttgatag gatttcccgt60 cggctgccac gaaagtgcgt ttctttgtgt tctcgggttg gaaccgtgat ttccacagac120 ccttgaaata cactgcgttg acgaggacca gtctggtgag cacaccatca ataagatctg180 gggacagcag attgtcaatc atatccctgg tttcattttt aacccatgca ttgatggaat240 cacaggcaga ggctggatcc tcaaagttca cattccggac ctcacactgg aacacatctt300 tgttccttgt aacaaaaggc acttcaattt cagaggcatt cttaacaaac acggcgttag360 ccactgtcac aatgtcttta ttcttcttgg agac394 <210> 370 <211> 653 <212> DNA <213> Homo sapiens <400> 370 ccaccacacc caattccttg ctggtatcat ggcagccgcc acgtgccagg attaccggct60 acatcatcaa gtatgagaag cctgggtctc ctcccagaga agtggtccct cggccccgcc120 ctggtgtcac agaggctact attactggcc tggaaccggg aaccgaatat acaatttatg180 tcattgccct gaagaataat cagaagagcg agcccctgat tggaaggaaa aagacagacg240 agcttcccca actggtaacc cttccacacc ccaatcttca tggaccagag atcttggatg300 ttccttccac agttcaaaag acccctttcg tcacccaccc tgggtatgac actggaaatg360 gtattcagct tcctggcact tctggtcagc aacccagtgt tggg'caacaa atgatctttg420 aggaacatgg ttttaggcgg accacaccgc ccacaacggc cacccccata aggcataggc480 caagaccata cccgccgaat gtaggacaag aagctctctc tcagacaacc atctcatggg540 ccccattcca ggacacttct gagtacatca tttcatgtca tcctgttggc actgatgaag600 aacccttaca gttcagggtt cctggaactt ctaccagtgc cactctgaca gga653 <210> 371 <211> 268 <212> DNA <213> Homo sapiens <400> 371 ctgcccagcc cccattggcg agtttgagaa ggtgtgcagc aatgacaaca agaccttcga60 ctcttcctgc cacttctttg ccacaaagtg caccctggag ggcaccaaga agggccacaa120 gctccacctg gactacatcg ggccttgcaa atacatcccc ccttgcctgg actctgagct180 gaccgaattc cccctgcgca tacgggactg gctcaagaac gtcctggtca ccctgtatga240 gagggatgag gacaacaacc ttctgact268 <210> 372 <211> 392 <212> DNA <213> Homo sapiens <400> 372 gctggtgccc ctggtgaacg tggacctcct ggattggcag gggccccagg acttagaggt60 ggaactggtc cccctggtcc cgaaggagga aagggtgctg ctggtcctcc tgggccacct120 ggtgctgctg gtactcctgg tctgcaagga atgcctggag aaagaggagg tcttggaagt180 cctggtccaa agggtgacaa gggtgaacca ggcggtccag gtgctgatgg tgtcccaggg240 aaagatggcc caaggggtcc tactggtcct attggtcctc ctggcccagc tggccagcct300 ggagataagg gtgaaggtgg tgcccccgga cttccaggta tagctggacc tcgtggtagc360 cctggtgaga gaggtgaaac ctcggccgcg ac392 <210> 373 <211> 388 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1) . . .(388) <223> n = A, T,C or G <400> 373 ccaagcgctc agatcggcaa ggggcaccan ttttgatctg cccagtgcac agccccacaa60 ccaggtcagc gatgaaggta tcttcagtct cccccgaacg atgagacacc atgacgcccc120 aaccattggc ctgggccagc ttgcacgcct gaagagactc ggtcacggag ccaatctggt180 tgactttgag caggaggcag ttgcaggact tctcgttcac ggccttggcg atcctctttg240 ggttggtcac tgtgagatca tcccccacta cctggattcc tgcactggct gtgaacttct300 gccaagctcc ccagtcatcc tggtcaaagg gatcttcgat agacaccact gggtagtcct360 tgatgaagga cttgtacagg tcagccag388 <210> 374 <211> 393 <212> DNA <213> Homo sapiens <400> 374 ctgacgaccg cgtgaacccc tgcattgggg gtgtcatcct cttccatgag acactctacc60 agaaggcgga tgatgggcgt cccttccccc aagttatcaa atccaagggc ggtgttgtgg120 gcatcaaggt agacaagggc gtggtccccc tggcagggac aaatggcgag actaccaccc180 aagggttgga tgggctgtct gagcgctgtg cccagtacaa gaaggacgga gctgacttcg240 ccaagtggcg ttgtgtgctg aagattgggg aacacacccc ctcagccctc gccatcatgg300 aaaatgccaa tgttctggcc cgttatgcca gtatctgcca gcagaatggc attgtgccca360 tcgtggagcc tgagatcctc cctgatgggg acc393 <210>

<211>

<212>

<213>

DNA

Homo sapiens <220>

<221>

<222>

misc (1) . (394) feature <223> η = A,T,C or G <400> 375 ccacaaatgg cgtggtccat gtcatcaccn ttnttctgca gcctccagcc aacagacctc60 aggaaagagg ggatgaactt gcagactctg cgcttgagat cttcaaacaa gcatcagcgt120 tttccagggc ttcccagagg tctgtgcgac tagcccctgt ctatcaaaag ttattagaga180 ggatgaagca ttagcttgaa gcactacagg aggaatgcac cacggcagct ctccgccaat240 ttctctcaga tttccacaga gactgtttga atgttttcaa aaccaagtat cacactttaa300 tgtacatggg ccgcaccata atgagatgtg agccttgtgc atgtggggga ggagggagag360 agatgtactt tttaaatcat gttcccccta aaca394 <210> 376 <211> 392 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1) . . . (392) <223> n = A, T,C or G <400> 376 ctgcccagcc cccattggcg agtttgattn ggtgtgcagc aatgacaaca agaccttcga60 ctcttcctgc cacttctttg ccacaaagtg caccctggag ggcaccaaga agggccacaa120 gctccacctg gactacatcg ggccttgcaa atacatcccc ccttgcctgg actctgagct180 gaccgaattc cccctgcgca tgcgggactg gctcaagaac gtcctggtca ccctgtatga240 gagggatgag gacaacaacc ttctgactga gaagcagaag ctgcgggtga agaagatcca300 tgagaatgag aagcgcctgg aggcaggaga ccaccccgtg gagctgctgg cccgggactt360 cgagaagaac tataacatgt acatcttccc tg392 <210> 377 <211> 292 <212> DNA <213> Homo sapiens <400> 377 caatgtttga cgcttaaccc ccccaatttc tgtgagatgg atggccagtg caagcgtgac60 ttgaagtgtt gcatgggcat gtgtgggaaa tcctgcgttt cccctgtgaa agcttgattc120 ctgccatatg gaggaggctc tggagtcctg ctctgtgtgg tccaggtcct ttccaccctg180 agacttggct ccaccactga tatcctcctt tggggaaagg cttggcacac agcaggcttt240 caagaagtgc cagttgatca atgaataaat aaacgagcct atttctcttt gc292 <210> 378 <211> 395 <212> DNA <213> Homo sapiens <400> 378 ctgctgcttc agcgaagggt ttctggcata tccaatgata aggctgccaa agactgttcc60 aataccagca ccagaaccag ccactcctac tgttgcagca cctgcaccaa taaatttggc120 agcagtatca atgtctctgc tgattgcact ggtctgaaac tccctttgga ttagctgaga180 cacaccattc tgggccctga ttttcctaag atagaactcc aactctttgc cctctagcac240 atagccatct.gctcggccac actgtcccgg ccttgaagcg atgcacgcaa gaagcttgcc 300 ctgctggaac tgctcctcca ggagactgct gattttggca ttctttttcc tttcatcata 360 tttcttctga attttttaga tcgttttttg tttaa395 <210> 379 <211> 223 <212> DNA <213> Homo sapiens <400> 379 ccagatgaaa tgctgccgca atggctgtgg gaaggtgtcc tgtgtcactc ccaatttctg60 agctccagcc accaccaggc tgagcagtga ggagagaaag tttctgcctg gccctgcatc120 tggttccagc ccacctgccc tccccttttt cgggactctg tattccctct tgggctgacc180 acagcttctc cctttcccaa ccaataaagt aaccactttc ago223 <210> 380 <211> 317 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1) . . .(317) <223> n = A,T,C or G <400> 380 tcgaccacag tattccaacc ctcctgtgcn tngagaagtg atggagggtg ctgacaacca60 gggtgcagga gaacaaggta gaccagtgag gcagaatatg tatcggggat atagaccacg120 attccgcagg ggccctcctc gccaaagaca gcctagagag gacggcaatg aagaagataa180 agaaaatcaa ggagatgaga cccaaggtca gcagccacct caacgtcggt accgccgcaa240 cttcaattac cgacgcagac gcccagaaaa ccctaaacca caagatggca aagagacaaa300 agcagccgat ccaccag317 <210> 381 <211> 392 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1)..(392) <223> n = A,T,C or G <400> 381 cctgaaggaa gagctggcct acctgaatnn naaccatgag gaggaaatca gtacgctgag60 gggccaagtg ggaggccagg tcagtgtgga ggtggattcc gctccgggca ccgatctcgc120 caagatcctg agtgacatgc gaagccaata tgaggtcatg gccgagcaga accggaagga180 tgctgaagcc tggttcacca gccggactga agaattgaac cgggaggtcg ctggccacac240 ggagcagctc cagatgagca ggtccgaggt tactgacctg cggcgcaccc ttcagggtct300 tgagattgag ctgcagtcac agacctcggc cgcgaccacg ctaagccgaa ttccagcaca360 ctggcggccg ttactagtgg atccgagctc gg392 <210> 382 <211> 234 <212> DNA <213> Homo, sapiens <400> 382 cctcgatgtc taaatgagcg tggtaaagga tggtgcctgc tggggtctcg tagatacctc 60 gggacttcat tccaatgaag cggttctcca cgatgtcaat acggcccacg ccatgcttgc 120 ccgcgacttc gttcaggtac atgaagagct ccaaggaggt ctggtgggtg gtgccatcct 180 tgacgttggt caccttcaca gggacccctt ttttgaactc catctccaga atgt 234 <210> 383 <211> 396 <212> DNA <213> Homo sapiens <220>

