EP1053319A2 - Human genes and gene expression products ii - Google Patents
Human genes and gene expression products iiInfo
- Publication number
- EP1053319A2 EP1053319A2 EP99904288A EP99904288A EP1053319A2 EP 1053319 A2 EP1053319 A2 EP 1053319A2 EP 99904288 A EP99904288 A EP 99904288A EP 99904288 A EP99904288 A EP 99904288A EP 1053319 A2 EP1053319 A2 EP 1053319A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- sequence
- polynucleotide
- protein
- seq
- cell
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
Definitions
- the present invention relates to novel polynucleotides, particularly to novel polynucleotides of human origin that are expressed in a selected cell type, are differentially expressed in one cell type relative to another cell type (e.g., in cancerous cells, or in cells of a specific tissue origin) and/or share homology to polynucleotides encoding a gene product having an identified functional domain and/or activity.
- This invention provides novel human polynucleotides, the polypeptides encoded by these polynucleotides, and the genes and proteins corresponding to these novel polynucleotides.
- This invention relates to novel human polynucleotides and variants thereof, their encoded polypeptides and variants thereof, to genes corresponding to these polynucleotides and to proteins expressed by the genes.
- the invention also relates to diagnostic and therapeutic agents employing such novel human polynucleotides, their corresponding genes or gene products, e.g., these genes and proteins, including probes, antisense constructs, and antibodies.
- the polynucleotides of the invention correspond to a polynucleotide comprising the sequence information of at least one of SEQ ID NOS: 1-3544, 3546-4510, 4512-4725, 4727-4748, and 4750-5252, which for convenience sake is referred to herein as "SEQ ID NOS: 1-5252.” Accordingly, in one embodiment, the present invention features a library of polynucleotides, the library comprising the sequence information of at least one of "SEQ ID NOS: 1-5252". In related aspects, the invention features a library provided on a nucleic acid array, or in a computer-readable format.
- the library is comprises a differentially expressed polynucleotide comprising a sequence selected from one of the differentially expressed polynucleotides disclosed herein.
- the library comprises: 1) a polynucleotide that is differentially expressed in a human breast cancer cell, where the polynucleotide comprises a sequence selected from the group consisting of SEQ ID NOS:15, 36, 44, 45, 89, 146, 154, 159, 165, 172, 174, 183, 203, 261, 364, 366, 387, 419, 420, 496, 503, 510, 512, 529, 552, 560, 564, 570, 590, 606, 644, 646, 693, 707, 711, 726, 746, 754, 756, 875, 902, 921, 942, 990, 1095, 1104, 1122, 1131, 1142, 1170, 1184, 1205, 1286, 1289, 1354, 1387,
- the invention features recombinant host cells and vectors comprising the polynucleotides of the invention, as well as isolated polypeptides encoded by the polynucleotides of the invention and antibodies that specifically bind such polypeptides.
- the invention features an isolated polynucleotide comprising a sequence encoding a polypeptide of a protein family or having a functional domain selected from the group consisting of: 4 transmembrane segments integral membrane proteins, 7 transmembrane receptors (rhodopsin family or secretin family), eukaryotic aspartyl proteases, ATPases associated with various cellular activities (AAA), Bcl-2, cyclins, DEAD box protein family, DEAD/H helicase protein family, MAP kinase kinase protein family, novel 3'5'-cyclic nucleotide phosphodiesterases, protein kinases, ras protein family, G-protein alpha subunit, phorbol esters/diacylglycerol binding proteins, protein kinase, trypsin, protein tyrosine phosphatase, wnt family of developmental signaling proteins,
- the invention features a polynucleotide comprising a sequence of one of the SEQ ID NOS: listed in Table 3 or Table 20.
- the invention features a method of detecting differentially expressed genes correlated with a cancerous state of a mammalian cell, where the method comprises the step of detecting at least one differentially expressed gene product in a test sample derived from a cell suspected of being cancerous, where the gene product is encoded by a gene corresponding to a sequence of at least one of the differentially expressed polynucleotides disclosed herein. Detection of the differentially expressed gene product is correlated with a cancerous state of the cell from which the test sample was derived. In one embodiment, the detecting is by hybridization of the test sample to a reference array, wherein the reference array comprises an identifying sequence of at least one of the differentially expressed polynucleotides disclosed herein.
- the cell is a breast tissue derived cell
- the differentially expressed gene product is encoded by a gene corresponding to a sequence of at least one of SEQ ID NOS:15, 36, 44, 45, 89, 146, 154, 159, 165, 172, 174, 183, 203, 261, 364, 366, 387, 419, 420, 496, 503, 510, 512, 529, 552, 560, 564, 570, 590, 606, 644, 646, 693, 707, 711, 726, 746, 754, 756, 875, 902, 921, 942, 990, 1095, 1104, 1122, 1131, 1142, 1170, 1184, 1205, 1286, 1289, 1354, 1387, 1435, 1535, 1751, 1764, 1777, 1795, 1860, 1869, 1882, 1890, 1915, 1933, 1934, 1979, 1980, 2007, 2023, 2040, 2059,
- the cell is a colon tissue derived cell, and differentially expressed gene product is encoded by a gene corresponding to a sequence ofat least one of SEQ ID NOS: 65, 228, 252, 253, 280, 355, 491, 581, 603, 680, 693, 716, 726, 746, 752, 753, 1241, 1264, 1401, 1442, 1514, 1851, 1915, 2024, 2066, 33, 250, 282, 370, 387, 443, 460, 545, 560, 703, 704, 1095, 1104, 1205, 1354, 1387, 1734, 1742, 1780, 1899, 1954, 2262, and 2325.
- the cell is a lung tissue derived cell
- differentially expressed gene product is encoded by a gene corresponding to a sequence ofat least one of SEQ ID NOS:10, 54, 65, 171, 174, 203, 252, 253, 254, 285, 419, 420, 466, 491, 525, 526, 552, 571, 574, 590, 693, 700, 726, 742, 746, 861, 922, 990, 1088, 1288, 1355, 1417, 1422, 1444, 1454, 1570, 1597, 1979, 2007, 2024, 2034, 2038, 2126, and 2245.
- the cell is any of a lung, breast, or colon cell and the differentially expressed gene product is encoded by a gene corresponding to a sequence of at least one of SEQ ID NOS:648 and 1899.
- the cell is any of a breast, colon, or lung cell and the differentially expressed gene product is encoded by a gene corresponding to a sequence of at least one of SEQ ID NOS: 65, 174, 203, 252, 253, 387, 419, 420, 491, 552, 560, 581, 590, 648, 693, 726, 746, 990, 1095, 1124, 1205, 1354, 1387, , 1780, 1899, 1915, 1979, 2007, 2024, 2245, and 2325.
- SEQ ID NOS SEQ ID NOS: 65, 174, 203, 252, 253, 387, 419, 420, 491, 552, 560, 581, 590, 648, 693, 726, 746, 990, 1095, 1124, 1205, 1354, 1387, , 1780, 1899, 1915, 1979, 2007, 2024, 2245, and 2325.
- the invention relates to polynucleotides comprising the disclosed nucleotide sequences, to full length cDNA, mRNA and genes corresponding to these sequences, and to polypeptides and proteins encoded by these polynucleotides and genes.
- polynucleotides that encode polypeptides and proteins encoded by the polynucleotides of the Sequence Listing are also included.
- the various polynucleotides that can encode these polypeptides and proteins differ because of the degeneracy of the genetic code, in that most amino acids are encoded by more than one triplet codon. The identity of such codons is well-known in this art, and this information can be used for the construction of the polynucleotides within the scope of the invention.
- Polynucleotides encoding polypeptides and proteins that are variants of the polypeptides and proteins encoded by the polynucleotides and related cDNA and genes are also within the scope of the invention.
- the variants differ from wild type protein in having one or more amino acid substitutions that either enhance, add, or diminish a biological activity of the wild type protein. Once the amino acid change is selected, a polynucleotide encoding that variant is constructed according to the invention.
- polynucleotide compositions encompassed by the invention methods for obtaining cDNA or genomic DNA encoding a full-length gene product, expression of these polynucleotides and genes, identification of structural motifs of the polynucleotides and genes, identification of the function of a gene product encoded by a gene corresponding to a polynucleotide of the invention, use of the provided polynucleotides as probes and in mapping and in tissue profiling, use of the corresponding polypeptides and other gene products to raise antibodies, and use of the polynucleotides and their encoded gene products for therapeutic and diagnostic purposes.
- polynucleotide compositions The scope of the invention with respect to polynucleotide compositions includes, but is not necessarily limited to, polynucleotides having a sequence set forth in any one of "SEQ ID NOS: 1-5252"; polynucleotides obtained from the biological materials described herein or other biological sources (particularly human sources) by hybridization under stringent conditions (particularly conditions of high stringency); genes corresponding to the provided polynucleotides; variants of the provided polynucleotides and their corresponding genes, particularly those variants that retain a biological activity of the encoded gene product (e.g., a biological activity ascribed to a gene product corresponding to the provided polynucleotides as a result of the assignment of the gene product to a protein family(ies) and/or identification of a functional domain present in the gene product).
- SEQ ID NOS: 1-5252 polynucleotides obtained from the biological materials described herein or other biological sources (particularly human sources) by hybridization under
- nucleic acid compositions contemplated by and within the scope of the present invention will be readily apparent to one of ordinary skill in the art when provided with the disclosure here.
- the invention features polynucleotides that are expressed in cells of human tissue, specifically human colon, breast, and/or lung tissue.
- Novel nucleic acid compositions of the invention of particular interest comprise a sequence set forth in any one of "SEQ ID NOS: 1-5252" or an identifying sequence thereof.
- an "identifying sequence” is a contiguous sequence of residues at least about 10 nt to about 20 nt in length, usually at least about 50 nt to about 100 nt in length, that uniquely identifies a polynucleotide sequence, e.g., exhibits less than 90%, usually less than about 80% to about 85% sequence identity to any contiguous nucleotide sequence of more than about 20 nt.
- the subject novel nucleic acid compositions include full length cDNAs or mRNAs that encompass an identifying sequence of contiguous nucleotides from any one of "SEQ ID NOS: 1-5252.”
- the polynucleotides of the invention also include polynucleotides having sequence similarity or sequence identity.
- Nucleic acids having sequence similarity are detected by hybridization under low stringency conditions, for example, at 50°C and 10XSSC (0.9 M saline/0.09 M sodium citrate) and remain bound when subjected to washing at 55°C in IXSSC. Sequence identity can be determined by hybridization under stringent conditions, for example, at 50°C or higher and 0. IXSSC (9 mM saline/0.9 mM sodium citrate). Hybridization methods and conditions are well known in the art, see, e.g., U.S. Patent No. 5,707,829. Nucleic acids that are substantially identical to the provided polynucleotide sequences, e.g.
- allelic variants, genetically altered versions of the gene, etc. bind to the provided polynucleotide sequences ("SEQ ID NOS: 1-5252") under stringent hybridization conditions.
- probes particularly labeled probes of DNA sequences
- the source of homologous genes can be any species, e.g. primate species, particularly human; rodents, such as rats and mice; canines, felines, bovines, ovines, equines, yeast, nematodes, etc.
- hybridization is performed using at least 15 contiguous nucleotides ofat least one of "SEQ ID NOS:l-5252.” That is, when at least 15 contiguous nucleotides of one of the disclosed SEQ ID NOs. is used as a probe, the probe will preferentially hybridize with a gene or mRNA (of the biological material) comprising the complementary sequence, allowing the identification and retrieval of the nucleic acids of the biological material that uniquely hybridize to the selected probe. Probes from more than one SEQ ID NO. will hybridize with the same gene or mRNA if the cDNA from which they were derived corresponds to one mRNA. Probes of more than 15 nucleotides can be used, but 15 nucleotides represents enough sequence for unique identification.
- the polynucleotides of the invention also include naturally occurring variants of the nucleotide sequences (e.g., degenerate variants, allelic variants, etc.). Variants of the polynucleotides of the invention are identified by hybridization of putative variants with nucleotide sequences disclosed herein, preferably by hybridization under stringent conditions For example, by using appropriate wash conditions, variants of the polynucleotides of the invention can be identified where the allelic variant exhibits at most about 25-30%) base pair mismatches relative to the selected polynucleotide probe. In general, allelic variants contain 15-25% base pair mismatches, and can contain as little as even 5-15%, or 2-5%, or 1-2% base pair mismatches, as well as a single base-pair mismatch.
- allelic variants contain 15-25% base pair mismatches, and can contain as little as even 5-15%, or 2-5%, or 1-2% base pair mismatches, as well as a single
- the invention also encompasses homologs corresponding to the polynucleotides of "SEQ ID NOS: 1-5252", where the source of homologous genes can be any mammalian species, e.g., primate species, particularly human; rodents, such as rats; canines, felines, bovines, ovines, equines, yeast, nematodes, etc. Between mammalian species, e.g., human and mouse, homologs have substantial sequence similarity, e.g., at least 75% sequence identity, usually at least 90%, more usually at least 95% between nucleotide sequences.
- Sequence similarity is calculated based on a reference sequence, which may be a subset of a larger sequence, such as a conserved motif, coding region, flanking region, etc.
- a reference sequence will usually be at least about 18 contiguous nt long, more usually at least about 30 nt long, and may extend to the complete sequence that is being compared.
- Algorithms for sequence analysis are known in the art, such as BLAST, described in Altschul et al, J. Mol. Biol. (1990) 275:403-10.
- variants of the invention have a sequence identity greater than at least about 65%, preferably at least about 75%, more preferably at least about 85%, and can be greater than at least about 90% or more as determined by the Smith- Waterman homology search algorithm as implemented in MPSRCH program (Oxford Molecular).
- a preferred method of calculating percent identity is the Smith- Waterman algorithm, using the following.
- Global DNA sequence identity must be greater than 65% as determined by the Smith- Waterman homology search algorithm as implemented in MPSRCH program (Oxford Molecular) using an affine gap search with the following search parameters: gap open penalty, 12; and gap extension penalty, 1.
- the subject nucleic acids can be cDNAs or genomic DNAs, as well as fragments thereof, particularly fragments that encode a biologically active gene product and/or are useful in the methods disclosed herein (e.g., in diagnosis, as a unique identifier of a differentially expressed gene of interest, etc.).
- cDNA as used herein is intended to include all nucleic acids that share the arrangement of sequence elements found in native mature mRNA species, where sequence elements are exons and 3' and 5' non-coding regions. Normally mRNA species have contiguous exons, with the intervening introns, when present, being removed by nuclear RNA splicing, to create a continuous open reading frame encoding a polypeptide of the invention.
- a genomic sequence of interest comprises the nucleic acid present between the initiation codon and the stop codon, as defined in the listed sequences, including all of the introns that are normally present in a native chromosome. It can further include the 3' and 5' untranslated regions found in the mature mRNA. It can further include specific transcriptional and translational regulatory sequences, such as promoters, enhancers, etc., including about 1 kb, but possibly more, of flanking genomic DNA at either the 5' and 3' end of the transcribed region.
- the genomic DNA can be isolated as a fragment of 100 kbp or smaller; and substantially free of flanking chromosomal sequence.
- the genomic DNA flanking the coding region, either 3' and 5', or internal regulatory sequences as sometimes found in introns contains sequences required for proper tissue, stage-specific, or disease- state specific expression.
- nucleic acid compositions of the subject invention can encode all or a part of the subject polypeptides. Double or single stranded fragments can be obtained from the DNA sequence by chemically synthesizing oligonucleotides in accordance with conventional methods, by restriction enzyme digestion, by PCR amplification, etc.
- Isolated polynucleotides and polynucleotide fragments of the invention comprise at least about 10, about 15, about 20, about 35, about 50, about 100, about 150 to about 200, about 250 to about 300, or about 350 contiguous nucleotides selected from the polynucleotide sequences as shown in "SEQ ID NOS: 1-5252.”
- fragments will be ofat least 15 nt, usually at least 18 nt or 25 nt, and up to at least about 50 contiguous nt in length or more.
- the polynucleotide molecules comprise a contiguous sequence of at least twelve nucleotides selected from the group consisting of the polynucleotides shown in "SEQ ID NOS: 1-5252.”
- Probes specific to the polynucleotides of the invention can be generated using the polynucleotide sequences disclosed in "SEQ ID NOS: 1-5252.”
- the probes are preferably at least about 12, 15, 16, 18, 20, 22, 24, or 25 nucleotide fragment of a corresponding contiguous sequence of "SEQ ID NOS:l-5252", and can be less than 2, 1, 0.5, 0.1, or 0.05 kb in length.
- the probes can be synthesized chemically or can be generated from longer polynucleotides using restriction enzymes.
- the probes can be labeled, for example, with a radioactive, biotinylated, or fluorescent tag.
- probes are designed based upon an identifying sequence of a polynucleotide of one of "SEQ ID NOS: 1-5252.” More preferably, probes are designed based on a contiguous sequence of one of the subject polynucleotides that remain unmasked following application of a masking program for masking low complexity (e.g., XBLAST) to the sequence., i.e., one would select an unmasked region, as indicated by the polynucleotides outside the poly-n stretches of the masked sequence produced by the masking program.
- a masking program for masking low complexity e.g., XBLAST
- polynucleotides of the subject invention are isolated and obtained in substantial purity, generally as other than an intact chromosome.
- the polynucleotides either as DNA or RNA, will be obtained substantially free of other naturally-occurring nucleic acid sequences, generally being at least about 50%, usually at least about 90% pure and are typically "recombinant", e.g., flanked by one or more nucleotides with which it is not normally associated on a naturally occurring chromosome.
- the polynucleotides of the invention can be provided as a linear molecule or within a circular molecule. They can be provided within autonomously replicating molecules (vectors) or within molecules without replication sequences. They can be regulated by their own or by other regulatory sequences, as is known in the art.
- the polynucleotides of the invention can be introduced into suitable host cells using a variety of techniques which are available in the art, such as transferrin polycation-mediated DNA transfer, transfection with naked or encapsulated nucleic acids, liposome-mediated DNA transfer, intracellular transportation of DNA-coated latex beads, protoplast fusion, viral infection, electroporation, gene gun, calcium phosphate-mediated transfection, and the like.
- the subject nucleic acid compositions can be used to, for example, produce polypeptides, as probes for the detection of mRNA of the invention in biological samples (e.g., extracts of human cells) to generate additional copies of the polynucleotides, to generate ribozymes or antisense oligonucleotides, and as single stranded DNA probes or as triple-strand forming oligonucleotides.
- the probes described herein can be used to, for example, determine the presence or absence of the polynucleotide sequences as shown in "SEQ ID NOS: 1-5252" or variants thereof in a sample. These and other uses are described in more detail below.
- Full-length cDNA molecules comprising the disclosed polynucleotides are obtained as follows.
- a polynucleotide having a sequence of one of "SEQ ID NOS: 1-5252", or a portion thereof comprising at least 12, 15, 18, or 20 nucleotides, is used as a hybridization probe to detect hybridizing members of a cDNA library using probe design methods, cloning methods, and clone selection techniques such as those described in U.S. Patent No. 5,654,173.
- Libraries of cDNA are made from selected tissues, such as normal or tumor tissue, or from tissues of a mammal treated with, for example, a pharmaceutical agent.
- the tissue is the same as the tissue from which the polynucleotides of the invention were isolated, as both the polynucleotides described herein and the cDNA represent expressed genes.
- the cDNA library is made from the biological material described herein in the Examples.
- many cDNA libraries are available commercially. (Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., (1989) Cold Spring Harbor Press, Cold Spring Harbor, NY). The choice of cell type for library construction can be made after the identity of the protein encoded by the gene corresponding to the polynucleotide of the invention is known.
- the libraries are prepared from mRNA of human colon cells, more preferably, human colon cancer cells, even more preferably, from a highly metastatic colon cell, Kml2L4-A.
- the cDNA can be prepared by using primers based on sequence from "SEQ ID NOS: 1-5252.”
- the cDNA library can be made from only poly-adenylated mRNA.
- poly-T primers can be used to prepare cDNA from the mRNA.
- RNA protection experiments are performed as follows. Hybridization of a full-length cDNA to an mRNA will protect the RNA from RNase degradation. If the cDNA is not full length, then the portions of the mRNA that are not hybridized will be subject to RNase degradation. This is assayed, as is known in the art, by changes in electrophoretic mobility on polyacrylamide gels, or by detection of released monoribonucleotides.
- Genomic DNA is isolated using the provided polynucleotides in a manner similar to the isolation of full-length cDNAs. Briefly, the provided polynucleotides, or portions thereof, are used as probes to libraries of genomic DNA.
- the library is obtained from the cell type that was used to generate the polynucleotides of the invention, but this is not essential. Most preferably, the genomic DNA is obtained from the biological material described herein in the Examples.
- Such libraries can be in vectors suitable for carrying large segments of a genome, such as PI or YAC, as described in detail in Sambrook et al, 9.4-9.30.
- genomic sequences can be isolated from human BAC libraries, which are commercially available from Research Genetics, Inc., Huntville, Alabama, USA, for example.
- chromosome walking is performed, as described in Sambrook et al., such that adjacent and overlapping fragments of genomic DNA are isolated. These are mapped and pieced together, as is known in the art, using restriction digestion enzymes and DNA ligase.
- corresponding full-length genes can be isolated using both classical and PCR methods to construct and probe cDNA libraries.
- Northern blots preferably, are performed on a number of cell types to determine which cell lines express the gene of interest at the highest level.
- Classical methods of constructing cDNA libraries are taught in Sambrook et al, supra. With these methods, cDNA can be produced from mRNA and inserted into viral or expression vectors. Typically, libraries of mRNA comprising poly(A) tails can be produced with poly(T) primers. Similarly, cDNA libraries can be produced using the instant sequences as primers.
- PCR methods are used to amplify the members of a cDNA library that comprise the desired insert.
- the desired insert will contain sequence from the full length cDNA that corresponds to the instant polynucleotides.
- Such PCR methods include gene trapping and RACE methods.
- Gene trapping entails inserting a member of a cDNA library into a vector. The vector then is denatured to produce single stranded molecules. Next, a substrate-bound probe, such a biotinylated oligo, is used to trap cDNA inserts of interest. Biotinylated probes can be linked to an avidin-bound solid substrate.
- PCR methods can be used to amplify the trapped cDNA.
- the labeled probe sequence is based on the polynucleotide sequences of the invention. Random primers or primers specific to the library vector can be used to amplify the trapped cDNA.
- Such gene trapping techniques are described in Gruber et al, WO 95/04745 and Gruber et al., U.S. Pat. No. 5,500,356. Kits are commercially available to perform gene trapping experiments from, for example, Life Technologies, Gaithersburg, Maryland, USA.
- RACE Rapid amplification of cDNA ends
- a common primer is designed to anneal to an arbitrary adaptor sequence ligated to cDNA ends (Apte and Siebert, Biotechniques (1993) 75:890-893; Edwards et al, Nuc. Acids Res. (1991) 79:5227-5232).
- a single gene-specific RACE primer is paired with the common primer, preferential amplification of sequences between the single gene specific primer and the common primer occurs.
- Commercial cDNA pools modified for use in RACE are available.
- Another PCR-based method generates full-length cDNA library with anchored ends without needing specific knowledge of the cDNA sequence. This method is described in WO 96/40998.
- the promoter region of a gene generally is located 5' to the initiation site for RNA polymerase II. Hundreds of promoter regions contain the "TATA" box, a sequence such as TATTA or TATAA, which is sensitive to mutations.
- the promoter region can be obtained by performing 5' RACE using a primer from the coding region of the gene. Alternatively, the cDNA can be used as a probe for the genomic sequence, and the region 5' to the coding region is identified by "walking up.” If the gene is highly expressed or differentially expressed, the promoter from the gene can be of use in a regulatory construct for a heterologous gene.
- DNA encoding variants can be prepared by site-directed mutagenesis, described in detail in Sambrook et al., 15.3-15.63.
- the choice of codon or nucleotide to be replaced can be based on disclosure herein on optional changes in amino acids to achieve altered protein structure and/or function.
- nucleic acid comprising nucleotides having the sequence of one or more polynucleotides of the invention can be synthesized.
- the invention encompasses nucleic acid molecules ranging in length from 15 nucleotides (corresponding to at least 15 contiguous nucleotides of one of "SEQ ID NOS: 1-5252") up to a maximum length suitable for one or more biological manipulations, including replication and expression, of the nucleic acid molecule.
- the invention includes but is not limited to (a) nucleic acid having the size of a full gene, and comprising at least one of "SEQ ID NOS: 1-5252;”; (b) the nucleic acid of (a) also comprising at least one additional gene, operably linked to permit expression of a fusion protein; (c) an expression vector comprising (a) or (b); (d) a plasmid comprising (a) or (b) ; and (e) a recombinant viral particle comprising (a) or (b).
- construction or preparation of (a) - (e) are well within the skill in the art.
- sequence of a nucleic acid comprising at least 15 contiguous nucleotides ofat least any one of "SEQ ID NOS : 1 -5252,”, preferably the entire sequence of at least any one of "SEQ ID NOS: 1-5252,” is not limited and can be any sequence of A, T, G, and/or C (for DNA) and A, U, G, and/or C (for RNA) or modified bases thereof, including inosine and pseudouridine.
- sequence will depend on the desired function and can be dictated by coding regions desired, the intron-like regions desired, and the regulatory regions desired.
- nucleic acid obtained is referred to herein as a polynucleotide comprising the sequence of any one of "SEQ ID NOS: 1-5252.”
- polynucleotide e.g. , a polynucleotide having a sequence of one of
- SEQ ID NOS: 1-5252 the corresponding cDNA, or the full-length gene is used to express a partial or complete gene product. Constructs of polynucleotides having sequences of "SEQ ID NOS: 1-5252” can be generated synthetically. Alternatively, single- step assembly of a gene and entire plasmid from large numbers of oligodeoxyribonucleotides is described by, e.g., Stemmer et al, Gene (Amsterdam) (1995) 164(l):49-52>. In this method, assembly PCR (the synthesis of long DNA sequences from large numbers of oligodeoxyribonucleotides (oligos)) is described.
- the method is derived from DNA shuffling (Stemmer, Nature (1994) 370:389-391), and does not rely on DNA ligase, but instead relies on DNA polymerase to build increasingly longer DNA fragments during the assembly process.
- Appropriate polynucleotide constructs are purified using standard recombinant
- yeast Expression systems in yeast include those described in Hinnen et al, Proc. Natl. Acad. Sci. (USA) (1978) 75:1929; Ito et ⁇ /., J Bacteriol (1983) 755:163; Kurtz et al., Mol Cell. Biol. (1986) 5:142; Kunze et al, J. Basic Microbiol. (1985) 25:141; Gleeson et al, J. Gen. Microbiol. (1986) 732:3459; Roggenkamp et al, Mol. Gen. Genet. (1986) 202:302; Das et al, J Bacteriol. (1984) 75S:1165; De Louvencourt et al, J. Bacteriol.
- Mammalian Cells Mammalian expression is accomplished as described in Dijkema et al, EMBO J. (1985) 4:761, Gorman et al, Proc. Natl Acad. Sci. (USA) (1982) 79:6777, Boshart et al, Cell (1985) 47:521 and U.S. Patent No. 4,399,216. Other features of mammalian expression are facilitated as described in Ham and Wallace, Meth. Enz. (1979) 53:44, Barnes and Sato, Anal Biochem. (1980) 702:255, U.S. Patent Nos. 4,767,704, 4,657,866, 4,927,762, 4,560,655, WO 90/103430, WO 87/00195, and U.S. RE 30,985.
- Polynucleotide molecules comprising a polynucleotide sequence provided herein propagated by placing the molecule in a vector.
- Viral and non- viral vectors are used, including plasmids.
- the choice of plasmid will depend on the type of cell in which propagation is desired and the purpose of propagation. Certain vectors are useful for amplifying and making large amounts of the desired DNA sequence.
- Other vectors are suitable for expression in cells in culture.
- Still other vectors are suitable for transfer and expression in cells in a whole animal or person. The choice of appropriate vector is well within the skill of the art. Many such vectors are available commercially.
- the partial or full-length polynucleotide is inserted into a vector typically by means of DNA ligase attachment to a cleaved restriction enzyme site in the vector.
- the desired nucleotide sequence can be inserted by homologous recombination in vivo. Typically this is accomplished by attaching regions of homology to the vector on the flanks of the desired nucleotide sequence. Regions of homology are added by ligation of oligonucleotides, or by polymerase chain reaction using primers comprising both the region of homology and a portion of the desired nucleotide sequence, for example.
- polynucleotides set forth in "SEQ ID NOS: 1-5252" or their corresponding full- length polynucleotides are linked to regulatory sequences as appropriate to obtain the desired expression properties. These can include promoters (attached either at the 5' end of the sense strand or at the 3' end of the antisense strand), enhancers, terminators, operators, repressors, and inducers.
- the promoters can be regulated or constitutive. In some situations it may be desirable to use conditionally active promoters, such as tissue-specific or developmental stage-specific promoters.
- These are linked to the desired nucleotide sequence using the techniques described above for linkage to vectors. Any techniques known in the art can be used.
- the resulting replicated nucleic acid, RNA, expressed protein or polypeptide is within the scope of the invention as a product of the host cell or organism.
- the product is recovered by any appropriate means known in the art.
- Translations of the nucleotide sequence of the provided polynucleotides, cDNAs or full genes can be aligned with individual known sequences. Similarity with individual sequences can be used to determine the activity of the polypeptides encoded by the polynucleotides of the invention. For example, sequences that show similarity with a chemokine sequence can exhibit chemokine activities. Also, sequences exhibiting similarity with more than one individual sequence can exhibit activities that are characteristic of either or both individual sequences.
- the full length sequences and fragments of the polynucleotide sequences of the nearest neighbors can be used as probes and primers to identify and isolate the full length sequence corresponding to provided polynucleotides.
- the nearest neighbors can indicate a tissue or cell type to be used to construct a library for the full-length sequences corresponding to the provided polynucleotides..
- a selected polynucleotide is translated in all six frames to determine the best alignment with the individual sequences.
- the sequences disclosed herein in the Sequence Listing are in a 5' to 3' orientation and translation in three frames can be sufficient (with a few specific exceptions as described in the Examples). These amino acid sequences are referred to, generally, as query sequences, which will be aligned with the individual sequences. Databases with individual sequences are described in "Computer Methods for Macromolecular Sequence Analysis” Methods in Enzymology (1996) 266 ' ,
- Query and individual sequences can be aligned using the methods and computer programs described above, and include BLAST, available over the world wide web at http://ww.ncbi.nlm.nih.gov/BLAST/.
- Another alignment algorithm is Fasta, available in the Genetics Computing Group (GCG) package, Madison, Wisconsin, USA, a wholly owned subsidiary of Oxford Molecular Group, Inc. Other techniques for alignment are described in Doolittle, supra.
- GCG Genetics Computing Group
- an alignment program that permits gaps in the sequence is utilized to align the sequences.
- the Smith- Waterman is one type of algorithm that permits gaps in sequence alignments. See Meth. Mol Biol. (1997) 70: 173-187.
- the GAP program using the Needleman and Wunsch alignment method can be utilized to align sequences.
- An alternative search strategy uses MPSRCH software, which runs on a MASPAR computer.
- MPSRCH uses a Smith- Waterman algorithm to score sequences on a massively parallel computer. This approach improves ability to identify sequences that are distantly related matches, and is especially tolerant of small gaps and nucleotide sequence errors.
- Amino acid sequences encoded by the provided polynucleotides can be used to search both protein and DNA databases.
- Results of individual and query sequence alignments can be divided into three categories, high similarity, weak similarity, and no similarity.
- Individual alignment results ranging from high similarity to weak similarity provide a basis for determining polypeptide activity and/or structure. Parameters for categorizing individual results include: percentage of the alignment region length where the strongest alignment is found, percent sequence identity, and p value.
- the percentage of the alignment region length is calculated by counting the number of residues of the individual sequence found in the region of strongest alignment, e.g., contiguous region of the individual sequence that contains the greatest number of residues that are identical to the residues of the corresponding region of the aligned query sequence. This number is divided by the total residue length of the query sequence to calculate a percentage. For example, a query sequence of 20 amino acid residues might be aligned with a 20 amino acid region of an individual sequence. The individual sequence might be identical to amino acid residues 5, 9-15, and 17-19 of the query sequence. The region of strongest alignment is thus the region stretching from residue 9-19, an 11 amino acid stretch. The percentage of the alignment region length is: 11 (length of the region of strongest alignment) divided by (query sequence length) 20 or 55%).
- Percent sequence identity is calculated by counting the number of amino acid matches between the query and individual sequence and dividing total number of matches by the number of residues of the individual sequences found in the region of strongest alignment. Thus, the percent identity in the example above would be 10 matches divided by 11 amino acids, or approximately, 90.9%
- P value is the probability that the alignment was produced by chance.
- the p value can be calculated according to Karlin et al, Proc. Natl. Acad. Sci. (1990) 37:2264 and Karlin et al., Proc. Natl. Acad. Sci. (1993) 90.
- the p value of multiple alignments using the same query sequence can be calculated using an heuristic approach described in Altschul et al., Nat. Genet. (1994) 6: 19.
- Alignment programs such as BLAST program can calculate the p value.
- Another factor to consider for determining identity or similarity is the location of the similarity or identity. Strong local alignment can indicate similarity even if the length of alignment is short.
- Sequence identity scattered throughout the length of the query sequence also can indicate a similarity between the query and profile sequences.
- the boundaries of the region where the sequences align can be determined according to Doolittle, supra; BLAST or FAST programs; or by determining the area where sequence identity is highest. High Similarity.
- the percent of the alignment region length is typically at least about 55% of total length query sequence; more typically, at least about 58%; even more typically; at least about 60% of the total residue length of the query sequence.
- percent length of the alignment region can be as much as about 62%; more usually, as much as about 64%; even more usually, as much as about 66%).
- the region of alignment typically, exhibits at least about 75% of sequence identity; more typically, at least about 78%; even more typically; at least about 80% sequence identity.
- percent sequence identity can be as much as about 82%; more usually, as much as about 84%; even more usually, as much as about 86%.
- the p value is used in conjunction with these methods. If high similarity is found, the query sequence is considered to have high similarity with a profile sequence when the p value is less than or equal to about IO "2 ; more usually; less than or equal to about IO "3 ; even more usually; less than or equal to about IO "4 . More typically, the p value is no more than about 10 "5 ; more typically; no more than or equal to about 10 "10 ; even more typically; no more than or equal to about IO "15 for the query sequence to be considered high similarity.
- weak Similarity In general, where alignment results considered to be of weak similarity, there is no minimum percent length of the alignment region nor minimum length of alignment. A better showing of weak similarity is considered when the region of alignment is, typically, at least about 15 amino acid residues in length; more typically, at least about 20; even more typically; at least about 25 amino acid residues in length. Usually, length of the alignment region can be as much as about 30 amino acid residues; more usually, as much as about 40; even more usually, as much as about 60 amino acid residues. Further, for weak similarity, the region of alignment, typically, exhibits at least about 35% of sequence identity; more typically, at least about 40%; even more typically; at least about 45% sequence identity.
- percent sequence identity can be as much as about 50%; more usually, as much as about 55%; even more usually, as much as about 60%. If low similarity is found, the query sequence is considered to have weak similarity with a profile sequence when the p value is usually less than or equal to about IO "2 ; more usually; less than or equal to about IO "3 ; even more usually; less than or equal to about 10 "4 . More typically, the p value is no more than about IO "5 ; more usually; no more than or equal to about IO "10 ; even more usually; no more than or equal to about IO "15 for the query sequence to be considered weak similarity.
- Sequence identity alone can be used to determine similarity of a query sequence to an individual sequence and can indicate the activity of the sequence. Such an alignment, preferably, permits gaps to align sequences.
- the query sequence is related to the profile sequence if the sequence identity over the entire query sequence is at least about 15%; more typically, at least about 20%; even more typically, at least about 25%; even more typically, at least about 50%.
- Sequence identity alone as a measure of similarity is most useful when the query sequence is usually, at least 80 residues in length; more usually, 90 residues; even more usually, at least 95 amino acid residues in length. More typically, similarity can be concluded based on sequence identity alone when the query sequence is preferably 100 residues in length; more preferably, 120 residues in length; even more preferably, 150 amino acid residues in length.
- Translations of the provided polynucleotides can be aligned with amino acid profiles that define either protein families or common motifs. Also, translations of the provided polynucleotides can be aligned to multiple sequence alignments (MSA) comprising the polypeptide sequences of members of protein families or motifs. Similarity or identity with profile sequences or MS As can be used to determine the activity of the gene products (e.g., polypeptides) encoded by the provided polynucleotides or corresponding cDNA or genes. For example, sequences that show an identity or similarity with a chemokine profile or MSA can exhibit chemokine activities.
- MSA sequence alignments
- MSAs can designed manually by (1) creating an MSA, which is an alignment of the amino acid sequence of members that belong to the family and (2) constructing a statistical representation of the alignment. Such methods are described, for example, in Birney et al, Nucl Acid Res. (1996) 24(14): 2730-2739. MSAs of some protein families and motifs are publicly available. For example, http://genome.wustl.edu Pfam/ includes MSAs of 547 different families and motifs. These MSAs are described also in
- Similarity between a query sequence and a protein family or motif can be determined by (a) comparing the query sequence against the profile and/or (b) aligning the query sequence with the members of the family or motif.
- a program such as Searchwise is used to compare the query sequence to the statistical representation of the multiple alignment, also known as a profile.
- the program is described in Birney et al, supra.
- Other techniques to compare the sequence and profile are described in Sonnhammer et al, supra and Doolittle, supra.
- methods described by Feng et al, J. Mol Evol (1987) 25:351 and Higgins et al, CABIOS (1989) 5:151 can be used align the query sequence with the members of a family or motif, also known as a MSA.
- Computer programs such as PILEUP, can be used. See Feng et al, infra. In general, the following factors are used to determine if a similarity between a query sequence and a profile or MSA exists: (1) number of conserved residues found in the query sequence, (2) percentage of conserved residues found in the query sequence, (3) number of frameshifts, and (4) spacing between conserved residues.
- Some alignment programs that both translate and align sequences can make any number of frameshifts when translating the nucleotide sequence to produce the best alignment.
- the fewer frameshifts needed to produce an alignment the stronger the similarity or identity between the query and profile or MSAs.
- a weak similarity resulting from no frameshifts can be a better indication of activity or structure of a query sequence, than a strong similarity resulting from two frameshifts.
- three or fewer frameshifts are found in an alignment; more preferably two or fewer frameshifts; even more preferably, one or fewer frameshifts; even more preferably, no frameshifts are found in an alignment of query and profile or MSAs.
- conserved residues are those amino acids found at a particular position in all or some of the family or motif members. For example, most chemokines contain four conserved cysteines. Alternatively, a position is considered conserved if only a certain class of amino acids is found in a particular position in all or some of the family members. For example, the N-terminal position can contain a positively charged amino acid, such as lysine, arginine, or histidine.
- a residue of a polypeptide is conserved when a class of amino acids or a single amino acid is found at a particular position in at least about 40% of all class members; more typically, at least about 50%; even more typically, at least about 60% of the members.
- a residue is conserved when a class or single amino acid is found in at least about 70% of the members of a family or motif; more usually, at least about 80%; even more usually, at least about 90%; even more usually, at least about 95%.
- a residue is considered conserved when three unrelated amino acids are found at a particular position in the some or all of the members; more usually, two unrelated amino acids. These residues are conserved when the unrelated amino acids are found at particular positions in at least about 40% of all class member; more typically, at least about 50%; even more typically, at least about 60% of the members. Usually, a residue is conserved when a class or single amino acid is found in at least about 70% of the members of a family or motif; more usually, at least about 80%; even more usually, at least about 90%; even more usually, at least about 95%.
- a query sequence has similarity to a profile or MSA when the query sequence comprises at least about 25% of the conserved residues of the profile or MSA; more usually, at least about 30%; even more usually; at least about 40%.
- the query sequence has a stronger similarity to a profile sequence or MSA when the query sequence comprises at least about 45% of the conserved residues of the profile or MSA; more typically, at least about 50%; even more typically; at least about 55%.
- Profiles The identify and function of the gene that correlates to a polynucleotide described herein can be determined by screening the polynucleotides or their corresponding amino acid sequences against profiles of protein families. Such profiles focus on common structural motifs among proteins of each family. Publicly available profiles are described above in Section IVA. Additional or alternative profiles are described below.
- a signal sequence is usually encoded by both secreted and membrane-bound polypeptide genes to direct a polypeptide to the surface of the cell.
- the signal sequence usually comprises a stretch of hydrophobic residues.
- Such signal sequences can fold into helical structures.
- Membrane-bound polypeptides typically comprise at least one transmembrane region that possesses a stretch of hydrophobic amino acids that can transverse the membrane. Some transmembrane regions also exhibit a helical structure.
- Hydrophobic fragments within a polypeptide can be identified by using computer algorithms. Such algorithms include Hopp & WoodSi Proc. Natl. Acad. Sci. USA (1981) 73:3824-3828; Kyte & Doolittle, J.
- Another method of identifying secreted and membrane-bound polypeptides is to translate the polynucleotides of the invention in all six frames and determine if at least 8 contiguous hydrophobic amino acids are present. Those translated polypeptides with at least 8; more typically, 10; even more typically, 12 contiguous hydrophobic amino acids are considered to be either a putative secreted or membrane bound polypeptide.
- Hydrophobic amino acids include alanine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan, tyrosine, and valine.
- RNA oligonucleotides can also be synthesized, for example, using RNA phosphoramidites.
- This method can be performed on an automated synthesizer, such as Applied Biosystems, Models 392 and 394, Foster City, California, USA. See Applied Biosystems User Bulletin 53 and Ogilvie et al, Pure & Applied Chem. (1987) 59:325.
- Phosphorothioate oligonucleotides can also be synthesized for antisense construction.
- a sulfurizing reagent such as tetraethylthiruam disulfide (TETD) in acetonitrile can be used to convert the internucleotide cyanoethyl phosphite to the phosphorothioate triester within 15 minutes at room temperature.
- TETD replaces the iodine reagent, while all other reagents used for standard phosphoramidite chemistry remain the same.
- Such a synthesis method can be automated using Models 392 and 394 by Applied Biosystems, for example.
- Oligonucleotides of up to 200 nucleotides can be synthesized, more typically, 100 nucleotides, more typically 50 nucleotides; even more typically 30 to 40 nucleotides. These synthetic fragments can be annealed and ligated together to construct larger fragments. See, for example, Sambrook et al, supra. A. Ribozymes
- Trans-cleaving catalytic RNAs are RNA molecules possessing endoribonuclease activity. Ribozymes are specifically designed for a particular target, and the target message must contain a specific nucleotide sequence. They are engineered to cleave any RNA species site-specifically in the background of cellular RNA. The cleavage event renders the mRNA unstable and prevents protein expression. Importantly, ribozymes can be used to inhibit expression of a gene of unknown function for the purpose of determining its function in an in vitro or in vivo context, by detecting the phenotypic effect.
- ribozyme motif is the hammerhead, for which the substrate sequence requirements are minimal. Design of the hammerhead ribozyme is disclosed in Usman et al, Current Opin. Struct. Biol. (1996) 6:527. Ribozymes can also be prepared and used as described in Long et al, FASEBJ. (1993) 7:25; Symons, Ann. Rev. Biochem. (1992) 67:641; Perrotta et al, Biochem. (1992) 37:16; Ojwang et al, Proc. Natl Acad.
- Ribozyme cleavage of HIV-I RNA is described in U.S. Patent No. 5,144,019; methods of cleaving RNA using ribozymes is described in U.S. Patent No. 5,116,742; and methods for increasing the specificity of ribozymes are described in U.S. Patent No. 5,225,337 and Koizumi et al, Nucleic Acid Res. (1989) 77:7059.
- Preparation and use of ribozyme fragments in a hammerhead structure are also described by Koizumi et al, Nucleic Acids Res. (1989) 77:7059.
- ribozyme fragments in a hairpin structure are described by Chowrira and Burke, Nucleic Acids Res. (1992) 20:2835. Ribozymes can also be made by rolling transcription as described in Daubendiek and Kool, Nat. Biotechnol (1997) 15(3):213. The hybridizing region of the ribozyme can be modified or can be prepared as a branched structure as described in Horn and Urdea, Nucleic Acids Res. (1989) 77:6959. The basic structure of the ribozymes can also be chemically altered in ways familiar to those skilled in the art, and chemically synthesized ribozymes can be administered as synthetic oligonucleotide derivatives modified by monomeric units. In a therapeutic context, liposome mediated delivery of ribozymes improves cellular uptake, as described in Birikh et al, Eur. J. Biochem. (1997) 245:1.
- Ribozymes are designed to specifically bind and cut the corresponding mRNA species. Ribozymes thus provide a means to inhibit the expression of any of the proteins encoded by the disclosed polynucleotides or their full-length genes. The full-length gene need not be known in order to design and use specific inhibitory ribozymes. In the case of a polynucleotide or full-length cDNA of unknown function, ribozymes corresponding to that nucleotide sequence can be tested in vitro for efficacy in cleaving the target transcript. Those ribozymes that effect cleavage in vitro are further tested in vivo.
- the ribozyme can also be used to generate an animal model for a disease, as described in Birikh et al, supra.
- An effective ribozyme is used to determine the function of the gene of interest by blocking its transcription and detecting a change in the cell.
- an effective ribozyme is designed and delivered in a gene therapy for blocking transcription and expression of the gene.
- ribozymes proceed beginning with knowledge of a portion of the coding sequence of the gene to be inhibited.
- a partial polynucleotide sequence provides adequate sequence for constructing an effective ribozyme.
- a target cleavage site is selected in the target sequence, and a ribozyme is constructed based on the 5' and 3' nucleotide sequences that flank the cleavage site.
- Retroviral vectors are engineered to express monomeric and multimeric hammerhead ribozymes targeting the mRNA of the target coding sequence. These monomeric and multimeric ribozymes are tested in vitro for an ability to cleave the target mRNA.
- a cell line is stably transduced with the retroviral vectors expressing the ribozymes, and the transduction is confirmed by Northern blot analysis and reverse-transcription polymerase chain reaction (RT-PCR).
- RT-PCR reverse-transcription polymerase chain reaction
- the cells are screened for inactivation of the target mRNA by such indicators as reduction of expression of disease markers or reduction of the gene product of the target mRNA.
- Antisense nucleic acids are designed to specifically bind to RNA, resulting in the formation of RNA-DNA or RNA-RNA hybrids, with an arrest of DNA replication, reverse transcription or messenger RNA translation.
- Antisense polynucleotides based on a selected polynucleotide sequence can interfere with expression of the corresponding gene.
- Antisense polynucleotides are typically generated within the cell by expression from antisense constructs that contain the antisense strand as the transcribed strand.
- Antisense polynucleotides based on the disclosed polynucleotides will bind and/or interfere with the translation of mRNA comprising a sequence complementary to the antisense polynucleotide.
- the expression products of control cells and cells treated with the antisense construct are compared to detect the protein product of the gene corresponding to the polynucleotide upon which the antisense construct is based.
- the protein is isolated and identified using routine biochemical methods.
- polynucleotides of the invention can be used as additional potential therapeutics.
- the choice of polynucleotide can be narrowed by first testing them for binding to "hot spot" regions of the genome of cancerous cells. If a polynucleotide is identified as binding to a "hot spot", testing the polynucleotide as an antisense compound in the corresponding cancer cells clearly is warranted.
- dominant negative mutations are readily generated for corresponding proteins that are active as homomultimers.
- a mutant polypeptide will interact with wild-type polypeptides (made from the other allele) and form a non-functional multimer.
- a mutation is in a substrate-binding domain, a catalytic domain, or a cellular localization domain.
- the mutant polypeptide will be overproduced. Point mutations are made that have such an effect.
- fusion of different polypeptides of various lengths to the terminus of a protein can yield dominant negative mutants.
- General strategies are available for making dominant negative mutants (see, e.g., Herskowitz, Nature (1987) 329:219). Such techniques can be used to create loss of function mutations, which are useful for determining protein function.
- polypeptides of the invention include those encoded by the disclosed polynucleotides. These polypeptides can also be encoded by nucleic acids that, by virtue of the degeneracy of the genetic code, are not identical in sequence to the disclosed polynucleotides. Thus, the invention includes within its scope a polypeptide encoded by a polynucleotide having the sequence of any one of "SEQ ID NOS: 1-5252" or a variant thereof.
- polypeptide refers to both the full length polypeptide encoded by the recited polynucleotide, the polypeptide encoded by the gene represented by the recited polynucleotide, as well as portions or fragments thereof.
- Polypeptides also includes variants of the naturally occurring proteins, where such variants are homologous or substantially similar to the naturally occurring protein, and can be of an origin of the same or different species as the naturally occurring protein (e.g., human, murine, or some other species that naturally expresses the recited polypeptide, usually a mammalian species).
- variant polypeptides have a sequence that has at least about 80%, usually at least about 90%, and more usually at least about 98% sequence identity with a differentially expressed polypeptide of the invention, as measured by
- the variant polypeptides can be naturally or non-naturally glycosylated, i.e., the polypeptide has a glycosylation pattern that differs from the glycosylation pattern found in the corresponding naturally occurring protein.
- the invention also encompasses homologs of the disclosed polypeptides (or fragments thereof) where the homologs are isolated from other species, i.e. other animal or plant species, where such homologs, usually mammalian species, e.g. rodents, such as mice, rats; domestic animals, e.g., horse, cow, dog, cat; and humans.
- homolog a polypeptide having at least about 35%, usually at least about 40% and more usually at least about 60% amino acid sequence identity a particular differentially expressed protein as identified above, where sequence identity is determined using the BLAST algorithm, with the parameters described supra.
- the polypeptides of the subject invention are provided in a non-naturally occurring environment, e.g. are separated from their naturally occurring environment.
- the subject protein is present in a composition that is enriched for the protein as compared to a control.
- purified polypeptide is provided, where by purified is meant that the protein is present in a composition that is substantially free of non-differentially expressed polypeptides, where by substantially free is meant that less than 90%), usually less than 60% and more usually less than 50%) of the composition is made up of non-differentially expressed polypeptides.
- variants include mutants, fragments, and fusions.
- Mutants can include amino acid substitutions, additions or deletions.
- the amino acid substitutions can be conservative amino acid substitutions or substitutions to eliminate non-essential amino acids, such as to alter a glycosylation site, a phosphorylation site or an acetylation site, or to minimize misfolding by substitution or deletion of one or more cysteine residues that are not necessary for function.
- Conservative amino acid substitutions are those that preserve the general charge, hydrophobicity/hydrophilicity, and/or steric bulk of the amino acid substituted.
- substitutions between the following groups are conservative: Gly/Ala, Val/Ile/Leu, Asp/Glu, Lys/Arg, Asn/Gln, Ser/Cys, Thr, and Phe/Trp/Tyr.
- Variants can be designed so as to retain biological activity of a particular region of the protein (e.g., a functional domain and/or, where the polypeptide is a member of a protein family, a region associated with a consensus sequence).
- a particular region of the protein e.g., a functional domain and/or, where the polypeptide is a member of a protein family, a region associated with a consensus sequence.
- Osawa et al, Biochem. Mol Int. (1994) 34:1003 discusses the actin binding region of a protein from several different species. The actin binding regions of the these species are considered homologous based on the fact that they have amino acids that fall within "homologous residue groups.” Homologous residues are judged according to the following groups (using single letter amino acid designations): STAG; ILVMF; HRK; DEQN; and FYW. For example, and S, a T, an A or a G can be in a position and the function (in this case act
- Amino acid residues were classified into one of three groups depending on their polarity: polar (Arg, Lys, His, Gin, Asn, Asp, and Glu); weak polar (Ala, Pro, Gly, Thr, and Ser), and nonpolar (Cys, Val, Met, He, Leu, Phe, Tyr, and Tip). Amino acid replacements during protein evolution were very conservative: 88% and 76% of them in the interior or exterior, respectively, were within the same group of the three. Inter-group replacements are such that weak polar residues are replaced more often by nonpolar residues in the interior and more often by polar residues on the exterior.
- variants can be constructed according to methods disclosed in U.S. Patent No. 4,959,314, which discloses substitution of cysteines with other amino acids, and methods for assaying biological activity and effect of the substitution. Such methods are suitable for proteins according to this invention that have cysteine residues suitable for such substitutions, for example to eliminate disulfide bond formation. Variants also include fragments of the polypeptides disclosed herein, particularly biologically active fragments and/or fragments corresponding to functional domains.
- Fragments of interest will typically be at least about 10 aa to at least about 15 aa in length, usually at least about 50 aa in length, and can be as long as 300 aa in length or longer, but will usually not exceed about 1000 aa in length, where the fragment will have a stretch of amino acids that is identical to a polypeptide encoded by a polynucleotide having a sequence of any "SEQ ID NOS: 1-5252", or a homolog thereof.
- the protein variants described herein are encoded by polynucleotides that are within the scope of the invention.
- the genetic code can be used to select the appropriate codons to construct the corresponding variants.
- a library of polynucleotides is a collection of sequence information, which information is provided in either biochemical form (e.g., as a collection of polynucleotide molecules), or in electronic form (e.g., as a collection of polynucleotide sequences stored in a computer-readable form, as in a computer system and/or as part of a computer program).
- the sequence information of the polynucleotides can be used in a variety of ways, e.g., as a resource for gene discovery, as a representation of sequences expressed in a selected cell type (e.g., cell type markers), and/or as markers of a given disease or disease state.
- a disease marker is a representation of a gene product that is present in all cells affected by disease either at an increased or decreased level relative to a normal cell (e.g., a cell of the same or similar type that is not substantially affected by disease).
- a polynucleotide sequence in a library can be a polynucleotide that represents an mRNA, polypeptide, or other gene product encoded by the polynucleotide, that is either overexpressed or underexpressed in a breast ductal cell affected by cancer relative to a normal (i.e., substantially disease-free) breast cell.
- the nucleotide sequence information of the library can be embodied in any suitable form, e.g., electronic or biochemical forms.
- a library of sequence information embodied in electronic form includes an accessible computer data file (or, in biochemical form, a collection of nucleic acid molecules) that contains the representative nucleotide sequences of genes that are differentially expressed (e.g., overexpressed or underexpressed) as between, for example, i) a cancerous cell and a normal cell; ii) a cancerous cell and a dysplastic cell; iii) a cancerous cell and a cell affected by a disease or condition other than cancer; iv) a metastatic cancerous cell and a normal cell and/or non-metastatic cancerous cell; v) a malignant cancerous cell and a non-malignant cancerous cell (or a normal cell) and/or vi) a dysplastic cell relative to a normal cell.
- Biochemical embodiments of the library include a collection of nucleic acids that have the sequences of the genes in the library, where the nucleic acids can correspond to the entire gene in the library or to a fragment thereof, as described in greater detail below.
- the polynucleotide libraries of the subject invention include sequence information of a plurality of polynucleotide sequences, where at least one of the polynucleotides has a sequence of any of "SEQ ID NOS:l-5252.”
- plurality is meant at least 2, usually at least 3 and can include up to all of "SEQ ID NOS: 1-5252.”
- the length and number of polynucleotides in the library will vary with the nature of the library, e.g., if the library is an oligonucleotide array, a cDNA array, a computer database of the sequence information, etc.
- the nucleic acid sequence information can be present in a variety of media.
- Media refers to a manufacture, other than an isolated nucleic acid molecule, that contains the sequence information of the present invention.
- Such a manufacture provides the genome sequence or a subset thereof in a form that can be examined by means not directly applicable to the sequence as it exists in a nucleic acid.
- the nucleotide sequence of the present invention e.g. the nucleic acid sequences of any of the polynucleotides of "SEQ ID NOS: 1-5252," can be recorded on computer readable media, e.g. any medium that can be read and accessed directly by a computer.
- Such media include, but are not limited to: magnetic storage media, such as a floppy disc, a hard disc storage medium, and a magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media.
- sequence information can be provided in conjunction or connection with other computer-readable information and/or other types of computer-readable files (e.g., searchable files, executable files, etc, including, but not limited to, for example, search program software, etc.).
- computer-readable information e.g., searchable files, executable files, etc, including, but not limited to, for example, search program software, etc.
- the information can be accessed for a variety of purposes.
- Computer software to access sequence information is publicly available.
- the BLAST Altschul et al., supra.
- BLAZE Bruntlag et al. Comp. Chem. (1993) 17:203
- search algorithms on a Sybase system can be used to identify open reading frames (ORFs) within the genome that contain homology to ORFs from other organisms.
- a computer-based system refers to the hardware means, software means, and data storage means used to analyze the nucleotide sequence information of the present invention.
- the minimum hardware of the computer-based systems of the present invention comprises a central processing unit (CPU), input means, output means, and data storage means.
- CPU central processing unit
- the data storage means can comprise any manufacture comprising a recording of the present sequence information as described above, or a memory access means that can access such a manufacture.
- Search means refers to one or more programs implemented on the computer-based system, to compare a target sequence or target structural motif with the stored sequence information.
- Target sequence can be any DNA or amino acid sequence of six or more nucleotides or two or more amino acids, preferably from about 10 to 100 amino acids or from about 30 to 300 nucleotide residues.
- target structural motif refers to any rationally selected sequence or combination of sequences in which the sequence(s) are chosen based on a three-dimensional configuration that is formed upon the folding of the target motif, or on consensus sequences of regulatory or active sites.
- target motifs include, but arc not limited to, enzyme active sites and signal sequences.
- Nucleic acid target motifs include, but are not limited to, hairpin structures, promoter sequences and other expression elements such as binding sites for transcription factors.
- a variety of structural formats for the input and output means can be used to input and output the information in the computer-based systems of the present invention.
- One format for an output means ranks fragments of the genome possessing varying degrees of homology to a target sequence or target motif. Such presentation provides a skilled artisan with a ranking of sequences and identifies the degree of sequence similarity contained in the identified fragment.
- comparing means can be used to compare a target sequence or target motif with the data storage means to identify sequence fragments of the genome.
- a skilled artisan can readily recognize that any one of the publicly available homology search programs can be used as the search means for the computer based systems of the present invention.
- the "library” of the invention also encompasses biochemical libraries of the polynucleotides of "SEQ ID NOS: 1-5252," e.g., collections of nucleic acids representing the provided polynucleotides.
- the biochemical libraries can take a variety of forms, e.g., a solution of cDNAs, a pattern of probe nucleic acids stably associated with a surface of a solid support (i.e., an array) and the like.
- nucleic acid arrays in which one or more of "SEQ ID NOS:l-5252"is represented on the array.
- array is meant a an article of manufacture that has at least a substrate with at least two distinct nucleic acid targets on one of its surfaces, where the number of distinct nucleic acids can be considerably higher, typically being at least 10 nt, usually at least 20 nt and often at least 25 nt.
- array formats have been developed and are known to those of skill in the art, including those described in 5,242,974; 5,384,261; 5,405,783; 5,412,087; 5,424,186; 5,429,807; 5,436,327; 5,445,934; 5,472,672; 5,527,681 ; 5,529,756; 5,545,531; 5,554,501; 5,556,752; 5,561,071; 5,599,895; 5,624,711; 5,639,603; 5,658,734; WO 93/17126; WO 95/11995; WO 95/35505; EP 742287; and EP 799897.
- the arrays of the subject invention find use in a variety of applications, including gene expression analysis, drug screening, mutation analysis and the like, as disclosed in the above-listed exemplary patent documents.
- analogous libraries of polypeptides are also provided, where the where the polypeptides of the library will represent at least a portion of the polypeptides encoded by "SEQ ID NOS: 1-5252.”
- Polynucleotide probes are used for a variety of purposes, such as chromosome mapping of the polynucleotide and detection of transcription levels. Additional disclosure about preferred regions of the disclosed polynucleotide sequences is found in the Examples.
- a probe that hybridizes specifically to a polynucleotide disclosed herein should provide a detection signal at least 5-, 10-, or 20-fold higher than the background hybridization provided with other unrelated sequences.
- Nucleotide probes are used to detect expression of a gene corresponding to the provided polynucleotide. In Northern blots, mRNA is separated electrophoretically and contacted with a probe. A probe is detected as hybridizing to an mRNA species of a particular size. The amount of hybridization is quantitated to determine relative amounts of expression, for example under a particular condition. Probes are used for in situ hybridization to cells to detect expression. Probes can also be used in vivo for diagnostic detection of hybridizing sequences. Probes are typically labeled with a radioactive isotope. Other types of detectable labels can be used such as chromophores, fluors, and enzymes.
- nucleotide hybridization assays are described in WO92/02526 and U.S. Patent No. 5,124,246.
- the Polymerase Chain Reaction (PCR) is another means for detecting small amounts of target nucleic acids (see, e.g., Mullis et al, Meth. Enzymol (1987) 755:335; U.S. Patent No. 4,683,195; and U.S. Patent No. 4,683,202).
- Two primer polynucleotides nucleotides hybridize with the target nucleic acids and are used to prime the reaction.
- the primers can be composed of sequence within or 3' and 5' to the polynucleotides of the Sequence Listing.
- primers are 3' and 5' to these polynucleotides, they need not hybridize to them or the complements.
- a thermostable polymerase creates copies of target nucleic acids from the primers using the original target nucleic acids as a template. After a large amount of target nucleic acids is generated by the polymerase, it is detected by methods such as Southern blots. When using the Southern blot method, the labeled probe will hybridize to a polynucleotide of the Sequence Listing or complement.
- mRNA or cDNA can be detected by traditional blotting techniques described in Sambrook et al, "Molecular Cloning: A Laboratory Manual” (New York, Cold Spring Harbor Laboratory, 1989).
- mRNA or cDNA generated from mRNA using a polymerase enzyme can be purified and separated using gel electrophoresis. The nucleic acids on the gel are then blotted onto a solid support, such as nitrocellulose. The solid support is exposed to a labeled probe and then washed to remove any unhybridized probe. Next, the duplexes containing the labeled probe are detected. Typically, the probe is labeled with radioactivity. Mapping.
- Polynucleotides of the present invention are used to identify a chromosome on which the corresponding gene resides. Such mapping can be useful in identifying the function of the polynucleotide-related gene by its proximity to other genes with known function. Function can also be assigned to the polynucleotide-related gene when particular syndromes or diseases map to the same chromosome. For example, use of polynucleotide probes in identification and quantification of nucleic acid sequence aberrations is described in U.S. Patent No. 5,783,387.
- FISH fluorescence in situ hybridization
- Polynucleotides are mapped to particular chromosomes using, for example, radiation hybrids or chromosome-specific hybrid panels. See Leach et al, Advances in Genetics, (1995) 33:63-99; Walter et al, Nature Genetics (1994) 7:22; Walter and
- RHMAP can be used to construct a map based on the data from radiation hybridization with a measure of the relative likelihood of one order versus another.
- RHMAP is available via the world wide web at http://www.sph.umich.edu/group/statgen/software.
- polynucleotides based on the polynucleotides of the invention can be used to probe these regions. For example, if through profile searching a provided polynucleotide is identified as corresponding to a gene encoding a kinase, its ability to bind to a cancer-related chromosomal region will suggest its role as a kinase in one or more stages of tumor cell development growth. Although some experimentation would be required to elucidate the role, the polynucleotide constitutes a new material for isolating a specific protein that has potential for developing a cancer diagnostic or therapeutic.
- Tissue Typing or Profiling Expression of specific mRNA corresponding to the provided polynucleotides can vary in different cell types and can be tissue-specific. This variation of mRNA levels in different cell types can be exploited with nucleic acid probe assays to determine tissue types. For example, PCR, branched DNA probe assays, or blotting techniques utilizing nucleic acid probes substantially identical or complementary to polynucleotides listed in the Sequence Listing can determine the presence or absence of the corresponding cDNA or mRNA. For example, a metastatic lesion is identified by its developmental organ or tissue source by identifying the expression of a particular marker of that organ or tissue.
- a polynucleotide is expressed only in a specific tissue type, and a metastatic lesion is found to express that polynucleotide, then the developmental source of the lesion has been identified. Expression of a particular polynucleotide is assayed by detection of either the corresponding mRNA or the protein product. Immunological methods, such as antibody staining, are used to detect a particular protein product. Hybridization methods can be used to detect particular mRNA species, including but not limited to in situ hybridization and Northern blotting.
- a polynucleotide of the invention will be useful in forensics, genetic analysis, mapping, and diagnostic applications if the corresponding region of a gene is polymo ⁇ hic in the human population.
- Particular polymo ⁇ hic forms of the provided polynucleotides can be used to either identify a sample as deriving from a suspect or rule out the possibility that the sample derives from the suspect. Any means for detecting a polymo ⁇ hism in a gene are used, including but not limited to electrophoresis of protein polymo ⁇ hic variants, differential sensitivity to restriction enzyme cleavage, and hybridization to allele-specific probes.
- Expression products of a polynucleotide of the invention are prepared and used for raising antibodies for experimental, diagnostic, and therapeutic pu ⁇ oses. For polynucleotides to which a corresponding gene has not been assigned, this provides an additional method of identifying the corresponding gene.
- the polynucleotide or related cDNA is expressed as described above, and antibodies are prepared. These antibodies are specific to an epitope on the polypeptide encoded by the polynucleotide, and can precipitate or bind to the corresponding native protein in a cell or tissue preparation or in a cell-free extract of an in vitro expression system.
- Immunogens for raising antibodies are prepared by mixing the polypeptides encoded by the polynucleotides of the present invention with adjuvants. Alternatively, polypeptides are made as fusion proteins to larger immunogenic proteins. Polypeptides are also covalently linked to other larger immunogenic proteins, such as keyhole limpet hemocyanin. Immunogens are typically administered intradermally, subcutaneously, or intramuscularly. Immunogens are administered to experimental animals such as rabbits, sheep, and mice, to generate antibodies. Optionally, the animal spleen cells are isolated and fused with myeloma cells to form hybridomas which secrete monoclonal antibodies. Such methods are well known in the art.
- the selected polynucleotide is administered directly, such as by intramuscular injection, and expressed in vivo.
- the expressed protein generates a variety of protein-specific immune responses, including production of antibodies, comparable to administration of the protein.
- polyclonal and monoclonal antibodies specific for polypeptides encoded by a selected polynucleotide are made using standard methods known in the art.
- the antibodies specifically bind to epitopes present in the polypeptides encoded by polynucleotides disclosed in the Sequence Listing.
- epitopes which involve non-contiguous amino acids may require more, for example at least 15, 25, or 50 amino acids.
- a short sequence of a polynucleotide may then be unsuitable for use as an epitope to raise antibodies for identifying the corresponding novel protein, because of the potential for cross-reactivity with a known protein.
- the antibodies can be useful for other pu ⁇ oses, particularly if they identify common structural features of a known protein and a novel polypeptide encoded by a polynucleotide of the invention.
- Antibodies that specifically bind to human polypeptides encoded by the provided polypeptides should provide a detection signal at least 5-, 10-, or 20-fold higher than a detection signal provided with other proteins when used in Western blots or other immunochemical assays.
- antibodies that specifically polypeptides of the invention do not bind to other proteins in immunochemical assays at detectable levels and can immunoprecipitate the specific polypeptide from solution.
- human antibodies are purified by methods well known in the art.
- the antibodies are affinity purified by passing antiserum over a column to which the corresponding selected polypeptide or fusion protein is bound.
- the bound antibodies can then be eluted from the column, for example using a buffer with a high salt concentration.
- genetically engineered antibody derivatives are made, such as single chain antibodies, according to methods well known in the art.
- Polynucleotide arrays provide a high throughput technique that can assay a large number of polynucleotide sequences in a sample. This technology can be used as a diagnostic and as a tool to test for differential expression to determine function of an encoded protein.
- Arrays can be created by spotting polynucleotide probes onto a substrate (e.g., glass, nitrocelllose, etc.) in a two-dimensional matrix or array having bound probes. The probes can be bound to the substrate by either covalent bonds or by non-specific interactions, such as hydrophobic interactions.
- Samples of polynucleotides can be detectably labeled (e.g., using radioactive or fluorescent labels) and then hybridized to the probes. Double stranded polynucleotides, comprising the labeled sample polynucleotides bound to probe polynucleotides, can be detected once the unbound portion of the sample is washed away. Techniques for constructing arrays and methods of using these arrays are described in EP No. 0 799 897; PCT No. WO 97/29212; PCT No. WO 97/27317; EP No. 0 785 280; PCT No. WO 97/02357; U.S. Pat. No. 5,593,839; U.S. Pat. No.
- arrays can be used to examine differential expression of genes and can be used to determine gene function.
- arrays of the instant polynucleotide sequences can be used to determine if any of the provided polynucleotides are differentially expressed between a test cell and control cell (e.g., cancer cells and normal cells).
- high expression of a particular message in a cancer cell can indicate a cancer specific protein.
- Exemplary uses of arrays are further described in, for example, Pappalarado et al, Sem. Radiation Oncol (1998) 3:217; and Ramsay Nature Biotechnol (1998) 76:40.
- the polynucleotides of the invention can also be used to detect differences in expression levels between two cells, e.g. , as a method to identify abnormal or diseased tissue in a human.
- tissue can be selected according to the putative biological function.
- the expression of a gene corresponding to a specific polynucleotide is compared between a first tissue that is suspected of being diseased and a second, normal tissue of the human.
- the tissue suspected of being abnormal or diseased can be derived from a different tissue type of the human, but preferably it is derived from the same tissue type; for example an intestinal polyp or other abnormal growth should be compared with normal intestinal tissue.
- the normal tissue can be the same tissue as that of the test sample, or any normal tissue of the patient, especially those that express the polynucleotide-related gene of interest (e.g., brain, thymus, testis, heart, prostate, placenta, spleen, small intestine, skeletal muscle, pancreas, and the mucosal lining of the colon).
- a difference between the polynucleotide-related gene, mRNA, or protein in the two tissues which are compared, for example in molecular weight, amino acid or nucleotide sequence, or relative abundance, indicates a change in the gene, or a gene which regulates it, in the tissue of the human that was suspected of being diseased.
- polynucleotide-related genes in the two tissues are compared by any means known in the art.
- the two genes can be sequenced, and the sequence of the gene in the tissue suspected of being diseased compared with the gene sequence in the normal tissue.
- the genes corresponding to a provided polynucleotide, or portions thereof, in the two tissues are amplified, for example using nucleotide primers based on the nucleotide sequence shown in the Sequence Listing, using the polymerase chain reaction.
- the amplified genes or portions of genes are hybridized to detectably labeled nucleotide probes selected from a nucleotide sequence shown in the Sequence Listing.
- a difference in the nucleotide sequence of the isolated gene in the tissue suspected of being diseased compared with the normal nucleotide sequence suggests a role of the gene product encoded by the subject polynucleotide in the disease, and provides guidance for preparing a therapeutic agent.
- mRNA corresponding to a provided polynucleotide in the two tissues is compared.
- PolyA + RNA is isolated from the two tissues as is known in the art.
- one of skill in the art can readily determine differences in the size or amount of mRNA transcripts between the two tissues using Northern blots and detectably labeled nucleotide probes selected from the nucleotide sequence shown in the Sequence Listing.
- Increased or decreased expression of a given mRNA in a tissue sample suspected of being diseased, compared with the expression of the same mRNA in a normal tissue suggests that the expressed protein has a role in the disease, and also provides a lead for preparing a therapeutic agent.
- the comparison can also be accomplished by analyzing polypeptides between the matched samples.
- the sizes of the proteins in the two tissues are compared, for example, using antibodies of the present invention to detect polypeptides in Western blots of protein extracts from the two tissues.
- Other changes, such as expression levels and subcellular localization, can also be detected immunologically, using antibodies to the corresponding protein.
- a higher or lower level of expression of a given polypeptide in a tissue suspected of being diseased, compared with the same protein expression level in a normal tissue is indicative that the expressed protein has a role in the disease, and provides guidance for preparing a therapeutic agent.
- comparison of polynucleotide sequences or of gene expression products, e.g., mRNA and protein, between a human tissue that is suspected of being diseased and a normal tissue of a human are used to follow disease progression or remission in the human.
- Such comparisons are made as described above.
- increased or decreased expression of a gene corresponding to an inventive polynucleotide in the tissue suspected of being neoplastic can indicate the presence of neoplastic cells in the tissue.
- the degree of increased expression of a given gene in the neoplastic tissue relative to expression of the same gene in normal tissue, or differences in the amount of increased expression of a given gene in the neoplastic tissue over time, is used to assess the progression of the neoplasia in that tissue or to monitor the response of the neoplastic tissue to a therapeutic protocol over time.
- the expression pattern of any two cell types can be compared, such as low and high metastatic tumor cell lines, malignant or non-malignant cells, or cells from tissue which have and have not been exposed to a therapeutic agent.
- a genetic predisposition to disease in a human is detected by comparing expression levels of an mRNA or protein corresponding to a polynucleotide of the invention in a fetal tissue with levels associated in normal fetal tissue.
- Fetal tissues that are used for this pu ⁇ ose include, but are not limited to, amniotic fluid, chorionic villi, blood, and the blastomere of an in vitro-fertilized embryo.
- the comparable normal polynucleotide-related gene is obtained from any tissue.
- the mRNA or protein is obtained from a normal tissue of a human in which the polynucleotide-related gene is expressed. Differences such as alterations in the nucleotide sequence or size of the same product of the fetal polynucleotide-related gene or mRNA, or alterations in the molecular weight, amino acid sequence, or relative abundance of fetal protein, can indicate a germline mutation in the polynucleotide-related gene of the fetus, which indicates a genetic predisposition to disease. Particular diagnostic and prognostic uses of the disclosed polynucleotides are described in more detail below. E. Diagnostic. Prognostic, and Other Uses Based On Differential Expression
- diagnostic methods of the invention for involve detection of a level or amount of a gene product, particularly a differentially expressed gene product, in a test sample obtained from a patient suspected of having or being susceptible to a disease (e.g., breast cancer, lung cancer, colon cancer and/or metastatic forms thereof), and comparing the detected levels to those levels found in normal cells (e.g., cells substantially unaffected by cancer) and/or other control cells (e.g., to differentiate a cancerous cell from a cell affected by dysplasia).
- a disease e.g., breast cancer, lung cancer, colon cancer and/or metastatic forms thereof
- normal cells e.g., cells substantially unaffected by cancer
- other control cells e.g., to differentiate a cancerous cell from a cell affected by dysplasia
- the severity of the disease can be assessed by comparing the detected levels of a differentially expressed gene product with those levels detected in samples representing the levels of differentially gene product associated with varying degrees of severity of disease.
- the term "differentially expressed gene” is intended to encompass a polynucleotide that can, for example, include an open reading frame encoding a gene product (e.g., a polypeptide), and/or introns of such genes and adjacent 5' and 3' non-coding nucleotide sequences involved in the regulation of expression, up to about 20 kb beyond the coding region, but possibly further in either direction.
- the gene can be introduced into an appropriate vector for extrachromosomal maintenance or for integration into a host genome.
- a difference in expression level associated with a decrease in expression level of at least about 25%, usually at least about 50% to 75%, more usually at least about 90% or more is indicative of a differentially expressed gene of interest, i.e., a gene that is underexpressed or down-regulated in the test sample relative to a control sample.
- a difference in expression level associated with an increase in expression ofat least about 25%, usually at least about 50% to 75%, more usually at least about 90% and can be at least about 1 ' -fold, usually at least about 2-fold to about 10-fold, and can be about 100-fold to about 1 ,000-fold increase relative to a control sample is indicative of a differentially expressed gene of interest, i.e., an overexpressed or up- regulated gene.
- “Differentially expressed polynucleotide” as used herein means a nucleic acid molecule (RNA or DNA) having a sequence that represents a differentially expressed gene, e.g., the differentially expressed polynucleotide comprises a sequence (e.g., an open reading frame encoding a gene product) that uniquely identifies a differentially expressed gene so that detection of the differentially expressed polynucleotide in a sample is correlated with the presence of a differentially expressed gene in a sample.
- RNA or DNA nucleic acid molecule
- the differentially expressed polynucleotide comprises a sequence (e.g., an open reading frame encoding a gene product) that uniquely identifies a differentially expressed gene so that detection of the differentially expressed polynucleotide in a sample is correlated with the presence of a differentially expressed gene in a sample.
- “Differentially expressed polynucleotides” is also meant to encompass fragments of the disclosed polynucleotides, e.g., fragments retaining biological activity, as well as nucleic acids homologous, substantially similar, or substantially identical (e.g., having about 90%> sequence identity) to the disclosed polynucleotides.
- Methods of the subject invention useful in diagnosis or prognosis typically involve comparison of the abundance of a selected differentially expressed gene product in a sample of interest with that of a control to determine any relative differences in the expression of the gene product, where the difference can be measured qualitatively and/or quantitatively. Quantitation can be accomplished, for example, by comparing the level of expression product detected in the sample with the amounts of product present in a standard curve.
- a comparison can be made visually; by using a technique such as densitometry, with or without computerized assistance; by preparing a representative library of cDNA clones of mRNA isolated from a test sample, sequencing the clones in the library to determine that number of cDNA clones corresponding to the same gene product, and analyzing the number of clones corresponding to that same gene product relative to the number of clones of the same gene product in a control sample; or by using an array to detect relative levels of hybridization to a selected sequence or set of sequences, and comparing the hybridization pattern to that of a control. The differences in expression are then correlated with the presence or absence of an abnormal expression pattern.
- diagnostic assays of the invention involve detection of a gene product of a the polynucleotide sequence (e.g., mRNA or polypeptide) that corresponds to a sequence of "SEQ ID NOS: 1-5252.”
- the patient from whom the sample is obtained can be apparently healthy, susceptible to disease (e.g., as determined by family history or exposure to certain environmental factors), or can already be identified as having a condition in which altered expression of a gene product of the invention is implicated.
- the diagnosis can be determined based on detected gene product expression levels of a gene product encoded by at least one, preferably at least two or more, at least 3 or more, or at least 4 or more of the polynucleotides having a sequence set forth in "SEQ ID NOS: 1-5252,” and can involve detection of expression of genes corresponding to all of "SEQ ID NOS: 1-5252" and/or additional sequences that can serve as additional diagnostic markers and/or reference sequences.
- the diagnostic method is designed to detect the presence or susceptibility of a patient to cancer
- the assay preferably involves detection of a gene product encoded by a gene corresponding to a polynucleotide that is differentially expressed in cancer.
- a higher level of expression of a polynucleotide corresponding to SEQ ID NO:2024 relative to a level associated with a normal sample can indicate the presence of cancer in the patient from whom the sample is derived.
- detection of a lower level of a polynucleotide corresponding to SEQ ID NO:590 relative to a normal level is indicative of the presence of cancer in the patient.
- differentially expressed polynucleotides are described in the Examples below. Given the provided polynucleotides and information regarding their relative expression levels provided herein, assays using such polynucleotides and detection of their expression levels in diagnosis and prognosis will be readily apparent to the ordinarily skilled artisan.
- detectable labels include fluorochromes,(e.g. fluorescein isothiocyanate (FITC), rhodamine, Texas Red, phycoerythrin, allophycocyanin, 6-carboxyfluorescein (6-FAM), 2',7'-dimethoxy-4',5'- dichloro-6-carboxyfluorescein, 6-carboxy-X-rhodamine (ROX), 6-carboxy-2',4',7',4,7- hexachlorofluorescein (HEX), 5 -carboxy fluorescein (5-FAM) or N,N,N',N'-tetramethyl-6- carboxyrhodamine (TAMRA)), radioactive labels, (e.g.
- fluorochromes e.g. fluorescein isothiocyanate (FITC), rhodamine, Texas Red, phycoerythrin, allophycocyanin, 6-carboxyfluoresc
- the detectable label can involve a two stage systems (e.g., biotin-avidin, hapten-anti-hapten antibody, etc.)
- Reagents specific for the polynucleotides and polypeptides of the invention such as antibodies and nucleotide probes, can be supplied in a kit for detecting the presence of an expression product in a biological sample.
- the kit can also contain buffers or labeling components, as well as instructions for using the reagents to detect and quantify expression products in the biological sample. Exemplary embodiments of the diagnostic methods of the invention are described below in more detail.
- the test sample is assayed for the level of a differentially expressed polypeptide.
- Diagnosis can be accomplished using any of a number of methods to determine the absence or presence or altered amounts of the differentially expressed polypeptide in the test sample.
- detection can utilize staining of cells or histological sections with labeled antibodies, performed in accordance with conventional methods. Cells can be permeabilized to stain cytoplasmic molecules.
- antibodies that specifically bind a differentially expressed polypeptide of the invention are added to a sample, and incubated for a period of time sufficient to allow binding to the epitope, usually at least about 10 minutes.
- the antibody can be detectably labeled for direct detection (e.g., using radioisotopes, enzymes, fluorescers, chemiluminescers, and the like), or can be used in conjunction with a second stage antibody or reagent to detect binding (e.g., biotin with horseradish peroxidase- conjugated avidin, a secondary antibody conjugated to a fluorescent compound, e.g. fluorescein, rhodamine, Texas red, etc.).
- the absence or presence of antibody binding can be determined by various methods, including flow cytometry of dissociated cells, microscopy, radiography, scintillation counting, etc. Any suitable alternative methods can of qualitative or quantitative detection of levels or amounts of differentially expressed polypeptide can be used, for example ELISA, western blot, immunoprecipitation, radioimmunoassay, etc.
- the detected level of differentially expressed polypeptide in the test sample is compared to a level of the differentially expressed gene product in a reference or control sample, e.g., in a normal cell (negative control) or in a cell having a known disease state (positive control).
- mRNA detection The diagnostic methods of the invention can also or alternatively involve detection of mRNA encoded by a gene corresponding to a differentially expressed polynucleotides of the invention. Any suitable qualitative or quantitative methods known in the art for detecting specific mRNAs can be used.
- mRNA can be detected by, for example, in situ hybridization in tissue sections, by reverse transcriptase-PCR, or in Northern blots containing poly A+ mRNA.
- the level of mRNA of the invention in a tissue sample suspected of being cancerous or dysplastic is compared with the expression of the mRNA in a reference sample, e.g., a positive or negative control sample (e.g., normal tissue, cancerous tissue, etc.).
- a positive or negative control sample e.g., normal tissue, cancerous tissue, etc.
- mRNA expression levels in a sample can be determined by generation of a library of expressed sequence tags (ESTs) from the sample, where the EST library is representative of sequences present in the sample (Adams, et al., (1991) Science 252:1651). Enumeration of the relative representation of ESTs within the library can be used to approximate the relative representation of the gene transcript within the starting sample.
- ESTs expressed sequence tags
- EST analysis of a test sample can then be compared to EST analysis of a reference sample to determine the relative expression levels of a selected polynucleotide, particularly a polynucleotide corresponding to one or more of the differentially expressed genes described herein.
- gene expression in a test sample can be performed using serial analysis of gene expression (SAGE) methodology (Velculescu et al., Science (1995) 270:484).
- SAGE serial analysis of gene expression
- SAGE involves the isolation of short unique sequence tags from a specific location within each transcript. The sequence tags are concatenated, cloned, and sequenced. The frequency of particular transcripts within the starting sample is reflected by the number of times the associated sequence tag is encountered with the sequence population.
- Gene expression in a test sample can also be analyzed using differential display (DD) methodology.
- DD differential display
- fragments defined by specific sequence delimiters e.g., restriction enzyme sites
- the relative representation of an expressed gene with a sample can then be estimated based on the relative representation of the fragment associated with that gene within the pool of all possible fragments.
- Methods and compositions for carrying out DD are well known in the art, see, e.g., U.S. 5,776,683; and U.S. 5,807,680.
- hybridization analysis which is based on the specificity of nucleotide interactions.
- Oligonucleotides or cDNA can be used to selectively identify or capture DNA or RNA of specific sequence composition, and the amount of RNA or cDNA hybridized to a known capture sequence determined qualitatively or quantitatively, to provide information about the relative representation of a particular message within the pool of cellular messages in a sample.
- Hybridization analysis can be designed to allow for concurrent screening of the relative expression of hundreds to thousands of genes by using, for example, array-based technologies having high density formats, including filters, microscope slides, or microchips, or solution-based technologies that use spectroscopic analysis (e.g., mass spectrometry).
- spectroscopic analysis e.g., mass spectrometry
- the diagnostic methods of the invention can focus on the expression of a single differentially expressed gene.
- the diagnostic method can involve detecting a differentially expressed gene, or a polymo ⁇ hism of such a gene (e.g., a polymo ⁇ hism in an coding region or control region), that is associated with disease.
- Disease-associated polymo ⁇ hisms can include deletion or truncation of the gene, mutations that alter expression level and/or affect activity of the encoded protein, etc.
- Changes in the promoter or enhancer sequence that affect expression levels of an differentially gene can be compared to expression levels of the normal allele by various methods known in the art.
- Methods for determining promoter or enhancer strength include quantitation of the expressed natural protein; insertion of the variant control element into a vector with a reporter gene such as ⁇ -galactosidase, luciferase, chloramphenicol acetyltransferase, etc. that provides for convenient quantitation; and the like.
- a number of methods are available for analyzing nucleic acids for the presence of a specific sequence, e.g. a disease associated polymo ⁇ hism. Where large amounts of DNA are available, genomic DNA is used directly. Alternatively, the region of interest is cloned into a suitable vector and grown in sufficient quantity for analysis. Cells that express a differentially expressed gene can be used as a source of mRNA, which can be assayed directly or reverse transcribed into cDNA for analysis.
- the nucleic acid can be amplified by conventional techniques, such as the polymerase chain reaction (PCR), to provide sufficient amounts for analysis, and a detectable label can be included in the amplification reaction (e.g., using a detectably labeled primer or detectably labeled oligonucleotides) to facilitate detection.
- PCR polymerase chain reaction
- a detectable label can be included in the amplification reaction (e.g., using a detectably labeled primer or detectably labeled oligonucleotides) to facilitate detection.
- the use of the polymerase chain reaction is described in Saiki, et al, Science (1985) 239:487, and a review of techniques can be found in Sambrook, et al, Molecular Cloning: A Laboratory Manual, (1989) pp. 14.2.
- the sample nucleic acid e.g. amplified or cloned fragment, is analyzed by one of a number of methods known in the art.
- the nucleic acid can be sequenced by dideoxy or other methods, and the sequence of bases compared to a selected sequence, e.g., to a wild- type sequence.
- Hybridization with the polymo ⁇ hic or variant sequence can also be used to determine its presence in a sample (e.g., by Southern blot, dot blot, etc.).
- the hybridization pattern of a polymo ⁇ hic or variant sequence and a control sequence to an array of oligonucleotide probes immobilized on a solid support can also be used as a means of identifying polymo ⁇ hic or variant sequences associated with disease.
- Single strand conformational polymo ⁇ hism (SSCP) analysis, denaturing gradient gel electrophoresis (DGGE), and heteroduplex analysis in gel matrices are used to detect conformational changes created by DNA sequence variation as alterations in electrophoretic mobility.
- a polymo ⁇ hism creates or destroys a recognition site for a restriction endonuclease
- the sample is digested with that endonuclease, and the products size fractionated to determine whether the fragment was digested. Fractionation is performed by gel or capillary electrophoresis, particularly acrylamide or agarose gels.
- Screening for mutations in an differentially expressed gene can be based on the functional or antigenic characteristics of the protein.
- Protein truncation assays are useful in detecting deletions that can affect the biological activity of the protein.
- Various immunoassays designed to detect polymo ⁇ hisms in proteins can be used in screening. Where many diverse genetic mutations lead to a particular disease phenotype, functional protein assays have proven to be effective screening tools.
- the activity of the encoded protein can be determined by comparison with the wild-type protein.
- the diagnostic and/or prognostic methods of the invention involve detection of expression of a selected set of genes in a test sample to produce a test expression pattern (TEP).
- TEP test expression pattern
- REP reference expression pattern
- the selected set of genes includes at least one of the genes of the invention, which genes correspond to the polynucleotide sequences of "SEQ ID NOS: 1-5252.”
- SEQ ID NOS: 1-5252 Of particular interest is a selected set of genes that includes gene differentially expressed in the disease for which the test sample is to be screened.
- Reference sequences or “reference polynucleotides” as used herein in the context of differential gene expression analysis and diagnosis/prognosis refers to a selected set of polynucleotides, which selected set includes at least one or more of the differentially expressed polynucleotides described herein.
- a plurality of reference sequences preferably comprising positive and negative control sequences, can be included as reference sequences. Additional suitable reference sequences are found in Genbank, Unigene, and other nucleotide sequence databases (including, e.g., expressed sequence tag (EST), partial, and full-length sequences).
- EST expressed sequence tag
- Reference array means an array having reference sequences for use in hybridization with a sample, where the reference sequences include all, at least one of, or any subset of the differentially expressed polynucleotides described herein. Usually such an array will include at least 3 different reference sequences, and can include any one or all of the provided differentially expressed sequences.
- Arrays of interest can further comprise sequences, including polymo ⁇ hisms, of other genetic sequences, particularly other sequences of interest for screening for a disease or disorder (e.g., cancer, dysplasia, or other related or unrelated diseases, disorders, or conditions).
- the oligonucleotide sequence on the array will usually be at least about 12 nt in length, and can be of about the length of the provided sequences, or can extend into the flanking regions to generate fragments of 100 nt to 200 nt in length or more.
- a “reference expression pattern” or “REP” as used herein refers to the relative levels of expression of a selected set of genes, particularly of differentially expressed genes, that is associated with a selected cell type, e.g. , a normal cell, a cancerous cell, a cell exposed to an environmental stimulus, and the like.
- a “test expression pattern” or “TEP” refers to relative levels of expression of a selected set of genes, particularly of differentially expressed genes, in a test sample (e.g., a cell of unknown or suspected disease state, from which mRNA is isolated).
- Diagnosis generally includes determination of a subject's susceptibility to a disease or disorder, determination as to whether a subject is presently affected by a disease or disorder, as well as to the prognosis of a subject affected by a disease or disorder (e.g., identification of pre-metastatic or metastatic cancerous states, stages of cancer, or responsiveness of cancer to therapy).
- the present invention particularly encompasses diagnosis of subjects in the context of breast cancer (e.g.
- carcinoma in situ e.g., ductal carcinoma in situ
- estrogen receptor (ER)-positive breast cancer e.g., ER-negative breast cancer, or other forms and/or stages of breast cancer
- lung cancer e.g., small cell carcinoma, non-small cell carcinoma, mesothelioma, and other forms and/or stages of lung cancer
- colon cancer e.g., adenomatous polyp, colorectal carcinoma, and other forms and/or stages of colon cancer.
- sample or biological sample as used throughout here are generally meant to refer to samples of biological fluids or tissues, particularly samples obtained from tissues, especially from cells of the type associated with the disease for which the diagnostic application is designed (e.g., ductal adenocarcinoma), and the like.
- samples is also meant to encompass derivatives and fractions of such samples (e.g., cell lysates). Where the sample is solid tissue, the cells of the tissue can be dissociated or tissue sections can be analyzed.
- REPs can be generated in a variety of ways according to methods well known in the art.
- REPs can be generated by hybridizing a control sample to an array having a selected set of polynucleotides (particularly a selected set of differentially expressed polynucleotides), acquiring the hybridization data from the array, and storing the data in a format that allows for ready comparison of the REP with a TEP.
- all expressed sequences in a control sample can be isolated and sequenced, e.g., by isolating mRNA from a control sample, converting the mRNA into cDNA, and sequencing the cDNA. The resulting sequence information roughly or precisely reflects the identity and relative number of expressed sequences in the sample.
- the sequence information can then be stored in a format (e.g., a computer-readable format) that allows for ready comparison of the REP with a TEP.
- the REP can be normalized prior to or after data storage, and/or can be processed to selectively remove sequences of expressed genes that are of less interest or that might complicate analysis (e.g., some or all of the sequences associated with housekeeping genes can be eliminated from REP data).
- TEPs can be generated in a manner similar to REPs, e.g., by hybridizing a test sample to an array having a selected set of polynucleotides, particularly a selected set of differentially expressed polynucleotides, acquiring the hybridization data from the array, and storing the data in a format that allows for ready comparison of the TEP with a REP.
- the REP and TEP to be used in a comparison can be generated simultaneously, or the TEP can be compared to previously generated and stored REPs.
- comparison of a TEP with a REP involves hybridizing a test sample with a reference array, where the reference array has one or more reference sequences for use in hybridization with a sample.
- the reference sequences include all, at least one of, or any subset of the differentially expressed polynucleotides described herein.
- Hybridization data for the test sample is acquired, the data normalized, and the produced TEP compared with a REP generated using an array having the same or similar selected set of differentially expressed polynucleotides.
- Probes that correspond to sequences differentially expressed between the two samples will show decreased or increased hybridization efficiency for one of the samples relative to the other.
- Reference arrays can be produced according to any suitable methods known in the art. For example, methods of producing large arrays of oligonucleotides are described in U.S. 5,134,854, and U.S. 5,445,934 using light-directed synthesis techniques.
- a heterogeneous array of monomers is converted, through simultaneous coupling at a number of reaction sites, into a heterogeneous array of polymers.
- microarrays are generated by deposition of pre-synthesized oligonucleotides onto a solid substrate, for example as described in PCT published application no. WO 95/35505.
- the polynucleotides of the reference and test samples can be generated using a detectable fluorescent label, and hybridization of the polynucleotides in the samples detected by scanning the microarrays for the presence of the detectable label.
- Methods and devices for detecting fluorescently marked targets on devices are known in the art.
- detection devices include a microscope and light source for directing light at a substrate.
- a photon counter detects fluorescence from the substrate, while an x-y translation stage varies the location of the substrate.
- a confocal detection device that can be used in the subject methods is described in U.S. Patent no. 5,631,734.
- a scanning laser microscope is described in Shalon et al., Genome Res. (1996) 6:639.
- a scan using the appropriate excitation line, is performed for each fluorophore used.
- the digital images generated from the scan are then combined for subsequent analysis.
- the ratio of the fluorescent signal from one sample e.g., a test sample
- another sample e.g., a reference sample
- data analysis can include the steps of determining fluorescent intensity as a function of substrate position from the data collected, removing outliers, i.e. data deviating from a predetermined statistical distribution, and calculating the relative binding affinity of the targets from the remaining data.
- the resulting data can be displayed as an image with the intensity in each region varying according to the binding affinity between targets and probes.
- the test sample is classified as having a gene expression profile corresponding to that associated with a disease or non-disease state by comparing the TEP generated from the test sample to one or more REPs generated from reference samples (e.g., from samples associated with cancer or specific stages of cancer, dysplasia, samples affected by a disease other than cancer, normal samples, etc.).
- the criteria for a match or a substantial match between a TEP and a REP include expression of the same or substantially the same set of reference genes, as well as expression of these reference genes at substantially the same levels (e.g., no significant difference between the samples for a signal associated with a selected reference sequence after normalization of the samples, or at least no greater than about 25% to about 40% difference in signal strength for a given reference sequence.
- a pattern match between a TEP and a REP includes a match in expression, preferably a match in qualitative or quantitative expression level, ofat least one of, all or any subset of the differentially expressed genes of the invention.
- Pattern matching can be performed manually, or can be performed using a computer program.
- Methods for preparation of substrate matrices e.g., arrays
- design of oligonucleotides for use with such matrices labeling of probes, hybridization conditions, scanning of hybridized matrices, and analysis of patterns generated, including comparison analysis, are described in, for example, U.S. 5,800,992.
- Cancerous cells can have the ability to compress, invade, and destroy normal tissue. Cancerous cells may also metastasize to other parts of the body via the bloodstream or the lymph system and colonize in these other areas. Different cancers are classified by the cell from which the cancerous cell is derived and from its cellular mo ⁇ hology and/or state of differentiation. Somatic genetic abnormalities cause cancer initiation and progression. Cancer generally is clonally formed, i.e.
- the genes known to be involved in cancer initiation and progression are involved in numerous cellular functions, including developmental differentiation, cell cycle regulation, cell signaling, immunological response, DNA replication, and DNA repair.
- novel surrogate tumor specific features with response to treatment and outcome in patients has defined certain prognostic indicators that allow the design of tailored therapy based on the molecular profile of the tumor.
- These therapies include antibody targeting and gene therapy.
- a promising level of one or more marker polynucleotides can provide impetus for not aggressively treating a particular patient, thus sparing the patient the deleterious side effects of aggressive therapy. Determining expression of certain polynucleotides and comparison of a patients profile with known expression in normal tissue and variants of the disease allows a determination of the best possible treatment for a patient, both in terms of specificity of treatment and in terms of comfort level of the patient.
- Surrogate tumor markers such as polynucleotide expression
- Two classifications widely used in oncology that can benefit from identification of the expression levels of the polynucleotides of the invention are staging of the cancerous disorder, and grading the nature of the cancerous tissue.
- Staging is a process used by physicians to describe how advanced the cancerous state is in a patient. Staging assists the physician in determining a prognosis, planning treatment and evaluating the results of such treatment.
- Different staging systems are used for different types of cancer, but each generally involves the following determinations: the type of tumor, indicated by T; whether the cancer has metastasized to nearby lymph nodes, indicated by N; and whether the cancer has metastasized to more distant parts of the body, indicated by M.
- This system of staging is called the TNM system.
- Stage I if a cancer is only detectable in the area of the primary lesion without having spread to any lymph nodes it is called Stage I. If it has spread only to the closest lymph nodes, it is called Stage II.
- Stage III the cancer has generally spread to the lymph nodes in near proximity to the site of the primary lesion. Cancers that have spread to a distant part of the body, such as the liver, bone, brain or another site, are called Stage IV, the most advanced stage.
- the determination of staging is done using pathological techniques and is based more on the presence or absence of malignant tissue rather than the characteristics of the tumor type. Presence or absence of malignant tissue is based primarily on the gross mo ⁇ hology of the cells in the areas biopsied.
- the polynucleotides of the invention can facilitate fine-tuning of the staging process by identifying markers for the aggresivity of a cancer, e.g. the metastatic potential, as well as the presence in different areas of the body.
- a Stage II cancer with a polynucleotide signifying a high metastatic potential cancer can be used to change a borderline Stage II tumor to a Stage III tumor, justifying more aggressive therapy.
- Grade is a term used to describe how closely a tumor resembles normal tissue of its same type. Based on the microscopic appearance of a tumor, pathologists will identify the grade of a tumor based on parameters such as cell mo ⁇ hology, cellular organization, and other markers of differentiation. As a general rule, the grade of a tumor corresponds to its rate of growth or aggressiveness. That is, undifferentiated or high-grade tumors grow more quickly than well differentiated or low- grade tumors. Information about tumor grade is useful in planning treatment and predicting prognosis.
- GX Grade cannot be assessed; 2) GI Well differentiated; G2 Moderately well differentiated; 3) G3 Poorly differentiated; 4) G4 Undifferentiated.
- Gleason system that is specific for prostate cancer, which uses grade numbers to describe the degree of differentiation. Lower Gleason scores indicate well-differentiated cells. Intermediate scores denote tumors with moderately differentiated cells. Higher scores describe poorly differentiated cells. Grade is also important in some types of brain tumors and soft tissue sarcomas.
- the polynucleotides of the invention can be especially valuable in determining the grade of the tumor, as they not only can aid in determining the differentiation status of the cells of a tumor, they can also identify factors other than differentiation that are valuable in determining the aggressivity of a tumor, such as metastatic potential.
- Familial Cancer Genes A number of cancer syndromes are linked to Mendelian inheritance of a predisposition to develop particular cancers.
- the following table contains a list of cancer types that can be inherited, and for which the gene or genes responsible have been identified. Most of the cancer types listed can occur as part of several different genetic conditions, each caused by alterations in a different gene.
- TSC2 Tuberous sclerosis 2
- HNPCC Hereditary non-polyposis colon cancer
- HNPCC Hereditary non-polyposis colon cancer
- HNPCC Hereditary non-polyposis colon cancer
- HNPCC Hereditary non-polyposis colon cancer
- HNPCC Hereditary non-polyposis colon cancer
- HNPCC Hereditary non-polyposis colon cancer
- HNPCC Hereditary non-polyposis colon cancer
- PMSl Hereditary non-polyposis colon cancer
- HNPCC Hereditary non-polyposis colon cancer
- MEN1 Endocrine Multiple endocrine neoplasia 1
- HNPCC Endometrial Hereditary non-polyposis colon cancer
- HNPCC Hereditary non-polyposis colon cancer
- HNPCC Hereditary non-polyposis colon cancer
- HNPCC Hereditary non-polyposis colon cancer
- HNPCC hMSH2 Hereditary non-polyposis colon cancer
- HNPCC hMLHl Hereditary non-polyposis colon cancer
- HNPCC hPMSl
- HNPCC Hereditary non-polyposis colon cancer
- HNPCC Hereditary non-polyposis colon cancer 1 hMSH2 Hereditary non-polyposis colon cancer (HNPCC) 2 hMLHl Hereditary non-polyposis colon cancer (HNPCC) 3 hPMSl Hereditary non-polyposis colon cancer (HNPCC) 4 hPMS2
- the polynucleotides of the invention can be especially useful to monitor patients having any of the above syndromes to detect potentially malignant events at a molecular level before they are detectable at a gross mo ⁇ hological level.
- a number of genes are involved in multiple forms of cancer.
- a polynucleotide of the invention identified as important for metastatic colon cancer can also have clinical implications for a patient diagnosed with stomach cancer or endometrial cancer.
- Lung Cancer Lung cancer is one of the most common cancers in the United States, accounting for about 15 percent of all cancer cases, or 170,000 new cases each year. At this time, over half of the lung cancer cases in the United States are in men, but the number found in women is increasing and will soon equal that in men.
- lung cancer Today more women die of lung cancer than of breast cancer. Lung cancer is especially difficult to diagnose and treat because of the large size of the lungs, which allows cancer to develop for years undetected. In fact, lung cancer can spread outside the lungs without causing any symptoms. Adding to the confusion, the most common symptom of lung cancer, a persistent cough, can often be mistaken for a cold or bronchitis. Although there are more than a dozen different kinds of lung cancer, the two main types of lung cancer are small cell and nonsmall cell, which encompass about 90% of all lung cancer cases. Small cell carcinoma (also called oat cell carcinoma), which usually starts in one of the larger bronchial tubes, grows fairly rapidly, and is likely to be large by the time of diagnosis.
- small cell carcinoma also called oat cell carcinoma
- Nonsmall cell lung cancer is made up of three general subtypes of lung cancer.
- Epidermoid carcinoma also called squamous cell carcinoma
- Adenocarcinoma starts growing near the outside surface of the lung and can vary in both size and growth rate.
- Some slowly growing adenocarcinomas are described as alveolar cell cancer.
- Large cell carcinoma starts near the surface of the lung, grows rapidly, and the growth is usually fairly large when diagnosed.
- Other less common forms of lung cancer are carcinoid, cylindroma, mucoepidermoid, and malignant mesothelioma.
- CT scans, MRIs, X-rays, sputum cytology, and biopsies are used to diagnose nonsmall cell lung cancer.
- the form and cellular origin of the lung cancer is diagnosed primarily through biopsy from either a surgical biopsy or a needle aspiration of lung tissue, and usually the biopsy is prompted from an abnormality identified on an X-ray.
- sputum cytology can reveal lung cancers in patients with normal X-rays or can determine the type of lung cancer, but because it cannot pinpoint the tumor's location, a positive sputum cytology test is usually followed by further tests.
- the polynucleotides of the invention can be used to distinguish types of lung cancer as well as identifying traits specific to a certain patient's cancer. For example, if the patient's biopsy expresses a polynucleotide that is associated with a low metastatic potential, it may justify leaving a larger portion of the patient's lung in surgery to remove the lesion. Alternatively, a smaller lesion with expression of a polynucleotide that is associated with high metastatic potential may justify a more radical removal of lung tissue and/or the surrounding lymph nodes, even if no metastasis can be identified through pathological examination.
- polynucleotides of the invention can be used in the diagnosis, prognosis and management of colorectal cancer.
- the differential expression of a polynucleotide in hype ⁇ lasia can be used as a diagnostic marker for metastatic lung cancer.
- the polynucleotides of the invention that would be especially useful for this pu ⁇ ose are those that exhibit differential expression between high metastatic versus low metastatic lung cancer , i.e.
- NCI National Cancer Institute
- Ductal carcinoma in situ Ductal carcinoma in situ is the most common type of noninvasive breast cancer.
- DCIS the malignant cells have not metastasized through the walls of the ducts into the fatty tissue of the breast.
- Comedocarcinoma is a type of DCIS that is more likely than other types of DCIS to come back in the same area after lumpectomy. It is more closely linked to eventual development of invasive ductal carcinoma than other forms of DCIS.
- Infiltrating (or invasive) ductal carcinoma (IDC) this type of cancer has metastasized through the wall of the duct and invaded the fatty tissue of the breast. At this point, it has the potential to use the lymphatic system and bloodstream for metastasis to more distant parts of the body. Infiltrating ductal carcinoma accounts for about 80% of breast cancers.
- LCIS Lobular carcinoma in situ
- ILC Infiltrating (or invasive) lobular carcinoma
- ILC is similar to IDC, in that it has the potential metastasize elsewhere in the body. About 10% to 15% of invasive breast cancers are invasive lobular carcinomas. ILC can be more difficult to detect by mammogram than IDC.
- ILC Inflammatory breast cancer: This rare type of invasive breast cancer accounts for about 1% of all breast cancers and is extremely aggressive. Multiple skin symptoms associated with this cancer are caused by cancer cells blocking lymph vessels or channels in the skin over the breast.
- Medullary carcinoma This special type of infiltrating breast cancer has a relatively well defined, distinct boundary between tumor tissue and normal tissue. It accounts for about 5% of breast cancers. The prognosis for this kind of breast cancer is better than for other types of invasive breast cancer.
- Mucinous carcinoma This rare type of invasive breast cancer originates from mucus-producing cells. The prognosis for mucinous carcinoma is better than for the more common types of invasive breast cancer.
- Paget's disease of the nipple This type of breast cancer starts in the ducts and spreads to the skin of the nipple and the areola. It is a rare type of breast cancer, occurring in only 1% of all cases. Paget's disease can be associated with in situ carcinoma, or with infiltrating breast carcinoma. If no lump can be felt in the breast tissue, and the biopsy shows DCIS but no invasive cancer, the prognosis is excellent.
- Phyllodes tumor This very rare type of breast tumor forms from the stroma of the breast, in contrast to carcinomas which develop in the ducts or lobules. Phyllodes (also spelled phylloides) tumors are usually benign, but are malignant on rare occasions. Nevertheless, malignant phyllodes tumors are very rare and less than 10 women per year in the US die of this disease. Benign phyllodes tumors are successfully treated by removing the mass and a narrow margin of normal breast tissue.
- tubular carcinoma Accounting for about 2%> of all breast cancers, tubular carcinomas are a special type of infiltrating breast carcinoma. They have a better prognosis than usual infiltrating ductal or lobularcarcinomas. High-quality mammography combined with clinical breast exam remains the only screening method clearly tied to reduction in breast cancer mortality. Lower dose x-rays, digitized computer rather than film images, and the use of computer programs to assist diagnosis, are almost ready for widespread dissemination. Other technologies also are being developed, including magnetic resonance imaging and ultrasound. In addition, a very low radiation exposure technique, positron emission tomography has the potential for detecting early breast cancer.
- breast cancer can thus be generally diagnosed by detection of expression of a gene or genes associated with breast tumors. Where enough information is available about the differential gene expression between various types of breast tumor tissues, the specific type of breast tumor can also be diagnosed.
- ER estrogen receptor
- Malignant breast cancer is often divided into two groups, ER-positive and ER-negative, based on the estrogen receptor status of the tissue.
- the ER status represents different survival length and response to hormone therapy, and is thought to represent either: 1) an indicator of different stages of the disease, or 2) an indicator that allows differentiation between two similar but distinct diseases.
- a number of other genes are known to vary expression between either different stages of cancer or different types of similar breast cancer.
- polynucleotides of the invention can be used in the diagnosis and management of breast cancer.
- the differential expression of a polynucleotide in human breast tumor tissue can be used as a diagnostic marker for human breast cancer.
- the polynucleotides of the invention that would be especially useful for this pu ⁇ ose are those that exhibit differential expression between breast cancer tissue with a high metastatic potential and a low metastatic potential, i.e.
- Determination of the aggressive nature and/or the metastatic potential of a breast cancer can also be determined by comparing levels of one or more polynucleotides of the invention and comparing levels of another sequence known to vary in cancerous tissue, e.g. ER expression.
- development of breast cancer can be detected by examining the ratio of SEQ ID NO: to the levels of steroid hormones (e.g. , testosterone or estrogen) or to other hormones (e.g. , growth hormone, insulin).
- steroid hormones e.g. , testosterone or estrogen
- other hormones e.g. , growth hormone, insulin
- Diagnosis of breast cancer can also involve comparing the expression of a polynucleotide of the invention with the expression of other sequences in non-malignant breast tissue samples in comparison to one or more forms of the diseased tissue.
- a comparison of expression of one or more polynucleotides of the invention between the samples provides information on relative levels of these polynucleotides as well as the ratio of these polynucleotides to the expression of other sequences in the tissue of interest compared to normal.
- This risk of breast cancer is elevated significantly by the presence of an inherited risk for breast cancer, such as a mutation in BRCA-1 or BRCA-2.
- New diagnostic tools are being developed to address the needs of higher risk patients to complement mammography and physical examinations for early detection of breast cancer, particularly among younger women.
- the presence of antigen or expression markers in nipple aspirate fluid (NAF) samples collected from one or both breasts can be useful for useful for risk assessment or early cancer detection.
- NAF nipple aspirate fluid
- the polynucleotides of the invention can be used in multivariate analysis with expression studies with genes such as p53 and EGFR as risk predictors and as surrogate endpoint biomarkers for breast cancer. As well as being used for diagnosis and risk assessment, the expression of certain genes can also correlated to prognosis of a disease state.
- the expression of particular gene have been used as prognostic indicators for breast cancer including increased expression of c-erbB-2, pS2, ER, progesterone receptor, epidermal growth factor receptor (EGFR), neu, myc, bcl-2, int2, cytosolic tyrosine kinase, cyclin E,prad-1, hst, uPA, PAI-1, PAI-2, cathepsin D, as well as the presence of a number of cancer-specific antigens, e.g. CEA, CA M26, CA M29 and CA 15.3. Davis, Br. J. BiomedSci. (1996) 53:157.
- the expression of the polynucleotides of the invention can be of prognostic value for determining the metastatic potential of a malignant breast cancer, as this molecules are differentially expressed between high and low metastatic potential tissues tumors.
- the levels of these polynucleotides in patients with malignant breast cancer can compared to normal tissue, malignant tissue with a known high potential metastatic level, and malignant tissue with a known lower level of metastatic potential to provide a prognosis for a particular patient.
- Such a prognosis is predictive of the extent and nature of the cancer.
- the determined prognosis is useful in determining the prognosis of a patient with breast cancer, both for initial treatment of the disease and for longer-term monitoring of the same patient. If samples are taken from the same individual over a period of time, differences in polynucleotide expression that are specific to that patient can be identified and closely watched.
- Colorectal cancer is one of the most common neoplasms in humans and perhaps the most frequent form of hereditary neoplasia. Prevention and early detection are key factors in controlling and curing colorectal cancer. Indeed, colorectal cancer is the second most preventable cancer, after lung cancer. Colorectal cancer begins as polyps, which are small, benign growths of cells that form on the inner lining of the colon. Over a period of several years, some of these polyps accumulate additional mutations and become cancerous. About 20 percent of all cases of colon cancer are thought to be related to heredity. Currently, multiple familial colorectal cancer disorders have been identified, which are summarized as follows:
- Familial adenomatous polyposis This condition results in a person having hundreds or even thousands of polyps in the colon and rectum that usually first appear during the teenage years. Cancer nearly always develops in one or more of these polyps between the ages of 30 and 50.
- Gardner's syndrome Like FAP, Gardner's syndrome results in polyps and colorectal cancers that develop at a young age. It can also cause benign tumors of the skin, soft connective tissue and bones.
- Hereditary nonpolyposis colon cancer HNPCC: People with this condition tend to develop colorectal cancer at a young age, without first having many polyps. HNPCC has an autosomal dominant pattern of inheritance with variable but high penetrance estimated to be about 90%. HNPCC underlies 0.5%- 10% of all cases of colorectal cancer.
- Familial colorectal cancer in Ashkenazi Jews Recent research has found an inherited tendency to developing colorectal cancer among some Jews of Eastern European descent. Like people with FAP, Gardner's syndrome, and HNPCC, their increased risk is due to an inherited mutation present in about 6% of American Jews.
- Colorectal cancer can thus be generally diagnosed by detection of expression of a gene or genes associated with colorectal tumors.
- polynucleotides of the invention can be used in the diagnosis, prognosis and management of colorectal cancer.
- the differential expression of a polynucleotide in hype ⁇ lasia can be used as a diagnostic marker for colon cancer.
- the polynucleotides of the invention that would be especially useful for this pu ⁇ ose are those that exhibit differential expression between malignant metastatic colon cancer and normal patient tissue , i.e.
- SEQ ID NOS:228, 280 355, 491, 603, 680, 752, 753, 1241, 1264, 1401, 1442, 1514, 1851, 1915, 2024, 2066, 33, 250, 282, 370, 387, 443, 460, 545, 560, 703, 704, 1095, 1104, 1205, 1354, 1387, 1734, 1742, 1954, 2262, 2325, 1899, 252, 253, 491, 581, 693, 726, 746, 1780, 1899, 65, 252, 253, 581, 693, 716, 726, 746, 1780, 1899, and 1780.
- Detection of malignant colon cancer can be determined using expression levels of any of these sequences alone or in combination with the levels of expression. Determination of the aggressive nature and/or the metastatic potential of a colon cancer can also be determined by comparing levels of one or more polynucleotides of the invention and comparing total levels of another sequence known to vary in cancerous tissue, e.g. p53 expression. In addition, development of colon cancer can be detected by examining the ratio of any of the polynucleotides of the invention to the levels of oncogenes (e.g. ras) or tumor suppressor genes (e.g. FAP or p53). Thus expression of specific marker polynucleotides can be used to discriminate between normal and cancerous breast tissue, to discriminate between breast cancers with different cells of origin, to discriminate between breast cancers with different potential metastatic rates, etc.
- oncogenes e.g. ras
- tumor suppressor genes e.g. FAP or p53
- Polypeptides encoded by the instant polynucleotides and corresponding full length genes can be used to screen peptide libraries to identify binding partners, such as receptors, from among the encoded polypeptides.
- a library of peptides can be synthesized following the methods disclosed in U.S. Pat. No. 5,010,175 ('175), and in WO 91/17823. As described below in brief, one prepares a mixture of peptides, which is then screened to identify the peptides exhibiting the desired signal transduction and receptor binding activity.
- a suitable peptide synthesis support e.g., a resin
- the concentration of each amino acid in the reaction mixture is balanced or adjusted in inverse proportion to its coupling reaction rate so that the product is an equimolar mixture of amino acids coupled to the starting resin.
- the bound amino acids are then deprotected, and reacted with another balanced amino acid mixture to form an equimolar mixture of all possible dipeptides. This process is repeated until a mixture of peptides of the desired length (e.g., hexamers) is formed. Note that one need not include all amino acids in each step: one can include only one or two amino acids in some steps (e.g., where it is known that a particular amino acid is essential in a given position), thus reducing the complexity of the mixture.
- the mixture of peptides is screened for binding to the selected polypeptide. The peptides are then tested for their ability to inhibit or enhance activity. Peptides exhibiting the desired activity are then isolated and sequenced.
- the method described in WO 91/17823 is similar. However, instead of reacting the synthesis resin with a mixture of activated amino acids, the resin is divided into twenty equal portions (or into a number of portions corresponding to the number of different amino acids to be added in that step), and each amino acid is coupled individually to its portion of resin. The resin portions are then combined, mixed, and again divided into a number of equal portions for reaction with the second amino acid. In this manner, each reaction can be easily driven to completion. Additionally, one can maintain separate "subpools" by treating portions in parallel, rather than combining all resins at each step. This simplifies the process of determining which peptides are responsible for any observed receptor binding or signal transduction activity.
- the subpools containing, e.g., 1-2,000 candidates each are exposed to one or more polypeptides of the invention.
- Each subpool that produces a positive result is then resynthesized as a group of smaller subpools (sub-subpools) containing, e.g. , 20-100 candidates, and reassayed.
- Positive sub-subpools can be resynthesized as individual compounds, and assayed finally to determine the peptides that exhibit a high binding constant.
- These peptides can be tested for their ability to inhibit or enhance the native activity.
- the methods described in WO 91/7823 and U.S. Patent No. 5,194,392 (herein inco ⁇ orated by reference) enable the preparation of such pools and subpools by automated techniques in parallel, such that all synthesis and resynthesis can be performed in a matter of days.
- Peptide agonists or antagonists are screened using any available method, such as signal transduction, antibody binding, receptor binding, mitogenic assays, chemotaxis assays, etc.
- the methods described herein are presently preferred.
- the assay conditions ideally should resemble the conditions under which the native activity is exhibited in vivo, that is, under physiologic pH, temperature, and ionic strength. Suitable agonists or antagonists will exhibit strong inhibition or enhancement of the native activity at concentrations that do not cause toxic side effects in the subject.
- Agonists or antagonists that compete for binding to the native polypeptide can require concentrations equal to or greater than the native concentration, while inhibitors capable of binding irreversibly to the polypeptide can be added in concentrations on the order of the native concentration.
- novel polypeptide binding partner such as a receptor, encoded by a gene or a cDNA corresponding to a polynucleotide of the invention, and at least one peptide agonist or antagonist of the novel binding partner.
- agonists and antagonists can be used to modulate, enhance, or inhibit receptor function in cells to which the receptor is native, or in cells that possess the receptor as a result of genetic engineering.
- novel receptor shares biologically important characteristics with a known receptor, information about agonist/antagonist binding can facilitate development of improved agonists/antagonists of the known receptor.
- compositions and Therapeutic Uses can comprise polypeptides, antibodies, or polynucleotides of the claimed invention.
- the pharmaceutical compositions will comprise a therapeutically effective amount of either polypeptides, antibodies, or polynucleotides of the claimed invention.
- therapeutically effective amount refers to an amount of a therapeutic agent to treat, ameliorate, or prevent a desired disease or condition, or to exhibit a detectable therapeutic or preventative effect.
- the effect can be detected by, for example, chemical markers or antigen levels.
- Therapeutic effects also include reduction in physical symptoms, such as decreased body temperature.
- the precise effective amount for a subject will depend upon the subject's size and health, the nature and extent of the condition, and the therapeutics or combination of therapeutics selected for administration. Thus, it is not useful to specify an exact effective amount in advance. However, the effective amount for a given situation is determined by routine experimentation and is within the judgment of the clinician.
- an effective dose will generally be from about 0.01 mg/ kg to 50 mg/kg or 0.05 mg/kg to about 10 mg/kg of the DNA constructs in the individual to which it is administered.
- a pharmaceutical composition can also contain a pharmaceutically acceptable carrier.
- pharmaceutically acceptable carrier refers to a carrier for administration of a therapeutic agent, such as antibodies or a polypeptide, genes, and other therapeutic agents.
- the term refers to any pharmaceutical carrier that does not itself induce the production of antibodies harmful to the individual receiving the composition, and which can be administered without undue toxicity.
- Suitable carriers can be large, slowly metabolized macromolecules such as proteins, polysaccharides, polylactic acids, polyglycolic acids, polymeric amino acids, amino acid copolymers, and inactive virus particles. Such carriers are well known to those of ordinary skill in the art.
- Pharmaceutically acceptable salts can be used therein, for example, mineral acid salts such as hydrochlorides, hydrobromides, phosphates, sulfates, and the like; and the salts of organic acids such as acetates, propionates, malonates, benzoates, and the like.
- Pharmaceutically acceptable carriers in therapeutic compositions can include liquids such as water, saline, glycerol and ethanol.
- Auxiliary substances, such as wetting or emulsifying agents, pH buffering substances, and the like, can also be present in such vehicles.
- the therapeutic compositions are prepared as injectables, either as liquid solutions or suspensions; solid forms suitable for solution in, or suspension in, liquid vehicles prior to injection can also be prepared. Liposomes are included within the definition of a pharmaceutically acceptable carrier.
- compositions of the invention can be (1) administered directly to the subject (e.g., as polynucleotide or polypeptides); (2) delivered ex vivo, to cells derived from the subject (e.g., as in ex vivo gene therapy); or (3) delivered in vitro for expression of recombinant proteins (e.g., polynucleotides).
- Direct delivery of the compositions will generally be accomplished by injection, either subcutaneously, intraperitoneally, intravenously or intramuscularly, or delivered to the interstitial space of a tissue.
- the compositions can also be administered into a tumor or lesion. Other modes of administration include oral and pulmonary administration, suppositories, and transdermal applications, needles, and gene guns or hyposprays. Dosage treatment can be a single dose schedule or a multiple dose schedule.
- cells useful in ex vivo applications include, for example, stem cells, particularly hematopoetic, lymph cells, macrophages, dendritic cells, or tumor cells.
- nucleic acids for both ex vivo and in vitro applications can be accomplished by, for example, dextran-mediated transfection, calcium phosphate precipitation, polybrene mediated transfection, protoplast fusion, electroporation, encapsulation of the polynucleotide(s) in liposomes, and direct microinjection of the DNA into nuclei, all well known in the art.
- a gene corresponding to a polynucleotide of the invention has been found to correlate with a proliferative disorder, such as neoplasia, dysplasia, and hype ⁇ lasia
- the disorder can be amenable to treatment by administration of a therapeutic agent based on the provided polynucleotide or corresponding polypeptide.
- Preparation of antisense polynucleotides is discussed above.
- Neoplasias that are treated with the antisense composition include, but are not limited to, cervical cancers, melanomas, colorectal adenocarcinomas, Wilms' tumor, retinoblastoma, sarcomas, myosarcomas, lung carcinomas, leukemias, such as chronic myelogenous leukemia, promyelocytic leukemia, monocytic leukemia, and myeloid leukemia, and lymphomas, such as histiocytic lymphoma.
- Proliferative disorders that are treated with the therapeutic composition include disorders such as anhydric hereditary ectodermal dysplasia, congenital alveolar dysplasia, epithelial dysplasia of the cervix, fibrous dysplasia of bone, and mammary dysplasia.
- Hype ⁇ lasias for example, endometrial, adrenal, breast, prostate, or thyroid hype ⁇ lasias or pseudoepitheliomatous hype ⁇ lasia of the skin, are treated with antisense therapeutic compositions based upon a polynucleotide of the invention.
- downregulation or inhibition of expression of a gene corresponding to a polynucleotide of the invention can have therapeutic application. For example, decreasing gene expression can help to suppress tumors in which enhanced expression of the gene is implicated.
- the dose of the antisense composition and the means of administration are determined based on the specific qualities of the therapeutic composition, the condition, age, and weight of the patient, the progression of the disease, and other relevant factors.
- Administration of the therapeutic antisense agents of the invention includes local or systemic administration, including injection, oral administration, particle gun or catheterized administration, and topical administration.
- the therapeutic antisense composition contains an expression construct comprising a promoter and a polynucleotide segment of at least 12, 22, 25, 30, or 35 contiguous nucleotides of the antisense strand of a polynucleotide disclosed herein. Within the expression construct, the polynucleotide segment is located downstream from the promoter, and transcription of the polynucleotide segment initiates at the promoter.
- a small metastatic lesion is located and the therapeutic composition injected several times in several different locations within the body of tumor.
- arteries which serve a tumor are identified, and the therapeutic composition injected into such an artery, in order to deliver the composition directly into the tumor.
- a tumor that has a necrotic center is aspirated and the composition injected directly into the now empty center of the tumor.
- the antisense composition is directly administered to the surface of the tumor, for example, by topical application of the composition.
- X-ray imaging is used to assist in certain of the above delivery methods.
- Receptor-mediated targeted delivery of therapeutic compositions containing an antisense polynucleotide, subgenomic polynucleotides, or antibodies to specific tissues is also used.
- Receptor-mediated DNA delivery techniques are described in, for example, Findeis et al, Trends Biotechnol (1993) 77:202; Chiou et al, Gene Therapeutics: Methods And Applications Of Direct Gene Transfer (J.A. Wolff, ed.) (1994); Wu et al, J. Biol Chem. (1988) 263:621 ; Wu et al, J. Biol Chem. (1994) 269:542; Zenke et al, Proc. Natl. Acad. Sci. (USA) (1990) 37:3655; Wu et al, J. Biol Chem. (1991) 266:338.
- receptor-mediated targeted delivery of therapeutic compositions containing antibodies of the invention is used to deliver the antibodies to specific tissue.
- compositions containing antisense subgenomic polynucleotides are administered in a range of about 100 ng to about 200 mg of DNA for local administration in a gene therapy protocol. Concentration ranges of about 500 ng to about 50 mg, about 1 ⁇ g to about 2 mg, about 5 ⁇ g to about 500 ⁇ g, and about 20 ⁇ g to about 100 ⁇ g of DNA can also be used during a gene therapy protocol. Factors such as method of action and efficacy of transformation and expression are considerations which will affect the dosage required for ultimate efficacy of the antisense subgenomic polynucleotides.
- Therapeutic agents also include antibodies to proteins and polypeptides encoded by the polynucleotides of the invention and related genes, as described in U.S. Patent No. 5,654,173.
- the therapeutic polynucleotides and polypeptides of the present invention can be utilized in gene delivery vehicles.
- the gene delivery vehicle can be of viral or non- viral origin (see generally, Jolly, Cancer Gene Therapy (1994) 7:51; Kimura, Human Gene Therapy (1994) 5:845; Connelly, Human Gene Therapy (1995) 7:185; and Kaplitt, Nature Genetics (1994) 6:148).
- Gene therapy vehicles for delivery of constructs including a coding sequence of a therapeutic of the invention can be administered either locally or systemically. These constructs can utilize viral or non- viral vector approaches. Expression of such coding sequences can be induced using endogenous mammalian or heterologous promoters. Expression of the coding sequence can be either constitutive or regulated.
- the present invention can employ recombinant retroviruses which are constructed to carry or express a selected nucleic acid molecule of interest.
- Retrovirus vectors that can be employed include those described in EP 0 415 731; WO 90/07936; WO 94/03622; WO 93/25698; WO 93/25234; U.S. Patent No. 5, 219,740; WO 93/11230; WO 93/10218; Vile and Hart, Cancer Res. (1993) 53:3860; Vile et al, Cancer Res. (1993) 53:962; Ram et al., Cancer Res. (1993) 53:83; Takamiya et al, J. Neurosci. Res.
- Preferred recombinant retroviruses include those described in WO 91/02805.
- Packaging cell lines suitable for use with the above-described retroviral vector constructs can be readily prepared (see, e.g., WO 95/30763 and WO 92/05266), and used to create producer cell lines (also termed vector cell lines) for the production of recombinant vector particles.
- producer cell lines also termed vector cell lines
- packaging cell lines are made from human (such as HT1080 cells) or mink parent cell lines, thereby allowing production of recombinant retroviruses that can survive inactivation in human serum.
- the present invention also employs alphavirus-based vectors that can function as gene delivery vehicles.
- alphavirus-based vectors can be constructed from a wide variety of alphaviruses, including, for example, Sindbis virus vectors, Semliki forest virus (ATCC VR-67; ATCC VR-1247), Ross River virus (ATCC VR-373; ATCC VR-1246) and Venezuelan equine encephalitis virus (ATCC VR-923; ATCC VR-1250; ATCC VR 1249;
- ATCC VR-532 Representative examples of such vector systems include those described in U.S. Patent Nos. 5,091,309; 5,217,879; and 5,185,440; WO 92/10578; WO 94/21792;
- Gene delivery vehicles of the present invention can also employ parvovirus such as adeno-associated virus (AAV) vectors.
- AAV adeno-associated virus
- Representative examples include the AAV vectors disclosed by Srivastava in WO
- adenoviral vectors include those described by Berkner, Biotechniques (1988) 6:616; Rosenfeld et al, Science (1991) 252:431; WO 93/19191;
- adenoviral gene therapy vectors employable in this invention also include those described in WO 94/12649,
- Naked DNA can also be employed.
- Exemplary naked DNA introduction methods are described in WO 90/11092 and U.S. Patent No. 5,580,859.
- Liposomes that can act as gene delivery vehicles are described in U.S. Patent No. 5,422,120; WO 95/13796; WO 94/23697; WO 91/14445; and EP 0524968.
- non-viral delivery suitable for use includes mechanical delivery systems such as the approach described in Woffendin et al, Proc. Natl. Acad. Sci. USA (1994) 97(24): 11581.
- the coding sequence and the product of expression of such can be delivered through deposition of photopolymerized hydrogel materials.
- Other conventional methods for gene delivery that can be used for delivery of the coding sequence include, for example, use of hand-held gene transfer particle gun, as described in U.S. Patent No. 5,149,655; use of ionizing radiation for activating transferred gene, as described in U.S. Patent No. 5,206,152 and WO 92/11033.
- Example 1 Source of Biological Materials and Overview of Novel Polynucleotides Expressed by the Biological Materials Human colon cancer cell line Kml2L4-A (Morika, W. A. K. et al., Cancer
- the KML4-A is a highly metastatic subline derived from KM12C (Yeatman et al.
- KM12C and KM12C-derived cell lines are well-recognized in the art as a model cell line for the study of colon cancer (see, e.g., Moriakawa et al, supra; Radinsky et al. Clin. Cancer Res. (1995) 7:19; Yeatman et al, (1995) supra; Yeatman et al. Clin. Exp. Metastasis (1996) 74:246).
- masking does not influence the final search results, except to eliminate sequences of relative little interest due to their low complexity, and to eliminate multiple "hits" based on similarity to repetitive regions common to multiple sequences, e.g., Alu repeats.
- Masking resulted in the elimination of 43 sequences.
- the remaining sequences were then used in a BLASTN vs. Genbank search with search parameters of greater than 70% overlap, 99% identity, and a p value of less than l x l 0 "40 , which search resulted in the discarding of 1,432 sequences. Sequences from this search also were discarded if the inclusive parameters were met, but the sequence was ribosomal or vector-derived.
- the resulting sequences from the previous search were classified into three groups (1, 2 and 3 below) and searched in a BLASTX vs. NRP (non-redundant proteins) database search: (1) unknown (no hits in the Genbank search), (2) weak similarity (greater than 45%) identity and p value of less than 1 x IO "5 ), and (3) high similarity (greater than 60% overlap, greater than 80%> identity, and p value less than 1 x IO '5 ).
- This search resulted in discard of 98 sequences as having greater than 70%> overlap, greater than 99%) identity, and p value of less than 1 x 10 "40 .
- sequences were classified as unknown (no hits), weak similarity, and high similarity (parameters as above). Two searches were performed on these sequences.
- a BLAST vs. EST database search resulted in discard of 1771 sequences (sequences with greater than 99% overlap, greater than 99% similarity and a p value of less than 1 x 10 "40 ; sequences with a p value of less than 1 x 10 "65 when compared to a database sequence of human origin were also excluded).
- a BLASTN vs. Patent GeneSeq database resulted in discard of 15 sequences (greater than 99% identity; p value less than 1 x IO "40 ; greater than 99% overlap).
- sequences were subjected to screening using other mles and redundancies in the dataset. Sequences with a p value of less than 1 x 10 _1 ' ' in relation to a database sequence of human origin were specifically excluded. The final result provided the 2502 sequences listed in the accompanying Sequence Listing. The Sequence Listing is arranged beginning with sequences with no similarity to any sequence in a database searched, and ending with sequences with the greatest similarity. Each identified polynucleotide represents sequence from at least a partial mRNA transcript.
- Polynucleotides that were determined to be novel were assigned a sequence identification number.
- the novel polynucleotides were assigned sequence identification numbers SEQ ID NOS: 1-2502.
- the DNA sequences corresponding to the novel polynucleotides are provided in the Sequence Listing. The majority of the sequences are presented in the Sequence Listing in the 5' to 3' direction. A small number of sequences are listed in the Sequence Listing in the 5' to 3' direction but the sequence as written is actually 3' to 5'. These sequences are readily identified with the designation "AR" in the Sequence Name in Table 1 (inserted before the claims). The sequences correctly listed in the 5' to 3' direction in the Sequence Listing are designated "AF.”
- Table 1 provides: 1) the SEQ ID NO assigned to each sequence for use in the present specification; 2) the filing date of the U.S.
- two or more polynucleotides of the invention may represent different regions of the same mRNA transcript and the same gene.
- SEQ ID NOS: are identified as belonging to the same clone, then either sequence can be used to obtain the full-length mRNA or gene.
- some sequences are identified with multiple SEQ ID NOS, since these sequences were present in more than one filing. For example, SEQ ID NO:87 and SEQ ID NO: 1000 represent the same sequence.
- SEQ ID NOS:2503-5106 In order to confirm the sequences of SEQ ID NOS:2502, inserts of the clones corresponding to these polynucleotides were re-sequenced. These "validation" sequences are provided in SEQ ID NOS:2503-5106. Of these validation sequences, SEQ ID NOS:3040, 3545, 3863, 4511, 4726, and 4749 are not tme validation sequences. Instead, SEQ ID NOS :3545, 4511, 4726, and 4749 represent "placeholder" sequences, i.e., sequences that were inserted into the Sequence Listing only to prevent renumbering of the subsequent sequences during generation of the Sequence Listing.
- SEQ ID NOS: 1-5252 “SEQ ID NOS: 1-5106,” or other ranges of SEQ ID NOS that include these placeholder sequences should be read to exclude SEQ ID NOS:3545, 4511, 4726, and 4749.
- validation sequences were often longer than the original polynucleotide sequences they validate, and thus often provide additional sequence information.
- Validation sequences can be correlated with the original sequences they validate by referring to Table 1. For example, validation sequences of SEQ ID NOS:2503-3039, 3041- 3544, 3546-3862 3864-4510, and 4512-4725 share the clone name of the sequence of SEQ ID NOS: 1-2502 that they validate.
- SEQ ID NOS:1-2502 as well as the validation sequences SEQ ID NOS:2503-3039, 3041-3544, 3546-3862 3864-4510, and 4512-4725 xxxlf were translated in all three reading frames to determine the best alignment with the individual sequences.
- These amino acid sequences and nucleotide sequences are referred, generally, as query sequences, which are aligned with the individual sequences. Query and individual sequences were aligned using the BLAST programs, available over the world wide web at http://ww.ncbi.nlm.nih.gov/BLAST/.
- Table 2 shows the results of the alignments. Table 2 refers to each sequence by its SEQ ID NO:, the accession numbers and descriptions of nearest neighbors from the Genbank and Non-Redundant Protein searches, and the p values of the search results.
- SEQ ID NOS: 1-5106 For each of "SEQ ID NOS: 1-5106,” the best alignment to a protein or DNA sequence is included in Table 2.
- the activity of the polypeptide encoded by “SEQ ID NOS: 1-5106” is the same or similar to the nearest neighbor reported in Table 2.
- the accession number of the nearest neighbor is reported, providing a reference to the activities exhibited by the nearest neighbor.
- the search program and database used for the alignment also are indicated as well as a calculation of the p value.
- Full length sequences or fragments of the polynucleotide sequences of the nearest neighbors can be used as probes and primers to identify and isolate the full length sequence of "SEQ ID NOS: 1-5106.”
- the nearest neighbors can indicate a tissue or cell type to be used to constmct a library for the full-length sequences of "SEQ ID NOS: 1-5106.”
- SEQ ID NOS: 1-5106 and the translations thereof may be human homologs of known genes of other species or novel allelic variants of known human genes. In such cases, these new human sequences are suitable as diagnostics or therapeutics. As diagnostics, the human sequences “SEQ ID NOS: 1-5106" exhibit greater specificity in detecting and differentiating human cell lines and types than homologs of other species. The human polypeptides encoded by "SEQ ID NOS 1-5106" are likely to be less immunogenic when administered to humans than homologs from other species. Further, on administration to humans, the polypeptides encoded by "SEQ ID NOS: 1-5106" can show greater specificity or can be better regulated by other human proteins than are homologs from other species.
- the validation sequences (“SEQ ID NOS:2503-5106”) were used to conduct a profile search as described in the specification above.
- Several of the polynucleotides of the invention were found to encode polypeptides having characteristics of a polypeptide belonging to a known protein families (and thus represent new members of these protein families) and/or comprising a known functional domain (Table 3, inserted prior to claims).
- the invention encompasses fragments, fusions, and variants of such polynucleotides that retain biological activity associated with the protein family and/or functional domain identified herein.
- Start and stop indicate the position within the individual sequences that align with the query sequence having the indicated SEQ ID NO.
- the direction (Dir) indicates the orientation of the query sequence with respect to the individual sequence, where forward (for) indicates that the alignment is in the same direction (left to right) as the sequence provided in the Sequence Listing and reverse (rev) indicates that the alignment is with a sequence complementary to the sequence provided in the Sequence Listing.
- Some polynucleotides exhibited multiple profile hits because, for example, the particular sequence contains overlapping profile regions, and/or the sequence contains two different functional domains. These profile hits are described in more detail below.
- the acronyms used in Table 3 are provided in parentheses following the full name of the protein family or functional domain to which they refer. a) Seven Transmembrane Integral Membrane Proteins — Rhodopsin Family (7tm 1).
- Several of the validation sequences, and thus their corresponding sequence within SEQ ID NOS: 1-2502 correspond to a sequence encoding a polypeptide that is a member of the seven transmembrane receptor rhodopsin family.
- G-protein coupled receptors of the seven transmembrane rhodopsin family are an extensive group of hormones, neurotransmitters, and light receptors which transduce extracellular signals by interaction with guanine nucleotide-binding (G) proteins (Strosberg A.D. Eur. J. Biochem. (1991) 796:1, Kerlavage A.R Curr. Opin. Struct. Biol. (1991) 7:394, Probst, et al., DNA Cell Biol. (1992) 77:1, Savarese, et al., Biochem. J. (1992) 233:1, http://www. crdb.uthscsa.edu/.
- the receptors that are currently known to belong to this family are: 1) 5-hydroxytryptamine (serotonin) 1A to IF, 2A to 2C, 4, 5A, 5B, 6 and 7 (Branchek T., Curr. Biol. (1993) 3:315); 2) acetylcholine, muscarinic-type, Ml to M5; 3) adenosine Al, A2A, A2B and A3 (Stiles G.L. J. Biol. Chem.
- Opioids delta-, kappa- and mu-types Uhl G.R., et al., Trends Neurosci. (1994) 77:89; 30) Oxytocin (OT-R); 31) Platelet activating factor (PAF-R); 32) Prostacyclin; 33) Prostaglandin D2; 34) Prostaglandin E2, EP1 to EP4 subtypes; 35) Prostaglandin F2; 36) Purinoreceptors (ATP) (Barnard E.A., et al., Trends Pharmacol Sci.
- these receptors The stmcture of these receptors is thought to be identical. They have seven hydrophobic regions, each of which most probably spans the membrane. The N-terminus is located on the extracellular side of the membrane and is often glycosylated, while the C- terminus is cytoplasmic and generally phosphorylated. Three extracellular loops alternate with three intracellular loops to link the seven transmembrane regions. Most, but not all of these receptors, lack a signal peptide. The most conserved parts of these proteins are the transmembrane regions and the first two cytoplasmic loops.
- a conserved acidic-Arg- aromatic triplet is present in the N-terminal extremity of the second cytoplasmic loop (Attwood T.K., Eliopoulos E.E., Findlay J.B.C. Gene (1991) 93:153-159) and could be implicated in the interaction with G proteins.
- Every receptor in the 7 transmember secretin family is encoded on multiple exons, and several of these functionally distinct products.
- the N-terminal extracellular domain of these receptors contains five conserved cysteines residues that may be involved in disulfide bonds, with a consensus pattern in the region that spans the first three cysteines.
- One of the most highly conserved regions spans the C-terminal part of the last transmembrane region and the beginning of the adjacent intracellular region. This second region is used as a second signature pattern.
- the two consensus patterns are: 1) C-x(3)-[FYWLIV]-D-x(3,4)-C-[FW]-x(2)-[STAGV]-x(8,9)-C-[PF]
- SEQ IS NO:2656 represents a polynucleotide encoding an Ank repeat- containing protein.
- the ankyrin motif is a 33 amino acid sequence named after the protein ankyrin which has 24 tandem 33-amino-acid motifs.
- Ank repeats were originally identified in the cell-cycle-control protein cdclO (Breeden et al, Nature (1987) 329:651).
- Proteins containing ankyrin repeats include ankyrin, myotropin, I-kappaB proteins, cell cycle protein cdclO, the Notch receptor (Matsuno et al, Development (1997) 124(21) :4265); G9a (or BAT8) of the class III region of the major histocompatibility complex (Biochem J. 290:811-818, 1993), FABP, GABP, 53BP2, Linl2, glp-1, SW14, and SW16.
- the functions of the ankyrin repeats are compatible with a role in protein-protein interactions (Bork, Proteins (1993) 17(4):363; Lambert and Bennet, Eur. J. Biochem.
- the 90 kD N-terminal domain of ankyrin contains a series of 24 33-amino-acid ank repeats. (Lux et al, Nature (1990) 344:36-42, Lambert et al, PNAS USA (1990) 37:1730.)
- the 24 ank repeats form four folded subdomains of 6 repeats each. These four repeat subdomains mediate interactions with at least 7 different families of membrane proteins.
- Ankyrin contains two separate binding sites for anion exchanger dimers.
- One site utilizes repeat subdomain two (repeats 7-12) and the other requires both repeat subdomains 3 and 4 (repeats 13-24). Since the anion exchangers exist in dimers, ankyrin binds 4 anion exchangers at the same time (Michaely and Bennett, J. Biol Chem. (1995) 270(37) :22050). The repeat motifs are involved in ankyrin interaction with tubulin, spectrin, and other membrane proteins. (Lux et al, Nature (1990) 344:36.) The Rel/NF-kappaB/Dorsal family of transcription factors have activity that is controlled by sequestration in the cytoplasm in association with inhibitory proteins referred to as I-kappaB.
- I-kappaB proteins contain 5 to 8 copies of 33 amino acid ankyrin repeats and certain NF-kappaB/rel proteins are also regulated by cis-acting ankyrin repeat containing domains including pl05NF-kappaB which contains a series of ankyrin repeats (Diehl and Hannink, J. Virol. (1993) 67(12):ll6l).
- the I-kappaBs and Cactus inhibit activators through differential interactions with the Rel- homology domain.
- the gene family includes proto-oncogenes, thus broadly implicating I- kappaB in the control of both normal gene expression and the aberrant gene expression that makes cells cancerous. (Nolan and Baltimore, Curr Opin Genet Dev. (1992) 2(2) :211-220).
- rel/NF-kappaB and pp40/I-kappaB( both the ankyrin repeats and the carboxy -terminal domain are required for inhibiting DNA-binding activity and direct association of pp40/I-kappaB( with rel/NF-kappaB protein.
- the ankyrin repeats and the carboxy -terminal of pp40/I-kappaB( form a stmcture that associates with the rel homology domain to inhibit DNA binding activity (Inoue et al, PNAS USA (1992) 39:4333).
- the 4 ankyrin repeats in the amino terminus of the transcription factor subunit GABP are required for its interaction with the GABP subunit to form a functional high affinity DNA-binding protein. These repeats can be crosslinked to DNA when GABP is bound to its target sequence.
- Myotrophin a 12.5 kDa protein having a key role in the initiation of cardiac hypertrophy, comprises ankyrin repeats.
- the ankyrin repeats are characteristic of a hai ⁇ in-like protmding tip followed by a helix-turn-helix motif.
- Eukaryotic Aspartyl Proteases (asp).
- Aspartyl proteases known as acid proteases, (EC 3.4.23.-) are a widely distributed family of proteolytic enzymes (Foltmann B., Essays Biochem. (1981) 77:52; Davies D.R., Annu. Rev. Biophys. Chem.
- Aspartate proteases of eukaryotes are monomeric enzymes which consist of two domains. Each domain contains an active site centered on a catalytic aspartyl residue. The two domains most probably evolved from the duplication of an ancestral gene encoding a primordial domain.
- eukaryotic aspartyl proteases include: 1) Vertebrate gastric pepsins A and C (also known as gastricsin); 2) Vertebrate chymosin (rennin), involved in digestion and used for making cheese; 3) Vertebrate lysosomal cathepsins D (EC 3.4.23.5) and E (EC 3.4.23.34); 4) Mammalian renin (EC 3.4.23.15) whose function is to generate angiotensin I from angiotensinogen in the plasma; 5) Fungal proteases such as aspergillopepsin A (EC 3.4.23.18), candidapepsin (EC 3.4.23.24), mucoropepsin (EC 3.4.23.23) (mucor rennin), endothiapepsin (EC 3.4.23.22), polyporopepsin (EC 3.4.23.29), and rhizopuspepsin (EC 3.4.23.21); and 6)
- PEP4 is implicated in posttranslational regulation of vacuolar hydrolases; 7) Yeast barrie ⁇ epsin (EC 3.4.23.35) (gene BAR1); a protease that cleaves alpha-factor and thus acts as an antagonist of the mating pheromone; and 8) Fission yeast sxal which is involved in degrading or processing the mating pheromones.
- retrovimses and some plant vimses encode for an aspartyl protease which is an homodimer of a chain of about 95 to 125 amino acids.
- the protease is encoded as a segment of a polyprotein which is cleaved during the maturation process of the vims. It is generally part of the pol polyprotein and, more rarely, of the gag polyprotein. Because the sequence around the two aspartates of eukaryotic aspartyl proteases and around the single active site of the viral proteases is conserved, a single signature pattern can be used to identify members of both groups of proteases.
- the consensus pattern is: [LIVMFGAC]-[LIVMTADN]-[LIVFSA]-D-[ST]-G- [STAV]-[STAPDENQ]- x-[LIVMFSTNC]-x-[LIVMFGTA], where D is the active site residue.
- ATPases Associated with Various Cellular Activities
- the AAA protein family is composed of a large number of ATPases that share a conserved region of about 220 amino acids that contains an ATP-binding site (Froehlich et al, J. Cell Biol. (1991) 774:443; Erdmann et al Cell (1991) 64:499; Peters et al, EMBOJ. (1990) 9:1757; Kunau et al, Biochimie (1993) 75:209-224; Confalonieri et al, BioEssays (1995) 77:639; http://yeamob.pci.chemie.uni- tuebingen.de/AAA/Description.html).
- the proteins that belong to this family either contain one or two AAA domains.
- Proteins containing two AAA domains include: 1) Mammalian and drosophila NSF (N-ethylmaleimide-sensitive fusion protein) and the fungal homolog, SEC 18, which are involved in intracellular transport between the endoplasmic reticulum and Golgi, as well as between different Golgi cisternae; 2) Mammalian transitional endoplasmic reticulum ATPase (previously known as p97 or VCP), which is involved in the transfer of membranes from the endoplasmic reticulum to the golgi apparatus. This ATPase forms a ring-shaped homooligomer composed of six subunits.
- Proteins containing a single AAA domain include: 1) Escherichia coli and other bacteria ftsH (or hflB) protein.
- FtsH is an ATP-dependent zinc metallopeptidase that degrades the heat-shock sigma-32 factor, and is an integral membrane protein with a large cytoplasmic C-terminal domain that contain both the AAA and the protease domains; 2) Yeast protein YME1, a protein important for maintaining the integrity of the mitochondrial compartment. YME1 is also a zinc-dependent protease; 3) Yeast protein AFG3 (or YTA10). This protein also contains an AAA domain followed by a zinc-dependent protease domain; 4) Subunits from regulatory complex of the 26S proteasome (Hilt et al, Trends Biochem. Sci.
- ubiquitinated proteins which subunits include: a) Mammalian 4 and homologs in other higher eukaryotes, in yeast (gene YTA5) and fission yeast (gene mts2); b) Mammalian 6 (TBP7) and homologs in other higher eukaryotes and in yeast (gene YTA2); c) Mammalian subunit 7 (MSS1) and homologs in other higher eukaryotes and in yeast (gene CIM5 or YTA3); d) Mammalian subunit 8 (P45) and homologs in other higher eukaryotes and in yeast (SUG1 or CIM3 or TBY1) and fission yeast (gene letl); e) Other probable subunits include human TBPl, which influences HIV gene expression by interacting with the vims tat transactivator protein, and yeast YTA1 and YTA6;
- AAA domains in these proteins act as ATP-dependent protein clamps(Confalonieri et al (1995) BioEssays 77:639).
- ATP-binding 'A' and 'B' motifs which are located in the N-terminal half of this domain, thereis a highly conserved region located in the central part of the domain which was used in the development of the signature pattern.
- Bcl-2 family (Bcl-2).
- SEQ ID NO:3404 SEQ ID NO:3404, and thus the corresponding sequence it validates, represents a polynucleotide encoding an apoptosis regulator protein of the Bcl-2 family. Active cell suicide (apoptosis) is induced by events such as growth factor withdrawal and toxins.
- BH1, BH2, BH3, or BH4 domain contain either a BH1, BH2, BH3, or BH4 domain.
- All anti-apoptotic proteins contain BH1 and BH2 domains; some of them contain an additional N-terminal BH4 domain (Bcl-2, Bcl-x(L), Bcl-w), which is never seen in pro-apoptotic proteins, except for Bcl-x(S).
- all pro-apoptotic proteins contain a BH3 domain (except for Bad) necessary for dimerization with other proteins of Bcl-2 family and cmcial for their killing activity; some of them also contain BH1 and BH2 domains (Bax, Bak).
- the BH3 domain is also present in some anti-apoptotic protein, such as Bcl-2 or Bcl-x(L). Proteins that are known to contain these domains are listed below.
- Vertebrate protein Bcl-2 blocks apoptosis; it prolongs the survival of hematopoietic cells in the absence of required growth factors and also in the presence of various stimuli inducing cellular death.
- Two isoforms of bcl-2 (alpha and beta) are generated by alternative splicing. Bcl-2 is expressed in a wide range of tissues at various times during development. It forms heterodimers with the Bax proteins.
- Vertebrate protein Bcl-x Two isoforms of Bcl-x (Bcl-x(L) and Bcl-x(S)) are generated by alternative splicing. While the longer product (Bcl-x(L)) can protect a growth-factor-dependent cell line from apoptosis, the shorter form blocks the protective effect of Bcl-2 and Bcl-x(L) and acts as an anti-anti-apoptosis protein.
- Bax blocks the anti-apoptosis ability of Bcl-2 with which it forms heterodimers. There is no evidence that Bax has any activity in the absence of Bcl-2. Three isoforms of bax (alpha, beta and gamma) are generated by alternative splicing.
- Mammalian protein Bak which promotes cell death and counteracts the protection from apoptosis provided by Bcl-2.
- Mammalian protein Bcl-w which promotes cell survival.
- Mammalian protein bad which promotes cell death, and counteracts the protection from apoptosis provided by Bcl-x(L), but not that of Bcl-2.
- MCL1 Human induced myeloid leukemia cell differentiation protein MCL1.
- MCL1 is probably involved in programming of differentiation and concomitant maintenance of viability but not proliferation. Its expression increases early during phorbol ester induced differentiation in myeloid leukemia cell line ML-1.
- Mammalian activator of apoptosis Harakiri (Inohara et al., 1997, EMBO J. 16:1686-1694) (also known as neuronal death protein Dp5). This is a small protein of 92 residues that activates apoptosis. It contains a BH3 domain, but no BHl, BH2 or BH4 domains.
- Bromodomain (bromodomain). SEQ ID NOS:4036 and 4489, and thus the corresponding sequences they validate, represent polynucleotides encoding a polypeptide having a bromodomain region (Haynes et al., 1992, Nucleic Acids Res. 20:2693-2603,
- TFIID 250 Kd subunit TBP-associated factor p250
- gene CCG1 Higher eukaryotes transcription initiation factor TFIID 250 Kd subunit
- P250 is associated with the TFIID TATA-box binding protein and seems essential for progression of the GI phase of the cell cycle.
- SEQ ID NO:3408, 2951, and 4850 represent polynucleotides encoding a novel member of the family of basic region plus leucine zipper transcription factors.
- the bZIP superfamily (Hurst, Protein Prof. (1995) 2:105; and Ellenberger, Curr. Opin. Struct. Biol. (1994) 4:12) of eukaryotic DNA-binding transcription factors encompasses proteins that contain a basic region mediating sequence- specific DNA-binding followed by a leucine zipper required for dimerization.
- Members of the family include transcription factor AP-1, which binds selectively to enhancer elements in the cis control regions of SV40 and metallothionein IIA.
- AP-1 also known as c-jun, is the cellular homolog of the avian sarcoma vims 17 (AS VI 7) oncogene v-jun.
- jun-B and jun-D probable transcription factors that are highly similar to jun/AP-1 ; the fos protein, a proto-oncogene that forms a non-covalent dimer with c-jun; the fos-related proteins fra-1, and fos B; and mammalian cAMP response element (CRE) binding proteins CREB, CREM, ATF-1, ATF-3, ATF-4, ATF-5, ATF-6 and LRF-1.
- CRE mammalian cAMP response element
- SEQ ID NOS:3618, 3895, and 4536 represent polynucleotides encoding cyclins
- SEQ ID NO:55 and 56 show the corresponding full-length polynucleotides.
- SEQ ID NO:57 and 58 show, respectively, the translations of SEQ ID NO:55 and 56.
- Cyclins (Nurse, 1990, Nature 344:503-508; Norbury et al., 1991, Curr. Biol. 1 :23-24; and Lew et al., 1992, Trends Cell Biol. 2:77-81) are eukaryotic proteins that play an active role in controlling nuclear cell division cycles. There are two main groups of cyclins.
- G2/M cyclins are essential for the control of the cell cycle at the G2/M (mitosis) transition. G2/M cyclins accumulate steadily during G2 and are abmptly destroyed as cells exit from mitosis (at the end of the M-phase). Gl/S cyclins are essential for the control of the cell cycle at the Gl/S (start) transition.
- cyclin-box The best conserved region is in the central part of the cyclins' sequences, known as the "cyclin-box," from which a 32 residue consensus pattern was derived: R-x(2)- [LIVMSA]-x(2)-[FYWS]-[LIVM]-x(8)-[LIVMFC]-x(4)-[LIVMFYA]-x(2)-[STAGC]- [LIVMFYQ]-x-[LIVMFYC]-[LIVMFY]-D-[RKH]-[LIVMFYW]. j) Eukaryotic thiol (cysteine) proteases active sites (Cys-protease).
- Eukaryotic thiol proteases (Dufour E., Biochimie (1988) 70:1335); are a family of proteolytic enzymes which contain an active site cysteine. Catalysis proceeds through a thioester intermediate and is facilitated by a nearby histidine side chain; an asparagine completes the essential catalytic triad.
- the proteases that belong to this family are:
- vertebrate lysosomal cathepsins B (Kirschke H., et al., Protein Prof. (1995) 2:1587- 1643); 2) vertebrate lysosomal dipeptidyl peptidase l (also known as cathepsin C) (Kirschke H., et al., supra); 3) vertebrate calpains (Calpains are intracellular calcium- activated thiol protease that contain both an N-terminal catalytic domain and a C-terminal calcium-binding domain); 4) mammalian cathepsin K, which seems involved in osteoclastic bone reso ⁇ tion (Shi G.-P., et al., FEBS Lett.
- bleomycin hydrolase which catalyzes the inactivation of the antitumor dmg BLM (a glycopeptide)
- Plant enzymes such as: barley aleurain, EP-B1/B4; kidney bean EP-Cl, rice bean SH-EP; kiwi fruit actinidin; papaya latex papin, chymopapain, caricain, and proteinase IV; pea turgor-responsive protein 15 A; pineapple stem bromelain; rape COT44; rice oryzain alpha, beta, and gamma; tomato low- temperature induced, Arabidopsis thaliana A494, RD19A and RD21A; 8) - House-dust mites allergens DerPl and EurMl ; 9) cathepsin B-like proteinases from the worms Caenorhabditis elegans (genes gcp-1, cpr
- bacterial peptidases are also part of this family: 1) aminopeptidase C from Lactococcus lactis (gene pepC) (Chapot-Chartier M.P., et al., Appl Environ. Microbiol. (1993) 59:330); and 2) thiol protease tpr from Po ⁇ hyromonas gingivalis.
- aminopeptidase C from Lactococcus lactis (gene pepC) (Chapot-Chartier M.P., et al., Appl Environ. Microbiol. (1993) 59:330)
- thiol protease tpr from Po ⁇ hyromonas gingivalis.
- Three other proteins are structurally related to this family, but may have lost their proteolytic activity.
- soybean oil body protein P34 which has its active site cysteine replaced by a glycine
- rat testin which is a sertoli cell secretory protein highly similar to cathepsin L but with the active site cysteine is replaced by a serine
- SERA Plasmodium falciparum serine-repeat protein
- sequences around the three active site residues are well conserved and can be used as signature patterns:
- Consensus pattern #1 Q-x(3)-[GE]-x-C-[YW]-x(2)-[STAGC]-[STAGCV] (where C is the active site residue)
- Consensus pattern #2 [LIVMGSTAN]-x-H-[GSACE]-[LIVM]-x-[LIVMAT](2)-G- x-[GSADNH] (where H is the active site residue);
- Consensus patent #3 [FYCH]-[WI]-[LIVT]-x-[KRQAG]-N-[ST]-W-x(3)-[FYW]- G-x(2)-G- [LFYW]-[LIVMFYG]-x-[LIVMF] (where N is the active site residue).
- DAG_PE_bind Phorbol Esters/Diacylglvcerol Binding
- Phorbol esters are analogues of DAG and potent tumor promoters that cause a variety of physiological changes when administered to both cells and tissues.
- DAG activates a family of serine/threonine protein kinases, collectively known as protein kinase C (PKC) (Azzi et al, Eur. J. Biochem. (1992) 203:547).
- PKC protein kinase C
- Phorbol esters can directly stimulate PKC.
- the N-terminal region of PKC, known as Cl has been shown (Ono et al., Proc. Natl. Acad. Sci. USA (1989) 36:4868) to bind PE and DAG in a phospholipid and zinc-dependent fashion.
- the Cl region contains one or two copies (depending on the isozyme of PKC) of a cysteine-rich domain about 50 amino-acid residues long and essential for DAG/PE-binding.
- a cysteine-rich domain about 50 amino-acid residues long and essential for DAG/PE-binding.
- Such a domain has also been found in, for example, the following proteins.
- DGK Diacylglycerol kinase (EC 2.7.1.107) (DGK) (Sakane et al, Nature (1990) 344:345), the enzyme that converts DAG into phosphatidate. It contains two copies of the DAG/PE-binding domain in its N-terminal section. At least five different forms of DGK are known in mammals; and
- N-chimaerin a brain specific protein which shows sequence similarities with the BCR protein at its C-terminal part and contains a single copy of the DAG/PE-binding domain at its N-terminal part. It has been shown (Ahmed et al, Biochem. J. (1990)
- the DAG/PE-binding domain binds two zinc ions; the ligands of these metal ions are probably the six cysteines and two histidines that are conserved in this domain.
- the signature pattern completely spans the DAG/PE domain.
- the consensus pattern is: H-x- [LIVMFYW]-x(8,l l)-C-x(2)-C-x(3)-[LIVMFC]-x(5,10)-C-x(2)-C-x(4)-[HD]-x(2)-C- x(5,9)-C. All the C and H are probably involved in binding zinc.
- DEAD and DEAH box families ATP-dependent helicases signatures (Dead box helic).
- SEQ ID NOS:4821 and 5083 and thus the sequences they validate, represent polynucleotides encoding a novel member of the DEAD box family.
- a number of eukaryotic and prokaryotic proteins have been characterized (Schmid S.R., et al, Mol. Microbiol. (1992) 6:283; Linder P., et al., Nature (1989) 337:121; Wassarman D.A., et al., Nature (1991) 349:463) on the basis of their stmctural similarity. All are involved in ATP- dependent, nucleic-acid unwinding. Proteins currently known to belong to this family are:
- Initiation factor eIF-4A is a subunit of a high molecular weight complex involved in 5 'cap recognition and the binding of mRNA to ribosomes. It is an ATP-dependent RNA-helicase.
- PRP5 and PRP28 are involved in various ATP-requiring steps of the pre-mRNA splicing process.
- PI 10 a mouse protein expressed specifically during spermatogenesis.
- MSS116 a yeast protein required for mitochondrial splicing.
- SPB4 a yeast protein involved in the maturation of 25 S ribosomal RNA.
- p68 a human nuclear antigen. p68 has ATPase and DNA-helicase activities in vitro. It is involved in cell growth and division. 10) Rm62 (p62), a Drosophila putative RNA helicase related to p68.
- DBP2 a yeast protein related to p68.
- DHH1 a yeast protein
- DRS1 a yeast protein involved in ribosome assembly.
- MAK5 a yeast protein involved in maintenance of dsRNA killer plasmid.
- ROK 1 a yeast protein.
- Vasa a Drosophila protein important for oocyte formation and specification of embryonic posterior stmctures.
- Me31B a Drosophila maternally expressed protein of unknown function.
- dbpA an Escherichia coli putative RNA helicase.
- rhlE an Escherichia coli putative RNA helicase.
- rmB an Escherichia coli protein that shows RNA-dependent ATPase activity, which interacts with 23 S ribosomal RNA.
- Bacillus subtilis hypothetical protein yxiN All of the above proteins share a number of conserved sequence motifs. Some of them are specific to this family while others are shared by other ATP-binding proteins or by proteins belonging to the helicases 'superfamily' (Hodgman T.C., Nature (1988) 333:22 and Nature (1988) 333:578 (Errata); http://www.expasy.ch/www/linder/HELICASES_TEXT.html).
- One of these motifs, called the 'D-E-A-D-box' represents a special version of the B motif of ATP-binding proteins.
- Proteins currently known to belong to this DEAH subfamily are:
- PRP2, PRP 16, PRP22 and PRP43 yeast proteins are all involved in various ATP -requiring steps of the pre-mRNA splicing process.
- Fission yeast prhl which my be involved in pre-mRNA splicing.
- Fission yeast radl5 (rhp3) and mammalian DNA excision repair protein XPD (ERCC-2) are the homologs of RAD3.
- Yeast CHL1 (or CTF1), which is important for chromosome transmission and normal cell cycle progression in G(2)/M. 6) Yeast TPSl. 7) Yeast hypothetical protein YKL078w. 8) Caenorhabditis elegans hypothetical proteins C06E1.10 and K03H1.2. 9) Poxviruses' early transcription factor 70 Kd subunit which acts with RNA polymerase to initiate transcription from early gene promoters. 10) 18, a putative vaccinia vims helicase. 11) h ⁇ A, an Escherichia coli putative RNA helicase. The following signature patterns are used to identify member for both subfamilies:
- Consensus pattern [LIVMF](2)-D-E-A-D-[RKEN]-x-[LIVMFYGSTN]
- Consensus pattern [GSAH]-x-[LIVMF](3)-D-E-[ALIV]-H-[NECR].
- EFhand EFhand
- Many calcium-binding proteins belong to the same evolutionary family and share a type of calcium-binding domain known as the EF-hand (Kawasaki et al, Protein. Prof. (1995) 2:305-490).
- This type of domain consists of a twelve residue loop flanked on both sides by a twelve residue alpha-helical domain.
- the calcium ion is coordinated in a pentagonal bipyramidal configuration.
- the six residues involved in the binding are in positions 1, 3, 5, 7, 9 and 12; these residues are denoted by X, Y, Z, -Y, -X and -Z.
- the invariant Glu or Asp at position 12 provides two oxygens for liganding Ca (bidentate ligand).
- the consensus pattern includes the complete EF-hand loop as well as the first residue which follows the loop and which seem to always be hydrophobic: D-x-[DNS]- ⁇ ILVFYW ⁇ -[DENSTG]-[DNQGHRK]- ⁇ GP ⁇ -[LIVMC]-[DENQSTAGC]-x(2)-[DE]- [LIVMFYW].
- SEQ ID NO:2849 and thus the sequence it validates, represents a polynucleotide encoding a polypeptide with N-terminal homology in ETS domain. Proteins of this family contain a conserved domain, the "ETS-domain,” that is involved in DNA binding.
- the domain appears to recognize purine-rich sequences; it is about 85 to 90 amino acids in length, and is rich in aromatic and positively charged residues (Wasylyk, et al., , Eur. J. Biochem. (1993) 277:718).
- the ets gene family encodes a novel class of DNA-binding proteins, each of which binds a specific DNA sequence. These proteins comprise an ets domain that specifically interacts with sequences containing the common core tri-nucleotide sequence GGA. In addition to an ets domain, native ets proteins comprise other sequences which can modulate the biological specificity of the protein. Ets genes and proteins are involved in a variety of essential biological processes including cell growth, differentiation and development, and three members are implicated in oncogenic process. o) Type II f ⁇ bronectin collagen-binding domain (Fntvpell).
- Fibronectin is a plasma protein that binds cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin.
- the major part of the sequence of fibronectin consists of the repetition of three types of domains, which are called type I, II, and III (Skorstengaard K., et al., Eur. J. Biochem. (1986) 767:441).
- Type II domain is approximately forty residues long, contains four conserved cysteines involved in disulfide bonds and is part of the collagen-binding region of fibronectin.
- Type II domains have also been found in the following proteins: 1) blood coagulation factor XII (Hageman factor) (1 copy); 2) bovine seminal plasma proteins PDC-109 (BSP-A1/A2) and BSP-A3 (Seidah N.G., et al., Biochem. J. (1987) 243:195. (twice); 3) cation-independent mannose- 6-phosphate receptor (which is also the insulin-like growth factor II receptor) Komfeld S., Annu. Rev. Biochem. (1992) 67:307) (1 copy); 4) Mannose receptor of macrophages (Taylor M.E., et al., J Biol. Chem.
- Hepatocyte growth factor activator (Miyazawa K., et al., J. Biol. Chem. (1993) 263:10024) (1 copy).
- a schematic representation of the position of the invariant residues and the topology of the disulfide bonds in fibronectin type II domain is shown below: xxCxxPFx#xxxxxxxCxxxxxxxxxxxxxxWCxxxxx#xxx#x#Cxx where 'C represents the conserved cysteine involved in a disulfide bond and '#' represents a large hydrophobic residue.
- the consensus pattern for identifying members of this family is: C-x(2)-P-F-x-[FYWI]-x(7)-C-x(8,10)-W-C- x(4)-[DNSR]-[FYW]- x(3,5)-[FYW]-x-[FYWI]-C (where the four C's are involved in disulfide bonds).
- G-alpha G-Protein Alpha Subunit
- G-proteins are a family of membrane-associated proteins that couple extracellularly-activated integral- membrane receptors to intracellular effectors, such as ion channels and enzymes that vary the concentration of second messenger molecules.
- G-proteins are composed of 3 subunits (alpha, beta and gamma) which, in the resting state, associate as a trimer at the inner face of the plasma membrane.
- the alpha subunit has a molecule of guanosine diphosphate (GDP) bound to it. Stimulation of the G-protein by an activated receptor leads to its exchange for GTP (guanosine triphosphate).
- GDP guanosine diphosphate
- alpha and beta-gamma subunits are then able to interact with effectors, either individually or in a cooperative manner.
- the intrinsic GTPase activity of the alpha subunit hydrolyses the bound GTP to GDP. This returns the alpha subunit to its inactive conformation and allows it to reassociate with the beta-gamma subunit, thus restoring the system to its resting state.
- G-protein alpha subunits are 350-400 amino acids in length and have molecular weights in the range 40-45 kDa. Seventeen distinct types of alpha subunit have been identified in mammals.
- alpha-s alpha-s, alpha-q, alpha-i and alpha-12 (Simon et al, Science (1993) 252:802).
- alpha subunits are substrates for ADP-ribosylation by cholera or pertussis toxins. They are often N-terminally acylated, usually with myristate and/or palmitoylate, and these fatty acid modifications are probably important for membrane association and high- affinity interactions with other proteins.
- SEQ ID NO: 4241 and thus the sequence it validates, represents a polynucleotide encoding a protein having a homeobox domain.
- the 'homeobox' is a protein domain of 60 amino acids (Gehring In: Guidebook to the Homebox Genes, Duboule D., Ed., ppl-10, Oxford University Press, Oxford, (1994); Buerglin In: Guidebook to the Homebox Genes, pp25-72, Oxford University Press, Oxford, (1994); Gehring Trends Biochem. Sci. (1992) 77:277-280; Gehring et alAnnu. Rev. Genet. (1986) 20:147-173; Schofield Trends Neurosci.
- Drosophila homeotic and segmentation proteins first identified in number of Drosophila homeotic and segmentation proteins. It is extremely well conserved in many other animals, including vertebrates. This domain binds DNA through a helix-tum-helix type of structure. Several proteins that contain a homeobox domain play an important role in development. Most of these proteins are sequence-specific DNA-binding transcription factors. The homeobox domain is also very similar to a region of the yeast mating type proteins. These are sequence-specific DNA- binding proteins that act as master switches in yeast differentiation by controlling gene expression in a cell type-specific fashion.
- a schematic representation of the homeobox domain is shown below.
- the helix- turn-helix region is shown by the symbols ⁇ ' (for helix), and 't' (for turn).
- the pattern detects homeobox sequences 24 residues long and spans positions 34 to 57 of the homeobox domain.
- the consensus pattern is as follows: [LIVMFYG]-[ASLVR]-x(2)- [LIVMSTACN]-x-[LIVM]-x(4)-[LIV]-[RKNQESTAIY]-[LIVFSTNKH]-W-[FYVC]-x- [NDQTAH]-x(5)-[RKNAIMW].
- MAP kinases are involved in signal transduction, and are important in cell cycle and cell growth controls.
- the MAP kinase kinases (MAPKK) are dual-specificity protein kinases which phosphorylate and activate MAP kinases.
- MAPKK homologues have been found in yeast, invertebrates, amphibians, and mammals.
- the MAPKK/MAPK phosphorylation switch constitutes a basic module activated in distinct pathways in yeast and in vertebrates.
- MAPKK regulation studies have led to the discovery ofat least four MAPKK convergent pathways in higher organisms. One of these is similar to the yeast pheromone response pathway which includes the stel 1 protein kinase.
- MAPKKs are apparently essential transducers through which signals must pass before reaching the nucleus.
- SEQ ID NO:4482 represents a polynucleotide encoding a novel 3'5'-cyclic nucleotide phosphodiesterases (PDEases).
- PDEases catalyze the hydrolysis of cAMP or cGMP to the corresponding nucleoside 5' monophosphates (Charbonneau H., et al, Proc. Natl Acad. Sci. U.S.A. (1986) 33:9308).
- There are at least seven different subfamilies of PDEases (Beavo J.A., et al., Trends Pharmacol. Sci.
- the signature pattern is determined from a stretch of 12 residues that contains two conserved histi dines: H-D-[LIVMFY]-x-H-x-[AG]-x(2)-[NQ]-x-[LIVMFY].
- z Protein Kinase (protkinase).
- Protein kinases catalyze phosphorylation of proteins in a variety of pathways, and are implicated in cancer. Eukaryotic protein kinases (Hanks S.K., et al., FASEB J. (1995) 9:576; Hunter T., Meth.
- Enzymol (1991) 200:3; Hanks S.K., et al, Meth. Enzymol (1991) 200:38; Hanks S.K., Curr. Opin. Struct. Biol (1991) 7:369; Hanks S.K., et al, Science (1988) 247:42) are enzymes that belong to a very extensive family of proteins which share a conserved catalytic core common to both serine/threonine and tyrosine protein kinases. There are a number of conserved regions in the catalytic domain of protein kinases. Two of the conserved regions are the basis for the signature pattern in the protein kinase profile.
- the first region which is located in the N-terminal extremity of the catalytic domain, is a glycine-rich stretch of residues in the vicinity of a lysine residue, which has been shown to be involved in ATP binding.
- the second region which is located in the central part of the catalytic domain, contains a conserved aspartic acid residue which is important for the catalytic activity of the enzyme (Knighton D.R., et al, Science (1991) 253:407).
- the protein kinase profile includes two signature patterns for this second region: one specific for serine/threonine kinases and the other for tyrosine kinases.
- a third profile is based on the alignment in (Hanks S.K., et al, FASEB J. (1995) 9:576) and covers the entire catalytic domain.
- the consensus patterns are as follows: 1) Consensus pattern: [LIV]-G- ⁇ P ⁇ -G- ⁇ P ⁇ -[FYWMGSTNH]-[SGA]- ⁇ PW ⁇ - [LIVCAT]- ⁇ PD ⁇ -x-[GSTACLIVMFY]-x(5,18)-[LIVMFYWCSTAR]-[AIVP]- [LIVMFAGCKR]-K, where K binds ATP.
- the majority of known protein kinases are detected by this pattern. Proteins kinases that are not detected by this consensus include viral kinases, which are quite divergent in this region and are completely missed bythis pattern.
- Consensus pattern [LIVMFYC]-x-[HY]-x-D-[LIVMFY]-K-x(2)-N- [LIVMFYCT](3), where D is an active site residue.
- This consensus sequence identifies most serine/threonine-specific protein kinases with only 10 exceptions. Half of the exceptions are viral kinases, while the other exceptions include Epstein-Barr virus BGLF4 and Drosophila ninaC, which have Ser and Arg, respectively, instead of the conserved Lys. These latter two protein kinases are detected by the tyrosine kinase specific pattern described below.
- the protein kinase profile also detects receptor guanylate cyclases and 2-5A-dependent ribonucleases. Sequence similarities between these two families and the eukaryotic protein kinase family have been noticed previously. The profile also detects Arabidopsis thaliana kinase-like protein TMKL1 which seems to have lost its catalytic activity.
- a protein analyzed includes the two of the above protein kinase signatures, the probability of it being a protein kinase is close to 100%.
- Eukaryotic-type protein kinases have also been found in prokaryotes such as Myxococcus xanthus (Munoz-Dorado J., et al, Cell (1991) 67:995) and Yersinia pseudotuberculosis. The patterns shown above has been updated since their publication in (Bairoch A., et al. , Nature (1988) 337 :22). aa) Ras family proteins (ras).