<221> misc_feature <222> (1) . . . (396) <223> n = A,T,C or G <400> 383 ccttgacctt ttcagcaagt gggaaggtgt tttccgtctc cacagacaag gccaggactc60 gtttgnaccc gttgatgata gaatggggta ctgatgcaac agttgggtag ccaatctgca120 gacagacact ggcaacattg cggacaccca ggatttcaat ggtgcccctg gagattttag180 tggtgatacc taaagcctgg aaaaaggagg tcttctcggg cccgagacca gtgttctggg240 ctggcacagt gacttcacat ggggcaatgg caccagcacg ggcagcagac ctgcccgggc300 ggccgctcga aagccgaatt ccagcacact ggcggccgrt actagtggat ccgagctcgg360 taccaagctt ggcgtaatca tggtcatagc tgtttc396 <210> 384 <211> 396 <212> DNA <213> Homo sapiens <400> 384 gctgaatagg cacagagggc acctgtacac cttcagacca gtctgcaacc tcaggctgag60 tagcagtgaa ctcaggagcg ggagcagtcc attcaccctg aaattcctcc ttggtcactg120 ccttctcagc agcagcctgc tcttcttttt caatctcttc aggatctctg tagaagtaca180 gatcaggcat gacctcccat gggtgttcac gggaaatggt accacgcatg cgcagaactt240 cccgagccag catccaccac atcaaaccca ctgagtgagc tcccttgttg ttgcatggaa300 tggcaatgtc cacatagcgc agaggagaat ctgtgttaca cagcgcaatg gtaggtaggt360 taacataaga tgcctccgtg agaggctggt ggtcag396 <210> 385 <211> 2943 <212> DNA <213> Homo sapiens <400> 385 cagccaccgg agtggatgcc atctgcaccc accgccctga ccccacaggc cctgggctgg60 acagagagca gctgtatttg gagctgagcc agctgaccca cagcatcact gagctgggcc120 cctacaccct ggacagggac agtctctatg tcaatggttt cacacagcgg agctctgtgc180 ccaccactag cattcctggg acccccacag tggacctggg aacatctggg actccagttt240 ctaaacctgg tccctcggct gccagccctc tcctggtgct attcactctc aacttcacca300 tcaccaacct gcggtatgag gagaacatgc agcaccctgg ctccaggaag ttcaacacca360 cggagagggt ccttcagggc ctggtccctg ttcaagagca ccagtgttgg ccctctgtac420 tctggctgca gactgacttt gctcaggcct gaaaaggatg ggacagccac tggagtggat480 gccatctgca cccaccaccc tgaccccaaa agccctaggc tggacagaga gcagctgtat540 tgggagctga gccagctgac ccacaatatc actgagctgg gcccctatgc cctggacaac600 gacagcctct ttgtcaatgg tttcactcat cggagctctg tgtccaccac cagcactcct660 gggaccccca cagtgtatct gggagcatct aagactccag cctcgatatt tggcccttca 720 gctgccagcc atctcctgat actattcacc ctcaacttca ccatcactaa cctgcggtat 780 gaggagaaca tgtggcctgg ctccaggaag ttcaacacta cagagagggt ccttcagggc 840 ctgctaaggc ccttgttcaa gaacaccagt gttggccctc tgtactctgg ctgcaggctg 900 accttgctca ggccagagaa agatggggaa gccaccggag tggatgccat ctgcacccac 960 cgccctgacc ccacaggccc tgggctggac agagagcagc tgtatttgga gctgagccag1020 ctgacccaca gcatcactga gctgggcccc tacacactgg acagggacag tctctatgtc1080 aatggtttca cccatcggag ctctgtaccc accaccagca ccggggtggt cagcgaggag1140 ccattcacac tgaacttcac catcaacaac ctgcgctaca tggcggacat gggccaaccc1200 ggctccctca agttcaacat cacagacaac gtcatgaagc acctgctcag tcctttgttc1260 cagaggagca gcctgggtgc acggtacaca ggctgcaggg tcatcgcact aaggtctgtg1320 aagaacggtg ctgagacacg ggtggacctc ctctgcacct acctgcagcc cctcagcggc1380 ccaggtctgc ctatcaagca ggtgttccat gagctgagcc agcagaccca tggcatcacc1440 cggctgggcc cctactctct ggacaaagac agcctctacc ttaacggtta caatgaacct1500 ggtccagatg agcctcctac aactcccaag ccagccacca cattcctgcc tcctctgtca1560 gaagccacaa cagccatggg gtaccacctg aagaccctca cactcaactt caccatctcc1620 aatctccagt attcaccaga tatgggcaag ggctcagcta cattcaactc caccgagggg1680 gtccttcagc acctgctcag acccttgttc cagaagagca gcatgggccc cttctacttg1740 ggttgccaac tgatctccct caggcctgag aaggatgggg cagccactgg tgtggacacc1800 acctgcacct accaccctga ccctgtgggc cccgggctgg acatacagca gctttactgg1860 gagctgagtc agctgaccca tggtgtcacc caactgggct tctatgtcct ggacagggat1920 agcctcttca tcaatggcta tgcaccccag aatttatcaa tccggggcga gtaccagata1980 aatttccaca ttgtcaactg gaacctcagt aatccagacc ccacatcctc agagtacatc2040 accctgctga gggacatcca ggacaaggtc accacactct acaaaggcag tcaactacat2100 gacacattcc gcttctgcct ggtcaccaac ttgacgatgg actccgtgtt ggtcactgtc2160 aaggcattgt tctcctccaa tttggacccc agcctggtgg agcaagtctt tctagataag2220 accctgaatg cctcattcca ttggctgggc tccacctacc agttggtgga catccatgtg2280 acagaaatgg agtcatcagt ttatcaacca acaagcagct ccagcaccca gcacttctac2340 ctgaatttca ccatcaccaa cctaccatat tcccaggaca aagcccagcc aggcaccacc2400 aattaccaga ggaacaaaag gaatattgag gatgcggcac cacaccgggg tggactccct2460 gtgtaacttc tcgccactgg ctcggagagt agacagagtt gccatctatg aggaatttct2520 gcggatgacc cggaatggta cccagctgca gaacttcacc ctggacagga gcagtgtcct2580 tgtggatggg tattttccca acagaaatga gcccttaact gggaattctg accttccctt2640 ctgggctgtc atcctcatcg gcttggcagg actcctggga ctcatcacat gcctgatctg2700 cggtgtcctg gtgaccaccc gccggcggaa gaaggaagga gaatacaacg tccagcaaca2760 gtgcccaggc tactaccagt cacacctaga cctggaggat ctgcaatgac tggaacttgc2820 cggtgcctgg ggtgcctttc ccccagccag ggtccaaaga agcttggctg gggcagaaat2880 aaaccatatt ggtcggaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa2940 aaa2943 <210> 386 <211> 2608 <212> DNA <213> Homo sapiens <400> 386 gttcaagagc accagtgttg gccctctgta ctctggctgc agactgactt tgctcaggcc60 tgaaaaggat gggacagcca ctggagtgga tgccatctgc acccaccacc ctgaccccaa120 aagccctagg ctggacagag agcagctgta ttgggagctg agccagctga cccacaatat180 cactgagctg ggcccctatg ccctggacaa cgacagcctc tttgtcaatg gtttcactca240 tcggagctct gtgtccacca