- SEQ IDNO:3671 and thus the sequence it validates, represent polynucleotides encoding the ras family of small GTP/GDP-binding proteins (Valencia et al., 1991, Biochemistry 30:4637-4648). Ras family members generally require a specific guanine nucleotide exchange factor (GEF) and a specific GTPase activating protein (GAP) as stimulators of overall GTPase activity.
- GEF guanine nucleotide exchange factor
- GAP GTPase activating protein
- the highest degree of sequence conservation is found in four regions that are directly involved in guanine nucleotide binding. The first two constitute most of the phosphate and Mg2+ binding site (PM site) and are located in the first half of the G-domain.
- the other two regions are involved in guanosine binding and are located in the C-terminal half of the molecule. Motifs and conserved stmctural features of the ras-related proteins are described in Valencia et al., 1991, Biochemistry 30:4637-4648.
- Thioredoxin family active site (Thioredox). SEQ ID NO:3936, and thus the sequence it validates, represent a polynucleotide encoding a protein having a thioredoxin family active site. Thioredoxins (Holmgren A., Annu. Rev. Biochem. (1985) 54:237; Gleason F.K., et al., FEMS Microbiol Rev. (1988) 54:271; Holmgren A. J Biol. Chem.
- Proteins (1991) 77:13) are small proteins of approximately one hundred amino- acid residues which participate in various redox reactions via the reversible oxidation of an active center disulfide bond. They exist in either a reduced form or an oxidized form where the two cysteine residues are linked in an intramolecular disulfide bond. Thioredoxin is present in prokaryotes and eukaryotes and the sequence around the redox-active disulfide bond is well conserved.
- PDI protein disulphide isomerases
- PDI major isozyme a multifunctional protein that also function as the beta subunit of prolyl 4-hydroxylase (EC 1.14.11.2), as a component of oligosaccharyl transferase (EC 2.4.1.119), as thyroxine deiodinase, as glutathione-insulin transhydrogenase, and as a thyroid hormone-binding protein
- ERp60 ER-60; 58 Kd microsomal protein
- All PDI contains two or three (ERp72) copies of the thioredoxin domain.
- the consensus pattern is: [LIVMF]-[LIVMSTA]-x-[LIVMFYC]-[FYWSTHE]-x(2)- [FYWGTN]-C- [GATPLVE]-[PHYWSTA]-C-x(6)-[LIVMFYWT] (where the two C's form the redox-active bond.
- cc TNFR/NGFR family cvsteine-rich region (TNFR c6).
- SEQ ID NO:3927 and thus the sequence it validates, represent a polynucleotide encoding a protein having a TNFR/NGFR family cysteine-rich region.
- cysteine-rich domain of about 110 to 160 amino acids in their N-terminal part, that can be subdivided into four (or in some cases, three) modules of about 40 residues containing 6 conserved cysteines. Proteins known to belong to this family (Mallet S., et al., Immunol Today (1991) 12:220; Sprang S.R., Trends Biochem. Sci. (1990) 15:366; Krammer P.H., et al., Curr. Biol. (1992) 2:383; Bazan J.F., Curr. Biol.
- TNFFR Tumor Necrosis Factor type I and type II receptors
- the signature pattern for the cysteine-rich region is based mainly on the position of the six conserved cysteines in each of the repeats: Consensus pattern: C-x(4,6)-[FYH]-x(5,10)-C-x(0,2)-C- x(2,3)-C-x(7,l l)-C-x(4,6)-[DNEQSKP]-x(2)-C (where the six C's are involved in disulfide bonds).
- Consensus pattern C-x(4,6)-[FYH]-x(5,10)-C-x(0,2)-C- x(2,3)-C-x(7,l l)-C-x(4,6)-[DNEQSKP]-x(2)-C (where the six C's are involved in disulfide bonds).
- dd Four Transmembrane Integral Membrane Proteins (transmembrane4).
- transmembrane 4 family includes a number of evolutionarily-related eukaryotic cell surface antigens (Levy et al, J. Biol. Chem., (1991) 266:14597; Tomlinson et al, Eur. J. Immunol (1993) 23:136; Barclay et al. The leucocyte antigen factbooks. (1993) Academic Press, London/San Diego).
- the proteins belonging to this family include: 1) Mammalian antigen CD9
- MIC3 Mammalian leukocyte antigen CD37, expressed on B lymphocytes; 3) Mammalian leukocyte antigen CD53 (OX- 44), which is implicated in growth regulation in hematopoietic cells; 4) Mammalian lysosomal membrane protein CD63 (melanoma-associated antigen ME491; antigen AD1); 5) Mammalian antigen CD81 (cell surface protein TAPA-1), which is implicated in regulation of lymphoma cell growth; 6) Mammalian antigen CD82 (protein R2; antigen C33; Kangai 1 (KAI1)), which associates with CD4 or CD8 and delivers costimulatory signals for the TCR/CD3 pathway; 7) Mammalian antigen CD151 (SFA-1; platelet- endothelial tetraspan antigen 3 (PETA-3)); 8) Mammalian cell surface glycoprotein A15 (TALLA- 1 ; MXS, which is involved in platelet activation and aggregation;
- the members of the 4 transmembrane family share several characteristics. First, they all are apparently type III membrane proteins, which are integral membrane proteins containing an N-terminal membrane-anchoring domain which is not cleaved during biosynthesis and which functions both as a translocation signal and as a membrane anchor.
- the family members also contain three additional transmembrane regions, at least seven conserved cysteines residues, and are of approximately the same size (218 to 284 residues). These proteins are collectively know as the "transmembrane 4 superfamily" (TM4) because they span plasma membrane four times.
- TMa is the transmembrane anchor
- TM2 to TM4 represents transmembrane regions 2 to 4
- 'C are conserved cysteines
- the consensus pattern spans a conserved region including two cysteines located in a short cytoplasmic loop between two transmembrane domains: Consensus pattern: G-x(3)-[LIVMF]-x(2)-[GSA]-[LIVMF](2)-G-C-x-[GA]- [STA]- x(2)-[EG]-x(2)-[CWN]-[LIVM](2).
- Trypsin trypsin
- SEQ ID NOS:3381, 4684, and 4688 correspond to novel serine proteases of the trypsin family.
- the catalytic activity of the serine proteases from the trypsin family is provided by a charge relay system involving an aspartic acid residue hydrogen-bonded to a histidine, which itself is hydrogen- bonded to a serine.
- the sequences in the vicinity of the active site serine and histidine residues are well conserved in this family of proteases (Brenner S., Nature (1988) 334:528).
- Proteases known to belong to the trypsin family include: 1) Acrosin; 2) Blood coagulation factors VII, IX, X, XI and XII, thrombin, plasminogen, and protein C; 3) Cathepsin G; 4) Chymotrypsins; 5) Complement components Clr, Cls, C2, and complement factors B, D and I; 6) Complement-activating component of RA-reactive factor; 7) Cytotoxic cell proteases (granzymes A to H); 8) Duodenase I; 9) Elastases 1, 2, 3A, 3B (protease E), leukocyte (medullasin).; 10) Enterokinase (EC 3.4.21.9) (enteropeptidase); 11) Hepatocyte growth factor activator; 12) Hepsin; 13) Glandular (tissue) kallikreins (including EGF-binding protein types A, B, and C, NGF-gamma chain, gamma
- Beta-transducin is one of the three subunits (alpha, beta, and gamma) of the guanine nucleoti de-binding proteins (G proteins) which act as intermediaries in the transduction of signals generated by transmembrane receptors
- G-beta exists as a small multigene family of highly conserved proteins of about 340 amino acid residues. Structurally, G-beta consists of eight tandem repeats of about 40 residues, each containing a central T ⁇ -Asp motif (this type of repeat is sometimes called a WD-40 repeat).
- Such a repetitive segment has been shown to exist in a number of other proteins including: human LIS1, a neuronal protein involved in type-1 lissencephaly; and mammalian coatomer beta' subunit (beta'-COP), a component of a cytosolic protein complex that reversibly associates with Golgi membranes to form vesicles that mediate biosynthetic protein transport.
- human LIS1 a neuronal protein involved in type-1 lissencephaly
- beta'-COP mammalian coatomer beta' subunit
- the consensus pattern for the WD domain/G-Beta repeat family is: [LIVMSTAC]- [LIVMFYWSTAGC]-[LIMSTAG]-[LIVMSTAGC]-x(2)-[DN]-x(2)-[LIVMWSTAC]-x- [LIVMFSTAG]-W-[DEN]-[LIVMFSTAGCN].
- gg wnt Family of Developmental Signaling Proteins (Wnt dev sign).
- wnt-2 also known as i ⁇
- wnt-3 also known as i ⁇
- wnt-3 also known as i ⁇
- wnt-3 also known as i ⁇
- wnt-3 also known as i ⁇
- wnt-3 also known as i ⁇
- wnt-3 also known as i ⁇
- wnt-3 also known as i ⁇
- wnt-3 is implicated in segmentation polarity.
- wg wingless
- All these proteins share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines that are probably involved in disulfide bonds.
- the Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters.
- the consensus pattern which is based upon a highly conserved region including three cysteines, is as follows: C-K-C-H-G-[LIVMT]-S-G-x-C. All sequences known to belong to this family are detected by the provided consensus pattern.
- hh Protein Tyrosine Phosphatase (Y phosphatase).
- Y phosphatase Protein Tyrosine Phosphatase
- PTPase catalyze the removal of a phosphate group attached to a tyrosine residue. These enzymes are very important in the control of cell growth, proliferation, differentiation and transformation. Multiple forms of PTPase have been characterized and can be classified into two categories: soluble PTPases and transmembrane receptor proteins that contain PTPase domain(s).
- Soluble PTPases include PTPN3 (HI) and PTPN4 (MEG), enzymes that contain an N-terminal band 4.1 -like domain and could act at junctions between the membrane and cytoskeleton; PTPN6 (PTP-1C; HCP; SHP) and PTPN11 (PTP-2C; SH-PTP3; Syp), enzymes that contain two copies of the SH2 domain at its N-terminal extremity.
- Dual specificity PTPases include DUSP 1 (PTPN 10; MAP kinase phosphatase- 1 ;
- MKP-1 which dephosphorylates MAP kinase on both Thr- 183 and Tyr-185
- DUSP2 a nuclear enzyme that dephosphorylates MAP kinases ERK1 and ERK2 on both Thr and Tyr residues.
- receptor PTPases are made up of a variable length extracellular domain, followed by a transmembrane region and a C-terminal catalytic cytoplasmic domain.
- Some of the receptor PTPases contain fibronectin type III (FN-III) repeats, immunoglobulin-like domains, MAM domains or carbonic anhydrase-like domains in their extracellular region.
- the cytoplasmic region generally contains two copies of the PTPAse domain. The first seems to have enzymatic activity, while the second is inactive but seems to affect substrate specificity of the first. In these domains, the catalytic cysteine is generally conserved but some other, presumably important, residues are not.
- PTPase domains consist of about 300 amino acids. There are two conserved cysteines and the second one has been shown to be absolutely required for activity. Furthermore, a number of conserved residues in its immediate vicinity have also been shown to be important.
- the consensus pattern for PTPases is: [LIVMF]-H-C-x(2)-G-x(3)- [STC]-[STAGP]-x-[LIVMFY]; C is the active site residue.
- Zinc Finger C2H2 Type (Zincfing C2H2).
- Zinc finger domains are nucleic acid-binding protein stmctures first identified in the Xenopus transcription factor TFIIIA. These domains have since been found in numerous nucleic acid-binding proteins.
- a zinc finger domain is composed of 25 to 30 amino acid residues. Two cysteine or histidine residues are positioned at both extremities of the domain, which are involved in the tetrahedral coordination of a zinc atom. It has been proposed that such a domain interacts with about five nucleotides.
- C2H2 the first pair of zinc coordinating residues are cysteines, while the second pair are histidines.
- Mammalian proteins having a C2H2 zipper include (number in parenthesis indicates number of zinc finger regions in the protein): basonuclin (6), BCL-6/LAZ-3 (6), erythroid krueppel-like transcription factor (3), transcription factors Spl (3), Sp2 (3), Sp3 (3) and Sp(4) 3, transcriptional repressor YYl (4), Wilms' tumor protein (4), EGRl/Krox24 (3), EGR2/Krox20 (3), EGR3/Pilot (3), EGR4/AT133 (4), Evi-1 (10), GLIl (5), GLI2 (4+), GLI3 (3+), HIV-EP1/ZNF40 (4), HIV-EP2 (2), KR1 (9+), KR2 (9), KR3 (15+), KR4 (14+), KR5 (11+), HF.12 (6+), REX-1 (4), ZfX (13), Zf (13), Zfp-35 (18), ZNF7 (15), ZNF8 (7), ZNF35
- C2H2 zinc fingers In addition to the conserved zinc ligand residues, it has been shown that a number of other positions are also important for the stmctural integrity of the C2H2 zinc fingers. (Rosenfeld et al, J. Biomol Struct. Dyn. (1993) 77:557) The best conserved position is found four residues after the second cysteine; it is generally an aromatic or aliphatic residue.
- the consensus pattern for C2H2 zinc fingers is: C-x(2,4)-C-x(3)-[LIVMFYWC]- x(8)-H-x(3,5)-H. The two C's and two H's are zinc ligands. ii) Zinc finger.
- C3HC4 type fRTNG finger signature (Zincfing C3H4).
- SEQ ID NOS:3774 and 4477 and thus the sequences they validate, represent polynucleotides encoding a polypeptide having a C3HC4 type zinc finger signature.
- a number of eukaryotic and viral proteins contain this signature, which is primarily a conserved cysteine-rich domain of 40 to 60 residues (Borden K.L.B., et al., Curr. Opin. Struct. Biol. (1996) 6:395) that binds two atoms of zinc, and is probably involved in mediating protein- protein interactions.
- the 3D stmcture of the zinc ligation system is uniqueto the RING domain and is refered to as the "cross-brace" motif.
- the spacing of the cysteines in such a domain is C-x(2)-C-x(9 to 39)-C-x(l to 3)-H-x(2 to 3)-C-x(2)-C-x(4 to 48)-C-x(2)-C.
- Proteins that include the C3HC4 domain include:
- RAG1 Mammalian V(D)J recombination activating protein
- Rpt-1 is a trans-acting factor that regulates gene expression directed by the promoter region of the interleukin-2 receptor alpha chainor the LTR promoter region of HIV- 1.
- Rfp is a developmentally regulated protein that may function in male germ cell development. Recombination of the N-terminal section of rfp with a protein tyrosine kinase produces the ret transforming protein.
- BRCA1 Mammalian breast cancer type 1 susceptibility protein (BRCA1) ([El] http://bioinformatics.weizmann.ac.il/hotmolecbase/entries/brcal.htm). 8) Mammalian cbl proto-oncogene.
- MATl Vertebrate CDK-activating kinase assembly factor MATl, a protein that stabilizes the complex between the CDK7 kinase and cyclin H (MATl stands for 'Menage A Trois').
- CAK Vertebrate CDK-activating kinase assembly factor
- PAF-1 Mammalian peroxisome assembly factor- 1 (PAF-1) (PMP35), which is somewhat involved in the biogenesis of peroxisomes.
- PAF-1 Mammalian peroxisome assembly factor- 1
- PMP35 Mammalian peroxisome assembly factor- 1
- T-LR Trypanosoma protein ESAG-8 (T-LR), which may be involved in the postranscriptional regulation of genes in VSG expression sites or may interact with adenylate cyclase to regulate its activity.
- the two proteins belong to the Polycomb group of genes needed to maintain the segment-specific repression of homeotic selector genes.
- Drosophila protein male-specific msl-2 a DNA-binding protein which is involved in X chromosome dosage compensation (the elevation of transcription of the male single X chromosome).
- He ⁇ esvimses trans-acting transcriptional protein ICP0/IE110 This protein which has been characterized in many different he ⁇ esvimses is a trans-activator and/or - repressor of the expression of many viral and cellular promoters.
- the relative expression levels of the polynucleotides of the invention was assessed in several libraries prepared from various sources, including cell lines and patient tissue samples.
- Table 4 provides a summary of these libraries, including the shortened library name (used hereafter), the mRNA source used to prepared the cDNA library, the "nickname" of the library that is used in the tables below (in quotes), and the approximate number of clones in the library.
- the KM12L4 and KM12C cell lines are described in Example 1 above.
- the MDA- MB-231 cell line was originally isolated from pleural effusions (Cailleau, J. Natl. Cancer. Inst. (1974) 53:661), is of high metastatic potential, and forms poorly differentiated adenocarcinoma grade II in nude mice consistent with breast carcinoma.
- the MCF7 cell line was derived from a pleural effusion of a breast adenocarcinoma and is non-metastatic.
- the MV-522 cell line is derived from a human lung carcinoma and is of high metastatic potential.
- the UCP-3 cell line is a low metastatic human lung carcinoma cell line; the MV-522 is a high metastatic variant of UCP-3.
- the samples of libraries 15-20 are derived from two different patients (UC#2, and UC#3).
- the bFGF-treated HMEC were prepared by incubation with bFGF at 1 Ong/ml for 2 hrs; the VEGF -treated HMEC were prepared by incubation with 20ng/ml BEGF for 2 hrs. Following incubation with the respective growth factor, the cells were washed and lysis buffer added for RNA preparation.
- Each of the libraries is composed of a collection of cDNA clones that in turn are representative of the mRNAs expressed in the indicated mRNA source.
- the sequences were assigned to clusters.
- the concept of "cluster of clones" is derived from a sorting/grouping of cDNA clones based on their hybridization pattern to a panel of roughly 300 7bp oligonucleotide probes (see Drmanac et al, Genomics (1996) 37(1):29). Random cDNA clones from a tissue library are hybridized at moderate stringency to 300 7bp oligonucleotides.
- Each oligonucleotide has some measure of specific hybridization to that specific clone.
- the combination of 300 of these measures of hybridization for 300 probes equals the "hybridization signature" for a specific clone.
- Clones with similar sequence will have similar hybridization signatures.
- groups of clones in a library can be identified and brought together computationally. These groups of clones are termed "clusters".
- the "purity" of each cluster can be controlled.
- artifacts of clustering may occur in computational clustering just as artifacts can occur in "wet-lab” screening of a cDNA library with 400 bp cDNA fragments, at even the highest stringency.
- the stringency used in the implementation of cluster herein provides groups of clones that are in general from the same cDNA or closely related cDNAs. Closely related clones can be a result of different length clones of the same cDNA, closely related clones from highly related gene families, or splice variants of the same cDNA.
- Differential expression for a selected cluster was assessed by first determining the number of cDNA clones corresponding to the selected cluster in the first library (Clones in 1 st ), and the determining the number of cDNA clones corresponding to the selected cluster in the second library (Clones in 2 nd ). Differential expression of the selected cluster in the first library relative to the second library is expressed as a "ratio" of percent expression between the two libraries.
- the "ratio" is calculated by: 1) calculating the percent expression of the selected cluster in the first library by dividing the number of clones corresponding to a selected cluster in the first library by the total number of clones analyzed from the first library; 2) calculating the percent expression of the selected cluster in the second library by dividing the number of clones corresponding to a selected cluster in a second library by the total number of clones analyzed from the second library; 3) dividing the calculated percent expression from the first library by the calculated percent expression from the second library. If the "number of clones" corresponding to a selected cluster in a library is zero, the value is set at 1 to aid in calculation.
- the formula used in calculating the ratio takes into account the "depth" of each of the libraries being compared, i.e., the total number of clones analyzed in each library.
- a polynucleotide is said to be significantly differentially expressed between two samples when the ratio value is greater than at least about 2, preferably greater than at least about 3, more preferably greater than at least about 5 , where the ratio value is calculated using the method described above.
- the significance of differential expression is determined using a z score test (Zar, Biostatistical Analysis, Prentice Hall, Inc., USA, "Differences between Proportions," pp 296-298 (1974).
- Example 5 Polynucleotides Differentially Expressed in High Metastatic Potential Breast Cancer Cells Versus Low Metastatic Breast Cancer Cells
- a number of polynucleotide sequences have been identified that are differentially expressed between cells derived from high metastatic potential breast cancer tissue and low metastatic breast cancer cells. Expression of these sequences in breast cancer can be valuable in determining diagnostic, prognostic and/or treatment information. For example, sequences that are highly expressed in the high metastatic potential cells can be indicative of increased expression of genes or regulatory sequences involved in the metastatic process. A patient sample displaying an increased level of one or more of these polynucleotides may thus warrant more aggressive treatment.
- sequences that display higher expression in the low metastatic potential cells can be associated with genes or regulatory sequences that inhibit metastasis, and thus the expression of these polynucleotides in a sample may warrant a more positive prognosis than the gross pathology would suggest.
- differential expression of these polynucleotides can be used as a diagnostic marker, a prognostic marker, for risk assessment, patient treatment and the like.
- These polynucleotide sequences can also be used in combination with other known molecular and/or biochemical markers.
- a number of polynucleotide sequences have been identified that are differentially expressed between cells derived from high metastatic potential lung cancer tissue and low metastatic lung cancer cells. Expression of these sequences in lung cancer tissue can be valuable in determining diagnostic, prognostic and/or treatment information. For example, sequences that are highly expressed in the high metastatic potential cells are associated can be indicative of increased expression of genes or regulatory sequences involved in the metastatic process. A patient sample displaying an increased level of one or more of these polynucleotides may thus warrant more aggressive treatment.
- sequences that display higher expression in the low metastatic potential cells can be associated with genes or regulatory sequences that inhibit metastasis, and thus the expression of these polynucleotides in a sample may warrant a more positive prognosis than the gross pathology would suggest.
- differential expression of these polynucleotides can be used as a diagnostic marker, a prognostic marker, for risk assessment, patient treatment and the like.
- These polynucleotide sequences can also be used in combination with other known molecular and/or biochemical markers.
- Example 7 Polynucleotides Differentially Expressed in High Metastatic Potential Colon Cancer Cells Versus Low Metastatic Colon Cancer Cells
- a number of polynucleotide sequences have been identified that are differentially expressed between cells derived from high metastatic potential colon cancer tissue and low metastatic colon cancer cells. Expression of these sequences in colon cancer tissue can be valuable in determining diagnostic, prognostic and/or treatment information. For example, sequences that are highly expressed in the high metastatic potential cells can be indicative of increased expression of genes or regulatory sequences involved in the metastatic process. A patient sample displaying an increased level of one or more of these polynucleotides may thus warrant more aggressive treatment.
- sequences that display higher expression in the low metastatic potential cells can be associated with genes or regulatory sequences that inhibit metastasis, and thus the expression of these polynucleotides in a sample may warrant a more positive prognosis than the gross pathology would suggest.
- the differential expression of these polynucleotides can be used as a diagnostic marker, a prognostic marker, for risk assessment, patient treatment and the like.
- These polynucleotide sequences can also be used in combination with other known molecular and/or biochemical markers.
- a number of polynucleotide sequences have been identified that are differentially expressed between cells derived from high metastatic potential colon cancer tissue and normal tissue. Expression of these sequences in colon cancer tissue can be valuable in determining diagnostic, prognostic and/or treatment information. For example, sequences that are highly expressed in the high metastatic potential cells are associated can be indicative of increased expression of genes or regulatory sequences involved in the advanced disease state which involves processes such as angiogenesis, dedifferentiation, cell replication, and metastasis. A patient sample displaying an increased level of one or more of these polynucleotides may thus warrant more aggressive treatment.
- differential expression of these polynucleotides can be used as a diagnostic marker, a prognostic marker, for risk assessment, patient treatment and the like.
- These polynucleotide sequences can also be used in combination with other known molecular and/or biochemical markers.
- Table 11 Differentially expressed polynucleotides isolated from samples from two patients (UC#2 and UC#3) : Higher expression in high metastatic potential colon tissue (UC#2:libl7; UC#3:lib20) vs. normal colon tissue (UC#2:libl5; UC#3:libl8)
- Table 12 Differentially expressed polynucleotides isolated from samples from two patients (UC#2 and UC#3) : Higher expression in normal colon tissue (UC#2:libl5; UC#3:libl8)vs. high metastatic potential colon tissue (UC#2:libl7; UC#3:lib20).
- Example 9 Polynucleotides Differentially Expressed in High Colon Tumor Potential Patient Tissue Versus Metastasized Colon Cancer Patient Tissue
- a number of polynucleotide sequences have been identified that are differentially expressed between cells derived from high tumor potential colon cancer tissue and cells derived from high metastatic potential colon cancer cells. Expression of these sequences in colon cancer tissue can be valuable in determining diagnostic, prognostic and/or treatment information associated with the transformation of precancerous tissue to malignant tissue. This information can be useful in the prevention of achieving the advanced malignant state in these tissues, and can be important in risk assessment for a patient.
- a number of polynucleotide sequences have been identified that are differentially expressed between cells derived from high tumor potential colon cancer tissue and normal tissue. Expression of these sequences in colon cancer tissue can be valuable in determining diagnostic, prognostic and/or treatment information associated with the prevention of achieving the malignant state in these tissues, and can be important in risk assessment for a patient. For example, sequences that are highly expressed in the potential colon cancer cells are associated with or can be indicative of increased expression of genes or regulatory sequences involved in early tumor progression. A patient sample displaying an increased level of one or more of these polynucleotides may thus warrant closer attention or more frequent screening procedures to catch the malignant state as early as possible.
- Table 14 Differentially expressed polynucleotides detected in samples from two patients (UC#2 and UC#3): Higher expression in tumor potential colon tissue (UC#2:libl6; UC#3:libl9)vs. normal colon tissue (UC#2:libl5; UC#3:libl8)
- Example 11 Polynucleotides Differentially Expressed in Growth Factor-Stimulated Human Microvascular Endothelial Cells (HMEC) Relative to Untreated HMEC
- HMEC human microvascular endothelial cells
- Sequences that are differentially expressed between growth factor-treated HMEC and untreated HMEC can represent sequences encoding gene products involved in angiogenesis, metastasis (cell migration), and other development and oncogenic processes.
- sequences that are more highly expressed in HMEC treated with growth factors (such as bFGF or VEGF) relative to untreated HMEC can serve as markers of cancer cells of higher metastatic potential. Detection of expression of these sequences in colon cancer tissue can be valuable in determining diagnostic, prognostic and/or treatment information associated with the prevention of achieving the malignant state in these tissues, and can be important in risk assessment for a patient. A patient sample displaying an increased level of one or more of these polynucleotides may thus warrant closer attention or more frequent screening procedures to catch the malignant state as early as possible.
- growth factors such as bFGF or VEGF
- Example 12 Polynucleotides Differentially Expressed Across Multiple Libraries
- polynucleotide sequences have been identified that are differentially expressed between cancerous cells and normal cells across all three tissue types tested (i.e., breast, colon, and lung). Expression of these sequences in a tissue or any origin can be valuable in determining diagnostic, prognostic and/or treatment information associated with the prevention of achieving the malignant state in these tissues, and can be important in risk assessment for a patient. These polynucleotides can also serve as non-tissue specific markers of, for example, risk of metastasis of a tumor. The following table summarizes identified polynucleotides that were differentially expressed but without tissue type- specificity in the breast, colon, and lung libraries tested.
- HMEC human microvascular endothelial cell
- bFGF bFGF treated
- VEGF VEGF treated
- Example 12 Polynucleotides Exhibiting Colon-Specific Expression
- the cDNA libraries described herein were also analyzed to identify those polynucleotides that were specifically expressed in colon cells or tissue, i.e., the polynucleotides were identified in libraries prepared from colon cell lines or tissue, but not in libraries of breast or lung origin.
- the polynucleotides that were expressed in a colon cell line and/or in colon tissue, but were present in the breast or lung cDNA libraries described herein, are shown in Table 19 (inserted before claims).
- Example 13 Identification of Contiguous Sequences Having a Polynucleotide of the Invention
- the novel polynucleotides were used to screen publicly available and proprietary databases to determine if any of the polynucleotides of SEQ ID NOS: 1-2502 would facilitate identification of a contiguous sequence, e.g., the polynucleotides would provide sequence that would result in 5' extension of another DNA sequence, resulting in production of a longer contiguous sequence composed of the provided polynucleotide and the other DNA sequence(s). Contiging was performed using the Gelmerge application (default settings) of GCG from the Univ. of Wisconsin.
- contiged sequences were generated. These contiged sequences are provided as SEQ ID NOS:5107-5252 (see Table 1). The contiged sequences can be correlated with the sequences of SEQ ID NOS: 1-2502 upon which the contiged sequences are based by, for example, identifying those sequences of SEQ ID NOS: 1 -2502 and the contiged sequences of SEQ ID NOS: 5107-5252 that share the same clone name in Table 1.
- the contiged sequences (SEQ ID NO:5107-5252) thus represent longer sequences that encompass a polynucleotide sequence of the invention.
- the contiged sequences were then translated in all three reading frames to determine the best alignment with individual sequences using the BLAST programs as described above for SEQ ID NOS: 1-2502 and the validation sequences "SEQ ID NOS:2503-5106.” Again the sequences were masked using the XBLAST program for masking low complexity as described above in Example 1 (Table 2).
- Several of the contiged sequences were found to encode polypeptides having characteristics of a polypeptide belonging to a known protein families (and thus represent new members of these protein families) and/or comprising a known functional domain (Table 20).
- the invention encompasses fragments, fusions, and variants of such polynucleotides that retain biological activity associated with the protein family and/or functional domain identified herein.
- CMCC Chiron Master Culture Collection
- the ATCC deposit is composed of a pool of cDNA clones
- the deposit was prepared by first transfecting each of the clones into separate bacterial cells. The clones were then deposited as a pool of equal mixtures in the composite deposit. Particular clones can be obtained from the composite deposit using methods well known in the art.
- a bacterial cell containing a particular clone can be identified by isolating single colonies, and identifying colonies containing the specific clone through standard colony hybridization techniques, using an oligonucleotide probe or probes designed to specifically hybridize to a sequence of the clone insert (e.g., a probe based upon unmasked sequence of the encoded polynucleotide having the indicated SEQ ID NO).
- the probe should be designed to have a T m of approximately 80°C (assuming 2°C for each A or T and 4°C for each G or C). Positive colonies can then be picked, grown in culture, and the recombinant clone isolated.
- probes designed in this manner can be used to PCR to isolate a nucleic acid molecule from the pooled clones according to methods well known in the art, e.g., by purifying the cDNA from the deposited culture pool, and using the probes in PCR reactions to produce an amplified product having the corresponding desired polynucleotide sequence.
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Abstract
This invention relates to novel human polynucleotides and variants thereof, their encoded polypeptides and variants thereof, to genes corresponding to these polynucleotides and to proteins expressed by the genes. The invention also relates to diagnostic and therapeutic agents employing such novel human polynucleotides, their corresponding genes or gene products, e.g., these genes and proteins, including probes, antisense constructs, and antibodies.
Description
HUMAN GENES AND GENE EXPRESSION PRODUCTS II
Field of the Invention
The present invention relates to novel polynucleotides, particularly to novel polynucleotides of human origin that are expressed in a selected cell type, are differentially expressed in one cell type relative to another cell type (e.g., in cancerous cells, or in cells of a specific tissue origin) and/or share homology to polynucleotides encoding a gene product having an identified functional domain and/or activity.
Background of the Invention
Identification of novel polynucleotides, particularly those that encode an expressed gene product, is important in the advancement of drug discovery, diagnostic technologies, and the understanding of the progression and nature of complex diseases such as cancer.
Identification of genes expressed in different cell types isolated from sources that differ in disease state or stage, developmental stage, exposure to various environmental factors, the tissue of origin, the species from which the tissue was isolated, and the like is key to identifying the genetic factors that are responsible for the phenotypes associated with these various differences
This invention provides novel human polynucleotides, the polypeptides encoded by these polynucleotides, and the genes and proteins corresponding to these novel polynucleotides.
Summary of the Invention
This invention relates to novel human polynucleotides and variants thereof, their encoded polypeptides and variants thereof, to genes corresponding to these polynucleotides and to proteins expressed by the genes. The invention also relates to diagnostic and therapeutic agents employing such novel human polynucleotides, their corresponding genes or gene products, e.g., these genes and proteins, including probes, antisense constructs, and antibodies. The polynucleotides of the invention correspond to a polynucleotide comprising the sequence information of at least one of SEQ ID NOS: 1-3544, 3546-4510, 4512-4725, 4727-4748, and 4750-5252, which for convenience sake is referred to herein as "SEQ ID NOS: 1-5252."
Accordingly, in one embodiment, the present invention features a library of polynucleotides, the library comprising the sequence information of at least one of "SEQ ID NOS: 1-5252". In related aspects, the invention features a library provided on a nucleic acid array, or in a computer-readable format. In one embodiment, the library is comprises a differentially expressed polynucleotide comprising a sequence selected from one of the differentially expressed polynucleotides disclosed herein. In specific related embodiments, the library comprises: 1) a polynucleotide that is differentially expressed in a human breast cancer cell, where the polynucleotide comprises a sequence selected from the group consisting of SEQ ID NOS:15, 36, 44, 45, 89, 146, 154, 159, 165, 172, 174, 183, 203, 261, 364, 366, 387, 419, 420, 496, 503, 510, 512, 529, 552, 560, 564, 570, 590, 606, 644, 646, 693, 707, 711, 726, 746, 754, 756, 875, 902, 921, 942, 990, 1095, 1104, 1122, 1131, 1142, 1170, 1184, 1205, 1286, 1289, 1354, 1387, 1435, 1535, 1751, 1764, 1777, 1795, 1860, 1869, 1882, 1890, 1915, 1933, 1934, 1979, 1980, 2007, 2023, 2040, 2059, 2223, 2245, 2300, 2325, 2409, 2462, 2488, 2486, and 2492; 2) a polynucleotide differentially expressed in a human colon cancer cell, where the polynucleotide comprises a sequence selected from the group consisting of SEQ ID NOS: , 33, 65, 228, 250, 252, 253, 280, 282, 355, 370, 387, 443, 460, 491, 545, 560, 581, 603, 680, 693, 703, 704, 716, 726, 746, 752, 753, 1095, 1104, 1205, 1241, 1264, 1354, 1387, 1401, 1442, 1514, 1734, 1742, 1780, 1851, 1899, 1915, 1954, 2024, 2066, 2262, and 2325; 3) a polynucleotide differentially expressed in a human lung cancer cell, where the polynucleotide comprises a sequence selected from the group consisting of SEQ ID NOS: 10, 54, 65, 171, 174, , 203, 252, 253, 254, , 285, 419, 420, 466, 491, 525, 526, 552, 571, 574, 590, 693, 700, 726, 742, 746, 861, 922, 990, 1088, 1288, 1355, 1417, 1422, 1444, 1454, 1570, 1597, 1979, 2007, 2024, 2034, 2038, 2126, and 2245; 4) a polynucleotide differentially expressed in growth factor-treated human microvascular endothelial cells (HMEC) relative to untreated HMEC, where the polynucleotide comprises a sequence selected from the group consisting of SEQ ID NOS:648, 1899, and 648; or 5) polynucleotides that are differentially expressed across multiple libraries, where the polynucleotide comprises a sequence selected from the group consisting of SEQ ID NOS: 65, 174, 203, 252, 253, 387, 419, 420, 491, 552, 560, 581, 590, 648, 693, 726, 746, 990, 1095, 1124, 1205, 1354, 1387, 1780, 1899, 1915, 1979, 2007, 2024, 2245, and 2325,
In another aspect, the invention features an isolated polynucleotide comprising a nucleotide sequence having at least 90% sequence identity to an identifying sequence of "SEQ ID NOS: 1-5252" or a degenerate variant thereof. In related aspects, the invention features recombinant host cells and vectors comprising the polynucleotides of the invention, as well as isolated polypeptides encoded by the polynucleotides of the invention and antibodies that specifically bind such polypeptides.
In one embodiment, the invention features an isolated polynucleotide comprising a sequence encoding a polypeptide of a protein family or having a functional domain selected from the group consisting of: 4 transmembrane segments integral membrane proteins, 7 transmembrane receptors (rhodopsin family or secretin family), eukaryotic aspartyl proteases, ATPases associated with various cellular activities (AAA), Bcl-2, cyclins, DEAD box protein family, DEAD/H helicase protein family, MAP kinase kinase protein family, novel 3'5'-cyclic nucleotide phosphodiesterases, protein kinases, ras protein family, G-protein alpha subunit, phorbol esters/diacylglycerol binding proteins, protein kinase, trypsin, protein tyrosine phosphatase, wnt family of developmental signaling proteins,
WW/rsp5/WWP domain containing proteins, Ank repeat, basic region plus leucine zipper domain, bromodomain, eukaryotic thiol (cysteine) protease active site, EF-hand, ETS domain, type II fibronectin collagen binding domain, thioredoxin, homeobox domain, TNFR/NGFR family cysteine-rich region, WD domain/G-beta repeats, zinc finger (C2H2 type), zinc finger (CCHC class), and zinc finger (C3HC4 type). In a specific related embodiment, the invention features a polynucleotide comprising a sequence of one of the SEQ ID NOS: listed in Table 3 or Table 20.
In another aspect, the invention features a method of detecting differentially expressed genes correlated with a cancerous state of a mammalian cell, where the method comprises the step of detecting at least one differentially expressed gene product in a test sample derived from a cell suspected of being cancerous, where the gene product is encoded by a gene corresponding to a sequence of at least one of the differentially expressed polynucleotides disclosed herein. Detection of the differentially expressed gene product is correlated with a cancerous state of the cell from which the test sample was derived. In one embodiment, the detecting is by hybridization of the test sample to a
reference array, wherein the reference array comprises an identifying sequence of at least one of the differentially expressed polynucleotides disclosed herein.
In one embodiment of the method of the invention, the cell is a breast tissue derived cell, and the differentially expressed gene product is encoded by a gene corresponding to a sequence of at least one of SEQ ID NOS:15, 36, 44, 45, 89, 146, 154, 159, 165, 172, 174, 183, 203, 261, 364, 366, 387, 419, 420, 496, 503, 510, 512, 529, 552, 560, 564, 570, 590, 606, 644, 646, 693, 707, 711, 726, 746, 754, 756, 875, 902, 921, 942, 990, 1095, 1104, 1122, 1131, 1142, 1170, 1184, 1205, 1286, 1289, 1354, 1387, 1435, 1535, 1751, 1764, 1777, 1795, 1860, 1869, 1882, 1890, 1915, 1933, 1934, 1979, 1980, 2007, 2023, 2040, 2059, 2223, 2245, 2300, 2325, 2409, 2462, 2486 2488, and 2492.
In another embodiment of the method of the invention, the cell is a colon tissue derived cell, and differentially expressed gene product is encoded by a gene corresponding to a sequence ofat least one of SEQ ID NOS: 65, 228, 252, 253, 280, 355, 491, 581, 603, 680, 693, 716, 726, 746, 752, 753, 1241, 1264, 1401, 1442, 1514, 1851, 1915, 2024, 2066, 33, 250, 282, 370, 387, 443, 460, 545, 560, 703, 704, 1095, 1104, 1205, 1354, 1387, 1734, 1742, 1780, 1899, 1954, 2262, and 2325.
In yet another embodiment of the method of the invention, the cell is a lung tissue derived cell, and differentially expressed gene product is encoded by a gene corresponding to a sequence ofat least one of SEQ ID NOS:10, 54, 65, 171, 174, 203, 252, 253, 254, 285, 419, 420, 466, 491, 525, 526, 552, 571, 574, 590, 693, 700, 726, 742, 746, 861, 922, 990, 1088, 1288, 1355, 1417, 1422, 1444, 1454, 1570, 1597, 1979, 2007, 2024, 2034, 2038, 2126, and 2245.
In another embodiment, the cell is any of a lung, breast, or colon cell and the differentially expressed gene product is encoded by a gene corresponding to a sequence of at least one of SEQ ID NOS:648 and 1899.
In still another embodiment, the cell is any of a breast, colon, or lung cell and the differentially expressed gene product is encoded by a gene corresponding to a sequence of at least one of SEQ ID NOS: 65, 174, 203, 252, 253, 387, 419, 420, 491, 552, 560, 581, 590, 648, 693, 726, 746, 990, 1095, 1124, 1205, 1354, 1387, , 1780, 1899, 1915, 1979, 2007, 2024, 2245, and 2325.
Other aspects and embodiments of the invention will be readily apparent to the ordinarily skilled artisan upon reading the description provided herein.
Detailed Description of the Invention The invention relates to polynucleotides comprising the disclosed nucleotide sequences, to full length cDNA, mRNA and genes corresponding to these sequences, and to polypeptides and proteins encoded by these polynucleotides and genes.
Also included are polynucleotides that encode polypeptides and proteins encoded by the polynucleotides of the Sequence Listing. The various polynucleotides that can encode these polypeptides and proteins differ because of the degeneracy of the genetic code, in that most amino acids are encoded by more than one triplet codon. The identity of such codons is well-known in this art, and this information can be used for the construction of the polynucleotides within the scope of the invention.
Polynucleotides encoding polypeptides and proteins that are variants of the polypeptides and proteins encoded by the polynucleotides and related cDNA and genes are also within the scope of the invention. The variants differ from wild type protein in having one or more amino acid substitutions that either enhance, add, or diminish a biological activity of the wild type protein. Once the amino acid change is selected, a polynucleotide encoding that variant is constructed according to the invention. The following detailed description describes the polynucleotide compositions encompassed by the invention, methods for obtaining cDNA or genomic DNA encoding a full-length gene product, expression of these polynucleotides and genes, identification of structural motifs of the polynucleotides and genes, identification of the function of a gene product encoded by a gene corresponding to a polynucleotide of the invention, use of the provided polynucleotides as probes and in mapping and in tissue profiling, use of the corresponding polypeptides and other gene products to raise antibodies, and use of the polynucleotides and their encoded gene products for therapeutic and diagnostic purposes.
I. Polynucleotide Compositions The scope of the invention with respect to polynucleotide compositions includes, but is not necessarily limited to, polynucleotides having a sequence set forth in any one of
"SEQ ID NOS: 1-5252"; polynucleotides obtained from the biological materials described herein or other biological sources (particularly human sources) by hybridization under stringent conditions (particularly conditions of high stringency); genes corresponding to the provided polynucleotides; variants of the provided polynucleotides and their corresponding genes, particularly those variants that retain a biological activity of the encoded gene product (e.g., a biological activity ascribed to a gene product corresponding to the provided polynucleotides as a result of the assignment of the gene product to a protein family(ies) and/or identification of a functional domain present in the gene product). Other nucleic acid compositions contemplated by and within the scope of the present invention will be readily apparent to one of ordinary skill in the art when provided with the disclosure here. The invention features polynucleotides that are expressed in cells of human tissue, specifically human colon, breast, and/or lung tissue. Novel nucleic acid compositions of the invention of particular interest comprise a sequence set forth in any one of "SEQ ID NOS: 1-5252" or an identifying sequence thereof. An "identifying sequence" is a contiguous sequence of residues at least about 10 nt to about 20 nt in length, usually at least about 50 nt to about 100 nt in length, that uniquely identifies a polynucleotide sequence, e.g., exhibits less than 90%, usually less than about 80% to about 85% sequence identity to any contiguous nucleotide sequence of more than about 20 nt. Thus, the subject novel nucleic acid compositions include full length cDNAs or mRNAs that encompass an identifying sequence of contiguous nucleotides from any one of "SEQ ID NOS: 1-5252." The polynucleotides of the invention also include polynucleotides having sequence similarity or sequence identity. Nucleic acids having sequence similarity are detected by hybridization under low stringency conditions, for example, at 50°C and 10XSSC (0.9 M saline/0.09 M sodium citrate) and remain bound when subjected to washing at 55°C in IXSSC. Sequence identity can be determined by hybridization under stringent conditions, for example, at 50°C or higher and 0. IXSSC (9 mM saline/0.9 mM sodium citrate). Hybridization methods and conditions are well known in the art, see, e.g., U.S. Patent No. 5,707,829. Nucleic acids that are substantially identical to the provided polynucleotide sequences, e.g. allelic variants, genetically altered versions of the gene, etc., bind to the provided polynucleotide sequences ("SEQ ID NOS: 1-5252") under stringent hybridization conditions. By using probes, particularly labeled probes of DNA sequences, one can
isolate homologous or related genes. The source of homologous genes can be any species, e.g. primate species, particularly human; rodents, such as rats and mice; canines, felines, bovines, ovines, equines, yeast, nematodes, etc.
Preferably, hybridization is performed using at least 15 contiguous nucleotides ofat least one of "SEQ ID NOS:l-5252." That is, when at least 15 contiguous nucleotides of one of the disclosed SEQ ID NOs. is used as a probe, the probe will preferentially hybridize with a gene or mRNA (of the biological material) comprising the complementary sequence, allowing the identification and retrieval of the nucleic acids of the biological material that uniquely hybridize to the selected probe. Probes from more than one SEQ ID NO. will hybridize with the same gene or mRNA if the cDNA from which they were derived corresponds to one mRNA. Probes of more than 15 nucleotides can be used, but 15 nucleotides represents enough sequence for unique identification.
The polynucleotides of the invention also include naturally occurring variants of the nucleotide sequences (e.g., degenerate variants, allelic variants, etc.). Variants of the polynucleotides of the invention are identified by hybridization of putative variants with nucleotide sequences disclosed herein, preferably by hybridization under stringent conditions For example, by using appropriate wash conditions, variants of the polynucleotides of the invention can be identified where the allelic variant exhibits at most about 25-30%) base pair mismatches relative to the selected polynucleotide probe. In general, allelic variants contain 15-25% base pair mismatches, and can contain as little as even 5-15%, or 2-5%, or 1-2% base pair mismatches, as well as a single base-pair mismatch.
The invention also encompasses homologs corresponding to the polynucleotides of "SEQ ID NOS: 1-5252", where the source of homologous genes can be any mammalian species, e.g., primate species, particularly human; rodents, such as rats; canines, felines, bovines, ovines, equines, yeast, nematodes, etc. Between mammalian species, e.g., human and mouse, homologs have substantial sequence similarity, e.g., at least 75% sequence identity, usually at least 90%, more usually at least 95% between nucleotide sequences. Sequence similarity is calculated based on a reference sequence, which may be a subset of a larger sequence, such as a conserved motif, coding region, flanking region, etc. A reference sequence will usually be at least about 18 contiguous nt long, more usually at
least about 30 nt long, and may extend to the complete sequence that is being compared. Algorithms for sequence analysis are known in the art, such as BLAST, described in Altschul et al, J. Mol. Biol. (1990) 275:403-10.
In general, variants of the invention have a sequence identity greater than at least about 65%, preferably at least about 75%, more preferably at least about 85%, and can be greater than at least about 90% or more as determined by the Smith- Waterman homology search algorithm as implemented in MPSRCH program (Oxford Molecular). For the purposes of this invention, a preferred method of calculating percent identity is the Smith- Waterman algorithm, using the following. Global DNA sequence identity must be greater than 65% as determined by the Smith- Waterman homology search algorithm as implemented in MPSRCH program (Oxford Molecular) using an affine gap search with the following search parameters: gap open penalty, 12; and gap extension penalty, 1.
The subject nucleic acids can be cDNAs or genomic DNAs, as well as fragments thereof, particularly fragments that encode a biologically active gene product and/or are useful in the methods disclosed herein (e.g., in diagnosis, as a unique identifier of a differentially expressed gene of interest, etc.). The term "cDNA" as used herein is intended to include all nucleic acids that share the arrangement of sequence elements found in native mature mRNA species, where sequence elements are exons and 3' and 5' non-coding regions. Normally mRNA species have contiguous exons, with the intervening introns, when present, being removed by nuclear RNA splicing, to create a continuous open reading frame encoding a polypeptide of the invention.
A genomic sequence of interest comprises the nucleic acid present between the initiation codon and the stop codon, as defined in the listed sequences, including all of the introns that are normally present in a native chromosome. It can further include the 3' and 5' untranslated regions found in the mature mRNA. It can further include specific transcriptional and translational regulatory sequences, such as promoters, enhancers, etc., including about 1 kb, but possibly more, of flanking genomic DNA at either the 5' and 3' end of the transcribed region. The genomic DNA can be isolated as a fragment of 100 kbp or smaller; and substantially free of flanking chromosomal sequence. The genomic DNA flanking the coding region, either 3' and 5', or internal regulatory sequences as sometimes
found in introns, contains sequences required for proper tissue, stage-specific, or disease- state specific expression.
The nucleic acid compositions of the subject invention can encode all or a part of the subject polypeptides. Double or single stranded fragments can be obtained from the DNA sequence by chemically synthesizing oligonucleotides in accordance with conventional methods, by restriction enzyme digestion, by PCR amplification, etc. Isolated polynucleotides and polynucleotide fragments of the invention comprise at least about 10, about 15, about 20, about 35, about 50, about 100, about 150 to about 200, about 250 to about 300, or about 350 contiguous nucleotides selected from the polynucleotide sequences as shown in "SEQ ID NOS: 1-5252." For the most part, fragments will be ofat least 15 nt, usually at least 18 nt or 25 nt, and up to at least about 50 contiguous nt in length or more. In a preferred embodiment, the polynucleotide molecules comprise a contiguous sequence of at least twelve nucleotides selected from the group consisting of the polynucleotides shown in "SEQ ID NOS: 1-5252." Probes specific to the polynucleotides of the invention can be generated using the polynucleotide sequences disclosed in "SEQ ID NOS: 1-5252." The probes are preferably at least about 12, 15, 16, 18, 20, 22, 24, or 25 nucleotide fragment of a corresponding contiguous sequence of "SEQ ID NOS:l-5252", and can be less than 2, 1, 0.5, 0.1, or 0.05 kb in length. The probes can be synthesized chemically or can be generated from longer polynucleotides using restriction enzymes. The probes can be labeled, for example, with a radioactive, biotinylated, or fluorescent tag. Preferably, probes are designed based upon an identifying sequence of a polynucleotide of one of "SEQ ID NOS: 1-5252." More preferably, probes are designed based on a contiguous sequence of one of the subject polynucleotides that remain unmasked following application of a masking program for masking low complexity (e.g., XBLAST) to the sequence., i.e., one would select an unmasked region, as indicated by the polynucleotides outside the poly-n stretches of the masked sequence produced by the masking program.
The polynucleotides of the subject invention are isolated and obtained in substantial purity, generally as other than an intact chromosome. Usually, the polynucleotides, either as DNA or RNA, will be obtained substantially free of other naturally-occurring nucleic acid sequences, generally being at least about 50%, usually at least about 90% pure and are
typically "recombinant", e.g., flanked by one or more nucleotides with which it is not normally associated on a naturally occurring chromosome.
The polynucleotides of the invention can be provided as a linear molecule or within a circular molecule. They can be provided within autonomously replicating molecules (vectors) or within molecules without replication sequences. They can be regulated by their own or by other regulatory sequences, as is known in the art. The polynucleotides of the invention can be introduced into suitable host cells using a variety of techniques which are available in the art, such as transferrin polycation-mediated DNA transfer, transfection with naked or encapsulated nucleic acids, liposome-mediated DNA transfer, intracellular transportation of DNA-coated latex beads, protoplast fusion, viral infection, electroporation, gene gun, calcium phosphate-mediated transfection, and the like.
The subject nucleic acid compositions can be used to, for example, produce polypeptides, as probes for the detection of mRNA of the invention in biological samples (e.g., extracts of human cells) to generate additional copies of the polynucleotides, to generate ribozymes or antisense oligonucleotides, and as single stranded DNA probes or as triple-strand forming oligonucleotides. The probes described herein can be used to, for example, determine the presence or absence of the polynucleotide sequences as shown in "SEQ ID NOS: 1-5252" or variants thereof in a sample. These and other uses are described in more detail below.
Use of Polynucleotides to Obtain Full-Length cDNA and Full-Length Human Gene and Promoter Region
Full-length cDNA molecules comprising the disclosed polynucleotides are obtained as follows. A polynucleotide having a sequence of one of "SEQ ID NOS: 1-5252", or a portion thereof comprising at least 12, 15, 18, or 20 nucleotides, is used as a hybridization probe to detect hybridizing members of a cDNA library using probe design methods, cloning methods, and clone selection techniques such as those described in U.S. Patent No. 5,654,173. Libraries of cDNA are made from selected tissues, such as normal or tumor tissue, or from tissues of a mammal treated with, for example, a pharmaceutical agent. Preferably, the tissue is the same as the tissue from which the polynucleotides of the invention were isolated, as both the polynucleotides described herein and the cDNA
represent expressed genes. Most preferably, the cDNA library is made from the biological material described herein in the Examples. Alternatively, many cDNA libraries are available commercially. (Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., (1989) Cold Spring Harbor Press, Cold Spring Harbor, NY). The choice of cell type for library construction can be made after the identity of the protein encoded by the gene corresponding to the polynucleotide of the invention is known. This will indicate which tissue and cell types are likely to express the related gene, and thus represent a suitable source for the mRNA for generating the cDNA. Where the provided polynucleotides are isolated from cDNA libraries, the libraries are prepared from mRNA of human colon cells, more preferably, human colon cancer cells, even more preferably, from a highly metastatic colon cell, Kml2L4-A.
Techniques for producing and probing nucleic acid sequence libraries are described, for example, in Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., (1989) Cold Spring Harbor Press, Cold Spring Harbor, NY. The cDNA can be prepared by using primers based on sequence from "SEQ ID NOS: 1-5252." In one embodiment, the cDNA library can be made from only poly-adenylated mRNA. Thus, poly-T primers can be used to prepare cDNA from the mRNA.
Members of the library that are larger than the provided polynucleotides, and preferably that encompass the complete coding sequence of the native message, are obtained. In order to confirm that the entire cDNA has been obtained, RNA protection experiments are performed as follows. Hybridization of a full-length cDNA to an mRNA will protect the RNA from RNase degradation. If the cDNA is not full length, then the portions of the mRNA that are not hybridized will be subject to RNase degradation. This is assayed, as is known in the art, by changes in electrophoretic mobility on polyacrylamide gels, or by detection of released monoribonucleotides. Sambrook et al., Molecular
Cloning: A Laboratory Manual, 2nd Ed., (1989) Cold Spring Harbor Press, Cold Spring Harbor, NY. In order to obtain additional sequences 5' to the end of a partial cDNA, 5' RACE (PCR Protocols: A Guide to Methods and Applications, (1990) Academic Press, Inc.) is performed. Genomic DNA is isolated using the provided polynucleotides in a manner similar to the isolation of full-length cDNAs. Briefly, the provided polynucleotides, or portions
thereof, are used as probes to libraries of genomic DNA. Preferably, the library is obtained from the cell type that was used to generate the polynucleotides of the invention, but this is not essential. Most preferably, the genomic DNA is obtained from the biological material described herein in the Examples. Such libraries can be in vectors suitable for carrying large segments of a genome, such as PI or YAC, as described in detail in Sambrook et al, 9.4-9.30. In addition, genomic sequences can be isolated from human BAC libraries, which are commercially available from Research Genetics, Inc., Huntville, Alabama, USA, for example. In order to obtain additional 5 ' or 3' sequences, chromosome walking is performed, as described in Sambrook et al., such that adjacent and overlapping fragments of genomic DNA are isolated. These are mapped and pieced together, as is known in the art, using restriction digestion enzymes and DNA ligase.
Using the polynucleotide sequences of the invention, corresponding full-length genes can be isolated using both classical and PCR methods to construct and probe cDNA libraries. Using either method, Northern blots, preferably, are performed on a number of cell types to determine which cell lines express the gene of interest at the highest level. Classical methods of constructing cDNA libraries are taught in Sambrook et al, supra. With these methods, cDNA can be produced from mRNA and inserted into viral or expression vectors. Typically, libraries of mRNA comprising poly(A) tails can be produced with poly(T) primers. Similarly, cDNA libraries can be produced using the instant sequences as primers.
PCR methods are used to amplify the members of a cDNA library that comprise the desired insert. In this case, the desired insert will contain sequence from the full length cDNA that corresponds to the instant polynucleotides. Such PCR methods include gene trapping and RACE methods. Gene trapping entails inserting a member of a cDNA library into a vector. The vector then is denatured to produce single stranded molecules. Next, a substrate-bound probe, such a biotinylated oligo, is used to trap cDNA inserts of interest. Biotinylated probes can be linked to an avidin-bound solid substrate. PCR methods can be used to amplify the trapped cDNA. To trap sequences corresponding to the full length genes, the labeled probe sequence is based on the polynucleotide sequences of the invention. Random primers or primers specific to the library vector can be used to amplify the trapped cDNA. Such gene trapping techniques are described in Gruber et al, WO
95/04745 and Gruber et al., U.S. Pat. No. 5,500,356. Kits are commercially available to perform gene trapping experiments from, for example, Life Technologies, Gaithersburg, Maryland, USA.
"Rapid amplification of cDNA ends," or RACE, is a PCR method of amplifying cDNAs from a number of different RNAs. The cDNAs are ligated to an oligonucleotide linker, and amplified by PCR using two primers. One primer is based on sequence from the instant polynucleotides, for which full length sequence is desired, and a second primer comprises sequence that hybridizes to the oligonucleotide linker to amplify the cDNA. A description of this methods is reported in WO 97/19110. In preferred embodiments of RACE, a common primer is designed to anneal to an arbitrary adaptor sequence ligated to cDNA ends (Apte and Siebert, Biotechniques (1993) 75:890-893; Edwards et al, Nuc. Acids Res. (1991) 79:5227-5232). When a single gene-specific RACE primer is paired with the common primer, preferential amplification of sequences between the single gene specific primer and the common primer occurs. Commercial cDNA pools modified for use in RACE are available.
Another PCR-based method generates full-length cDNA library with anchored ends without needing specific knowledge of the cDNA sequence. This method is described in WO 96/40998.
The promoter region of a gene generally is located 5' to the initiation site for RNA polymerase II. Hundreds of promoter regions contain the "TATA" box, a sequence such as TATTA or TATAA, which is sensitive to mutations. The promoter region can be obtained by performing 5' RACE using a primer from the coding region of the gene. Alternatively, the cDNA can be used as a probe for the genomic sequence, and the region 5' to the coding region is identified by "walking up." If the gene is highly expressed or differentially expressed, the promoter from the gene can be of use in a regulatory construct for a heterologous gene.
Once the full-length cDNA or gene is obtained, DNA encoding variants can be prepared by site-directed mutagenesis, described in detail in Sambrook et al., 15.3-15.63. The choice of codon or nucleotide to be replaced can be based on disclosure herein on optional changes in amino acids to achieve altered protein structure and/or function.
As an alternative method to obtaining DNA or RNA from a biological material, nucleic acid comprising nucleotides having the sequence of one or more polynucleotides of the invention can be synthesized. Thus, the invention encompasses nucleic acid molecules ranging in length from 15 nucleotides (corresponding to at least 15 contiguous nucleotides of one of "SEQ ID NOS: 1-5252") up to a maximum length suitable for one or more biological manipulations, including replication and expression, of the nucleic acid molecule. The invention includes but is not limited to (a) nucleic acid having the size of a full gene, and comprising at least one of "SEQ ID NOS: 1-5252;"; (b) the nucleic acid of (a) also comprising at least one additional gene, operably linked to permit expression of a fusion protein; (c) an expression vector comprising (a) or (b); (d) a plasmid comprising (a) or (b) ; and (e) a recombinant viral particle comprising (a) or (b). Once provided with the polynucleotides disclosed herein, construction or preparation of (a) - (e) are well within the skill in the art.
The sequence of a nucleic acid comprising at least 15 contiguous nucleotides ofat least any one of "SEQ ID NOS : 1 -5252,", preferably the entire sequence of at least any one of "SEQ ID NOS: 1-5252," is not limited and can be any sequence of A, T, G, and/or C (for DNA) and A, U, G, and/or C (for RNA) or modified bases thereof, including inosine and pseudouridine. The choice of sequence will depend on the desired function and can be dictated by coding regions desired, the intron-like regions desired, and the regulatory regions desired. Where the entire sequence of any one of "SEQ ID NOS: 1-5252" is within the nucleic acid, the nucleic acid obtained is referred to herein as a polynucleotide comprising the sequence of any one of "SEQ ID NOS: 1-5252."
II. Expression of Polypeptide Encoded by Full-Length cDNA or Full-Length Gene The provided polynucleotide (e.g. , a polynucleotide having a sequence of one of
"SEQ ID NOS: 1-5252"), the corresponding cDNA, or the full-length gene is used to express a partial or complete gene product. Constructs of polynucleotides having sequences of "SEQ ID NOS: 1-5252" can be generated synthetically. Alternatively, single- step assembly of a gene and entire plasmid from large numbers of oligodeoxyribonucleotides is described by, e.g., Stemmer et al, Gene (Amsterdam) (1995) 164(l):49-52>. In this method, assembly PCR (the synthesis of long DNA sequences from
large numbers of oligodeoxyribonucleotides (oligos)) is described. The method is derived from DNA shuffling (Stemmer, Nature (1994) 370:389-391), and does not rely on DNA ligase, but instead relies on DNA polymerase to build increasingly longer DNA fragments during the assembly process. Appropriate polynucleotide constructs are purified using standard recombinant
DNA techniques as described in, for example, Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., (1989) Cold Spring Harbor Press, Cold Spring Harbor, NY, and under current regulations described in United States Dept. of HHS, National Institute of Health (NIH) Guidelines for Recombinant DNA Research. The gene product encoded by a polynucleotide of the invention is expressed in any expression system, including, for example, bacterial, yeast, insect, amphibian and mammalian systems. Suitable vectors and host cells are described in U.S. Patent No. 5,654,173.
Bacteria. Expression systems in bacteria include those described in Chang et al, Nature (1978) 275:615; Goeddel et al, Nature (1979) 237:544; Goeddel et al, Nucleic Acids Res. (1980) S:4057; EP 0 036,776; U.S. Patent No. 4,551,433; DeBoer et al, Proc. Natl Acad. Sci. (USA) (1983) £0:21-25; and Siebenlist et al, Cell (1980) 20:269.
Yeast. Expression systems in yeast include those described in Hinnen et al, Proc. Natl. Acad. Sci. (USA) (1978) 75:1929; Ito et α/., J Bacteriol (1983) 755:163; Kurtz et al., Mol Cell. Biol. (1986) 5:142; Kunze et al, J. Basic Microbiol. (1985) 25:141; Gleeson et al, J. Gen. Microbiol. (1986) 732:3459; Roggenkamp et al, Mol. Gen. Genet. (1986) 202:302; Das et al, J Bacteriol. (1984) 75S:1165; De Louvencourt et al, J. Bacteriol. (1983) 154:131; Van den Berg et al, Bio/Technology (1990) 5:135; Kunze et al, J. Basic Microbiol. (1985) 25:141; Cregg et al, Mol. Cell. Biol. (1985) 5:3376; U.S. Patent Nos. 4,837,148 and 4,929,555; Beach and Nurse, Nature (1981) 300:706; Davidow et al, Curr. Genet. (1985) 70:380; Gaillardin et al, Curr. Genet. (1985) 70:49; Ballance et al, Biochem. Biophys. Res. Commun. (1983) 772:284-289; Tilburn et al, Gene (1983) 2(5:205-221; Yelton et al, Proc. Natl Acad. Sci. (USA) (1984) 37:1470-1474; Kelly and Hynes, EMBOJ. (1985) 4:475479; EP 0 244,234; and WO 91/00357.
Insect Cells. Expression of heterologous genes in insects is accomplished as described in U.S. Patent No. 4,745,051 ; Friesen et al, "The Regulation of Baculovirus
Gene Expression", in: The Molecular Biology Of Baculoviruses (1986) (W. Doerfler, ed.);
EP 0 127,839; EP 0 155,476; and Vlak et al, J. Gen. Virol. (1988) 69:165-116; Miller et al, Ann. Rev. Microbiol. (1988) 42:111; Carbonell et al, Gene (1988) 73:409; Maeda et al, Nature (1985) 375:592-594; Lebacq-Verheyden et al, Mol Cell. Biol. (1988) 3:3129; Smith et al, Proc. Natl. Acad. Sci. (USA) (1985) 32:8844; Miyajima et al, Gene (1987) 53:273; and Martin et al, DNA (1988) 7:99. Numerous baculoviral strains and variants and corresponding permissive insect host cells from hosts are described in Luckow et al, Bio/Technology (1988) 6:47-55, Miller et al, Generic Engineering (1986) 3:277-279, and Maeda et al, Nature (1985) 375:592-594.
Mammalian Cells. Mammalian expression is accomplished as described in Dijkema et al, EMBO J. (1985) 4:761, Gorman et al, Proc. Natl Acad. Sci. (USA) (1982) 79:6777, Boshart et al, Cell (1985) 47:521 and U.S. Patent No. 4,399,216. Other features of mammalian expression are facilitated as described in Ham and Wallace, Meth. Enz. (1979) 53:44, Barnes and Sato, Anal Biochem. (1980) 702:255, U.S. Patent Nos. 4,767,704, 4,657,866, 4,927,762, 4,560,655, WO 90/103430, WO 87/00195, and U.S. RE 30,985.
Polynucleotide molecules comprising a polynucleotide sequence provided herein propagated by placing the molecule in a vector. Viral and non- viral vectors are used, including plasmids. The choice of plasmid will depend on the type of cell in which propagation is desired and the purpose of propagation. Certain vectors are useful for amplifying and making large amounts of the desired DNA sequence. Other vectors are suitable for expression in cells in culture. Still other vectors are suitable for transfer and expression in cells in a whole animal or person. The choice of appropriate vector is well within the skill of the art. Many such vectors are available commercially. The partial or full-length polynucleotide is inserted into a vector typically by means of DNA ligase attachment to a cleaved restriction enzyme site in the vector. Alternatively, the desired nucleotide sequence can be inserted by homologous recombination in vivo. Typically this is accomplished by attaching regions of homology to the vector on the flanks of the desired nucleotide sequence. Regions of homology are added by ligation of oligonucleotides, or by polymerase chain reaction using primers comprising both the region of homology and a portion of the desired nucleotide sequence, for example.
The polynucleotides set forth in "SEQ ID NOS: 1-5252" or their corresponding full- length polynucleotides are linked to regulatory sequences as appropriate to obtain the desired expression properties. These can include promoters (attached either at the 5' end of the sense strand or at the 3' end of the antisense strand), enhancers, terminators, operators, repressors, and inducers. The promoters can be regulated or constitutive. In some situations it may be desirable to use conditionally active promoters, such as tissue-specific or developmental stage-specific promoters. These are linked to the desired nucleotide sequence using the techniques described above for linkage to vectors. Any techniques known in the art can be used. When any of the above host cells, or other appropriate host cells or organisms, are used to replicate and/or express the polynucleotides or nucleic acids of the invention, the resulting replicated nucleic acid, RNA, expressed protein or polypeptide, is within the scope of the invention as a product of the host cell or organism. The product is recovered by any appropriate means known in the art. Once the gene corresponding to a selected polynucleotide is identified, its expression can be regulated in the cell to which the gene is native. For example, an endogenous gene of a cell can be regulated by an exogenous regulatory sequence as disclosed in U.S. Patent No. 5,641,670.
III. Identification of Functional and Structural Motifs of Novel Genes
A. Screening Polynucleotide Sequences and Amino Acid Sequences Against Publicly Available Databases
Translations of the nucleotide sequence of the provided polynucleotides, cDNAs or full genes can be aligned with individual known sequences. Similarity with individual sequences can be used to determine the activity of the polypeptides encoded by the polynucleotides of the invention. For example, sequences that show similarity with a chemokine sequence can exhibit chemokine activities. Also, sequences exhibiting similarity with more than one individual sequence can exhibit activities that are characteristic of either or both individual sequences. The full length sequences and fragments of the polynucleotide sequences of the nearest neighbors can be used as probes and primers to identify and isolate the full length
sequence corresponding to provided polynucleotides. The nearest neighbors can indicate a tissue or cell type to be used to construct a library for the full-length sequences corresponding to the provided polynucleotides..
Typically, a selected polynucleotide is translated in all six frames to determine the best alignment with the individual sequences. The sequences disclosed herein in the Sequence Listing are in a 5' to 3' orientation and translation in three frames can be sufficient (with a few specific exceptions as described in the Examples). These amino acid sequences are referred to, generally, as query sequences, which will be aligned with the individual sequences. Databases with individual sequences are described in "Computer Methods for Macromolecular Sequence Analysis" Methods in Enzymology (1996) 266',
Doolittle, Academic Press, Inc., a division of Harcourt Brace & Co., San Diego, California, USA. Databases include Genbank, EMBL, and DNA Database of Japan (DDBJ).
Query and individual sequences can be aligned using the methods and computer programs described above, and include BLAST, available over the world wide web at http://ww.ncbi.nlm.nih.gov/BLAST/. Another alignment algorithm is Fasta, available in the Genetics Computing Group (GCG) package, Madison, Wisconsin, USA, a wholly owned subsidiary of Oxford Molecular Group, Inc. Other techniques for alignment are described in Doolittle, supra. Preferably, an alignment program that permits gaps in the sequence is utilized to align the sequences. The Smith- Waterman is one type of algorithm that permits gaps in sequence alignments. See Meth. Mol Biol. (1997) 70: 173-187. Also, the GAP program using the Needleman and Wunsch alignment method can be utilized to align sequences. An alternative search strategy uses MPSRCH software, which runs on a MASPAR computer. MPSRCH uses a Smith- Waterman algorithm to score sequences on a massively parallel computer. This approach improves ability to identify sequences that are distantly related matches, and is especially tolerant of small gaps and nucleotide sequence errors. Amino acid sequences encoded by the provided polynucleotides can be used to search both protein and DNA databases.
Results of individual and query sequence alignments can be divided into three categories, high similarity, weak similarity, and no similarity. Individual alignment results ranging from high similarity to weak similarity provide a basis for determining polypeptide activity and/or structure. Parameters for categorizing individual results include: percentage
of the alignment region length where the strongest alignment is found, percent sequence identity, and p value.
The percentage of the alignment region length is calculated by counting the number of residues of the individual sequence found in the region of strongest alignment, e.g., contiguous region of the individual sequence that contains the greatest number of residues that are identical to the residues of the corresponding region of the aligned query sequence. This number is divided by the total residue length of the query sequence to calculate a percentage. For example, a query sequence of 20 amino acid residues might be aligned with a 20 amino acid region of an individual sequence. The individual sequence might be identical to amino acid residues 5, 9-15, and 17-19 of the query sequence. The region of strongest alignment is thus the region stretching from residue 9-19, an 11 amino acid stretch. The percentage of the alignment region length is: 11 (length of the region of strongest alignment) divided by (query sequence length) 20 or 55%).
Percent sequence identity is calculated by counting the number of amino acid matches between the query and individual sequence and dividing total number of matches by the number of residues of the individual sequences found in the region of strongest alignment. Thus, the percent identity in the example above would be 10 matches divided by 11 amino acids, or approximately, 90.9%
P value is the probability that the alignment was produced by chance. For a single alignment, the p value can be calculated according to Karlin et al, Proc. Natl. Acad. Sci. (1990) 37:2264 and Karlin et al., Proc. Natl. Acad. Sci. (1993) 90. The p value of multiple alignments using the same query sequence can be calculated using an heuristic approach described in Altschul et al., Nat. Genet. (1994) 6: 19. Alignment programs such as BLAST program can calculate the p value. Another factor to consider for determining identity or similarity is the location of the similarity or identity. Strong local alignment can indicate similarity even if the length of alignment is short. Sequence identity scattered throughout the length of the query sequence also can indicate a similarity between the query and profile sequences. The boundaries of the region where the sequences align can be determined according to Doolittle, supra; BLAST or FAST programs; or by determining the area where sequence identity is highest.
High Similarity. In general, in alignment results considered to be of high similarity, the percent of the alignment region length is typically at least about 55% of total length query sequence; more typically, at least about 58%; even more typically; at least about 60% of the total residue length of the query sequence. Usually, percent length of the alignment region can be as much as about 62%; more usually, as much as about 64%; even more usually, as much as about 66%). Further, for high similarity, the region of alignment, typically, exhibits at least about 75% of sequence identity; more typically, at least about 78%; even more typically; at least about 80% sequence identity. Usually, percent sequence identity can be as much as about 82%; more usually, as much as about 84%; even more usually, as much as about 86%.
The p value is used in conjunction with these methods. If high similarity is found, the query sequence is considered to have high similarity with a profile sequence when the p value is less than or equal to about IO"2; more usually; less than or equal to about IO"3; even more usually; less than or equal to about IO"4. More typically, the p value is no more than about 10"5; more typically; no more than or equal to about 10"10; even more typically; no more than or equal to about IO"15 for the query sequence to be considered high similarity.
Weak Similarity. In general, where alignment results considered to be of weak similarity, there is no minimum percent length of the alignment region nor minimum length of alignment. A better showing of weak similarity is considered when the region of alignment is, typically, at least about 15 amino acid residues in length; more typically, at least about 20; even more typically; at least about 25 amino acid residues in length. Usually, length of the alignment region can be as much as about 30 amino acid residues; more usually, as much as about 40; even more usually, as much as about 60 amino acid residues. Further, for weak similarity, the region of alignment, typically, exhibits at least about 35% of sequence identity; more typically, at least about 40%; even more typically; at least about 45% sequence identity. Usually, percent sequence identity can be as much as about 50%; more usually, as much as about 55%; even more usually, as much as about 60%. If low similarity is found, the query sequence is considered to have weak similarity with a profile sequence when the p value is usually less than or equal to about IO"2; more usually; less than or equal to about IO"3; even more usually; less than or equal to about 10"4. More
typically, the p value is no more than about IO"5; more usually; no more than or equal to about IO"10; even more usually; no more than or equal to about IO"15 for the query sequence to be considered weak similarity.
Similarity Determined by Sequence Identity Alone. Sequence identity alone can be used to determine similarity of a query sequence to an individual sequence and can indicate the activity of the sequence. Such an alignment, preferably, permits gaps to align sequences. Typically, the query sequence is related to the profile sequence if the sequence identity over the entire query sequence is at least about 15%; more typically, at least about 20%; even more typically, at least about 25%; even more typically, at least about 50%. Sequence identity alone as a measure of similarity is most useful when the query sequence is usually, at least 80 residues in length; more usually, 90 residues; even more usually, at least 95 amino acid residues in length. More typically, similarity can be concluded based on sequence identity alone when the query sequence is preferably 100 residues in length; more preferably, 120 residues in length; even more preferably, 150 amino acid residues in length.
Determining Activity from Alignments with Profile and Multiple Aligned Sequences. Translations of the provided polynucleotides can be aligned with amino acid profiles that define either protein families or common motifs. Also, translations of the provided polynucleotides can be aligned to multiple sequence alignments (MSA) comprising the polypeptide sequences of members of protein families or motifs. Similarity or identity with profile sequences or MS As can be used to determine the activity of the gene products (e.g., polypeptides) encoded by the provided polynucleotides or corresponding cDNA or genes. For example, sequences that show an identity or similarity with a chemokine profile or MSA can exhibit chemokine activities. Profiles can designed manually by (1) creating an MSA, which is an alignment of the amino acid sequence of members that belong to the family and (2) constructing a statistical representation of the alignment. Such methods are described, for example, in Birney et al, Nucl Acid Res. (1996) 24(14): 2730-2739. MSAs of some protein families and motifs are publicly available. For example, http://genome.wustl.edu Pfam/ includes MSAs of 547 different families and motifs. These MSAs are described also in
Sonnhammer et al., Proteins (1997) 28: 405-420. Other sources over the world wide web
include the site at http://www.embl-heidelberg.de/argos/ali/ali.html; alternatively, a message can be sent to ALf@EMBL-HEIDELBERG.DE for the information. A brief description of these MSAs is reported in Pascarella et al, Prot. Eng. (1996) 9(3) :249-25l. Techniques for building profiles from MSAs are described in Sonnhammer et al, supra; Birney et al, supra; and "Computer Methods for Macromolecular Sequence Analysis," Methods in Enzymology (1996) 266, Doolittle, Academic Press, Inc., a division of Harcourt Brace & Co., San Diego, California, USA.
Similarity between a query sequence and a protein family or motif can be determined by (a) comparing the query sequence against the profile and/or (b) aligning the query sequence with the members of the family or motif. Typically, a program such as Searchwise is used to compare the query sequence to the statistical representation of the multiple alignment, also known as a profile. The program is described in Birney et al, supra. Other techniques to compare the sequence and profile are described in Sonnhammer et al, supra and Doolittle, supra. Next, methods described by Feng et al, J. Mol Evol (1987) 25:351 and Higgins et al, CABIOS (1989) 5:151 can be used align the query sequence with the members of a family or motif, also known as a MSA. Computer programs, such as PILEUP, can be used. See Feng et al, infra. In general, the following factors are used to determine if a similarity between a query sequence and a profile or MSA exists: (1) number of conserved residues found in the query sequence, (2) percentage of conserved residues found in the query sequence, (3) number of frameshifts, and (4) spacing between conserved residues.
Some alignment programs that both translate and align sequences can make any number of frameshifts when translating the nucleotide sequence to produce the best alignment. The fewer frameshifts needed to produce an alignment, the stronger the similarity or identity between the query and profile or MSAs. For example, a weak similarity resulting from no frameshifts can be a better indication of activity or structure of a query sequence, than a strong similarity resulting from two frameshifts. Preferably, three or fewer frameshifts are found in an alignment; more preferably two or fewer frameshifts; even more preferably, one or fewer frameshifts; even more preferably, no frameshifts are found in an alignment of query and profile or MSAs.
Conserved residues are those amino acids found at a particular position in all or some of the family or motif members. For example, most chemokines contain four conserved cysteines. Alternatively, a position is considered conserved if only a certain class of amino acids is found in a particular position in all or some of the family members. For example, the N-terminal position can contain a positively charged amino acid, such as lysine, arginine, or histidine.
Typically, a residue of a polypeptide is conserved when a class of amino acids or a single amino acid is found at a particular position in at least about 40% of all class members; more typically, at least about 50%; even more typically, at least about 60% of the members. Usually, a residue is conserved when a class or single amino acid is found in at least about 70% of the members of a family or motif; more usually, at least about 80%; even more usually, at least about 90%; even more usually, at least about 95%.
A residue is considered conserved when three unrelated amino acids are found at a particular position in the some or all of the members; more usually, two unrelated amino acids. These residues are conserved when the unrelated amino acids are found at particular positions in at least about 40% of all class member; more typically, at least about 50%; even more typically, at least about 60% of the members. Usually, a residue is conserved when a class or single amino acid is found in at least about 70% of the members of a family or motif; more usually, at least about 80%; even more usually, at least about 90%; even more usually, at least about 95%.
A query sequence has similarity to a profile or MSA when the query sequence comprises at least about 25% of the conserved residues of the profile or MSA; more usually, at least about 30%; even more usually; at least about 40%. Typically, the query sequence has a stronger similarity to a profile sequence or MSA when the query sequence comprises at least about 45% of the conserved residues of the profile or MSA; more typically, at least about 50%; even more typically; at least about 55%.
B. Screening Polynucleotide and Amino Acid Sequences Against Protein
Profiles The identify and function of the gene that correlates to a polynucleotide described herein can be determined by screening the polynucleotides or their corresponding amino acid sequences against profiles of protein families. Such profiles focus on common
structural motifs among proteins of each family. Publicly available profiles are described above in Section IVA. Additional or alternative profiles are described below.
In comparing a novel polynucleotide with known sequences, several alignment tools are available. Examples include PileUp, which creates a multiple sequence alignment, and is described in Feng et al., J. Mol. Evol. (1987) 25:351. Another method, GAP, uses the alignment method of Needleman et al., J. Mol. Biol. (1970) 43:443. GAP is best suited for global alignment of sequences. A third method, BestFit, functions by inserting gaps to maximize the number of matches using the local homology algorithm of Smith et al, Adv. Appl Math. (1981) 2:482.
C. Identification of Secreted & Membrane-Bound Polypeptides Both secreted and membrane-bound polypeptides of the present invention are of particular interest. For example, levels of secreted polypeptides can be assayed in body fluids that are convenient, such as blood, urine, prostatic fluid and semen. Membrane- bound polypeptides are useful for constructing vaccine antigens or inducing an immune response. Such antigens would comprise all or part of the extracellular region of the membrane-bound polypeptides. Because both secreted and membrane-bound polypeptides comprise a fragment of contiguous hydrophobic amino acids, hydrophobicity predicting algorithms can be used to identify such polypeptides. A signal sequence is usually encoded by both secreted and membrane-bound polypeptide genes to direct a polypeptide to the surface of the cell. The signal sequence usually comprises a stretch of hydrophobic residues. Such signal sequences can fold into helical structures. Membrane-bound polypeptides typically comprise at least one transmembrane region that possesses a stretch of hydrophobic amino acids that can transverse the membrane. Some transmembrane regions also exhibit a helical structure. Hydrophobic fragments within a polypeptide can be identified by using computer algorithms. Such algorithms include Hopp & WoodSi Proc. Natl. Acad. Sci. USA (1981) 73:3824-3828; Kyte & Doolittle, J. Mol Biol (1982) 757: 105-132; and RAOAR algorithm, Degli Esposti et al, Eur. J. Biochem. (1990) 790: 207-219. Another method of identifying secreted and membrane-bound polypeptides is to translate the polynucleotides of the invention in all six frames and determine if at least 8
contiguous hydrophobic amino acids are present. Those translated polypeptides with at least 8; more typically, 10; even more typically, 12 contiguous hydrophobic amino acids are considered to be either a putative secreted or membrane bound polypeptide. Hydrophobic amino acids include alanine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan, tyrosine, and valine.
IV. Identification of the Function of an Expression Product of a Full-Length Gene Corresponding to a Polynucleotide Ribozymes, antisense constructs, and dominant negative mutants can be used to determine function of the expression product of a gene corresponding to a polynucleotide provided herein. These methods and compositions are particularly useful where the provided novel polynucleotide exhibits no significant or substantial homology to a sequence encoding a gene of known function. Antisense molecules and ribozymes can be constructed from synthetic polynucleotides. Typically, the phosphoramidite method of oligonucleotide synthesis is used. See Beaucage et al, Tet. Lett. (1981) 22:1859 and U.S. Patent No. 4,668,777. Automated devices for synthesis are available to create oligonucleotides using this chemistry. Examples of such devices include Biosearch 8600, Models 392 and 394 by Applied Biosystems, a division of Perkin-Elmer Corp., Foster City, California, USA; and Expedite by Perceptive Biosystems, Framingham, Massachusetts, USA. Synthetic RNA, phosphate analog oligonucleotides, and chemically derivatized oligonucleotides can also be produced, and can be covalently attached to other molecules. RNA oligonucleotides can be synthesized, for example, using RNA phosphoramidites. This method can be performed on an automated synthesizer, such as Applied Biosystems, Models 392 and 394, Foster City, California, USA. See Applied Biosystems User Bulletin 53 and Ogilvie et al, Pure & Applied Chem. (1987) 59:325.
Phosphorothioate oligonucleotides can also be synthesized for antisense construction. A sulfurizing reagent, such as tetraethylthiruam disulfide (TETD) in acetonitrile can be used to convert the internucleotide cyanoethyl phosphite to the phosphorothioate triester within 15 minutes at room temperature. TETD replaces the iodine reagent, while all other reagents used for standard phosphoramidite chemistry
remain the same. Such a synthesis method can be automated using Models 392 and 394 by Applied Biosystems, for example.
Oligonucleotides of up to 200 nucleotides can be synthesized, more typically, 100 nucleotides, more typically 50 nucleotides; even more typically 30 to 40 nucleotides. These synthetic fragments can be annealed and ligated together to construct larger fragments. See, for example, Sambrook et al, supra. A. Ribozymes
Trans-cleaving catalytic RNAs (ribozymes) are RNA molecules possessing endoribonuclease activity. Ribozymes are specifically designed for a particular target, and the target message must contain a specific nucleotide sequence. They are engineered to cleave any RNA species site-specifically in the background of cellular RNA. The cleavage event renders the mRNA unstable and prevents protein expression. Importantly, ribozymes can be used to inhibit expression of a gene of unknown function for the purpose of determining its function in an in vitro or in vivo context, by detecting the phenotypic effect.
One commonly used ribozyme motif is the hammerhead, for which the substrate sequence requirements are minimal. Design of the hammerhead ribozyme is disclosed in Usman et al, Current Opin. Struct. Biol. (1996) 6:527. Ribozymes can also be prepared and used as described in Long et al, FASEBJ. (1993) 7:25; Symons, Ann. Rev. Biochem. (1992) 67:641; Perrotta et al, Biochem. (1992) 37:16; Ojwang et al, Proc. Natl Acad.
Sci. (USA) (1992) 39:10802; and U.S. Patent No. 5,254,678. Ribozyme cleavage of HIV-I RNA is described in U.S. Patent No. 5,144,019; methods of cleaving RNA using ribozymes is described in U.S. Patent No. 5,116,742; and methods for increasing the specificity of ribozymes are described in U.S. Patent No. 5,225,337 and Koizumi et al, Nucleic Acid Res. (1989) 77:7059. Preparation and use of ribozyme fragments in a hammerhead structure are also described by Koizumi et al, Nucleic Acids Res. (1989) 77:7059. Preparation and use of ribozyme fragments in a hairpin structure are described by Chowrira and Burke, Nucleic Acids Res. (1992) 20:2835. Ribozymes can also be made by rolling transcription as described in Daubendiek and Kool, Nat. Biotechnol (1997) 15(3):213.
The hybridizing region of the ribozyme can be modified or can be prepared as a branched structure as described in Horn and Urdea, Nucleic Acids Res. (1989) 77:6959. The basic structure of the ribozymes can also be chemically altered in ways familiar to those skilled in the art, and chemically synthesized ribozymes can be administered as synthetic oligonucleotide derivatives modified by monomeric units. In a therapeutic context, liposome mediated delivery of ribozymes improves cellular uptake, as described in Birikh et al, Eur. J. Biochem. (1997) 245:1.
Using the polynucleotide sequences of the invention and methods known in the art, ribozymes are designed to specifically bind and cut the corresponding mRNA species. Ribozymes thus provide a means to inhibit the expression of any of the proteins encoded by the disclosed polynucleotides or their full-length genes. The full-length gene need not be known in order to design and use specific inhibitory ribozymes. In the case of a polynucleotide or full-length cDNA of unknown function, ribozymes corresponding to that nucleotide sequence can be tested in vitro for efficacy in cleaving the target transcript. Those ribozymes that effect cleavage in vitro are further tested in vivo. The ribozyme can also be used to generate an animal model for a disease, as described in Birikh et al, supra. An effective ribozyme is used to determine the function of the gene of interest by blocking its transcription and detecting a change in the cell. Where the gene is found to be a mediator in a disease, an effective ribozyme is designed and delivered in a gene therapy for blocking transcription and expression of the gene.