ccagcactcc tgggaccccc acagtgtatc tgggagcatc300 taagactcca gcctcgatat ttggcccttc agctgccagc catctcctga tactattcac360 cctcaacttc.accatcacta acctgcggta tgaggagaac atgtggcctg gctccaggaa 420 gttcaacact acagagaggg tccttcaggg cctgctaagg cccttgttca agaacaccag480 tgttggccct ctgtactctg gctgcaggct gaccttgctc aggccagaga aagatgggga540 agccaccgga gtggatgcca tctgcaccca ccgccctgac cccacaggcc ctgggctgga 600 cagagagcag ctgtatttgg agctgagcca gctgacccac agcatcactg agctgggccc 660 ctacacactg gacagggaca gtctctatgt caatggtttc acccatcgga gctctgtacc 720 caccaccagc accggggtgg tcagcgagga gccattcaca ctgaacttca ccatcaacaa 780 cctgcgctac atggcggaca tgggccaacc cggctccctc aagttcaaca tcacagacaa 840 cgtcatgaag cacctgctca gtcctttgtt ccagaggagc agcctgggtg cacggtacac900 aggctgcagg gtcatcgcac taaggtctgt gaagaacggt gctgagacac gggtggacct960 cctctgcacc tacctgcagc ccctcagcgg cccaggtctg cctatcaagc aggtgttcca1020 tgagctgagc cagcagaccc atggcatcac ccggctgggc ccctactctc tggacaaaga1080 cagcctctac cttaacggtt acaatgaacc tggtccagat gagcctccta caactcccaa1140 gccagccacc acattcctgc ctcctctgtc agaagccaca acagccatgg ggtaccacct1200 gaagaccctc acactcaact tcaccatctc caatctccag tattcaccag atatgggcaa1260 gggctcagct acattcaact ccaccgaggg ggtccttcag cacctgctca gacccttgtt1320 ccagaagagc agcatgggcc ccttctactt gggttgccaa ctgatctccc tcaggcctga1380 gaaggatggg gcagccactg gtgtggacac cacctgcacc taccaccctg accctgtggg1440 ccccgggctg gacatacagc agctttactg ggagctgagt cagctgaccc atggtgtcac1500 ccaactgggc ttctatgtcc tggacaggga tagcctcttc atcaatggct atgcacccca1560 gaatttatca atccggggcg agtaccagat aaatttccac attgtcaact ggaacctcag1620 taatccagac cccacatcct cagagtacat caccctgcta agggacatcc aggacaaggt1680 caccacactc tacaaaggca gtcaactaca tgacacattc cgcttctgcc tggtcaccaa1740 ״ttgacgatg gactccgtgc tggtcactgt caaggcattg ttctcctcca atttggaccc1800 cagcctggtg gagcaagtct ttctagataa gaccctgaat gcctcattcc attggctaggI860 ctccacctac cagttggtgg acatccatgt gacagaaatg gagtcatcag tttatcaacc1920 aacaagcagc tccagcaccc agcacttcta cctgaatttc accatcacca acctaccata1980 ttcccaggac aaagcccagc caggcaccac caattaccag aggaacaaaa ggaatattga2040 ggatgcgctc aaccaactct tccgaaacag cagcatcaag agttattttt ctgactgtca2100 agtttcaaca ttcaggtctg tccccaacag gcaccacacc ggggtggact ccctgtgtaa2160 cttctcgcca ctggctcgga gagtagacag agttgccatc tatgaggaat ttctgcggat2220 gacccggaat ggtacccagc tgcagaactt caccctggac aggagcagtg tccttgtgga2280 tgggtatttt cccaacagaa atgagccctt aactgggaat tctgaccttc ccttctgggc2340 tgtcatcctc atcggcttgg caggactcct gggactcatc acatgcctga tctgcggtgt2400 cctggtgacc acccgccggc ggaagaagga aggagaatac aacgtccagc aacagtgccc2460 aggctactac cagtcacacc tagacctgga ggatctgcaa tgactgga'ac ttgccggrgc2520 ctggggtgcc tttcccccag ccagggtcca aagaagcttg gctggggcag aaataaacca2580 tattggtcgg acacaaaaaa aaaaaaaa2608 <210> 387 <211> 1761 <212> DNA <213> Homo sapiens <400> 387 ctgaacttca ccatcaacaa cctgcgctac atggcggaca tgggccaacc cggctccctc60 aagttcaaca tcacagacaa cgtcatgaag cacctgctca gtcctttgtt ccagaggagc120 agcctgggtg cacggtacac aggctgcagg gtcatcgcac taaggtctgt gaagaacggt180 gctgagacac gggtggacct cctctgcagg taggtgcaga ggaggtccac ggcatcaccc240 ggctgggccc ctactctcrg gacaaagaca gcctctacct taacgctccc aagccagcca300 ccacattcct gcctcctctg tcagaagcca caacagccat ggggtaccac ctgaagaccc360 tcacactcaa cttcaccatc tccaatctcc agtattcacc agatatgggc aagggctcag420 ctacattcaa ctccaccgag ggggtccttc agcacctgct cagacccttg ttccagaaga480 gcagcatggg ccccttctac ttgggttgcc aactgatctc cctcaggcct gagaaggatg540 gggcagccac tggtgtggac accacctgca cctaccaccc tgaccctgtg ggccccgggc600 tggacataca gcagctttac tgggagctga gtcagctgac ccatggtgtc acccaactgg660 gcttctatgt cctggacagg gatagcctct tcatcaatgg ctatgcaccc cagaatttat720 caatccgggg cgagtaccag ataaatttcc acattgtcaa ctggaacctc agtaatccag780 accccacatc ctcagagtac atcaccctgc tgagggacat ccaggacaag gtcaccacac 840 tctacaaagg cagtcaacta catgacacat tccgcttctg cctggtcacc aacttgacga 900 tggactccgt gttggtcact gtcaaggcat tgttctcctc caatttggac cccagcctgg 960 tggagcaagt ctttctagat aagaccctga atgcctcatt ccattggctg ggctccacct 1020 accagttggt ggacatccat gtgacagaaa tggagtcatc agtttatcaa ccaacaagca 1080 gctccagcac ccagcacttc tacctgaatt tcaccatcac caacctacca tattcccagg1140 acaaagccca gccaggcacc accaattacc agaggaacaa aaggaatatt gaggatgcgc1200 tcaaccaact cttccgaaac agcagcatca agagttattt ttctgactgt caagtttcaa1260 cattcaggtc tgtccccaac aggcaccaca ccggggtgga ctccctgtgt aacttctcgc1320 cactggctcg gagagtagac agagttgcca tctatgagga atttctgcgg atgacccgga1380 atggtaccca gctgcagaac ttcaccctgg acaggagcag tgtccttgtg gatgggtatt1440 ttcccaacag aaatgagccc ttaactggga attctgacct tcccttctgg gctgtcatcc1500 tcatcggctt ggcaggactc ctgggactca tcacatgcct gatctgcggt gtcctggtga1560 ccacccgccg gcggaagaag gaaggagaat acaacgtcca gcaacagtgc ccaggctact1620 accagtcaca cctagacctg gaggatctgc aatgactgga acttgccggt gcctggggtg1680 cctttccccc agccagggtc caaagaagct tggctggggc agaaataaac catattggtc1740 ggacacaaaa aaaaaaaaaa a1761 <210> 388 <211> 772 <212> PRT <213> Homo sapiens <400> 388

Met Ser Met Val Ser His Ser Gly Ala Leu Cys Pro Pro Leu Ala Phe 5 1015

Leu Gly Pro Pro Gin Trp Thr Trp Glu His Leu Gly Leu Gin Phe Leu 20 2530

Asn Leu Val Pro Arg Leu Pro Ala Leu Ser Trp Cys Tyr Ser Leu Ser 35 4045

Thr Ser Pro Ser Pro Thr Cys Gly Met Arg Arg Thr Cys Ser Thr Leu 50 5560

Ala Pro Gly Ser Ser Thr Pro Arg Arg Gly Ser Phe Arg Ala Trp Ser 65 70 7580

Leu Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu 85 9095

Thr Leu Leu Arg Pro Glu Lys Asp Gly Thr Ala Thr Gly Val Asp Ala 100 105no

He Cys Thr His His Pro Asp Pro Lys Ser Pro Arg Leu Asp Arg Glu 115 120!25

Gin Leu Tyr Trp Glu Leu Ser Gin Leu Thr His Asn He Thr Glu Leu 130 135140

Gly Pro Tyr Ala Leu Asp Asn Asp Ser Leu Phe Val .Asn Gly PheThr

145 150 155160

His Arg Ser Ser Val Ser Thr Thr Ser Thr Pro Gly Thr Pro ThrVal

165 170 !75

<td> Tyr</td><td> Leu</td><td> Gly</td><td> Ala 180</td><td> Ser</td><td> Lys</td><td> Thr</td><td colspan="2"> Pro Ala 185</td><td> Ser</td><td> He</td><td> Phe</td><td> Gly</td><td> Pro 190</td><td> Ser</td><td> Ala</td>

<td> Ala</td><td> Ser</td><td> His</td><td> Leu</td><td> Leu</td><td> He</td><td> Leu</td><td> Phe</td><td> Thr</td><td> Leu</td><td> Asn</td><td> Phe</td><td> Thr</td><td> He</td><td> Thr</td><td> Asn</td>

<td></td><td></td><td> 195</td><td></td><td></td><td></td><td></td><td> 200</td><td></td><td></td><td></td><td></td><td> 205</td><td></td><td></td><td></td>

<td> Leu</td><td> Arg</td><td> Tyr</td><td> Glu</td><td> Glu</td><td> Asn</td><td> Met</td><td> Trp</td><td> Pro</td><td> Gly</td><td> Ser</td><td> Arg</td><td> Lys</td><td> Phe</td><td> Asn</td><td> Thr</td>

<td></td><td> 210</td><td></td><td></td><td></td><td></td><td> 215</td><td></td><td></td><td></td><td></td><td> 220</td><td></td><td></td><td></td><td></td>

<td> Thr</td><td> Glu</td><td> Arg</td><td> Val</td><td> Leu</td><td> Gin</td><td> Gly</td><td> Leu</td><td> Leu</td><td> Arg</td><td> Pro</td><td> Leu</td><td> Phe</td><td> Lys</td><td> Asn</td><td> Thr</td>

<td> 225</td><td></td><td></td><td></td><td></td><td> 230</td><td></td><td></td><td></td><td></td><td> 235</td><td></td><td></td><td></td><td></td><td> 240</td>

<td> Ser</td><td> Val</td><td> Gly</td><td> Pro</td><td> Leu</td><td> Tyr</td><td> Ser</td><td> Gly</td><td> Cys</td><td> Arg</td><td> Leu</td><td> Thr</td><td> Leu</td><td> Leu</td><td> Arg</td><td> Pro</td>

<td></td><td></td><td></td><td></td><td> 245</td><td></td><td></td><td></td><td></td><td> 250</td><td></td><td></td><td></td><td></td><td> 255</td><td></td>

<td> Glu</td><td> Lys</td><td> Asp</td><td> Gly</td><td> Glu</td><td> Ala</td><td> Thr</td><td> Gly</td><td> Val</td><td> Asp</td><td> Ala</td><td> He</td><td> Cys</td><td> Thr</td><td> His</td><td> Arg</td>

<td></td><td></td><td></td><td> 260</td><td></td><td></td><td></td><td></td><td> 265</td><td></td><td></td><td></td><td></td><td> 270</td><td></td><td></td>

<td> Pro</td><td> Asp</td><td> Pro</td><td> Thr</td><td> Gly</td><td> Pro</td><td> Gly</td><td> Leu</td><td> Asp</td><td> Arg</td><td> Glu</td><td> Gin</td><td> Leu</td><td> Tyr</td><td> Leu</td><td> Glu</td>

<td></td><td></td><td> 275</td><td></td><td></td><td></td><td></td><td> 280</td><td></td><td></td><td></td><td></td><td> 285</td><td></td><td></td><td></td>

<td> Leu</td><td> Ser</td><td> Gin</td><td> Leu</td><td> Thr</td><td> His</td><td> Ser</td><td> He</td><td> Thr</td><td> Glu</td><td> Leu</td><td> Gly</td><td> Pro</td><td> Tyr</td><td> Thr</td><td> Leu</td>

<td></td><td> 290</td><td></td><td></td><td></td><td></td><td> 295</td><td></td><td></td><td></td><td></td><td> 300</td><td></td><td></td><td></td><td></td>

<td> Asp</td><td> Arg</td><td> Asp</td><td> Ser</td><td> Leu</td><td> Tyr</td><td> Val</td><td> Asn</td><td> Gly</td><td> Phe</td><td> Thr</td><td> His</td><td> Arg</td><td> Ser</td><td> Ser</td><td> Val</td>

<td> 305</td><td></td><td></td><td></td><td></td><td> 310</td><td></td><td></td><td></td><td></td><td> 315</td><td></td><td></td><td></td><td></td><td> 320</td>

<td> Pro</td><td> Thr</td><td> Thr</td><td> Ser</td><td> Thr</td><td> Gly</td><td> Val</td><td> Val</td><td> Ser</td><td> Glu</td><td> Glu</td><td> Pro</td><td> Phe</td><td> Thr</td><td> Leu</td><td> Asn</td>

<td></td><td></td><td></td><td></td><td> 325</td><td></td><td></td><td></td><td></td><td> 330</td><td></td><td></td><td></td><td></td><td> 335</td><td></td>