Therapeutic and functional genomic applications of ribozymes proceed beginning with knowledge of a portion of the coding sequence of the gene to be inhibited. Thus, for many genes, a partial polynucleotide sequence provides adequate sequence for constructing an effective ribozyme. A target cleavage site is selected in the target sequence, and a ribozyme is constructed based on the 5' and 3' nucleotide sequences that flank the cleavage site. Retroviral vectors are engineered to express monomeric and multimeric hammerhead ribozymes targeting the mRNA of the target coding sequence. These monomeric and multimeric ribozymes are tested in vitro for an ability to cleave the target mRNA. A cell line is stably transduced with the retroviral vectors expressing the ribozymes, and the transduction is confirmed by Northern blot analysis and reverse-transcription polymerase chain reaction (RT-PCR). The cells are screened for inactivation of the target mRNA by
such indicators as reduction of expression of disease markers or reduction of the gene product of the target mRNA.
B. Antisense
Antisense nucleic acids are designed to specifically bind to RNA, resulting in the formation of RNA-DNA or RNA-RNA hybrids, with an arrest of DNA replication, reverse transcription or messenger RNA translation. Antisense polynucleotides based on a selected polynucleotide sequence can interfere with expression of the corresponding gene. Antisense polynucleotides are typically generated within the cell by expression from antisense constructs that contain the antisense strand as the transcribed strand. Antisense polynucleotides based on the disclosed polynucleotides will bind and/or interfere with the translation of mRNA comprising a sequence complementary to the antisense polynucleotide. The expression products of control cells and cells treated with the antisense construct are compared to detect the protein product of the gene corresponding to the polynucleotide upon which the antisense construct is based. The protein is isolated and identified using routine biochemical methods.
Given the extensive background literature and clinical experience in antisense therapy, one skilled in the art can use selected polynucleotides of the invention as additional potential therapeutics. The choice of polynucleotide can be narrowed by first testing them for binding to "hot spot" regions of the genome of cancerous cells. If a polynucleotide is identified as binding to a "hot spot", testing the polynucleotide as an antisense compound in the corresponding cancer cells clearly is warranted.
C. Dominant Negative Mutations
As an alternative method for identifying function of the gene corresponding to a polynucleotide disclosed herein, dominant negative mutations are readily generated for corresponding proteins that are active as homomultimers. A mutant polypeptide will interact with wild-type polypeptides (made from the other allele) and form a non-functional multimer. Thus, a mutation is in a substrate-binding domain, a catalytic domain, or a cellular localization domain. Preferably, the mutant polypeptide will be overproduced. Point mutations are made that have such an effect. In addition, fusion of different polypeptides of various lengths to the terminus of a protein can yield dominant negative mutants. General strategies are available for making dominant negative mutants (see, e.g.,
Herskowitz, Nature (1987) 329:219). Such techniques can be used to create loss of function mutations, which are useful for determining protein function.
V. Construction of Polypeptides of the Invention and Variants Thereof The polypeptides of the invention include those encoded by the disclosed polynucleotides. These polypeptides can also be encoded by nucleic acids that, by virtue of the degeneracy of the genetic code, are not identical in sequence to the disclosed polynucleotides. Thus, the invention includes within its scope a polypeptide encoded by a polynucleotide having the sequence of any one of "SEQ ID NOS: 1-5252" or a variant thereof.
In general, the term "polypeptide" as used herein refers to both the full length polypeptide encoded by the recited polynucleotide, the polypeptide encoded by the gene represented by the recited polynucleotide, as well as portions or fragments thereof. "Polypeptides" also includes variants of the naturally occurring proteins, where such variants are homologous or substantially similar to the naturally occurring protein, and can be of an origin of the same or different species as the naturally occurring protein (e.g., human, murine, or some other species that naturally expresses the recited polypeptide, usually a mammalian species). In general, variant polypeptides have a sequence that has at least about 80%, usually at least about 90%, and more usually at least about 98% sequence identity with a differentially expressed polypeptide of the invention, as measured by
BLAST using the parameters described above. The variant polypeptides can be naturally or non-naturally glycosylated, i.e., the polypeptide has a glycosylation pattern that differs from the glycosylation pattern found in the corresponding naturally occurring protein. The invention also encompasses homologs of the disclosed polypeptides (or fragments thereof) where the homologs are isolated from other species, i.e. other animal or plant species, where such homologs, usually mammalian species, e.g. rodents, such as mice, rats; domestic animals, e.g., horse, cow, dog, cat; and humans. By homolog is meant a polypeptide having at least about 35%, usually at least about 40% and more usually at least about 60% amino acid sequence identity a particular differentially expressed protein as identified above, where sequence identity is determined using the BLAST algorithm, with the parameters described supra.
In general, the polypeptides of the subject invention are provided in a non-naturally occurring environment, e.g. are separated from their naturally occurring environment. In certain embodiments, the subject protein is present in a composition that is enriched for the protein as compared to a control. As such, purified polypeptide is provided, where by purified is meant that the protein is present in a composition that is substantially free of non-differentially expressed polypeptides, where by substantially free is meant that less than 90%), usually less than 60% and more usually less than 50%) of the composition is made up of non-differentially expressed polypeptides.
Also within the scope of the invention are variants; variants of polypeptides include mutants, fragments, and fusions. Mutants can include amino acid substitutions, additions or deletions. The amino acid substitutions can be conservative amino acid substitutions or substitutions to eliminate non-essential amino acids, such as to alter a glycosylation site, a phosphorylation site or an acetylation site, or to minimize misfolding by substitution or deletion of one or more cysteine residues that are not necessary for function. Conservative amino acid substitutions are those that preserve the general charge, hydrophobicity/hydrophilicity, and/or steric bulk of the amino acid substituted. For example, substitutions between the following groups are conservative: Gly/Ala, Val/Ile/Leu, Asp/Glu, Lys/Arg, Asn/Gln, Ser/Cys, Thr, and Phe/Trp/Tyr.
Variants can be designed so as to retain biological activity of a particular region of the protein (e.g., a functional domain and/or, where the polypeptide is a member of a protein family, a region associated with a consensus sequence). In a non-limiting example, Osawa et al, Biochem. Mol Int. (1994) 34:1003, discusses the actin binding region of a protein from several different species. The actin binding regions of the these species are considered homologous based on the fact that they have amino acids that fall within "homologous residue groups." Homologous residues are judged according to the following groups (using single letter amino acid designations): STAG; ILVMF; HRK; DEQN; and FYW. For example, and S, a T, an A or a G can be in a position and the function (in this case actin binding) is retained.
Additional guidance on amino acid substitution is available from studies of protein evolution. Go et al, Int. J. Peptide Protein Res. (1980) 75:211, classified amino acid residue sites as interior or exterior depending on their accessibility. More frequent
substitution on exterior sites was confirmed to be general in eight sets of homologous protein families regardless of their biological functions and the presence or absence of a prosthetic group. Virtually all types of amino acid residues had higher mutabilities on the exterior than in the interior. No correlation between mutability and polarity was observed of amino acid residues in the interior and exterior, respectively. Amino acid residues were classified into one of three groups depending on their polarity: polar (Arg, Lys, His, Gin, Asn, Asp, and Glu); weak polar (Ala, Pro, Gly, Thr, and Ser), and nonpolar (Cys, Val, Met, He, Leu, Phe, Tyr, and Tip). Amino acid replacements during protein evolution were very conservative: 88% and 76% of them in the interior or exterior, respectively, were within the same group of the three. Inter-group replacements are such that weak polar residues are replaced more often by nonpolar residues in the interior and more often by polar residues on the exterior.
Additional guidance for production of polypeptide variants is provided in Querol et al., Prot. Eng. (1996) 9:265, which provides general rules for amino acid substitutions to enhance protein thermostability. New glycosylation sites can be introduced as discussed in Olsen and Thomsen, J. Gen. Microbiol. (1991) 737:579. An additional disulfide bridge can be introduced, as discussed by Perry and Wetzel, Science (1984) 226:555; Pantoliano et al, Biochemistry (1987) 26:2011; Matsumura et al, Nature (1989) 342:291; Nishikawa et al, Protein Eng. (1990) 3:443; Takagi et al, J. Biol. Chem. (1990) 265:6874; Clarke et al., Biochemistry (1993) 32:4322; and Wakarchuk et al, Protein Eng. (1994) 7:1379. Metal binding sites can be introduced, according to Toma et al, Biochemistry (1991) 30:97, and Haezerbrouck et al, Protein Eng. (1993) 6:643. Substitutions with prolines in loops can be made according to Masul et al, Appl Env. Microbiol (1994) 60:3579; and Hardy et al, FEBS Lett. 317:89. Cysteine-depleted muteins are considered variants within the scope of the invention.
These variants can be constructed according to methods disclosed in U.S. Patent No. 4,959,314, which discloses substitution of cysteines with other amino acids, and methods for assaying biological activity and effect of the substitution. Such methods are suitable for proteins according to this invention that have cysteine residues suitable for such substitutions, for example to eliminate disulfide bond formation.
Variants also include fragments of the polypeptides disclosed herein, particularly biologically active fragments and/or fragments corresponding to functional domains. Fragments of interest will typically be at least about 10 aa to at least about 15 aa in length, usually at least about 50 aa in length, and can be as long as 300 aa in length or longer, but will usually not exceed about 1000 aa in length, where the fragment will have a stretch of amino acids that is identical to a polypeptide encoded by a polynucleotide having a sequence of any "SEQ ID NOS: 1-5252", or a homolog thereof.
The protein variants described herein are encoded by polynucleotides that are within the scope of the invention. The genetic code can be used to select the appropriate codons to construct the corresponding variants.
VI. Computer-Related Embodiments
In general, a library of polynucleotides is a collection of sequence information, which information is provided in either biochemical form (e.g., as a collection of polynucleotide molecules), or in electronic form (e.g., as a collection of polynucleotide sequences stored in a computer-readable form, as in a computer system and/or as part of a computer program). The sequence information of the polynucleotides can be used in a variety of ways, e.g., as a resource for gene discovery, as a representation of sequences expressed in a selected cell type (e.g., cell type markers), and/or as markers of a given disease or disease state. In general, a disease marker is a representation of a gene product that is present in all cells affected by disease either at an increased or decreased level relative to a normal cell (e.g., a cell of the same or similar type that is not substantially affected by disease). For example, a polynucleotide sequence in a library can be a polynucleotide that represents an mRNA, polypeptide, or other gene product encoded by the polynucleotide, that is either overexpressed or underexpressed in a breast ductal cell affected by cancer relative to a normal (i.e., substantially disease-free) breast cell.
The nucleotide sequence information of the library can be embodied in any suitable form, e.g., electronic or biochemical forms. For example, a library of sequence information embodied in electronic form includes an accessible computer data file (or, in biochemical form, a collection of nucleic acid molecules) that contains the representative nucleotide sequences of genes that are differentially expressed (e.g., overexpressed or underexpressed)
as between, for example, i) a cancerous cell and a normal cell; ii) a cancerous cell and a dysplastic cell; iii) a cancerous cell and a cell affected by a disease or condition other than cancer; iv) a metastatic cancerous cell and a normal cell and/or non-metastatic cancerous cell; v) a malignant cancerous cell and a non-malignant cancerous cell (or a normal cell) and/or vi) a dysplastic cell relative to a normal cell. Other combinations and comparisons of cells affected by various diseases or stages of disease will be readily apparent to the ordinarily skilled artisan. Biochemical embodiments of the library include a collection of nucleic acids that have the sequences of the genes in the library, where the nucleic acids can correspond to the entire gene in the library or to a fragment thereof, as described in greater detail below.
The polynucleotide libraries of the subject invention include sequence information of a plurality of polynucleotide sequences, where at least one of the polynucleotides has a sequence of any of "SEQ ID NOS:l-5252." By plurality is meant at least 2, usually at least 3 and can include up to all of "SEQ ID NOS: 1-5252." The length and number of polynucleotides in the library will vary with the nature of the library, e.g., if the library is an oligonucleotide array, a cDNA array, a computer database of the sequence information, etc.
Where the library is an electronic library, the nucleic acid sequence information can be present in a variety of media. "Media" refers to a manufacture, other than an isolated nucleic acid molecule, that contains the sequence information of the present invention.
Such a manufacture provides the genome sequence or a subset thereof in a form that can be examined by means not directly applicable to the sequence as it exists in a nucleic acid. For example, the nucleotide sequence of the present invention, e.g. the nucleic acid sequences of any of the polynucleotides of "SEQ ID NOS: 1-5252," can be recorded on computer readable media, e.g. any medium that can be read and accessed directly by a computer. Such media include, but are not limited to: magnetic storage media, such as a floppy disc, a hard disc storage medium, and a magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media. One of skill in the art can readily appreciate how any of the presently known computer readable mediums can be used to create a manufacture comprising a recording of the present sequence information.
"Recorded" refers to a process for storing information on computer readable medium, using any such methods as known in the art. Any convenient data storage structure can be chosen, based on the means used to access the stored information. A variety of data processor programs and formats can be used for storage, e.g. word processing text file, database format, etc. In addition to the sequence information, electronic versions of the libraries of the invention can be provided in conjunction or connection with other computer-readable information and/or other types of computer-readable files (e.g., searchable files, executable files, etc, including, but not limited to, for example, search program software, etc.). By providing the nucleotide sequence in computer readable form, the information can be accessed for a variety of purposes. Computer software to access sequence information is publicly available. For example, the BLAST (Altschul et al., supra.) and BLAZE (Brutlag et al. Comp. Chem. (1993) 17:203) search algorithms on a Sybase system can be used to identify open reading frames (ORFs) within the genome that contain homology to ORFs from other organisms.
As used herein, "a computer-based system" refers to the hardware means, software means, and data storage means used to analyze the nucleotide sequence information of the present invention. The minimum hardware of the computer-based systems of the present invention comprises a central processing unit (CPU), input means, output means, and data storage means. A skilled artisan can readily appreciate that any one of the currently available computer-based system are suitable for use in the present invention. The data storage means can comprise any manufacture comprising a recording of the present sequence information as described above, or a memory access means that can access such a manufacture. "Search means" refers to one or more programs implemented on the computer-based system, to compare a target sequence or target structural motif with the stored sequence information. Search means are used to identify fragments or regions of the genome that match a particular target sequence or target motif. A variety of known algorithms are publicly known and commercially available, e.g. MacPattern (EMBL), BLASTN and BLASTX (NCBI). A "target sequence" can be any DNA or amino acid
sequence of six or more nucleotides or two or more amino acids, preferably from about 10 to 100 amino acids or from about 30 to 300 nucleotide residues.
A "target structural motif," or "target motif," refers to any rationally selected sequence or combination of sequences in which the sequence(s) are chosen based on a three-dimensional configuration that is formed upon the folding of the target motif, or on consensus sequences of regulatory or active sites. There are a variety of target motifs known in the art. Protein target motifs include, but arc not limited to, enzyme active sites and signal sequences. Nucleic acid target motifs include, but are not limited to, hairpin structures, promoter sequences and other expression elements such as binding sites for transcription factors.
A variety of structural formats for the input and output means can be used to input and output the information in the computer-based systems of the present invention. One format for an output means ranks fragments of the genome possessing varying degrees of homology to a target sequence or target motif. Such presentation provides a skilled artisan with a ranking of sequences and identifies the degree of sequence similarity contained in the identified fragment.
A variety of comparing means can be used to compare a target sequence or target motif with the data storage means to identify sequence fragments of the genome. A skilled artisan can readily recognize that any one of the publicly available homology search programs can be used as the search means for the computer based systems of the present invention.
As discussed above, the "library" of the invention also encompasses biochemical libraries of the polynucleotides of "SEQ ID NOS: 1-5252," e.g., collections of nucleic acids representing the provided polynucleotides. The biochemical libraries can take a variety of forms, e.g., a solution of cDNAs, a pattern of probe nucleic acids stably associated with a surface of a solid support (i.e., an array) and the like. Of particular interest are nucleic acid arrays in which one or more of "SEQ ID NOS:l-5252"is represented on the array. By array is meant a an article of manufacture that has at least a substrate with at least two distinct nucleic acid targets on one of its surfaces, where the number of distinct nucleic acids can be considerably higher, typically being at least 10 nt, usually at least 20 nt and often at least 25 nt. A variety of different array formats have been developed and are known to those of
skill in the art, including those described in 5,242,974; 5,384,261; 5,405,783; 5,412,087; 5,424,186; 5,429,807; 5,436,327; 5,445,934; 5,472,672; 5,527,681 ; 5,529,756; 5,545,531; 5,554,501; 5,556,752; 5,561,071; 5,599,895; 5,624,711; 5,639,603; 5,658,734; WO 93/17126; WO 95/11995; WO 95/35505; EP 742287; and EP 799897. The arrays of the subject invention find use in a variety of applications, including gene expression analysis, drug screening, mutation analysis and the like, as disclosed in the above-listed exemplary patent documents.
In addition to the above nucleic acid libraries, analogous libraries of polypeptides are also provided, where the where the polypeptides of the library will represent at least a portion of the polypeptides encoded by "SEQ ID NOS: 1-5252."
VII. Utilities
A. Use of Polynucleotide Probes in Mapping, and in Tissue Profiling Polynucleotide probes, generally comprising at least 12 contiguous nucleotides of a polynucleotide as shown in the Sequence Listing, are used for a variety of purposes, such as chromosome mapping of the polynucleotide and detection of transcription levels. Additional disclosure about preferred regions of the disclosed polynucleotide sequences is found in the Examples. A probe that hybridizes specifically to a polynucleotide disclosed herein should provide a detection signal at least 5-, 10-, or 20-fold higher than the background hybridization provided with other unrelated sequences.
Probes in Detection of Expression Levels. Nucleotide probes are used to detect expression of a gene corresponding to the provided polynucleotide. In Northern blots, mRNA is separated electrophoretically and contacted with a probe. A probe is detected as hybridizing to an mRNA species of a particular size. The amount of hybridization is quantitated to determine relative amounts of expression, for example under a particular condition. Probes are used for in situ hybridization to cells to detect expression. Probes can also be used in vivo for diagnostic detection of hybridizing sequences. Probes are typically labeled with a radioactive isotope. Other types of detectable labels can be used such as chromophores, fluors, and enzymes. Other examples of nucleotide hybridization assays are described in WO92/02526 and U.S. Patent No. 5,124,246.
The Polymerase Chain Reaction (PCR) is another means for detecting small amounts of target nucleic acids (see, e.g., Mullis et al, Meth. Enzymol (1987) 755:335; U.S. Patent No. 4,683,195; and U.S. Patent No. 4,683,202). Two primer polynucleotides nucleotides hybridize with the target nucleic acids and are used to prime the reaction. The primers can be composed of sequence within or 3' and 5' to the polynucleotides of the Sequence Listing. Alternatively, if the primers are 3' and 5' to these polynucleotides, they need not hybridize to them or the complements. A thermostable polymerase creates copies of target nucleic acids from the primers using the original target nucleic acids as a template. After a large amount of target nucleic acids is generated by the polymerase, it is detected by methods such as Southern blots. When using the Southern blot method, the labeled probe will hybridize to a polynucleotide of the Sequence Listing or complement.
Furthermore, mRNA or cDNA can be detected by traditional blotting techniques described in Sambrook et al, "Molecular Cloning: A Laboratory Manual" (New York, Cold Spring Harbor Laboratory, 1989). mRNA or cDNA generated from mRNA using a polymerase enzyme can be purified and separated using gel electrophoresis. The nucleic acids on the gel are then blotted onto a solid support, such as nitrocellulose. The solid support is exposed to a labeled probe and then washed to remove any unhybridized probe. Next, the duplexes containing the labeled probe are detected. Typically, the probe is labeled with radioactivity. Mapping. Polynucleotides of the present invention are used to identify a chromosome on which the corresponding gene resides. Such mapping can be useful in identifying the function of the polynucleotide-related gene by its proximity to other genes with known function. Function can also be assigned to the polynucleotide-related gene when particular syndromes or diseases map to the same chromosome. For example, use of polynucleotide probes in identification and quantification of nucleic acid sequence aberrations is described in U.S. Patent No. 5,783,387.
For example, fluorescence in situ hybridization (FISH) on normal metaphase spreads facilitates comparative genomic hybridization to allow total genome assessment of changes in relative copy number of DNA sequences. See Schwartz and Samad, Curr. Opin. Biotechnol (1994) 3:70; Kallioniemi et al, Sem. Cancer Biol (1993) 4:41; Valdes
et al, Methods in Molecular Biology (1997) 63:1, Boultwood, ed., Human Press, Totowa, NJ.
Polynucleotides are mapped to particular chromosomes using, for example, radiation hybrids or chromosome-specific hybrid panels. See Leach et al, Advances in Genetics, (1995) 33:63-99; Walter et al, Nature Genetics (1994) 7:22; Walter and
Goodfellow, Trends in Genetics (1992) 9:352. Panels for radiation hybrid mapping are available from Research Genetics, Inc., Huntsville, Alabama, USA. Databases for markers using various panels are available via the world wide web at http:/F/shgc- www.stanford.edu; and http://www-genome.wi.mit.edu/cgi-bin/contig/rhmapper.pl. The statistical program RHMAP can be used to construct a map based on the data from radiation hybridization with a measure of the relative likelihood of one order versus another. RHMAP is available via the world wide web at http://www.sph.umich.edu/group/statgen/software.
In addition, commercial programs are available for identifying regions of chromosomes commonly associated with disease, such as cancer. Polynucleotides based on the polynucleotides of the invention can be used to probe these regions. For example, if through profile searching a provided polynucleotide is identified as corresponding to a gene encoding a kinase, its ability to bind to a cancer-related chromosomal region will suggest its role as a kinase in one or more stages of tumor cell development growth. Although some experimentation would be required to elucidate the role, the polynucleotide constitutes a new material for isolating a specific protein that has potential for developing a cancer diagnostic or therapeutic.
Tissue Typing or Profiling. Expression of specific mRNA corresponding to the provided polynucleotides can vary in different cell types and can be tissue-specific. This variation of mRNA levels in different cell types can be exploited with nucleic acid probe assays to determine tissue types. For example, PCR, branched DNA probe assays, or blotting techniques utilizing nucleic acid probes substantially identical or complementary to polynucleotides listed in the Sequence Listing can determine the presence or absence of the corresponding cDNA or mRNA. For example, a metastatic lesion is identified by its developmental organ or tissue source by identifying the expression of a particular marker of that organ or tissue. If a
polynucleotide is expressed only in a specific tissue type, and a metastatic lesion is found to express that polynucleotide, then the developmental source of the lesion has been identified. Expression of a particular polynucleotide is assayed by detection of either the corresponding mRNA or the protein product. Immunological methods, such as antibody staining, are used to detect a particular protein product. Hybridization methods can be used to detect particular mRNA species, including but not limited to in situ hybridization and Northern blotting.
Use of Polymorphisms. A polynucleotide of the invention will be useful in forensics, genetic analysis, mapping, and diagnostic applications if the corresponding region of a gene is polymoφhic in the human population. Particular polymoφhic forms of the provided polynucleotides can be used to either identify a sample as deriving from a suspect or rule out the possibility that the sample derives from the suspect. Any means for detecting a polymoφhism in a gene are used, including but not limited to electrophoresis of protein polymoφhic variants, differential sensitivity to restriction enzyme cleavage, and hybridization to allele-specific probes. B. Antibody Production
Expression products of a polynucleotide of the invention, the corresponding mRNA or cDNA, or the corresponding complete gene are prepared and used for raising antibodies for experimental, diagnostic, and therapeutic puφoses. For polynucleotides to which a corresponding gene has not been assigned, this provides an additional method of identifying the corresponding gene. The polynucleotide or related cDNA is expressed as described above, and antibodies are prepared. These antibodies are specific to an epitope on the polypeptide encoded by the polynucleotide, and can precipitate or bind to the corresponding native protein in a cell or tissue preparation or in a cell-free extract of an in vitro expression system.
Immunogens for raising antibodies are prepared by mixing the polypeptides encoded by the polynucleotides of the present invention with adjuvants. Alternatively, polypeptides are made as fusion proteins to larger immunogenic proteins. Polypeptides are also covalently linked to other larger immunogenic proteins, such as keyhole limpet hemocyanin. Immunogens are typically administered intradermally, subcutaneously, or intramuscularly. Immunogens are administered to experimental animals such as rabbits,
sheep, and mice, to generate antibodies. Optionally, the animal spleen cells are isolated and fused with myeloma cells to form hybridomas which secrete monoclonal antibodies. Such methods are well known in the art. According to another method known in the art, the selected polynucleotide is administered directly, such as by intramuscular injection, and expressed in vivo. The expressed protein generates a variety of protein-specific immune responses, including production of antibodies, comparable to administration of the protein.
Preparations of polyclonal and monoclonal antibodies specific for polypeptides encoded by a selected polynucleotide are made using standard methods known in the art. The antibodies specifically bind to epitopes present in the polypeptides encoded by polynucleotides disclosed in the Sequence Listing. Typically, at least 6, 8, 10, or 12 contiguous amino acids are required to form an epitope. However, epitopes which involve non-contiguous amino acids may require more, for example at least 15, 25, or 50 amino acids. A short sequence of a polynucleotide may then be unsuitable for use as an epitope to raise antibodies for identifying the corresponding novel protein, because of the potential for cross-reactivity with a known protein. However, the antibodies can be useful for other puφoses, particularly if they identify common structural features of a known protein and a novel polypeptide encoded by a polynucleotide of the invention.
Antibodies that specifically bind to human polypeptides encoded by the provided polypeptides should provide a detection signal at least 5-, 10-, or 20-fold higher than a detection signal provided with other proteins when used in Western blots or other immunochemical assays. Preferably, antibodies that specifically polypeptides of the invention do not bind to other proteins in immunochemical assays at detectable levels and can immunoprecipitate the specific polypeptide from solution.
To test for the presence of serum antibodies to the polypeptide of the invention in a human population, human antibodies are purified by methods well known in the art.
Preferably, the antibodies are affinity purified by passing antiserum over a column to which the corresponding selected polypeptide or fusion protein is bound. The bound antibodies can then be eluted from the column, for example using a buffer with a high salt concentration.
In addition to the antibodies discussed above, genetically engineered antibody derivatives are made, such as single chain antibodies, according to methods well known in the art.
C. Use of Polynucleotides to Construct Arrays for Diagnostics Polynucleotide arrays provide a high throughput technique that can assay a large number of polynucleotide sequences in a sample. This technology can be used as a diagnostic and as a tool to test for differential expression to determine function of an encoded protein. Arrays can be created by spotting polynucleotide probes onto a substrate (e.g., glass, nitrocelllose, etc.) in a two-dimensional matrix or array having bound probes. The probes can be bound to the substrate by either covalent bonds or by non-specific interactions, such as hydrophobic interactions. Samples of polynucleotides can be detectably labeled (e.g., using radioactive or fluorescent labels) and then hybridized to the probes. Double stranded polynucleotides, comprising the labeled sample polynucleotides bound to probe polynucleotides, can be detected once the unbound portion of the sample is washed away. Techniques for constructing arrays and methods of using these arrays are described in EP No. 0 799 897; PCT No. WO 97/29212; PCT No. WO 97/27317; EP No. 0 785 280; PCT No. WO 97/02357; U.S. Pat. No. 5,593,839; U.S. Pat. No. 5,578,832; EP No. 0 728 520; U.S. Pat. No. 5,599,695; EP No. 0 721 016; U.S. Pat. No. 5,556,752; PCT No. WO 95/22058; and U.S. Pat. No. 5,631,734. As discussed in some detail above, arrays can be used to examine differential expression of genes and can be used to determine gene function. For example, arrays of the instant polynucleotide sequences can be used to determine if any of the provided polynucleotides are differentially expressed between a test cell and control cell (e.g., cancer cells and normal cells). For example, high expression of a particular message in a cancer cell, which is not observed in a corresponding normal cell, can indicate a cancer specific protein. Exemplary uses of arrays are further described in, for example, Pappalarado et al, Sem. Radiation Oncol (1998) 3:217; and Ramsay Nature Biotechnol (1998) 76:40.
D. Differential Expression
The polynucleotides of the invention can also be used to detect differences in expression levels between two cells, e.g. , as a method to identify abnormal or diseased tissue in a human. For polynucleotides corresponding to profiles of protein families, the
choice of tissue can be selected according to the putative biological function. In general, the expression of a gene corresponding to a specific polynucleotide is compared between a first tissue that is suspected of being diseased and a second, normal tissue of the human. The tissue suspected of being abnormal or diseased can be derived from a different tissue type of the human, but preferably it is derived from the same tissue type; for example an intestinal polyp or other abnormal growth should be compared with normal intestinal tissue. The normal tissue can be the same tissue as that of the test sample, or any normal tissue of the patient, especially those that express the polynucleotide-related gene of interest (e.g., brain, thymus, testis, heart, prostate, placenta, spleen, small intestine, skeletal muscle, pancreas, and the mucosal lining of the colon). A difference between the polynucleotide-related gene, mRNA, or protein in the two tissues which are compared, for example in molecular weight, amino acid or nucleotide sequence, or relative abundance, indicates a change in the gene, or a gene which regulates it, in the tissue of the human that was suspected of being diseased. Examples of detection of differential expression and its use in diagnosis of cancer are described in U.S. Patent Nos. 5,688,641 and 5,677,125. The polynucleotide-related genes in the two tissues are compared by any means known in the art. For example, the two genes can be sequenced, and the sequence of the gene in the tissue suspected of being diseased compared with the gene sequence in the normal tissue. The genes corresponding to a provided polynucleotide, or portions thereof, in the two tissues are amplified, for example using nucleotide primers based on the nucleotide sequence shown in the Sequence Listing, using the polymerase chain reaction. The amplified genes or portions of genes are hybridized to detectably labeled nucleotide probes selected from a nucleotide sequence shown in the Sequence Listing. A difference in the nucleotide sequence of the isolated gene in the tissue suspected of being diseased compared with the normal nucleotide sequence suggests a role of the gene product encoded by the subject polynucleotide in the disease, and provides guidance for preparing a therapeutic agent.
Alternatively, mRNA corresponding to a provided polynucleotide in the two tissues is compared. PolyA+ RNA is isolated from the two tissues as is known in the art. For example, one of skill in the art can readily determine differences in the size or amount of mRNA transcripts between the two tissues using Northern blots and detectably labeled
nucleotide probes selected from the nucleotide sequence shown in the Sequence Listing. Increased or decreased expression of a given mRNA in a tissue sample suspected of being diseased, compared with the expression of the same mRNA in a normal tissue, suggests that the expressed protein has a role in the disease, and also provides a lead for preparing a therapeutic agent.
The comparison can also be accomplished by analyzing polypeptides between the matched samples. The sizes of the proteins in the two tissues are compared, for example, using antibodies of the present invention to detect polypeptides in Western blots of protein extracts from the two tissues. Other changes, such as expression levels and subcellular localization, can also be detected immunologically, using antibodies to the corresponding protein. A higher or lower level of expression of a given polypeptide in a tissue suspected of being diseased, compared with the same protein expression level in a normal tissue, is indicative that the expressed protein has a role in the disease, and provides guidance for preparing a therapeutic agent. Similarly, comparison of polynucleotide sequences or of gene expression products, e.g., mRNA and protein, between a human tissue that is suspected of being diseased and a normal tissue of a human, are used to follow disease progression or remission in the human. Such comparisons are made as described above. For example, increased or decreased expression of a gene corresponding to an inventive polynucleotide in the tissue suspected of being neoplastic can indicate the presence of neoplastic cells in the tissue. The degree of increased expression of a given gene in the neoplastic tissue relative to expression of the same gene in normal tissue, or differences in the amount of increased expression of a given gene in the neoplastic tissue over time, is used to assess the progression of the neoplasia in that tissue or to monitor the response of the neoplastic tissue to a therapeutic protocol over time.
The expression pattern of any two cell types can be compared, such as low and high metastatic tumor cell lines, malignant or non-malignant cells, or cells from tissue which have and have not been exposed to a therapeutic agent. A genetic predisposition to disease in a human is detected by comparing expression levels of an mRNA or protein corresponding to a polynucleotide of the invention in a fetal tissue with levels associated in normal fetal tissue. Fetal tissues that are used for this puφose include, but are not limited
to, amniotic fluid, chorionic villi, blood, and the blastomere of an in vitro-fertilized embryo. The comparable normal polynucleotide-related gene is obtained from any tissue. The mRNA or protein is obtained from a normal tissue of a human in which the polynucleotide-related gene is expressed. Differences such as alterations in the nucleotide sequence or size of the same product of the fetal polynucleotide-related gene or mRNA, or alterations in the molecular weight, amino acid sequence, or relative abundance of fetal protein, can indicate a germline mutation in the polynucleotide-related gene of the fetus, which indicates a genetic predisposition to disease. Particular diagnostic and prognostic uses of the disclosed polynucleotides are described in more detail below. E. Diagnostic. Prognostic, and Other Uses Based On Differential Expression
In general, diagnostic methods of the invention for involve detection of a level or amount of a gene product, particularly a differentially expressed gene product, in a test sample obtained from a patient suspected of having or being susceptible to a disease (e.g., breast cancer, lung cancer, colon cancer and/or metastatic forms thereof), and comparing the detected levels to those levels found in normal cells (e.g., cells substantially unaffected by cancer) and/or other control cells (e.g., to differentiate a cancerous cell from a cell affected by dysplasia). Furthermore, the severity of the disease can be assessed by comparing the detected levels of a differentially expressed gene product with those levels detected in samples representing the levels of differentially gene product associated with varying degrees of severity of disease.
The term "differentially expressed gene" is intended to encompass a polynucleotide that can, for example, include an open reading frame encoding a gene product (e.g., a polypeptide), and/or introns of such genes and adjacent 5' and 3' non-coding nucleotide sequences involved in the regulation of expression, up to about 20 kb beyond the coding region, but possibly further in either direction. The gene can be introduced into an appropriate vector for extrachromosomal maintenance or for integration into a host genome. In general, a difference in expression level associated with a decrease in expression level of at least about 25%, usually at least about 50% to 75%, more usually at least about 90% or more is indicative of a differentially expressed gene of interest, i.e., a gene that is underexpressed or down-regulated in the test sample relative to a control sample. Furthermore, a difference in expression level associated with an increase in
expression ofat least about 25%, usually at least about 50% to 75%, more usually at least about 90% and can be at least about 1 ' -fold, usually at least about 2-fold to about 10-fold, and can be about 100-fold to about 1 ,000-fold increase relative to a control sample is indicative of a differentially expressed gene of interest, i.e., an overexpressed or up- regulated gene.
"Differentially expressed polynucleotide" as used herein means a nucleic acid molecule (RNA or DNA) having a sequence that represents a differentially expressed gene, e.g., the differentially expressed polynucleotide comprises a sequence (e.g., an open reading frame encoding a gene product) that uniquely identifies a differentially expressed gene so that detection of the differentially expressed polynucleotide in a sample is correlated with the presence of a differentially expressed gene in a sample. "Differentially expressed polynucleotides" is also meant to encompass fragments of the disclosed polynucleotides, e.g., fragments retaining biological activity, as well as nucleic acids homologous, substantially similar, or substantially identical (e.g., having about 90%> sequence identity) to the disclosed polynucleotides.
Methods of the subject invention useful in diagnosis or prognosis typically involve comparison of the abundance of a selected differentially expressed gene product in a sample of interest with that of a control to determine any relative differences in the expression of the gene product, where the difference can be measured qualitatively and/or quantitatively. Quantitation can be accomplished, for example, by comparing the level of expression product detected in the sample with the amounts of product present in a standard curve. A comparison can be made visually; by using a technique such as densitometry, with or without computerized assistance; by preparing a representative library of cDNA clones of mRNA isolated from a test sample, sequencing the clones in the library to determine that number of cDNA clones corresponding to the same gene product, and analyzing the number of clones corresponding to that same gene product relative to the number of clones of the same gene product in a control sample; or by using an array to detect relative levels of hybridization to a selected sequence or set of sequences, and comparing the hybridization pattern to that of a control. The differences in expression are then correlated with the presence or absence of an abnormal expression pattern. A variety of different methods for determining the nucleic acid abundance in a sample are known to
those of skill in the art, where particular methods of interest include those described in: Pietu et al Genome Res. (1996) 6:492; Zhao et al, Gene (1995) 756:207; Soares , Curr. Opin. Biotechnol. (1977) 3: 542; Raval, J Pharmacol Toxicol Methods (1994) 32:125; Chalifour et al, Anal Biochem (1994) 276:299; Stolz et al, Mol Biotechnol. (1996) 6:225; Hong et al, Bioscl Reports (1982) 2:907; and McGraw, Anal. Biochem. (1984) 743:298. Also of interest are the methods disclosed in WO 97/27317, the disclosure of which is herein incoφorated by reference.
In general, diagnostic assays of the invention involve detection of a gene product of a the polynucleotide sequence (e.g., mRNA or polypeptide) that corresponds to a sequence of "SEQ ID NOS: 1-5252." The patient from whom the sample is obtained can be apparently healthy, susceptible to disease (e.g., as determined by family history or exposure to certain environmental factors), or can already be identified as having a condition in which altered expression of a gene product of the invention is implicated.
In the assays of the invention, the diagnosis can be determined based on detected gene product expression levels of a gene product encoded by at least one, preferably at least two or more, at least 3 or more, or at least 4 or more of the polynucleotides having a sequence set forth in "SEQ ID NOS: 1-5252," and can involve detection of expression of genes corresponding to all of "SEQ ID NOS: 1-5252" and/or additional sequences that can serve as additional diagnostic markers and/or reference sequences. Where the diagnostic method is designed to detect the presence or susceptibility of a patient to cancer, the assay preferably involves detection of a gene product encoded by a gene corresponding to a polynucleotide that is differentially expressed in cancer. For example, a higher level of expression of a polynucleotide corresponding to SEQ ID NO:2024 relative to a level associated with a normal sample can indicate the presence of cancer in the patient from whom the sample is derived. In another example, detection of a lower level of a polynucleotide corresponding to SEQ ID NO:590 relative to a normal level is indicative of the presence of cancer in the patient. Further examples of such differentially expressed polynucleotides are described in the Examples below. Given the provided polynucleotides and information regarding their relative expression levels provided herein, assays using such polynucleotides and detection of their expression levels in diagnosis and prognosis will be readily apparent to the ordinarily skilled artisan.
Any of a variety of detectable labels can be used in connection with the various embodiments of the diagnostic methods of the invention. Suitable detectable labels include fluorochromes,(e.g. fluorescein isothiocyanate (FITC), rhodamine, Texas Red, phycoerythrin, allophycocyanin, 6-carboxyfluorescein (6-FAM), 2',7'-dimethoxy-4',5'- dichloro-6-carboxyfluorescein, 6-carboxy-X-rhodamine (ROX), 6-carboxy-2',4',7',4,7- hexachlorofluorescein (HEX), 5 -carboxy fluorescein (5-FAM) or N,N,N',N'-tetramethyl-6- carboxyrhodamine (TAMRA)), radioactive labels, (e.g. 32P, 35S, 3H, etc.), and the like. The detectable label can involve a two stage systems (e.g., biotin-avidin, hapten-anti-hapten antibody, etc.) Reagents specific for the polynucleotides and polypeptides of the invention, such as antibodies and nucleotide probes, can be supplied in a kit for detecting the presence of an expression product in a biological sample. The kit can also contain buffers or labeling components, as well as instructions for using the reagents to detect and quantify expression products in the biological sample. Exemplary embodiments of the diagnostic methods of the invention are described below in more detail.
Polypeptide detection in diagnosis. In one embodiment, the test sample is assayed for the level of a differentially expressed polypeptide. Diagnosis can be accomplished using any of a number of methods to determine the absence or presence or altered amounts of the differentially expressed polypeptide in the test sample. For example, detection can utilize staining of cells or histological sections with labeled antibodies, performed in accordance with conventional methods. Cells can be permeabilized to stain cytoplasmic molecules. In general, antibodies that specifically bind a differentially expressed polypeptide of the invention are added to a sample, and incubated for a period of time sufficient to allow binding to the epitope, usually at least about 10 minutes. The antibody can be detectably labeled for direct detection (e.g., using radioisotopes, enzymes, fluorescers, chemiluminescers, and the like), or can be used in conjunction with a second stage antibody or reagent to detect binding (e.g., biotin with horseradish peroxidase- conjugated avidin, a secondary antibody conjugated to a fluorescent compound, e.g. fluorescein, rhodamine, Texas red, etc.). The absence or presence of antibody binding can be determined by various methods, including flow cytometry of dissociated cells, microscopy, radiography, scintillation counting, etc. Any suitable alternative methods can
of qualitative or quantitative detection of levels or amounts of differentially expressed polypeptide can be used, for example ELISA, western blot, immunoprecipitation, radioimmunoassay, etc.
In general, the detected level of differentially expressed polypeptide in the test sample is compared to a level of the differentially expressed gene product in a reference or control sample, e.g., in a normal cell (negative control) or in a cell having a known disease state (positive control). mRNA detection. The diagnostic methods of the invention can also or alternatively involve detection of mRNA encoded by a gene corresponding to a differentially expressed polynucleotides of the invention. Any suitable qualitative or quantitative methods known in the art for detecting specific mRNAs can be used. mRNA can be detected by, for example, in situ hybridization in tissue sections, by reverse transcriptase-PCR, or in Northern blots containing poly A+ mRNA. One of skill in the art can readily use these methods to determine differences in the size or amount of mRNA transcripts between two samples. For example, the level of mRNA of the invention in a tissue sample suspected of being cancerous or dysplastic is compared with the expression of the mRNA in a reference sample, e.g., a positive or negative control sample (e.g., normal tissue, cancerous tissue, etc.).
Any suitable method for detecting and comparing mRNA expression levels in a sample can be used in connection with the diagnostic methods of the invention (see, e.g., U.S. 5,804,382). For example, mRNA expression levels in a sample can be determined by generation of a library of expressed sequence tags (ESTs) from the sample, where the EST library is representative of sequences present in the sample (Adams, et al., (1991) Science 252:1651). Enumeration of the relative representation of ESTs within the library can be used to approximate the relative representation of the gene transcript within the starting sample. The results of EST analysis of a test sample can then be compared to EST analysis of a reference sample to determine the relative expression levels of a selected polynucleotide, particularly a polynucleotide corresponding to one or more of the differentially expressed genes described herein. Alternatively, gene expression in a test sample can be performed using serial analysis of gene expression (SAGE) methodology (Velculescu et al., Science (1995)
270:484). In short, SAGE involves the isolation of short unique sequence tags from a specific location within each transcript. The sequence tags are concatenated, cloned, and sequenced. The frequency of particular transcripts within the starting sample is reflected by the number of times the associated sequence tag is encountered with the sequence population.
Gene expression in a test sample can also be analyzed using differential display (DD) methodology. In DD, fragments defined by specific sequence delimiters (e.g., restriction enzyme sites) are used as unique identifiers of genes, coupled with information about fragment length or fragment location within the expressed gene. The relative representation of an expressed gene with a sample can then be estimated based on the relative representation of the fragment associated with that gene within the pool of all possible fragments. Methods and compositions for carrying out DD are well known in the art, see, e.g., U.S. 5,776,683; and U.S. 5,807,680.
Alternatively, gene expression in a sample using hybridization analysis, which is based on the specificity of nucleotide interactions. Oligonucleotides or cDNA can be used to selectively identify or capture DNA or RNA of specific sequence composition, and the amount of RNA or cDNA hybridized to a known capture sequence determined qualitatively or quantitatively, to provide information about the relative representation of a particular message within the pool of cellular messages in a sample. Hybridization analysis can be designed to allow for concurrent screening of the relative expression of hundreds to thousands of genes by using, for example, array-based technologies having high density formats, including filters, microscope slides, or microchips, or solution-based technologies that use spectroscopic analysis (e.g., mass spectrometry). One exemplary use of arrays in the diagnostic methods of the invention is described below in more detail.
Use of a single gene in diagnostic applications. The diagnostic methods of the invention can focus on the expression of a single differentially expressed gene. For example, the diagnostic method can involve detecting a differentially expressed gene, or a polymoφhism of such a gene (e.g., a polymoφhism in an coding region or control region), that is associated with disease. Disease-associated polymoφhisms can include deletion or truncation of the gene, mutations that alter expression level and/or affect activity of the encoded protein, etc.
Changes in the promoter or enhancer sequence that affect expression levels of an differentially gene can be compared to expression levels of the normal allele by various methods known in the art. Methods for determining promoter or enhancer strength include quantitation of the expressed natural protein; insertion of the variant control element into a vector with a reporter gene such as β-galactosidase, luciferase, chloramphenicol acetyltransferase, etc. that provides for convenient quantitation; and the like.
A number of methods are available for analyzing nucleic acids for the presence of a specific sequence, e.g. a disease associated polymoφhism. Where large amounts of DNA are available, genomic DNA is used directly. Alternatively, the region of interest is cloned into a suitable vector and grown in sufficient quantity for analysis. Cells that express a differentially expressed gene can be used as a source of mRNA, which can be assayed directly or reverse transcribed into cDNA for analysis. The nucleic acid can be amplified by conventional techniques, such as the polymerase chain reaction (PCR), to provide sufficient amounts for analysis, and a detectable label can be included in the amplification reaction (e.g., using a detectably labeled primer or detectably labeled oligonucleotides) to facilitate detection. The use of the polymerase chain reaction is described in Saiki, et al, Science (1985) 239:487, and a review of techniques can be found in Sambrook, et al, Molecular Cloning: A Laboratory Manual, (1989) pp. 14.2. Alternatively, various methods are known in the art that utilize oligonucleotide ligation as a means of detecting polymoφhisms, for examples see Riley et al, Nucl Acids Res. (1990) 73:2887; and Delahunty et al, Am. J. Hum. Genet. (1996) 53:1239.
The sample nucleic acid, e.g. amplified or cloned fragment, is analyzed by one of a number of methods known in the art. The nucleic acid can be sequenced by dideoxy or other methods, and the sequence of bases compared to a selected sequence, e.g., to a wild-
type sequence. Hybridization with the polymoφhic or variant sequence can also be used to determine its presence in a sample (e.g., by Southern blot, dot blot, etc.). The hybridization pattern of a polymoφhic or variant sequence and a control sequence to an array of oligonucleotide probes immobilized on a solid support, as described in US 5,445,934, or in WO 95/35505, can also be used as a means of identifying polymoφhic or variant sequences associated with disease. Single strand conformational polymoφhism (SSCP) analysis, denaturing gradient gel electrophoresis (DGGE), and heteroduplex analysis in gel matrices are used to detect conformational changes created by DNA sequence variation as alterations in electrophoretic mobility. Alternatively, where a polymoφhism creates or destroys a recognition site for a restriction endonuclease, the sample is digested with that endonuclease, and the products size fractionated to determine whether the fragment was digested. Fractionation is performed by gel or capillary electrophoresis, particularly acrylamide or agarose gels.
Screening for mutations in an differentially expressed gene can be based on the functional or antigenic characteristics of the protein. Protein truncation assays are useful in detecting deletions that can affect the biological activity of the protein. Various immunoassays designed to detect polymoφhisms in proteins can be used in screening. Where many diverse genetic mutations lead to a particular disease phenotype, functional protein assays have proven to be effective screening tools. The activity of the encoded protein can be determined by comparison with the wild-type protein.
Pattern matching in diagnosis using arrays. In another embodiment, the diagnostic and/or prognostic methods of the invention involve detection of expression of a selected set of genes in a test sample to produce a test expression pattern (TEP). The TEP is compared to a reference expression pattern (REP), which is generated by detection of expression of the selected set of genes in a reference sample (e.g., a positive or negative control sample). The selected set of genes includes at least one of the genes of the invention, which genes correspond to the polynucleotide sequences of "SEQ ID NOS: 1-5252." Of particular interest is a selected set of genes that includes gene differentially expressed in the disease for which the test sample is to be screened. "Reference sequences" or "reference polynucleotides" as used herein in the context of differential gene expression analysis and diagnosis/prognosis refers to a selected set of
polynucleotides, which selected set includes at least one or more of the differentially expressed polynucleotides described herein. A plurality of reference sequences, preferably comprising positive and negative control sequences, can be included as reference sequences. Additional suitable reference sequences are found in Genbank, Unigene, and other nucleotide sequence databases (including, e.g., expressed sequence tag (EST), partial, and full-length sequences).
"Reference array" means an array having reference sequences for use in hybridization with a sample, where the reference sequences include all, at least one of, or any subset of the differentially expressed polynucleotides described herein. Usually such an array will include at least 3 different reference sequences, and can include any one or all of the provided differentially expressed sequences. Arrays of interest can further comprise sequences, including polymoφhisms, of other genetic sequences, particularly other sequences of interest for screening for a disease or disorder (e.g., cancer, dysplasia, or other related or unrelated diseases, disorders, or conditions). The oligonucleotide sequence on the array will usually be at least about 12 nt in length, and can be of about the length of the provided sequences, or can extend into the flanking regions to generate fragments of 100 nt to 200 nt in length or more.
A "reference expression pattern" or "REP" as used herein refers to the relative levels of expression of a selected set of genes, particularly of differentially expressed genes, that is associated with a selected cell type, e.g. , a normal cell, a cancerous cell, a cell exposed to an environmental stimulus, and the like. A "test expression pattern" or "TEP" refers to relative levels of expression of a selected set of genes, particularly of differentially expressed genes, in a test sample (e.g., a cell of unknown or suspected disease state, from which mRNA is isolated). "Diagnosis" as used herein generally includes determination of a subject's susceptibility to a disease or disorder, determination as to whether a subject is presently affected by a disease or disorder, as well as to the prognosis of a subject affected by a disease or disorder (e.g., identification of pre-metastatic or metastatic cancerous states, stages of cancer, or responsiveness of cancer to therapy). The present invention particularly encompasses diagnosis of subjects in the context of breast cancer (e.g. , carcinoma in situ (e.g., ductal carcinoma in situ), estrogen receptor (ER)-positive breast
cancer, ER-negative breast cancer, or other forms and/or stages of breast cancer), lung cancer (e.g., small cell carcinoma, non-small cell carcinoma, mesothelioma, and other forms and/or stages of lung cancer), and colon cancer (e.g., adenomatous polyp, colorectal carcinoma, and other forms and/or stages of colon cancer). "Sample" or "biological sample" as used throughout here are generally meant to refer to samples of biological fluids or tissues, particularly samples obtained from tissues, especially from cells of the type associated with the disease for which the diagnostic application is designed (e.g., ductal adenocarcinoma), and the like. "Samples" is also meant to encompass derivatives and fractions of such samples (e.g., cell lysates). Where the sample is solid tissue, the cells of the tissue can be dissociated or tissue sections can be analyzed.
REPs can be generated in a variety of ways according to methods well known in the art. For example, REPs can be generated by hybridizing a control sample to an array having a selected set of polynucleotides (particularly a selected set of differentially expressed polynucleotides), acquiring the hybridization data from the array, and storing the data in a format that allows for ready comparison of the REP with a TEP. Alternatively, all expressed sequences in a control sample can be isolated and sequenced, e.g., by isolating mRNA from a control sample, converting the mRNA into cDNA, and sequencing the cDNA. The resulting sequence information roughly or precisely reflects the identity and relative number of expressed sequences in the sample. The sequence information can then be stored in a format (e.g., a computer-readable format) that allows for ready comparison of the REP with a TEP. The REP can be normalized prior to or after data storage, and/or can be processed to selectively remove sequences of expressed genes that are of less interest or that might complicate analysis (e.g., some or all of the sequences associated with housekeeping genes can be eliminated from REP data).
TEPs can be generated in a manner similar to REPs, e.g., by hybridizing a test sample to an array having a selected set of polynucleotides, particularly a selected set of differentially expressed polynucleotides, acquiring the hybridization data from the array, and storing the data in a format that allows for ready comparison of the TEP with a REP. The REP and TEP to be used in a comparison can be generated simultaneously, or the TEP can be compared to previously generated and stored REPs.
In one embodiment of the invention, comparison of a TEP with a REP involves hybridizing a test sample with a reference array, where the reference array has one or more reference sequences for use in hybridization with a sample. The reference sequences include all, at least one of, or any subset of the differentially expressed polynucleotides described herein. Hybridization data for the test sample is acquired, the data normalized, and the produced TEP compared with a REP generated using an array having the same or similar selected set of differentially expressed polynucleotides. Probes that correspond to sequences differentially expressed between the two samples will show decreased or increased hybridization efficiency for one of the samples relative to the other. Reference arrays can be produced according to any suitable methods known in the art. For example, methods of producing large arrays of oligonucleotides are described in U.S. 5,134,854, and U.S. 5,445,934 using light-directed synthesis techniques. Using a computer controlled system, a heterogeneous array of monomers is converted, through simultaneous coupling at a number of reaction sites, into a heterogeneous array of polymers. Alternatively, microarrays are generated by deposition of pre-synthesized oligonucleotides onto a solid substrate, for example as described in PCT published application no. WO 95/35505.
Methods for collection of data from hybridization of samples with a reference arrays are also well known in the art. For example, the polynucleotides of the reference and test samples can be generated using a detectable fluorescent label, and hybridization of the polynucleotides in the samples detected by scanning the microarrays for the presence of the detectable label. Methods and devices for detecting fluorescently marked targets on devices are known in the art. Generally, such detection devices include a microscope and light source for directing light at a substrate. A photon counter detects fluorescence from the substrate, while an x-y translation stage varies the location of the substrate. A confocal detection device that can be used in the subject methods is described in U.S. Patent no. 5,631,734. A scanning laser microscope is described in Shalon et al., Genome Res. (1996) 6:639. A scan, using the appropriate excitation line, is performed for each fluorophore used. The digital images generated from the scan are then combined for subsequent analysis. For any particular array element, the ratio of the fluorescent signal from one
sample (e.g., a test sample) is compared to the fluorescent signal from another sample (e.g., a reference sample), and the relative signal intensity determined.
Methods for analyzing the data collected from hybridization to arrays are well known in the art. For example, where detection of hybridization involves a fluorescent label, data analysis can include the steps of determining fluorescent intensity as a function of substrate position from the data collected, removing outliers, i.e. data deviating from a predetermined statistical distribution, and calculating the relative binding affinity of the targets from the remaining data. The resulting data can be displayed as an image with the intensity in each region varying according to the binding affinity between targets and probes.
In general, the test sample is classified as having a gene expression profile corresponding to that associated with a disease or non-disease state by comparing the TEP generated from the test sample to one or more REPs generated from reference samples (e.g., from samples associated with cancer or specific stages of cancer, dysplasia, samples affected by a disease other than cancer, normal samples, etc.). The criteria for a match or a substantial match between a TEP and a REP include expression of the same or substantially the same set of reference genes, as well as expression of these reference genes at substantially the same levels (e.g., no significant difference between the samples for a signal associated with a selected reference sequence after normalization of the samples, or at least no greater than about 25% to about 40% difference in signal strength for a given reference sequence. In general, a pattern match between a TEP and a REP includes a match in expression, preferably a match in qualitative or quantitative expression level, ofat least one of, all or any subset of the differentially expressed genes of the invention.
Pattern matching can be performed manually, or can be performed using a computer program. Methods for preparation of substrate matrices (e.g., arrays), design of oligonucleotides for use with such matrices, labeling of probes, hybridization conditions, scanning of hybridized matrices, and analysis of patterns generated, including comparison analysis, are described in, for example, U.S. 5,800,992.
F. Use of the Polynucleotides of the Invention in Cancer Oncogenesis involves the unbridled growth, dedifferentiation and abnormal migration of cells. Cancerous cells can have the ability to compress, invade, and destroy
normal tissue. Cancerous cells may also metastasize to other parts of the body via the bloodstream or the lymph system and colonize in these other areas. Different cancers are classified by the cell from which the cancerous cell is derived and from its cellular moφhology and/or state of differentiation. Somatic genetic abnormalities cause cancer initiation and progression. Cancer generally is clonally formed, i.e. gain of function of oncogenes and loss of function of tumor suppressor genes within a single cell transform the cell to be cancerous, and that single cell grows and divides to form a cancerous lesion. The genes known to be involved in cancer initiation and progression are involved in numerous cellular functions, including developmental differentiation, cell cycle regulation, cell signaling, immunological response, DNA replication, and DNA repair.
The identification and characterization of genetic or biochemical markers in blood or tissues that will detect the earliest changes along the carcinogenesis pathway and monitor the efficacy of various therapies and preventive interventions is a major goal of cancer research. Scientists have identified genetic changes in stool specimens that indicate the stages of colon cancer, and other biomarkers such as gene mutations, hormone receptors, proteins that inhibit metastasis, and enzymes that metabolize drugs are all being used to determine the severity and predict the course of breast, prostate, lung, and other cancers. Recent advances in the pathogenesis of certain cancers has been helpful in determining patient treatment. The level of expression of certain polynucleotides can be indicative of a poorer prognosis, and therefore warrant more aggressive chemo- or radiotherapy for a patient. The correlation of novel surrogate tumor specific features with response to treatment and outcome in patients has defined certain prognostic indicators that allow the design of tailored therapy based on the molecular profile of the tumor. These therapies include antibody targeting and gene therapy. Moreover, a promising level of one or more marker polynucleotides can provide impetus for not aggressively treating a particular patient, thus sparing the patient the deleterious side effects of aggressive therapy. Determining expression of certain polynucleotides and comparison of a patients profile with known expression in normal tissue and variants of the disease allows
a determination of the best possible treatment for a patient, both in terms of specificity of treatment and in terms of comfort level of the patient.
Surrogate tumor markers, such as polynucleotide expression, can also be used to better classify, and thus diagnose and treat, different forms and disease states of cancer. Two classifications widely used in oncology that can benefit from identification of the expression levels of the polynucleotides of the invention are staging of the cancerous disorder, and grading the nature of the cancerous tissue.
Staging. Staging is a process used by physicians to describe how advanced the cancerous state is in a patient. Staging assists the physician in determining a prognosis, planning treatment and evaluating the results of such treatment. Different staging systems are used for different types of cancer, but each generally involves the following determinations: the type of tumor, indicated by T; whether the cancer has metastasized to nearby lymph nodes, indicated by N; and whether the cancer has metastasized to more distant parts of the body, indicated by M. This system of staging is called the TNM system. Generally, if a cancer is only detectable in the area of the primary lesion without having spread to any lymph nodes it is called Stage I. If it has spread only to the closest lymph nodes, it is called Stage II. In Stage III, the cancer has generally spread to the lymph nodes in near proximity to the site of the primary lesion. Cancers that have spread to a distant part of the body, such as the liver, bone, brain or another site, are called Stage IV, the most advanced stage.
Currently, the determination of staging is done using pathological techniques and is based more on the presence or absence of malignant tissue rather than the characteristics of the tumor type. Presence or absence of malignant tissue is based primarily on the gross moφhology of the cells in the areas biopsied. The polynucleotides of the invention can facilitate fine-tuning of the staging process by identifying markers for the aggresivity of a cancer, e.g. the metastatic potential, as well as the presence in different areas of the body. Thus, a Stage II cancer with a polynucleotide signifying a high metastatic potential cancer can be used to change a borderline Stage II tumor to a Stage III tumor, justifying more aggressive therapy. Conversely, the presence of a polynucleotide signifying a lower metastatic potential allows more conservative staging of a tumor.
Grading of cancers. Grade is a term used to describe how closely a tumor resembles normal tissue of its same type. Based on the microscopic appearance of a tumor, pathologists will identify the grade of a tumor based on parameters such as cell moφhology, cellular organization, and other markers of differentiation. As a general rule, the grade of a tumor corresponds to its rate of growth or aggressiveness. That is, undifferentiated or high-grade tumors grow more quickly than well differentiated or low- grade tumors. Information about tumor grade is useful in planning treatment and predicting prognosis.
The American Joint Commission on Cancer has recommended the following guidelines for grading tumors: 1) GX Grade cannot be assessed; 2) GI Well differentiated; G2 Moderately well differentiated; 3) G3 Poorly differentiated; 4) G4 Undifferentiated. Although grading is used by pathologists to describe most cancers, it plays a more important role in treatment planning for certain types than for others. An example is the Gleason system that is specific for prostate cancer, which uses grade numbers to describe the degree of differentiation. Lower Gleason scores indicate well-differentiated cells. Intermediate scores denote tumors with moderately differentiated cells. Higher scores describe poorly differentiated cells. Grade is also important in some types of brain tumors and soft tissue sarcomas.
The polynucleotides of the invention can be especially valuable in determining the grade of the tumor, as they not only can aid in determining the differentiation status of the cells of a tumor, they can also identify factors other than differentiation that are valuable in determining the aggressivity of a tumor, such as metastatic potential.
Familial Cancer Genes. A number of cancer syndromes are linked to Mendelian inheritance of a predisposition to develop particular cancers. The following table contains a list of cancer types that can be inherited, and for which the gene or genes responsible have been identified. Most of the cancer types listed can occur as part of several different genetic conditions, each caused by alterations in a different gene.
Cancer Type Genetic Condition Gene
Brain Li-Fraumeni syndrome TP53
Brain Neurofibromatosis 1 NF1
Neurofϊbromatosis 2 NF2 von Hippel-Lindau syndrome VHL
Cancer Type Genetic Condition Gene
Tuberous sclerosis 2 TSC2
Breast Hereditary breast/ovarian cancer 1 BRCA1 Hereditary breast/ovarian cancer 2 BRCA2 Li-Fraumeni syndrome TP53 Ataxia telangiectasia ATM
Colon Familial adenomatous polyposis (FAP) APC Hereditary non-polyposis colon cancer (HNPCC) 1 HMSH2 Hereditary non-polyposis colon cancer (HNPCC) 2 hMLHl Hereditary non-polyposis colon cancer (HNPCC) 3 hPMSl Hereditary non-polyposis colon cancer (HNPCC) 4 hPMS2
Endocrine Multiple endocrine neoplasia 1 (MEN1) MEN1
(parathyroid, pituitary, GI endocrine)
Endocrine Multiple endocrine neoplasia 2 (MEN2) RET
(pheochromacytoma, medullary thyroid)
Endometrial Hereditary non-polyposis colon cancer (HNPCC) 1 hMSH2 Hereditary non-polyposis colon cancer (HNPCC) 2 hMLHl Hereditary non-polyposis colon cancer (HNPCC) 3 hPMSl Hereditary non-polyposis colon cancer (HNPCC) 4 hPMS2
Eye Hereditary retinoblastoma RBI
Hematologic Li-Fraumeni syndrome TP53 (lymphomas and leukemia) Ataxia telangiectasia ATM
Kidney Hereditary Wilms' tumor WT1 von Hippel-Lindau syndrome VHL Tuberous sclerosis 2 TSC2
Ovary Hereditary breast/ovarian cancer 1 BRCA1 Hereditary breast/ovarian cancer 2 BRCA2
Sarcoma Hereditary retinoblastoma RBI Li-Fraumeni syndrome TP53 Neurofϊbromatosis 1 NF1
Skin Hereditary melanoma 1 CDKN2 Hereditary melanoma 2 CDK4 Basal cell naevus (Gorlin) syndrome PTCH
Stomach Hereditary non-polyposis colon cancer (HNPCC) 1 hMSH2 Hereditary non-polyposis colon cancer (HNPCC) 2 hMLHl Hereditary non-polyposis colon cancer (HNPCC) 3 hPMSl Hereditary non-polyposis colon cancer (HNPCC) 4 hPMS2
The polynucleotides of the invention can be especially useful to monitor patients having any of the above syndromes to detect potentially malignant events at a molecular level before they are detectable at a gross moφhological level. As can be seen from the table, a number of genes are involved in multiple forms of cancer. Thus, a polynucleotide of the invention identified as important for metastatic colon cancer can also have clinical implications for a patient diagnosed with stomach cancer or endometrial cancer.
Lung Cancer. Lung cancer is one of the most common cancers in the United States, accounting for about 15 percent of all cancer cases, or 170,000 new cases each year. At this time, over half of the lung cancer cases in the United States are in men, but the number found in women is increasing and will soon equal that in men. Today more women die of lung cancer than of breast cancer. Lung cancer is especially difficult to diagnose and treat because of the large size of the lungs, which allows cancer to develop for years undetected. In fact, lung cancer can spread outside the lungs without causing any symptoms. Adding to the confusion, the most common symptom of lung cancer, a persistent cough, can often be mistaken for a cold or bronchitis. Although there are more than a dozen different kinds of lung cancer, the two main types of lung cancer are small cell and nonsmall cell, which encompass about 90% of all lung cancer cases. Small cell carcinoma (also called oat cell carcinoma), which usually starts in one of the larger bronchial tubes, grows fairly rapidly, and is likely to be large by the time of diagnosis. Nonsmall cell lung cancer (NSCLC) is made up of three general subtypes of lung cancer. Epidermoid carcinoma (also called squamous cell carcinoma) usually starts in one of the larger bronchial tubes and grows relatively slowly. The size of these tumors can range from very small to quite large. Adenocarcinoma starts growing near the outside surface of the lung and can vary in both size and growth rate. Some slowly growing adenocarcinomas are described as alveolar cell cancer. Large cell carcinoma starts near the surface of the lung, grows rapidly, and the growth is usually fairly large when diagnosed. Other less common forms of lung cancer are carcinoid, cylindroma, mucoepidermoid, and malignant mesothelioma.
Currently, CT scans, MRIs, X-rays, sputum cytology, and biopsies are used to diagnose nonsmall cell lung cancer. The form and cellular origin of the lung cancer is diagnosed primarily through biopsy from either a surgical biopsy or a needle aspiration of lung tissue, and usually the biopsy is prompted from an abnormality identified on an X-ray. In some cases, sputum cytology can reveal lung cancers in patients with normal X-rays or can determine the type of lung cancer, but because it cannot pinpoint the tumor's location, a positive sputum cytology test is usually followed by further tests. Since these tests are based in large part on gross moφhology of the tissue, the diagnosis of a particular kind of tumor is largely subjective, and the diagnosis can vary significantly between clinicians.
The polynucleotides of the invention can be used to distinguish types of lung cancer as well as identifying traits specific to a certain patient's cancer. For example, if the patient's biopsy expresses a polynucleotide that is associated with a low metastatic potential, it may justify leaving a larger portion of the patient's lung in surgery to remove the lesion. Alternatively, a smaller lesion with expression of a polynucleotide that is associated with high metastatic potential may justify a more radical removal of lung tissue and/or the surrounding lymph nodes, even if no metastasis can be identified through pathological examination.
Similarly, the expression of polynucleotides of the invention can be used in the diagnosis, prognosis and management of colorectal cancer. The differential expression of a polynucleotide in hypeφlasia can be used as a diagnostic marker for metastatic lung cancer. The polynucleotides of the invention that would be especially useful for this puφose are those that exhibit differential expression between high metastatic versus low metastatic lung cancer , i.e. SEQ ID NOS: 174, 254, 466, 571, 574, 590, 922, 1355, 1422, 2007, 2038, 2245, 10, 54, 65, 171, 203, 252, 253, 285, 419, 420, 491, 525, 526, 552, 693, 700, 726, 742, 746, 861, 990, 1088, 1288, 1417, 1444, 1454, 1570, 1597, 1979, 2024, 2034, and 2126. Detection of malignant lung cancer with a higher metastatic potential can be determined using expression levels of any of these sequences alone or in combination with the levels of expression of other known genes. Breast Cancer. The National Cancer Institute (NCI) estimates that about 1 in 8 women in the United States will develop breast cancer during her lifetime. Clinical breast examination and mammography are recommended as combined modalities for breast cancer screening, and the nature of the cancer will often depend upon the location of the tumor and the cell type from which the tumor is derived. The majority of breast cancers are adenocarcinomas subtypes, which can be summarized as follows:
Ductal carcinoma in situ (DCIS): Ductal carcinoma in situ is the most common type of noninvasive breast cancer. In DCIS, the malignant cells have not metastasized through the walls of the ducts into the fatty tissue of the breast. Comedocarcinoma is a type of DCIS that is more likely than other types of DCIS to come back in the same area after lumpectomy. It is more closely linked to eventual development of invasive ductal carcinoma than other forms of DCIS.
Infiltrating (or invasive) ductal carcinoma (IDC): this type of cancer has metastasized through the wall of the duct and invaded the fatty tissue of the breast. At this point, it has the potential to use the lymphatic system and bloodstream for metastasis to more distant parts of the body. Infiltrating ductal carcinoma accounts for about 80% of breast cancers.
Lobular carcinoma in situ (LCIS): While not a true cancer, LCIS (also called lobular neoplasia) is sometimes classified as a type of noninvasive breast cancer. It does not penetrate through the wall of the lobules. Although it does not itself usually become an invasive cancer, women with this condition have a higher risk of developing an invasive breast cancer in the same breast, or in the opposite breast.
Infiltrating (or invasive) lobular carcinoma (ILC): ILC is similar to IDC, in that it has the potential metastasize elsewhere in the body. About 10% to 15% of invasive breast cancers are invasive lobular carcinomas. ILC can be more difficult to detect by mammogram than IDC. Inflammatory breast cancer: This rare type of invasive breast cancer accounts for about 1% of all breast cancers and is extremely aggressive. Multiple skin symptoms associated with this cancer are caused by cancer cells blocking lymph vessels or channels in the skin over the breast.
Medullary carcinoma: This special type of infiltrating breast cancer has a relatively well defined, distinct boundary between tumor tissue and normal tissue. It accounts for about 5% of breast cancers. The prognosis for this kind of breast cancer is better than for other types of invasive breast cancer.
Mucinous carcinoma: This rare type of invasive breast cancer originates from mucus-producing cells. The prognosis for mucinous carcinoma is better than for the more common types of invasive breast cancer.
Paget's disease of the nipple: This type of breast cancer starts in the ducts and spreads to the skin of the nipple and the areola. It is a rare type of breast cancer, occurring in only 1% of all cases. Paget's disease can be associated with in situ carcinoma, or with infiltrating breast carcinoma. If no lump can be felt in the breast tissue, and the biopsy shows DCIS but no invasive cancer, the prognosis is excellent.
Phyllodes tumor: This very rare type of breast tumor forms from the stroma of the breast, in contrast to carcinomas which develop in the ducts or lobules. Phyllodes (also spelled phylloides) tumors are usually benign, but are malignant on rare occasions. Nevertheless, malignant phyllodes tumors are very rare and less than 10 women per year in the US die of this disease. Benign phyllodes tumors are successfully treated by removing the mass and a narrow margin of normal breast tissue.
Tubular carcinoma: Accounting for about 2%> of all breast cancers, tubular carcinomas are a special type of infiltrating breast carcinoma. They have a better prognosis than usual infiltrating ductal or lobularcarcinomas. High-quality mammography combined with clinical breast exam remains the only screening method clearly tied to reduction in breast cancer mortality. Lower dose x-rays, digitized computer rather than film images, and the use of computer programs to assist diagnosis, are almost ready for widespread dissemination. Other technologies also are being developed, including magnetic resonance imaging and ultrasound. In addition, a very low radiation exposure technique, positron emission tomography has the potential for detecting early breast cancer.
It is also possible to differentiate between non-cancerous breast tissue and malignant breast tissue by analyzing differential gene expression between tissues. In addition, there may be several possible alterations that lead to the various possible types of breast cancer. The different types of breast tumors (e.g., invasive vs. non-invasive, ductal vs. axillary lymph node) can be differentiable from one another by the identification of the differences in genes expressed by different types of breast tumor tissues (Porter- Jordan et al, Hematol Oncol Clin North Am (1994) 3.73). Breast cancer can thus be generally diagnosed by detection of expression of a gene or genes associated with breast tumors. Where enough information is available about the differential gene expression between various types of breast tumor tissues, the specific type of breast tumor can also be diagnosed.
For example, increased estrogen receptor (ER) expression in normal breast epithileum, while not itself indicative of malignant tissue, is a known risk marker for development of breast cancer. Khan S A et al, Cancer Res (1994) 54:993. Malignant breast cancer is often divided into two groups, ER-positive and ER-negative, based on the
estrogen receptor status of the tissue. The ER status represents different survival length and response to hormone therapy, and is thought to represent either: 1) an indicator of different stages of the disease, or 2) an indicator that allows differentiation between two similar but distinct diseases. K. Zhu et al, Med. Hypoth. (1997) 49:69. A number of other genes are known to vary expression between either different stages of cancer or different types of similar breast cancer.
Similarly, the expression of polynucleotides of the invention can be used in the diagnosis and management of breast cancer. The differential expression of a polynucleotide in human breast tumor tissue can be used as a diagnostic marker for human breast cancer. The polynucleotides of the invention that would be especially useful for this puφose are those that exhibit differential expression between breast cancer tissue with a high metastatic potential and a low metastatic potential, i.e. SEQ ID NOS: 15, 36, 44, 89, 172, 203, 261, 419, 420, 503, 552, 564, 570, 590, 693, 707, 711, 726, 746, 756, 990, 1122, 1142, 1286, 1289, 1435, 1860, 1933, 1934, 1979, 1980, 2007, 2023, 2409, 2486, 45, 146, 154, 159, 165, 174, 183, 364, 366, 387, 496, 510, 512, 529, 560, 606, 644, 646, 754, 875, 902, 921, 942, 1095, 1104, 1131, 1170, 1184, 1205, 1354, 1387, 1535, 1751, 1764, 1777, 1795, 1869, 1882, 1890, 1915, 2040, 2059, 2223, 2245, 2300, 2325, 2462, 2488, 2492; Detection of breast cancer can be determined using expression levels of any of these sequences alone or in combination. Determination of the aggressive nature and/or the metastatic potential of a breast cancer can also be determined by comparing levels of one or more polynucleotides of the invention and comparing levels of another sequence known to vary in cancerous tissue, e.g. ER expression. In addition, development of breast cancer can be detected by examining the ratio of SEQ ID NO: to the levels of steroid hormones (e.g. , testosterone or estrogen) or to other hormones (e.g. , growth hormone, insulin). Thus expression of specific marker polynucleotides can be used to discriminate between normal and cancerous breast tissue, to discriminate between breast cancers with different cells of origin, to discriminate between breast cancers with different potential metastatic rates, etc.
Diagnosis of breast cancer can also involve comparing the expression of a polynucleotide of the invention with the expression of other sequences in non-malignant breast tissue samples in comparison to one or more forms of the diseased tissue. A comparison of expression of one or more polynucleotides of the invention between the
samples provides information on relative levels of these polynucleotides as well as the ratio of these polynucleotides to the expression of other sequences in the tissue of interest compared to normal.
This risk of breast cancer is elevated significantly by the presence of an inherited risk for breast cancer, such as a mutation in BRCA-1 or BRCA-2. New diagnostic tools are being developed to address the needs of higher risk patients to complement mammography and physical examinations for early detection of breast cancer, particularly among younger women. The presence of antigen or expression markers in nipple aspirate fluid (NAF) samples collected from one or both breasts can be useful for useful for risk assessment or early cancer detection. Breast cytology and biomarkers obtained by random fine needle aspiration have been used to identify hypeφlasia with atypia and overexpression of p53 and EGFR. The polynucleotides of the invention can be used in multivariate analysis with expression studies with genes such as p53 and EGFR as risk predictors and as surrogate endpoint biomarkers for breast cancer. As well as being used for diagnosis and risk assessment, the expression of certain genes can also correlated to prognosis of a disease state. The expression of particular gene have been used as prognostic indicators for breast cancer including increased expression of c-erbB-2, pS2, ER, progesterone receptor, epidermal growth factor receptor (EGFR), neu, myc, bcl-2, int2, cytosolic tyrosine kinase, cyclin E,prad-1, hst, uPA, PAI-1, PAI-2, cathepsin D, as well as the presence of a number of cancer-specific antigens, e.g. CEA, CA M26, CA M29 and CA 15.3. Davis, Br. J. BiomedSci. (1996) 53:157. Poor prognosis has also been linked to a decrease in expression of certain genes, such as p53, Rb, nm23. The expression of the polynucleotides of the invention can be of prognostic value for determining the metastatic potential of a malignant breast cancer, as this molecules are differentially expressed between high and low metastatic potential tissues tumors. The levels of these polynucleotides in patients with malignant breast cancer can compared to normal tissue, malignant tissue with a known high potential metastatic level, and malignant tissue with a known lower level of metastatic potential to provide a prognosis for a particular patient. Such a prognosis is predictive of the extent and nature of the cancer. The determined prognosis is useful in determining the prognosis of a patient with breast cancer, both for initial treatment of the disease and for longer-term monitoring of the same
patient. If samples are taken from the same individual over a period of time, differences in polynucleotide expression that are specific to that patient can be identified and closely watched.
Colon Cancer. Colorectal cancer is one of the most common neoplasms in humans and perhaps the most frequent form of hereditary neoplasia. Prevention and early detection are key factors in controlling and curing colorectal cancer. Indeed, colorectal cancer is the second most preventable cancer, after lung cancer. Colorectal cancer begins as polyps, which are small, benign growths of cells that form on the inner lining of the colon. Over a period of several years, some of these polyps accumulate additional mutations and become cancerous. About 20 percent of all cases of colon cancer are thought to be related to heredity. Currently, multiple familial colorectal cancer disorders have been identified, which are summarized as follows:
Familial adenomatous polyposis (FAP): This condition results in a person having hundreds or even thousands of polyps in the colon and rectum that usually first appear during the teenage years. Cancer nearly always develops in one or more of these polyps between the ages of 30 and 50.
Gardner's syndrome: Like FAP, Gardner's syndrome results in polyps and colorectal cancers that develop at a young age. It can also cause benign tumors of the skin, soft connective tissue and bones. Hereditary nonpolyposis colon cancer (HNPCC): People with this condition tend to develop colorectal cancer at a young age, without first having many polyps. HNPCC has an autosomal dominant pattern of inheritance with variable but high penetrance estimated to be about 90%. HNPCC underlies 0.5%- 10% of all cases of colorectal cancer. An understanding of the mechanisms behind the development of HNPCC is emerging, and genetic presymptomatic testing, now being conducted in research settings, soon will be available on a widespread basis for individuals identified at risk for this disease.
Familial colorectal cancer in Ashkenazi Jews: Recent research has found an inherited tendency to developing colorectal cancer among some Jews of Eastern European descent. Like people with FAP, Gardner's syndrome, and HNPCC, their increased risk is due to an inherited mutation present in about 6% of American Jews.
Several tests are currently used to screen for colorectal cancer, including digital rectal examination, fecal occult blood test, sigmoidoscopy, colonoscopy, virtual colonoscopy and MRI. Each of these tests identifies potential colorectal cancer lesions, or a risk of development of these lesions, at a fairly gross moφhological level. The sequential alteration of a number of genes is associated with malignant adenocarcinoma, including the genes DCC, p53, ras, and FAP. For a review, see e.g. Fearon ER, et al, Cell (1990) 61(5):159; Hamilton SR et al, Cancer (1993) 72:957; Bodmer W, et al, Nat Genet. (1994) 4(3):2ll; Fearon ER, Ann N Y Acad Sci. (1995) 763:101. Molecular genetic alterations are thus promising as potential diagnostic and prognostic indicators in colorectal carcinoma and molecular genetics of colorectal carcinoma since it is possible to differentiate between different types of colorectal neoplasias using molecular markers. Colorectal cancer can thus be generally diagnosed by detection of expression of a gene or genes associated with colorectal tumors.
Similarly, the expression of polynucleotides of the invention can be used in the diagnosis, prognosis and management of colorectal cancer. The differential expression of a polynucleotide in hypeφlasia can be used as a diagnostic marker for colon cancer. The polynucleotides of the invention that would be especially useful for this puφose are those that exhibit differential expression between malignant metastatic colon cancer and normal patient tissue , i.e. SEQ ID NOS:228, 280, 355, 491, 603, 680, 752, 753, 1241, 1264, 1401, 1442, 1514, 1851, 1915, 2024, 2066, 33, 250, 282, 370, 387, 443, 460, 545, 560, 703, 704, 1095, 1104, 1205, 1354, 1387, 1734, 1742, 1954, 2262, 2325, 1899, 252, 253, 491, 581, 693, 726, 746, 1780, 1899, 65, 252, 253, 581, 693, 716, 726, 746, 1780, 1899, and 1780. Detection of malignant colon cancer can be determined using expression levels of any of these sequences alone or in combination with the levels of expression. Determination of the aggressive nature and/or the metastatic potential of a colon cancer can also be determined by comparing levels of one or more polynucleotides of the invention and comparing total levels of another sequence known to vary in cancerous tissue, e.g. p53 expression. In addition, development of colon cancer can be detected by examining the ratio of any of the polynucleotides of the invention to the levels of oncogenes (e.g. ras) or tumor suppressor genes (e.g. FAP or p53). Thus expression of specific marker polynucleotides can be used to discriminate between normal and cancerous
breast tissue, to discriminate between breast cancers with different cells of origin, to discriminate between breast cancers with different potential metastatic rates, etc.
G. Use of Polynucleotides to Screen for Peptide Analogs and Antagonists Polypeptides encoded by the instant polynucleotides and corresponding full length genes can be used to screen peptide libraries to identify binding partners, such as receptors, from among the encoded polypeptides.
A library of peptides can be synthesized following the methods disclosed in U.S. Pat. No. 5,010,175 ('175), and in WO 91/17823. As described below in brief, one prepares a mixture of peptides, which is then screened to identify the peptides exhibiting the desired signal transduction and receptor binding activity. In the '175 method, a suitable peptide synthesis support (e.g., a resin) is coupled to a mixture of appropriately protected, activated amino acids. The concentration of each amino acid in the reaction mixture is balanced or adjusted in inverse proportion to its coupling reaction rate so that the product is an equimolar mixture of amino acids coupled to the starting resin. The bound amino acids are then deprotected, and reacted with another balanced amino acid mixture to form an equimolar mixture of all possible dipeptides. This process is repeated until a mixture of peptides of the desired length (e.g., hexamers) is formed. Note that one need not include all amino acids in each step: one can include only one or two amino acids in some steps (e.g., where it is known that a particular amino acid is essential in a given position), thus reducing the complexity of the mixture. After the synthesis of the peptide library is completed, the mixture of peptides is screened for binding to the selected polypeptide. The peptides are then tested for their ability to inhibit or enhance activity. Peptides exhibiting the desired activity are then isolated and sequenced. The method described in WO 91/17823 is similar. However, instead of reacting the synthesis resin with a mixture of activated amino acids, the resin is divided into twenty equal portions (or into a number of portions corresponding to the number of different amino acids to be added in that step), and each amino acid is coupled individually to its portion of resin. The resin portions are then combined, mixed, and again divided into a number of equal portions for reaction with the second amino acid. In this manner, each reaction can be easily driven to completion. Additionally, one can maintain separate "subpools" by treating portions in parallel, rather than combining all resins at each step.
This simplifies the process of determining which peptides are responsible for any observed receptor binding or signal transduction activity.
In such cases, the subpools containing, e.g., 1-2,000 candidates each are exposed to one or more polypeptides of the invention. Each subpool that produces a positive result is then resynthesized as a group of smaller subpools (sub-subpools) containing, e.g. , 20-100 candidates, and reassayed. Positive sub-subpools can be resynthesized as individual compounds, and assayed finally to determine the peptides that exhibit a high binding constant. These peptides can be tested for their ability to inhibit or enhance the native activity. The methods described in WO 91/7823 and U.S. Patent No. 5,194,392 (herein incoφorated by reference) enable the preparation of such pools and subpools by automated techniques in parallel, such that all synthesis and resynthesis can be performed in a matter of days.
Peptide agonists or antagonists are screened using any available method, such as signal transduction, antibody binding, receptor binding, mitogenic assays, chemotaxis assays, etc. The methods described herein are presently preferred. The assay conditions ideally should resemble the conditions under which the native activity is exhibited in vivo, that is, under physiologic pH, temperature, and ionic strength. Suitable agonists or antagonists will exhibit strong inhibition or enhancement of the native activity at concentrations that do not cause toxic side effects in the subject. Agonists or antagonists that compete for binding to the native polypeptide can require concentrations equal to or greater than the native concentration, while inhibitors capable of binding irreversibly to the polypeptide can be added in concentrations on the order of the native concentration.
The end results of such screening and experimentation will be at least one novel polypeptide binding partner, such as a receptor, encoded by a gene or a cDNA corresponding to a polynucleotide of the invention, and at least one peptide agonist or antagonist of the novel binding partner. Such agonists and antagonists can be used to modulate, enhance, or inhibit receptor function in cells to which the receptor is native, or in cells that possess the receptor as a result of genetic engineering. Further, if the novel receptor shares biologically important characteristics with a known receptor, information about agonist/antagonist binding can facilitate development of improved agonists/antagonists of the known receptor.
H. Pharmaceutical Compositions and Therapeutic Uses Pharmaceutical compositions can comprise polypeptides, antibodies, or polynucleotides of the claimed invention. The pharmaceutical compositions will comprise a therapeutically effective amount of either polypeptides, antibodies, or polynucleotides of the claimed invention.
The term "therapeutically effective amount" as used herein refers to an amount of a therapeutic agent to treat, ameliorate, or prevent a desired disease or condition, or to exhibit a detectable therapeutic or preventative effect. The effect can be detected by, for example, chemical markers or antigen levels. Therapeutic effects also include reduction in physical symptoms, such as decreased body temperature. The precise effective amount for a subject will depend upon the subject's size and health, the nature and extent of the condition, and the therapeutics or combination of therapeutics selected for administration. Thus, it is not useful to specify an exact effective amount in advance. However, the effective amount for a given situation is determined by routine experimentation and is within the judgment of the clinician. For puφoses of the present invention, an effective dose will generally be from about 0.01 mg/ kg to 50 mg/kg or 0.05 mg/kg to about 10 mg/kg of the DNA constructs in the individual to which it is administered.
A pharmaceutical composition can also contain a pharmaceutically acceptable carrier. The term "pharmaceutically acceptable carrier" refers to a carrier for administration of a therapeutic agent, such as antibodies or a polypeptide, genes, and other therapeutic agents. The term refers to any pharmaceutical carrier that does not itself induce the production of antibodies harmful to the individual receiving the composition, and which can be administered without undue toxicity. Suitable carriers can be large, slowly metabolized macromolecules such as proteins, polysaccharides, polylactic acids, polyglycolic acids, polymeric amino acids, amino acid copolymers, and inactive virus particles. Such carriers are well known to those of ordinary skill in the art.
Pharmaceutically acceptable salts can be used therein, for example, mineral acid salts such as hydrochlorides, hydrobromides, phosphates, sulfates, and the like; and the salts of organic acids such as acetates, propionates, malonates, benzoates, and the like. A thorough discussion of pharmaceutically acceptable excipients is available in Remingto 's Pharmaceutical Sciences (Mack Pub. Co., N.J. 1991).
Pharmaceutically acceptable carriers in therapeutic compositions can include liquids such as water, saline, glycerol and ethanol. Auxiliary substances, such as wetting or emulsifying agents, pH buffering substances, and the like, can also be present in such vehicles. Typically, the therapeutic compositions are prepared as injectables, either as liquid solutions or suspensions; solid forms suitable for solution in, or suspension in, liquid vehicles prior to injection can also be prepared. Liposomes are included within the definition of a pharmaceutically acceptable carrier.