<td> Phe</td><td> Thr</td><td> He</td><td> Asn</td><td> Asn</td><td> Leu</td><td> Arg</td><td> Tyr</td><td> Met</td><td> Ala</td><td> Asp</td><td> Met</td><td> Gly</td><td> Gin</td><td> Pro</td><td> Gly</td>

<td></td><td></td><td></td><td> 340</td><td></td><td></td><td></td><td></td><td> 345</td><td></td><td></td><td></td><td></td><td> 350</td><td></td><td></td>

<td> Ser</td><td> Leu</td><td> Lys</td><td> Phe</td><td> Asn</td><td> He</td><td> Thr</td><td> Asp</td><td> Asn</td><td> Val</td><td> Met</td><td> Lys</td><td> His</td><td> Leu</td><td> Leu</td><td> Ser</td>

<td></td><td></td><td> 355</td><td></td><td></td><td></td><td></td><td> 360</td><td></td><td></td><td></td><td></td><td> 365</td><td></td><td></td><td></td>

<td> Pro</td><td> Leu</td><td> Phe</td><td> Gin</td><td> Arg</td><td> Ser</td><td> Ser</td><td> Leu</td><td> Gly</td><td> Ala</td><td> Arg</td><td> Tyr</td><td> Thr</td><td> Gly</td><td> Cys</td><td> Arg</td>

<td></td><td> 370</td><td></td><td></td><td></td><td></td><td> 375</td><td></td><td></td><td></td><td></td><td> 380</td><td></td><td></td><td></td><td></td>

<td> Val</td><td> He</td><td> Ala</td><td> Leu</td><td> Arg</td><td> Ser</td><td> Val</td><td> Lys</td><td> Asn</td><td> Gly</td><td> Ala</td><td> Glu</td><td> Thr</td><td> Arg</td><td> Val</td><td> Asp</td>

<td> 385</td><td></td><td></td><td></td><td></td><td> 390</td><td></td><td></td><td></td><td></td><td> 395</td><td></td><td></td><td></td><td></td><td> 400</td>

<td> Leu</td><td> Leu</td><td> Cys</td><td> Thr</td><td> Tyr</td><td> Leu</td><td> Gin</td><td> Pro</td><td> Leu</td><td> Ser</td><td> Gly</td><td> Pro</td><td> Gly</td><td> Leu</td><td> Pro</td><td> He</td>

<td></td><td></td><td></td><td></td><td> 405</td><td></td><td></td><td></td><td></td><td> 410</td><td></td><td></td><td></td><td></td><td> 415</td><td></td>

<td> Lys</td><td> Gin</td><td> Val</td><td> Phe</td><td> His</td><td> Glu</td><td> Leu</td><td> Ser</td><td> Gin</td><td> Gin</td><td> Thr</td><td> His</td><td> Gly</td><td> He</td><td> Thr</td><td> Arg</td>

<td></td><td></td><td></td><td> 420</td><td></td><td></td><td></td><td></td><td> 425</td><td></td><td></td><td></td><td></td><td> 430</td><td></td><td></td>

<td> Leu</td><td> Gly</td><td> Pro</td><td> Tyr</td><td> Ser</td><td> Leu</td><td> Asp</td><td> Lys</td><td> Asp</td><td> Ser</td><td> Leu</td><td> Tyr</td><td> Leu</td><td> Asn</td><td> Gly</td><td> Tyr</td>

<td></td><td></td><td> 435</td><td></td><td></td><td></td><td></td><td> 440</td><td></td><td></td><td></td><td></td><td> .4 4 5</td><td></td><td></td><td></td>

<td> Asn</td><td> Glu</td><td> Pro</td><td> Gly</td><td> Pro</td><td> Asp</td><td> Glu</td><td> Pro</td><td> Pro</td><td> Thr</td><td> Thr</td><td> Pro</td><td> Lys</td><td> Pro</td><td> Ala</td><td> Thr</td>

<td></td><td> 450</td><td></td><td></td><td></td><td></td><td> 455</td><td></td><td></td><td></td><td></td><td> 460</td><td></td><td></td><td></td><td></td>

Thr Phe Leu Pro Pro Leu Ser Glu 465 470

Leu Lys Thr Leu Thr Leu. Asn Phe 485

Pro Asp Met Gly Lys Gly Ser Ala 500

Leu Gin His Leu Leu Arg Pro Leu

515520

Phe Tyr Leu Gly Cys Gin Leu lie .530535

Ala Ala Thr Gly Val Asp Thr Thr 545550

Gly Pro Gly Leu Asp He Gin Gin 565

Thr His Gly Val Thr Gin Leu Gly 580

Leu Phe He Asn Gly Tyr Ala Pro

595600

Tyr Gin lie Asn Phe His He Val 610615

Pro Thr Ser Ser Glu Tyr lie Thr 625630

Val Thr Thr Leu Tyr Lys Gly Ser 645

Cys Leu Val Thr Asn Leu Thr Met 660

Ala Leu Phe Ser Ser Asn Leu Asp 675680

Leu Asp Lys Thr Leu Asn Ala Ser 690695

Gin Leu Val Asp He His Val Thr 705710

Pro Thr Ser Ser Ser Ser Thr Gin 725

Thr Asn Leu Pro Tyr Ser Gin Asp 740

Ala Thr Thr Ala Met Gly Tyr His

475480

Thr lie Ser Asn Leu Gin Tyr Ser 490495

Thr Phe Asn Ser Thr Glu Gly Val

505510

Phe Gin Lys Ser Ser Met Gly Pro 525

Ser Leu Arg Pro Glu Lys Asp Gly 540

Cys Thr Tyr His Pro Asp Pro Val

555560

Leu Tyr Trp Glu Leu Ser Gin Leu 570575

Phe Tyr Val Leu Asp Arg Asp Ser

585590

Gin Asn Leu Ser lie Arg Gly Glu 605

Asn Trp Asn Leu Ser Asn Pro Asp 620

Leu Leu Arg Asp lie Gin Asp Lys

635640

Gin Leu His Asp Thr Phe Arg Phe 650655

Asp Ser Val Leu Val Thr Val Lys

665670

Pro Ser Leu Val Glu Gin Val Phe 685

Phe His Trp Leu Gly Ser Thr Tyr 700

Glu Met Glu Ser Ser Val Tyr Gin

715720

His Phe Tyr Leu Asn Phe Thr He 730735

Lys Ala Gin Pro Gly Thr Thr Asn

745750

Tyr Gin Arg Asn ,Lys Arg Asn He

755 760

Gly Leu Pro Val

Glu Asp Ala Ala Pro His Arg Gly <210> 389 <211> 833 <212> PRT <213> Homo sapiens <400> 389