Delivery Methods. Once formulated, the compositions of the invention can be (1) administered directly to the subject (e.g., as polynucleotide or polypeptides); (2) delivered ex vivo, to cells derived from the subject (e.g., as in ex vivo gene therapy); or (3) delivered in vitro for expression of recombinant proteins (e.g., polynucleotides). Direct delivery of the compositions will generally be accomplished by injection, either subcutaneously, intraperitoneally, intravenously or intramuscularly, or delivered to the interstitial space of a tissue. The compositions can also be administered into a tumor or lesion. Other modes of administration include oral and pulmonary administration, suppositories, and transdermal applications, needles, and gene guns or hyposprays. Dosage treatment can be a single dose schedule or a multiple dose schedule.
Methods for the ex vivo delivery and reimplantation of transformed cells into a subject are known in the art and described in e.g., International Publication No. WO 93/14778. Examples of cells useful in ex vivo applications include, for example, stem cells, particularly hematopoetic, lymph cells, macrophages, dendritic cells, or tumor cells. Generally, delivery of nucleic acids for both ex vivo and in vitro applications can be accomplished by, for example, dextran-mediated transfection, calcium phosphate precipitation, polybrene mediated transfection, protoplast fusion, electroporation, encapsulation of the polynucleotide(s) in liposomes, and direct microinjection of the DNA into nuclei, all well known in the art.
Once a gene corresponding to a polynucleotide of the invention has been found to correlate with a proliferative disorder, such as neoplasia, dysplasia, and hypeφlasia, the disorder can be amenable to treatment by administration of a therapeutic agent based on the provided polynucleotide or corresponding polypeptide.
Preparation of antisense polynucleotides is discussed above. Neoplasias that are treated with the antisense composition include, but are not limited to, cervical cancers, melanomas, colorectal adenocarcinomas, Wilms' tumor, retinoblastoma, sarcomas, myosarcomas, lung carcinomas, leukemias, such as chronic myelogenous leukemia, promyelocytic leukemia, monocytic leukemia, and myeloid leukemia, and lymphomas, such as histiocytic lymphoma. Proliferative disorders that are treated with the therapeutic composition include disorders such as anhydric hereditary ectodermal dysplasia, congenital alveolar dysplasia, epithelial dysplasia of the cervix, fibrous dysplasia of bone, and mammary dysplasia. Hypeφlasias, for example, endometrial, adrenal, breast, prostate, or thyroid hypeφlasias or pseudoepitheliomatous hypeφlasia of the skin, are treated with antisense therapeutic compositions based upon a polynucleotide of the invention. Even in disorders in which mutations in the corresponding gene are not implicated, downregulation or inhibition of expression of a gene corresponding to a polynucleotide of the invention can have therapeutic application. For example, decreasing gene expression can help to suppress tumors in which enhanced expression of the gene is implicated.
Both the dose of the antisense composition and the means of administration are determined based on the specific qualities of the therapeutic composition, the condition, age, and weight of the patient, the progression of the disease, and other relevant factors. Administration of the therapeutic antisense agents of the invention includes local or systemic administration, including injection, oral administration, particle gun or catheterized administration, and topical administration. Preferably, the therapeutic antisense composition contains an expression construct comprising a promoter and a polynucleotide segment of at least 12, 22, 25, 30, or 35 contiguous nucleotides of the antisense strand of a polynucleotide disclosed herein. Within the expression construct, the polynucleotide segment is located downstream from the promoter, and transcription of the polynucleotide segment initiates at the promoter.
Various methods are used to administer the therapeutic composition directly to a specific site in the body. For example, a small metastatic lesion is located and the therapeutic composition injected several times in several different locations within the body of tumor. Alternatively, arteries which serve a tumor are identified, and the therapeutic composition injected into such an artery, in order to deliver the composition directly into
the tumor. A tumor that has a necrotic center is aspirated and the composition injected directly into the now empty center of the tumor. The antisense composition is directly administered to the surface of the tumor, for example, by topical application of the composition. X-ray imaging is used to assist in certain of the above delivery methods. Receptor-mediated targeted delivery of therapeutic compositions containing an antisense polynucleotide, subgenomic polynucleotides, or antibodies to specific tissues is also used. Receptor-mediated DNA delivery techniques are described in, for example, Findeis et al, Trends Biotechnol (1993) 77:202; Chiou et al, Gene Therapeutics: Methods And Applications Of Direct Gene Transfer (J.A. Wolff, ed.) (1994); Wu et al, J. Biol Chem. (1988) 263:621 ; Wu et al, J. Biol Chem. (1994) 269:542; Zenke et al, Proc. Natl. Acad. Sci. (USA) (1990) 37:3655; Wu et al, J. Biol Chem. (1991) 266:338. Preferably, receptor-mediated targeted delivery of therapeutic compositions containing antibodies of the invention is used to deliver the antibodies to specific tissue.
Therapeutic compositions containing antisense subgenomic polynucleotides are administered in a range of about 100 ng to about 200 mg of DNA for local administration in a gene therapy protocol. Concentration ranges of about 500 ng to about 50 mg, about 1 μg to about 2 mg, about 5 μg to about 500 μg, and about 20 μg to about 100 μg of DNA can also be used during a gene therapy protocol. Factors such as method of action and efficacy of transformation and expression are considerations which will affect the dosage required for ultimate efficacy of the antisense subgenomic polynucleotides. Where greater expression is desired over a larger area of tissue, larger amounts of antisense subgenomic polynucleotides or the same amounts readministered in a successive protocol of administrations, or several administrations to different adjacent or close tissue portions of, for example, a tumor site, may be required to effect a positive therapeutic outcome. In all cases, routine experimentation in clinical trials will determine specific ranges for optimal therapeutic effect. A more complete description of gene therapy vectors, especially retroviral vectors, is contained in U.S. Serial No. 08/869,309, which is expressly incoφorated herein, and in section G below.
For polynucleotide-related genes encoding polypeptides or proteins with anti- inflammatory activity, suitable use, doses, and administration are described in U.S. Patent No. 5,654,173. Therapeutic agents also include antibodies to proteins and polypeptides
encoded by the polynucleotides of the invention and related genes, as described in U.S. Patent No. 5,654,173.
I. Gene Therapy
The therapeutic polynucleotides and polypeptides of the present invention can be utilized in gene delivery vehicles. The gene delivery vehicle can be of viral or non- viral origin (see generally, Jolly, Cancer Gene Therapy (1994) 7:51; Kimura, Human Gene Therapy (1994) 5:845; Connelly, Human Gene Therapy (1995) 7:185; and Kaplitt, Nature Genetics (1994) 6:148). Gene therapy vehicles for delivery of constructs including a coding sequence of a therapeutic of the invention can be administered either locally or systemically. These constructs can utilize viral or non- viral vector approaches. Expression of such coding sequences can be induced using endogenous mammalian or heterologous promoters. Expression of the coding sequence can be either constitutive or regulated.
The present invention can employ recombinant retroviruses which are constructed to carry or express a selected nucleic acid molecule of interest. Retrovirus vectors that can be employed include those described in EP 0 415 731; WO 90/07936; WO 94/03622; WO 93/25698; WO 93/25234; U.S. Patent No. 5, 219,740; WO 93/11230; WO 93/10218; Vile and Hart, Cancer Res. (1993) 53:3860; Vile et al, Cancer Res. (1993) 53:962; Ram et al., Cancer Res. (1993) 53:83; Takamiya et al, J. Neurosci. Res. (1992) 33:493; Baba et al., J. Neurosurg. (1993) 79:729; U.S. Patent No. 4,777,127; GB Patent No. 2,200,651; and EP 0 345 242. Preferred recombinant retroviruses include those described in WO 91/02805. Packaging cell lines suitable for use with the above-described retroviral vector constructs can be readily prepared (see, e.g., WO 95/30763 and WO 92/05266), and used to create producer cell lines (also termed vector cell lines) for the production of recombinant vector particles. Within particularly preferred embodiments of the invention, packaging cell lines are made from human (such as HT1080 cells) or mink parent cell lines, thereby allowing production of recombinant retroviruses that can survive inactivation in human serum.
The present invention also employs alphavirus-based vectors that can function as gene delivery vehicles. Such vectors can be constructed from a wide variety of alphaviruses, including, for example, Sindbis virus vectors, Semliki forest virus (ATCC VR-67; ATCC VR-1247), Ross River virus (ATCC VR-373; ATCC VR-1246) and
Venezuelan equine encephalitis virus (ATCC VR-923; ATCC VR-1250; ATCC VR 1249;
ATCC VR-532). Representative examples of such vector systems include those described in U.S. Patent Nos. 5,091,309; 5,217,879; and 5,185,440; WO 92/10578; WO 94/21792;
WO 95/27069; WO 95/27044; and WO 95/07994. Gene delivery vehicles of the present invention can also employ parvovirus such as adeno-associated virus (AAV) vectors.
Representative examples include the AAV vectors disclosed by Srivastava in WO
93/09239, Samulski et al., J Virol. (1989) 63:3822; Mendelson et al., Virol. (1988)
766:154; and Flotte et al, PNAS (1993) 90:10613.
Representative examples of adenoviral vectors include those described by Berkner, Biotechniques (1988) 6:616; Rosenfeld et al, Science (1991) 252:431; WO 93/19191;
Kolls et al, PNAS (1994) 97:215; Kass-Eisler et al, PNAS (1993) 90:11498; Guzman et al, Circulation (1993) 33:2838; Guzman et al., Cir. Res. (1993) 73:1202; Zabner et al,
Cell (1993) 75:207; Li et al, Hum. Gene Ther. (1993) 4:403; Cailaud et al, Eur. J.
Neurosci. (1993) 5:1287; Vincent et al, Nat. Genet. (1993) 5:130; Jaffe et al, Nat. Genet. (1992) 7:372; and Levrero et al, Gene (1991) 707:195. Exemplary adenoviral gene therapy vectors employable in this invention also include those described in WO 94/12649,
WO 93/03769; WO 93/19191; WO 94/28938; WO 95/11984 and WO 95/00655.
Administration of DNA linked to killed adenovims as described in Curiel, Hum. Gene
Ther. (1992) 3:147 can be employed. Other gene delivery vehicles and methods can be employed, including polycationic condensed DNA linked or unlinked to killed adenovims alone, for example Curiel, Hum.
Gene Ther. (1992) 3:147; ligand linked DNA, for example see Wu, J. Biol. Chem. (1989)
264:16985; eukaryotic cell delivery vehicles cells, for example see U.S. Pat. No. 5,814,482;
WO 95/07994; WO 96/17072; WO 95/30763; and WO 97/42338; deposition of photopolymerized hydrogel materials; hand-held gene transfer particle gun, as described in
U.S. Patent No. 5,149,655; ionizing radiation as described in U.S. Patent No. 5,206,152 and in WO92/11033; nucleic charge neutralization or fusion with cell membranes.
Additional approaches are described in Philip, Mol. Cell Biol (1994) 74:2411, and in
Woffendin, Proc. Natl Acad. Sci. (1994) 97:1581. Naked DNA can also be employed. Exemplary naked DNA introduction methods are described in WO 90/11092 and U.S. Patent No. 5,580,859. Liposomes that can act as
gene delivery vehicles are described in U.S. Patent No. 5,422,120; WO 95/13796; WO 94/23697; WO 91/14445; and EP 0524968.
Further non-viral delivery suitable for use includes mechanical delivery systems such as the approach described in Woffendin et al, Proc. Natl. Acad. Sci. USA (1994) 97(24): 11581. Moreover, the coding sequence and the product of expression of such can be delivered through deposition of photopolymerized hydrogel materials. Other conventional methods for gene delivery that can be used for delivery of the coding sequence include, for example, use of hand-held gene transfer particle gun, as described in U.S. Patent No. 5,149,655; use of ionizing radiation for activating transferred gene, as described in U.S. Patent No. 5,206,152 and WO 92/11033.
The present invention will now be illustrated by reference to the following examples which set forth particularly advantageous embodiments. However, it should be noted that these embodiments are illustrative and are not to be constmed as restricting the invention in any way.
EXAMPLES
Example 1 : Source of Biological Materials and Overview of Novel Polynucleotides Expressed by the Biological Materials Human colon cancer cell line Kml2L4-A (Morika, W. A. K. et al., Cancer
Research (1988) 43:6863) was used to constmct a cDNA library from mRNA isolated from the cells. As described in the above overview, a total of 4,693 sequences expressed by the Kml2L4-A cell line were isolated and analyzed; most sequences were about 275-300 nucleotides in length. The KM12L4-A cell line is derived from the KM12C cell line. The KM12C cell line, which is poorly metastatic (low metastatic) was established in culture from a Dukes' stage B surgical specimen (Morikawa et al. Cancer Res. (1988) 43:6863). The KML4-A is a highly metastatic subline derived from KM12C (Yeatman et al. Nucl. Acids. Res. (1995) 23:4007; Bao-Ling et al. Proc. Annu. Meet. Am. Assoc. Cancer. Res. (1995) 27:3269). The KM12C and KM12C-derived cell lines (e.g., KM12L4, KM12L4-A, etc.) are well-recognized in the art as a model cell line for the study of colon cancer (see, e.g., Moriakawa et al, supra; Radinsky et al. Clin. Cancer Res. (1995) 7:19; Yeatman et al, (1995) supra; Yeatman et al. Clin. Exp. Metastasis (1996) 74:246).
The sequences were first masked to eliminate low complexity sequences using the XBLAST masking program (Claverie "Effective Large-Scale Sequence Similarity Searches," In: Computer Methods for Macromolecular Sequence Analysis. Doolittle, ed., Meth. Enzymol. 266:212-227 Academic Press, NY, NY (1996); see particularly Claverie, in "Automated DNA Sequencing and Analysis Techniques" Adams et al, eds., Chap. 36, p. 267 Academic Press, San Diego, 1994 and Claverie et al. Comput. Chem. (1993) 17:191 ). Generally, masking does not influence the final search results, except to eliminate sequences of relative little interest due to their low complexity, and to eliminate multiple "hits" based on similarity to repetitive regions common to multiple sequences, e.g., Alu repeats. Masking resulted in the elimination of 43 sequences. The remaining sequences were then used in a BLASTN vs. Genbank search with search parameters of greater than 70% overlap, 99% identity, and a p value of less than l x l 0"40, which search resulted in the discarding of 1,432 sequences. Sequences from this search also were discarded if the inclusive parameters were met, but the sequence was ribosomal or vector-derived.
The resulting sequences from the previous search were classified into three groups (1, 2 and 3 below) and searched in a BLASTX vs. NRP (non-redundant proteins) database
search: (1) unknown (no hits in the Genbank search), (2) weak similarity (greater than 45%) identity and p value of less than 1 x IO"5), and (3) high similarity (greater than 60% overlap, greater than 80%> identity, and p value less than 1 x IO'5). This search resulted in discard of 98 sequences as having greater than 70%> overlap, greater than 99%) identity, and p value of less than 1 x 10"40.
The remaining sequences were classified as unknown (no hits), weak similarity, and high similarity (parameters as above). Two searches were performed on these sequences. First, a BLAST vs. EST database search resulted in discard of 1771 sequences (sequences with greater than 99% overlap, greater than 99% similarity and a p value of less than 1 x 10"40; sequences with a p value of less than 1 x 10"65 when compared to a database sequence of human origin were also excluded). Second, a BLASTN vs. Patent GeneSeq database resulted in discard of 15 sequences (greater than 99% identity; p value less than 1 x IO"40; greater than 99% overlap).
The remaining sequences were subjected to screening using other mles and redundancies in the dataset. Sequences with a p value of less than 1 x 10 _1 ' ' in relation to a database sequence of human origin were specifically excluded. The final result provided the 2502 sequences listed in the accompanying Sequence Listing. The Sequence Listing is arranged beginning with sequences with no similarity to any sequence in a database searched, and ending with sequences with the greatest similarity. Each identified polynucleotide represents sequence from at least a partial mRNA transcript.
Polynucleotides that were determined to be novel were assigned a sequence identification number.
The novel polynucleotides were assigned sequence identification numbers SEQ ID NOS: 1-2502. The DNA sequences corresponding to the novel polynucleotides are provided in the Sequence Listing. The majority of the sequences are presented in the Sequence Listing in the 5' to 3' direction. A small number of sequences are listed in the Sequence Listing in the 5' to 3' direction but the sequence as written is actually 3' to 5'. These sequences are readily identified with the designation "AR" in the Sequence Name in Table 1 (inserted before the claims). The sequences correctly listed in the 5' to 3' direction in the Sequence Listing are designated "AF." Table 1 provides: 1) the SEQ ID NO assigned to each sequence for use in the present specification; 2) the filing date of the U.S. priority application in which the sequence was first filed; 3) the SEQ ID NO assigned to the sequence in the priority application; 4) the sequence name used as an internal identifier of
the sequence; 5) the name assigned to the clone from which the sequence was isolated; and 6) the number of the cluster to which the sequence is assigned (Cluster ID; where the cluster ID is 0, the sequence was not assigned to any cluster
Because the provided polynucleotides represent partial mRNA transcripts, two or more polynucleotides of the invention may represent different regions of the same mRNA transcript and the same gene. Thus, if two or more SEQ ID NOS: are identified as belonging to the same clone, then either sequence can be used to obtain the full-length mRNA or gene. In addition, some sequences are identified with multiple SEQ ID NOS, since these sequences were present in more than one filing. For example, SEQ ID NO:87 and SEQ ID NO: 1000 represent the same sequence.
In order to confirm the sequences of SEQ ID NOS: 1-2502, inserts of the clones corresponding to these polynucleotides were re-sequenced. These "validation" sequences are provided in SEQ ID NOS:2503-5106. Of these validation sequences, SEQ ID NOS:3040, 3545, 3863, 4511, 4726, and 4749 are not tme validation sequences. Instead, SEQ ID NOS :3545, 4511, 4726, and 4749 represent "placeholder" sequences, i.e., sequences that were inserted into the Sequence Listing only to prevent renumbering of the subsequent sequences during generation of the Sequence Listing. Thus, reference to "SEQ ID NOS: 1-5252," "SEQ ID NOS: 1-5106," or other ranges of SEQ ID NOS that include these placeholder sequences should be read to exclude SEQ ID NOS:3545, 4511, 4726, and 4749.
The validation sequences were often longer than the original polynucleotide sequences they validate, and thus often provide additional sequence information. Validation sequences can be correlated with the original sequences they validate by referring to Table 1. For example, validation sequences of SEQ ID NOS:2503-3039, 3041- 3544, 3546-3862 3864-4510, and 4512-4725 share the clone name of the sequence of SEQ ID NOS: 1-2502 that they validate.
Example 2: Results of Public Database Search to Identify Function of Gene Products
SEQ ID NOS:1-2502, as well as the validation sequences SEQ ID NOS:2503-3039, 3041-3544, 3546-3862 3864-4510, and 4512-4725 xxxlf were translated in all three reading frames to determine the best alignment with the individual sequences. These amino acid sequences and nucleotide sequences are referred, generally, as query sequences, which are aligned with the individual sequences. Query and individual sequences were
aligned using the BLAST programs, available over the world wide web at http://ww.ncbi.nlm.nih.gov/BLAST/. Again the sequences were masked to various extents to prevent searching of repetitive sequences or poly-A sequences, using the XBLAST program for masking low complexity as described above in Example 1. Table 2 (inserted before the claims) shows the results of the alignments. Table 2 refers to each sequence by its SEQ ID NO:, the accession numbers and descriptions of nearest neighbors from the Genbank and Non-Redundant Protein searches, and the p values of the search results.
For each of "SEQ ID NOS: 1-5106," the best alignment to a protein or DNA sequence is included in Table 2. The activity of the polypeptide encoded by "SEQ ID NOS: 1-5106" is the same or similar to the nearest neighbor reported in Table 2. The accession number of the nearest neighbor is reported, providing a reference to the activities exhibited by the nearest neighbor. The search program and database used for the alignment also are indicated as well as a calculation of the p value. Full length sequences or fragments of the polynucleotide sequences of the nearest neighbors can be used as probes and primers to identify and isolate the full length sequence of "SEQ ID NOS: 1-5106." The nearest neighbors can indicate a tissue or cell type to be used to constmct a library for the full-length sequences of "SEQ ID NOS: 1-5106."
"SEQ ID NOS: 1-5106" and the translations thereof may be human homologs of known genes of other species or novel allelic variants of known human genes. In such cases, these new human sequences are suitable as diagnostics or therapeutics. As diagnostics, the human sequences "SEQ ID NOS: 1-5106" exhibit greater specificity in detecting and differentiating human cell lines and types than homologs of other species. The human polypeptides encoded by "SEQ ID NOS 1-5106" are likely to be less immunogenic when administered to humans than homologs from other species. Further, on administration to humans, the polypeptides encoded by "SEQ ID NOS: 1-5106" can show greater specificity or can be better regulated by other human proteins than are homologs from other species.
Example 3: Members of Protein Families
The validation sequences ("SEQ ID NOS:2503-5106") were used to conduct a profile search as described in the specification above. Several of the polynucleotides of the invention were found to encode polypeptides having characteristics of a polypeptide
belonging to a known protein families (and thus represent new members of these protein families) and/or comprising a known functional domain (Table 3, inserted prior to claims). Thus the invention encompasses fragments, fusions, and variants of such polynucleotides that retain biological activity associated with the protein family and/or functional domain identified herein.
Start and stop indicate the position within the individual sequences that align with the query sequence having the indicated SEQ ID NO. The direction (Dir) indicates the orientation of the query sequence with respect to the individual sequence, where forward (for) indicates that the alignment is in the same direction (left to right) as the sequence provided in the Sequence Listing and reverse (rev) indicates that the alignment is with a sequence complementary to the sequence provided in the Sequence Listing.
Some polynucleotides exhibited multiple profile hits because, for example, the particular sequence contains overlapping profile regions, and/or the sequence contains two different functional domains. These profile hits are described in more detail below. The acronyms used in Table 3 are provided in parentheses following the full name of the protein family or functional domain to which they refer. a) Seven Transmembrane Integral Membrane Proteins — Rhodopsin Family (7tm 1). Several of the validation sequences, and thus their corresponding sequence within SEQ ID NOS: 1-2502, correspond to a sequence encoding a polypeptide that is a member of the seven transmembrane receptor rhodopsin family. G-protein coupled receptors of the seven transmembrane rhodopsin family (also called R7G) are an extensive group of hormones, neurotransmitters, and light receptors which transduce extracellular signals by interaction with guanine nucleotide-binding (G) proteins (Strosberg A.D. Eur. J. Biochem. (1991) 796:1, Kerlavage A.R Curr. Opin. Struct. Biol. (1991) 7:394, Probst, et al., DNA Cell Biol. (1992) 77:1, Savarese, et al., Biochem. J. (1992) 233:1, http://www. crdb.uthscsa.edu/. http://swift.embl-heidelberg.de/7tm/. The receptors that are currently known to belong to this family are: 1) 5-hydroxytryptamine (serotonin) 1A to IF, 2A to 2C, 4, 5A, 5B, 6 and 7 (Branchek T., Curr. Biol. (1993) 3:315); 2) acetylcholine, muscarinic-type, Ml to M5; 3) adenosine Al, A2A, A2B and A3 (Stiles G.L. J. Biol. Chem. ( 1992) 267:6451 ; 4) adrenergic alpha- 1 A to - 1 C; alpha-2A to -2D; beta- 1 to -3 (Friell T. et al., Trends Neurosci. (1988) 77:321); 5) angiotensin II types I and II; 6) bombesin subtypes 3 and 4; 7) bradykinin Bl and B2; 8) c3a and C5a anaphylatoxin; 9) cannabinoid CB1 and CB2; 10) chemokines C-C CC-CKR-1 to CC-CKR-8; 11)
Chemokines C-X-C CXC-CKR-1 to CXC-CKR-4; 12) Cholecystokinin-A and cholecystokinin-B/gastrin Dopamine Dl to D5 (Stevens C.F., Curr. Biol. (1991) 7:20); 13) Endothelin ET-a and ET-b (Sakurai T. et al., Trends Pharmacol. Sci. (1992) 73:103-107); 14) fMet-Leu-Phe (fMLP) (Nformyl peptide); 15) Follicle stimulating hormone (FSH-R); 16) Galanin; 17) Gastrin-releasing peptide (GRP-R); 18) Gonadotropin-releasing hormone (GNRH-R); 19) Histamine HI and H2 (gastric receptor I); 20) Lutropin- choriogonadotropic hormone (LSH-R) (Salesse R., et al., Biochimie (1991) 73:109); 21) Melanocortin MC1R to MC5R; 22) Melatonin; 23) Neuromedin B (NMB-R); 24) Neuromedin K (NK-3R); 25) Neuropeptide Y types 1 to 6; 26) Neurotensin (NT-R); 27) Octopamine (tyramine), from insects; 28) Odorants (Lancet D., et al., Curr. Biol.
(1993)3:668; 29) Opioids delta-, kappa- and mu-types (Uhl G.R., et al., Trends Neurosci. (1994) 77:89; 30) Oxytocin (OT-R); 31) Platelet activating factor (PAF-R); 32) Prostacyclin; 33) Prostaglandin D2; 34) Prostaglandin E2, EP1 to EP4 subtypes; 35) Prostaglandin F2; 36) Purinoreceptors (ATP) (Barnard E.A., et al., Trends Pharmacol Sci. (1994)75:67; 37); Somatostatin types 1 to 5; 38) Substance-K (NK-2R); Substance-P (NK- 1R); 39) Thrombin; 40) Thromboxane A2; 41) Thyrotropin (TSH-R) (Salesse R., et al., Biochimie (1991) 73:109); 42) Thyrotropin releasing factor (TRH-R); 42) Vasopressin Via, VI b and V2; 43) Visual pigments (opsins and rhodopsin) (Applebury M.L., et al., Vision Res. (1986) 26:1881; 44) Proto-oncogene mas; 45) A number of oφhan receptors (whose ligand is not known) from mammals and birds; 46) Caenorhabditis elegans putative receptors C06G4.5, C38C10.1, C43C3.2; 47) T27D1.3 and ZC84.4; 48) Three putative receptors encoded in the genome of cytomegalovirus: US27, US28, and UL33; and 49) ECRF3, a putative receptor encoded in the genome of heφesvims saimiri.
The stmcture of these receptors is thought to be identical. They have seven hydrophobic regions, each of which most probably spans the membrane. The N-terminus is located on the extracellular side of the membrane and is often glycosylated, while the C- terminus is cytoplasmic and generally phosphorylated. Three extracellular loops alternate with three intracellular loops to link the seven transmembrane regions. Most, but not all of these receptors, lack a signal peptide. The most conserved parts of these proteins are the transmembrane regions and the first two cytoplasmic loops. A conserved acidic-Arg- aromatic triplet is present in the N-terminal extremity of the second cytoplasmic loop (Attwood T.K., Eliopoulos E.E., Findlay J.B.C. Gene (1991) 93:153-159) and could be implicated in the interaction with G proteins.
A consensus pattern that contains the conserved triplet and that also spans the major part of the third transmembrane helix is used to detect this widespread family of proteins: [GSTALIVMFYWC]-[GSTANCPDE]-{EDPKRH}-x(2)-[LIVMNQGA]-x(2)- [LIVMFT]- [GSTANC]-[LIVMFYWSTAC]-[DENH]-R-[FYWCSH]-x(2)- [LIVM]. b) Seven Transmembrane Integral Membrane Proteins — Secretin Family (7tm 2V
Several of the validation sequences, and thus their corresponding sequence within SEQ ID NOS:1-2502, correspond to a sequence encoding a polypeptide that is a member of the seven transmembrane receptor secretin family. A number of peptide hormones bind to G- protein coupled receptors that, while structurally similar to the majority of G-protein coupled receptors (R7G) (see profile for 7 transmembrane receptors (rhodopsin family), do not show any similarity at the level of their sequence, thus new family whose current known members (Jueppner et al. Science (1991) 254:1024; Hamann et al. Genomics (1996) 32: 144). are: 1) calcitonin receptor, 2) calcitonin gene-related peptide receptor; 3) corticotropin releasing factor receptor types 1 and 2; 4) gastric inhibitory polypeptide receptor; 5) glucagon receptor; 6) glucagon-like peptide 1 receptor; 7) growth hormone- releasing hormone receptor; 7) parathyroid hormone / parathyroid hormone-related peptide types 1 and 2; 8) pituitary adenylate cyclase activating polypeptide receptor; 9) secretin receptor; 10) vasoactive intestinal peptide receptor types 1 and 2; 10) insects diuretic hormone receptor; 11) Caenorhabditis elegans putative receptor C13B9.4; 12) Caenorhabditis elegans putative receptor ZK643.3; 13) human leucocyte CD97 (which contains 3 EGF-like domains in its N-terminal section); 14) human cell surface glycoprotein EMR1 (which contains 6 EGF-like domains in it N-terminal section); and 15) mouse cell surface glycoprotein F4/80 (which contains 7 EGF-like domains in its N- terminal section). All of 1) through 10) are coupled to G-proteins which activate both adenylyl cyclase and the phosphatidylinositol-calcium pathway.
Like classical R7G the secretin family of 7 transmembrane proteins contain seven transmembrane regions. Their N-terminus is located on the extracellular side of the membrane and potentially glycosylated, while their C-terminus is cytoplasmic. But apart from these topological similarities they do not share any region of sequence similarity and are therefore probably not evolutionary related.
Every receptor in the 7 transmember secretin family is encoded on multiple exons, and several of these functionally distinct products. The N-terminal extracellular domain of these receptors contains five conserved cysteines residues that may be involved in disulfide
bonds, with a consensus pattern in the region that spans the first three cysteines. One of the most highly conserved regions spans the C-terminal part of the last transmembrane region and the beginning of the adjacent intracellular region. This second region is used as a second signature pattern. The two consensus patterns are: 1) C-x(3)-[FYWLIV]-D-x(3,4)-C-[FW]-x(2)-[STAGV]-x(8,9)-C-[PF]
2) Q-G-[LMFCA]-[LIVMFT]-[LIV]-x-[LIVFST]-[LIF]-[VFYH]-C- [LFY]-x-N-x(2)-V c) Ank Repeats (ANK). SEQ IS NO:2656, and thus its corresponding sequence within SEQ ID NOS: 1-2502, represents a polynucleotide encoding an Ank repeat- containing protein. The ankyrin motif is a 33 amino acid sequence named after the protein ankyrin which has 24 tandem 33-amino-acid motifs. Ank repeats were originally identified in the cell-cycle-control protein cdclO (Breeden et al, Nature (1987) 329:651). Proteins containing ankyrin repeats include ankyrin, myotropin, I-kappaB proteins, cell cycle protein cdclO, the Notch receptor (Matsuno et al, Development (1997) 124(21) :4265); G9a (or BAT8) of the class III region of the major histocompatibility complex (Biochem J. 290:811-818, 1993), FABP, GABP, 53BP2, Linl2, glp-1, SW14, and SW16. The functions of the ankyrin repeats are compatible with a role in protein-protein interactions (Bork, Proteins (1993) 17(4):363; Lambert and Bennet, Eur. J. Biochem. (1993) 277:1; Kerr et al, Current Op. Cell Biol. (1992) 4:496; Bennet et al, J. Biol. Chem. (1980) 255:6424). The 90 kD N-terminal domain of ankyrin contains a series of 24 33-amino-acid ank repeats. (Lux et al, Nature (1990) 344:36-42, Lambert et al, PNAS USA (1990) 37:1730.) The 24 ank repeats form four folded subdomains of 6 repeats each. These four repeat subdomains mediate interactions with at least 7 different families of membrane proteins. Ankyrin contains two separate binding sites for anion exchanger dimers. One site utilizes repeat subdomain two (repeats 7-12) and the other requires both repeat subdomains 3 and 4 (repeats 13-24). Since the anion exchangers exist in dimers, ankyrin binds 4 anion exchangers at the same time (Michaely and Bennett, J. Biol Chem. (1995) 270(37) :22050). The repeat motifs are involved in ankyrin interaction with tubulin, spectrin, and other membrane proteins. (Lux et al, Nature (1990) 344:36.) The Rel/NF-kappaB/Dorsal family of transcription factors have activity that is controlled by sequestration in the cytoplasm in association with inhibitory proteins referred to as I-kappaB. (Gilmore, Cell (1990) 62:841; Nolan and Baltimore, Curr Opin Genet Dev. (1992) 2:211 ; Baeuerle, Biochim Biophys Acta (1991) 1072:63; Schmitz et al, Trends Cell
Biol. (1991) 7:130.) I-kappaB proteins contain 5 to 8 copies of 33 amino acid ankyrin repeats and certain NF-kappaB/rel proteins are also regulated by cis-acting ankyrin repeat containing domains including pl05NF-kappaB which contains a series of ankyrin repeats (Diehl and Hannink, J. Virol. (1993) 67(12):ll6l). The I-kappaBs and Cactus (also containing ankyrin repeats) inhibit activators through differential interactions with the Rel- homology domain. The gene family includes proto-oncogenes, thus broadly implicating I- kappaB in the control of both normal gene expression and the aberrant gene expression that makes cells cancerous. (Nolan and Baltimore, Curr Opin Genet Dev. (1992) 2(2) :211-220). In the case of rel/NF-kappaB and pp40/I-kappaB(, both the ankyrin repeats and the carboxy -terminal domain are required for inhibiting DNA-binding activity and direct association of pp40/I-kappaB( with rel/NF-kappaB protein. The ankyrin repeats and the carboxy -terminal of pp40/I-kappaB( form a stmcture that associates with the rel homology domain to inhibit DNA binding activity (Inoue et al, PNAS USA (1992) 39:4333).
The 4 ankyrin repeats in the amino terminus of the transcription factor subunit GABP are required for its interaction with the GABP subunit to form a functional high affinity DNA-binding protein. These repeats can be crosslinked to DNA when GABP is bound to its target sequence. (Thompson et al, Science (1991) 253:762; LaMarco et al, Science (1991) 253:789). Myotrophin, a 12.5 kDa protein having a key role in the initiation of cardiac hypertrophy, comprises ankyrin repeats. The ankyrin repeats are characteristic of a haiφin-like protmding tip followed by a helix-turn-helix motif. The V- shaped helix-tum-helix of the repeats stack sequentially in bundles and are stabilized by compact hydrophobic cores, whereas the protmding tips are less ordered. d) Eukaryotic Aspartyl Proteases (asp). Several of the validation sequences, and thus their corresponding sequence within SEQ ID NOS: 1-2502, correspond to a sequence encoding a novel eukaryotic aspartyl protease. Aspartyl proteases, known as acid proteases, (EC 3.4.23.-) are a widely distributed family of proteolytic enzymes (Foltmann B., Essays Biochem. (1981) 77:52; Davies D.R., Annu. Rev. Biophys. Chem. (1990) 79:189; Rao J.K.M., et al, Biochemistry (1991) 30:4663) known to exist in vertebrates, fungi, plants, retro vi ses and some plant vimses. Aspartate proteases of eukaryotes are monomeric enzymes which consist of two domains. Each domain contains an active site centered on a catalytic aspartyl residue. The two domains most probably evolved from the duplication of an ancestral gene encoding a primordial domain. Currently known eukaryotic aspartyl proteases include: 1) Vertebrate gastric pepsins A and C (also known as
gastricsin); 2) Vertebrate chymosin (rennin), involved in digestion and used for making cheese; 3) Vertebrate lysosomal cathepsins D (EC 3.4.23.5) and E (EC 3.4.23.34); 4) Mammalian renin (EC 3.4.23.15) whose function is to generate angiotensin I from angiotensinogen in the plasma; 5) Fungal proteases such as aspergillopepsin A (EC 3.4.23.18), candidapepsin (EC 3.4.23.24), mucoropepsin (EC 3.4.23.23) (mucor rennin), endothiapepsin (EC 3.4.23.22), polyporopepsin (EC 3.4.23.29), and rhizopuspepsin (EC 3.4.23.21); and 6) Yeast saccharopepsin (EC 3.4.23.25) (proteinase A) (gene PEP4). PEP4 is implicated in posttranslational regulation of vacuolar hydrolases; 7) Yeast barrieφepsin (EC 3.4.23.35) (gene BAR1); a protease that cleaves alpha-factor and thus acts as an antagonist of the mating pheromone; and 8) Fission yeast sxal which is involved in degrading or processing the mating pheromones.
Most retrovimses and some plant vimses, such as badnavimses, encode for an aspartyl protease which is an homodimer of a chain of about 95 to 125 amino acids. In most retrovimses, the protease is encoded as a segment of a polyprotein which is cleaved during the maturation process of the vims. It is generally part of the pol polyprotein and, more rarely, of the gag polyprotein. Because the sequence around the two aspartates of eukaryotic aspartyl proteases and around the single active site of the viral proteases is conserved, a single signature pattern can be used to identify members of both groups of proteases. The consensus pattern is: [LIVMFGAC]-[LIVMTADN]-[LIVFSA]-D-[ST]-G- [STAV]-[STAPDENQ]- x-[LIVMFSTNC]-x-[LIVMFGTA], where D is the active site residue. e) ATPases Associated with Various Cellular Activities (ATPases). Several of the validation sequences, and thus their corresponding sequence within SEQ ID NOS: 1-2502, correspond to a sequence that encodes a novel member of the "ATPases Associated with diverse cellular Activities" (AAA) protein family. The AAA protein family is composed of a large number of ATPases that share a conserved region of about 220 amino acids that contains an ATP-binding site (Froehlich et al, J. Cell Biol. (1991) 774:443; Erdmann et al Cell (1991) 64:499; Peters et al, EMBOJ. (1990) 9:1757; Kunau et al, Biochimie (1993) 75:209-224; Confalonieri et al, BioEssays (1995) 77:639; http://yeamob.pci.chemie.uni- tuebingen.de/AAA/Description.html). The proteins that belong to this family either contain one or two AAA domains.
Proteins containing two AAA domains include: 1) Mammalian and drosophila NSF (N-ethylmaleimide-sensitive fusion protein) and the fungal homolog, SEC 18, which are
involved in intracellular transport between the endoplasmic reticulum and Golgi, as well as between different Golgi cisternae; 2) Mammalian transitional endoplasmic reticulum ATPase (previously known as p97 or VCP), which is involved in the transfer of membranes from the endoplasmic reticulum to the golgi apparatus. This ATPase forms a ring-shaped homooligomer composed of six subunits. The yeast homolog, CDC48, plays a role in spindle pole proliferation; 3) Yeast protein PAS 1 essential for peroxisome assembly and the related protein PAS1 from Pichia pastoris; 4) Yeast protein AFG2; 5) Sulfolobus acidocaldarius protein SAV and Halobacterium salinarium cdcH, which may be part of a transduction pathway connecting light to cell division. Proteins containing a single AAA domain include: 1) Escherichia coli and other bacteria ftsH (or hflB) protein. FtsH is an ATP-dependent zinc metallopeptidase that degrades the heat-shock sigma-32 factor, and is an integral membrane protein with a large cytoplasmic C-terminal domain that contain both the AAA and the protease domains; 2) Yeast protein YME1, a protein important for maintaining the integrity of the mitochondrial compartment. YME1 is also a zinc-dependent protease; 3) Yeast protein AFG3 (or YTA10). This protein also contains an AAA domain followed by a zinc-dependent protease domain; 4) Subunits from regulatory complex of the 26S proteasome (Hilt et al, Trends Biochem. Sci. (1996) 27:96), which is involved in the ATP-dependent degradation of ubiquitinated proteins, which subunits include: a) Mammalian 4 and homologs in other higher eukaryotes, in yeast (gene YTA5) and fission yeast (gene mts2); b) Mammalian 6 (TBP7) and homologs in other higher eukaryotes and in yeast (gene YTA2); c) Mammalian subunit 7 (MSS1) and homologs in other higher eukaryotes and in yeast (gene CIM5 or YTA3); d) Mammalian subunit 8 (P45) and homologs in other higher eukaryotes and in yeast (SUG1 or CIM3 or TBY1) and fission yeast (gene letl); e) Other probable subunits include human TBPl, which influences HIV gene expression by interacting with the vims tat transactivator protein, and yeast YTA1 and YTA6; 5) Yeast protein BCS1, a mitochondrial protein essential for the expression of the Rieske iron-sulfur protein; 6) Yeast protein MSP1, a protein involved in intramitochondrial sorting of proteins; 7) Yeast protein PAS8, and the corresponding proteins PAS5 from Pichia pastoris and PAY4 from Yarrowia lipolytica; 8) Mouse protein SKD1 and its fission yeast homolog
(SpAC2Gl 1.06); 9) Caenorhabditis elegans meiotic spindle formation protein mei-1; 10) Yeast protein SAP1 ' 11) Yeast protein YTA7; and 12) Mycobacterium leprae hypothetical protein A2126A.
In general, the AAA domains in these proteins act as ATP-dependent protein clamps(Confalonieri et al (1995) BioEssays 77:639). In addition to the ATP-binding 'A' and 'B' motifs, which are located in the N-terminal half of this domain, thereis a highly conserved region located in the central part of the domain which was used in the development of the signature pattern. The consensus pattern is: [LIVMT]-x-[LIVMT]- [LIVMF]-x-[GATMC]-[ST]-[NS]-x(4)-[LIVM]- D-x-A-[LIFA]-x-R. f) Bcl-2 family (Bcl-2). SEQ ID NO:3404, and thus the corresponding sequence it validates, represents a polynucleotide encoding an apoptosis regulator protein of the Bcl-2 family. Active cell suicide (apoptosis) is induced by events such as growth factor withdrawal and toxins. It is controlled by regulators, which have either an inhibitory effect on programmed cell death (anti-apoptotic) or block the protective effect of inhibitors (pro- apoptotic) (Vaux, 1993, Curr. Biol. 3:877-878, and White, 1996, Genes Dev. 10:2859- 2869). Many vimses have found a way of countering defensive apoptosis by encoding their own anti-apoptosis genes, preventing their target cells from dying prematurely. All proteins belonging to the Bcl-2 family (Reed et al., 1996, Adv. Exp. Med. Biol.
406:99-112) contain either a BH1, BH2, BH3, or BH4 domain. All anti-apoptotic proteins contain BH1 and BH2 domains; some of them contain an additional N-terminal BH4 domain (Bcl-2, Bcl-x(L), Bcl-w), which is never seen in pro-apoptotic proteins, except for Bcl-x(S). On the other hand, all pro-apoptotic proteins contain a BH3 domain (except for Bad) necessary for dimerization with other proteins of Bcl-2 family and cmcial for their killing activity; some of them also contain BH1 and BH2 domains (Bax, Bak). The BH3 domain is also present in some anti-apoptotic protein, such as Bcl-2 or Bcl-x(L). Proteins that are known to contain these domains are listed below.
1. Vertebrate protein Bcl-2. Bcl-2 blocks apoptosis; it prolongs the survival of hematopoietic cells in the absence of required growth factors and also in the presence of various stimuli inducing cellular death. Two isoforms of bcl-2 (alpha and beta) are generated by alternative splicing. Bcl-2 is expressed in a wide range of tissues at various times during development. It forms heterodimers with the Bax proteins.
2. Vertebrate protein Bcl-x. Two isoforms of Bcl-x (Bcl-x(L) and Bcl-x(S)) are generated by alternative splicing. While the longer product (Bcl-x(L)) can protect a growth-factor-dependent cell line from apoptosis, the shorter form blocks the protective effect of Bcl-2 and Bcl-x(L) and acts as an anti-anti-apoptosis protein.
3. Mammalian protein Bax. Bax blocks the anti-apoptosis ability of Bcl-2 with which
it forms heterodimers. There is no evidence that Bax has any activity in the absence of Bcl-2. Three isoforms of bax (alpha, beta and gamma) are generated by alternative splicing.
4. Mammalian protein Bak, which promotes cell death and counteracts the protection from apoptosis provided by Bcl-2.
5. Mammalian protein Bcl-w, which promotes cell survival.
6. Mammalian protein bad, which promotes cell death, and counteracts the protection from apoptosis provided by Bcl-x(L), but not that of Bcl-2.
7. Human protein Bik, which promotes cell death, but cannot counteract the protection from apoptosis provided by Bcl-2.
8. Mouse protein Bid, which induces caspases and apoptosis, and counteracts the protection from apoptosis provided by Bcl-2.
9. Human induced myeloid leukemia cell differentiation protein MCL1. MCL1 is probably involved in programming of differentiation and concomitant maintenance of viability but not proliferation. Its expression increases early during phorbol ester induced differentiation in myeloid leukemia cell line ML-1.
10. Mouse hemopoietic-specific early response protein A 1.
11. Mammalian activator of apoptosis Harakiri (Inohara et al., 1997, EMBO J. 16:1686-1694) (also known as neuronal death protein Dp5). This is a small protein of 92 residues that activates apoptosis. It contains a BH3 domain, but no BHl, BH2 or BH4 domains.
The following consensus patterns have been developed for the four BH domains: l) [LVME]-[FT]-x-[GSD]-[GL]-x(l,2)-[NS]-[YW]-G-R-[LIV]- [LIVC]-[GAT]-
[LIVMF](2)-x-F-[GSAE]-[GSARY] 2) W-[LIM]-x(3)-[GR]-G-[WQ]-[DENSAV]-x-[FLGA]-[LIVFTC]
3) [LIVAT]-x(3)-L-[KARQ]-x-[IVAL]-G-D-[DESG]-[LIMFV]-[DENSHQ]-[LVSHRQ]-
[NSR]
4) [DS]-[NT]-R-[AE]-[LI]-V-x-[KD]-[FY]-[LIV]-[GHS]-Y-K-L- [SR]-Q-[RK]-G-[HY]-x-
[CW]. g Bromodomain (bromodomain). SEQ ID NOS:4036 and 4489, and thus the corresponding sequences they validate, represent polynucleotides encoding a polypeptide having a bromodomain region (Haynes et al., 1992, Nucleic Acids Res. 20:2693-2603,
Tamkun et al., 1992, Cell 68:561-572, and Tamkun, 1995, Curr. Opin. Genet. Dev. 5:473-
477), which is a conserved region of about 70 amino acids found in the following proteins: 1) Higher eukaryotes transcription initiation factor TFIID 250 Kd subunit (TBP-associated factor p250) (gene CCG1); P250 is associated with the TFIID TATA-box binding protein and seems essential for progression of the GI phase of the cell cycle. 2) Human RJNG3, a protein of unknown function encoded in the MHC class II locus; 3) Mammalian CREB- binding protein (CBP), which mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein; 4) Mammalian homologs of brabma, including three brabma-like human: SNF2a(hBRM), SNF2b, and BRG1; 5) Human BS69, a protein that binds to adenovims El A and inhibits E1A transactivation; 6) Human peregrin (or Brl40). The bromodomain is thought to be involved in protein-protein interactions and may be important for the assembly or activity of multicomponent complexes involved in transcriptional activation. The consensus pattern, which spans a major part of the bromodomain, is: [STANVF]-x(2)-F-x(4)-[DNS]-x(5,7)-[DENQTF]-Y-[HFY]-x(2)- [LIVMFY]-x(3)-[LIVM]-x(4)-[LIVM]-x(6,8)-Y-x(12,13)-[LIVM]-x(2)-N-[SACF]-x(2)- [FY]. h) Basic Region Plus Leucine Zipper Transcription Factors (BZIP). SEQ ID NO:3408, 2951, and 4850, and thus the corresponding sequences these sequences validate, represent polynucleotides encoding a novel member of the family of basic region plus leucine zipper transcription factors. The bZIP superfamily (Hurst, Protein Prof. (1995) 2:105; and Ellenberger, Curr. Opin. Struct. Biol. (1994) 4:12) of eukaryotic DNA-binding transcription factors encompasses proteins that contain a basic region mediating sequence- specific DNA-binding followed by a leucine zipper required for dimerization. Members of the family include transcription factor AP-1, which binds selectively to enhancer elements in the cis control regions of SV40 and metallothionein IIA. AP-1 , also known as c-jun, is the cellular homolog of the avian sarcoma vims 17 (AS VI 7) oncogene v-jun.
Other members of this protein family include jun-B and jun-D, probable transcription factors that are highly similar to jun/AP-1 ; the fos protein, a proto-oncogene that forms a non-covalent dimer with c-jun; the fos-related proteins fra-1, and fos B; and mammalian cAMP response element (CRE) binding proteins CREB, CREM, ATF-1, ATF-3, ATF-4, ATF-5, ATF-6 and LRF-1. The consensus pattern for this protein family is: [KR]-x(l,3)- [RKSAQ]-N-x(2)-[SAQ](2)-x-[RKTAENQ]-x-R-x-[RK]. i) Cvclins (cvclin). SEQ ID NOS:3618, 3895, and 4536, and thus the corresponding sequences these sequences validate, represent polynucleotides encoding
cyclins, and SEQ ID NO:55 and 56, respectively, show the corresponding full-length polynucleotides. SEQ ID NO:57 and 58 show, respectively, the translations of SEQ ID NO:55 and 56. Cyclins (Nurse, 1990, Nature 344:503-508; Norbury et al., 1991, Curr. Biol. 1 :23-24; and Lew et al., 1992, Trends Cell Biol. 2:77-81) are eukaryotic proteins that play an active role in controlling nuclear cell division cycles. There are two main groups of cyclins. G2/M cyclins are essential for the control of the cell cycle at the G2/M (mitosis) transition. G2/M cyclins accumulate steadily during G2 and are abmptly destroyed as cells exit from mitosis (at the end of the M-phase). Gl/S cyclins are essential for the control of the cell cycle at the Gl/S (start) transition. The best conserved region is in the central part of the cyclins' sequences, known as the "cyclin-box," from which a 32 residue consensus pattern was derived: R-x(2)- [LIVMSA]-x(2)-[FYWS]-[LIVM]-x(8)-[LIVMFC]-x(4)-[LIVMFYA]-x(2)-[STAGC]- [LIVMFYQ]-x-[LIVMFYC]-[LIVMFY]-D-[RKH]-[LIVMFYW]. j) Eukaryotic thiol (cysteine) proteases active sites (Cys-protease). SEQ ID NOS:3344, 3684, 3688, and 4801, and thus also the sequences they validate, repreasent polynucleotides encoding proteins having a eukaryotic thiol (cysteine) protease active site. Eukaryotic thiol proteases (Dufour E., Biochimie (1988) 70:1335); are a family of proteolytic enzymes which contain an active site cysteine. Catalysis proceeds through a thioester intermediate and is facilitated by a nearby histidine side chain; an asparagine completes the essential catalytic triad. The proteases that belong to this family are:
1) vertebrate lysosomal cathepsins B (Kirschke H., et al., Protein Prof. (1995) 2:1587- 1643); 2) vertebrate lysosomal dipeptidyl peptidase l (also known as cathepsin C) (Kirschke H., et al., supra); 3) vertebrate calpains (Calpains are intracellular calcium- activated thiol protease that contain both an N-terminal catalytic domain and a C-terminal calcium-binding domain); 4) mammalian cathepsin K, which seems involved in osteoclastic bone resoφtion (Shi G.-P., et al., FEBS Lett. (1995) 357:129); 5) human cathepsin O ([ 4] Velasco G., Ferrando A.A., Puente X.S., Sanchez L.M., Lopez-Otin C. J. Biol. Chem. (1994) 269:27136); 6) bleomycin hydrolase (which catalyzes the inactivation of the antitumor dmg BLM (a glycopeptide)); 7) Plant enzymes such as: barley aleurain, EP-B1/B4; kidney bean EP-Cl, rice bean SH-EP; kiwi fruit actinidin; papaya latex papin, chymopapain, caricain, and proteinase IV; pea turgor-responsive protein 15 A; pineapple stem bromelain; rape COT44; rice oryzain alpha, beta, and gamma; tomato low- temperature induced, Arabidopsis thaliana A494, RD19A and RD21A; 8) - House-dust
mites allergens DerPl and EurMl ; 9) cathepsin B-like proteinases from the worms Caenorhabditis elegans (genes gcp-1, cpr-3, cpr-4, cpr-5 and cpr-6), Schistosoma mansoni (antigen SM31) and Japonica (antigen SJ31), Haemonchus contortus (genes AC-1 and AC-2), and Ostertagia ostertagi (CP-1 and CP-3); 10) slime mold cysteine proteinases CP1 and CP2; 11) cruzipain from Trypanosoma cmzi and bmcei; 12) throphozoite cysteine proteinase (TCP) from various Plasmodium species; 13) proteases from Leishmania mexicana, Theileria annulata and Theileria parva; 14) Baculovimses cathepsin-like enzyme (v-cath); 15) Drosophila small optic lobes protein (gene sol), a neuronal protein that contains a calpain-like domain; 16) yeast thiol protease BLH1/YCP1/LAP3; 17) Caenorhabditis elegans hypothetical protein C06G4.2, a calpain-like protein.
In addition, two bacterial peptidases are also part of this family: 1) aminopeptidase C from Lactococcus lactis (gene pepC) (Chapot-Chartier M.P., et al., Appl Environ. Microbiol. (1993) 59:330); and 2) thiol protease tpr from Poφhyromonas gingivalis. Three other proteins are structurally related to this family, but may have lost their proteolytic activity. These include: 1) soybean oil body protein P34 (which has its active site cysteine replaced by a glycine); 2) rat testin (which is a sertoli cell secretory protein highly similar to cathepsin L but with the active site cysteine is replaced by a serine); and 3) Plasmodium falciparum serine-repeat protein (SERA) (which is the major blood stage antigen and possesses a C-terminal thiol-protease-like domain (Higgins D.G., et al., Nature (1989) 340:604), with the active site cysteine is replaced by a serine).
The sequences around the three active site residues are well conserved and can be used as signature patterns:
Consensus pattern #1 : Q-x(3)-[GE]-x-C-[YW]-x(2)-[STAGC]-[STAGCV] (where C is the active site residue) Consensus pattern #2: [LIVMGSTAN]-x-H-[GSACE]-[LIVM]-x-[LIVMAT](2)-G- x-[GSADNH] (where H is the active site residue);
Consensus patent #3: [FYCH]-[WI]-[LIVT]-x-[KRQAG]-N-[ST]-W-x(3)-[FYW]- G-x(2)-G- [LFYW]-[LIVMFYG]-x-[LIVMF] (where N is the active site residue). k) Phorbol Esters/Diacylglvcerol Binding (DAG_PE_bind). SEQ ID NO:4659, and thus the sequence it validates, represents a polynucleotide encoding a protein belonging to the family including phorbol esters/diacylglycerol binding proteins. Diacylglycerol (DAG) is an important second messenger. Phorbol esters (PE) are analogues of DAG and potent tumor promoters that cause a variety of physiological changes when administered to both
cells and tissues. DAG activates a family of serine/threonine protein kinases, collectively known as protein kinase C (PKC) (Azzi et al, Eur. J. Biochem. (1992) 203:547). Phorbol esters can directly stimulate PKC. The N-terminal region of PKC, known as Cl, has been shown (Ono et al., Proc. Natl. Acad. Sci. USA (1989) 36:4868) to bind PE and DAG in a phospholipid and zinc-dependent fashion. The Cl region contains one or two copies (depending on the isozyme of PKC) of a cysteine-rich domain about 50 amino-acid residues long and essential for DAG/PE-binding. Such a domain has also been found in, for example, the following proteins.
(1) Diacylglycerol kinase (EC 2.7.1.107) (DGK) (Sakane et al, Nature (1990) 344:345), the enzyme that converts DAG into phosphatidate. It contains two copies of the DAG/PE-binding domain in its N-terminal section. At least five different forms of DGK are known in mammals; and
(2) N-chimaerin, a brain specific protein which shows sequence similarities with the BCR protein at its C-terminal part and contains a single copy of the DAG/PE-binding domain at its N-terminal part. It has been shown (Ahmed et al, Biochem. J. (1990)
272:161, and Ahmed et al, Biochem. J. (1991) 230:233) to be able to bind phorbol esters. The DAG/PE-binding domain binds two zinc ions; the ligands of these metal ions are probably the six cysteines and two histidines that are conserved in this domain. The signature pattern completely spans the DAG/PE domain. The consensus pattern is: H-x- [LIVMFYW]-x(8,l l)-C-x(2)-C-x(3)-[LIVMFC]-x(5,10)-C-x(2)-C-x(4)-[HD]-x(2)-C- x(5,9)-C. All the C and H are probably involved in binding zinc.
1) DEAD and DEAH box families ATP-dependent helicases signatures (Dead box helic). SEQ ID NOS:4821 and 5083, and thus the sequences they validate, represent polynucleotides encoding a novel member of the DEAD box family. A number of eukaryotic and prokaryotic proteins have been characterized (Schmid S.R., et al, Mol. Microbiol. (1992) 6:283; Linder P., et al., Nature (1989) 337:121; Wassarman D.A., et al., Nature (1991) 349:463) on the basis of their stmctural similarity. All are involved in ATP- dependent, nucleic-acid unwinding. Proteins currently known to belong to this family are:
1) Initiation factor eIF-4A. Found in eukaryotes, this protein is a subunit of a high molecular weight complex involved in 5 'cap recognition and the binding of mRNA to ribosomes. It is an ATP-dependent RNA-helicase.
2) PRP5 and PRP28. These yeast proteins are involved in various ATP-requiring steps of the pre-mRNA splicing process.
3) PI 10, a mouse protein expressed specifically during spermatogenesis.
4) An3, a Xenopus putative RNA helicase, closely related to PI 10.
5) SPP81/DED1 and DBPl, two yeast proteins involved in pre-mRNA splicing and related to PI 10. 6) Caenorhabditis elegans helicase glh-1.
7) MSS116, a yeast protein required for mitochondrial splicing.
8) SPB4, a yeast protein involved in the maturation of 25 S ribosomal RNA.
9) p68, a human nuclear antigen. p68 has ATPase and DNA-helicase activities in vitro. It is involved in cell growth and division. 10) Rm62 (p62), a Drosophila putative RNA helicase related to p68.
11) DBP2, a yeast protein related to p68.
12) DHH1, a yeast protein.
13) DRS1, a yeast protein involved in ribosome assembly.
14) MAK5, a yeast protein involved in maintenance of dsRNA killer plasmid. 15) ROK 1 , a yeast protein.
16) stel3, a fission yeast protein.
17) Vasa, a Drosophila protein important for oocyte formation and specification of embryonic posterior stmctures.
18) Me31B, a Drosophila maternally expressed protein of unknown function. 19) dbpA, an Escherichia coli putative RNA helicase.
20) deaD, an Escherichia coli putative RNA helicase which can suppress a mutation in the φsB gene for ribosomal protein S2.
21) rhlB, an Escherichia coli putative RNA helicase.
22) rhlE, an Escherichia coli putative RNA helicase. 23) rmB, an Escherichia coli protein that shows RNA-dependent ATPase activity, which interacts with 23 S ribosomal RNA.
24) Caenorhabditis elegans hypothetical proteins T26G10.1, ZK512.2 and ZK686.2.
25) Yeast hypothetical protein YHR065c. 26) Yeast hypothetical protein YHR169w.
27) Fission yeast hypothetical protein SpAC31A2.07c.
28) Bacillus subtilis hypothetical protein yxiN.
All of the above proteins share a number of conserved sequence motifs. Some of them are specific to this family while others are shared by other ATP-binding proteins or by proteins belonging to the helicases 'superfamily' (Hodgman T.C., Nature (1988) 333:22 and Nature (1988) 333:578 (Errata); http://www.expasy.ch/www/linder/HELICASES_TEXT.html). One of these motifs, called the 'D-E-A-D-box', represents a special version of the B motif of ATP-binding proteins. Some other proteins belong to a subfamily which have His instead of the second Asp and are thus said to be 'D-E-A-H-box' proteins (Wassarman D.A., et al., Nature (1991) 349:463; Harosh I., et al., Nucleic Acids Res. (1991) 79:6331; Koonin E.V., et al., J. Gen. Virol. (1992) 73:989; http://www.expasy.ch/www/linder/HELICASES_TEXT.html). Proteins currently known to belong to this DEAH subfamily are:
1) PRP2, PRP 16, PRP22 and PRP43. These yeast proteins are all involved in various ATP -requiring steps of the pre-mRNA splicing process. 2) Fission yeast prhl, which my be involved in pre-mRNA splicing. 3) Male-less (mle), a Drosophila protein required in males, for dosage compensation of X chromosome linked genes. 4) RAD3 from yeast. RAD3 is a DNA helicase involved in excision repair of DNA damaged by UV light, bulky adducts or cross-linking agents. Fission yeast radl5 (rhp3) and mammalian DNA excision repair protein XPD (ERCC-2) are the homologs of RAD3. 5) Yeast CHL1 (or CTF1), which is important for chromosome transmission and normal cell cycle progression in G(2)/M. 6) Yeast TPSl. 7) Yeast hypothetical protein YKL078w. 8) Caenorhabditis elegans hypothetical proteins C06E1.10 and K03H1.2. 9) Poxviruses' early transcription factor 70 Kd subunit which acts with RNA polymerase to initiate transcription from early gene promoters. 10) 18, a putative vaccinia vims helicase. 11) hφA, an Escherichia coli putative RNA helicase. The following signature patterns are used to identify member for both subfamilies:
Consensus pattern: [LIVMF](2)-D-E-A-D-[RKEN]-x-[LIVMFYGSTN] Consensus pattern: [GSAH]-x-[LIVMF](3)-D-E-[ALIV]-H-[NECR]. m) EF Hand (EFhand). Several of the validation sequences, and thus the sequences they validate, correspond to polynucleotides encoding a novel protein in the family of EF- hand proteins. Many calcium-binding proteins belong to the same evolutionary family and share a type of calcium-binding domain known as the EF-hand (Kawasaki et al, Protein. Prof. (1995) 2:305-490). This type of domain consists of a twelve residue loop flanked on both sides by a twelve residue alpha-helical domain. In an EF-hand loop the calcium ion is
coordinated in a pentagonal bipyramidal configuration. The six residues involved in the binding are in positions 1, 3, 5, 7, 9 and 12; these residues are denoted by X, Y, Z, -Y, -X and -Z. The invariant Glu or Asp at position 12 provides two oxygens for liganding Ca (bidentate ligand). Proteins known to contain EF-hand regions include: Calmodulin (Ca=4, except in yeast where Ca=3) ("Ca=" indicates approximate number of EF-hand regions); diacylglycerol kinase (EC 2.7.1.107) (DGK) (Ca=2); 2) FAD-dependent glycerol-3- phosphate dehydrogenase (EC 1.1.99.5) from mammals (Ca=l); guanylate cyclase activating protein (GCAP) (Ca=3); MIF related proteins 8 (MRP-8 or CFAG) and 14 (MRP- 14) (Ca=2); myosin regulatory light chains (Ca=l); oncomodulin (Ca=2); osteonectin (basement membrane protein BM-40) (SPARC); and proteins that contain an "osteonectin" domain (QR1, matrix glycoprotein SCI).
The consensus pattern includes the complete EF-hand loop as well as the first residue which follows the loop and which seem to always be hydrophobic: D-x-[DNS]- {ILVFYW}-[DENSTG]-[DNQGHRK]-{GP}-[LIVMC]-[DENQSTAGC]-x(2)-[DE]- [LIVMFYW]. n) Ets Domain fEts Nterm). SEQ ID NO:2849, and thus the sequence it validates, represents a polynucleotide encoding a polypeptide with N-terminal homology in ETS domain. Proteins of this family contain a conserved domain, the "ETS-domain," that is involved in DNA binding. The domain appears to recognize purine-rich sequences; it is about 85 to 90 amino acids in length, and is rich in aromatic and positively charged residues (Wasylyk, et al., , Eur. J. Biochem. (1993) 277:718).
The ets gene family encodes a novel class of DNA-binding proteins, each of which binds a specific DNA sequence. These proteins comprise an ets domain that specifically interacts with sequences containing the common core tri-nucleotide sequence GGA. In addition to an ets domain, native ets proteins comprise other sequences which can modulate the biological specificity of the protein. Ets genes and proteins are involved in a variety of essential biological processes including cell growth, differentiation and development, and three members are implicated in oncogenic process. o) Type II fϊbronectin collagen-binding domain (Fntvpell). A few of the validation sequences, and thus the sequences they validate, represent polynucleotides encoding a polypeptide having a type II fibronectin collagen binding domain. Fibronectin is a plasma protein that binds cell surfaces and various compounds including collagen, fibrin, heparin,
DNA, and actin. The major part of the sequence of fibronectin consists of the repetition of three types of domains, which are called type I, II, and III (Skorstengaard K., et al., Eur. J. Biochem. (1986) 767:441). Type II domain is approximately forty residues long, contains four conserved cysteines involved in disulfide bonds and is part of the collagen-binding region of fibronectin. In fibronectin the type II domain is duplicated. Type II domains have also been found in the following proteins: 1) blood coagulation factor XII (Hageman factor) (1 copy); 2) bovine seminal plasma proteins PDC-109 (BSP-A1/A2) and BSP-A3 (Seidah N.G., et al., Biochem. J. (1987) 243:195. (twice); 3) cation-independent mannose- 6-phosphate receptor (which is also the insulin-like growth factor II receptor) Komfeld S., Annu. Rev. Biochem. (1992) 67:307) (1 copy); 4) Mannose receptor of macrophages (Taylor M.E., et al., J Biol. Chem. (1990) 265:12156) (1 copy); 5) 180 Kd secretory phospholipase A2 receptor (1 copy) Lambeau G., et al., J Biol. Chem. (1994) 269:1575; 6) DEC-205 receptor (1 copy); 6) Jiang W., et al., Nature (1995) 375:151); 7) 72 Kd type IV collagenase (EC 3.4.24.24) (MMP-2) (Collier I.E., et al., J. Biol. Chem. (1988) 263:6579) (3 copies); 7) 92 Kd type IV collagenase (EC 3.4.24.24) (MMP-9) (3 copies); 8)
Hepatocyte growth factor activator (Miyazawa K., et al., J. Biol. Chem. (1993) 263:10024) (1 copy).
A schematic representation of the position of the invariant residues and the topology of the disulfide bonds in fibronectin type II domain is shown below: xxCxxPFx#xxxxxxxCxxxxxxxxWCxxxxx#xxx#x#Cxx where 'C represents the conserved cysteine involved in a disulfide bond and '#' represents a large hydrophobic residue. The consensus pattern for identifying members of this family, which pattern spans this entire domain, is: C-x(2)-P-F-x-[FYWI]-x(7)-C-x(8,10)-W-C- x(4)-[DNSR]-[FYW]- x(3,5)-[FYW]-x-[FYWI]-C (where the four C's are involved in disulfide bonds). p) G-Protein Alpha Subunit (G-alpha). Several of the validation sequences, and thus the sequences they validate, correspond to a gene encoding a novel polypeptide of the G-protein alpha subunit family. Guanine nucleotide binding proteins (G-proteins) are a family of membrane-associated proteins that couple extracellularly-activated integral- membrane receptors to intracellular effectors, such as ion channels and enzymes that vary the concentration of second messenger molecules. G-proteins are composed of 3 subunits (alpha, beta and gamma) which, in the resting state, associate as a trimer at the inner face of
the plasma membrane. The alpha subunit has a molecule of guanosine diphosphate (GDP) bound to it. Stimulation of the G-protein by an activated receptor leads to its exchange for GTP (guanosine triphosphate). This results in the separation of the alpha from the beta and gamma subunits, which always remain tightly associated as a dimer. Both the alpha and beta-gamma subunits are then able to interact with effectors, either individually or in a cooperative manner. The intrinsic GTPase activity of the alpha subunit hydrolyses the bound GTP to GDP. This returns the alpha subunit to its inactive conformation and allows it to reassociate with the beta-gamma subunit, thus restoring the system to its resting state. G-protein alpha subunits are 350-400 amino acids in length and have molecular weights in the range 40-45 kDa. Seventeen distinct types of alpha subunit have been identified in mammals. These fall into 4 main groups on the basis of both sequence similarity and function: alpha-s, alpha-q, alpha-i and alpha-12 (Simon et al, Science (1993) 252:802). Many alpha subunits are substrates for ADP-ribosylation by cholera or pertussis toxins. They are often N-terminally acylated, usually with myristate and/or palmitoylate, and these fatty acid modifications are probably important for membrane association and high- affinity interactions with other proteins. The atomic stmcture of the alpha subunit of the G-protein involved in mammalian vision, transducin, has been elucidated in both GTP- and GDB-bound forms, and shows considerable similarity in both primary and tertiary stmcture in the nucleotide-binding regions to other guanine nucleotide binding proteins, such as p21 -ras and EF-Tu. q) Helicases conserved C-terminal domain (helicase C). SEQ ID NOS:2503, 4469, and 5020, and thus the sequences they validate, represent polynucleotides encoding novel members of the DEAD/H helicase family. The DEAD and DEAH families are described above. r) Homeobox domain (homeobox). SEQ ID NO: 4241, and thus the sequence it validates, represents a polynucleotide encoding a protein having a homeobox domain. The 'homeobox' is a protein domain of 60 amino acids (Gehring In: Guidebook to the Homebox Genes, Duboule D., Ed., ppl-10, Oxford University Press, Oxford, (1994); Buerglin In: Guidebook to the Homebox Genes, pp25-72, Oxford University Press, Oxford, (1994); Gehring Trends Biochem. Sci. (1992) 77:277-280; Gehring et alAnnu. Rev. Genet. (1986) 20:147-173; Schofield Trends Neurosci. (1987) 70:3-6; http://copan.bioz.unibas.ch/ homeo.html) first identified in number of Drosophila homeotic and segmentation proteins. It is extremely well conserved in many other animals, including vertebrates. This domain
binds DNA through a helix-tum-helix type of structure. Several proteins that contain a homeobox domain play an important role in development. Most of these proteins are sequence-specific DNA-binding transcription factors. The homeobox domain is also very similar to a region of the yeast mating type proteins. These are sequence-specific DNA- binding proteins that act as master switches in yeast differentiation by controlling gene expression in a cell type-specific fashion.
A schematic representation of the homeobox domain is shown below. The helix- turn-helix region is shown by the symbols Η' (for helix), and 't' (for turn).
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxHHHHHHHHtttHHHHHHHHHxxxxxxxxxx
1 60
The pattern detects homeobox sequences 24 residues long and spans positions 34 to 57 of the homeobox domain. The consensus pattern is as follows: [LIVMFYG]-[ASLVR]-x(2)- [LIVMSTACN]-x-[LIVM]-x(4)-[LIV]-[RKNQESTAIY]-[LIVFSTNKH]-W-[FYVC]-x- [NDQTAH]-x(5)-[RKNAIMW]. x) MAP kinase kinase (mkk). Several validation sequences, and thus the sequences they validate, represent novel members of the MAP kinase kinase family. MAP kinases (MAPK) are involved in signal transduction, and are important in cell cycle and cell growth controls. The MAP kinase kinases (MAPKK) are dual-specificity protein kinases which phosphorylate and activate MAP kinases. MAPKK homologues have been found in yeast, invertebrates, amphibians, and mammals. Moreover, the MAPKK/MAPK phosphorylation switch constitutes a basic module activated in distinct pathways in yeast and in vertebrates. MAPKK regulation studies have led to the discovery ofat least four MAPKK convergent pathways in higher organisms. One of these is similar to the yeast pheromone response pathway which includes the stel 1 protein kinase. Two other pathways require the activation of either one or both of the serine/threonine kinase-encoded oncogenes c-Raf-1 and c-Mos. Additionally, several studies suggest a possible effect of the cell cycle control regulator cyclin-dependent kinase 1 (cdc2) on MAPKK activity. Finally, MAPKKs are apparently essential transducers through which signals must pass before reaching the nucleus. For review, see, e.g., Biologique Biol Cell (1993) 79:193-207; Nishida et al, Trends Biochem Sci (1993) 73:128-31; Ruderman Curr Opin Cell Biol (1993) 5:207-13; Dhanasekaran et al, Oncogene (1998) 77:1447-55; Kiefer et al, Biochem Soc Trans (1997) 25:491-8; and Hill, Cell Signal (1996) 3:533-44.
y) 3'5'-cyclic nucleotide phosphodiesterases signature (PDEase). SEQ ID NO:4482, and thus the sequence it validates, represents a polynucleotide encoding a novel 3'5'-cyclic nucleotide phosphodiesterases (PDEases). PDEases catalyze the hydrolysis of cAMP or cGMP to the corresponding nucleoside 5' monophosphates (Charbonneau H., et al, Proc. Natl Acad. Sci. U.S.A. (1986) 33:9308). There are at least seven different subfamilies of PDEases (Beavo J.A., et al., Trends Pharmacol. Sci. (1990) 77:150; http://weber.u.washington.edu/~pde/: 1) Type 1, calmodulin/calcium-dependent PDEases; 2) Type 2, cGMP-stimulated PDEases; 3) Type 3, cGMP-inhibited PDEases; 4) Type 4, cAMP-specific PDEases.; 5) Type 5, cGMP-specific PDEases; 6) Type 6, rhodopsin- sensitive cGMP-specific PDEases; and 7) Type 7, High affinity cAMP-specific PDEases. All PDEase forms share a conserved domain of about 270 residues. The signature pattern is determined from a stretch of 12 residues that contains two conserved histi dines: H-D-[LIVMFY]-x-H-x-[AG]-x(2)-[NQ]-x-[LIVMFY]. z) Protein Kinase (protkinase). Several validation sequences, and thus the sequences they validate, represent polynucleotides encoding protein kinases. Protein kinases catalyze phosphorylation of proteins in a variety of pathways, and are implicated in cancer. Eukaryotic protein kinases (Hanks S.K., et al., FASEB J. (1995) 9:576; Hunter T., Meth. Enzymol (1991) 200:3; Hanks S.K., et al, Meth. Enzymol (1991) 200:38; Hanks S.K., Curr. Opin. Struct. Biol (1991) 7:369; Hanks S.K., et al, Science (1988) 247:42) are enzymes that belong to a very extensive family of proteins which share a conserved catalytic core common to both serine/threonine and tyrosine protein kinases. There are a number of conserved regions in the catalytic domain of protein kinases. Two of the conserved regions are the basis for the signature pattern in the protein kinase profile. The first region, which is located in the N-terminal extremity of the catalytic domain, is a glycine-rich stretch of residues in the vicinity of a lysine residue, which has been shown to be involved in ATP binding. The second region, which is located in the central part of the catalytic domain, contains a conserved aspartic acid residue which is important for the catalytic activity of the enzyme (Knighton D.R., et al, Science (1991) 253:407). The protein kinase profile includes two signature patterns for this second region: one specific for serine/threonine kinases and the other for tyrosine kinases. A third profile is based on the alignment in (Hanks S.K., et al, FASEB J. (1995) 9:576) and covers the entire catalytic domain. The consensus patterns are as follows:
1) Consensus pattern: [LIV]-G-{P}-G-{P}-[FYWMGSTNH]-[SGA]-{PW}- [LIVCAT]-{PD}-x-[GSTACLIVMFY]-x(5,18)-[LIVMFYWCSTAR]-[AIVP]- [LIVMFAGCKR]-K, where K binds ATP. The majority of known protein kinases are detected by this pattern. Proteins kinases that are not detected by this consensus include viral kinases, which are quite divergent in this region and are completely missed bythis pattern.
2) Consensus pattern: [LIVMFYC]-x-[HY]-x-D-[LIVMFY]-K-x(2)-N- [LIVMFYCT](3), where D is an active site residue. This consensus sequence identifies most serine/threonine-specific protein kinases with only 10 exceptions. Half of the exceptions are viral kinases, while the other exceptions include Epstein-Barr virus BGLF4 and Drosophila ninaC, which have Ser and Arg, respectively, instead of the conserved Lys. These latter two protein kinases are detected by the tyrosine kinase specific pattern described below.
3) Consensus pattern: [LIVMFYC]-x-[HY]-x-D-[LIVMFY]-[RSTAC]-x(2)-N- [LIVMFYC], where D is an active site residue. All tyrosine-specific protein kinases are detected by this consensus pattern, with the exception of human ERBB3 and mouse blk. This pattern also detects most bacterial aminoglycoside phosphotransferases (Benner S., Nature (1987) 329:21; Kirby R., J. Mol Evol. (1992) 30:489) and heφesviruses ganciclovir kinases (Littler E., et al, Nature (1992) 353:160), which are structurally and evolutionary related to protein kinases.
The protein kinase profile also detects receptor guanylate cyclases and 2-5A- dependent ribonucleases. Sequence similarities between these two families and the eukaryotic protein kinase family have been noticed previously. The profile also detects Arabidopsis thaliana kinase-like protein TMKL1 which seems to have lost its catalytic activity.
If a protein analyzed includes the two of the above protein kinase signatures, the probability of it being a protein kinase is close to 100%. Eukaryotic-type protein kinases have also been found in prokaryotes such as Myxococcus xanthus (Munoz-Dorado J., et al, Cell (1991) 67:995) and Yersinia pseudotuberculosis. The patterns shown above has been updated since their publication in (Bairoch A., et al. , Nature (1988) 337 :22). aa) Ras family proteins (ras). SEQ IDNO:3671, and thus the sequence it validates, represent polynucleotides encoding the ras family of small GTP/GDP-binding proteins (Valencia et al., 1991, Biochemistry 30:4637-4648). Ras family members generally require
a specific guanine nucleotide exchange factor (GEF) and a specific GTPase activating protein (GAP) as stimulators of overall GTPase activity. Among ras-related proteins, the highest degree of sequence conservation is found in four regions that are directly involved in guanine nucleotide binding. The first two constitute most of the phosphate and Mg2+ binding site (PM site) and are located in the first half of the G-domain. The other two regions are involved in guanosine binding and are located in the C-terminal half of the molecule. Motifs and conserved stmctural features of the ras-related proteins are described in Valencia et al., 1991, Biochemistry 30:4637-4648.
A major consensus pattern of ras proteins is: D-T-A-G-Q-E-K-[LF]-G-G-L-R- [DE]-G-Y-Y. bb) Thioredoxin family active site (Thioredox). SEQ ID NO:3936, and thus the sequence it validates, represent a polynucleotide encoding a protein having a thioredoxin family active site. Thioredoxins (Holmgren A., Annu. Rev. Biochem. (1985) 54:237; Gleason F.K., et al., FEMS Microbiol Rev. (1988) 54:271; Holmgren A. J Biol. Chem. (1989) 264:13963; Eklund H., et al. Proteins (1991) 77:13) are small proteins of approximately one hundred amino- acid residues which participate in various redox reactions via the reversible oxidation of an active center disulfide bond. They exist in either a reduced form or an oxidized form where the two cysteine residues are linked in an intramolecular disulfide bond. Thioredoxin is present in prokaryotes and eukaryotes and the sequence around the redox-active disulfide bond is well conserved.
A number of eukaryotic proteins contain domains evolutionary related to thioredoxin, and all of them are protein disulphide isomerases (PDI). PDI (Freedman R.B., et al., Biochem. Soc. Trans. (1988) 76:96; Kivirikko K.I., et al., FASEB J. (1989) 3:1609; Freedman R.B., et al. Trends Biochem. Sci. (1994) 79:331) is an endoplasmic reticulum enzyme that catalyzes the rearrangement of disulfide bonds in various proteins. The various forms of PDI which are currently known are: 1) PDI major isozyme; a multifunctional protein that also function as the beta subunit of prolyl 4-hydroxylase (EC 1.14.11.2), as a component of oligosaccharyl transferase (EC 2.4.1.119), as thyroxine deiodinase, as glutathione-insulin transhydrogenase, and as a thyroid hormone-binding protein; 2) ERp60 (ER-60; 58 Kd microsomal protein), which is a protease; 3) ERp72; and 4) P5.
All PDI contains two or three (ERp72) copies of the thioredoxin domain. The consensus pattern is: [LIVMF]-[LIVMSTA]-x-[LIVMFYC]-[FYWSTHE]-x(2)-
[FYWGTN]-C- [GATPLVE]-[PHYWSTA]-C-x(6)-[LIVMFYWT] (where the two C's form the redox-active bond. cc) TNFR/NGFR family cvsteine-rich region (TNFR c6). SEQ ID NO:3927, and thus the sequence it validates, represent a polynucleotide encoding a protein having a TNFR/NGFR family cysteine-rich region. A number of proteins, some of which are known to be receptors for growth factors, have been found to contain a cysteine-rich domain of about 110 to 160 amino acids in their N-terminal part, that can be subdivided into four (or in some cases, three) modules of about 40 residues containing 6 conserved cysteines. Proteins known to belong to this family (Mallet S., et al., Immunol Today (1991) 12:220; Sprang S.R., Trends Biochem. Sci. (1990) 15:366; Krammer P.H., et al., Curr. Biol. (1992) 2:383; Bazan J.F., Curr. Biol. (1993) 3:603) are: 1) Tumor Necrosis Factor type I and type II receptors (TNFR) (Both receptors bind TNF-alpha and TNF-beta, but are only similar in the cysteine-rich region.); 2) Shope fibroma vims soluble TNF receptor (protein T2); 3) Lymphotoxin alpha/beta receptor; 4) Low-affinity nerve growth factor receptor (LA-NGFR); 5) CD40 (Bp50), the receptor for the CD40L (or TRAP) cytokine; 6) CD27, the receptor for the CD27L cytokine; 8) CD30, the receptor for the CD30L cytokine; 9) T-cell protein 4- IBB, the receptor for the 4-1BBL putative cytokine; 10) FAS antigen (or APO-1), the receptor for FASL, a protein involved in apoptosis (programmed cell death); 11) T-cell antigen OX40, the receptor for the OX40L cytokine; 12) Wsl-1, a receptor (for a yet undefined ligand) that mediates apoptosis; 13) Vaccinia vims protein A53 (SalF19R).
The six cysteines all involved in intrachain disulfide bonds (Banner D.W., et al, Cell (1993) 73:431). A schematic representation of the stmcture of the 40 residue module of these receptors is shown below: xCxxxxxxxxxxxxxCxCxxCxxxxxxxxxCxxxxCxx where 'C represents the conserved cysteine involved in a disulfide bond. The signature pattern for the cysteine-rich region is based mainly on the position of the six conserved cysteines in each of the repeats: Consensus pattern: C-x(4,6)-[FYH]-x(5,10)-C-x(0,2)-C- x(2,3)-C-x(7,l l)-C-x(4,6)-[DNEQSKP]-x(2)-C (where the six C's are involved in disulfide bonds). dd) Four Transmembrane Integral Membrane Proteins (transmembrane4). Several of the validation sequences, and thus the sequences they validate, correspond to a sequence encoding a polypeptide that is a member of the 4 transmembrane segments integral
membrane protein family (transmembrane 4 family). The transmembrane 4 family of proteins includes a number of evolutionarily-related eukaryotic cell surface antigens (Levy et al, J. Biol. Chem., (1991) 266:14597; Tomlinson et al, Eur. J. Immunol (1993) 23:136; Barclay et al. The leucocyte antigen factbooks. (1993) Academic Press, London/San Diego). The proteins belonging to this family include: 1) Mammalian antigen CD9
(MIC3), which is involved in platelet activation and aggregation; 2) Mammalian leukocyte antigen CD37, expressed on B lymphocytes; 3) Mammalian leukocyte antigen CD53 (OX- 44), which is implicated in growth regulation in hematopoietic cells; 4) Mammalian lysosomal membrane protein CD63 (melanoma-associated antigen ME491; antigen AD1); 5) Mammalian antigen CD81 (cell surface protein TAPA-1), which is implicated in regulation of lymphoma cell growth; 6) Mammalian antigen CD82 (protein R2; antigen C33; Kangai 1 (KAI1)), which associates with CD4 or CD8 and delivers costimulatory signals for the TCR/CD3 pathway; 7) Mammalian antigen CD151 (SFA-1; platelet- endothelial tetraspan antigen 3 (PETA-3)); 8) Mammalian cell surface glycoprotein A15 (TALLA- 1 ; MXS 1 ); 9) Mammalian novel antigen 2 (NAG-2); 10) Human tumor- associated antigen CO-029; 1 1) Schistosoma mansoni and japonicum 23 Kd surface antigen (SM23 / SJ23).
The members of the 4 transmembrane family share several characteristics. First, they all are apparently type III membrane proteins, which are integral membrane proteins containing an N-terminal membrane-anchoring domain which is not cleaved during biosynthesis and which functions both as a translocation signal and as a membrane anchor. The family members also contain three additional transmembrane regions, at least seven conserved cysteines residues, and are of approximately the same size (218 to 284 residues). These proteins are collectively know as the "transmembrane 4 superfamily" (TM4) because they span plasma membrane four times.
A schematic diagram of the domain stmcture of these proteins is as follows: +.+ + + — + + + + +- — +
1 1 TMa I Extra | TM2| Cyt | TM3 | Extracellular | TM4 | Cyt|
+.+. — + + — c C + CC C- — C—+- — C — +
where Cyt is the cytoplasmic domain, TMa is the transmembrane anchor; TM2 to TM4 represents transmembrane regions 2 to 4, 'C are conserved cysteines, and '* 'indicates the position of the consensus pattern. The consensus pattern spans a conserved region including two cysteines located in a short cytoplasmic loop between two transmembrane domains: Consensus pattern: G-x(3)-[LIVMF]-x(2)-[GSA]-[LIVMF](2)-G-C-x-[GA]- [STA]- x(2)-[EG]-x(2)-[CWN]-[LIVM](2). ee) Trypsin (trypsin). SEQ ID NOS:3381, 4684, and 4688, and thus the sequences they validate, correspond to novel serine proteases of the trypsin family. The catalytic activity of the serine proteases from the trypsin family is provided by a charge relay system involving an aspartic acid residue hydrogen-bonded to a histidine, which itself is hydrogen- bonded to a serine. The sequences in the vicinity of the active site serine and histidine residues are well conserved in this family of proteases (Brenner S., Nature (1988) 334:528). Proteases known to belong to the trypsin family include: 1) Acrosin; 2) Blood coagulation factors VII, IX, X, XI and XII, thrombin, plasminogen, and protein C; 3) Cathepsin G; 4) Chymotrypsins; 5) Complement components Clr, Cls, C2, and complement factors B, D and I; 6) Complement-activating component of RA-reactive factor; 7) Cytotoxic cell proteases (granzymes A to H); 8) Duodenase I; 9) Elastases 1, 2, 3A, 3B (protease E), leukocyte (medullasin).; 10) Enterokinase (EC 3.4.21.9) (enteropeptidase); 11) Hepatocyte growth factor activator; 12) Hepsin; 13) Glandular (tissue) kallikreins (including EGF-binding protein types A, B, and C, NGF-gamma chain, gamma-renin, prostate specific antigen (PSA) and tonin); 14) Plasma kallikrein; 15) Mast cell proteases (MCP) 1 (chymase) to 8; 16) Myeloblastin (proteinase 3) (Wegener's autoantigen); 17) Plasminogen activators (urokinase-type, and tissue-type); 18) Trypsins I, II, III, and IV; 19) Tryptases; 20) Snake venom proteases such as ancrod, batroxobin, cerastobin, flavoxobin, and protein C activator; 21) Collagenase from common cattle gmb and collagenolytic protease from Atlantic sand fiddler crab; 22) Apolipoprotein(a); 23) Blood fluke cercarial protease; 24) Drosophila trypsin like proteases: alpha, easter, snake- locus; 25) Drosophila protease stubble (gene sb); and 26) Major mite fecal allergen Der p
III. All the above proteins belong to family SI in the classification of peptidases (Rawlings N.D., et al, Meth. Enzymol. (1994) 244:19; http://www.expasy.ch/cgi- bin/lists 7peptidas.txt) and originate from eukaryotic species. It should be noted that bacterial proteases that belong to family S2A are similar enough in the regions of the active site residues that they can be picked up by the same patterns.
The consensus patterns for this trypsin protein family are: 1) [LIVM]-[ST]-A- [STAGJ-H-C, where H is the active site residue. All sequences known to belong to this class detected by the pattern, except for complement components Clr and Cls, pig plasminogen, bovine protein C, rodent urokinase, ancrod, gyroxin and two insect trypsins; 2) [DNSTAGC]-[GSTAPIMVQH]-x(2)-G-[DE]-S-G-[GS]-[SAPHV]- [LIVMFYWH]-
[LIVMFYSTANQH], where S is the active site residue. All sequences known to belong to this family are detected by the above consensus sequences, except for 18 different proteases which have lost the first conserved glycine. If a protein includes both the serine and the histidine active site signatures, the probability of it being a trypsin family serine protease is 100%. ff) WD Domain, G-Beta Repeats (WD domain). A few of the validation sequences, and the sequences they validate, represent novel members of the WD domain/G-beta repeat family. Beta-transducin (G-beta) is one of the three subunits (alpha, beta, and gamma) of the guanine nucleoti de-binding proteins (G proteins) which act as intermediaries in the transduction of signals generated by transmembrane receptors
(Gilman, Annu. Rev. Biochem. (1987) 56:615). The alpha subunit binds to and hydrolyzes GTP; the functions of the beta and gamma subunits are less clear but they seem to be required for the replacement of GDP by GTP as well as for membrane anchoring and receptor recognition. In higher eukaryotes, G-beta exists as a small multigene family of highly conserved proteins of about 340 amino acid residues. Structurally, G-beta consists of eight tandem repeats of about 40 residues, each containing a central Tφ-Asp motif (this type of repeat is sometimes called a WD-40 repeat). Such a repetitive segment has been shown to exist in a number of other proteins including: human LIS1, a neuronal protein involved in type-1 lissencephaly; and mammalian coatomer beta' subunit (beta'-COP), a component of a cytosolic protein complex that reversibly associates with Golgi membranes to form vesicles that mediate biosynthetic protein transport.
The consensus pattern for the WD domain/G-Beta repeat family is: [LIVMSTAC]-
[LIVMFYWSTAGC]-[LIMSTAG]-[LIVMSTAGC]-x(2)-[DN]-x(2)-[LIVMWSTAC]-x- [LIVMFSTAG]-W-[DEN]-[LIVMFSTAGCN]. gg) wnt Family of Developmental Signaling Proteins (Wnt dev sign). Several of the validation sequences, and thus the sequences they validate, correspond to novel members of the wnt family of developmental signaling proteins. Wnt-1 (previously known as int-1), the seminal member of this family, (Nusse R., Trends Genet. (1988) 4:291) is a proto-oncogene induced by the integration of the mouse mammary tumor vims. It is thought to play a role in intercellular communication and seems to be a signalling molecule important in the development of the central nervous system (CNS). The sequence of wnt-1 is highly conserved in mammals, fish, and amphibians. Wnt-1 was found to be a member of a large family of related proteins (Nusse R., et al, Cell (1992) 69:1073; McMahon A.P., Trends Genet. (1992) 3:1; Moon R.T., BioEssays (1993) 75:91) that are all thought to be developmental regulators. These proteins are known as wnt-2 (also known as iφ), wnt-3, - 3 A, -4, -5 A, -5B, -6, -7A, -7B, -8, -8B, -9 and -10. At least four members of this family are present in Drosophila; one of them, wingless (wg), is implicated in segmentation polarity. All these proteins share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines that are probably involved in disulfide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. The consensus pattern, which is based upon a highly conserved region including three cysteines, is as follows: C-K-C-H-G-[LIVMT]-S-G-x-C. All sequences known to belong to this family are detected by the provided consensus pattern. hh) Protein Tyrosine Phosphatase (Y phosphatase). Several of the validation sequences, and thus the sequences they validate, represent a polynucleotide encoding a protein tyrosine kinase. Tyrosine specific protein phosphatases (EC 3.1.3.48) (PTPase) (Fischer et al, Science (1991) 253:401; Charbonneau et al, Annu. Rev. Cell Biol (1992) 3:463; Trowbridge, J. Biol. Chem. (1991) 266:23517; Tonks et al, Trends Biochem. Sci. (1989) 74:497; and Hunter, Cell (1989) 53:1013) catalyze the removal of a phosphate group attached to a tyrosine residue. These enzymes are very important in the control of cell growth, proliferation, differentiation and transformation. Multiple forms of PTPase have been characterized and can be classified into two categories: soluble PTPases and transmembrane receptor proteins that contain PTPase domain(s).
Soluble PTPases include PTPN3 (HI) and PTPN4 (MEG), enzymes that contain an N-terminal band 4.1 -like domain and could act at junctions between the membrane and cytoskeleton; PTPN6 (PTP-1C; HCP; SHP) and PTPN11 (PTP-2C; SH-PTP3; Syp), enzymes that contain two copies of the SH2 domain at its N-terminal extremity. Dual specificity PTPases include DUSP 1 (PTPN 10; MAP kinase phosphatase- 1 ;
MKP-1) which dephosphorylates MAP kinase on both Thr- 183 and Tyr-185; and DUSP2 (PAC-1), a nuclear enzyme that dephosphorylates MAP kinases ERK1 and ERK2 on both Thr and Tyr residues.
Structurally, all known receptor PTPases are made up of a variable length extracellular domain, followed by a transmembrane region and a C-terminal catalytic cytoplasmic domain. Some of the receptor PTPases contain fibronectin type III (FN-III) repeats, immunoglobulin-like domains, MAM domains or carbonic anhydrase-like domains in their extracellular region. The cytoplasmic region generally contains two copies of the PTPAse domain. The first seems to have enzymatic activity, while the second is inactive but seems to affect substrate specificity of the first. In these domains, the catalytic cysteine is generally conserved but some other, presumably important, residues are not.
PTPase domains consist of about 300 amino acids. There are two conserved cysteines and the second one has been shown to be absolutely required for activity. Furthermore, a number of conserved residues in its immediate vicinity have also been shown to be important. The consensus pattern for PTPases is: [LIVMF]-H-C-x(2)-G-x(3)- [STC]-[STAGP]-x-[LIVMFY]; C is the active site residue. ii)Zinc Finger, C2H2 Type (Zincfing C2H2). Several of the validation sequences, and thus the sequences they validate, correspond to polynucleotides encoding novel members of the of the C2H2 type zinc finger protein family. Zinc finger domains (Klug et al, Trends Biochem. Sci. (1987) 72:464; Evans et al, Cell (1988) 52:1; Payre et al, FEBS Lett. (1988) 234:245; Miller et al, EMBOJ. (1985) 4:1609; and Berg, Proc. Natl. Acad. Sci. USA (1988) 35:99) are nucleic acid-binding protein stmctures first identified in the Xenopus transcription factor TFIIIA. These domains have since been found in numerous nucleic acid-binding proteins. A zinc finger domain is composed of 25 to 30 amino acid residues. Two cysteine or histidine residues are positioned at both extremities of the domain, which are involved in the tetrahedral coordination of a zinc atom. It has been proposed that such a domain interacts with about five nucleotides.
Many classes of zinc fingers are characterized according to the number and
positions of the histidine and cysteine residues involved in the zinc atom coordination. In the first class to be characterized, called C2H2, the first pair of zinc coordinating residues are cysteines, while the second pair are histidines. A number of experimental reports have demonstrated the zinc-dependent DNA or RNA binding property of some members of this class.
Mammalian proteins having a C2H2 zipper include (number in parenthesis indicates number of zinc finger regions in the protein): basonuclin (6), BCL-6/LAZ-3 (6), erythroid krueppel-like transcription factor (3), transcription factors Spl (3), Sp2 (3), Sp3 (3) and Sp(4) 3, transcriptional repressor YYl (4), Wilms' tumor protein (4), EGRl/Krox24 (3), EGR2/Krox20 (3), EGR3/Pilot (3), EGR4/AT133 (4), Evi-1 (10), GLIl (5), GLI2 (4+), GLI3 (3+), HIV-EP1/ZNF40 (4), HIV-EP2 (2), KR1 (9+), KR2 (9), KR3 (15+), KR4 (14+), KR5 (11+), HF.12 (6+), REX-1 (4), ZfX (13), Zf (13), Zfp-35 (18), ZNF7 (15), ZNF8 (7), ZNF35 (10), ZNF42/MZF-1 (13), ZNF43 (22), ZNF46/Kup (2), ZNF76 (7), ZNF91 (36), ZNF133 (3). In addition to the conserved zinc ligand residues, it has been shown that a number of other positions are also important for the stmctural integrity of the C2H2 zinc fingers. (Rosenfeld et al, J. Biomol Struct. Dyn. (1993) 77:557) The best conserved position is found four residues after the second cysteine; it is generally an aromatic or aliphatic residue. The consensus pattern for C2H2 zinc fingers is: C-x(2,4)-C-x(3)-[LIVMFYWC]- x(8)-H-x(3,5)-H. The two C's and two H's are zinc ligands. ii) Zinc finger. C3HC4 type fRTNG finger), signature (Zincfing C3H4). SEQ ID NOS:3774 and 4477, and thus the sequences they validate, represent polynucleotides encoding a polypeptide having a C3HC4 type zinc finger signature. A number of eukaryotic and viral proteins contain this signature, which is primarily a conserved cysteine-rich domain of 40 to 60 residues (Borden K.L.B., et al., Curr. Opin. Struct. Biol. (1996) 6:395) that binds two atoms of zinc, and is probably involved in mediating protein- protein interactions. The 3D stmcture of the zinc ligation system is uniqueto the RING domain and is refered to as the "cross-brace" motif. The spacing of the cysteines in such a domain is C-x(2)-C-x(9 to 39)-C-x(l to 3)-H-x(2 to 3)-C-x(2)-C-x(4 to 48)-C-x(2)-C. Proteins that include the C3HC4 domain include:
1) Mammalian V(D)J recombination activating protein (RAG1). RAG1 activates the rearrangement of immunoglobulin and T-cell receptor genes.
2) Mouse φt-1. Rpt-1 is a trans-acting factor that regulates gene expression directed
by the promoter region of the interleukin-2 receptor alpha chainor the LTR promoter region of HIV- 1.
3) Human rfp. Rfp is a developmentally regulated protein that may function in male germ cell development. Recombination of the N-terminal section of rfp with a protein tyrosine kinase produces the ret transforming protein.
4) Human 52 Kd Ro/SS-A protein. A protein of unknown function from the Ro/SS- A ribonucleoprotein complex. Sera from patients with systemic lupus erythematosus or primary Sjogren's syndrome often contain antibodies that react with the Ro proteins.
5) Human histocompatibility locus protein RINGl. 6) Human PML, a probable transcription factor. Chromosomal translocation ofPML with retinoic receptor alpha creates a fusion protein which is thecause of acute promyelocytic leukemia (APL).
7) Mammalian breast cancer type 1 susceptibility protein (BRCA1) ([El] http://bioinformatics.weizmann.ac.il/hotmolecbase/entries/brcal.htm). 8) Mammalian cbl proto-oncogene.
9) Mammalian bmi-1 proto-oncogene.
10) Vertebrate CDK-activating kinase (CAK) assembly factor MATl, a protein that stabilizes the complex between the CDK7 kinase and cyclin H (MATl stands for 'Menage A Trois'). 11) Mammalian mel-18 protein. Mel- 18 which is expressed in a variety of tumorcells is a transcriptional repressor that recognizes and bind a specific DNA sequence.
12) Mammalian peroxisome assembly factor- 1 (PAF-1) (PMP35), which is somewhat involved in the biogenesis of peroxisomes. In humans, defects in PAF-1 are responsible for a form of Zellweger syndrome, an autosomal recessivedisorder associated with peroxisomal deficiencies.
13) Human MATl protein, which interacts with the CDK7-cyclin H complex.
14) Human RINGl protein.
15) Xenopus XNF7 protein, a probable transcription factor. 16) Trypanosoma protein ESAG-8 (T-LR), which may be involved in the postranscriptional regulation of genes in VSG expression sites or may interact with adenylate cyclase to regulate its activity.
17) Drosophila proteins Posterior Sex Combs (Psc) and Suppressor two of zeste
(Su(z)2). The two proteins belong to the Polycomb group of genes needed to maintain the segment-specific repression of homeotic selector genes.
18) Drosophila protein male-specific msl-2, a DNA-binding protein which is involved in X chromosome dosage compensation (the elevation of transcription of the male single X chromosome).
19) Arabidopsis thaliana protein COP1 which is involved in the regulation ofphotomoφhogenesis.
20) Fungal DNA repair proteins RAD5, RAD16, RAD18 and rad8.
21) Heφesvimses trans-acting transcriptional protein ICP0/IE110. This protein which has been characterized in many different heφesvimses is a trans-activator and/or - repressor of the expression of many viral and cellular promoters.
22) Baculovimses protein CG30.
23) Baculovimses major immediate early protein (PE-38).
24) Baculovimses immediate-early regulatory protein IE-N/IE-2. 25) Caenorhabditis elegans hypothetical proteins F54G8.4, R05D3.4 and T02C 1.1.
26) Yeast hypothetical proteins YER116c and YKR017c. The signature pattern for the C3HC4 finger is based on the central region of the domain:
Consensus pattern: C-x-H-x-[LIVMFY]-C-x(2)-C-[LIVMYA].
Example 4: Differential Expression of Polynucleotides of the Invention: Description of Libraries and Detection of Differential Expression
The relative expression levels of the polynucleotides of the invention was assessed in several libraries prepared from various sources, including cell lines and patient tissue samples. Table 4 provides a summary of these libraries, including the shortened library name (used hereafter), the mRNA source used to prepared the cDNA library, the "nickname" of the library that is used in the tables below (in quotes), and the approximate number of clones in the library.
Table 4 Description of cDNA Libraries
The KM12L4 and KM12C cell lines are described in Example 1 above. The MDA- MB-231 cell line was originally isolated from pleural effusions (Cailleau, J. Natl. Cancer. Inst. (1974) 53:661), is of high metastatic potential, and forms poorly differentiated
adenocarcinoma grade II in nude mice consistent with breast carcinoma. The MCF7 cell line was derived from a pleural effusion of a breast adenocarcinoma and is non-metastatic. The MV-522 cell line is derived from a human lung carcinoma and is of high metastatic potential. The UCP-3 cell line is a low metastatic human lung carcinoma cell line; the MV-522 is a high metastatic variant of UCP-3. These cell lines are well-recognized in the art as models for the study of human breast and lung cancer (see, e.g., Chandrasekaran et al, Cancer Res. (1979) 39:870 (MDA-MB-231 and MCF-7); Gastpar et al. JMed Chem (1998) 47:4965 (MDA-MB-231 and MCF-7); Ranson et al, Br J Cancer (1998) 77:1586 (MDA-MB-231 and MCF-7); Kuang et al , Nucleic Acids Res (1998) 26: 1116 (MDA-MB- 231 and MCF-7); Varki et al, IntJ Cancer (1987) 40:46 (UCP-3); Varki et al, Tumour Biol. (1990) 77:327; (MV-522 and UCP-3); Varki et al , Anticancer Res. (1990) 70:637; (MV-522); Kelner et al, Anticancer Res (1995) 75:867 (MV-522); and Zhang et al, Anticancer Drugs (1997) 3:696 (MV522)). The samples of libraries 15-20 are derived from two different patients (UC#2, and UC#3). The bFGF-treated HMEC were prepared by incubation with bFGF at 1 Ong/ml for 2 hrs; the VEGF -treated HMEC were prepared by incubation with 20ng/ml BEGF for 2 hrs. Following incubation with the respective growth factor, the cells were washed and lysis buffer added for RNA preparation.
Each of the libraries is composed of a collection of cDNA clones that in turn are representative of the mRNAs expressed in the indicated mRNA source. In order to facilitate the analysis of the millions of sequences in each library, the sequences were assigned to clusters. The concept of "cluster of clones" is derived from a sorting/grouping of cDNA clones based on their hybridization pattern to a panel of roughly 300 7bp oligonucleotide probes (see Drmanac et al, Genomics (1996) 37(1):29). Random cDNA clones from a tissue library are hybridized at moderate stringency to 300 7bp oligonucleotides. Each oligonucleotide has some measure of specific hybridization to that specific clone. The combination of 300 of these measures of hybridization for 300 probes equals the "hybridization signature" for a specific clone. Clones with similar sequence will have similar hybridization signatures. By developing a sorting/grouping algorithm to analyze these signatures, groups of clones in a library can be identified and brought together computationally. These groups of clones are termed "clusters". Depending on the stringency of the selection in the algorithm (similar to the stringency of hybridization in a
classic library cDNA screening protocol), the "purity" of each cluster can be controlled. For example, artifacts of clustering may occur in computational clustering just as artifacts can occur in "wet-lab" screening of a cDNA library with 400 bp cDNA fragments, at even the highest stringency. The stringency used in the implementation of cluster herein provides groups of clones that are in general from the same cDNA or closely related cDNAs. Closely related clones can be a result of different length clones of the same cDNA, closely related clones from highly related gene families, or splice variants of the same cDNA.
Differential expression for a selected cluster was assessed by first determining the number of cDNA clones corresponding to the selected cluster in the first library (Clones in 1st), and the determining the number of cDNA clones corresponding to the selected cluster in the second library (Clones in 2nd). Differential expression of the selected cluster in the first library relative to the second library is expressed as a "ratio" of percent expression between the two libraries. In general, the "ratio" is calculated by: 1) calculating the percent expression of the selected cluster in the first library by dividing the number of clones corresponding to a selected cluster in the first library by the total number of clones analyzed from the first library; 2) calculating the percent expression of the selected cluster in the second library by dividing the number of clones corresponding to a selected cluster in a second library by the total number of clones analyzed from the second library; 3) dividing the calculated percent expression from the first library by the calculated percent expression from the second library. If the "number of clones" corresponding to a selected cluster in a library is zero, the value is set at 1 to aid in calculation. The formula used in calculating the ratio takes into account the "depth" of each of the libraries being compared, i.e., the total number of clones analyzed in each library. In general, a polynucleotide is said to be significantly differentially expressed between two samples when the ratio value is greater than at least about 2, preferably greater than at least about 3, more preferably greater than at least about 5 , where the ratio value is calculated using the method described above. The significance of differential expression is determined using a z score test (Zar, Biostatistical Analysis, Prentice Hall, Inc., USA, "Differences between Proportions," pp 296-298 (1974).
Example 5: Polynucleotides Differentially Expressed in High Metastatic Potential Breast Cancer Cells Versus Low Metastatic Breast Cancer Cells
A number of polynucleotide sequences have been identified that are differentially expressed between cells derived from high metastatic potential breast cancer tissue and low metastatic breast cancer cells. Expression of these sequences in breast cancer can be valuable in determining diagnostic, prognostic and/or treatment information. For example, sequences that are highly expressed in the high metastatic potential cells can be indicative of increased expression of genes or regulatory sequences involved in the metastatic process. A patient sample displaying an increased level of one or more of these polynucleotides may thus warrant more aggressive treatment. In another example, sequences that display higher expression in the low metastatic potential cells can be associated with genes or regulatory sequences that inhibit metastasis, and thus the expression of these polynucleotides in a sample may warrant a more positive prognosis than the gross pathology would suggest.
The differential expression of these polynucleotides can be used as a diagnostic marker, a prognostic marker, for risk assessment, patient treatment and the like. These polynucleotide sequences can also be used in combination with other known molecular and/or biochemical markers.
The following tables summarize polynucleotides that are differentially expressed between high metastatic potential breast cancer cells and low metastatic potential breast cancer cells.
Table 5. Differentially expressed polynucleotides: Higher expression in high metastatic potential breast cancer (lib3) relative to low metastatic breast cancer cells (lib4)
SEQ ID Sequence Name Cluster • Lib3 Lib4 Iib3/lib4 Zscore
NOS: ID clones clones
45 RTA00000197AR.f.l2.1 3513 17 5 3.317240 2.287632
146 RTA00000185AF.a.l9.2 5749 9 0 8.780930 2.629923
154 RTA00000196F.e.7.1 1039 10 2 4.878294 1.978215
159 RTA00000182AF.1.12.1 1027 41 17 2.353059 2.926571
165 RTA00000192AF.g.23.1 6455 6 0 5.853953 2.011224
174 RTA00000181AF.e.22.3 3442 17 4 4.146550 2.562391
183 RTA00000198AF.C.17.1 6923 6 0 5.853953 2.011224
364 RTA00000187AF.g.l3.1 2991 10 1 9.756589 2.371428
366 RTA00000192AF.O.19.1 3549 10 1 9.756589 2.371428
387 RTA00000191AF.J.14.1 1002 42 20 2.048883 2.570309
496 RTA00000190AF.p.3.1 2378 34 0 33.17240 5.588184
510 RTA00000178AF.n.23.1 3298 12 1 1 1.70790 2.729313
512 RTA00000191AF.C.3.1 3549 10 1 9.756589 2.371428
529 RTA00000178AF.b.l3.1 31 14 9 1 8.780930 2.174815
560 RTA00000184AF.i.23.3 1577 25 3 8.130490 3.903813
606 RTA00000179AR.e.01.4 2493 33 9 3.577416 3.469507
SEQ ID Sequence Name Cluster Lib3 Lib4 Iib3/lib4 Zscore
NOS: ID clones clones
644 RTA00000197F. 2.1 3605 14 1 13.65922 3.050936
646 RTA00000186AF.d.24.1 3114 9 1 8.780930 2.174815
754 RTA00000T 87AF.1.1 1.1 4482 14 3 4.553074 2.374769
875 RTA00000401F.m.02.1 1573 34 7 4.738914 3.982056
902 RTA00000422F.C.02.1 2902 18 5 3.512372 2.443314
921 RTA00000418F.m.l9.1 8890 6 0 5.853953 2.011224
942 RTA00000351R.g.l l .l 3077 17 4 4.146550 2.562391
1095 RTA00000408F.1.13.1 4423 12 1 11.70790 2.729313
1 104 RTA00000404F.m.l0.2 779 60 22 2.660887 3.974953
1 131 RTA00000400F.k.22.1 2512 7 0 6.829612 2.235371
1 170 RTA00000340R.f.05.1 3202 18 3 5.853953 2.998867
1184 RTA00000422F.C.17.1 1360 26 11 2.306102 2.226876
1205 RTA00000118A.a.23.1 3500 12 3 3.902635 2.018050
1354 RTA00000401F.k.l4.1 211 121 43 2.745458 5.856098
2124 RTA00000191AFJ.14.1 1002 42 20 2.048883 2.570309
1535 RTA00000405F.1.11.1 2055 29 8 3.536763 3.213373
1751 RTA00000423F.J.03.1 5391 6 0 5.853953 2.011224
1764 RTA00000399F.O.24.1 2272 17 1 16.58620 3.483575
1777 RTA00000401F.J.15.1 3061 14 0 13.65922 3.428594
1795 RTA00000348R.O.12.1 2263 6 0 5.853953 2.011224
1869 RTA00000340F.f.22.1 1720 57 8 6.951569 5.855075
1882 RTA00000401F.g.22.1 1147 28 12 2.276537 2.294031
1890 RTA00000346F.O.16.1 176 170 44 3.769591 8.366611
1915 RTA00000400F.g.02.1 1508 21 5 4.097767 2.879196
2040 RTA00000527F.J.02.2 4896 11 0 10.73224 2.974502
2059 RTA00000528F.i.22.1 2478 17 5 3.317240 2.287632
2223 RTA00000528F.J.11.1 1070 26 6 4.227855 3.289393
2245 RTA00000527F.k.09.1 213 17 4 4.146550 2.562391
2300 RTA00000528F.b.03.1 2078 1 1 2 5.366124 2.174565
2325 RTA00000525F.d.l3.1 349 77 1 75.12573 8.384408
2462 RTA00000528F.g.22.2 920 76 32 2.317189 4.010278
2488 RTA00000528F.h.02.2 1701 18 4 4.390465 2.714073
2492 RTA00000528F.C.11.1 1701 18 4 4.390465 2.714073
Table 6. Differentially expressed polynucleotides: Higher expression in low metastatic breast cancer cells (lib4) relative to high metastatic potential breast cancer (lib3)
SEQ ID Sequence Name Cluster ID Lib4 Lib 3 Iib4/lib3 Zscore
NOS: Clones Clones
15 RTA00000177AR.n.8.1 4188 4 13 3.33108 1.99126
36 RTA00000181AF.p.4.3 40392 1 8 8.19958 2.03713
44 RTA00000199F.f.08.2 12445 0 11 11.2744 3.05623
89 RTA00000177AF.n.8.3 4188 4 13 3.33108 1.99126
172 RTA00000186AF.p.09.2 6879 3 43 14.6909 5.83444
203 RTA00000201F.d.09.1 1827 37 157 4.34910 8.71727
261 RTA00000192AF.a.24.1 13183 0 7 7.17463 2.30057
419 RTA00000182AF.J.20.1 4769 2 20 10.2494 3.68254
420 RTA00000181AF.C.11.1 4769 2 20 10.2494 3.68254
503 RTA00000197AF.k.9.1 3138 1 10 10.2494 2.45316
552 RTA00000193AF.b.24.1 35 386 1967 5.22298 33.2328
564 RTA00000200AF.g.l8.1 1600 0 23 23.5738 4.64683
SEQ ID Sequence Name Cluster ID Lib4 Lib 3 Iib4/lib3 Zscore
NOS: Clones Clones
570 RTA00000183AF.a.l9.2 3788 0 6 6.14969 2.07158
590 RTA00000190AF.d.2.1 2444 26 55 2.16815 3.22244
693 RTA00000198F.m.l2.1 4 987 2807 2.91492 30.3819
707 RTA00000179AF.p.l5.1 5622 2 13 6.66216 2.62993
711 RTA00000198F.L2.1 8076 0 9 9.22453 2.70385
726 RTA00000200R.f.l0.1 4 987 2807 2.91492 30.3819
746 RTA00000178AF.i.01.2 4 987 2807 2.91492 30.3819
756 RTA00000404F.a.02.1 9738 1 13 13.3243 2.98623
990 RTA00000126A.O.23.1 6268 3 18 6.14969 3.11179
1122 RTA00000401F.O.06.1 2679 4 23 5.89345 3.52846
1142 RTA00000411F.a.l5.1 73812 0 12 12.2993 3.21838
1286 RTA00000345F.n.l2.1 7337 3 16 5.46639 2.80694
1289 RTA00000126A.g.7.1 1902 13 48 3.78442 4.45002
1435 RTA00000345F.e.l l .l 4392 1 8 8.19958 2.03713
1860 RTA00000340F.p.l8.1 287 6 173 29.5526 12.5749
1933 RTA00000400F.f.l l.l 4088 0 82 84.0457 9.05778
1934 RTA00000341F.O.12.1 2883 9 21 2.39154 2.07600
1979 RTA00000122A.h.24.1 48 412 1020 2.53749 16.5262
1980 RTA00000346FJ.13.1 5337 5 17 3.48482 2.40321
2007 RTA00000400F.g.08.1 1275 15 32 2.18655 2.41857
2023 RTA00000523F.d.l9.1 26489 1 8 8.19958 2.03713
2409 RTA00000526F.d.l7.1 2757 4 16 4.09979 2.51500
1220 RTA00000528F.d.04.1 2395 12 37 3.16025 3.51521
Example 6: Polynucleotides Differentially Expressed in High Metastatic Potential Lung
Cancer Cells Versus Low Metastatic Lung Cancer Cells A number of polynucleotide sequences have been identified that are differentially expressed between cells derived from high metastatic potential lung cancer tissue and low metastatic lung cancer cells. Expression of these sequences in lung cancer tissue can be valuable in determining diagnostic, prognostic and/or treatment information. For example, sequences that are highly expressed in the high metastatic potential cells are associated can be indicative of increased expression of genes or regulatory sequences involved in the metastatic process. A patient sample displaying an increased level of one or more of these polynucleotides may thus warrant more aggressive treatment. In another example, sequences that display higher expression in the low metastatic potential cells can be associated with genes or regulatory sequences that inhibit metastasis, and thus the expression of these polynucleotides in a sample may warrant a more positive prognosis than the gross pathology would suggest.
The differential expression of these polynucleotides can be used as a diagnostic marker, a prognostic marker, for risk assessment, patient treatment and the like. These
polynucleotide sequences can also be used in combination with other known molecular and/or biochemical markers.
The following tables summarize polynucleotides that are differentially expressed between high metastatic potential lung cancer cells and low metastatic potential lung cancer cells:
Table 7 Differentially expressed polynucleotides: Higher expression in high metastatic potential lung cancer cells (lib8) relative to low metastatic lung cancer cells (lib9)
SEQ ID Sequence Name Cluster ID Lib8 Lib9 Iib8/lib9 Zscore
NO: clones clones
10 RTA00000198AF.n.l6.1 3721 9 0 12.5772 3.20845
54 RTA00000200F.O.22.1 983 8 1 1 1.1797 2.53243
65 RTA00000198AF.m.l6.1 51 348 66 7.36849 17.4315
171 RTA00000198R.C.07.1 19181 6 0 8.38484 2.48169
203 RTA00000201F.d.09.1 1827 45 15 4.19242 5.09891
252 RTA00000181AF.e.l8.3 8 1355 122 15.5211 39.0214
253 RTA00000181AF.e.l7.3 8 1355 122 15.5211 39.0214
285 RTA00000181AR.J.14.3 5399 12 0 16.7696 3.80239
419 RTA00000182AF.J.20.1 4769 10 3 4.65824 2.29362
420 RTA00000181AF.C.11.1 4769 10 3 4.65824 2.29362
491 RTA00000196F.k.l l.l 3 986 392 3.51507 22.4683
525 RTA00000198AF.C.7.1 19181 6 0 8.38484 2.48169
526 RTA00000185AF.e.20.1 5865 12 0 16.7696 3.80239
552 RTA00000193AF.b.24.1 35 868 11 1 10.273 34.2897
693 RTA00000198F.m.l2.1 4 506 209 3.38335 15.7309
700 RTA00000183AF.U8.2 40129 7 0 9.78231 2.74441
726 RTA00000200R.f.l0.1 4 506 209 3.38335 15.7309
742 RTA00000177AF.m.l.l 14929 23 16 2.00886 2.02420
746 RTA00000178AF.i.01.2 4 506 209 3.38335 15.7309
861 RTA00000339F.f.l l.l 5832 5 0 6.98736 2.18988
990 RTA00000126A.O.23.1 6268 5 0 6.98736 2.18988
1088 RTA00000399F.f.l l.l 40167 8 0 1 1.1797 2.98512
1288 RTA00000423F.e.l l.l 2566 11 2 7.68610 2.85611
1417 RTA00000339F.O.07.1 2566 11 2 7.68610 2.85611
1444 RTA00000419F.p.03.1 1937 10 3 4.65824 2.29362
1454 RTA00000340F.1.05.1 38935 7 0 9.78231 2.74441
1570 RTA00000403F.a.l7.1 13686 8 0 11.1797 2.98512
1597 RTA00000401F.n.23.1 1552 8 1 1 1.1797 2.53243
1979 RTA00000122A.h.24.1 48 342 155 3.08345 12.2138
2024 RTA00000528F.b.23.1 1605 22 4 7.68610 4.23808
2034 RTA00000528F.m.l6.1 4468 6 1 8.38484 1.97787
2126 RTA00000526F.d.01.1 4468 6 1 8.38484 1.97787
Table 8 Differentially expressed polynucleotides: Higher expression in low metastatic lung cancer cells (lib9) relative to high metastatic potntial lung cancer cells SEQ ID Sequence Name Cluster Lib8 Lib9 Iib9/lib8 Zscore NO: ID clones clones
174 RTA00000181AF.e.22.3 3442 5 23 3.291654 2.368262
254 RTA00000178AF.n.2.1 17083 0 8 5.724617 2.034117
466 RTA00000177AF.p.20.1 4141 4 27 4.830145 3.070829
571 RTA00000198AF.b.l4.1 801 16 46 2.057284 2.411087
574 RTA00000192AF.f.3.1 5257 5 25 3.577885 2.596857
590 RTA00000190AF.d.2.1 2444 12 37 2.206362 2.299984
922 RTA00000399F.1.14.1 3354 5 20 2.862308 1.998763
1355 RTA00000406F.m.04.1 14959 1 1 41 2.667151 2.865855
1422 RTA00000405F.h.07.2 4984 3 16 3.816411 2.058861
2007 RTA00000400F.g.08.1 1275 10 42 3.005423 3.147111
2038 RTA00000527F.p.06.1 1292 8 33 2.951755 2.724411
2245 RTA00000527F.k.09.1 213 137 403 2.104945 7.661033
Example 7: Polynucleotides Differentially Expressed in High Metastatic Potential Colon Cancer Cells Versus Low Metastatic Colon Cancer Cells
A number of polynucleotide sequences have been identified that are differentially expressed between cells derived from high metastatic potential colon cancer tissue and low metastatic colon cancer cells. Expression of these sequences in colon cancer tissue can be valuable in determining diagnostic, prognostic and/or treatment information. For example, sequences that are highly expressed in the high metastatic potential cells can be indicative of increased expression of genes or regulatory sequences involved in the metastatic process. A patient sample displaying an increased level of one or more of these polynucleotides may thus warrant more aggressive treatment. In another example, sequences that display higher expression in the low metastatic potential cells can be associated with genes or regulatory sequences that inhibit metastasis, and thus the expression of these polynucleotides in a sample may warrant a more positive prognosis than the gross pathology would suggest. The differential expression of these polynucleotides can be used as a diagnostic marker, a prognostic marker, for risk assessment, patient treatment and the like. These polynucleotide sequences can also be used in combination with other known molecular and/or biochemical markers.
The following table summarizes identified polynucleotides with differential expression between high metastatic potential colon cancer cells and low metastatic potential colon cancer cells:
Table 9 Differentially expressed polynucleotides: Higher expression in high metastatic potential colon cancer (libl) relative to low metastatic colon cancer cells (lib2) SEQ ID Sequence Name Cluster ID Libl Lib2 Hbl/lib2 Zscore NO: clones clones 228 RTA00000187AR.h.l5.2 6660 7 0 6.489973399 2.169320547
280 RTA00000193AF.b.l 8.1 7542 8 0 7.417112456 2.36964728
355 RTA00000184AR.b.24.1 5777 9 1 8.344251513 2.09555146
491 RTA00000196F.k.l l.l 3 5268 2164 2.257009497 32.96556438
603 RTA00000183AR.d.l l.3 6420 8 0 7.417112456 2.36964728
680 RTA00000177AF.f.l0.1 6420 8 0 7.4171 12456 2.36964728
752 RTA00000192AF.O.7.1 5275 11 2 5.099264814 2.083995588
753 RTA00000192AF.O.17.1 5275 11 2 5.099264814 2.083995588
1241 RTA00000346F.1.13.1 7542 8 0 7.417112456 2.36964728
1264 RTA00000349R.g.l0.1 5777 9 1 8.344251513 2.09555146
1401 RTA00000421F.m.l4.1 3524 21 6 3.2449867 2.499690198
1442 RTA00000350R.g.l0.1 9026 7 0 6.489973399 2.169320547
1514 RTA00000399F.O.06.1 13574 7 0 6.489973399 2.169320547
1851 RTA00000421F.a.06.1 2385 27 4 6.258188635 3.743586088
1915 RTA00000400F.g.02.1 1508 46 17 2.508729213 3.230059264
2024 RTA00000528F.b.23.1 1605 36 1 1 3.034273278 3.244010467
2066 RTA00000528F.m.l2.1 5768 12 0 3.046665462
Table 10 Differentially expressed polynucleotides: Higher expression in low metastatic colon cancer cells (lib2)relative to high metastatic potential colon cancer (libl)
SEQ ID Sequence Name Cluster Libl Lib2 lib2/libl Zscore
NOS: ID clones clones
33 RTA00000178AR.a.20.1 945 9 21 2.51670 2.21703
250 RTA00000192AFJ.21.1 2289 3 23 8.26916 3.92187
282 RTA00000193AF.C.15.1 3726 3 14 5.03340 2.58312
370 RTA00000179AF.C.15.3 2995 4 13 3.50540 2.09770
387 RTA00000191AF.J.14.1 1002 12 65 5.84234 6.26259
443 RTA00000197AR.i.l7.1 3516 5 17 3.66719 2.52439
460 RTA00000179AF.C.15.1 2995 4 13 3.50540 2.09770
545 RTA00000196F.a.2.1 3575 5 14 3.02004 2.00158
560 RTA00000184AF.i.23.3 1577 12 40 3.59528 4.01991
703 RTA00000198F.1.09.1 361 1 2 13 7.01081 2.73040
704 RTA00000190AF.O.12.1 3438 5 14 3.02004 2.00158 1095 RTA00000408F.1.13.1 4423 1 8 8.62869 2.11495 1104 RTA00000404F.m.l0.2 779 27 54 2.15717 3.23169 1205 RTA00000118A.a.23.1 3500 3 13 4.67387 2.40298 1354 RTA00000401F.k.l4.1 211 109 206 2.03843 6.08597 1387 RTA00000191AFJ.14.1 1002 12 65 5.84234 6.26259 1734 RTA00000345F.b.l7.1 945 9 21 2.51670 2.21703 1742 RTA00000422F.b.22.1 2368 14 34 2.61942 3.00662 1954 RTA00000401F.J.23.1 570 59 148 2.70560 6.66631 2262 RTA00000527F.O.12.1 688 29 60 2.23155 3.53946 2325 RTA00000525F.d.l3.1 349 69 138 2.15717 5.27497
Example 8: Polynucleotides Differentially Expressed in High Metastatic Potential Colon Cancer Patient Tissue Versus Normal Patient Tissue
A number of polynucleotide sequences have been identified that are differentially expressed between cells derived from high metastatic potential colon cancer tissue and normal tissue. Expression of these sequences in colon cancer tissue can be valuable in determining diagnostic, prognostic and/or treatment information. For example, sequences that are highly expressed in the high metastatic potential cells are associated can be indicative of increased expression of genes or regulatory sequences involved in the advanced disease state which involves processes such as angiogenesis, dedifferentiation, cell replication, and metastasis. A patient sample displaying an increased level of one or more of these polynucleotides may thus warrant more aggressive treatment.
The differential expression of these polynucleotides can be used as a diagnostic marker, a prognostic marker, for risk assessment, patient treatment and the like. These polynucleotide sequences can also be used in combination with other known molecular and/or biochemical markers.
The following tables summarize polynucleotides that are differentially expressed between high metastatic potential colon cancer cells and normal colon cells:
Table 11 Differentially expressed polynucleotides isolated from samples from two patients (UC#2 and UC#3) : Higher expression in high metastatic potential colon tissue (UC#2:libl7; UC#3:lib20) vs. normal colon tissue (UC#2:libl5; UC#3:libl8)
SEQ ID Sequence Name Cluster lib 15 lib 17 Iibl7/libl5 Zscore
NO: ID clones clones
65 RTA00000198AF.m.l6.1 51 1 10 9.27022 2.28830
1780 RTA00000118A.J.24.1 18 4 23 5.33037 3.27028
1899 RTA00000345F.J.09.1 13 14 80 5.29727 6.34580
SEQ ID Sequence Name Cluster lib 18 lib20 Iib20/libl8 Zscore
NO: ID clones clones
1899 RTA00000345F.J.09.1 13 12 23 2.24234 2.16077
Table 12 Differentially expressed polynucleotides isolated from samples from two patients (UC#2 and UC#3) : Higher expression in normal colon tissue (UC#2:libl5; UC#3:libl8)vs. high metastatic potential colon tissue (UC#2:libl7; UC#3:lib20).
SEQ ID Sequence Name Cluster Lib5 Llib7 Iibl5/libl7 Z Score: NO: ID Clones Clones >2.5899%; > 1.96
491 RTA00000196F.k.l l.l 3 242 26 10.04 13.78900072
SEQ ID Sequence Name Cluster Lib 18 Lib20 Iibl 8/lib20 Zscore
NO: ID clones clones
491 RTA00000196F.k.l l . l 3 409 46 7.59993 15.3998
Example 9: Polynucleotides Differentially Expressed in High Colon Tumor Potential Patient Tissue Versus Metastasized Colon Cancer Patient Tissue
A number of polynucleotide sequences have been identified that are differentially expressed between cells derived from high tumor potential colon cancer tissue and cells derived from high metastatic potential colon cancer cells. Expression of these sequences in colon cancer tissue can be valuable in determining diagnostic, prognostic and/or treatment information associated with the transformation of precancerous tissue to malignant tissue. This information can be useful in the prevention of achieving the advanced malignant state in these tissues, and can be important in risk assessment for a patient.
The following table summarizes identified polynucleotides with differential expression between high tumor potential colon cancer tissue and cells derived from high metastatic potential colon cancer cells:
Table 13 Differentially expressed polynucleotides High tumor potential colon tissue vs. metastatic colon tissue SEQ ID Sequence Name Cluster ID L19 L20 Iibl9/lib20 Zscore NO: clones clones 252 RTA00000181AF.e.l8.3 8 14 1 10.4712 2.56699 253 RTA00000181AF.e.l7.3 8 14 1 10.4712 2.56699 491 RTA00000196F.k.l l.l 3 328 46 5.33318 11.8962 581 RTA00000191AF.p.3.2 17 24 2 8.97535 3.41950 693 RTA00000198F.m.l2.1 4 26 8 2.43082 2.09705 726 RTA00000200R.f.l0.1 4 26 8 2.43082 2.09705 746 RTA00000178AF.i.01.2 4 26 8 2.43082 2.09705 1780 RTA00000118A.J.24.1 18 80 13 4.60274 5.51440 1899 RTA00000345FJ.09.1 13 148 23 4.81287 7.68618
Example 10: Polynucleotides Differentially Expressed in High Tumor Potential Colon
Cancer Patient Tissue Versus Normal Patient Tissue
A number of polynucleotide sequences have been identified that are differentially expressed between cells derived from high tumor potential colon cancer tissue and normal tissue. Expression of these sequences in colon cancer tissue can be valuable in determining diagnostic, prognostic and/or treatment information associated with the prevention of achieving the malignant state in these tissues, and can be important in risk assessment for a
patient. For example, sequences that are highly expressed in the potential colon cancer cells are associated with or can be indicative of increased expression of genes or regulatory sequences involved in early tumor progression. A patient sample displaying an increased level of one or more of these polynucleotides may thus warrant closer attention or more frequent screening procedures to catch the malignant state as early as possible.
The following tables summarize polynucleotides that are differentially expressed between high metastatic potential colon cancer cells and normal colon cells:
Table 14 Differentially expressed polynucleotides detected in samples from two patients (UC#2 and UC#3): Higher expression in tumor potential colon tissue (UC#2:libl6; UC#3:libl9)vs. normal colon tissue (UC#2:libl5; UC#3:libl8)
SEQ ID Sequence Name Cluster Lib 15 Lib 16 Iibl6/libl5 Zscore
NO: ID clones clones
1899 RTA00000345F.J.09.1 13 14 50 3.43709 4.22436
SEQ ID Sequence Name Cluster Libl 8 Lib 19 Iibl9/libl8 Zscore
NO: ID clones clones
65 RTA00000198AF.m.l6.1 51 0 14 12.2505 3.23250
252 RTA00000181AF.e.l8.3 8 1 14 12.2505 2.84687
253 RTA00000181AF.e.l7.3 8 1 14 12.2505 2.84687
581 RTA00000191AF.p.3.2 17 4 24 5.25021 3.24580
693 RTA00000198F.m.l2.1 4 6 26 3.79182 2.98901
716 RTA00000200F.p.05.1 3984 0 7 6.12525 2.09621
726 RTA00000200R.f.l0.1 4 6 26 3.79182 2.98901
746 RTA00000178AF.i.01.2 4 6 26 3.79182 2.98901
1780 RTA00000118A.J.24.1 18 10 80 7.00028 6.65963
1899 RTA00000345F.J.09.1 13 12 148 10.7921 9.86174
Table 15 Differentially expressed polynucleotides: Higher expression in normal colon tissue (UC#2:libl5) vs. tumor potential colon tissue (UC#2:libl6)
SEQ ID Sequence Name Cluster Lib 15 Lib 16 Iibl5/libl6 Zscore
NO: ID clones clones
491 RTA00000196F.k.l l.l 3 242 39 6.44765 12.3988
Example 11 : Polynucleotides Differentially Expressed in Growth Factor-Stimulated Human Microvascular Endothelial Cells (HMEC) Relative to Untreated HMEC
A number of polynucleotide sequences have been identified that are differentially expressed between human microvascular endothelial cells (HMEC) that have been treated with growth factors relative to untreated HMEC.
Sequences that are differentially expressed between growth factor-treated HMEC and untreated HMEC can represent sequences encoding gene products involved in angiogenesis, metastasis (cell migration), and other development and oncogenic processes.
For example, sequences that are more highly expressed in HMEC treated with growth factors (such as bFGF or VEGF) relative to untreated HMEC can serve as markers of
cancer cells of higher metastatic potential. Detection of expression of these sequences in colon cancer tissue can be valuable in determining diagnostic, prognostic and/or treatment information associated with the prevention of achieving the malignant state in these tissues, and can be important in risk assessment for a patient. A patient sample displaying an increased level of one or more of these polynucleotides may thus warrant closer attention or more frequent screening procedures to catch the malignant state as early as possible.
The following table summarizes identified polynucleotides with differential expression between growth factor-treated and untreated HMEC.
Table 16 Differentially expressed polynucleotides: Higher expression in bFGF treated HMEC (libl 3) vs. untreated HMEC (lib 12)
SEQ ID Sequence Name Cluster Lib 12 Lib 13 Iibl3/libl2 Zscore
NO: ID clones clones
648 RTA00000199F.i.9.1 7 25 52 2.07199 2.94741
Table 17 Differentially expressed polynucleotides: Higher expression in VEGF treated HMEC (libl 4) vs. untreated HMEC (libl 2) SEQ ID Sequence Name Cluster Lib 12 Lib 14 ibl4/libl2 Zscore NO: ID clones clones
648 RTA00000199F.i.9.1 7 25 67 >.62449 4.17666
1899 RTA00000345F.J.09.1 13 22 49 ..181 14 2.99887
Example 12: Polynucleotides Differentially Expressed Across Multiple Libraries
A number of polynucleotide sequences have been identified that are differentially expressed between cancerous cells and normal cells across all three tissue types tested (i.e., breast, colon, and lung). Expression of these sequences in a tissue or any origin can be valuable in determining diagnostic, prognostic and/or treatment information associated with the prevention of achieving the malignant state in these tissues, and can be important in risk assessment for a patient. These polynucleotides can also serve as non-tissue specific markers of, for example, risk of metastasis of a tumor. The following table summarizes identified polynucleotides that were differentially expressed but without tissue type- specificity in the breast, colon, and lung libraries tested.
Table 18 Polynucleotides Differentially Expressed Across Multiple Library
Comparisons
SEQ ID Cluster Clones in 1st Clones in 2nd Ratio Cell or Tissue Sample and Cancer
NO. Lib Lib State Compared
(Z Score)
SEQ ID Cluster Clones in 1st Clones in 2nd Ratio Cell or Tissue Sample and Cancer NO. Lib Lib State Compared (Z Score)
2024 1605 libl lib2 libl/lib2 colon: high met > low met
36 11 3.0342732 (3.2440104) lib8 lib9 Iib8/lib9 lung: high met > low met
22 4 7.6861036 (4.2380835)
65 51 lib8 lib9 Iib8/lib9 lung: high met > low met
348 66 7.3684960 (17.431560) lib 18 libl9 libl 9/lib 18 pt #3 colon: tumor > normal
0 14 12.250507 (3.2325073) libl5 lib 17 Iibl7/libl5 pt #2 colon: met > normal
1 10 9.2702249 (2.2883061)
174 3442 lib8 lib9 Iib9/lib8 lung: low met > high met
5 23 3.2916548 (2.3682625) lib3 lib4 Iib3/lib4 breast: high met > low met
17 4 4.1465504 (2.5623912)
203 1827 lib8 lib9 Iib8/lib9 lung: high met > low met
45 15 4.1924201 (5.0989192) lib3 lib4 Iib4/lib3 breast: low met > high met
37 157 4.3491051 (8.7172773)
2245 213 lib8 lib9 Iib9/lib8 lung: low met > high met
137 403 2.1049458 (7.6610331) lib3 lib4 Iib3/lib4 breast: high met > low met
17 4 4.1465504 (2.5623912)
990 6268 lib8 lib9 Iib8/lib9 lung: high met > low met
5 0 6.9873669 (2.1898837) lib3 lib4 Iib4/lib3 breast: low met > high met
3 18 6.1496901 (3.1 117967)
252 8 lib8 lib9 Iib8/lib9 lung: high met > low met
1355 122 15.521118 (39.021411) lib 19 lib20 Iibl9/lib20 pt. #3 colon: tumor > met
14 1 10.471247 (2.5669948) lib 18 libl9 Iibl9/libl8 pt #3 colon: tumor > normal
1 14 12.250507 (2.8468716)
253 8 lib8 lib9 Iib8/lib9 lung: high met > low met
1355 122 15.521118 (39.021411) lib 19 lib20 Iibl9/lib20 pt. #3 colon: tumor > met
14 1 10.471247 (2.5669948) liblδ lib 19 Iibl9/libl8 pt #3 colon: tumor > normal
1 14 12.250507 (2.8468716)
2325 349 lib3 lib4 Iib3/lib4 breast: high met > low met 77 1 75.125736 (8.3844087) libl lib2 lib2/libl colon: low met > high met 69 138 2.1571737 (5.2749799)
SEQ ID Cluster Clones in 1st Clones in 2nd Ratio Cell or Tissue Sample and Cancer NO. Lib Lib State Compared (Z Score)
1095 4423 lib3 Hb4 Hb3/lib4 breast: high met > low met
12 1 1 1.707907 (2.7293134) libl lib2 lib2/libl colon: low met > high met
1 8 8.6286948 (2.1149516)
1124 779 Hb3 lib4 Iib3/lib4 breast: high met > low met
60 22 2.6608879 (3.9749537) libl lib2 lib2/libl colon: low met > high met
27 54 2.1571737 (3.2316908)
387 1002 Hb3 lib4 Iib3/lib4 breast: high met > low met
42 20 2.0488837 (2.5703094) libl lib2 lib2/libl colon: low met > high met
12 65 5.8423454 (6.2625969)
419 4769 lib8 lib9 Iib8/lib9 lung: high met > low met
10 3 4.6582446 (2.2936274) lib3 lib4 Iib4/lib3 breast: low met > high met
2 20 10.249483 (3.6825426)
420 4769 lib8 lib9 Iib8/lib9 lung: high met > low met
10 3 4.6582446 (2.2936274) lib3 lib4 Iib4/lib3 breast: low met > high met
2 20 10.249483 (3.6825426)
1205 3500 lib3 lib4 Iib3/lib4 breast: high met > low met
12 3 3.9026356 (2.0180506) libl lib2 lib2/libl colon: low met > high met
3 13 4.6738763 (2.4029818)
491 3 libl lib2 libl/lib2 colon: high met > low met
5268 2164 2.2570094 (32.965564) lib8 lib9 Iib8/lib9 lung: high met > low met
986 392 3.5150733 (22.468331) lib 19 lib20 Iibl9/lib20 pt #3 colon: tumor > met
328 46 5.3331820 (11.896271) lib 18 lib20 Iibl8/lib20 pt #3 colon: normal > met
409 46 7.5999342 (15.399861) lib 15 lib 17 Iibl5/libl7 pt#2 colon: normal > met
242 26 10.04 (13.789000) lib 15 lib 16 Iibl5/libl6 pt#2 colon: normal > tumor
242 39 6.44765 12.39883
552 35 libβ lib9 Iib8/lib9 lung: high met > low met
868 11 110.27335 (34.289704) lib3 lib4 Iib4/lib3 breast: low met > high met
386 1967 5.2229880 (33.232871)
560 1577 >3 lib4 Iib3/lib4 breast: high met > low met
25 3 8.1304909 (3.9038139)
SEQ ID Cluster Clones in 1st Clones in 2nd Ratio Cell or Tissue Sample and Cancer NO. Lib Lib State Compared (Z Score) libl lib2 lib2/libl colon: low met > high met
12 40 3.5952895 (4.0199130)
581 17 libl9 lib20 Iibl9/lib20 pt #3 colon: tumor > met
24 2 8.9753551 (3.4195074) lib 18 lib 19 Iibl9/libl8 pt #3 colon: tumor > normal
4 24 5.2502174 (3.2458055)
590 2444 lib3 lib4 Iib4/lib3 breast: low met > high met
26 55 2.1681599 (3.2224421) lib8 lib9 Iib9/lib8 lung: low met > high met
12 37 2.2063628 (2.2999846)
1354 21 1 lib3 lib4 Iib3/lib4 breast: high met > low met
121 43 2.7454588 (5.8560985) libl lib2 lib2/libl colon: low met > high met
109 206 2.0384302 (6.0859794)
1387 1002 lib3 lib4 Iib3/lib4 breast: high met > low met
42 20 2.0488837 (2.5703094) libl lib2 lib2/libl colon: low met > high met
12 65 5.8423454 (6.2625969)
648 7 libl2 lib 14 Iibl4/libl2 HMEC: VEGF > untreated
25 67 2.6244913 (4.1766696) lib 12 lib 13 Iibl3/libl2 HMEC: bFGF > untreated
25 52 2.0719962 (2.9474155)
693 4 lib8 lib9 Iib8/lib9 lung: high met > low met
506 209 3.3833566 (15.730912) lib3 lib4 Iib4/lib3 breast: low met > high met
987 2807 2.9149240 (30.381945) lib 19 lib20 Iibl9/lib20 pt#3 colon: tumor > met
26 8 2.4308253 (2.0970580) lib 18 lib 19 Iibl9/libl8 pt#3 colon: tumor > normal
6 26 3.7918237 (2.9890107)
726 4 lib8 lib9 Iib8/lib9 lung: high met > low met
506 209 3.3833566 (15.730912) lib3 lib4 Iib4/lib3 breast: low met > high met
987 2807 2.9149240 (30.381945) libl9 lib20 Iibl9/lib20 pt#3 colon: tumor > met
26 8 2.4308253 (2.0970580) lib 18 lib 19 libl 9/lib 18 pt#3 colon: tumor > normal
6 26 3.7918237 (2.9890107)
746 Iib8 lib9 Iib8/lib9 lung: high met > low met
506 209 3.3833566 (15.730912) lib3 lib4 Iib4/lib3 breast: low met > high met 987 2807 2.9149240 (30.381945)
SEQ ID Cluster Clones in 1st Clones in 2nd Ratio Cell or Tissue Sample and Cancer NO. Lib Lib State Compared (Z Score) lib 19 lib20 Iibl9/lib20 pt#3 colon: tumor > met
26 8 2.4308253 (2.0970580) lib 18 lib 19 libl 9/lib 18 pt#3 colon: tumor > normal
6 26 3.7918237 (2.9890107)
1780 18 lib 19 lib20 Iibl9/lib20 pt#3 colon: tumor > met
80 13 4.6027462 (5.5144093) lib 18 libl9 libl 9/lib 18 pt#3 colon: tumor > normal
10 80 7.0002899 (6.6596394) lib 15 libl 7 Iibl7/libl5 pt#3 colon: met > normal
4 23 5.3303793 (3.2702852)
1899 13 lib 19 lib20 Iibl9/lib20 pt#3 colon: tumor > met
148 23 4.8128716 (7.6861840) libl8 lib20 Iib20/libl8 pt#3 colon: met > normal
12 23 2.2423439 (2.1607719) lib 18 libl9 libl 9/lib 18 pt#3 colon: tumor > normal
12 148 10.7921 13 (9.8617485) lib 15 lib 17 Iibl7/libl5 pt#2 colon: met > normal
14 80 5.2972714 (6.3458044) lib 15 lib 16 Iibl6/libl5 pt#2 colon: tumor > normal
14 50 3.4370927 (4.2243697) lib 12 lib 14 Iibl4/libl2 HMEC: VEGF > untreated
22 49 2.1811410 (2.9988774)
1915 1508 libl lib2 libl/lib2 colon: high met > low met
46 17 2.5087292 (3.2300592) lib3 lib4 Iib3/lib4 breast: high met > low met
21 5 4.0977674 (2.8791960)
1979 48 lib8 lib9 Iib8/lib9 lung: high met > low met
342 155 3.0834574 (12.213852) lib3 lib4 Iib4/lib3 breast: low met > high met
412 1020 2.5374934 (16.526285)
2007 1275 lib3 lib4 Iib4/lib3 breast: low met > high met 15 32 2.1865564 (2.4185764) lib8 lib9 Iib9/lib8 lung: low met > high met 10 42 3.0054239 3.1471113 high met = high metastatic potential; low met = low metastatic potential; met = metastasized; tumor = non-metastasized tumor; pt = patient; #2 = UC#2; #3 = UC#3;
HMEC = human microvascular endothelial cell; bFGF = bFGF treated; VEGF = VEGF treated
Example 12: Polynucleotides Exhibiting Colon-Specific Expression
The cDNA libraries described herein were also analyzed to identify those polynucleotides that were specifically expressed in colon cells or tissue, i.e., the polynucleotides were identified in libraries prepared from colon cell lines or tissue, but not in libraries of breast or lung origin. The polynucleotides that were expressed in a colon cell line and/or in colon tissue, but were present in the breast or lung cDNA libraries described herein, are shown in Table 19 (inserted before claims).
No clones corresponding to the colon-specific polynucleotides in the table above were present in any of Libraries 3, 4, 8, 9, 12, 13, 14, or 15. The polynucleotide provided above can be used as markers of cells of colon origin, and find particular use in reference arrays, as described above.
Example 13: Identification of Contiguous Sequences Having a Polynucleotide of the Invention The novel polynucleotides were used to screen publicly available and proprietary databases to determine if any of the polynucleotides of SEQ ID NOS: 1-2502 would facilitate identification of a contiguous sequence, e.g., the polynucleotides would provide sequence that would result in 5' extension of another DNA sequence, resulting in production of a longer contiguous sequence composed of the provided polynucleotide and the other DNA sequence(s). Contiging was performed using the Gelmerge application (default settings) of GCG from the Univ. of Wisconsin.
Using these parameters, 146 contiged sequences were generated. These contiged sequences are provided as SEQ ID NOS:5107-5252 (see Table 1). The contiged sequences can be correlated with the sequences of SEQ ID NOS: 1-2502 upon which the contiged sequences are based by, for example, identifying those sequences of SEQ ID NOS: 1 -2502 and the contiged sequences of SEQ ID NOS: 5107-5252 that share the same clone name in Table 1.
The contiged sequences (SEQ ID NO:5107-5252) thus represent longer sequences that encompass a polynucleotide sequence of the invention. The contiged sequences were then translated in all three reading frames to determine the best alignment with individual sequences using the BLAST programs as described above for SEQ ID NOS: 1-2502 and the validation sequences "SEQ ID NOS:2503-5106." Again the sequences were masked using the XBLAST program for masking low complexity as described above in Example 1
(Table 2). Several of the contiged sequences were found to encode polypeptides having characteristics of a polypeptide belonging to a known protein families (and thus represent new members of these protein families) and/or comprising a known functional domain (Table 20). Thus the invention encompasses fragments, fusions, and variants of such polynucleotides that retain biological activity associated with the protein family and/or functional domain identified herein.
Table 20 Profile hits using contiged sequences
SEQ Biological Activity (Profile) Start Stop Score Direction Sequence Name ID NO
5111 7tm_2 71 915 8090 for RTA00000399F.O.01.1
5120 7tm_2 101 919 8475 rev RTA00000341F.m.21.1
5174 7tm_2 3 963 9431 for RTA00000192AF.h.l9.1
5197 7tm_2 214 1073 8528 rev RTA00000192AF.f.3.1
5208 ANK 546 629 4920 for RTA00000190AF.f.5.1
5120 asp 126 1067 6620 rev RTA00000341F.m.21.1.
5241 asp 1 12 1094 6553 for RTA00000418F.i.06.1
5243 asp 347 1028 5981 for RTA00000339F.b.02.1
5197 ATPases 1 13 781 5690 for RTA00000192AF.f.3.1
5239 ATPases 1 348 15955 for RTA00000401F.m.07.1
5241 ATPases 110 823 6782 for RTA00000418F.i.06.1
5243 ATPases 338 874 5832 for RTA00000339F.b.02.1
5125 protkinase 59 685 5791 for RTA00000182AF.C.5.1
5217 protkinase 75 1035 5405 for RTA00000181AF.p.l2.3
5237 protkinase 25 546 5107 rev RTA000001 18A.n.5.1
5248 protkinase 14 422 5103 rev RTA00000419F.k.05.1
5252 protkinase 89 755 5499 for RTA00000404F.m.l7.2
5120 Wnt_dev_sign 3 948 11036 for RTA00000341F.m.21.1
All stop/start sequences are provided in the forward direction.
Descriptions of the profiles for the indicated protein families and functional domains are provided in Example 3 above.
Those skilled in the art will recognize, or be able to ascertain, using not more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such specific embodiments and equivalents are intended to be encompassed by the following claims.
All publications and patent applications cited in this specification are herein incorporated by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention.
Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims.
Deposit Information:
The following materials were deposited with the American Type Culture Collection: CMCC = (Chiron Master Culture Collection)
cDNA Libraries Deposited with ATCC
cDNA Library ES25 cDNA Library ES26
January 22, 1999 January 22, 1999
ATCC No. ATCC No.
M00001675D:B08 M00001479C:F10
M00001589B:E12 M00003842D:F08
M00001607D:A11 M00003901A:C09
M00001636A:E07 M00003982A:B06
M00001530A:B12 M00003824A:A06
M00001495B:B08 M00003845D:C03
M00001487C:F01 M00003856A:B07
M00001644B:D06 M00004104B:A02
M00003751C:A04 M00004110C:E03
In addition, libraries of selected clones were deposited. The details of these deposits are provided in Tables 21-24.
This deposit is provided merely as convenience to those of skill in the art, and is not an admission that a deposit is required under 35 U.S.C. §112. The sequence of the polynucleotides contained within the deposited material, as well as the amino acid sequence of the polypeptides encoded thereby, are incorporated herein by reference and are controlling in the event of any conflict with the written description of sequences herein. A license may be required to make, use, or sell the deposited material, and no such license is granted hereby.
Retrieval of Individual Clones from Deposit of Pooled Clones
Where the ATCC deposit is composed of a pool of cDNA clones, the deposit was prepared by first transfecting each of the clones into separate bacterial cells. The clones were then deposited as a pool of equal mixtures in the composite deposit. Particular clones can be obtained from the composite deposit using methods well known in the art. For example, a bacterial cell containing a particular clone can be identified by isolating single colonies, and identifying colonies containing the specific clone through standard colony hybridization techniques, using an oligonucleotide probe or probes designed to specifically hybridize to a sequence of the clone insert (e.g., a probe based upon unmasked sequence of the encoded polynucleotide having the indicated SEQ ID NO). The probe should be designed to have a Tm of approximately 80°C (assuming 2°C for each A or T and 4°C for each G or C). Positive colonies can then be picked, grown in culture, and the recombinant clone isolated. Alternatively, probes designed in this manner can be used to PCR to isolate a nucleic acid molecule from the pooled clones according to methods well known in the art,
e.g., by purifying the cDNA from the deposited culture pool, and using the probes in PCR reactions to produce an amplified product having the corresponding desired polynucleotide sequence.
Table 1.