Phe Lys Ser Thr Ser Val Gly Pro 5

Leu Leu Arg Pro Glu Lys Asp Gly 20

Cys Thr His His Pro Asp Pro Lys

3540

Leu Tyr Trp Glu Leu Ser Gin Leu 5055

Pro Tyr Ala Leu Asp Asn Asp Ser 6570

Arg Ser Ser Val Ser Thr Thr Ser 85

Leu Gly Ala Ser Lys Thr Pro Ala 100

Ser His Leu Leu He Leu Phe Thr 115120

Arg Tyr Glu Glu Asn Met Trp Pro 130135

Glu Arg Val Leu Gin Gly Leu Leu 145150

Val Gly Pro Leu Tyr Ser Gly Cys 165

Lys Asp Gly Glu Ala Thr Gly Val 180

Asp Pro Thr Gly Pro Gly Leu Asp

195200

Leu Tyr Ser Gly Cys Arg Leu Thr .15

Thr Ala Thr Gly Val Asp Ala He 2530

Ser Pro Arg Leu Asp Arg Glu Gin 45

Thr His Asn He Thr Glu Leu Gly 60

Leu Phe Val Asn Gly Phe Thr His

7580

Thr Pro Gly Thr Pro Thr Val Tyr 9095

Ser He Phe Gly Pro Ser Ala Ala

105110

Leu Asn Phe Thr lie Thr Asn Leu

Gly Ser Arg Lys Phe Asn Thr Thr 140

Arg Pro Leu Phe Lys Asn Thr Ser

155160

Arg Leu Thr Leu Leu Arg Pro Glu 170175

Asp Ala He Cys Thr His Arg Pro 185190

Arg Glu Gin Leu Tyr Leu Glu Leu

Ser Gin Leu Thr His Ser He Thr Glu Leu Gly Pro Tyr Thr Leu Asp

210 215 220

Arg Asp Ser Leu Tyr Val Asn Gly

225 230

Thr Thr Ser Thr Gly Val Val Ser 245

Thr He Asn Asn Leu Arg Tyr Met 260

Leu Lys Phe Asn He Thr Asp Asn

275280

Leu Phe Gin Arg Ser Ser Leu Gly 290295 lie Ala Leu Arg Ser Val Lys Asn

305310

Leu Cys Thr Tyr Leu Gin Pro Leu 325

Gin Val Phe His Glu Leu Ser Gin 340

Gly Pro Tyr Ser Leu Asp Lys Asp

355360

Glu Pro Gly Pro Asp Glu Pro Pro 370375

Phe Leu Pro Pro Leu Ser Glu Ala

38539Q

Lys Thr Leu Thr Leu Asn Phe Thr 405

Asp Met Gly Lys Gly Ser Ala Thr 420

Gin His Leu Leu Arg Pro Leu Phe

435440

Tyr Leu Gly Cys Gin Leu lie Ser 450455

Ala Thr Gly Val Asp Thr Thr Cys

465470

Pro Gly Leu Asp He Gin Gin Leu 485

His Gly Val Thr Gin Leu Gly Phe 500

Phe lie Asn Gly Tyr Ala Pro Gin

Phe Thr His Arg Ser Ser Val Pro ²³⁵240

Glu Glu Pro Phe Thr Leu Asn Phe ²⁵⁰255

Ala Asp Met Gly Gin Pro Gly Ser

265270

Val Met Lys His Leu Leu Ser Pro 285

Ala Arg Tyr Thr Gly Cys Arg Val 300

Gly Ala Glu Thr Arg Val Asp Leu ³¹⁵320

Ser Gly Pro Gly Leu Pro lie Lys ' ³³⁰335

Gin Thr His Gly He Thr Arg Leu ³⁴³350

Ser Leu Tyr Leu Asn Gly Tyr Asn 365

Thr Thr Pro Lys Pro Ala Thr Thr 380

Thr Thr Ala Met Gly Tyr His Leu

395400 lie Ser Asn Leu Gin Tyr Ser Pro

Phe Asn Ser Thr Glu Gly Val Leu ⁴²⁵430

Gin Lys Ser Ser Met Gly Pro Phe 445

Leu Arg Pro Glu Lys Asp Gly Ala 4 60

Thr Tyr His Pro Asp Pro Val Gly ⁴⁷⁵480

Tyr Trp Glu Leu Ser Gin Leu Thr ⁴⁹⁰495

Tyr Val Leu Asp Arg Asp Ser Leu ⁵⁰⁵510

Asn Leu Ser He Arg Gly Glu Tyr

515520

Gin lie Asn Phe His He Val Asn 530535

Thr Ser Ser Glu Tyr He Thr Leu 545550

Thr Thr Leu Tyr Lys Gly Ser Gin 565

Leu Val Thr Asn Leu Thr Met Asp 580

Leu Phe Ser Ser Asn Leu Asp Pro

595600

Asp Lys Thr Leu Asn Ala Ser Phe 610615

Leu Val Asp He His Val Thr Glu 625630

Thr Ser Ser Ser Ser Thr Gin His 645

Asn Leu Pro Tyr Ser Gin Asp Lys 660

Gin Arg Asn Lys Arg Asn He Glu

675680

Asn Ser Ser He Lys Ser Tyr Phe 690695

Arg Ser Val Pro Asn Arg His His

705710

Phe Ser Pro Leu Ala Arg Arg Val 725

Phe Leu Arg Met Thr Arg Asn Gly 740

Asp Arg Ser Ser Val Leu Val Asp

755760

Pro Leu Thr Gly Asn Ser Asp Leu 770775

Gly Leu Ala Gly Leu Leu Gly Leu

785790

Trp Asn Leu Ser Asn Pro Asp Pro 540

Leu Arg Asp lie Gin Asp Lys Val

555550

Leu His Asp Thr Phe Arg Phe Cys 570575

Ser Val Leu Val Thr Val Lys Ala

585590

Ser Leu Val Glu Gin Val Phe Leu 605

His Trp Leu Gly Ser Thr Tyr Gin 620

Met Glu Ser Ser Val Tyr Gin Pro

635540

Phe Tyr Leu Asn Phe Thr He Thr 650655

Ala Gin Pro Gly Thr Thr Asn Tyr

665670

Asp Ala Leu Asn Gin Leu Phe Arg 685

Ser Asp Cys Gin Val Ser Thr Phe 700

Thr Gly Val Asp Ser Leu Cys Asn

715720

Asp Arg Val Ala He Tyr Glu Glu 730735

Thr Gin Leu Gin Asn Phe Thr Leu

745750

Gly Tyr Phe Pro Asn Arg Asn Glu 765

Pro Phe Trp Ala Val lie Leu lie 780

He Thr Cys Leu He Cys Gly Val

795 800

Leu Val Thr Thr Arg Arg Arg Lys Lys Glu Gly Glu Tyr Asn Val Gin

805 810815

Gin Gin Cys Pro Gly Tyr Tyr Gin

Ser His Leu Asp Leu Glu Asp Leu

825 830

Gin ♦

<210> 390 <211> 438 <212> PRT <213> Homo sapiens

<td colspan="3"> &lt;400&gt; 390 Met Gly Tyr</td><td> His</td><td> Leu 5</td><td> Lys</td><td> Thr</td><td> Leu</td><td> Thr</td><td> Leu 10</td><td> Asn</td><td> Phe</td><td> Thr</td><td> He</td><td> Ser 15</td><td> Asn</td>

<td> Leu</td><td> Gin</td><td> Tyr</td><td> Ser 20</td><td> Pro</td><td> Asp</td><td> Met</td><td> Gly</td><td> Lys 25</td><td> Gly</td><td> Ser</td><td> Ala</td><td> Thr</td><td> Phe 30</td><td> Asn</td><td> Ser</td>

<td> Thr</td><td> Glu</td><td> Gly 35</td><td> Val</td><td> Leu</td><td> Gin</td><td> His</td><td> Leu 40</td><td> Leu</td><td> Arg</td><td> Pro</td><td> Leu</td><td> Phe 45</td><td> Gin</td><td> Lys</td><td> Ser</td>

<td> Ser</td><td> Met 50</td><td> Gly</td><td> Pro</td><td> Phe</td><td> Tyr</td><td> Leu 55</td><td> Gly</td><td> Cys</td><td> Gin</td><td> Leu</td><td> He 60</td><td> Ser</td><td> Leu</td><td> Arg</td><td> Pro</td>

<td> Glu 65</td><td> Lys</td><td> Asp</td><td> Gly</td><td> Ala</td><td> Ala 70</td><td> Thr</td><td> Gly</td><td> Val</td><td> Asp</td><td> Thr 75</td><td> Thr</td><td> Cys</td><td> Thr</td><td> Tyr</td><td> His 80</td>