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
1 1/28/98 1 RTA00000197AF.i. l 6.1 M00001490A:D1 1 16402 n 1/28/98 2 RTA00000188AF.n.15.1 M00003804A:H04 0
3 1/28/98 3 RTA00000197AF.e.24.1 M00001456B:F10 39250
4 1/28/98 4 RTA00000198R.f.04.1 M00001607D:F07 5023
5 1/28/98 5 RTA00000195R.C.1 1.1 M0000381 1A:E03 66087
6 1/28/98 6 RTA00000195AF.C.16.1 M00003829C:A1 1 23508
7 1/28/98 7 RTA00000197AR.e.l2.1 M00001454B:G07 22095
8 1/28/98 8 RTA00000200AF.h. l l .2 M00004146A:C08 8399
9 1/28/98 9 RTA00000177AF.g.22.1 M00001347C:G08 7031
10 1/28/98 10 RTA00000198AF.n.l 6.1 M00001694C:H10 3721
1 1 1/28/98 1 1 RTA00000199AF.i.l 7.1 M00003880C:F10 9615
12 1/28/98 12 RTA00000183AF.L15.2 M00001529B:C04 2642
13 1/28/98 13 RTA00000190AF.i.5.1 M00003919A:A10 0
14 1/28/98 14 RTA00000196R.C.1 1.2 M00001352A:E12 13658
15 1/28/98 15 RTA00000177AR.n.8.1 M00001356D:F06 4188
16 1/28/98 16 RTA00000196AF.e. l6.1 M00001363C:H02 39252
17 1/28/98 17 RTA00000183AR.e.l4.2 M00001506B:D09 17437
18 1/28/98 18 RTA00000196AF.C.17.1 M00001352C:F06 39602
19 1/28/98 19 RTA00000185AF.a.8.1 M00001570D:A03 4868
20 1/28/98 20 RTA00000181 AF.1.14.2 M00001454D:D06 2364
21 1/28/98 21 RTA00000131A.g.l9.2 M00001449A:G10 36535
22 1/28/98 22 RTA00000187AR.O.10.2 M00001718D:F07 8984
23 1/28/98 23 RTA00000198R.b.08.1 M00001567C:H12 22636
24 1/28/98 24 RTA00000200AF.f.l l .l M000041 1 1 D:D1 1 0
25 1/28/98 25 RTA00000196AF.C.1.1 M00001349C:C05 8171
26 1/28/98 26 RTA00000200R.g.09.1 M00004131 B:H09 22785
27 1/28/98 27 RTA00000192AF.i.l2.1 M00004169C:C12 5319
28 1/28/98 28 RTA00000178AR.O.01.5 M00001387B:H07 0
29 1/28/98 29 RTA00000200AF.b.l 9.1 M00004042D:H02 22847
30 1/28/98 30 RTA00000184AR.n.07.2 M00001561 C:F06 0
31 1/28/98 31 RTA00000200F.m.l 5.1 M00004236C:D10 22601
32 1/28/98 32 RTA00000198R.m. l9.1 M00001680D:D02 40041
33 1/28/98 33 RTA00000178AR.a.20.1 M00001362C:H1 1 945
34 1/28/98 34 RTA00000197AF.n.8.1 M00001536D:A12 4101
35 1/28/98 35 RTA00000191AF.n.17.1 M00004091 B:D1 1 7848
36 1/28/98 36 RTA00000181AF.p.4.3 M00001460A:A03 40392
37 1/28/98 37 RTA00000181AF.n.l 5.2 M00001457A:B07 86128
38 1/28/98 38 RTA00000196R.k.07.1 M00001399C:D09 22443
39 1/28/98 39 RTA00000189AR.b.l 9.1 M00003832B:E01 5294
40 1/28/98 40 RTA00000200AR.e.02.1 M00004090A:F09 36059
41 1/28/98 41 RTA00000184F.k. l2.1 M00001557D:D09 8761
42 1/28/98 42 RTA00000184F.J.21.1 M00001557A:D02 7065
43 1/28/98 43 RTA00000179AF.C.14.3 M00001392D:H04 0
44 1/28/98 44 RTA00000199F.f.08.2 M00003841 D:E03 12445
45 1/28/98 45 RTA00000197AR.f.l2.1 M00001458C:E01 3513
46 1/28/98 46 RTA00000182AF.f.l3.1 M00001470C:B10 8010
47 1/28/98 47 RTA00000192AF.m.l2.1 M00004191 D:B 1 1 0
48 1/28/98 48 RTA00000177AR.a.23.5 M00001339D:G02 6995
49 1/28/98 49 RTA00000198R.O.05.1 M00003750A:D01 26702
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
50 1/28/98 50 RTA00000201 R.a.02.1 M00004295B:D02 35362
51 1/28/98 51 RTA00000199R. 07.1 M00003901 C:A03 12973
52 1/28/98 52 RTA00000201R.b.02.1 M00004319D:G09 22660
53 1/28/98 53 RTA00000199AF.p.9.1 M00003988A:E10 10430
54 1/28/98 54 RTA00000200F.O.22.1 M00004282B:A04 983
55 1/28/98 55 RTA00000186AF.i.21.1 M00001636C:H09 6033
56 1/28/98 56 RTA00000177AF.e.9.1 M00001343D:C04 37442
57 1/28/98 57 RTA00000198AF.k.20.1 M00001660C:B12 22553
58 1/28/98 58 RTA00000199F.b.01.2 M00003778A:D08 191 18
59 1/28/98 59 RTA00000195AF.b.l3.1 M00001560D:A03 12605
59 2/24/98 78 RTA00000195AF.b.l3.1 M00001560D:A03 12605
60 1/28/98 60 RTA00000196AR.U2.3 M00001389D:G1 1 38800
61 1/28/98 61 RTA00000197AF.h.l l .l M00001476D:G03 22264
62 1/28/98 62 RTA00000190AF.a.l8.2 M00003900D:B10 0
63 1/28/98 63 RTA00000184AF.R.19.1 M00001558B:D08 8022
64 1/28/98 64 RTA00000198AF.p.l2.1 M00003763D:E10 8878
65 1/28/98 65 RTA00000198AF.m.l 6.1 M00001679D:D05 51
66 1/28/98 66 RTA00000199F.C.09.2 M00003800A:C09 16824
67 1/28/98 67 RTA00000200AF.g.07.1 M00004128B:G01 0
68 1/28/98 68 RTA00000184F.k. l9.1 M00001558B:D08 8022
69 1/28/98 69 RTA00000186AF.h.8.1 M00001632C:C09 35547
70 1/28/98 70 RTA00000192AF.e.3.1 M00004138B:H02 13272
71 1/28/98 71 RTA00000193AR.O.16.3 M00004409B:A1 1 52972
72 1/28/98 72 RTA00000200F.a.6.1 M00004029B:F1 1 36952
73 1/28/98 73 RTA00000177AF.e.21.3 M00001344A:H07 4306
74 1/28/98 74 RTA00000196AF.h.20.1 M00001385B.-F10 0
75 1/28/98 75 RTA00000180AR.h.l9.2 M00001428A:H10 84182
76 1/28/98 76 RTA00000200AF.h.05.2 M00004142D:E10 10950
77 1/28/98 77 RTA00000197AF.n.2.1 M00001535A:D02 6229
78 1/28/98 78 RTA00000199R.f.09.1 M00003842B:D09 22907
79 1/28/98 79 RTA00000199AF.p.4.1 M00003985C:F01 10282
80 1/28/98 80 RTA00000196AF.p.l3.2 M00001432A:E06 6125
81 1/28/98 81 RTA00000196AF.b.l5.1 M00001347B:E01 5102
82 1/28/98 82 RTA00000183AF.1.18.1 MO0001535D:C01 3484
83 1/28/98 83 RTA00000186AFT.24.2 M00001629B:E06 0
84 1/28/98 84 RTA00000191AF.h.l4.1 M00004056B:D09 13553
85 1/28/98 85 RTA00000200R.O.03.1 M00004257C:H06 22807
86 1/28/98 86 RTA00000189AF.1.22.1 M00003879C:G10 33333
87 2/24/98 245 RTA00000195AF.d.20.1 M000041 17A:D1 1 37574
87 1/28/98 87 RTA00000195AF.d.20.1 M000041 17A:D1 1 37574
88 1/28/98 88 RTA00000197AF.e.23.1 M00001456B:C09 37157
89 1/28/98 89 RTA00000177AF.n.8.3 M00001356D:F06 4188
90 1/28/98 90 RTA00000199F.f.l 5.2 M00003845A:H12 8772
91 1/28/98 91 RTA00000198AF.J.19.1 M00001653C:F12 38914
92 1/28/98 92 RTA00000198AF.J.18.1 M00001653B:G07 22759
93 1/28/98 93 RTA00000200F.O.1 1.1 M00004270A:F1 1 0
94 1/28/98 94 RTA00000195AF.b.4.1 M00001490C:D07 0
95 1/28/98 95 RTA00000180AF.g.3.1 M00001425A:C1 1 9024
96 1/28/98 96 RTA00000197AF.J.20.1 M00001496C:C1 1 4915
97 1/28/98 97 RTA00000197AF.O.2.1 M00001541 C:B07 5739
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
98 1/28/98 98 RTA00000200AF.f.l4.1 M000041 15D:C08 22051
99 1/28/98 99 RTA00000184AF.d.8.1 M00001548A:A08 4393
100 1/28/98 100 RTA00000200R.f.l4.1 M000041 15D:C08 22051
101 1/28/98 101 RTA00000191 AF.d.08.2 M00003997B:G07 970
102 1/28/98 102 RTA00000199R.J.08.1 M00003884D:G07 37844
103 1/28/98 103 RTA00000199F.e.l 0.1 M00003822A:F02 22906
104 1 /28/98 104 RTA00000196R.h.03.1 M00001381 A:D02 6636
105 1/28/98 105 RTA00000179AF.g.l 2.3 M00001398A:G03 36390
106 1/28/98 106 RTA00000197AF.n.21.1 M00001540B:C09 0
107 1/28/98 107 RTA00000196R.i.l 3.1 M00001390A:A09 9857
108 1/28/98 108 RTA00000183AR.h.23.2 M00001528A:F09 18957
109 1/28/98 109 RTA00000197AF.d.l2.1 M00001451 D:C10 39546
1 10 1/28/98 1 10 RTA00000197R.H.01.1 M00001470A:H01 13075
1 1 1 1/28/98 1 1 1 RTA00000198AF.O.12.1 M00003751 D:B02 22038
1 12 1/28/98 1 12 RTA00000177AF.m.8.1 M00001354C:C10 8010
1 13 1/28/98 1 13 RTA00000196AF.d.09.1 M00001354B:B 10 16934
1 14 1/28/98 1 14 RTA00000200R.f.02.1 M00004108A:A09 7138
1 15 1/28/98 1 15 RTA00000179AR.O.20.3 M00001409D:F1 1 2409
1 16 1/28/98 1 16 RTA00000181 AR.k.24.3 M00001454B:C12 7005
1 17 1/28/98 1 17 RTA00000199AF.J.18.1 M00003889D:B09 5140
1 18 1/28/98 1 18 RTA00000199F.b.24.2 M00003794A:B03 0
1 19 1/28/98 1 19 RTA00000181 AR.L24.2 M00001454B:C12 7005
120 1/28/98 120 RTA00000178AR.m. l9.5 M00001384D:H07 0
121 1/28/98 121 RTA00000199AF.O.16.1 M00003979A:F03 16721
122 1/28/98 122 RTA00000197AF.1.15.1 M00001517B:G08 4947
123 1/28/98 123 RTA00000191 AF. 6.1 M00004078B:A1 1 5451
124 1/28/98 124 RTA00000199AR.m.06.1 M00003933C:D06 19122
125 1/28/98 125 RTA00000197AF.k.l 5.1 M00001504D:D1 1 22750
126 1/28/98 126 RTA00000201 F.d. l6.1 M00004388B:A08 0
127 1/28/98 127 RTA00000178AF.k.l 8.1 M00001382A:F04 9755
128 1/28/98 128 RTA00000196F.U2.1 M00001389D:G1 1 38800
129 1/28/98 129 RTA00000134A.d.l 0.1 M00001528A:F09 18957
130 1/28/98 130 RTA00000196AF.h.23.1 M00001386A:C02 13357
131 1/28/98 131 RTA00000185AF.d.l l .2 M00001579D:C03 6539
132 1/28/98 132 RTA00000178AF.f.20.3 M00001372C:F07 39881
133 1/28/98 133 RTA00000181AR.n.20.3 M00001457B:E03 0
134 1/28/98 134 RTA00000197F.e.l l .l M00001454B:G03 2306
135 1/28/98 135 RTA00000196AF.C.22.1 M00001352D:C05 22548
136 1/28/98 136 RTA00000197AF.C.10.1 M00001448B:F06 10400
137 1/28/98 137 RTA00000181 AF.m.4.3 M00001455A:E09 13238
138 1/28/98 138 RTA00000182AF.a.3.3 M00001462B:A10 0
139 1/28/98 139 RTA00000191AF.d.01.2 M00003996A:A06 7031
140 1/28/98 140 RTA00000199F.a.2.1 M00003772A:D07 12674
141 1/28/98 141 RTA00000196AF.C.6.1 M00001350A:D06 23148
142 1/28/98 142 RTA00000198AF. 19.1 M00001660B:C04 75879
143 1/28/98 143 RTA00000199R.h.09.1 M00003867C:H09 76020
144 1/28/98 144 RTA00000198AF.O.18.1 M00003755A:A09 13018
145 1/28/98 145 RTA00000178AF.h.24.1 M00001376B:C06 6745
146 1/28/98 146 RTA00000185AF.a.l 9.2 M00001571 C:H06 5749
147 1/28/98 147 RTA00000185AF.C.24.2 M00001578B:E04 23001
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
148 1/28/98 148 RTA00000199F.h.l 7.2 M00003871 A:A05 36254
149 1/28/98 149 RTA00000181AR.h.06.3 M00001450D:D04 87226
150 1/28/98 150 RTA00000184F.k.09.1 M00001557C:H07 7065
151 1/28/98 151 RTA00000200R.1.17.1 M00004217C:D03 12771
152 1/28/98 152 RTA00000196AF.C.20.1 M00001352C:H02 8934
153 1/28/98 153 RTA00000200F.n.l 7.2 M00004252C:E03 19064
154 1/28/98 154 RTA00000196F.e.7.1 M00001360D:E1 1 1039
155 1/28/98 155 RTA00000197F.e.8.1 M00001454A:C 1 1 3135
156 1/28/98 156 RTA00000199R.O.12.1 M00003977A:E04 16128
157 1/28/98 157 RTA00000188AF.n.01.1 M00003801A:B10 36412
158 1/28/98 158 RTA00000198AF.k.03.1 M00001655A:F06 22765
159 1/28/98 159 RTA00000182AF.I.12.1 M00001487A:A05 1027
160 1/28/98 160 RTA00000192AF.b.20.1 M000041 18D:E08 0
161 1/28/98 161 RTA00000183AF.e.23.2 M00001506D:A09 0
162 1/28/98 162 RTA00000201 F.e.l5.1 M00004444B:D1 1 9960
163 1/28/98 163 RTA00000192AR.e.l3.3 M00004142A:B12 9457
164 1/28/98 164 RTA00000193AR.i. l4.4 M00004307C:A06 9457
165 1/28/98 165 RTA00000192AF.g.23.1 M00004157C:A09 6455
166 1/28/98 166 RTA00000198AF.f.21.1 M00001614D:D09 22676
167 1/28/98 167 RTA00000179AF.d.22.3 M00001394C:C1 1 7955
168 1/28/98 168 RTA00000177AR.k.23.1 M00001352D:D02 35550
169 1/28/98 169 RTA00000196AF.g.24.1 M00001380C:F02 8685
170 1/28/98 170 RTA00000197AF.d.23.1 M00001453A:E1 1 16130
171 1/28/98 171 RTA00000198R.C.07.1 M00001575D:G05 19181
172 1/28/98 172 RTA00000186AF.p.09.2 M00001655C:E04 6879
173 1/28/98 173 RTA00000200AR.b.07.1 M00004039C:C01 17125
174 1/28/98 174 RTA00000181AF.e.22.3 M00001448D:F09 3442
175 1/28/98 175 RTA00000200F.i.5.1 M00004156B:A12 22892
176 1/28/98 176 RTA00000183AF.h.l9.1 M00001528A:A01 5175
177 1/28/98 177 RTA00000197AF.C.3.1 M00001447C:C01 3145
178 1/28/98 178 RTA00000200F.O.03.1 M00004257C:H06 22807
179 1/28/98 179 RTA00000179AF.f.20.3 M00001397B:B09 16154
180 1/28/98 180 RTA00000199AF.J.12.1 M00003887A:A06 22461
181 1/28/98 181 RTA00000198AF.d.2.1 M00001585A:F07 0
182 1/28/98 182 RTA00000196AF.h.l6.1 M00001384C:E03 39895
183 1/28/98 183 RTA00000198AF.C.17.1 M00001579C:E08 6923
184 1/28/98 184 RTA00000197AF.f.7.1 M00001457C:C1 1 19261
185 2/24/98 234 RTA00000195AF.d.4.1 M00003881 D:D06 22766
185 1/28/98 185 RTA00000195AF.d.4.1 M00003881D:D06 22766
186 1/28/98 186 RTA00000198R.p.09.1 M00003761D:E02 10473
187 1/28/98 187 RTA00000180AR.J.04.4 M00001429C:G12 22300
188 1/28/98 188 RTA00000188AF.O.05.1 M00003806D:G05 4668
189 1/28/98 189 RTA00000197AF.h. l 0.1 M00001476B:F10 15554
190 1/28/98 190 RTA00000134A.C.7.1 M00001528A:A01 5175
191 1/28/98 191 RTA00000187AF.p.23.1 M00003748B:F02 39804
192 1/28/98 192 RTA00000185AF.m.7.1 M00001605C:D12 39804
193 1/28/98 193 RTA00000199AF.n.3.1 M00003946D:C1 1 0
194 1/28/98 194 RTA00000200R.k.01.1 M00004188C:A09 40049
195 1/28/98 195 RTA00000198AF.C.10.1 M00001577B:H02 77149
196 1/28/98 196 RTA00000198F.e.l0.1 M00001599B:E09 9727
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
197 1/28/98 197 RTA00000198F.1.12.1 M00001669C:B01 8592
198 1/28/98 198 RTAOOOOO 197AR.e.07.1 M00001453D:G12 86969
199 1/28/98 199 RTAOOOOO 199R.C.09.1 M00003800A:C09 16824
200 1/28/98 200 RTAOOOOO 182AF 2.1 M00001469D:D02 4794
201 1/28/98 201 RTAOOOOO 198AF.p.18.1 M00003769B:D03 23081
202 1/28/98 202 RTA00000200R.1.17.2 M00004217C:D03 12771
203 1/28/98 203 RTA00000201 F.d.09.1 M00004380B:A05 1827
204 1/28/98 204 RTA00000180AR.O.5.2 M00001437D:C04 7848
205 1/28/98 205 RTA00000189AF.g. l l . l M00003858D:F12 0
206 1/28/98 206 RTA00000181AF.O.04.2 M00001457C:C12 22205
207 1/28/98 207 RTAOOOOO 199AF.1.19.1 M00003924B:D04 22460
208 1/28/98 208 RTAOOOOO 198AF.h.22.1 M00001635C:A03 22366
209 1/28/98 209 RTAOOOOO 182AF.C.5.1 M00001464D:F06 6397
210 1/28/98 210 RTAOOOOO 189AR.b.12.1 M00003829B:G03 17233
21 1 1/28/98 21 1 RTA00000199AF.m. l 5.1 M00003939A:A02 10101
212 1/28/98 212 RTAOOOOO 197 AF.j .9.1 M00001494B:C01 13236
213 1/28/98 213 RTA00000200F.O.04.1 M00004260D:C12 12514
214 1/28/98 214 RTA00000200AF.f.22.1 M00004121 C:F06 16521
215 1/28/98 215 RTAOOOOO 192AR.e.14.3 M00004142A:D08 3300
216 1/28/98 216 RTAOOOOO 188AF.g.9.1 M00003774B:B08 4959
217 1/28/98 217 RTAOOOOO 198 AF.h.3.1 M00001625D:C07 22562
218 1/28/98 218 RTAOOOOO 188AF.0.18.1 M0000381 1 D:A12 13678
219 1/28/98 219 RTAOOOOO 198AF.m.19.1 M00001680D:D02 40041
220 1/28/98 220 RTA00000200AF.h.01.2 M00004141 D:A09 0
221 1/28/98 221 RTAOOOOO 189AF.L 17.1 M00003868C:H10 16814
222 1/28/98 222 RTAOOOOO 185 AF.i.4.1 M00001594A:B12 13942
223 1/28/98 223 RTA00000197F.i.9.1 M00001488D:C10 0
224 1/28/98 224 RTAOOOOO 188AF.m.1 1.1 M00003799A:D09 0
225 1/28/98 225 RTA00000189AF.b.5.1 M00003828A:E04 3784
226 1/28/98 226 RTA00000191AR.O.09.4 M00004096A:G02 0
227 1/28/98 227 RTA00000201 R.d.02.2 M00004375A:H01 2599
228 1/28/98 228 RTA00000187AR.h.l 5.2 M00001679A:A06 6660
229 1/28/98 229 RTA00000198 AF.g.3.1 M00001615C:F03 0
230 1/28/98 230 RTAOOOOO 185AR.b.18.1 M00001575B:C09 12171
231 1/28/98 231 RTA00000192AF.1.13.2 M00004185C:C03 1 1443
232 1/28/98 232 RTAOOOOO 186 AF.j .03.2 M00001638A:E07 0
233 1/28/98 233 RTA00000197AF.1.8.1 M0000151 1 B:C06 39954
234 1/28/98 234 RTA00000191 AF.f.8.1 M00004035A:A04 6541
235 1/28/98 235 RTA00000201 AF.a.02.1 M00004295B:D02 35362
236 1/28/98 236 RTA00000183AR.h.23.1 M00001528A:F09 18957
237 1/28/98 237 RTAOOOOO 197AF. 10.1 M00001500D:B1 1 0
238 1/28/98 238 RTAOOOOO 187AR.L 12.1 M00001679D:F02 78415
239 1/28/98 239 RTA00000201 R.d.02.1 M00004375A:H01 2599
240 1/28/98 240 RTAOOOOO 178AF.e.1.1 M00001369A:H12 2664
241 1/28/98 241 RTA00000200AF.1.17.1 M00004217C:D03 12771
242 1/28/98 242 RTAOOOOO 198AF.m.17.1 M00001679D:F06 77992
243 1/28/98 243 RTA00000181 AF.m. l 5.3 M00001455D:A1 1 12081
244 1/28/98 244 RTAOOOOO 199F.f.12.2 M00003844C:A08 8131
245 1/28/98 245 RTA00000200AF.L7.1 M00004193C:G1 1 0
246 1/28/98 246 RTAOOOOO 199 AF.1.4.1 M0000391 1 D:B04 4410
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
247 1/28/98 247 RTA00000198AF. 08.1 M00001656C:G08 17436
248 1/28/98 248 RTAOOOOO 198R.C.14.1 M00001578D:C04 39814
249 1/28/98 249 RTA00000200R.O.03.2 M00004257C:H06 22807
250 1/28/98 250 RTAOOOOO 192 AF.j .21.1 M00004176D:B12 2289
251 1/28/98 251 RTA00000192AF.n.13.1 M00004197D:H01 8210
252 1/28/98 252 RTA00000181 AF.e.l 8.3 M00001448D:C09 8
253 1/28/98 253 RTA00000181AF.e.l 7.3 M00001448D:C09 8
254 1/28/98 254 RTAOOOOO 178AF.n.2.1 M00001385C:H1 1 17083
255 1/28/98 255 RTA00000199AF.J.17.1 M00003889A:D10 5121
256 1/28/98 256 RTAOOOOO 184AR.e.15.1 M00001549C:E06 16347
257 1/28/98 257 RTA00000198AF.e.20.1 M00001604C:E09 9810
258 1/28/98 258 RTAOOOOO 199F.h.12.2 M00003868B:D12 16621
259 1/28/98 259 RTAOOOOO 197AF.J .4.1 M00001492D:A1 1 17209
260 1/28/98 260 RTAOOOOO 198R.m.17.1 M00001679D:F06 77992
261 1/28/98 261 RTAOOOOO 192 AF.a.24.1 M000041 14C:F1 1 13183
262 1/28/98 262 RTA00000186AF.C.17.1 M00001619D:G05 8551
263 1/28/98 263 RTAOOOOO 190AF.n.6.1 M00003965A:B1 1 0
264 1/28/98 264 RTAOOOOO 179 AF.k.3.3 M00001401A:H07 0
265 1/28/98 265 RTAOOOOO 177AF.e.14.1 M00001343D:H07 23255
266 1/28/98 266 RTAOOOOO 199FT.21.2 M00003847C:E09 13344
267 1/28/98 267 RTAOOOOO 186AF.g.1 1.2 M00001630B:H09 5214
268 1/28/98 268 RTAOOOOO 186AF.h.01.2 M00001632A:F12 0
269 1/28/98 269 RTA00000183AF. 13.1 M00001534B:C12 0
270 1/28/98 270 RTA00000178R.1.08.1 M00001383A:C03 39648
271 1/28/98 271 RTA00000201 F.d.02.1 M00004375A:H01 2599
272 1/28/98 272 RTAOOOOO 199F.g.08.2 M00003853D:G08 0
273 1/28/98 273 RTA00000201 F.C.08.1 M00004353C:H07 0
274 1/28/98 274 RTA00000191AF.O.17.1 M00004102A:H02 5957
275 1/28/98 275 RTA00000191AF.O.17.2 M00004102A:H02 "5957
276 1/28/98 276 RTAOOOOO 198 AF.j.15.1 M00001653B:E09 4369
277 1/28/98 277 RTAOOOOO 198AR.i.08.1 M00001639A:F10 9807
278 1/28/98 278 RTA00000198AF.p. l 6.1 M00003768A:E02 71877
279 1/28/98 279 RTAOOOOO 196AF.h.24.1 M00001386A:D1 1 7308
280 1/28/98 280 RTA00000193AF.b. l 8.1 M00004233C:H09 7542
281 1/28/98 281 RTAOOOOO 188AF.n.10.1 M00003802D:B1 1 10283
282 1/28/98 282 RTA00000193AF.C.15.1 M00004248B:E08 3726
283 1/28/98 283 RTAOOOOO 177AF.Ϊ.8.4 M00001350A:H01 7187
284 1/28/98 284 RTA00000199F.d.l0.2 M00003808C:B05 22049
285 1/28/98 285 RTA00000181ARJ.14.3 M00001453B:E10 5399
286 1/28/98 286 RTA00000181AR.k.2.3 M00001453C:A1 1 0
287 1/28/98 287 RTA00000200AF.b.07.1 M00004039C:C01 17125
288 1/28/98 288 RTA00000181AR.i.06.3 M00001452A:C07 191 19
289 1/28/98 289 RTA00000196F.k.07.1 M00001399C:D09 22443
290 1/28/98 290 RTA00000201 F.f. l 0.1 M00004498D:D05 5231
291 1/28/98 291 RTA00000200AF.e.l6.1 M00004101 C:G08 12068
292 1/28/98 292 RTAOOOOO 199AF.m.18.1 M00003939C:F04 0
293 1/28/98 293 RTA00000197AF.e. l3.1 M00001454C:F02 662
294 1/28/98 294 RTA00000198AF. 23.1 M00001661 B:C08 8995
295 1/28/98 295 RTA00000181AR.U9.2 M00001452C:B06 16970
296 1/28/98 296 RTAOOOOO 196AFT.20.1 M00001371 D:G01 22774
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
297 1/28/98 297 RTAOOOOO 178AF.f.9.3 M00001371 C:E09 7172
298 1/28/98 298 RTA00000197AR.e. l l . l M00001454B:G03 2306
299 1/28/98 299 RTAOOOOO 196AF.f.5.1 M00001366D:G02 1 1937
300 2/24/98 464 RTAOOOOO 195AF.C.12.1 M00003818B:G12 37582
300 1/28/98 300 RTAOOOOO 195AF.C.12.1 M00003818B:G12 37582
301 1/28/98 301 RTA00000181 AR.i.19.3 M00001452C:B06 16970
302 1/28/98 302 RTA00000186AF.d.l .2 M00001621 C:C08 40044
303 1/28/98 303 RTAOOOOO 186 AR.e.03.3 M00001623D:C 10 221 10
304 1/28/98 304 RTA00000182AR.C.5.1 M00001464D:F06 6397
305 1/28/98 305 RTA00000200AF.b.l 5.1 M00004040D:F01 10627
306 1/28/98 306 RTAOOOOO 199AF.p.12.1 M00003989A:H 1 1 12578
307 1/28/98 307 RTA00000200F.n.05.2 M00004246C:A09 18989
308 1/28/98 308 RTAOOOOO 178 AF.j .20.1 M00001380C:E05 15066
309 1/28/98 309 RTAOOOOO 198AF.h.12.1 M00001632C:A02 9503
310 1/28/98 310 RTA00000188AF.m.08.1 M00003798D:H08 22155
31 1 1/28/98 31 1 RTA00000191AR.J.4.2 M00004071 D:A10 5198
312 1/28/98 312 RTAOOOOO 193 AF.h.2.1 M00004290A:B03 3273
313 1/28/98 313 RTA00000183AF.O.1 1.1 M00001540D:D02 0
314 1/28/98 314 RTA00000182AF.O.5.1 M00001493B:D09 5007
315 1/28/98 315 RTA00000199R.d.23.1 M00003815D:H09 37477
316 1/28/98 316 RTAOOOOO 198 AF.h.24.1 M00001636C:C01 8390
317 1/28/98 317 RTA00000198AF.p.09.1 M00003761D:E02 10473
318 1/28/98 318 RTA00000200AF.g.l 7.1 M00004138A:H09 0
319 1/28/98 319 RTA00000200F.n.05.1 M00004246C.-A09 18989
320 1/28/98 320 RTAOOOOO 196AF.m.13.1 M00001415B:E09 16290
321 1/28/98 321 RTA00000181AR.b.21.1 M00001444C:D05 3266
322 1/28/98 322 RTAOOOOO 184 AR.b.21.1 M00001546B:B02 39788
323 1/28/98 323 RTAOOOOO 182AF.m.21.1 M00001490C:C12 18699
324 1/28/98 324 RTAOOOOO 184F.J.06.1 M00001556B:G02 1 1294
325 1/28/98 325 RTAOOOOO 182AF.d.18.4 M00001467D:H05 37435
326 1/28/98 326 RTAOOOOO 197AR.e.19.1 M00001455D:A09 8047
327 1/28/98 327 RTAOOOOO 182AF.L 1.3 M00001479B:A01 7033
328 1/28/98 328 RTA00000200AF.g.09.1 M00004131 B:H09 22785
329 1/28/98 329 RTA00000186AF.b.9.1 M00001616C:F07 0
330 1/28/98 330 RTA00000177AR.m.l 7.4 M00001355B:G10 14391
331 1/28/98 331 RTAOOOOO 197AR.C.20.1 M00001449D:A06 16282
332 1/28/98 332 RTA00000193AR.n.04.3 M00004375C:D01 9850
333 1/28/98 333 RTA00000196F.k.l 5.1 M00001400A:F06 8320
334 1/28/98 334 RTA00000181AR.b.21.3 M00001444C:D05 3266
335 1/28/98 335 RTAOOOOO 182 AF.e.3.2 M00001468B:H06 0
336 1/28/98 336 RTAOOOOO 186AFT.24.1 M00001629B:E06 0
337 1/28/98 337 RTA00000177AR.m.l 7.3 M00001355B:G10 14391
338 1/28/98 338 RTAOOOOO] 84AF.i.1.1 M00001554B:C07 0
339 1/28/98 339 RTAOOOOO 193 AF.d.1.1 M00004250D:D10 0
340 1/28/98 340 RTA00000185AF.n.8.1 M00001608B:A03 0
341 1/28/98 341 RTA00000181AF.1.06.2 M00001454C:C08 0
342 1/28/98 342 RTAOOOOO 196AF.d.10.1 M00001354C:B06 22256
343 1/28/98 343 RTA00000201 F.a.l 8.1 M00004314B:G07 16837
344 1/28/98 344 RTA00000198AF.O.02.1 M00003748A:B07 68756
345 1/28/98 345 RTAOOOOO 187AF.h.21.1 M00001679A:F01 39171
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
346 1/28/98 346 RTAOOOOO 197AR. 22.1 M00001505C:H01 1 1394
347 1/28/98 347 RTAOOOOO 199F.b.03.2 M00003779B:E12 38340
348 1/28/98 348 RTA00000200F.n.07.2 M00004247C:C12 8663
349 1/28/98 349 RTAOOOOO 191 AF.j.15.1 M00004073B:B01 6308
350 1/28/98 350 RTA00000193AR.C.7.2 M00004241 D:F1 1 9850
351 1/28/98 351 RTAOOOOO 179AF.C.22.1 M00001393B:B09 22515
352 1/28/98 352 RTA00000197AF.p.3.1 M00001550A:A03 7239
353 1/28/98 353 RTA00000198F.a.9.1 M00001557D:C08 0
354 1/28/98 354 RTAOOOOO 198R. 03.1 M00001655A:F06 22765
355 1/28/98 355 RTA00000184AR.b.24.1 M00001546B:C05 5777
356 1/28/98 356 RTAOOOOO 180AF.1.12.2 M00001433B:H1 1 0
357 1/28/98 357 RTA00000184AF.O.15.1 M00001564D:C09 0
358 1 /28/98 358 RTAOOOOO 198AF.g.7.1 M00001616C:C09 13386
359 1/28/98 359 RTAOOOOO 196AF.b.17.1 M00001348A:D04 12193
360 1/28/98 360 RTA00000198F.i.5.1 M00001638A:D10 39989
361 1/28/98 361 RTAOOOOO 177AR.g.16.4 M00001347A:B10 13576
362 1/28/98 362 RTAOOOOO 197AR.C.24.1 M00001450A:B 12 82498
363 1/28/98 363 RTAOOOOO 196AF.e.14.1 M00001362C:A10 12850
364 1/28/98 364 RTAOOOOO 187AF.g.13.1 M00001676C:C1 1 2991
365 1/28/98 365 RTAOOOOO 196F.1.20.2 M00001410B:G05 22678
366 1/28/98 366 RTA00000192AF.O.19.1 M00004208D:H08 3549
367 1/28/98 367 RTA00000196FL24.1 M00001392C:D10 4233
368 1/28/98 368 RTAOOOOO 198AF. 18.1 M00001660A:C12 17432
369 1/28/98 369 RTAOOOOO 196F.m.3.1 M00001413A:F02 10453
370 1/28/98 370 RTAOOOOO 179AF.C.15.3 M00001392D:H06 2995
371 1/28/98 371 RTAOOOOO 197F.e.7.1 M00001453D:G12 86969
372 1/28/98 372 RTAOOOOO 186AF.d.23.1 M00001623B:G07 22187
373 1/28/98 373 RTA00000196F.e.l2.1 M00001361C:H1 1 10147
374 1/28/98 374 RTAOOOOO 178AF.1.1 1.1 M00001383A:G04 23286
375 1/28/98 375 RTAOOOOO 177AF.m.18.1 M00001355B:G1 1 0
376 1/28/98 376 RTA00000177AF.m.l8.3 M0O0O1355B:Gl l 0
377 1/28/98 377 RTAOOOOO 178AF.m.19.1 M00001384D:H07 0
378 1/28/98 378 RTA00000181AF. 24.3 M00001454B:C 12 7005
379 1/28/98 379 RTAOOOOO 180AF.1.06.2 M00001433A:G07 5625
380 1/28/98 380 RTAOOOOO 182 AF.k.24.1 M00001485D:B10 5625
381 1/28/98 381 RTAOOOOO 199AF.m.14.1 M00003938A:B04 10580
382 1/28/98 382 RTA00000200AF.J.6.1 M00004176B:E08 22902
383 1/28/98 383 RTAOOOOO 199FT.20.2 M00003847B:G03 0
384 1/28/98 384 RTAOOOOO 196AF.h.17.1 M00001384C:F12 39215
385 1/28/98 385 RTA00000201 F.C.24.1 M00004374D:E10 35731
386 1/28/98 386 RTAOOOOO 197 AR.j.04.1 M00001492D:A1 1 17209
387 2/24/98 632 RTAOOOOO 191 AF.j.l 4.1 M00004073A:H12 1002
387 1/28/98 387 RTA00000191AF.J.14.1 M00004073A:H12 1002
388 1/28/98 388 RTAOOOOO 185AF.n.17.1 M00001609B:A1 1 5336
389 1/28/98 389 RTA00000181 AR. 2.2 M00001453C:A1 1 0
390 1/28/98 390 RTAOOOOO 197AR.f.07.1 M00001457C:C 1 1 19261
391 1/28/98 391 RTAOOOOO 179 AF.e.20.3 M00001396A:C03 4009
392 1/28/98 392 RTA00000185AF.D.1 1.2 M00001573C:D03 9024
393 1/28/98 393 RTAOOOOO 188AF.b.14.1 M00003754D:D02 0
394 1/28/98 394 RTAOOOOO 198 AF.p.22.1 M00003771A:G10 0
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
395 1/28/98 395 RTAOOOOO 196R.C.21.2 M00001352C:H 10 0
396 1/28/98 396 RTAOOOOO 179AR.b.02.3 M00001391 B:G12 0
397 1/28/98 397 RTAOOOOO 198AF.b.22.1 M00001571 B:E03 38956
398 1/28/98 398 RTA00000177AR.1.13.3 M00001353A:G12 8078
399 1/28/98 399 RTA00000186AF.m. l 5.2 M00001649C:B10 40122
400 1/28/98 400 RTAOOOOO 186AR.e.07.3 M00001623D:G03 4175
401 1/28/98 401 RTAOOOOO 195F.e.04.1 M00004465B:D04 6731
402 1/28/98 402 RTAOOOOO 177AF.b.21.4 M00001341A:F12 4443
403 1/28/98 403 RTAOOOOO 184AFT.13.1 M00001550D:H02 3784
404 1/28/98 404 RTA00000195AF.b.6.1 M00001496C:G10 39490
405 1/28/98 405 RTAOOOOO 197 AF.b.24.1 M00001446C:D09 23171
406 1/28/98 406 RTAOOOOO 199FT.09.2 M00003842B:D09 22907
407 1/28/98 407 RTAOOOOO 178AF.e.20.1 M00001370D:E12 3135
408 1/28/98 408 RTA00000183AR.I.15.1 M00001535C:E01 39383
409 1/28/98 409 RTAOOOOO 180AF.d.1.3 M00001418D:B06 8526
410 1/28/98 410 RTA00000201 F.a.20.1 M00004316A:G09 22639
41 1 1/28/98 41 1 RTAOOOOO 179AF.J.13.3 M00001400B:H06 0
412 2/24/98 678 RTAOOOOO 195 AF.c.24.1 M00003860D:H07 0
412 1/28/98 412 RTAOOOOO 195 AF.c.24.1 M00003860D:H07 0
413 1/28/98 413 RTA00000200F.a.l2.1 M00004031D:B05 16751
414 1/28/98 414 RTA00000185AR.b.l 5.1 M00001573D:F04 39813
415 1/28/98 415 RTA00000200AF.f.09.1 M000041 1 1 C:E1 1 12863
416 1/28/98 416 RTAOOOOO 199F.a.5.1 M00003773B:G01 22134
417 1/28/98 417 RTA00000200R.d.l 6.1 M00004085A:B02 39875
418 1/28/98 418 RTAOOOOO 187AR. 01.1 M00001679D:B05 78356
419 1/28/98 419 RTAOOOOO 182AF.J .20.1 M00001483B:D03 4769
420 1/28/98 420 RTA00000181AF.C.11.1 M00001445D:A06 4769
421 1/28/98 421 RTA00000200AF.i.21.1 M00004167D:A07 5316
422 1/28/98 422 RTAOOOOO 189AF.b.12.1 M00003829B:G03 17233
423 1/28/98 423 RTAOOOOO 188AR.b.17.1 M00003755A:B03 10662
424 1/28/98 424 RTAOOOOO 187AR.J.24.1 M00001679D:B05 78356
425 1/28/98 425 RTA00000200AF.C.16.1 M00004064D:A1 1 23433
426 1/28/98 426 RTAOOOOO 199AF.0.19.1 M00003980D:E09 36927
427 1/28/98 427 RTA00000187AR.d.9.2 M00001664D:G07 5483
428 1/28/98 428 RTAOOOOO 185AF.b.15.2 M00001573D:F04 39813
429 1/28/98 429 RTAOOOOO 196F.i.19.1 M00001390C:C1 1 39498
430 1/28/98 430 RTA00000198R. 23.1 M00001661 B:C08 8995
431 1/28/98 431 RTAOOOOO 199AF. 15.1 M00003905C:G10 8275
432 1/28/98 432 RTAOOOOO 198AF.O.05.1 M00003750A:D01 26702
433 1/28/98 433 RTAOOOOO 198R.J.18.1 M00001653B:G07 22759
434 1/28/98 434 RTAOOOOO 187AR.d.2.2 M00001664C:H10 4892
435 1/28/98 435 RTAOOOOO 182 AR.c.22.1 M00001467A:D08 16283
436 1/28/98 436 RTA00000200AF.k.l l . l M00004197C:F03 9796
437 1/28/98 437 RTA00000198R.a.23.1 M00001563B:D1 1 10700
438 1/28/98 438 RTAOOOOO! 80AR.g.03.4 M00001425A:C1 1 9024
439 1/28/98 439 RTAOOOOO 185AF.d.14.2 M00001579D:G07 8071
440 1/28/98 440 RTAOOOOO 177ART.13.4 M00001345A:G1 1 10480
441 1/28/98 441 RTA00000185AF.e.6.1 M00001583B:E10 0
442 1/28/98 442 RTA00000191 AF.1.9.1 M00004081 C:H06 0
443 1/28/98 443 RTA00000197AR.i. l 7.1 M00001490A:E1 1 3516
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
444 1/28/98 444 RTAOOOOO 189AF.1.16.1 M00003879A:G05 0
445 1/28/98 445 RTA00000196AF.n.l3.1 M00001422C:F12 8396
446 1/28/98 446 RTA00000182AF.a.23.3 M00001463A:F06 9755
447 1/28/98 447 RTAOOOOO 198AF.d.8.1 M00001587A:H03 0
448 1/28/98 448 RTA00000200AF.J.9.1 M00004177C:A01 8608
449 1/28/98 449 RTA00000181 AF.m.22.3 M00001455D:F09 9283
450 1/28/98 450 RTA00000181 AF.m.21.3 M00001455D:F09 9283
451 1/28/98 451 RTA00000200AF.b.20.1 M00004043A:D02 40403
452 1/28/98 452 RTA00000199F.d. l9.2 M00003813D:H12 6707
453 1/28/98 453 RTA00000199AF.i.20.1 M00003881A:D09 9544
454 1/28/98 454 RTA00000200R.d.04.1 M00004078A:A06 5506
455 1/28/98 455 RTA00000198AF.d. l2.1 M00001589A:C01 21 142
456 1/28/98 456 RTA00000200AF.b.l2.1 M00004040B:F10 22053
457 1/28/98 457 RTA00000191AR.1.7.2 M00004081 C:D12 14391
458 1/28/98 458 RTAOOOOO 199R.d.16.1 M00003812C:A05 24191
459 1/28/98 459 RTAOOOOO 179AF.C.22.3 M00001393B:B09 22515
460 1/28/98 460 RTAOOOOO] 79AF.C.15.1 M00001392D:H06 2995
461 1/28/98 461 RTA00000190AF.e.l3.1 M00003908A:H09 38961
462 1/28/98 462 RTA00000196AF.n.l 7.1 M00001423D:A09 12477
463 1/28/98 463 RTAOOOOO 177 AR.k.23.4 M00001352D:D02 35550
464 1/28/98 464 RTA00000199AF.1.14.1 M00003917A:D02 22865
465 1/28/98 465 RTAOOOOO 187AF.k.20.1 M00001680B:C01 3648
466 1/28/98 466 RTAOOOOO 177AF.p.20.1 M00001361A:A05 4141
467 1/28/98 467 RTAOOOOO 195AF.b.19.1 M00001589A:D12 77678
468 1/28/98 468 RTAOOOOO 198AF.a.18.1 M00001561C.Ε11 0
469 1/28/98 469 RTAOOOOO 190AF.n.2.1 M00003963A:E03 5650
470 1/28/98 470 RTA000O0198AF.f.l6.1 M00001614A:E06 0
471 1/28/98 471 RTAOOOOO 188AF.e.2.1 M00003763B:H01 0
472 1/28/98 472 RTAOOOOO 192AF.p.17.1 M00004214C:H05 1 1451
473 1/28/98 473 RTAOOOOO 196F.i.3.1 M00001387A:E10 0
474 1/28/98 474 RTAOOOOO 192 AR.d.1.3 M00004130D:H01 14507
475 1/28/98 475 RTA00000187AR.m.3.3 M00001682C:B12 17055
476 1/28/98 476 RTA00000200R.g.l 5.1 M00004135B:G01 22898
477 1/28/98 477 RTAOOOOO 180AR.e.22.2 M00001423A:G05 7714
478 1/28/98 478 RTAOOOOO 192 AR.o.24.2 M00004210B:B05 7191
479 1/28/98 479 RTA00000197R.1.22.1 M00001528A:C1 1 6962
480 1/28/98 480 RTA00000181AF.O.08.2 M00001457C:H12 849
481 1/28/98 481 RTAOOOOO 179AR.1.22.2 M00001405B:E09 4314
482 1/28/98 482 RTAOOOOO 187AF.J.7.1 M00001679C:F01 78091
483 1/28/98 483 RTA00000192AF.h.l9.1 M00004162C:A07 4642
484 1/28/98 484 RTAOOOOO 199F.g.20.2 M00003860D:A01 15767
485 1/28/98 485 RTA00000196AF.C.14.1 M00001352B:F04 23105
486 1/28/98 486 RTAOOOOO 190AR.p.22.2 M00003979A:E1 1 16368
487 1/28/98 487 RTA00000198F.i.8.1 M00001639A:F10 9807
488 1/28/98 488 RTA00000179AR.1.22.4 M00001405B:E09 4314
489 1/28/98 489 RTAOOOOO 186AF.h.22.1 M00001634B:C10 16485
490 1/28/98 490 RTAOOOOO 198AF.n.05.1 M00001687A:G01 24157
491 1/28/98 491 RTAOOOOO 196F.k.1 1.1 M00001399C:H12 3
492 1/28/98 492 RTA00000198AF.b.8.1 M00001567C:H12 22636
493 1/28/98 493 RTA00000177AF.m. l 7.1 M00001355B:G10 14391
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
494 1/28/98 494 RTA00000200AF.k. l .l M00004188C:A09 40049
495 1/28/98 495 RTAOOOOO 185 AF.j .21.1 M00001597A:E12 0
496 1/28/98 496 RTAOOOOO 190 AF.p.3.1 M00003975B:F03 2378
497 1/28/98 497 RTA00000198AF.O.09.1 M00003751 B:A05 4310
498 1/28/98 498 RTAOOOOO 190AF.h.12.1 M00003917C:D03 12977
499 1/28/98 499 RTAOOOOO 199F.b.22.2 M00003791 C:E09 17018
500 1/28/98 500 RTAOOOOO 179AR.m.07.5 M00001405D:D1 1 0
501 1/28/98 501 RTA00000200R.U 1.1 M00004197C:F03 9796
502 1/28/98 502 RTA00000197AF.O.23.1 M00001549A:A09 12682
503 1/28/98 503 RTAOOOOO 197AF.k.9.1 M00001500C:C08 3138
504 1/28/98 504 RTA00000198AF.g.2.1 M00001615C:D02 16640
505 1/28/98 505 RTA00000188AF.n.03.1 M00003801 B:B10 9443
506 1 /28/98 506 RTAOOOOO 198R.O.09.1 M00003751 B:A05 4310
507 1/28/98 507 RTA00000198AF.C.5.1 M00001573D:F10 53802
508 1/28/98 508 RTAOOOOO 187AF.i.14.2 M00001679B:H07 19406
509 1/28/98 509 RTAOOOOO 183AF.p.17.1 M00001543A:H12 5158
510 1/28/98 510 RTA00000178AF.n.23.1 M00001387B:E02 3298
51 1 1/28/98 51 1 RTAOOOOO 196AF.g.10.1 M00001376B:A02 12498
512 1/28/98 512 RTA00000191 AF.C.3.1 M00003987D:D06 3549
513 1/28/98 513 RTA00000197AF.h.l4.1 M00001477B:F04 7045
514 1/28/98 514 RTA00000196AF.n.02.1 M00001417D:A04 39260
515 1/28/98 515 RTAOOOOO 196AF .18.1 M00001370D:A12 14506
516 1/28/98 516 RTA00000200AF.e.23.1 M00004107B:A06 14686
517 1/28/98 517 RTAOOOOO 184AF.e.14.1 M00001549C:D02 16347
518 1/28/98 518 RTAOOOOO 199 AF.n.22.1 M00003971A:A06 23064
519 1/28/98 519 RTA00000183AF.a.24.2 M00001499B:A1 1 10539
520 1/28/98 520 RTA00000195AF.C.8.1 M00001678B:H01 0
520 2/24/98 958 RTA00000195AF.C.8.1 M00001678B:H01 0
521 1/28/98 521 RTAOOOOO 197AF.p.12.1 M00001552B:G05 0
522 1/28/98 522 RTA00000178AR.h.l 7.2 M00001376A:C05 23824
523 1/28/98 523 RTA00000198AF.d.4.1 M00001586D:E02 22435
524 1/28/98 524 RTAOOOOO 191 AF.j .24.1 M00004076B:G03 0
525 1/28/98 525 RTAOOOOO 198AF.C.7.1 M00001575D:G05 19181
526 1/28/98 526 RTAOOOOO 185 AF.e.20.1 M00001585A:D06 5865
527 1/28/98 527 RTAOOOOO 198R.m.23.1 M00001684B:G03 38469
528 1/28/98 528 RTA00000200F.n.09.2 M00004249D:B08 12391
529 1/28/98 529 RTA00000178AF.b.l3.1 M00001364A:E1 1 31 14
530 1/28/98 530 RTAOOOOO 185 AF.d.24.2 M00001582D:F05 0
531 1/28/98 531 RTA00000195F.a.3.1 M00001368A:A03 27179
532 1/28/98 532 RTAOOOOO 177AF.o.4.1 M00001358C:C06 0
533 1/28/98 533 RTA00000177AR.m.l3.4 M00001355A:C12 4175
534 1/28/98 534 RTA00000201AF.e.01.1 M00004405D:C04 1 1397
535 1/28/98 535 RTA00000196AF.n.l9.1 M00001423D:D12 6881
536 1/28/98 536 RTAOOOOO 193 AR.a.2.3 M00004216D:D03 0
537 1/28/98 537 RTAOOOOO 188AF.g.14.1 M00003774C:D02 0
538 1/28/98 538 RTAOOOOO 177AR.m.13.3 M00001355A:C 12 4175
539 1/28/98 539 RTA00000197AR.b.l3.1 M00001445B:E04 9560
540 1/28/98 540 RTAOOOOO 179AF.b.10.3 M00001391D:D10 0
541 1/28/98 541 RTAOOOOO 197AR.b.16.1 M00001445C:A08 0
542 1/28/98 542 RTA00000198R.p.l2.1 M00003763D:E10 8878
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
543 1/28/98 543 RTA00000200AF.i.l 9.1 M00004167A:H03 14722
544 1/28/98 544 RTAOOOOO 196F.J.13.1 M00001396D:B03 23170
545 1/28/98 545 RTA00000196F.a.2.1 M00001338B:E02 3575
546 1/28/98 546 RTA00000197F.i.6.1 M00001487C:D06 12149
547 1/28/98 547 RTAOOOOO 196AF.g.8.1 M00001375B:G12 39665
548 1/28/98 548 RTAOOOOO 179 AF.f.23.3 M00001397B:G03 35258
549 1/28/98 549 RTAOOOOO 198AF.C.16.1 M00001579C:B1 1 26801
550 1/28/98 550 RTAOOOOO 183AF.g.14.1 M00001513D:A03 0
551 1/28/98 551 RTA00000200AR.C.24.1 M00004076D:D04 15972
552 1/28/98 552 RTAOOOOO 193 AF.b.24.1 M00004237D:D08 35
553 1/28/98 553 RTA00000201 F.b.22.1 M00004344B:H04 35728
554 1/28/98 554 RTAOOOOO 186AR.e.07.4 M00001623D:G03 4175
555 1/28/98 555 RTA00000198AFJ.08.1 M00001651 B:A1 1 10983
556 1/28/98 556 RTAOOOOO 199F.f.17.2 M00003845D:B04 22905
557 1/28/98 557 RTAOOOOO 198 AF.d.9.1 M0000I 587D:A10 8841
558 1/28/98 558 RTA00000186AR.h. l 4.1 M00001632D:H07 0
559 1/28/98 559 RTA00000197AF.p.20.1 M00001554B:B07 22795
560 1/28/98 560 RTAOOOOO 184AF.i.23.3 M00001556A:F1 1 1577
561 1/28/98 561 RTA00000185AR.d.l 0.1 M00001579C:H10 0
562 1/28/98 562 RTAOOOOO 196F.J.12.1 M00001396A:H03 19294
563 1/28/98 563 RTA00000192AR.O.16.2 M00004208B:F05 9061
564 1/28/98 564 RTA00000200AF.g.l 8. I M00004138B:B1 1 1600
565 1/28/98 565 RTA00000191AF.C.10.1 M00003989B:F1 1 40422
566 1/28/98 566 RTA00000195F.a.4.1 M00001372C:G12 20470
567 1/28/98 567 RTA00000177AR.m.l3.1 M00001355A:C12 4175
568 1/28/98 568 RTAOOOOO 196AF.p.01.2 M00001430A:A02 87143
569 1/28/98 569 RTA00000196AF.1.23.1 M00001412A:E04 12052
570 1/28/98 570 RTAOOOOO 183AF.a.19.2 M00001499A:A05 3788
571 1/28/98 571 RTAOOOOO 198AF.b.14.1 M00001569C:B06 801
572 1/28/98 572 RTA00000181AF.1.16.2 M00001454D:E05 13532
573 1/28/98 573 RTA00000196AF.b.7.1 M00001344A:G07 7774
574 1/28/98 574 RTAOOOOO 192 AF.f.3.1 M00004146C:CU 5257
575 1/28/98 575 RTA00000186AF.1.12.2 M00001645A:C12 19267
576 1/28/98 576 RTA00000196AF.C.7.1 M00001350B:G1 1 0
577 1/28/98 577 RTA00000190AF.a.24.2 M00003901B:A05 0
578 1/28/98 578 RTAOOOOO 180AF.g.17.1 M00001426A:A09 16653
579 1/28/98 579 RTA00000200F.i.7.1 M00004157D:B03 22322
580 1/28/98 580 RTAOOOOO 197F.a.12.1 M00001438B:B09 7895
581 1/28/98 581 RTA00000191AF.p.3.2 M00004104B:F1 1 17
582 1/28/98 582 RTA00000178AR.d.l2.4 M00001368A:D07 2476
583 1/28/98 583 RTAOOOOO 190AR.h.12.2 M00003917C:D03 12977
584 1/28/98 584 RTAOOOOO 190AR.C.03.1 M00003904C:A08 0
585 1/28/98 585 RTAOOOOO 198AF.n.18.1 M00001771A:A07 16715
586 1/28/98 586 RTAOOOOO 199R.0.1 1.1 M00003976C:A10 23172
587 1/28/98 587 RTAOOOOO 199F.a.3.1 M00003772D:E10 16617
588 1/28/98 588 RTA00000191AF.b.4.1 M00003983C:F03 14936
589 1/28/98 589 RTAOOOOO 192AF.1.1.1 M00004183C:D07 16392
590 1/28/98 590 RTA00000190AF.d.2.1 M00003906B:F12 2444
591 1/28/98 591 RTA00000197AF.h. l .l M00001470A:H01 13075
592 1/28/98 592 RTA00000186AF.e. l 8.1 M00001624C:A06 0
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
593 1/28/98 593 RTAOOOOO 196R.C 14.2 M00001352B:F04 23105
594 1/28/98 594 RTA00000181AR.e.04.3 M00001448A:G09 1 1825
595 1/28/98 595 RTAOOOOO 195R.a.06.1 M00001394A:E04 35265
595 2/24/98 1065 RTAOOOOO 195 R.a.06.1 M00001394A:E04 35265
596 1/28/98 596 RTAOOOOO 184AF.d.9.1 M00001548A:B1 1 6515
597 1/28/98 597 RTAOOOOO 198F.a.4.1 M00001557A:F01 9635
598 1/28/98 598 RTAOOOOO 197F.e.10.1 M00001454B:D08 13154
599 1/28/98 599 RTA00000179AF.O.5.1 M00001408D:D04 6172
600 1/28/98 600 RTAOOOOO 177AF.g.4.1 M00001346B:B07 41 19
601 1/28/98 601 RTA00000184AF.i.l0.2 M00001555A:B01 3744
602 1/28/98 602 RTA00000195AF.b.21.1 M00001595B:A09 39055
602 2/24/98 317 RTAOOOOO 195 AF.b.21.1 M00001595B:A09 39055
603 1/28/98 603 RTA00000183AR.d.l l .3 M00001504D:G06 6420
604 1/28/98 604 RTA00000200AF.J.15.1 M00004185D:E04 5849
605 1/28/98 605 RTAOOOOO 196F.e.9.1 M00001361A:H07 23300
606 1/28/98 606 RTA00000179AR.e.01.4 M00001395A:C09 2493
607 1/28/98 607 RTA00000200AF.k. l2.1 M00004198B:D02 7359
608 1/28/98 608 RTAOOOOO 192 AF.p.8.1 M00004212B:C07 2379
609 1/28/98 609 RTAOOOOO 196AF.n.05.1 M00001418B:F07 12531
610 1/28/98 610 RTA00000200AF.k.2.1 M00004188D:G08 35924
61 1 1/28/98 61 1 RTA00000196F.1.13.2 M00001408A:H04 0
612 1/28/98 612 RTA00000197AR.e.22.1 M00001456A:H02 78758
613 1/28/98 613 RTAOOOOO 177AF.k.18.4 M00001352C:A05 53729
614 1/28/98 614 RTA00000201F.f.03.1 M00004493B:D09 22633
615 1/28/98 615 RTAOOOOO 197R.p.20.1 M00001554B:B07 22795
616 1/28/98 616 RTAOOOOO 188AF.m.07.1 M00003798D:E03 23183
617 1/28/98 617 RTAOOOOO 179AF.d.13.3 M00001394A:F01 6583
618 1/28/98 618 RTAOOOOO 192AF.a.14.1 M000041 1 1 D:A08 6874
619 1/28/98 619 RTA00000201 F.g.08.1 M00004692A:E07 0
620 1/28/98 620 RTA00000201 R.g.08.1 M00004692A:E07 0
621 1/28/98 621 RTA00000201 R.g.08.2 M00004692A:E07 0
622 1/28/98 622 RTAOOOOO 186AR.m.14.2 M00001649B:G12 9800
623 1/28/98 623 RTAOOOOO 198R.b.24.1 M00001571D:B1 1 19047
624 1/28/98 624 RTA00000200F.O.15.1 M00004275A:B03 7866
625 1/28/98 625 RTAOOOOO 196AF.C 19.1 M00001352C:G09 5935
626 1/28/98 626 RTAOOOOO 185 AR.d.1 1.1 M00001579D:C03 6539
627 1/28/98 627 RTAOOOOO 199F.h.15.2 M00003870A:C05 22269
628 1/28/98 628 RTAOOOOO 198AF.g.16.1 M00001621 D:D03 6602
629 1/28/98 629 RTA00000199R.m.23.1 M00003945A:E09 40166
630 1/28/98 630 RTAOOOOO 183 AR.g.03.2 M00001512D:G09 3956
631 1/28/98 631 RTA00000200AF.h.l9.2 M00004151D:E03 0
632 1/28/98 632 RTAOOOOO 183 AR.g.03.1 M00001512D:G09 3956
633 1/28/98 633 RTA00000197F.i.8.1 M00001488A:E01 6292
634 1/28/98 634 RTAOOOOO 192 AF.j.6.1 M00004172C:D08 1 1494
635 1/28/98 635 RTAOOOOO] 8 lAF.p.7.3 M00001460A:E01 38773
636 1/28/98 636 RTAOOOOO 196F.k.20.1 M00001402B:F12 6324
637 1/28/98 637 RTA00000200AF.g. l 5.1 M00004135B:G01 22898
638 1/28/98 638 RTA00000193AF.1.05.2 M00004348A:A02 2815
639 1/28/98 639 RTAOOOOO 199AF.J.1.1 M00003881 C:G09 6006
640 1/28/98 640 RTAOOOOO 190 AF.f.5.1 M00003909A:H04 5015
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
641 1/28/98 641 RTA00000198F.3.10.1 M00001558A:E1 1 6695
642 1/28/98 642 RTA00000189AF.U4.1 M00003868B:G1 1 0
643 1/28/98 643 RTAOOOOO 184AF.C.9.1 M00001546C:G10 16245
644 1/28/98 644 RTA00000197F. 2.1 M00001489B:A06 3605
645 1/28/98 645 RTAOOOOO 177AF.k.9.1 M00001352A:E02 16245
646 1/28/98 646 RTAOOOOO 186 AF.d.24.1 M00001623C:H07 31 14
647 1/28/98 647 RTA00000197F.m. l l .l M00001530B:D10 16488
648 1/28/98 648 RTA00000199F.i.9.1 M00003878C:E04 7
649 1/28/98 649 RTA00000190AR.1.19.2 M00003946A:H10 88204
650 1/28/98 650 RTAOOOOO 183 AR.n.17.1 M00001539B:H06 9800
651 1/28/98 651 RTAOOOOO 189AR.d.22.2 M00003844C:B1 1 6539
652 1/28/98 652 RTAOOOOO 178 AR.m.21.4 M00001385A:F12 7861
653 1/28/98 653 RTAOOOOO 178 AR.m.21.5 M00001385A:F12 7861
654 1/28/98 654 RTAOOOOO 186AF.J.21.2 M00001639D:B07 22506
655 1/28/98 655 RTA00000186AF.g.8.2 M00001630B:A1 1 8065
656 1/28/98 656 RTA00000178AR.h.22.3 M00001376B:A08 19230
657 1/28/98 657 RTAOOOOO 178AR.h.22.2 M00001376B:A08 19230
658 1/28/98 658 RTAOOOOO 193 AF.3.1.1 M00004216D:C03 16501
659 1/28/98 659 RTAOOOOO 185 AR.k.23.2 M00001601A:E09 0
660 1/28/98 660 RTAOOOOO 197AF.p.16.1 M00001552D:G08 6013
661 1/28/98 661 RTA00000198R.b.04.1 M00001565A:H09 0
662 1/28/98 662 RTA00000201 R.3.15.1 M00004312B:H07 57347
663 1/28/98 663 RTAOOOOO 199F.g.21.2 M00003861C:H02 34826
664 1/28/98 664 RTAOOOOO 195R.3.23.1 M00001449C:H12 86432
665 1/28/98 665 RTA00000197AF.1.22.1 M00001528A:C1 1 6962
666 1/28/98 666 RTAOOOOO 198F.i.10.1 M00001640B:F03 12792
667 1/28/98 667 RTAOOOOO 197AF.d.16.1 M00001452A:E07 23505
668 1/28/98 668 RTA00000178AF.U 7.1 M00001377C:E12 0
669 1/28/98 669 RTA00000192AF.C.2.1 M00004121B:G01 0
670 1/28/98 670 RTAOOOOO 186AF.p.17.3 M00001656B:A07 38383
671 1/28/98 671 RTAOOOOO] 85 AR.d.08.1 M00001579C:E09 6562
672 1/28/98 672 RTA00000196AF.h.09.1 M00001382B:F12 8015
673 1/28/98 673 RTA00000199F.m.3.1 M00003931 B:A1 1 0
674 1/28/98 674 RTAOOOOO 197AR.e.24.1 M00001456B:F10 39250
675 1/28/98 675 RTAOOOOO 179 AR.b.21.3 M00001392C:D05 4366
676 1/28/98 676 RTA00000197AR.m.l4.1 M00001531 B:E09 14879
677 1/28/98 611 RTAOOOOO 197AF.L 19.1 M00001490B:H1 1 39554
678 1/28/98 678 RTAOOOOO 190 AF.j .3.1 M00003922A:D02 2705
679 1/28/98 679 RTAOOOOO 197AF.d.1 1.1 M00001451C:E01 27260
680 1/28/98 680 RTAOOOOO 177AFT.10.1 M00001345A:E01 6420
681 1/28/98 681 RTA00000180AF.1.04.2 M00001432D:F05 1 1 159
682 1/28/98 682 RTA00000125A.J.16.1 M00001544A:E06 0
683 1/28/98 683 RTAOOOOO 187AR.J.01.1 M00001679C:D01 79028
684 1/28/98 684 RTA00000200AR.b.l l .l M00004040A:G12 12043
685 1/28/98 685 RTA00000200F.i.9.1 M00004159C:F09 36756
686 1/28/98 686 RTA00000201F.f.07.1 M00004497A:H03 51 1 16
687 1/28/98 687 RTAOOOOO 197AF.g.4.1 M00001464B:B03 8821
688 1/28/98 688 RTAOOOOO 193 AF.g.3.1 M00004050D:A06 5567
689 1/28/98 689 RTAOOOOO 197 AF.o.4.1 M00001542B:C06 4121
690 1/28/98 690 RTA00000198R.1.21.1 M00001673A:A04 19194
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Dste of NO: in ID Priority Priority Appln Appln
691 1/28/98 691 RTAOOOOO 195F.3.10.1 M00001401 C:H03 6803
692 1/28/98 692 RTAOOOOO 199F.e.4.1 M00003820B:C05 0
693 1/28/98 693 RTA00000198F.m. l2.1 M00001679C:D05 4
694 1/28/98 694 RTA00000201 R.C.19.1 M00004370A:G05 22357
695 1/28/98 695 RTA00000197F.m.5.1 M00001528C:H04 10872
696 1/28/98 696 RTAOOOOO 180AR.d.16.3 M00001419D:C10 1 1393
697 1/28/98 697 RTA00000193AF.e.21.1 M00004271 B:B06 0
698 1/28/98 698 RTAOOOOO 179AF.g.1.3 M00001397C:A10 7588
699 1/28/98 699 RTAOOOOO 178AF.3.12.1 M00001362B:H06 0
700 1/28/98 700 RTA00000183AF.i.l 8.2 M00001529D:H02 40129
701 1/28/98 701 RTAOOOOO 199AF.0.10.1 M00003974C:E04 0
702 1/28/98 702 RTAOOOOO 177AR.b.8.5 M00001340B:A06 17062
703 1/28/98 703 RTAOOOOO 198F.1.09.1 M00001664B:D06 361 1
704 1/28/98 704 RTAOOOOO 190AF.0.12.1 M00003972D:C09 3438
705 1/28/98 705 RTAOOOOO] 96F.i.5.1 M00001387B:A06 0
706 1/28/98 706 RTA00000177AF.i.6.4 M00001350A:B08 0
707 1/28/98 707 RTAOOOOO 179AF.p.15.1 M0000141 1 D:F05 5622
708 1/28/98 708 RTA00000201 F.f.06.1 M00004496C:H03 23771
709 1/28/98 709 RTAOOOOO 192AF.d.18.1 M00004135D:G02 0
710 1/28/98 710 RTA00000196AF.1.3.1 M00001405B:D07 20864
71 1 1/28/98 71 1 RTA00000198F.i.2.1 M00001637B:E07 8076
712 1/28/98 712 RTA00000201F.b.21.1 M00004341 B:G03 9071
713 1/28/98 713 RTAOOOOO 198AF.g.21.1 M00001624A:F09 6273
714 1/28/98 714 RTA00000199R.g.07.1 M00003853D:D03 0
715 1/28/98 715 RTAOOOOO 197 AR.k.1 1.1 M00001500D:E10 53758
716 1/28/98 716 RTA00000200F.p.05.1 M00004285C:A08 3984
717 1/28/98 717 RTA00000200F.O.10.2 M00004269B:C08 36432
718 1/28/98 718 RTA00000196F.1.14.2 M00001408B:G06 23144
719 1/28/98 719 RTAOOOOO 183AF.b.12.1 M00001500A:B02 0
720 1/28/98 720 RTAOOOOO 197AF.f.14.1 M00001459B:C09 3732
721 1/28/98 721 RTAOOOOO 180AF.C.4.1 M00001417B:C04 5415
722 1/28/98 722 RTAOOOOO 199R.J .24.1 M00003895C:A10 0
723 1/28/98 723 RTAOOOOO 183 AF.p.24.1 M00001543C:F01 31 16
724 1/28/98 724 RTA00000177AR.f.l 5.4 M00001345B:E10 9062
725 1/28/98 725 RTA00000197AF.b.l .l M00001441D:E04 12134
726 1/28/98 726 RTA00000200R.f.l0.1 M000041 1 1D:B07 4
727 1/28/98 727 RTAOOOOO 184AF.n.12.2 M00001561D:C 1 1 3727
728 1/28/98 728 RTAOOOOO 177 ART.17.4 M00001345C:B01 8594
729 1/28/98 729 RTAOOOOO 184AF.3.19.1 M00001544C:C06 2628
730 1/28/98 730 RTAOOOOO 192 AF.o.1 1.1 M00004205D:F06 0
731 1/28/98 731 RTAOOOOO 184F.k.02.1 M00001557B:H10 5192
732 1/28/98 732 RTAOOOOO 186AF.p.01.2 M00001654D:G1 1 40440
733 1/28/98 733 RTA00000200AF.d.20.1 M00004087A:G08 26600
734 1/28/98 734 RTA00000200AF.d.21.1 M00004087C:D03 0
735 1/28/98 735 RTAOOOOO 192AF.b.1 1.1 M000041 17A:G01 40014
736 1/28/98 736 RTA00000196AF.O.13.1 M00001428B:A09 0
737 1/28/98 737 RTA00000189AR.m.9.1 M00003880B:C08 2917
738 1/28/98 738 RTAOOOOO 183 AF.o.8.1 M00001540C:B10 8927
739 1/28/98 739 RTA00000181AF.p.l2.3 M00001460C:H02 22204
740 1/28/98 740 RTAOOOOO 198AF.d.15.1 M00001590C:H08 5997
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
741 1/28/98 741 RTA00000196AF.n.22.1 M00001424B:H04 9572
742 1/28/98 742 RTAOOOOO 177AF.m.1.1 M00001353D:D10 14929
743 1/28/98 743 RTAOOOOO 178 AF.k.9.1 M00001381 B:F06 16342
744 1/28/98 744 RTAOOOOO 196F.m.4.1 M00001413A:F03 7958
745 1/28/98 745 RTAOOOOO 183 AF.m.1 1.1 M00001536D:G02 8927
746 1/28/98 746 RTA00000178AF.Ϊ.01.2 M00001376B:F03 4
747 1/28/98 747 RTAOOOOO 190AF.C.6.1 M00003904D:D10 4780
748 1/28/98 748 RTA00000198AF.b.24.1 M00001571 D:B 1 1 19047
749 1/28/98 749 RTAOOOOO 178AR.L 13.4 M00001377B:H01 0
750 1/28/98 750 RTA00000198AF.a.l 9.1 M00001561 D:C05 0
751 1/28/98 751 RTAOOOOO 179AF.C.4.3 M00001392D:B1 1 0
752 1/28/98 752 RTA00000192AF.O.7.1 M00004204D:C03 5275
753 1/28/98 753 RTAOOOOO 192AF.0.17.1 M00004208D:B10 5275
754 1/28/98 754 RTA00000187AF.1.1 1.1 M00001681A:F03 4482
755 1/28/98 755 RTAOOOOO 199F.C.21.2 M00003803C:D09 5070
756 2/24/98 1 RTA00000404F.a.02.1 M00001589B:E12 9738
757 2/24/98 2 RTA00000406F.d. l 6.1 M00003875C:G02 15040
758 2/24/98 3 RTA00000420F.d. l 8.1 M00004105C:B05 63074
759 2/24/98 4 RTA00000339F.i.20.1 M00001438D:C06 4356
760 2/24/98 5 RTA00000408F.O.12.2 M00001572A:A10 78578
761 2/24/98 6 RTAOOOOO 1 19A.J.15.1 M00001460A:E1 1 79623
762 2/24/98 7 RTA00000413F.d.l2.1 M00004088C:A12 66467
763 2/24/98 8 RTA00000423F.U2.1 M00003914D:E03 91 18
764 2/24/98 9 RTA00000406F.n.02.1 M00003918C:H10 15051
765 2/24/98 10 RTA00000350R.C.12.1 M00001550D:A04 9728
766 2/24/98 1 1 RTA0000041 1F.k.05.1 M00003850D:B05 64777
767 2/24/98 12 RTA00000339F.b.l 7.1 M00001366D:E12 10020
768 2/24/98 13 RTA00000406FT.18.1 M00003879B:G02 38587
769 2/24/98 14 RTA00000419F.b.09.1 M00001694C:F12 78128
770 2/24/98 15 RTA00000419F.C.19.1 M00003820A:A08 64346
771 2/24/98 16 RTA00000399F.a.02.1 M00001366D:C12 0
772 2/24/98 17 RTA0000041 1 F.m.l 5.1 M00003868D:B09 78014
773 2/24/98 18 RTA00000420F.g.l2.1 M00004895B:G04 0
774 2/24/98 19 RTAOOOOO 123 A.k.23.1 M00001533A:G05 80313
775 2/24/98 20 RTA00000404F.m.04.2 M00001641A:A1 1 22720
776 2/24/98 21 RTA0000041 1F.g.08.1 M00003822D:D04 45815
777 2/24/98 22 RTA00000130A.m.l 5.1 M00001622A:H12 81630
778 2/24/98 23 RTA0000041 1 F.k.20.1 M00003854B:A07 64973
779 2/24/98 24 RTA00000423F.1.09.1 M000041 18A:H08 9752
780 2/24/98 25 RTA00000418F.k.05.1 M00001637A:A06 73021
781 2/24/98 26 RTA00000423F.h.l 8.1 M00003876C:D02 37972
782 2/24/98 27 RTA00000420F.n.l9.2 M00005259B:C01 0
783 2/24/98 28 RTA00000422F.p.06.2 M00001661 A:B1 1 39282
784 2/24/98 29 RTA00000404F.n.l6.2 M00001649C:D05 39095
785 2/24/98 30 RTA0000041 1 F.m.24.1 M00003870B:B08 77568
786 2/24/98 31 RTAOOOOO 134A.J.10.1 M00001534A:G06 81383
787 2/24/98 32 RTA00000409FJ.02.1 M0000161 1 B:E06 76417
788 2/24/98 33 RTA00000403F.J..15.1 M00001539B:G07 23840
789 2/24/98 34 RTA0000041 1 F.n.l l . l M00003875A:B01 77276
790 2/24/98 35 RTA00000339F.U3.1 M00001434A:B10 5970
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
791 2/24/98 36 RTA00000414F.e.22.1 M00005257D:A06 0
792 2/24/98 37 RTA00000406F.O.15.1 M00003988D:A08 37482
793 2/24/98 38 RTA00000412F.g.04.2 M00003971 B:B07 64457
794 2/24/98 39 RTA00000187AF.I.7.1 M00001680D:F08 10539
795 2/24/98 40 RTA00000352R.1.06.1 M00004187D:H06 40343
796 2/24/98 41 RTA00000419F.b. l2.1 M00003806B:C09 63148
797 2/24/98 42 RTA00000423F. 17.2 M00004038A:F02 37512
798 2/24/98 43 RTA00000420F.g.04.1 M00004891 B:B12 0
799 2/24/98 44 RTA00000418F. 4.1 M00001639A:H06 76133
800 2/24/98 45 RTA00000409F.1.12.1 M00001615A:D06 26755
801 2/24/98 46 RTA00000404F.C.20.1 M00001594A:D08 39088
802 2/24/98 47 RTA00000423F.g.09.1 M00003904C:B06 38958
803 2/24/98 48 RTA0000041 1 F.b.24.1 M00001677B:A12 30041
804 2/24/98 49 RTA00000406F.d.l2.1 M00003875C:A01 38575
805 2/24/98 50 RTA0000041 1 F.f.02.1 M00003813A:D08 63386
806 2/24/98 51 RTAOOOOO 129 A.n.21.1 M00001604A:C 1 1 79381
807 2/24/98 52 RTA00000409F.m.l2.1 M00001618B:D09 73490
808 2/24/98 53 RTA00000410F.C.04.1 M00001633D:G09 74099
809 2/24/98 54 RTA00000399F.O.01.1 M00001595C:E01 3055
810 2/24/98 55 RTA00000406F.m.09.1 M00003914C:H05 26891
81 1 2/24/98 56 RTA0000041 1 F.b.06.1 M00001676C:A04 77884
812 2/24/98 57 RTA00000409F.1.21.1 M00001615B:G07 73143
813 2/24/98 58 RTA00000420F.m.l 8.1 M00005254D:A10 0
814 2/24/98 59 RTA00000346F.J.08.1 M00003879B:A06 39951
815 2/24/98 60 RTA00000413F.p.l 7.2 M00005136D:G06 0
816 2/24/98 61 RTA00000410F.n.07.1 M00001662A:G01 78823
817 2/24/98 62 RTA00000339F.n.l0.1 M00001453B:F08 13719
818 2/24/98 63 RTA00000404F.1.20.2 M00001639B:H05 38638
819 2/24/98 64 RTA00000413F.d. l 8.1 M00004090B:B04 65305
820 2/24/98 65 RTA00000404F.p.04.2 M00001652D:E05 39069
821 2/24/98 66 RTA00000405F.g.l9.2 M00001673A:G08 37150
822 2/24/98 67 RTA00000409F.a.22.1 M00001583B:F02 75200
823 2/24/98 68 RTA00000339F.n.03.1 M00001449B:B03 0
824 2/24/98 69 RTA00000405F.O.18.1 M00003839A:D07 1 1016
825 2/24/98 70 RTA00000409F.m. l3.1 M00001618B:E05 0
826 2/24/98 71 RTAOOOOO 120A.d.24.1 M00001464A:E10 5085
827 2/24/98 72 RTA00000347F.a.08.1 M00001592C:G04 3135
828 2/24/98 73 RTA00000413F.p.l5.2 M00005136D:D06 0
829 2/24/98 74 RTA00000408F.e.22.2 M00001476B:F08 26930
830 2/24/98 75 RTA00000350R.i.22.1 M00001608B:A03 0
831 2/24/98 76 RTA00000413F.d. l6.1 M00004088C:F01 63331
832 2/24/98 77 RTA00000420F.J.22.1 M00005173B:F01 0
833 1/28/98 59 RTA00000195AF.b. l3.1 M00001560D:A03 12605
833 2/24/98 78 RTA00000195AF.D.13.1 M00001560D:A03 12605
834 2/24/98 79 RTA00000419F.g.08.1 M00003842C:D1 1 66700
835 2/24/98 80 RTA00000122A.g. l 6.1 M00001514A:B04 81366
836 2/24/98 81 RTA00000419F.C.16.1 M00003819D:B01 65254
837 2/24/98 82 RTA0000041 1 F.b.03.1 M00001676B:E01 23634
838 2/24/98 83 RTA00000405F.e.l l .2 M00001663D:C06 9331
839 2/24/98 84 RTA00000352R.U5.1 M00004153B:B03 4363
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
840 2/24/98 85 RTA00000339F.k.22.1 M00001427C:D01 5556
841 2/24/98 86 RTA00000346F.g.22.1 M00003794D:G03 6371
842 2/24/98 87 RTA00000403F.1.20.1 M00001573A:A06 18267
843 2/24/98 88 RTA00000420F.i.24.1 M00005134B:E08 0
844 2/24/98 89 RTA00000406F.C.08.1 M00003870C:A10 22387
845 2/24/98 90 RTA0000041 1 F.a.02.1 M00001675B:E02 78537
846 2/24/98 91 RTA00000355R.e.l 5.1 M00004316A:G09 22639
847 2/24/98 92 RTA00000412F.1.04.1 M00003989D:F12 66372
848 2/24/98 93 RTA00000413F.p.24.1 M00005139A:H03 0
849 2/24/98 94 RTA00000406F.a.23.1 M00003867B:D10 38712
850 2/24/98 95 RTA00000423F.h.05.1 M00003906A:F04 14837
851 2/24/98 96 RTAOOOOO 120A.n.19.3 M00001467A:H07 80004
852 2/24/98 97 RTA00000403F.e.01.1 M00001473A:C1 1 38965
853 2/24/98 98 RTA0000041 1 F.1.03.1 M00003854D:A12 62702
854 2/24/98 99 RTA00000420F.m.l9.1 M00005254D:B08 0
855 2/24/98 100 RTA00000339F.O.23.1 M00001473C:D09 7801
856 2/24/98 101 RTAOOOOO 121 A.m.2.1 M00001507A:A1 1 81064
857 2/24/98 102 RTA00000420F.g.06.1 M00004891 C:D04 0
858 2/24/98 103 RTA00000418F.J.12.1 M00001626C:G08 73316
859 2/24/98 104 RTA00000421 F.n.03.1 M00001675C:A04 1638
860 2/24/98 105 RTA00000346F.d.08.1 M00001671A:A10 39955
861 2/24/98 106 RTA00000339F.f.l l .l M00001391 C:H02 5832
862 2/24/98 107 RTA00000125A.g. l6.1 M00001544A:C09 21497
863 2/24/98 108 RTA00000418F.O.18.1 M00001661 B:F06 78676
864 2/24/98 109 RTA00000422F.p.24.2 M00001658A:G09 5823
865 2/24/98 1 10 RTA00000408F.k.l4.1 M00001486B:E12 73856
866 2/24/98 1 1 1 RTA00000128A.i.20.1 M00001560A:F03 9900
867 2/24/98 1 12 RTA00000422F.C.1 1.1 M00003841 D:A04 2643
868 2/24/98 1 13 RTA00000401 F.e.02.1 M00003805B:C04 0
869 2/24/98 1 14 RTA00000341 F.m.21.1 M00004051 D:E01 0
870 2/24/98 1 15 RTA00000418F.h.l9.1 M00001590B:C05 0
871 2/24/98 1 16 RTA00000403F.O.15.1 M00001582B:E12 39140
872 2/24/98 1 17 RTA00000341 F.m.l3.1 M00003987B:E12 26502
873 2/24/98 1 18 RTA00000408F.h.03.1 M00001479D:H03 78382
874 2/24/98 1 19 RTA00000423F.k.05.1 M00004036D:F02 37472
875 2/24/98 120 RTA00000401 F.m.02.1 M00003907A:F01 1573
876 2/24/98 121 RTA00000418F.p. l9.1 M00001677D:B01 78544
877 2/24/98 122 RTA00000420F.f.06.1 M000041 15D:D08 64812
878 2/24/98 123 RTAOOOOO 122A.J.18.1 M00001516A:D05 81317
879 2/24/98 124 RTA00000420F.d.05.1 M00004092B:E05 64432
880 2/24/98 125 RTA00000403F.m. l 8.1 M00001576A:B09 39185
881 2/24/98 126 RTA00000422F .20.1 M00001653A:G07 22388
882 2/24/98 127 RTA0000041 1 F.J.05.1 M00003841 C:F06 40709
883 2/24/98 128 RTA00000403F.a.04.1 M00001448A:B12 23529
884 2/24/98 129 RTAOOOOO 1 18A.d.24.1 M00001416A:H02 81488
885 2/24/98 130 RTA00000406F.f.l2.1 M00003879A:C 1 1 21895
886 2/24/98 131 RTA00000418F.g.22.1 M00001585B:F01 74837
887 2/24/98 132 RTA00000418F.m.05.1 M00001650B:C 10 73600
888 2/24/98 133 RTA00000404F.1.20.1 M00001639B:H05 38638
889 2/24/98 134 RTA00000408F.i.08.2 M00001482A:H05 7581 1
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
890 2/24/98 135 RTA00000122A.d.5.1 M00001513A:F05 81 155
891 2/24/98 136 RTA00000419F.1.12.1 M00003901 C:B01 75710
892 2/24/98 137 RTA00000339R.a.06.1 M00001346A:E04 58694
893 2/24/98 138 RTA00000406F.f.03.1 M00003878C:D08 38687
894 2/24/98 139 RTA00000419F.b.l9.1 M00003809A:C01 65534
895 2/24/98 140 RTA00000128A.J.6.2 M00001560A:H10 5316
896 2/24/98 141 RTA00000418F. 19.1 M00001639C:C02 74932
897 2/24/98 142 RTA00000420F.J.19.1 M00005140C:B10 0
898 2/24/98 143 RTA00000420F.h. l3.1 M00004899D:G06 0
899 2/24/98 144 RTA00000349R .15.1 M00001472A:D08 75097
900 2/24/98 145 RTA00000419F.g.l2.1 M00003842C:G03 66171
901 2/24/98 146 RTA00000404F.n.l l .2 M00001649A:E1 1 38001
902 2/24/98 147 RTA00000422F.C.02.1 M000041 18B:A03 2902
903 2/24/98 148 RTA00000419F.n.04.1 M00003975C:F07 13102
904 2/24/98 149 RTA00000419F.O.24.1 M00004031A:F07 65092
905 2/24/98 150 RTA00000419F.L 19.1 M00003877C:G 12 75447
906 2/24/98 151 RTA00000341 F.C.21.1 M00003789C:F06 7899
907 2/24/98 152 RTA00000127A.i.20.1 M00001555A:B12 81418
908 2/24/98 153 RTA00000422F.g.22.1 M00001585B:A06 22561
909 2/24/98 154 RTA00000340F.b.21.1 M00001533D:A08 8001
910 2/24/98 155 RTA00000413F.h.l3.1 M00004107A:D01 65190
91 1 2/24/98 156 RTA00000125A.k.l .l M00001545A:B12 0
912 2/24/98 157 RTA00000339F.3.23.1 M00001361B:C07 4022
913 2/24/98 158 RTA00000348R.J.16.1 M00001410A:D07 7005
914 2/24/98 159 RTA00000348R.J.17.1 M00001391 D:C06 2641
915 2/24/98 160 RTA00000414F.f i 9.1 M00005260B:E1 1 0
916 2/24/98 161 RTA00000418F.n.22.1 M00001659D:B05 79062
917 2/24/98 162 RTA00000406F.1.08.1 M00003908D:D12 39016
918 2/24/98 163 RTA00000422F.1.23.1 M00001616D:C1 1 4240
919 2/24/98 164 RTA00000345F.k.06.1 M00001475A:A12 0
920 2/24/98 165 RTA00000409F.J.07.1 M0000161 1C:H1 1 75190
921 2/24/98 166 RTA00000418F.m.l9.1 M00001654D:A03 8890
922 2/24/98 167 RTA00000399F.1.14.1 M00001590B:G08 3354
923 2/24/98 168 RTA0000041 1 F.e.22.1 M00003812B:D07 63638
924 2/24/98 169 RTA00000347F.a.l 7.1 M00001366D:C06 16723
925 2/24/98 170 RTA00000422F.n.08.1 M00001632B:E05 38655
926 2/24/98 171 RTA00000404F.n.20.1 M00001650A:C1 1 26865
927 2/24/98 172 RTA00000420F.U 7.1 M00005101C:B09 0
928 2/24/98 173 RTA00000418F.d.l3.1 M00001570A:H01 74309
929 2/24/98 174 RTA00000404F.b.02.1 M00001591B:B12 38984
930 2/24/98 175 RTA00000410F.d.09.1 M00001635B:H01 76964
931 2/24/98 176 RTA00000403F.b. l0.1 M00001455C:G07 73268
932 2/24/98 177 RTA00000406F. 2.1 M00003903D:H1 1 39080
933 2/24/98 178 RTA00000406F.h.08.1 M00003901 C:A08 16228
934 2/24/98 179 RTA00000418F.i.l9.1 M00001596D:E03 79180
935 2/24/98 180 RTA00000400F.J.19.1 M00001653C:D10 4086
936 2/24/98 181 RTA00000412F.h.21.1 M00003974D:F02 64348
937 2/24/98 182 RTA00000404F.g.l4.1 M00001614D:B08 8858
938 2/24/98 183 RTAOOOOO 120A.g.18.1 M00001465A:C12 81255
939 2/24/98 184 RTAOOOOO 133 A.j.13.1 M00001507A:B02 16846
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
940 2/24/98 185 RTA00000423F.J.05.1 M00003903C:C05 37958
941 2/24/98 186 RTAOOOOO 132 A.k.6.1 M00001464A:E07 81284
942 2/24/98 187 RTA00000351 R.g.l l .l M00003779D:E08 3077
943 2/24/98 188 RTA00000406F.p.04.1 M00004030D:F1 1 37458
944 2/24/98 189 RTA00000347F.3.13.1 M00001402D:F02 22446
945 2/24/98 190 RTA00000419F.p.23.1 M00004039B:A05 64748
946 2/24/98 191 RTA00000419F.d.l 7.1 M00003828B:F09 64353
947 2/24/98 192 RTA00000421 F.k.l 5.1 M00001613D:B03 2222
948 2/24/98 193 RTA00000347F.b.l0.1 M00001546C:C07 8044
949 2/24/98 194 RTAOOOOO 124A.k.5.1 M00001538A:F12 80252
950 2/24/98 195 RTA00000404F.h.22.1 M00001619C:C07 18735
951 2/24/98 196 RTA00000418F.k.l0.1 M00001639A:G07 74454
952 2/24/98 197 RTA00000410F.O.05.1 M00001669A:B02 75262
953 2/24/98 198 RTA00000339R.1.14.1 M00001452A:C07 191 19
954 2/24/98 199 RTA00000403F.m.l3.2 M00001575D:A10 39077
955 2/24/98 200 RTA00000339F.C.02.1 M00001381 C:B08 12975
956 2/24/98 201 RTA00000404F.1.09.1 M00001638B:E12 39176
957 2/24/98 202 RTA00000419F.g.22.1 M00003845D:A09 64515
958 2/24/98 203 RTA00000404F.g.21.1 M00001615C:A1 1 37947
959 2/24/98 204 RTA00000351 R.k.l9.1 M00003841B:E03 936
960 2/24/98 205 RTAOOOOO 138A.n.4.1 M00001624A:G1 1 21920
961 2/24/98 206 RTA00000410F.b.l5.1 M00001633C:F09 77100
962 2/24/98 207 RTA00000414F.b.08.1 M00005212C:H02 0
963 2/24/98 208 RTA00000419F.J.23.1 M00003871A:C1 1 74470
964 2/24/98 209 RTA0000041 1 F.J.02.1 M00003841C:D07 65310
965 2/24/98 210 RTA00000419F.p.24.1 M00004039B:E12 63477
966 2/24/98 21 1 RTA00000404F.a.l9.1 M00001590B:C07 38624
967 2/24/98 212 RTA00000408F.k.06.1 M00001485C:H10 78393
968 2/24/98 213 RTAOOOOO 123 A.f.3.1 M00001531 A:H07 44017
969 2/24/98 214 RTA00000404F.h.l9.1 M00001619A:E05 8096
970 2/24/98 215 RTA00000403F.J.18.1 M00001539D:E10 5790
971 2/24/98 216 RTA00000420F.i.l 8.1 M00005101 C:E09 0
972 2/24/98 217 RTA00000399F.O.17.1 M00001599D:A09 1 106
973 2/24/98 218 RTA00000346F.e.l3.1 M00001660B:D03 74653
974 2/24/98 219 RTA00000419F.C.18.1 M00003819D:B1 1 41394
975 2/24/98 220 RTA00000413F.k.02.1 M00004690A:G08 0
976 2/24/98 221 RTA00000414FT.13.1 M00005259D:H08 0
977 2/24/98 222 RTA00000405F.e.09.1 M00001663C:F12 38978
978 2/24/98 223 RTA00000404F.e.22.1 M00001610A:H05 1 1344
979 2/24/98 224 RTA00000341 F.g.21.1 M00003914C:F09 8823
980 2/24/98 225 RTA00000414F.d.07.1 M00005229D:H09 0
981 2/24/98 226 RTAOOOOO 125A.k.10.1 M00001545A:F02 81644
982 2/24/98 227 RTA00000347F.C.06.1 M00001444D:C01 18846
983 2/24/98 228 RTA0000041 1 F.k.l9.1 M00003852D:E08 64200
984 2/24/98 229 RTA00000345F.i.09.1 M00001450A:D08 27250
985 2/24/98 230 RTA00000423F.k.01.1 M00004034D:E09 40426
986 2/24/98 231 RTA00000408F.d.06.1 M00001458D:C1 1 78997
987 2/24/98 232 RTAOOOOO 128 A.b.20.1 M00001558A:GO9 79761
988 2/24/98 233 RTA00O00403F. 08.1 M00001485C:B10 6176
989 2/24/98 234 RTA00000195AF.d.4.1 M00003881 D:D06 22766
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
989 1/28/98 185 RTAOOOOO 195 AF.d.4.1 M00003881 D:D06 22766
990 2/24/98 235 RTA00000126A.O.23.1 M00001551 A:B10 6268
991 2/24/98 236 RTA00000403F.h. l2.1 M00001483C:G09 15205
992 2/24/98 237 RTAOOOOO 1 19A.J .22.1 M00001460A:F07 80336
993 2/24/98 238 RTA00000340F.J.12.1 M00001624A:B06 3277
994 2/24/98 239 RTA00000346F.J.02.1 M00003832B:E01 5294
995 2/24/98 240 RTAOOOOO 126A.n.7.2 M00001551 A:D06 79557
996 2/24/98 241 RTA00000339F.d. l3.1 M00001395C:F1 1 0
997 2/24/98 242 RTA00000404F.J.08.1 M00001629B:B08 39066
998 2/24/98 243 RTA00000410F.C.14.1 M00001634A:H05 77809
999 2/24/98 244 RTAOOOOO 120A.g.23.1 M00001465A:E10 81 189
1000 2/24/98 245 RTAOOOOO 195 AF.d.20.1 M000041 17A:D1 1 37574
1000 1/28/98 87 RTA00000195AF.d.20.1 M000041 17A:D1 1 37574
1001 2/24/98 246 RTA00000414F.C.14.1 M00005218A:G05 0
1002 2/24/98 247 RTA00000412F.J.17.1 M00003982C:G04 64071
1003 2/24/98 248 RTA00000404F.k.24.1 M00001636A:C03 15256
1004 2/24/98 249 RTA000001 19A.J.10.1 M00001460A:C10 79646
1005 2/24/98 250 RTA00000410F.O.12.1 M00001669A:G 12 77376
1006 2/24/98 251 RTA000001 19A.i.9.1 M00001457A:G03 0
1007 2/24/98 252 RTA00000412F.g.24.1 M00003973C:C03 28741
1008 2/24/98 253 RTA00000400F.f. l 8.1 M00001637A:E10 3764
1009 2/24/98 254 RTA00000341 F.1.15.1 M00003986B:A08 5294
1010 2/24/98 255 RTA00000419F.O.16.1 M00003989C:G05 62867
101 1 2/24/98 256 RTA00000404F.m.03.2 M00001640A:H02 1 1799
1012 2/24/98 257 RTA0000041 1 F.C.17.1 M00001678D:G03 77664
1013 2/24/98 258 RTA00000406F.k.l 5.1 M00003907C:C04 38549
1014 2/24/98 259 RTA00000406F.a.02.1 M00003855C:F10 37744
1015 2/24/98 260 RTA00000414F.e.08.1 M00005236A:E04 0
1016 2/24/98 261 RTA00000341 F.b.06.1 M00003794A:E12 17008
1017 2/24/98 262 RTA00000409F.n.l4.1 M00001621 B:G05 78190
1018 2/24/98 263 RTA00000410F.p. l 7.1 M00001674D:C 10 47425
1019 2/24/98 264 RTA00000345FJ.08.1 M00001451 B:A04 16731
1020 2/24/98 265 RTA00000340F.k. l 6.1 M00001647B:C09 13157
1021 2/24/98 266 RTA00000419F.g. l5.1 M00003844D:A07 32519
1022 2/24/98 267 RTA00000423F.a.l 9.1 M00001676D:A02 21396
1023 2/24/98 268 RTA00000403F.e.23.1 M00001476A:D1 1 9626
1024 2/24/98 269 RTA00000422F.e.08.1 M00001573A:E01 39020
1025 2/24/98 270 RTA0000041 1 F.d.l5.1 M00001692A:B06 74890
1026 2/24/98 271 RTA00000414F.e.l 6.1 M00005236B:H 10 0
1027 2/24/98 272 RTA0000041 1 F.1.15.1 M00003857C:F 1 1 66704
1028 2/24/98 273 RTA00000400F.a. l l . l M00001612B:D1 1 0
1029 2/24/98 274 RTA00000405F.e.08.1 M00001663C:F10 37916
1030 2/24/98 275 RTA00000353RJ.24.1 M00001428B:D01 23089
1031 2/24/98 276 RTA00000423F.a. l 8.1 M00001675A:G 10 26761
1032 2/24/98 277 RTA00000418F.O.06.1 M00001660C:D1 1 75930
1033 2/24/98 278 RTA00000404F.C.10.1 M00001593B:E1 1 23534
1034 2/24/98 279 RTA00000418FL21 .1 M00001596D:E10 78728
1035 2/24/98 280 RTA00000418F.p.l5.1 M00001671C:C1 1 31066
1036 2/24/98 281 RTA0000041 1 F.I.13.1 M00003857C:C09 431 14
1037 2/24/98 282 RTA00000407F.a.24.1 M00004083A:E08 37560
SEQ ID Filing SEQ ID Sequence Nsme Clone Nsme Cluster
NO: Dste of NO: in ID
Priority Priority
Appln Appln
1038 2/24/98 283 RTA00000346F.n.06.1 M00004139C:A12 12439
1039 2/24/98 284 RTA00000412F.1.21.1 M00004029C:G10 65183
1040 2/24/98 285 RTA00000413F.i.02.1 M00004110D:A10 65857
1041 2/24/98 286 RTA00000404F.i.l9.1 M00001625B:C10 38698
1042 2/24/98 287 RTA00000410F.n.09.1 M00001662C:A04 11736
1043 2/24/98 288 RTA00000403F.a.ll.1 M00001448C.-F10 73109
1044 2/24/98 289 RTA00000420F.n.08.1 M00005257A:H11 0
1045 2/24/98 290 RTA00000411F.k.l6.1 M00003852C:B06 64759
1046 2/24/98 291 RTA00000405F.C.01.1 M00001657D:A04 19236
1047 2/24/98 292 RTA00000423F.U8.1 M00003918A:D08 14996
1048 2/24/98 293 RTA00000403F.1.04.1 M00001571C:A04 39278
1049 2/24/98 294 RTA00000405F.1.17.1 M00003805A.-F02 17225
1050 2/24/98 295 RTA00000406F.a.07.1 M00003856C:H09 26607
1051 2/24/98 296 RTA00000347F.d.06.1 M00001457C:F02 39122
1052 2/24/98 297 RTA00000419F.b.l8.1 M00003808D:D08 67034
1053 2/24/98 298 RTA00000406F.h.07.1 M00003901B:H04 38003
1054 2/24/98 299 RTA00000405F.1.15.1 M00001694A.Ε03 19575
1055 2/24/98 300 RTA00000406F.g.l7.1 M00003881B:F10 37979
1056 2/24/98 301 RTA00000401F.m.23.1 M00003914C:C02 2801
1057 2/24/98 302 RTA00000356RT.18.1 M00004692A:H10 0
1058 2/24/98 303 RTAOOOOO 130A.h.22.1 M00001617A:D06 80933
1059 2/24/98 304 RTA00000403F.n.l8.2 M00001577D:H06 8811
1060 2/24/98 305 RTA00000418F.p.06.1 M00001664A:F08 32628
1061 2/24/98 306 RTA00000404F.d.l3.1 M00001595D:A04 39036
1062 2/24/98 307 RTA00000420F.1.12.2 M00005230B:H09 0