<td> Pro</td><td> Asp</td><td> Pro</td><td> Val</td><td> Gly 85</td><td> Pro</td><td> Gly</td><td> Leu</td><td> Asp</td><td> He 90</td><td> Gin</td><td> Gin</td><td> Leu</td><td> Tyr</td><td> Trp 95</td><td> Glu</td>

<td> Leu</td><td> Ser</td><td> Gin</td><td> Leu 100</td><td> Thr</td><td> His</td><td> Gly</td><td> Val</td><td> Thr 105</td><td> Gin</td><td> Leu</td><td> Gly</td><td> Phe</td><td> Tyr 110</td><td> Val</td><td> Leu</td>

<td> Asp</td><td> Arg</td><td> Asp 115</td><td> Ser</td><td> Leu</td><td> Phe</td><td> lie</td><td> Asn 120</td><td> Gly</td><td> Tyr</td><td> Ala</td><td> Pro</td><td> Gin 125</td><td> Asn</td><td> Leu</td><td> Ser</td>

<td> He</td><td> Arg 130</td><td> Gly</td><td> Glu</td><td> Tyr</td><td> Gin</td><td> He 135</td><td> Asn</td><td> Phe</td><td> His</td><td> He</td><td> Val 140</td><td> Asn</td><td> Trp</td><td> Asn</td><td> Leu</td>

<td> Ser 145</td><td> Asn</td><td> Pro</td><td> Asp</td><td> Pro</td><td> Thr 150</td><td> Ser</td><td> Ser</td><td> Glu</td><td> Tyr</td><td> He 155</td><td> Thr</td><td> Leu</td><td> Leu</td><td> Arg</td><td> Asp 160</td>

<td> He</td><td> Gin</td><td> Asp</td><td> Lys</td><td> Val 165</td><td> Thr</td><td> Thr</td><td> Leu</td><td> Tyr</td><td> Lys 170</td><td> Gly</td><td> Ser</td><td> Gin</td><td> Leu</td><td> His 175</td><td> Asp</td>

<td> Thr</td><td> Phe</td><td> Arg</td><td> Phe 180</td><td> Cys</td><td> Leu</td><td> Val</td><td> Thr</td><td> Asn 185</td><td> Leu</td><td> Thr</td><td> Met</td><td> Asp</td><td> Ser 190</td><td> Val</td><td> Leu</td>

<td> Val</td><td> Thr</td><td> Val 195</td><td> Lys</td><td> Ala</td><td> Leu</td><td> Phe</td><td> Ser 200</td><td> Ser</td><td> Asn</td><td> Leu</td><td> Asp</td><td> Pro 205</td><td> Ser</td><td> Leu</td><td> Val</td>

<td> Glu</td><td> Gin 210</td><td> Val</td><td> Phe</td><td> Leu</td><td> Asp</td><td> Lys 215</td><td> Thr</td><td> Leu</td><td> Asn</td><td> Ala</td><td> Ser 220</td><td> Phe</td><td> His</td><td> Trp</td><td> Leu</td>

<td> Gly Ser Thr Tyr Gin 225</td><td> Leu Val Asp He His 230</td><td> Val Thr Glu Met Glu 235</td><td> Ser 240</td>

<td> Ser Val Tyr Gin Pro</td><td> Thr Ser Ser Ser Ser</td><td> Thr Gin His Phe Tyr</td><td> Leu</td>

<td> 245</td><td> 250</td><td> 255</td><td></td>

<td> Asn Phe Thr He Thr</td><td> Asn Leu Pro Tyr Ser</td><td> Gin Asp Lys Ala Gin</td><td> Pro</td>

<td> 260</td><td> 265</td><td> 270</td><td></td>

<td> Gly Thr Thr Asn Tyr</td><td> Gin Arg Asn Lys Arg</td><td> Asn He Glu Asp Ala</td><td> Leu</td>

<td> 275</td><td> 280</td><td> 285</td><td></td>

<td> Asn Gin Leu Phe Arg</td><td> Asn Ser Ser lie Lys</td><td> Ser Tyr Phe Ser Asp</td><td> Cys</td>

<td> 290</td><td> 295</td><td> 300</td><td></td>

<td> Gin Val Ser Thr Phe</td><td> Arg Ser Val Pro Asn</td><td> Arg His His Thr Gly</td><td> Val</td>

<td> 305</td><td> 310</td><td> 315</td><td> 320</td>

<td> Asp Ser Leu Cys Asn</td><td> Phe Ser Pro Leu Ala</td><td> Arg Arg Val Asp Arg</td><td> Val</td>

<td> 325</td><td> 330</td><td> 335</td><td></td>

<td> Ala He Tyr Glu Glu</td><td> Phe Leu Arg Met Thr</td><td> Arg Asn Gly Thr Gin</td><td> Leu</td>

<td> 340</td><td> 345</td><td> 350</td><td></td>

<td> Gin Asn Phe Thr Leu</td><td> Asp Arg Ser Ser Val</td><td> Leu Val Asp Gly Tyr</td><td> Phe</td>

<td> 355</td><td> 360</td><td> 365</td><td></td>

<td> Pro Asn Arg Asn Glu</td><td> Pro Leu Thr Gly Asn</td><td> Ser Asp Leu Pro Phe</td><td> Trp</td>

<td> 370</td><td> 375</td><td> 380</td><td></td>

<td> Ala Val He Leu He</td><td> Gly Leu Ala Gly Leu</td><td> Leu Gly Leu lie Thr</td><td> Cys</td>

<td> 385</td><td> 390</td><td> 395</td><td> 400</td>

<td> Leu He Cys Gly Val</td><td> Leu Val Thr Thr Arg</td><td> Arg Arg Lys Lys Glu</td><td> Gly</td>

<td> 405</td><td> 410</td><td> 415</td><td></td>

<td> Glu Tyr Asn Val Gin</td><td> Gin Gin Cys Pro Gly</td><td> Tyr Tyr Gin Ser His</td><td> Leu</td>

<td> 420</td><td> 425</td><td> 430</td><td></td>

<td> Asp Leu Glu Asp Leu</td><td> Gin</td><td></td><td></td>

<210> 391 <211> 2627 <212> DNA <213> Homo sapiens <400> 391 ccacgcgtcc gcccacgcgt ccggaaggca gcggcagcta cactcagcca gtacccagat60 acgctgggaa ccttccccag ccatggcttc cctggggcag atcctcttct ggagcataat120 tagcatcatc attattctgg ctggagcaat tgcactcatc attggctttg gtatttcagg180 gagacactcc atcacagtca ctactgtcgc ctcagctggg aacattgggg aggatggaat240 cctgagctgc acttttgaac ctgacatcaa actttctgat atcgtgatac aatggctgaa300 ggaaggtgtt ttaggcttgg tccatgagtt caaagaaggc aaagatgagc tgtcggagca360 ggatgaaatg ttcagaggcc ctctttgcgg ctgaaaaacg cacttctaaa ggcaagggga ggaagtgaat gtggactata gttcccccag cccacagtgg agtctccaat accagctttg gctctacaat gttacgatca agcaacaggg gatatcaaag gctaaactca aaggcttctc gcctctcagc ccttacctga gtcattgtta caacagggat atttctggga ggaaatgaat acaaaaagaa gccaaaagca catattagaa gttgggaaaa taaaatgcac gtggagacaa ctggggagtg agaggacagg gctgtaatgt tgctctgagg attccacaaa ttaagctgta aactcagggg cggctgcatt aaaggtgcct tggcttctct attttagcat aaacagagca ttttaaacaa acaaatgcgg gaaggacctt tcaccttgac ttccatcctg cgtggacagc cagctggggt g^tttcgccc tcaatgaggg agtggaggag tgctgctcaa cctcctacca tgtcaactgt gtcaggacta ggagccaaca aatctgtctg tttggctgct gcctcagcac cagtgaacag agttgacaag gagcttctaa gtttctttcc cctgagttct agctcaggtt caattcaaat taaggcaaca caaggacaat gactgcttga ctttgtttcc agcccccttc ggagccacgg tgactgtatt tcaagagaat gattaaatat ggacagcagt gtttgctgat tgcaactcac agatgctggc atgctaacct tgagtataaa atgccagctc agagaccttg tctgggcatc ccaagttgac agctgaactc tgagaatgtg acaacacata ctcctgtatg tgacagaatc ggagatcaaa tgtgtgtctc ttctttcttt tgctaaaata atgtgccttg ctacagaact atttcaccac tcatatctag aagtctggag gaaggctcca atatgaacaa taattcatgt gaactagaca gtgcatcccc agatctcagg atagtgcatg ttctttgtct aagcccctgg aaagtctatc gtatgtaccc taagacgctg ttagtaatgg gtcaaatgat tcccaactga caaatgccaa gtcggcgaca ccgattttat gtttatttct cagatgatgt tatatggcat tatgtcatca taagacctca gttttcaata cccatctccg ggggaatgtc gatacagtgc tactaccaac tgtacaggac gtctccccat agaaaccctg gttttgagta cttcctcaca ttagtcattg agagagccag aactctatcg gcctatggga aatgcctgat cttcattcta ccctgcaagc ttcttactct gaatttagat aacatatacc ttccatgaag attgaggcct tgaggaatga ccacactctt catgtgttaa acatgttgtt atagaaaact acatttccta caccaaaaaa caagtgatag ttggcaatgc 420 acctacaaat gttatatcat 480 actggagcct tcagcatgcc 540 cggtgtgagg ctccccgatg 600 cagggagcca acttctcgga 660 accatgaagg ttgtgtctgt 720 attgaaaatg acattgccaa 780 aggcggagtc acctacagct 840 gccatcagct gggcacttct 900 gccacaaaaa agcatgcaaa 960 cagatatgac ctagttttat 1020 tgagcaaaca agagcaagaa 1080 gataaatcta tcttcaaaga 1140 agtgtgttaa gagtgataag 1200 gacctccccc tgcctgtcac 1260 ctgaattttt agttatatgt 1320 ccaacatatc cacatcttat 1380 ctaattgact gccacttcgc 1440 tcacttttta tgatgcttcc 1500 agttgagaaa aatgatcata 1560 aaataaactg agcaccttct 1620 tcatccgtga atggtccagg 1680 caagctctga ggcttctcct 1740 gcatctagag cagtgggact 1800 tgaagacaat tttggttacc 1860 tagtggataa aggccaggga 1920 tacaactacc caatccgaag 1980 gaaaagggcc tggaaagagg 2040 gcaaataagc attctgtctc 2100 ggcaccagga taacatctct 2160 gggattatct tcagcttgtt 2220 caagttctgt aagagaaatg 2280 ctccagaccc ttcctggcca 2340 cacacacaga cttttgaaag 2400 agctttgaag gaaaagaata 2460 ccactgcctt cctggacctt 2520 gattttagag ttctgatcgt 2580 aaaaaaa 2627 <210> 392 <211> 310 <212> PRT <213> Homo sapiens <400> 392

His Ala Ser Ala His Ala Ser Gly Arg Gin Arg Gin Leu His Ser Ala

1015

Ser Thr Gin He Arg Trp Glu Pro Ser Pro Ala Met Ala Ser Leu Gly

2530

Gin He Leu Phe Trp Ser He He Ser lie lie lie He Leu Ala Gly

4045

Ala He Ala Leu He He Gly Phe Gly lie Ser Gly Arg His Ser He

5560

Thr Val Thr Thr Val Ala Ser Ala Gly Asn He Gly Glu Asp Glylie ^{65 70} 7580

Leu Ser Cys Thr Phe Glu Pro Asp lie Lys Leu Ser Asp He ValHe

9095

Gin Trp Leu Lys Glu Gly Val Leu Gly Leu Val His Glu Phe Lys Glu 100 105no

Gly Lys Asp Glu Leu Ser Glu Gin Asp Glu Met Phe Arg Gly Arg Thr 115 120125

Ala Val Phe Ala Asp Gin Val He Val Gly Asn Ala Ser Leu Arg Leu 130 135140

Lys Asn Val Gin Leu Thr Asp Ala Gly Thr Tyr Lys Cys Tyr HeHe

145 150 155

Thr Ser Lys Gly Lys Gly Asn Ala Asn Leu Glu Tyr Lys Thr GlyAla

165 170175

Phe Ser Met Pro Glu Val Asn Val Asp Tyr Asn Ala Ser Ser Glu Thr 180 185190

Leu Arg Cys Glu Ala Pro Arg Trp Phe Pro Gin Pro Thr Val Val Trp 195 200205

Ala Ser Gin Val Asp Gin Gly Ala Asn Phe Ser Glu Val Ser Asn Thr 210 215220

Ser Phe Glu Leu Asn Ser Glu Asn Val Thr Met Lys Val Val SerVal

225 230 235240

Leu Tyr Asn Val Thr He Asn Asn Thr Tyr Ser Cys Met He GluAsn

245 250255

Asp He Ala Lys Ala Thr Gly Asp He Lys Val Thr Glu Ser Glu lie 260 265270

Lys Arg Arg Ser His Leu Gin Leu Leu Asn Ser Lys Ala Ser Leu Cys 275 280285

Val Ser Ser Phe Phe Ala He Ser Trp Ala Leu Leu Pro Leu Ser Pro 290 295300

Tyr Leu Met Leu Lys <210> 393 <211> 283 <212> PRT <213> Homo sapiens <400> 393

Met Ala Ser Leu Gly Gin lie Leu 5

He He Leu Ala Gly Ala He Ala 20

Gly Arg His Ser He Thr Val Thr

3540

Gly Glu Asp Gly He Leu Ser Cys 5055

Ser Asp He Val lie Gin Trp Leu 6570

His Glu Phe Lys Glu Gly Lys Asp 85

Phe Arg Gly Arg Thr Ala Val Phe 100

Ala Ser Leu Arg Leu Lys Asn Val

115120

Lys Cys Tyr He lie Thr Ser Lys 130135

Tyr Lys Thr Gly Ala Phe Ser Met

145150

Ala Ser Ser Glu Thr Leu Arg Cys 165

Pro Thr Val Val Trp Ala Ser Gin 180

Glu Val Ser Asn Thr Ser Phe Glu

195200

Lys Val Val Ser Val Leu Tyr Asn 210215

Cys Met He Glu Asn Asp He Ala

225230

Thr Glu Ser Glu He Lys Arg Arg 245

Lys Ala Ser Leu Cys Val Ser Ser 260

Leu Pro Leu Ser Pro Tyr Leu Met

275 280

Phe Trp Ser He lie Ser He He ¹0 15

Leu lie lie Gly Phe Gly lie Ser 25 30

Thr Val Ala Ser Ala Gly Asn lie 45

Thr Phe Glu Pro Asp lie Lys Leu 60

Lys Glu Gly Val Leu Gly Leu Val

7580

Glu Leu Ser Glu Gin Asp Glu Met ⁹⁰95

Ala Asp Gin Val He Val Gly Asn 105

Gin Leu Thr Asp Ala Gly Thr Tyr 125

Gly Lys Gly Asn Ala Asn Leu Glu 140

Pro Glu Val Asn Val Asp Tyr Asn

155160

Glu Ala Pro Arg Trp Phe Pro Gin 170175

Val Asp Gin. Gly Ala Asn Phe Ser

185190

Leu Asn Ser Glu Asn Val Thr Met 205

Val Thr lie Asn Asn Thr Tyr Ser 220

Lys Ala Thr Gly Asp He Lys Val

235240

Ser His Leu Gin Leu Leu Asn Ser

250255

Phe Phe Ala lie Ser Trp Ala Leu

265270

Leu Lys