1063 2/24/98 308 RTA00000353R.d.ll.l M00004692A:H08 0
1064 2/24/98 309 RTA00000340F.n.01.1 M00001679A:G06 39081
1065 2/24/98 310 RTA00000419F.d.06.1 M00003820B:D07 65496
1066 2/24/98 311 RTA00000419F.n.09.1 M00003977C:A06 66070
1067 2/24/98 312 RTA00000399F.i.08.1 M00001575D:B10 38927
1068 2/24/98 313 RTA00000406F.g.07.1 M00003880C:E11 37925
1069 2/24/98 314 RTA00000423F.g.l3.1 M00003905A:E07 38028
1070 2/24/98 315 RTA00000419F.p.l2.1 M00004037A:E04 13767
1071 2/24/98 316 RTA00000414F.a.02.1 M00005178D:H04 0
1072 2/24/98 317 RTA00000195AF.b.21.1 M00001595B:A09 39055
1072 1/28/98 602 RTA00000195AF.b.21.1 M00001595B:A09 39055
1073 2/24/98 318 RTA00000403F.h.05.1 M00001482D:A04 39096
1074 2/24/98 319 RTA00000420F.b.21.1 M00004088D:B10 65057
1075 2/24/98 320 RTA00000422F.p.07.2 M00001661A:E06 39024
1076 2/24/98 321 RTA00000339F.C.21.1 M00001389C:A08 5325
1077 2/24/98 322 RTA00000339F.C.24.1 M00001364B:B06 5516
1078 2/24/98 323 RTA00000421F.n.l9.1 M00001679A:D10 16409
1079 2/24/98 324 RTA00000340F.p.l7.1 M00003750C:H05 0
1080 2/24/98 325 RTA00000345F. 21.1 M00001464B:C11 40204
1081 2/24/98 326 RTA00000419F.b.l5.1 M00003806D:D11 43969
1082 2/24/98 327 RTA00000405F.3.11.1 M00001655A:B11 39124
1083 2/24/98 328 RTA00000423F.L19.2 M00003985D:E10 17615
1084 2/24/98 329 RTA00000413F.e.l6.1 M00004093C:C02 63836
1085 2/24/98 330 RTA00000403F.i.04.1 M00001485B:D09 8930
1086 2/24/98 331 RTA00000404F.O.18.2 M00001651C:C05 39110
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: D3te of NO: in ID Priority Priority Appln Appln
1087 2/24/98 332 RTA00000409F.i.24.1 M00001611B:A09 76967
1088 2/24/98 333 RTA00000399F.f.ll.l M00001487C:F01 40167
1089 2/24/98 334 RTA00000408F.p.05.1 M00001575B:B02 9649
1090 2/24/98 335 RTA00000413F.d.02.1 M00004087B:A12 66172
1091 2/24/98 336 RTA00000340F.n.l3.1 M00001688D:B10 17055
1092 2/24/98 337 RTA00000340F.p.04.1 M00001679D:B02 78533
1093 2/24/98 338 RTA00000411F.C.05.1 M00001677B:H06 73368
1094 2/24/98 339 RTA00000403F.g.l0.1 M00001481A:G06 20211
1095 2/24/98 340 RTA00000408F.I.13.1 M00001530A:B12 4423
1096 2/24/98 341 RTA00000412F.g.20.2 M00003972C:F08 25018
1097 2/24/98 342 RTA00000404F.i.02.1 M00001619D:D10 39015
1098 2/24/98 343 RTA00000422F.g.21.1 M00001583A:F07 17232
1099 2/24/98 344 RTA00000403F.m.l5.2 M00001575D:D12 26901
1100 2/24/98 345 RTA00000412F.h.23.2 M00003974D:H04 65118
1101 2/24/98 346 RTA00000418F.J.08.1 M00001626C:C11 73382
1102 2/24/98 347 RTAOOOOO 125 A.n.4.1 M00001546A:D08 81984
1103 2/24/98 348 RTA00000412F.1.19.1 M00004029C:C05 65825
1104 2/24/98 349 RTA00000404F.m.l0.2 M00001641D:E02 779
1105 2/24/98 350 RTAOOOOO 129A.p.3.1 M00001604A:B08 32644
1106 2/24/98 351 RTA00000340F.p.20.1 M00003752B:C02 17008
1107 2/24/98 352 RTA00000411F.3.10.1 M00001675C:G01 73073
1108 2/24/98 353 RTA00000409F.n.l7.1 M00001621C:C10 76725
1109 2/24/98 354 RTA00000404F.C.03.2 M00001592C:F11 39198
1110 2/24/98 355 RTA00000420F.a.l9.1 M00004076A:D12 34192
1111 2/24/98 356 RTA00000409F.m.24.1 M00001620D:H02 3942
1112 2/24/98 357 RTA00000406F.n.l6.1 M00003972A:G09 5660
1113 2/24/98 358 RTA00000414F.e.06.1 M00005235A:A03 0
1114 2/24/98 359 RTA00000420F.d.l2.1 M00004096D:H03 64095
1115 2/24/98 360 RTA00000409F.J.19.1 M00001613A:F03 73792
1116 2/24/98 361 RTA00000422F.d.l6.1 M00001570C:G03 39133
1117 2/24/98 362 RTA00000418F.m.l6.1 M00001653B:E06 74986
1118 2/24/98 363 RTA00000405F.C.11.1 M00001659A:D12 39068
1119 2/24/98 364 RTA00000404F. 22.1 M00001635D:C12 39084
1120 2/24/98 365 RTA00000418F.k.07.1 M00001637A:F10 75067
1121 2/24/98 366 RTA00000403F.C.10.1 M00001456D:F05 75261
1122 2/24/98 367 RTA00000401F.O.06.1 M00004029C:C12 2679
1123 2/24/98 368 RTA00000346F.O.08.1 M00004149C:B02 0
1124 2/24/98 369 RTA00000410F.m.05.1 M00001657B:B04 74964
1125 2/24/98 370 RTA00000405F.i.20.1 M00001677A:G11 38532
1126 2/24/98 371 RTA00000403F.J.17.1 M00001539D:B10 38563
1127 2/24/98 372 RTA00000408F.p.24.1 M00001579A:E03 74286
1128 2/24/98 373 RTA00000418F.k.l8.1 M00001639C:A10 75385
1129 2/24/98 374 RTA00000422F.rn.04.] M00001615B:A09 38702
1130 2/24/98 375 RTA00000405F.g.l6.2 M00001672D:D04 9021
1131 2/24/98 376 RTA00000400F.L22.1 M00001656A:B07 2512
1132 2/24/98 377 RTA00000346F.i.01.1 M00003797A:D06 22260
1133 2/24/98 378 RTA00000403F.a.07.1 M00001448B:F09 73559
1134 2/24/98 379 RTA00000349R.J.07.1 M00001529B:C04 2642
1135 2/24/98 380 RTA00000403F.b.l9.1 M00001456B:A06 22327
1136 2/24/98 381 RTA00000418F.m.23.1 M00001654D:F11 77195
SEQ ID Filing SEQ ID Sequence Name Clone N3me Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
1137 2/24/98 382 RTA00000341F.h.l0.1 M00003901B:G11 0
1138 2/24/98 383 RTA00000404F.U8.1 M00001621C:H12 21912
1139 2/24/98 384 RTA00000422F.U4.1 M00001487A:F10 39300
1140 2/24/98 385 RTA00000418F.m.l4.1 M00001651B:E06 75711
1141 2/24/98 386 RTA00000406F.O.12.1 M00003986D:D02 37459
1142 2/24/98 387 RTA00000411F.a.l5.1 M00001675D:B08 73812
1143 2/24/98 388 RTA00000411F.a.07.1 M00001675C:C03 74547
1144 2/24/98 389 RTA00000411F.C.02.1 M00001677B:B04 72852
1145 2/24/98 390 RTA00000355R.3.14.1 M00004187D:G09 10207
1146 2/24/98 391 RTA00000130A.h.16.1 M00001617A:A08 80761
1147 2/24/98 392 RTA00000410F.p.23.1 M00001675B:C01 73948
1148 2/24/98 393 RTA00000418F.m.24.1 M00001654D:F12 77114
1149 2/24/98 394 RTA00000420F.m.02.1 M00005233A:G08 0
1150 2/24/98 395 RTA00000408F.J.19.2 M00001485C:C08 73752
1151 2/24/98 396 RTA00000406F.e.21.1 M00003877D:G05 9090
1152 2/24/98 397 RTA00000118A.d.l7.1 M00001416A:D09 81921
1153 2/24/98 398 RTA00000407F.b.04.1 M00004086D:B09 63221
1154 2/24/98 399 RTA00000411F.e.07.1 M00003810C:A03 65008
1155 2/24/98 400 RTA00000403F.f.08.1 M00001477A:G07 19107
1156 2/24/98 401 RTA00000132A.C.11.1 M00001454A:G03 87278
1157 2/24/98 402 RTA00000420F.e.l6.1 M00004110A:E04 63639
1158 2/24/98 403 RTA00000403F.d.22.1 M00001473A:A07 10692
1159 2/24/98 404 RTA00000404F.b.ll.l M00001591D:F06 39079
1160 2/24/98 405 RTA00000418F. 17.1 M00001639C:A09 75390
1161 2/24/98 406 RTAOOOOO 129A. 12.1 M00001601A:A06 79322
1162 2/24/98 407 RTA00000340R.m.07.1 M00001679D:F02 78415
1163 2/24/98 408 RTA00000405F.d.l4.1 M00001662A:C12 35209
1164 2/24/98 409 RTA00000406F.f.ll.l M00003879A:B08 38601
1165 2/24/98 410 RTA00000120A.h.5.1 M00001465A:G06 80344
1166 2/24/98 411 RTA00000420F.m.l2.1 M00005234D:B04 0
1167 2/24/98 412 RTA00000411F.g.06.1 M00003822D:C06 66065
1168 2/24/98 413 RTA00000408F.d.l6.1 M00001459B:D03 76318
1169 2/24/98 414 RTAOOOOO 120A.p.18.1 M00001468A:C05 6478
1170 2/24/98 415 RTA00000340RT.05.1 M00001569B:G11 3202
1171 2/24/98 416 RTA00000404F.C.19.1 M00001594A:D06 39026
1172 2/24/98 417 RTA00000423F.1.02.1 M00003978C:A03 5639
1173 2/24/98 418 RTA00000410F.3.01.1 M00001631D:B10 73354
1174 2/24/98 419 RTA00000408F.h.08.1 M00001480A:D03 74575
1175 2/24/98 420 RTA00000422F.b.l6.1 M00003813B:A11 17045
1176 2/24/98 421 RTA00000419F.f.l0.1 M00003835D:G06 66193
1177 2/24/98 422 RTA00000418F.I.04.1 M00001641C:D02 74140
1178 2/24/98 423 RTA00000410F.3.16.1 M00001633A:E06 73548
1179 2/24/98 424 RTA00000138A.e.l3.1 M00001605A:E06 79608
1180 2/24/98 425 RTA00000130A.b.5.] M00001605A:E09 79579
1181 2/24/98 426 RTA00000408F.J.15.2 M00001485B:F05 74759
1182 2/24/98 427 RTA00000410F.m.20.1 M00001660B:E03 74285
1183 2/24/98 428 RTA00000422F.f.14.1 M00001478B:D07 2036
1184 2/24/98 429 RTA00000422F.C.17.1 M00004099D:F01 1360
1185 2/24/98 430 RTA00000419F.e.04.1 M00003831C:G05 62963
1186 2/24/98 431 RTA00000399F.J.15.1 M00001578C:G06 1261
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
1 187 2/24/98 432 RTA00000418F.g.05.1 M00001579C:H06 73075
1 188 2/24/98 433 RTA00000419F.n.02.1 M00003958B:H08 65963
1 189 2/24/98 434 RTA00000348R.b. l 6.1 M00001347B:H04 6510
1 190 2/24/98 435 RTA00000340F.b.02.1 M00001503C:G05 10185
1 191 2/24/98 436 RTAOOOOO] 19A.m.15.1 M00001461 A:E05 80989
1 192 2/24/98 437 RTA00000403F.m.20.2 M00001576A:F1 1 707
1 193 2/24/98 438 RTA00000195R.d.09.1 M00003981 C:B04 8537
1 194 2/24/98 439 RTA00000413F.g.23.1 M00004103B:E09 40700
1 195 2/24/98 440 RTA00000403F.a. l 8.1 M00001448D:F12 75726
1 196 2/24/98 441 RTA00000404F.m.20.2 M00001647A:H08 39144
1 197 2/24/98 442 RTA00000347F.b.02.1 M00001450A:A02 39304
1 198 2/24/98 443 RTA00000414F. i 5.1 M00005260A:A12 0
1 199 2/24/98 444 RTA00000419F.h.04.1 M00003846A:D03 65034
1200 2/24/98 445 RTA00000408F.d.l2.1 M00001459B:A12 75782
1201 2/24/98 446 RTA00000133A.m. l 9.2 M00001512A:G05 80167
1202 2/24/98 447 RTA00000423F.b.04.3 M00001675D:E10 631 1
1203 2/24/98 448 RTAOOOOO 127A.3.3.1 M00001552A:H 10 13232
1204 2/24/98 449 RTA0000041 1 F.J.16.1 M00003843A:E08 17237
1205 2/24/98 450 RTAOOOOO 1 18A.a.23.1 M00001395A:H02 3500
1206 2/24/98 451 RTAOOOOO 126A.o.22.1 M00001551A:A1 1 81752
1207 2/24/98 452 RTA00000419F.n.13.1 M00003977D:A06 66026
1208 2/24/98 453 RTA00000130A.h.13.1 M00001617A:A01 80790
1209 2/24/98 454 RTA00000418F.n.19.1 M00001659C:F02 28761
1210 2/24/98 455 RTA00000399F.d.23.1 M00001481 B:A07 3310
121 1 2/24/98 456 RTA00000413F.O.06.1 M00005100A:B02 0
1212 2/24/98 457 RTA0000041 1 F.m.l9.1 M00003868D:D1 1 74924
1213 2/24/98 458 RTAOOOOO 130A.a.19.1 M00001605A:A06 0
1214 2/24/98 459 RTA00000419F.k.06.1 M00003871 D:A10 78493
1215 2/24/98 460 RTA00000341 F.J.12.1 M00003987C:G03 12195
1216 2/24/98 461 RTA00000412F.d. l 6.1 M00003906B:H06 26829
1217 2/24/98 462 RTAOOOOO 1 19A.J.23.1 M00001460A:G07 79835
1218 2/24/98 463 RTA00000403F.O.22.1 M00001583A:D01 25076
1219 2/24/98 464 RTA00000195AF.C.12.1 M00003818B:G 12 37582
1219 1/28/98 300 RTAOOOOO 195AF.C.12.1 M00003818B:G 12 37582
1220 2/24/98 465 RTA00000350R.p.l 8.1 M00001676B:F05 1 1460
1221 2/24/98 466 RTA00000406F. 24.1 M00003904D:B12 12767
1222 2/24/98 467 RTAOOOOO 123 A.n.13.2 M00001534A:D03 39167
1223 2/24/98 468 RTA00000423F.C.19.1 M00001680B:E10 40472
1224 2/24/98 469 RTA00000405F.g.24.1 M00001673D:D06 39076
1225 2/24/98 470 RTA0000041 1 FJ.06.1 M00003841C:H08 63545
1226 2/24/98 471 RTA00000419F.C.1 1.1 M00003817B:C04 65504
1227 2/24/98 472 RTA00000135AT.14.2 M00001542A:G 12 79969
1228 2/24/98 473 RTA00000403F.a.05.1 M00001448A:E1 1 18808
1229 2/24/98 474 RTA00000405F.e.l 7.1 M00001669A:C 10 38662
1230 2/24/98 475 RTA0000041 1 F.d.05.1 M00001681C:A08 75812
1231 2/24/98 476 RTA00000345F.h.01. l M00001441 B:D1 1 10834
1232 2/24/98 477 RTA00000418F.d.03.1 M00001567B:G 1 1 76824
1233 2/24/98 478 RTA00000418F.h.08.1 M00001589B:E07 76401
1234 2/24/98 479 RTA00000418F.m.l0.1 M00001651 A:H 1 1 791 10
1235 2/24/98 480 RTA0000041 1 F.i. l 5.1 M00003837C:G08 31612
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
1236 2/24/98 481 RTA00000413F.i.23.1 M000041 18B:F01 63073
1237 2/24/98 482 RTA0000041 1 F.e.24.1 M00003813A:B02 64781
1238 2/24/98 483 RTA00000406F.g.22.1 M00003881 D:C 12 38590
1239 2/24/98 484 RTAOOOOO 126A.n.13.2 M00001551 A:H06 79735
1240 2/24/98 485 RTA00000419F.a.02.1 M00001678A:F05 77993
1241 2/24/98 486 RTA00000346F.I.13.1 M00003980B:C 1 1 7542
1242 2/24/98 487 RTA00000420F.g.05.1 M00004891 B:D01 0
1243 2/24/98 488 RTA00000339F. 23.1 M00001429D:H 12 0
1244 2/24/98 489 RTA00000406F.J.19.1 M00003906A:F12 1685
1245 2/24/98 490 RTAOOOOO 120A.d.15.1 M00001464A:B02 80533
1246 2/24/98 491 RTA00000418FT.21.1 M00001579B:F04 75157
1247 2/24/98 492 RTA00000340F.O.18.1 M00001669D:C03 4261
1248 2/24/98 493 RTAOOOOO 129A.d.1.2 M00001587A:F05 80058
1249 2/24/98 494 RTA00000419F.k.l2.1 M00003876C:F02 0
1250 2/24/98 495 RTA00000400F.O.21.1 M00001669C:C08 16259
1251 2/24/98 496 RTA00000419F.m.20.1 M00003914A:B07 76720
1252 2/24/98 497 RTA00000350R.f.21.1 M00001610C:E07 221 10
1253 2/24/98 498 RTA00000406F.e. l 5.1 M00003877C:A1 1 39074
1254 2/24/98 499 RTAOOOOO 126A.p.18.2 M00001552A:E10 80881
1255 2/24/98 500 RTA0000041 1 F.C.10.1 M00001678D:B1 1 731 17
1256 2/24/98 501 RTA00000414F.f.05.1 M00005257D:H1 1 0
1257 2/24/98 502 RTA00000341 F.d.08.1 M00003824C:D07 0
1258 2/24/98 503 RTA00000420F.m.08.1 M00005233B:D04 0
1259 2/24/98 504 RTA00000413F.d.05.1 M00004087C:A01 64788
1260 2/24/98 505 RTA00000121 A.O.3.1 M0000151 1 A:A02 81437
1261 2/24/98 506 RTA00000403F.f.09.1 M00001477B:C02 0
1262 2/24/98 507 RTA00000420F.e.02.1 M00004107B:D07 40259
1263 2/24/98 508 RTA00000420F.i.20.1 M00005101 C:E12 0
1264 2/24/98 509 RTA00000349R.g. l 0.1 M00001495B:B08 5777
1265 2/24/98 510 RTA00000131 A.g.l 6.2 M00001449A:F01 0
1266 2/24/98 51 1 RTA00000341 F.b.l3.1 M00003762B:H09 0
1267 2/24/98 512 RTA00000414F.C.16.1 M00005228A:B03 0
1268 2/24/98 513 RTA00000126A. 7.2 M00001550A:E07 79866
1269 2/24/98 514 RTA00000404F.e.l3.1 M00001608D:E09 12046
1270 2/24/98 515 RTA00000419F.1.03.1 M00003879A:D02 79060
1271 2/24/98 516 RTA00000339FT.20.1 M00001399A:C03 6494
1272 2/24/98 517 RTA000001 18A.3.2.1 M00001395A:A12 38067
1273 2/24/98 518 RTA00000410F.m. l 8.1 M00001660B:A09 76365
1274 2/24/98 519 RTA00000404F.1.10.1 M00001638B:F10 23136
1275 2/24/98 520 RTA00000406F.C.20.1 M00003871 D:G06 38578
1276 2/24/98 521 RTA00000413F.b. l4.1 M00004078A:C 1 1 66591
1277 2/24/98 522 RTA00000406F.C.18.1 M00003871C:F12 14368
1278 2/24/98 523 RTA00000418F.J.09.1 M00001626C:D12 76352
1279 2/24/98 524 RTA00000419FT.23.1 M00003840D:H 10 65002
1280 2/24/98 525 RTA00000348R.d.24.1 M00001349B:G05 5774
1281 2/24/98 526 RTA0000041 1 F.3.05.1 M00001675B:H03 76699
1282 2/24/98 527 RTA00000419F.m.21.1 M00003914A:E04 77947
1283 2/24/98 528 RTA00000405F.n. l6.1 M00003825B:B10 21503
1284 2/24/98 529 RTA00000422F.O.19.2 M00001655C:E01 13084
1285 2/24/98 530 RTA00000408F.n.02.2 M00001539A:E01 76993
SEQ ID Filing SEQ ID Sequence Nsme Clone Nsme Cluster
NO: Dste of NO: in ID
Priority Priority
Appln Appln
1286 2/24/98 531 RTA00000345F.n.12.1 M00001528A:C04 7337
1287 2/24/98 532 RTA00000403F.a.24.1 M00001455B:A09 24128
1288 2/24/98 RTA00000423F.e. l l .1 M00003809B:E10 2566
1289 2/24/98 534 RTA00000126A.g.7.1 M00001548A:H04 1902
1290 2/24/98 535 RTAOOOOO 1 19A.g.7.1 M00001454A:F1 1 83580
1291 2/24/98 536 RTA0000041 1 F.i.02.1 M00003835B:H 1 1 66975
1292 2/24/98 537 RTA00000408F.1.09.1 M00001530A:A09 75487
1293 2/24/98 538 RTA00000423F.g.04.1 M00003903D:C 12 23012
1294 2/24/98 539 RTA00000346F.m. l 5.1 M00004037B:C04 13553
1295 2/24/98 540 RTA00000418F.U 8.1 M00001595C:B05 78024
1296 2/24/98 541 RTA0000041 1 F.h.l 5.1 M00003832A:A09 65160
1297 2/24/98 542 RTA00000410F.U 9.1 M00001641 B:C 10 78988
1298 2/24/98 543 RTA00000419F.L24.1 M00003878C:G08 75596
1299 2/24/98 544 RTA00000420F.1.21.2 M00005232A:H12 0
1300 2/24/98 545 RTA00000420F.e. l 5.1 M000041 10A:A10 20190
1301 2/24/98 546 RTA00000409F.i.09.1 M00001610B:C07 75279
1302 2/24/98 547 RTA00000419F.h.02.1 M00003845D:G08 63985
1303 2/24/98 548 RTA00000413F.b.l2.1 M00004077B:H1 1 64932
1304 2/24/98 549 RTA00000121A.li.18.1 M00001471 A:B04 16376
1305 2/24/98 550 RTA0000041 1 F.n.20.1 M00003875C:A09 75816
1306 2/24/98 551 RTA00000340F.b.05.1 M00001513A:G07 0
1307 2/24/98 552 RTA0000041 1 F.n.l2.1 M00003875A:C04 73308
1308 2/24/98 553 RTA00000408F.J.12.2 M00001485B:C03 18226
1309 2/24/98 554 RTA00000409F.i.03.1 M00001610A:E09 75968
1310 2/24/98 555 RTAOOOOO 133 A.d.22.1 M00001469A:G1 1 1 1797
131 1 2/24/98 556 RTA00000400F.U 1.1 M00001649C:H10 2587
1312 2/24/98 557 RTA00000409F.J.05.1 M0000161 1 C:C12 74128
1313 2/24/98 558 RTA00000419F.m.04.1 M00003906C:C05 74367
1314 2/24/98 559 RTA00000418F. 03.1 M00001634D:G1 1 78901
1315 2/24/98 560 RTA00000419F.d.l 6.1 M00003828B:E07 64357
1316 2/24/98 561 RTA00000420F.e.l 0.1 M00004108D:G04 65899
1317 2/24/98 562 RTA00000401 F.J.1 7.1 M00003901 B:C05 5483
1318 2/24/98 563 RTA00000406F.b.08.1 M00003867D:A06 18258
1319 2/24/98 564 RTA00000418F.k.08.1 M00001639A:C03 18259
1320 2/24/98 565 RTA00000420F.k.l 7.2 M00005217B:A06 0
1321 2/24/98 566 RTA00000414F.d.05.1 M00005229D:H03 0
1322 2/24/98 567 RTA00000410F.C.02.1 M00001633D:D12 75055
1323 2/24/98 568 RTA00000403F.m.03.1 M00001573D:D10 39179
1324 2/24/98 569 RTA00000403F.h. l 8.1 M00001484C:A04 39241
1325 2/24/98 570 RTA00000405F.n.l3.1 M00003824A:G 10 23810
1326 2/24/98 571 RTA00000355R.e. l4.1 M00004314B:G07 16837
1327 2/24/98 572 RTA00000422F.1.03.1 M00001610D:D05 39147
1328 2/24/98 573 RTA00000414F.C.23.1 M00005229B:G 12 0
1329 2/24/98 574 RTA00000403F.O.14.1 M00001579D:H09 38971
1330 2/24/98 575 RTA00000345F.3.1 8.1 M00001351 C:B06 5517
1331 2/24/98 576 RTA00000401 F.d.l 5.2 M00001693C:C 12 5297
1332 2/24/98 577 RTA00000419F.e.l l . l M00003833B:C 12 36780
1333 2/24/98 578 RTA00000127A.f.l l . l M00001554A:A08 81463
1334 2/24/98 579 RTA00000413F.m. l 6.1 M00004898C:F03 0
1335 2/24/98 580 RTA00000403F.O.07.1 M00001579C:A01 39037
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Dste of NO: in ID Priority Priority Appln Appln
1336 2/24/98 581 RTA00000403F.d. l9.1 M00001472C:A01 39243
1337 2/24/98 582 RTA00000414F.e.l4.1 M00005236B.-F10 0
1338 2/24/98 583 RTA00000406F.i. l 7.1 M00003904B:C03 37902
1339 2/24/98 584 RTA00000418F.d.22.1 M00001573B:C06 75324
1340 2/24/98 585 RTA00000340R.O.12.1 M00003746C:E02 53732
1341 2/24/98 586 RTAOOOOO 125 A.g.24.1 M00001544A:F05 80397
1342 2/24/98 587 RTAOOOOO 130A.O.21.1 M00001623A:F04 80218
1343 2/24/98 588 RTA00000420F.3.23.1 M00004078B:F12 42158
1344 2/24/98 589 RTA0000041 1 F.m. l 8.1 M00003868D:D09 75629
1345 2/24/98 590 RTA00000407F.b.22.1 M00004108B:B02 37487
1346 2/24/98 591 RTA00000409F.3.16.1 M00001583A:A05 73990
1347 2/24/98 592 RTA00000421 F.p.l8.1 M00003877B:H 10 750
1348 2/24/98 593 RTA00000341 F. 12.1 M00004103C:D04 62985
1349 2/24/98 594 RTAOOOOO 129A.C.18.2 M00001587A:B10 37216
1350 2/24/98 595 RTA00000410F.d. l0.1 M00001635B:H02 77561
1351 2/24/98 596 RTA00000351 R.i.03.1 M00003846B:D06 6874
1352 2/24/98 597 RTA00000135A.1.1.2 M00001545A:B 10 39426
1353 2/24/98 598 RTA00000420F.b. l 8.1 M00004086D:G08 66136
1354 2/24/98 599 RTA00000401 F.k. l4.1 M00003903A:H09 21 1
1355 2/24/98 600 RTA00000406F.m.04.1 M00003914B:A1 1 14959
1356 2/24/98 601 RTA00000403F.O.13.1 M00001579D:F04 39049
1357 2/24/98 602 RTA0000041 1F.f.06.1 M00003813B:E09 64186
1358 2/24/98 603 RTA00000399F.O.19.1 M00001607A:F1 1 2594
1359 2/24/98 604 RTA00000351 R.C.13.1 M00003747D:C05 1 1476
1360 2/24/98 605 RTA00000403F.C.14.1 M00001457D:A07 0
1361 2/24/98 606 RTA00000420F.1.20.2 M00005232A:C 10 0
1362 2/24/98 607 RTA00000420F.d.l6.1 M00004103D:F10 64485
1363 2/24/98 608 RTA00000404F.i.l2.1 M00001620D:G 1 1 39001
1364 2/24/98 609 RTA00000404F.O.10.2 M00001651 B:B12 16785
1365 2/24/98 610 RTA00000419F.d.07.1 M00003820B:D10 21421
1366 2/24/98 61 1 RTA00000404F.p.02.2 M00001652D:A06 39097
1367 2/24/98 612 RTAOOOOO 125A. 14.1 M00001545A:G05 79457
1368 2/24/98 613 RTAOOOOO 122A.J.22.1 M00001516A:F06 81 151
1369 2/24/98 614 RTA00000406F. 13.1 M00003904A:C04 37904
1370 2/24/98 615 RTAOOOOO 135 A.b.23.1 M00001538A:D12 35241
1371 2/24/98 616 RTA00000423F.C.1 1.1 M00001677D:B02 0
1372 2/24/98 61 7 RTA00000423FT.23.1 M00003816C:E09 15390
1373 2/24/98 618 RTA00000423F.1.04.1 M00004039B:G08 14320
1374 2/24/98 619 RTA00000420F.b.04.1 M00004081A:E02 63820
1375 2/24/98 620 RTA00000420F.3.07.1 M00004072C:F08 63405
1376 2/24/98 621 RTA00000408F.U 8.2 M00001482C:D02 74410
1377 2/24/98 622 RTA00000404F.1.07.1 M00001637C:C06 10798
1378 2/24/98 623 RTA00000341 F.J.05.1 M00003963D:B05 36177
1379 2/24/98 624 RTA00000420F.a. l 6.1 M00004075D:C 10 63345
1380 2/24/98 625 RTAOOOOO 126A.h.22.2 M00001549A:F01 0
1381 2/24/98 626 RTA00000410F.J.01.1 M00001641 B:F12 73399
1382 2/24/98 627 RTA00000408F.p.21.1 M00001579A:C03 77930
1383 2/24/98 628 RTA00000412F.d.l9.1 M00003907B:C03 75743
1384 2/24/98 629 RTA00000352R.C.04.1 M00003924A:D08 71976
1385 2/24/98 630 RTA00000413F.f. l9.1 M00004100B:C07 65189
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
1386 2/24/98 631 RTA0000041 1 F.e.03.1 M00001694D:C12 73648
1387 2/24/98 632 RTAOOOOO 191 AF.j.14.1 M00004073A:H12 1002
1387 1/28/98 387 RTA00000191 AF.J.14.1 M00004073A:H12 1002
1388 2/24/98 633 RTA00000341 F.d.02.1 M00003797A:G03 4706
1389 2/24/98 634 RTA00000418F.C.04.1 M00001487B:A1 1 41587
1390 2/24/98 635 RTA00000418F.O.17.1 M00001661 B:F03 79069
1391 2/24/98 636 RTA00000418F.e.21.1 M00001577B:A03 74773
1392 2/24/98 637 RTA00000419F.d. l4.1 M00003828A:D05 64945
1393 2/24/98 638 RTA00000418F.b.09.1 M00001478B:H08 19700
1394 2/24/98 639 RTA00000414F.d.09.1 M0000523 1 C:B01 0
1395 2/24/98 640 RTA00000405F.f.02.1 M00001669B:G02 38665
1396 2/24/98 641 RTA00000410F.J.20.1 M00001642D:G 10 73601
1397 2/24/98 642 RTA00000341 F.li.19.1 M00003916C:C05 0
1398 2/24/98 643 RTA00000420F.1.14.2 M00005230D:F06 0
1399 2/24/98 644 RTA000001 19A.J.9.1 M00001460A:B 12 82060
1400 2/24/98 645 RTA00000422F.p. l2.2 M00001661 C:F10 9840
1401 2/24/98 646 RTA00000421 F.m. l 4.1 M00001642A:F03 3524
1402 2/24/98 647 RTA00000418F.b.23.1 M00001485A:C05 28767
1403 2/24/98 648 RTA00000340F.U3.1 M00001624B:B10 79299
1404 2/24/98 649 RTA00000412F.g.03.1 M00003971 B:A10 64740
1405 2/24/98 650 RTAOOOOO 122A.g.17.1 M00001514A:B08 32655
1406 2/24/98 651 RTA00000403F.g. l l .l M00001481 A:H08 24238
1407 2/24/98 652 RTA00000419F.n.l2.1 M00003977D:A03 66086
1408 2/24/98 653 RTA00000352R.m.l2.1 M00004212B:C07 2379
1409 2/24/98 654 RTA00000421 F.a.05.1 M00001570C:G06 5278
1410 2/24/98 655 RTA00000351 R.p. l4.1 M00003915C:H04 13166
141 1 2/24/98 656 RTA00000403F.e.08.1 M00001473D:B 1 1 19126
1412 2/24/98 657 RTAOOOOO 124A. 20.1 M00001538A:C08 80913
1413 2/24/98 658 RTA00000121 A.n.2.1 M0000151 1 A:A05 33585
1414 2/24/98 659 RTA00000422F.m.24.1 M00001641 D:C04 39159
1415 2/24/98 660 RTA00000408F.e.24.2 M00001476C:C 1 1 75002
1416 2/24/98 661 RTA00000341 F.1.16.1 M00003986D:C08 8479
1417 2/24/98 662 RTA00000339F.O.07.1 M00001473D:G01 2566
1418 2/24/98 663 RTA00000403F.b. l2.1 M00001455D:A06 78775
1419 2/24/98 664 RTA00000404F.3.09.1 M00001589C:E06 38985
1420 2/24/98 665 RTA00000419F.p.20.1 M00004039A:C03 9458
1421 2/24/98 666 RTA00000403F.O.19.1 M00001582D:F02 78615
1422 2/24/98 667 RTA00000405F.h.07.2 M00001674A:G1 1 4984
1423 2/24/98 668 RTA00000408F.m.05.2 M00001530C:G 10 23384
1424 2/24/98 669 RTA00000410F.b. l0.1 M00001633C:B09 74504
1425 2/24/98 670 RTA00000131 A.i.6.1 M00001450A:B08 0
1426 2/24/98 671 RTA00000413F.h. l2.1 M00004107A:A12 66929
1427 2/24/98 672 RTA00000406F.L 14.1 M00003907C:C02 38651
1428 2/24/98 673 RTA00000406F.d.09.1 M00003875B:F12 38591
1429 2/24/98 674 RTA0000041 1 F.f. l 7.1 M00003814B:F12 65661
1430 2/24/98 675 RTA0000041 1 F. 10.1 M00003850D:H 1 1 64506
1431 2/24/98 676 RTA0000041 1 F.g.21.1 M00003823D:G05 64500
1432 2/24/98 677 RTAOOOOO 1 19A.h.24.1 M00001457A:C05 82266
1433 1/28/98 412 RTAOOOOO 195 AF.c.24.1 M00003860D:H07 0
1433 2/24/98 678 RTA00000195AF.C.24.1 M00003860D:H07 0
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
1434 2/24/98 679 RTA00000408F.m.22.2 M00001539A:C 12 72949
1435 2/24/98 680 RTA00000345F.e.l l . l M00001391C:C04 4392
1436 2/24/98 681 RTAOOOOO 120 A.c.24.1 M00001464A:D03 34278
1437 2/24/98 682 RTA00000410F.i.l 7.1 M00001641 B:B01 78147
1438 2/24/98 683 RTA00000403F.J.21.1 M00001540D:E02 24723
1439 2/24/98 684 RTA00000339F.k.20.1 M00001426D:D12 6662
1440 2/24/98 685 RTA00000129A.a. l3.2 M00001582A:A03 79780
1441 2/24/98 686 RTAOOOOO 129A.L21.1 M00001601 A:E12 82067
1442 2/24/98 687 RTA00000350R.g.l 0.1 M00001587C:C10 9026
1443 2/24/98 688 RTA00000413F.d.23.1 M00004090B:H06 66030
1444 2/24/98 689 RTA00000419F.p.03.1 M00004035A:G10 1937
1445 2/24/98 690 RTA00000341 F.b.05.1 M00003793D:A1 1 0
1446 2/24/98 691 RTA00000354R.n.08.1 M00003835A:A09 8802
1447 2/24/98 692 RTA0000041 1 F.d. l 0.1 M00001681 D:C 12 76445
1448 2/24/98 693 RTA00000404F.b. l9.1 M00001592B:A04 39281
1449 2/24/98 694 RTA00000418F.C.07.1 M00001529D:C05 73245
1450 2/24/98 695 RTA00000418F.J.15.1 M00001632C:H07 74855
1451 2/24/98 696 RTA00000404F.p. l2.2 M00001653B:C06 0
1452 2/24/98 697 RTA00000412F.d. l4.1 M00003905D:CO8 76757
1453 2/24/98 698 RTA00000413F.b.l 6.1 M00004078A:E05 65126
1454 2/24/98 699 RTA00000340F.1.05.1 M00001644B:D06 38935
1455 2/24/98 700 RTA00000350R.m. l4.1 M00001644C:B07 39171
1456 2/24/98 701 RTA00000418F.1.1 1.1 M00001641C:H07 77158
1457 2/24/98 702 RTA00000130A.d.5.1 M00001605A:H03 82051
1458 2/24/98 703 RTA00000339F.n.05.1 M00001449D:B01 39648
1459 2/24/98 704 RTA00000355R.a. l2.1 M00004159C:F09 36756
1460 2/24/98 705 RTA00000407F.a.23.1 M00004081 C:A10 23489
1461 2/24/98 706 RTA00000403F.a.09.1 M00001448B:H05 77820
1462 2/24/98 707 RTA00000403F.Ii.1 1.1 M00001483B:D04 39219
1463 2/24/98 708 RTA00000406F.J.13.1 M00003905D:B08 38688
1464 2/24/98 709 RTA00000352R.p.09.1 M00004228C:H03 16915
1465 2/24/98 710 RTA00000413F.g.24.1 M00004104D:A04 65481
1466 2/24/98 71 1 RTA00000404F.1.03.2 M00001636B:G 1 1 40272
1467 2/24/98 712 RTA00000407F.b. l 8.1 M00004102C:D09 37569
1468 2/24/98 713 RTA00000414F.b.l0.1 M00005212D:D09 0
1469 2/24/98 714 RTA00000420F.a.08.1 M00004073A:D10 19473
1470 2/24/98 715 RTA00000418F.b.01.1 M00001475C:G1 1 76040
1471 2/24/98 716 RTA00000420F.1.03.2 M00005217D:F12 0
1472 2/24/98 717 RTA00000404F.i.22.1 M00001625C:G05 39082
1473 2/24/98 718 RTA00000124A.L23.1 M00001538A:D03 81350
1474 2/24/98 719 RTA00000404F.e.l l .l M00001608C:E1 1 38991
1475 2/24/98 720 RTAOOOOO 129A.d.2.4 M00001587A:G06 801 19
1476 2/24/98 721 RTA00000422F.k. l4.1 M00001649D:A08 0
1477 2/24/98 722 RTA0000041 1 F.1.22.1 M00003858B:G05 64439
1478 2/24/98 723 RTA00000419F.O.15.1 M00003989C:D03 32487
1479 2/24/98 724 RTAOOOOO 1 19A.m.17.1 M00001461 A:F05 79536
1480 2/24/98 725 RTA00000410F.b.07.1 M00001633C:A05 78916
1481 2/24/98 726 RTA00000420F.b.l9.1 M00004088D:A1 1 36873
1482 2/24/98 727 RTA00000414F.d.02.1 M00005229B:H06 0
1483 2/24/98 728 RTA0000041 1 F.b.21.1 M00001677B:A02 10051
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
1484 2/24/98 729 RTA00000403F.m.20.1 M00001576A:F1 1 707
1485 2/24/98 730 RTA00000356R.C.16.1 M00004294C:C08 16915
1486 2/24/98 73 1 RTAOOOOO 1 19A.d.17.1 M00001453A:B01 0
1487 2/24/98 732 RTA00000412F.h. l l . l M00003974B:B1 1 63175
1488 2/24/98 733 RTA00000405F.d. l 8.1 M00001662C:B02 10494
1489 2/24/98 734 RTA00000414F.e.09.1 M00005236A:G 10 0
1490 2/24/98 735 RTA00000420F.a.l l . l M00004073C:D04 66460
1491 2/24/98 736 RTAOOOOO 120A.C.7.1 M00001462A:D03 80985
1492 2/24/98 737 RTA00000404F.e. l 5.1 M00001609B:C09 39101
1493 2/24/98 738 RTA00000422F.n.20.1 M00001669B:B12 38676
1494 2/24/98 739 RTA00000423F.h.20.1 M00003914A:G06 38639
1495 2/24/98 740 RTA00000399F.1.19.1 M00001590D:G07 40145
1496 2/24/98 741 RTA00000414F.b. l2.1 M00005212D:H01 0
1497 2/24/98 742 RTA00000410F.b.l 8.1 M00001633C:H 1 1 76701
1498 2/24/98 743 RTA00000345F.i.08.1 M00001449D:G 10 0
1499 2/24/98 744 RTA00000423F.g. l 5.1 M00003905A:F09 35173
1500 2/24/98 745 RTA00000413F.b.04.1 M00004076D:H07 66427
1501 2/24/98 746 RTA00000345F.e.02.1 M00001395A:E03 0
1502 2/24/98 747 RTA00000413F.n.24.1 M00004960C:E10 0
1503 2/24/98 748 RTA00000346F.f.l l . l M00003793C:D09 38528
1504 2/24/98 749 RTA00000351 R.i.l3.1 M00003858D:F12 0
1505 2/24/98 750 RTA00000403F.C.05.1 M00001456C:C1 1 74935
1506 2/24/98 751 RTA00000422F.i.02.1 M00001456C:B12 76436
1507 2/24/98 752 RTA00000410F.a.08.1 M00001632A:B10 73324
1508 2/24/98 753 RTA00000345F.O.13.1 M00001546B:F12 1 1500
1509 2/24/98 754 RTA00000419F.e.02.1 M00003830C:A03 65010
1510 2/24/98 755 RTA00000423F.d.l 7.1 M00001663A:C1 1 20630
151 1 2/24/98 756 RTA00000403F.g.l 3.1 M00001481 B:D09 38718
1512 2/24/98 757 RTA00000423F.h.l3.1 M00003871A:B09 14398
1513 2/24/98 758 RTA00000407F.3.01.1 M00004039A:H 1 1 12501
1514 2/24/98 759 RTA00000399F.O.06.1 M00001595D:G03 13574
1515 2/24/98 760 RTA00000423F.d.04.1 M00001694A:B 12 1 1307
1516 2/24/98 761 RTA0000041 1 F.f.l4.1 M00003814B:C12 62984
1517 2/24/98 762 RTA0000041 1 F.C.04.1 M00001677B:E06 76858
1518 2/24/98 763 RTA00000135A.m. l 8.1 M00001545A:C03 19255
1519 2/24/98 764 RTA00000413F.C.17.1 M00004085B:B05 36831
1520 2/24/98 765 RTA00000137A.J.15.4 M00001559A:C08 4213
1521 2/24/98 766 RTA00000404F.J.01.1 M00001625D:G10 26859
1522 2/24/98 767 RTA00000138A.p. l 0.1 M00001644A:H01 81625
1523 2/24/98 768 RTA00000121 A.k.5.1 M00001507A:E04 17530
1524 2/24/98 769 RTA00000340F.L10.1 M00001618A:F10 38561
1525 2/24/98 770 RTA00000421 F.f.05.1 M00001477B:E02 5266
1526 2/24/98 771 RTA00000423F.h.07.1 M0000391 1 B:F08 37933
1527 2/24/98 772 RTA00000413F.e.04.1 M00004090C:C07 64176
1528 2/24/98 773 RTA00000406F.h.03.1 M00003901 B:A09 38585
1529 2/24/98 774 RTA00000403F.e.24.1 M00001476B:D10 16432
1530 2/24/98 775 RTA00000405F.C.22.1 M00001660C:B06 39053
1531 2/24/98 776 RTA00000403F...1 1.1 M00001485D:E05 23535
1532 2/24/98 777 RTA00000419F.g.02.1 M00003842A:A03 62839
1533 2/24/98 778 RTA00000347F.e.05.1 M00001578D:C04 39814
SEQ ID Filing SEQ ID Sequence Name Clone Nsme Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
1534 2/24/98 779 RTA00000408F.1.16.1 M00001530A:F12 73468
1535 2/24/98 780 RTA00000405F.I.1 1.1 M00001693D:E08 2055
1536 2/24/98 781 RTA00000423F.f.09.1 M00003808C:A05 64823
1537 2/24/98 782 RTA00000419F.k.03.1 M00003871 C:B05 40822
1538 2/24/98 783 RTA00000406F.b.02.1 M00003867B:G08 38744
1539 2/24/98 784 RTA00000418F.O.14.1 M00001661 B:B05 33524
1540 2/24/98 785 RTA00000404F.1.03.1 M00001636B:G 1 1 40272
1541 2/24/98 786 RTA00000404F.b.09.1 M00001591 D:C07 39166
1542 2/24/98 787 RTA00000345F.i.24.1 M00001449C:C05 0
1543 2/24/98 788 RTA00000419F.i.04.1 M00003860B:F1 1 65791
1544 2/24/98 789 RTA00000423F.b.l3.1 M00001676C:E07 20619
1545 2/24/98 790 RTA00000345F.n.08.1 M00001517A:B1 1 0
1546 2/24/98 791 RTA00000399F.n. l5.1 M00001594D:C03 3213
1547 2/24/98 792 RTA00000406F.k. l l . l M00003907B:D05 38715
1548 2/24/98 793 RTA00000414F.e.21 .1 M00005257C:G01 0
1549 2/24/98 794 RTA00000406F.C.06.1 M00003870C:A01 37924
1550 2/24/98 795 RTA00000418F.n.07.1 M00001658B:A07 76316
1551 2/24/98 796 RTA00000419F.n.15.1 M00003977D:D04 63484
1552 2/24/98 797 RTA00000408F.n.06.2 M00001539A:H 12 76642
1553 2/24/98 798 RTA00000420F.C.04.1 M00004089A:B08 65007
1554 2/24/98 799 RTA0000041 1 F.J.15.1 M00003843A:E04 66871
1555 2/24/98 800 RTA00000403F.m.l2.1 M00001575D:A02 16933
1556 2/24/98 801 RTA00000128A.m.23.1 M00001561A:D01 81441
1557 2/24/98 802 RTA00000406F.g.03.1 M00003880B:D1 1 38690
1558 2/24/98 803 RTA00000405F.h.05.2 M00001674A:G07 75706
1559 2/24/98 804 RTAOOOOO 129A.n.24.1 M00001604A:C07 81409
1560 2/24/98 805 RTA00000406F.J.08.1 M00003905B:C06 6688
1561 2/24/98 806 RTA00000345F.f.08.1 M00001413B:H09 0
1562 2/24/98 807 RTA00000418F.11.1 1.1 M00001658D:G12 78977
1563 2/24/98 808 RTA00000418F.p.08.1 M00001669D:D06 73983
1564 2/24/98 809 RTA00000420F.i.23.1 M00005134A:D1 1 0
1565 2/24/98 810 RTAOOOOO 120A.h.9.1 M00001465A:B 12 80736
1566 2/24/98 81 1 RTA00000413F.a.l2.1 M00004072D:F09 63403
1567 2/24/98 812 RTA00000412F.O.05.1 M00004034A:A01 63575
1568 2/24/98 813 RTA00000346F.O.06.1 M00004136D:B02 4937
1569 2/24/98 814 RTA00000408F.1.24.1 M00001530B:G09 34263
1570 2/24/98 815 RTA00000403F.3.17.1 M00001448D:E12 13686
1571 2/24/98 816 RTA00000354R.11.04.1 M00003808C:B05 22049
1572 2/24/98 81 7 RTA00000420F.1.08.2 M00005228C:C05 0
1573 2/24/98 818 RTA00000406F.h.05.1 M00003901 B:C03 38542
1574 2/24/98 819 RTA00000410F.b.24.1 M00001633D:D09 75104
1575 2/24/98 820 RTA00000423F.d. l l . l M00001678C:C06 38950
1576 2/24/98 821 RTA00000420F.h.l 6.1 M00004927A:E06 0
1577 2/24/98 822 RTA00000419F.O.21.1 M00004031A:E01 10336
1578 2/24/98 823 RTAOOOOO 1 19A. 1.1 M00001460A:H1 1 81282
1579 2/24/98 824 RTA00000420F.f.07.1 M000041 19A:C09 66312
1580 2/24/98 825 RTA00000404F.k.22.2 M00001635D:C12 39084
1581 2/24/98 826 RTA00000422F.e.07.1 M00001579C:G05 38964
1582 2/24/98 827 RTA00000410FT.12.1 M00001637C:E03 73883
1583 2/24/98 828 RTA00000419F.n.05.1 M00003976C:D06 63713
SEQ ID Filing SEQ ID Sequence Name Clone Nsme Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
1584 2/24/98 829 RTA0000041 1 F.m. l l . l M00003867A:D12 73196
1585 2/24/98 830 RTA00000347F.b.08.1 M00001541 B:E05 17591
1586 2/24/98 831 RTA00000420F.d.21.1 M00004107B:B04 65313
1587 2/24/98 832 RTA00000403F.O.10.2 M00001579C:G05 38964
1588 2/24/98 833 RTA00000420F.J.20.1 M00005140D:C06 0
1589 2/24/98 834 RTA00000407F.b. l l . l M00004090C:C10 0
1590 2/24/98 835 RTA00000413F.C.10.1 M00004083B:C01 65600
1591 2/24/98 836 RTA0000041 1 F.b. l 7.1 M00001676D:B02 72893
1592 2/24/98 837 RTA00000420F.h.01.1 M00004897C:D06 0
1593 2/24/98 838 RTA00000408F.U 9.1 M00001487C:G03 77593
1594 2/24/98 839 RTA00000414F.b.01.1 M00005212B:A02 0
1595 2/24/98 840 RTA00000420F.b.20.1 M00004088D:B05 0
1596 2/24/98 841 RTA000001 19A.i.8.1 M00001457A:G 12 82593
1597 2/24/98 842 RTA00000401 F.n.23.1 M00003982A:B06 1552
1598 2/24/98 843 RTA00000418F.g.03.1 M00001579C:E06 78737
1599 2/24/98 844 RTA0000041 1 F.3.09.1 M00001675C:F01 78629
1600 2/24/98 845 RTA00000348R.b.04.1 M00001342B:E01 1890
1601 2/24/98 846 RTA00000419F.J.1 1.1 M00003868C:C07 73183
1602 2/24/98 847 RTA00000403F.1.1 1.1 M00001571 D:F05 25073
1603 2/24/98 848 RTA00000404F.n.l 8.2 M00001649C:E1 1 37169
1604 2/24/98 849 RTA00000122A.n. l 6.1 M00001517A:G08 80553
1605 2/24/98 850 RTA00000420F.C.07.1 M00004089A:E02 65555
1606 2/24/98 851 RTA00000423F.d.07.1 M00001678B:B12 0
1607 2/24/98 852 RTA00000414F.f.03.1 M00005257D:G07 0
1608 2/24/98 853 RTA00000408F .13.2 M00001485B:D10 42275
1609 2/24/98 854 RTA00000345F.3.07.1 M00001338C:E10 0
1610 2/24/98 855 RTA00000423F.3.01.1 M00001659C:F10 39103
161 1 2/24/98 856 RTA00000408F.d.02.1 M00001458D:A01 79169
1612 2/24/98 857 RTA00000404F.e.09.1 M00001608B:A09 39121
1613 2/24/98 858 RTA00000341 F.e.20.1 M00003891 D:B 10 67422
1614 2/24/98 859 RTA00000419F.m.22.1 M00003914A:G09 75600
1615 2/24/98 860 RTA00000419F.m.23.1 M00003958B:E1 1 64263
1616 2/24/98 861 RTA00000419F.b.06.1 M00001694B:B08 76728
1617 2/24/98 862 RTA00000414F.C.07.1 M00005216A:H01 0
1618 2/24/98 863 RTA00000406F.p.08.1 M00004032C:B02 37573
1619 2/24/98 864 RTA00000129A.n.17.1 M00001604A:A09 7981 1
1620 2/24/98 865 RTA00000414F.C.03.1 M00005216A:D09 0
1621 2/24/98 866 RTA00000407F.b.08.1 M00004088D:B03 37513
1622 2/24/98 867 RTA00000339F.1.21.1 M00001455D:D1 1 9781
1623 2/24/98 868 RTA00000406F.i.08.1 M00003903C:E12 37946
1624 2/24/98 869 RTA00000403F.h.07.1 M00001482D:H 1 1 26856
1625 2/24/98 870 RTA00000418F.n.24.1 M00001659D:C09 73153
1626 2/24/98 871 RTA00000403F.f.23.1 M00001479C:E01 39223
1627 2/24/98 872 RTA00000409F.1.20.1 M00001615B:G01 74394
1628 2/24/98 873 RTA00000418F.1.06.1 M00001641 C:F01 73317
1629 2/24/98 874 RTA00000346F.O.22.1 M00004300C:H09 7381
1630 2/24/98 875 RTAOOOOO 129A. 22.1 M00001601 A:E02 79639
1631 2/24/98 876 RTA00000423F.d. l 6.1 M00001678D:C 1 1 39173
1632 2/24/98 877 RTA00000418F.m.22.1 M00001654D:E12 74567
1633 2/24/98 878 RTA00000413F.C.12.1 M00004083B:G03 65334
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Dste of NO: in ID
Priority' Priority
Appln Appln
1634 2/24/98 879 RTA00000409F.b. l 9.1 M00001584D:H02 14479
1635 2/24/98 880 RTA00000418F.g.20.1 M00001585B:C03 74626
1636 2/24/98 881 RTA00000413F.d. l 5.1 M00004088C:E04 64943
1637 2/24/98 882 RTA00000355R.C.03.1 M00004244C:G07 3986
1638 2/24/98 883 RTA00000406F.C.09.1 M00003870C:E10 5671
1639 2/24/98 884 RTA00000412F.C.10.1 M00003903C:C04 76372
1640 2/24/98 885 RTA00000122A.J.17.1 M00001516A:D02 62736
1641 2/24/98 886 RTA00000420F.m.l 5.1 M00005235B:F10 0
1642 2/24/98 887 RTA00000339F.p.06.1 M00001484A:A10 4880
1643 2/24/98 888 RTA00000339R.C.04.1 M00001362D:H01 1805
1644 2/24/98 889 RTA00000346F.b. l 6.1 M00001615C:G05 16485
1645 2/24/98 890 RTA00000418F.J.19.1 M00001634D:D02 78399
1646 2/24/98 891 RTA00000137A.p. l 2.1 M00001587A:B01 80614
1647 2/24/98 892 RTA00000339F.m. l 7.1 M00001453B:H 12 20854
1648 2/24/98 893 RTA00000418F.p.l 0.1 M00001669D:F05 75323
1649 2/24/98 894 RTA00000408F.k. l 2.1 M00001486B:D07 77246
1650 2/24/98 895 RTAOOOOO 137A.j.1 1.4 M00001559A:A1 1 79752
1651 2/24/98 896 RTA00000423F.1.20.1 M00004105C:E09 12580
1652 2/24/98 897 RTA00000419F.H.24.1 M00003980A:F04 65995
1653 2/24/98 898 RTA00000418F.1.03.1 M00001641 C:C06 79058
1654 2/24/98 899 RTA00000406F.h.l0.1 M00003901 C:F09 22732
1655 2/24/98 900 RTA00000419F.m.l 3.1 M00003908A:F12 79052
1656 2/24/98 901 RTA00000418F .14.1 M00001632C:B10 32623
1657 2/24/98 902 RTA00000403F.3.10.1 M00001448C:E1 1 73952
1658 2/24/98 903 RTA00000420F.3.21.1 M00004078B:C1 1 66241
1659 2/24/98 904 RTA00000127A.e.6.1 M00001553A:E07 5885
1660 2/24/98 905 RTA00000405F.g.21.2 M00001673B:F07 38966
1661 2/24/98 906 RTA00000405F.g.21.1 M00001673B:F07 38966
1662 2/24/98 907 RTA00000419F.m.06.1 M00003906C:D06 75749
1663 2/24/98 908 RTA00000423F.g.03.1 M00003905C:G1 1 38007
1664 2/24/98 909 RTA00000420F.i.04.1 M00004959D:H 12 0
1665 2/24/98 910 RTA00000418F.f.03.1 M00001577B:F10 7891 1
1666 2/24/98 91 1 RTA00000406F.p. l3.1 M00004034C:G02 8584
1667 2/24/98 912 RTA00000404F.g. l3.1 M00001614C:E06 9436
1668 2/24/98 913 RTAOOOOO 120A.C.20.1 M00001464A:B07 43235
1669 2/24/98 914 RTA00000138A.m.l 5.1 M00001624A:A03 41603
1670 2/24/98 915 RTA00000408F.f.l4.2 M00001476D:F03 73024
1671 2/24/98 916 RTA00000418F.p.20.1 M00001677D:B07 78023
1672 2/24/98 917 RTA00000423F.e.21.1 M00003806B:G05 66961
1673 2/24/98 918 RTA00000419F.J.22.1 M00003871 A:A02 73525
1674 2/24/98 919 RTA00000410F.d. l 8.1 M00001635D:D05 75458
1675 2/24/98 920 RTA00000403F.b.24.1 M00001456B:G01 78838
1676 2/24/98 921 RTA00000422F.J.02.1 M00001594D:B08 10368
1677 2/24/98 922 RTA00000410F.e.09.1 M00001636A:F08 76093
1678 2/24/98 923 RTAOOOOO 126A.d.19.1 M00001548A:G01 79474
1679 2/24/98 924 RTA00000354R.m.02.1 MO0003890B:C08 12766
1680 2/24/98 925 RTA00000353R.li.10.1 M00001390C:C 1 1 39498
1681 2/24/98 926 RTA00000399F. 20.1 MO0OO1585C:D10 3003
1682 2/24/98 927 RTA0000041 1 F.d.21.1 M00001692B:E01 74794
1683 2/24/98 928 RTA00000340F.m.04.1 M00001679B:H07 19406
SEQ ID Filing SEQ ID Sequence Nsme Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
1684 2/24/98 929 RTA0000041 1 F.n.09.1 M00003875A:A07 78962
1685 2/24/98 930 RTAOOOOO 127A.h.22.2 M00001554A:E04 13155
1686 2/24/98 931 RTA00000420F.e.09.1 M00004108D:E07 66325
1687 2/24/98 932 RTA00000405F.p.03.1 M00003844A:A1 1 1 1346
1688 2/24/98 933 RTA00000419F.3.18.1 M00001680A:B02 78484
1689 2/24/98 934 RTA00000414F.e.01.1 M00005233D:H07 0
1690 2/24/98 935 RTA00000420F.L07.1 M00004960A:B08 0
1691 2/24/98 936 RTA00000121 A.n.23.1 M0000151 1 A:G01 26981
1692 2/24/98 937 RTA00000121 A.11.15.1 M0000151 1 A:G08 40849
1693 2/24/98 938 RTA00000403F.i.23.1 M00001487B:E10 1 1364
1694 2/24/98 939 RTA00000405F.a.03.1 M00001654C:E04 39065
1695 2/24/98 940 RTA00000414F .17.1 M00005260A:F04 0
1696 2/24/98 941 RTA00000419F.p.08.1 M00004036D:B04 65560
1697 2/24/98 942 RTA00000126A.n.6.2 M00001551 A:D04 79917
1698 2/24/98 943 RTA00000413F.C.03.1 M00004081 D:H09 64527
1699 2/24/98 944 RTA00000422F.L24.1 M00001610C:E06 391 18
1700 2/24/98 945 RTA00000412F.C.17.1 M00003905A:A06 75620
1701 2/24/98 946 RTA00000414F.b.07.1 M00005212C:D02 0
1702 2/24/98 947 RTA00000347F.g.08.1 M00004096B:F05 23121
1703 2/24/98 948 RTA00000419F.O.06.1 M00003986C:D09 64643
1704 2/24/98 949 RTA00000340R.J.07.1 M00001654C:D05 38954
1705 2/24/98 950 RTA00000423F.J.02.1 M00003903B:C02 38617
1706 2/24/98 951 RTA00000419F.C.04.1 M00003815C:D12 63749
1707 2/24/98 952 RTA0000041 1 F.3.01.1 M00001675B:D02 74524
1708 2/24/98 953 RTA00000406F.f.05.1 M00003878C:F06 22961
1709 2/24/98 954 RTA00000410F.n.05.1 M00001662A:C07 77830
1710 2/24/98 955 RTA00000404F.e.06.1 M00001607D:F06 39315
171 1 2/24/98 956 RTA00000423F.I.06.1 M00004062A:H06 38136
1712 2/24/98 957 RTA0000041 1 F.C.03.1 M00001677B:B06 79280
1713 2/24/98 958 RTA00000195AF.C.8.1 M00001678B:H01 0
1713 1/28/98 520 RTAOOOOO 195 AF.c.8.1 M00001678B:H01 0
1714 2/24/98 959 RTA00000340F.g.20.1 M00001609D:G 10 4089
1715 2/24/98 960 RTA00000404F.1.19.2 M00001639B:H01 16196
1716 2/24/98 961 RTA00000420F.n.21.2 M00005259B:D12 0
1717 2/24/98 962 RTA00000404F.p.05.2 M00001652D:E09 1896
1718 2/24/98 963 RTA00000405F.1.07.1 M00001693C:E09 38636
1719 2/24/98 964 RTA00000423F.1.15.1 M00004075B:G09 1 1219
1720 2/24/98 965 RTA0000041 1 F.11.06.1 M00003871 D:E1 1 73886
1721 2/24/98 966 RTA00000422F.k. l 5.1 M00001594A:G09 19253
1722 2/24/98 967 RTA00000406F.h. l6.1 M00003902B:D06 38618
1723 2/24/98 968 RTA00000419F.f.24.1 M00003841 B:E06 18717
1724 2/24/98 969 RTA0000041 1 F.d.l 8.1 M00001692A:G06 76063
1725 2/24/98 970 RTA00000414F.e. l 5.1 M00005236B:G03 0
1726 2/24/98 971 RTA0000041 1 F.Ϊ.1 1.1 M00003837C:E05 66849
1727 2/24/98 972 RTA00000408F.d. l 5.1 M00001459B:C1 1 78467
1728 2/24/98 973 RTA00000339F.b.22.1 M00001373D:B03 6867
1729 2/24/98 974 RTA00000340F.h.07.1 M00001608D:D1 1 19254
1730 2/24/98 975 RTA0000041 1 F.n.02.1 M00003870B:F04 78049
1731 2/24/98 976 RTA00000419F.b. l 7.1 M00003808D:D04 63261
1732 2/24/98 977 RTA00000350R.p. l 2.1 M00001657C:C07 0
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Dste of NO: in ID
Priority Priority
Appln Appln
1733 2/24/98 978 RTA00000130A.e.20.1 M00001606A:H09 79502
1734 2/24/98 979 RTA00000345F.b.l7.1 M00001362C:H11 945
1735 2/24/98 980 RTA00000411F.i.l3.1 M00003837C:F10 66138
1736 2/24/98 981 RTA00000420F.e.20.1 M00004110B:A07 64762
1737 2/24/98 982 RTAOOOOO 126A.p.23.2 M00001552A:F06 80915
1738 2/24/98 983 RTA00000423F.f.ll.l M00003809A:H04 0
1739 2/24/98 984 RTA00000406F.g.08.1 M00003880C:H03 37963
1740 2/24/98 985 RTA00000409F.a.08.1 M00001582D:B01 74978
1741 2/24/98 986 RTA00000406F.d.24.1 M00003876B:C05 37997
1742 2/24/98 987 RTA00000422F.b.22.1 M00004117B:A12 2368
1743 2/24/98 988 RTA00000407F.3.22.1 M00004081A:G01 15570
1744 2/24/98 989 RTA00000418F.U2.1 M00001592A:E02 78971
1745 2/24/98 990 RTA00000121A.h.l9.1 M00001471A:D04 80334
1746 2/24/98 991 RTA00000419F.b.l0.1 M00001694C:G04 78566
1747 2/24/98 992 RTA00000406F.m.l0.1 M00003914D:B02 38004
1748 2/24/98 993 RTA00000406F.O.05.1 M00003985B:G04 37894
1749 2/24/98 994 RTA00000408F.b.04.2 M00001455A:F04 39933
1750 2/24/98 995 RTA00000411F.k.04.1 M00003850D:A05 65407
1751 2/24/98 996 RTA00000423F.J.03.1 M00003903B:D03 5391
1752 2/24/98 997 RTAOOOOO 134A.1.9.1 M00001535A:D10 81814
1753 2/24/98 998 RTA00000341F.g.22.1 M00003914D:D10 0
1754 2/24/98 999 RTA00000418F.k.04.1 M00001637A:A03 75864
1755 2/24/98 1000 RTA00000351R.J.21.1 M00003859D:C05 31604
1756 2/24/98 1001 RTA00000413F.p.07.2 M00005102C:D03 0
1757 2/24/98 1002 RTA00000419F.p.l8.1 M00004038D:G06 63002
1758 2/24/98 1003 RTA00000420F. 08.2 M00005176C:C09 0
1759 2/24/98 1004 RTA00000419F.a.24.1 M00001680B:D02 79290
1760 2/24/98 1005 RTA00000339F.e.l7.1 M00001397D:G08 7568
1761 2/24/98 1006 RTAOOOOO 129A.e.14.1 M00001587A:F08 80053
1762 2/24/98 1007 RTA00000404F.a.01.1 M00001589B:B08 19251
1763 2/24/98 1008 RTA00000414F.f.07.1 M00005259C:B05 0
1764 2/24/98 1009 RTA00000399F.O.24.1 M00001607D:A11 2272
1765 2/24/98 1010 RTA00000408F.n.l6.2 M00001540C:B03 73720
1766 2/24/98 1011 RTA00000400F.C.04.1 M00001618A:F08 6445
1767 2/24/98 1012 RTA00000403F.g.06.1 M00001480C:A05 10505
1768 2/24/98 1013 RTA00000404F.b.l8.1 M00001592A:H05 13669
1769 2/24/98 1014 RTA00000412F.1.14.1 M00004029B:F01 62792
1770 2/24/98 1015 RTA00000129A.b.6.2 M00001582A:H01 39111
1771 2/24/98 1016 RTA00000406F.n.l2.1 M00003960A:G07 37517
1772 2/24/98 1017 RTA00000418F.e.03.1 M00001573B:G08 73442
1773 2/24/98 1018 RTA00000413F.J.21.1 M00004688A:A02 0
1774 2/24/98 1019 RTA00000403F.g.03.1 M00001479D:G06 23537
1775 2/24/98 1020 RTA00000412F.p.06.1 M00004038B:H10 65485
1776 2/24/98 1021 RTA00000419F.b.21.1 M00003809A:F0! 65366
1777 2/24/98 1022 RTA00000401F.J.15.1 M00003901A:C09 3061
1778 2/24/98 1023 RTA00000404F.f.l2.1 M00001611B:A05 39209
1779 2/24/98 1024 RTA00000351R.J.16.1 M00003857B:F07 64773
1780 2/24/98 1025 RTAOOOOO 118A.J .24.1 M00001450A:B03 18
1781 2/24/98 1026 RTA00000419FT.18.1 M00003839D:E11 64047
1782 2/24/98 1027 RTA00000423F.i.l6.1 M00003907D:A12 38604
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
1783 2/24/98 1028 RTA00000346F.d.l2.1 M00001676B:B09 1 1777
1784 2/24/98 1029 RTA0000041 1 F.f.04.1 M00003813A:G04 64526
1785 2/24/98 1030 RTAOOOOO 125A.C 17.1 M00001542A:E04 80619
1786 2/24/98 1031 RTA00000404F.g.08.1 M00001613D:H 10 38980
1787 2/24/98 1032 RTA00000423F.C.13.1 M00001678A:A1 1 39059
1788 2/24/98 1033 RTA00000414F.e.l9.1 M00005257C:E05 0
1789 2/24/98 1034 RTAOOOOO 124A.f.16.3 M00001536A:F1 1 47430
1790 2/24/98 1035 RTA00000404F.k. l 5.1 M00001634A:B04 18225
1791 2/24/98 1036 RTA00000339F. 08.1 M00001439B:A10 8133
1792 2/24/98 1037 RTA00000339F.1.12.1 M00001450A:G1 1 771 1
1793 2/24/98 1038 RTA00000406F.b.01.1 M00003867B:G07 39006
1794 2/24/98 1039 RTA00000407F.C.08.1 M000041 18D:B05 37549
1795 2/24/98 1040 RTA00000348R.O.12.1 M00001433C:F10 2263
1796 2/24/98 1041 RTA00000403F.b.05.1 M00001455B:E07 74300
1797 2/24/98 1042 RTA00000339F.g. l 0.1 M00001400C:D02 6327
1798 2/24/98 1043 RTA00000423F.b. l 7.1 M00001662B:F06 8200
1799 2/24/98 1044 RTA00000419F.n. l l . l M00003977C:B03 66477
1800 2/24/98 1045 RTA00000408F.J.05.2 M00001483C:G06 73878
1801 2/24/98 1046 RTA00000346F.J.06.1 M00003879A:A02 5767
1802 2/24/98 1047 RTA00000419F.C.14.1 M00003819B:G01 65727
1803 2/24/98 1048 RTA00000413F.O.07.2 M00005100A:C01 0
1804 2/24/98 1049 RTA00000405F.f.05.1 M00001669C:D09 14359
1805 2/24/98 1050 RTA00000405F.f.05.2 M00001669C:D09 14359
1806 2/24/98 1051 RTA00000346F.h.24.1 M00003797A:C1 1 4379
1807 2/24/98 1052 RTA00000420F.b.02.1 M00004081 A:A08 64013
1808 2/24/98 1053 RTA00000413F.b.24.1 M00004080A:F01 651 17
1809 2/24/98 1054 RTA00000412F.d.08.1 M00003905C:B02 75328
1810 2/24/98 1055 RTA00000346F.a.04.1 M00001607B:C05 5382
181 1 2/24/98 1056 RTA00000419F.m.l 8.1 M00003908C:G09 76014
1812 2/24/98 1057 RTA00000419F.I.24.1 M00003904D:B10 74628
1813 2/24/98 1058 RTA00000408F.C.06.1 M00001456D:E08 78619
1814 2/24/98 1059 RTA00000405F.h.21.2 M00001675C:D12 39072
1815 2/24/98 1060 RTA00000346F.g.02.1 M00003792A:B10 6901
1816 2/24/98 1061 RTA00000405F.g.05.2 M00001671 D:E10 38987
1817 2/24/98 1062 RTA0000041 1 F.f.20.1 M00003816C:C01 63501
1818 2/24/98 1063 RTA00000132A.n.7.1 M00001466A:F08 0
1819 2/24/98 1064 RTA00000420F.d.l9.1 M00004105C:C08 43146
1820 1/28/98 595 RTA00000195R.a.06.1 M00001394A:E04 35265
1820 2/24/98 1065 RTA00000195R.3.06.1 M00001394A:E04 35265
1821 2/24/98 1066 RTA00000123A.f.2.1 M0000153 1A:H03 80379
1822 2/24/98 1067 RTA0000041 1 F.J.1 1.1 M00003841 D:F06 66154
1823 2/24/98 1068 RTA00000341 F.f.03.1 M00003850A:F06 0
1824 2/24/98 1069 RTA00000346F.L05.1 M00003904C:A08 0
1825 2/24/98 1070 RTA00000346F.n.22.1 M00004137A:D06 0
1826 2/24/98 1071 RTA00000404F.k. l 8.2 M00001635A:C06 5475
1827 2/24/98 1072 RTA00000419F.J.03.1 M00003868B:G06 77578
1828 2/24/98 1073 RTA00000418F.3.10.1 M00001475B:C04 15245
1829 2/24/98 1074 RTA00000423F.h.l l .l M00003867C:E1 1 38977
1830 2/24/98 1075 RTA00000413F.b. l 7.1 M00004078A:F07 21704
1831 2/24/98 1076 RTA00000423F. 09.1 M00004035B:H09 26630
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
1832 2/24/98 1077 RTA00000414F.e.ll.l M00005236B:A12 0
1833 2/24/98 1078 RTA00000423F.f.03.1 M00003829C:D10 63852
1834 2/24/98 1079 RTA00000419F.e.l0.1 M00003833B:B03 63225
1835 2/24/98 1080 RTA00000351R.g.06.1 M00003771D:G05 0
1836 2/24/98 1081 RTA00000403F.d.02.1 M00001458D:D01 39224
1837 2/24/98 1082 RTA00000137A.O.22.1 M00001587A:D01 0
1838 2/24/98 1083 RTA00000418F.J.20.1 M00001634D:D04 77101
1839 2/24/98 1084 RTA00000403F.O.22.2 M00001583A:D01 25076
1840 2/24/98 1085 RTA00000403F.n.22.1 M00001578B:B05 26775
1841 2/24/98 1086 RTA00000403F.n.22.2 M00001578B:B05 26775
1842 2/24/98 1087 RTA00000401F.O.13.1 M00004040C:A01 3220
1843 2/24/98 1088 RTA00000339R.b.02.1 M00001344B:F12 0
1844 2/24/98 1089 RTA00000406F.J.21.1 M00003906A:H07 17822
1845 2/24/98 1090 RTA00000405F.g.22.1 M00001673C:A02 527
1846 2/24/98 1091 RTA00000356R.h.05.1 M00004107C:C02 35052
1847 2/24/98 1092 RTA00000125A.C.2.1 M00001542A:F06 40148
1848 2/24/98 1093 RTA00000340F.i.l5.1 M00001629C:E07 26815
1849 2/24/98 1094 RTA00000405F.li.03.2 M00001673D:F10 20633
1850 2/24/98 1095 RTA00000345F.C.12.1 M00001376A:C05 23824
1851 2/24/98 1096 RTA00000421F.a.06.1 M00001589C:A11 2385
1852 2/24/98 1097 RTA00000412F.O.03.1 M00004033D:D07 65039
1853 2/24/98 1098 RTA00000409F.d.l6.1 M00001590C:F10 76090
1854 2/24/98 1099 RTA00000400F.m.l6.I M00001660B:E04 3307
1855 2/24/98 1100 RTA00000414F.a.l2.1 M00005210A:E06 0
1856 2/24/98 1101 RTA00000408F.J.17.2 M00001485B:H03 78935
1857 2/24/98 1102 RTAOOOOO 126A.J.15.2 M00001549A:H11 40425
1858 2/24/98 1103 RTA00000346F.a.l6.1 M00001593A:B07 12082
1859 2/24/98 1104 RTAOOOOO 126A.b.10.1 M00001547A:F06 0
1860 2/24/98 1105 RTA00000340F-P-18.1 M00003751C:A04 287
1861 2/24/98 1106 RTA00000410F.b.l7.1 M00001633C:H05 77458
1862 2/24/98 1107 RTA00000419F.1.22.1 M00003903D:C06 78444
1863 2/24/98 1108 RTA00000346F.C.16.1 M00001652B:G10 9579
1864 2/24/98 1109 RTA00000422F.f.22.1 M00001584A:G03 38703
1865 2/24/98 1110 RTA00000404F.J.24.1 M00001631D:G05 39067
1866 2/24/98 1111 RTA00000406F.m.20.1 M00003918C:C12 38038
1867 2/24/98 1112 RTA00000418F.C.05.1 M00001487B:F02 76475
1868 2/24/98 1113 RTA00000418F.p.21.1 M00001677D:F03 78068
1869 2/24/98 1114 RTA00000340F.f.22.1 M00001594B:F12 1720
1870 2/24/98 1115 RTA00000340F.L08.1 M00001615B:F07 12005
1871 2/24/98 1116 RTA00000410F.O.04.1 M00001664D:F04 79018
1872 2/24/98 1117 RTA00000411F.1.16.1 M00003857C:G01 16122
1873 2/24/98 1118 RTA00000411F.J.03.1 M00003841C:F01 66263
1874 2/24/98 1119 RTAOOOOO 126A. 24.1 M00001550A:F07 39428
1875 2/24/98 1120 RTA00000353R.1.23.1 M00001418B:F07 12531
1876 2/24/98 1121 RTA00000120A.111.10.3 M00001467A:B03 81376
1877 2/24/98 1122 RTA00000419F.f.l6.1 M00003839D:E02 64679
1878 2/24/98 1123 RTA00000408F.C.23.1 M00001458C:D10 42261
1879 2/24/98 1124 RTAOOOOO 123 A.h.22.1 M00001532A:C01 17124
1880 2/24/98 1125 RTA00000118A.n.5.1 M00001451A:C10 0
1881 2/24/98 1126 RTAOOOOO 136A.h.6.1 M00001550A:D09 81620
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
1882 2/24/98 127 RTA00000401F.g.22.1 M00003871A:G09 1147
1883 2/24/98 128 RTA00000423F.a.02.3 M00001656B:A08 39210
1884 2/24/98 129 RTA00000401F.m.07.1 M00003907D:F11 2893
1885 2/24/98 130 RTA00000354R.p.01.1 M00004104C:H12 0
1886 2/24/98 131 RTA00000418F.e.20.1 M00001576C:G05 73741
1887 2/24/98 132 RTA00000119A.C.12.1 M00001453A:D08 4882
1888 2/24/98 133 RTA00000405F.1.03.1 M00001692D:B01 38580
1889 2/24/98 134 RTA00000418F.m.02.1 M00001650A:A12 74550
1890 2/24/98 135 RTA00000346F.O.16.1 M00004358D:C02 176
1891 2/24/98 136 RTA00000406F.C.05.1 M00003870A:H01 22077
1892 2/24/98 137 RTA00000345F.d.03.1 M00001376B:A08 19230
1893 2/24/98 1 138 RTA00000411F.k.21.1 M00003854B:D04 65349
1894 2/24/98 139 RTA00000404F.h.20.1 M00001619B:A09 15564
1895 2/24/98 140 RTA00000339F.C.05.1 M00001365A:H10 3908
1896 2/24/98 141 RTA00000347F.f.08.1 M00003972D:H02 5948
1897 2/24/98 142 RTA00000418F.i.06.1 M00001591B:B06 75151
1898 2/24/98 143 RTA00000423F.a.03.1 M00001656B:D05 26796
1899 2/24/98 144 RTA00000345F.J.09.1 M00001451B:F01 13
1900 2/24/98 145 RTA00000423F.k.21.2 M00003984D:B08 37499
1901 2/24/98 146 RTA00000347F.h.02.1 M00004072D:H12 562
1902 2/24/98 147 RTA00000404F.C.18.1 M00001594A:C01 38982
1903 2/24/98 148 RTA00000345F.d.23.1 M00001390D:E03 5862
1904 2/24/98 149 RTA00000339F.b.02.1 M00001344B:F12 0
1905 2/24/98 150 RTA00000411F.g.24.1 M00003825B:B11 65233
1906 2/24/98 151 RTA00000405F.g.l8.2 M00001672D:E08 5255
1907 2/24/98 152 RTA00000405F.m.07.1 M00003809B:B02 37733
1908 2/24/98 153 RTA00000411F.J.07.1 M00003841C:H11 66963
1909 2/24/98 154 RTA00000403F.m.09.2 M00001575B:G01 26814
1910 2/24/98 155 RTA00000353R.h.04.1 M00001375B:C06 17123
1911 2/24/98 156 RTA00000408F.f.l0.2 M00001476D:C05 75309
1912 2/24/98 157 RTA00000422F.m.l8.1 M00001647B:E04 23829
1913 2/24/98 158 RTA00000405F.O.03.1 M00003829C:H05 37575
1914 2/24/98 159 RTA00000413F.b.l8.1 M00004078C:F04 39873
1915 2/24/98 160 RTA00000400F.g.02.1 M00001638B:E03 1508
1916 2/24/98 161 RTA00000346F.m.05.1 M00003983B:C08 5644
1917 2/24/98 162 RTA00000408F.C.10.1 M00001458A:A11 18247
1918 2/24/98 163 RTA00000341F.b.l4.1 M00003763A:C01 5992
1919 2/24/98 164 RTA00000405F.m.21.1 M00003815C:C06 24218
1920 2/24/98 165 RTA00000408F.C.08.1 M00001456D:G11 73473
1921 2/24/98 166 RTA00000347F.h.01.1 M00004040A:G12 12043
1922 2/24/98 167 RTA00000410F.C.06.1 M00001633D:H06 77784
1923 2/24/98 168 RTA00000421F.b.06.1 M00001567A:B09 2113
1924 2/24/98 169 RTA00000405F.b.08.1 M00001656B:E01 39182
1925 2/24/98 170 RTA00000409F.I.24.1 M00001616C:A02 73174
1926 2/24/98 171 RTA00000406F.J.06.1 M00003905A:F10 38952
1927 2/24/98 172 RTA00000423F.h.03.1 M00003875D:D09 37903
1928 2/24/98 173 RTA00000339R.b.07.1 M00001360A:G10 6826
1929 2/24/98 1174 RTA00000121A.k.22.1 M00001507A:C05 79523
1930 2/24/98 175 RTA00000414F.b.04.1 M00005212B:E01 0
1931 2/24/98 1176 RTA00000411F.m.06.1 M00003858D:G06 24195
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
1932 2/24/98 1177 RTAOOOOO 126A.b.9.1 M00001547A:F11 81279
1933 2/24/98 1178 RTA00000400F.f.ll.l M00001636A:E07 4088
1934 2/24/98 1179 RTA00000341F.O.12.1 M00004144A:F04 2883
1935 2/24/98 1180 RTA00000404F.1.05.1 M00001636D:F09 38671
1936 2/24/98 1181 RTA00000346F.f.l4.1 M00003800B:F03 16998
1937 2/24/98 1182 RTA00000346F.d.21.1 M00001670B:G12 6641
1938 2/24/98 1183 RTA00000346F.J.21.1 M00003879D:A08 3095
1939 2/24/98 1184 RTA00000345F.H.08.1 M00001419D:C10 11393
1940 2/24/98 1185 RTA00000413F.b.20.1 M00004079D:G08 66063
1941 2/24/98 1186 RTA00000419F.p.l0.1 M00004036D:B09 41448
1942 2/24/98 1187 RTAOOOOO 120A.C.19.1 M00001464A:B03 81016
1943 2/24/98 1188 RTA00000341F.O.18.1 M00004169D:B11 37189
1944 2/24/98 1189 RTA00000339F.O.18.1 M00001469B:B01 6641
1945 2/24/98 1190 RTA00000405F.g.02.2 M00001671B:G05 10567
1946 2/24/98 1191 RTA00000340F.i.05.1 M00001614B:E08 0
1947 2/24/98 1192 RTA00000406F.m.l7.1 M00003918A:F09 0
1948 2/24/98 1193 RTA00000411F.k.l4.1 M00003851A:C10 63987
1949 2/24/98 1194 RTA00000420F.e.05.1 M00004107D:E12 63908
1950 2/24/98 1195 RTA00000422F.e.23.1 M00001567D:B03 19246
1951 2/24/98 1196 RTA00000413F.I.18.1 M00004895D:G07 0
1952 2/24/98 1197 RTAOOOOO 128 A.j.10.1 M00001560A:H06 80085
1953 2/24/98 1198 RTA00000412F.f.l0.2 M00003959A:A03 65405
1954 2/24/98 1199 RTA00000401F.J.23.1 M00003901C:D03 570
1955 2/24/98 1200 RTA00000422F.k.17.1 M00001652A:A01 38955
1956 2/24/98 1201 RTA00000409F.m.02.1 M00001616C:A11 9157
1957 2/24/98 1202 RTA00000347F.h.l0.1 M00004206A:E02 22779
1958 2/24/98 1203 RTA00000413F.e.l0.1 M00004092C:B03 31033
1959 2/24/98 1204 RTA00000419F.1.02.1 M00003879A:C01 75736
1960 2/24/98 1205 RTA00000419F. 05.1 M00003871C:E04 11757
1961 2/24/98 1206 RTA00000418F.b.20.1 M00001484D:G05 73560
1962 2/24/98 1207 RTA00000401F.J.21.1 M00003901B:F10 0
1963 2/24/98 1208 RTA00000347F.e.24.1 M00003823B:F07 8188
1964 2/24/98 1209 RTA00000408F.n.05.2 M00001539A:H02 77883
1965 2/24/98 1210 RTA00000419F.O.09.1 M00003987B:F08 66396
1966 2/24/98 1211 RTA00000399FT.14.1 M00001487D:C11 11483
1967 2/24/98 1212 RTA00000349R.O.03.1 M00001551D:H07 23006
1968 2/24/98 1213 RTA00000135A.a.23.1 M00001537A:H05 27054
1969 2/24/98 1214 RTA00000339F.J.07.1 M00001428D:B10 5673
1970 2/24/98 1215 RTA00000422F.O.08.2 M00001659D:D03 26832
1971 2/24/98 1216 RTA00000404F.e.07.1 M00001608A:D03 9034
1972 2/24/98 1217 RTA00000410F.J.17.1 M00001642D:F02 72912
1973 2/24/98 1218 RTA00000418F.m.l8.1 M00001653B:G10 76479
1974 2/24/98 1219 RTA00000347F.e.20.1 M00003771B:E05 39911
1975 2/24/98 1220 RTA00000419F.e.23.1 M00003834B:G04 65772
1976 2/24/98 1221 RTA00000403F.O.17.1 M00001582D:A02 23085
1977 2/24/98 1222 RTA00000423F.e.l3.1 M00003848A:C09 10998
1978 2/24/98 1223 RTA00000347F.a.l4.1 M00001429D:F11 7421
1979 2/24/98 1224 RTAOOOOO 122A.h.24.1 M00001514A:A12 48
1980 2/24/98 1225 RTA00000346F.J.13.1 M00003841C:E04 5337
1981 2/24/98 1226 RTA00000414F.C.12.1 M00005218A:F09 0
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
1982 2/24/98 1227 RTA0000041 1 F.g.05.1 M00003822D:B10 64664
1983 2/24/98 1228 RTA00000404F.h.l0.1 M00001618A:A03 37148
1984 2/24/98 1229 RTA00000422F.ιι.14.1 M00001642C:G02 26787
1985 2/24/98 1230 RTA00000399F.J.14.1 M00001578C:F05 16942
1986 2/24/98 1231 RTA00000120A.m.l 3.3 M00001467A:C 10 80608
1987 2/24/98 1232 RTA00000412F .03.1 M00003975D:C06 65617
1988 2/24/98 1233 RTA00000418F.1.02.1 M00001641 C:C05 39316
1989 2/24/98 1234 RTA00000352R.C.20.1 M00003982A:B12 7339
1990 2/24/98 1235 RTA0000041 1 F.J.04.1 M00003841 C:F03 66219
1991 2/24/98 1236 RTA00000414F.b.06.1 M00005212C:C03 0
1992 2/24/98 1237 RTA00000414F.C.24.1 M00005229B:H04 0
1993 2/24/98 1238 RTA00000420F.g.09.1 M00004895B:E12 0
1994 2/24/98 1239 RTA00000340F.O.22.1 M00001673B:B07 7356
1995 2/24/98 1240 RTA00000404F.a.l 8.1 M00001590B:B02 36267
1996 2/24/98 1241 RTA00000408F.1.14.1 M00001530A:E10 12001
1997 2/24/98 1242 RTA00000405F.d. l 0.1 M00001661 C:F1 1 39000
1998 2/24/98 1243 RTA00000404F.J.19.1 M00001630D:H 10 0
1999 2/24/98 1244 RTA00000418F.h.23.1 M00001591A:B08 75153
2000 2/24/98 1245 RTA00000422F.L22.1 M00001592C:E05 4098
2001 2/24/98 1246 RTA00000418F.J.1 1.1 M00001626C:E04 73853
2002 2/24/98 1247 RTA00000408F.O.13.1 M00001572A:B05 74895
2003 2/24/98 1248 RTA00000419F.O.07.1 M00003986C:E09 14059
2004 2/24/98 1249 RTA00000419F.n.l 7.1 M00003978D:G04 63186
2005 2/24/98 1250 RTA00000403FT.15.1 M00001477D:F10 22768
2006 2/24/98 1251 RTA00000408F.d.03.1 M00001458D:A02 22768
2007 2/24/98 1252 RTA00000400F.g.08.1 M00001639A:C 1 1 1275
2008 2/24/98 1253 RTA00000346F.f.02.1 M00003772C:B 12 62757
2009 2/24/98 1254 RTA00000341 F.p. l l .l M00004159C:G 12 0
2010 2/24/98 1255 RTA00000413F.i.21.1 M000041 18B:B04 64066
201 1 2/24/98 1256 RTA00000401 F. 19.1 M00003903D:D10 799
2012 2/24/98 1257 RTA00000419F.h.21.1 M00003856C:B08 64828
2013 2/24/98 1258 RTA00000403F.p.05.2 M00001583D:B08 24528
2014 2/24/98 1259 RTA00000420F.1.19.2 M00005231A:H04 0
2015 2/24/98 1260 RTA00000422F.f. l 8.1 M00001583D:B08 24528
2016 2/24/98 1261 RTA00000404F.m.l 7.2 M00001643B:E05 0
2017 2/24/98 1262 RTA00000122A.h.4.1 M00001514A:G03 33576
2018 2/24/98 1263 RTA00000341 F.i.22.1 M0000391 1 A:F10 7825
2019 2/24/98 1264 RTA00000345F.e.l 3.1 M00001392C:D05 4366
2020 2/24/98 1265 RTA00000340F.d.07.1 M00001532D:A06 0
2021 2/24/98 1266 RTA00000121A.a.2.1 M00001468A:H10 81843
2022 3/24/98 1 RTA00000527F.g. l 3.1 M00003845D:A04 36035
2023 3/24/98 2 RTA00000523F.d. l9.1 M00003824A:A06 26489
2024 3/24/98 3 RTA00000528F.b.23.1 M00001479C:F10 1605
2025 3/24/98 4 RTA00000426F.li.1 1.1 M00003905B:H05 75479
2026 3/24/98 5 RTA00000426F.p.04.1 M00004029B:H08 34149
2027 3/24/98 6 RTA00000523F.1.10.1 M00005134B:E01 0
2028 3/24/98 7 RTA00000523F.O.20.1 M00005177B:H02 0
2029 3/24/98 8 RTA00000428F.b.06.1 M00005228A:A09 0
2030 3/24/98 9 RTA00000522F.b.22.1 M00001573B:H12 75181
2031 3/24/98 10 RTA00000527FT.12.1 M00003829D:D12 5945
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
2032 3/24/98 1 1 RTA00000427F.1.1 1.1 M00005139A:F01 0
2033 3/24/98 12 RTA00000522F.a.23.1 M00001570C:A05 38613
2034 3/24/98 13 RTA00000528F.m.16.1 M00003845D:C03 4468
2035 3/24/98 14 RTA00000523F.b.02.1 M00003806C:A06 65163
2036 3/24/98 15 RTA00000425F.J.14.1 M00001639D:C12 73397
2037 3/24/98 16 RTA00000426F.m.22.1 M00003983A:G02 30002
2038 3/24/98 17 RTA00000527F.p.06.1 M00004029B:G 10 1292
2039 3/24/98 18 RTA00000522F.e.l 6.1 M00001590A:C08 75283
2040 3/24/98 19 RTA00000527F.J.02.2 M00003856A:B07 4896
2041 3/24/98 20 RTA00000522F.O.06.1 M00001659D:A09 26860
2042 3/24/98 21 RTA00000523F.h. l 7.1 M00003852A:B03 65586
2043 3/24/98 22 RTA00000527F.U 5.1 M00003982A:G03 22688
2044 3/24/98 23 RTA00000522F.p.07.1 M00001670A:C 1 1 76888
2045 3/24/98 24 RTA00000522F.n.08.1 M00001656A:D10 76343
2046 3/24/98 25 RTA00000425F.C.06.1 M00001585D:D1 1 78041
2047 3/24/98 26 RTA00000427F.b.23.1 M00003973D:F08 64297
2048 3/24/98 27 RTA00000527F.p.02.1 M00004029B:A01 36844
2049 3/24/98 28 RTA00000427F.d.08.1 M00003980C:E12 63967
2050 3/24/98 29 RTA00000524F.b.03.1 M00005212A:D10 0
2051 3/24/98 30 RTA00000426F.m.07.1 M00004028A:G03 63504
2052 3/24/98 31 RTA00000427F.C.10.1 M00003976B:E06 65478
2053 3/24/98 32 RTA00000424F.n.l4.1 M00001584D:C1 1 73008
2054 3/24/98 33 RTA00000524F.b.21.1 M00005216C:B09 0
2055 3/24/98 34 RTA00000424F.m.l 5.1 M00001612D:F06 73759
2056 3/24/98 35 RTA00000426F.f.l l .l M00003823C:B01 63102
2057 3/24/98 36 RTA00000428F.a.l6.1 M00005212D:F08 0
2058 3/24/98 37 RTA00000426FX.20.1 M00003854C:F01 65134
2059 3/24/98 38 RTA00000528F.i.22.1 M00001661 D:D05 2478
2060 3/24/98 39 RTA00000527F.C.23.1 M00003822C:A07 37742
2061 3/24/98 40 RTA00000426F.h.23.1 M0000391 1A:D12 75964
2062 3/24/98 41 RTA00000525F.b. l 7.1 M00004037B:A04 24715
2063 3/24/98 42 RTA00000527F.J.19.2 M00003853C:C06 38089
2064 3/24/98 43 RTA00000527F.p.07.1 M00004029C:B03 23343
2065 3/24/98 44 RTA00000527F.p.l 7.1 M00004030C:D12 17223
2066 3/24/98 45 RTA00000528F.m.l2.1 M00003842D:F08 5768
2067 3/24/98 46 RTA00000523F.C.09.1 M00003813C:D08 47389
2068 3/24/98 47 RTA00000523F.e.l 8.1 M00003829D:A1 1 62898
2069 3/24/98 48 RTA00000527F.L21.1 M00003982B:H 10 36051
2070 3/24/98 49 RTA00000527F.n.22.1 M00004027A:A08 24175
2071 3/24/98 50 RTA00000522F.k.l 5.1 M00001652D:G06 76866
2072 3/24/98 51 RTA00000522F.n.02.1 M00001655D:E08 74959
2073 3/24/98 52 RTA00000523F.1.07.1 M00004927C:H 1 1 0
2074 3/24/98 53 RTA00000525F.C.17.1 M00004040A:C08 38160
2075 3/24/98 54 RTA00000425F.f. l 9.1 M00001653D:G07 32635
2076 3/24/98 55 RTA00000528F.e.23.1 M00001593B:D10 19242
2077 3/24/98 56 RTA00000522F.n. l 6.1 M00001657D:A10 26769
2078 3/24/98 57 RTA00000427F.C.20.1 M00003978A:E01 26527
2079 3/24/98 58 RTA00000527F.k.06.1 M00003981 B:B12 12469
2080 3/24/98 59 RTA00000427F.n. l4.1 M00004960B:D12 0
2081 3/24/98 60 RTA00000523F.i.06.1 M00003855A:A01 66341
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
2082 3/24/98 61 RTA00000427F.f.21.1 M000041 18B:C1 1 36853
2083 3/24/98 62 RTA00000427F.J.19.1 M00004077A:G 12 41395
2084 3/24/98 63 RTA00000522F.b.01.1 M00001570C:B02 75691
2085 3/24/98 64 RTA00000424F.i.24.1 M00001596A:G06 79101
2086 3/24/98 65 RTA00000523F.C.01.1 M00003810A:A02 65710
2087 3/24/98 66 RTA00000427F.b. l 5.1 M00003971 C:F09 66891
2088 3/24/98 67 RTA00000527F.e.03.1 M00003825D:F01 25560
2089 3/24/98 68 RTA00000523F.11.04.1 M00005138B:D12 0
2090 3/24/98 69 RTA00000522F.J.15.2 M00001651 C:G12 76535
2091 3/24/98 70 RTA00000525F.e.07.1 M000041 15C:G03 38147
2092 3/24/98 71 RTA00000527F.J.20.2 M00003860D:E06 37603
2093 3/24/98 72 RTA00000426F.f. l 9.1 M00003854C:C09 66701
2094 3/24/98 73 RTA00000524F.b. l2.1 M00005213C:G01 0
2095 3/24/98 74 RTA00000527F.d. l9.1 M00003825B:F10 486
2096 3/24/98 75 RTA00000523F.i.22.1 M00003857A:E12 64688
2097 3/24/98 76 RTA00000523F.I.18.1 M00005134D:A06 0
2098 3/24/98 77 RTA00000425F.i. l 7.1 M00001633A:F1 1 43213
2099 3/24/98 78 RTA00000427F.O.05.1 M00004958B:D01 0
2100 3/24/98 79 RTA00000523F.1.15.1 M00005134C:E1 1 0
2101 3/24/98 80 RTA00000425F.p.l2.1 M00001638C:G01 73219
2102 3/24/98 81 RTA00000427F.J.07.1 M00004105A:B10 64819
2103 3/24/98 82 RTA00000523F.h.l 5.1 M00003851C:F09 65137
2104 3/24/98 83 RTA00000527F.i.05.2 M00003851C:B06 37481
2105 3/24/98 84 RTA00000527F.k. l 8.1 M00003982B:C 10 1 1332
2106 3/24/98 85 RTA00000427F.m.21.1 M00004900C:E1 1 0
2107 3/24/98 86 RTA00000523F.k.01.1 M00003966C:F03 41437
2108 3/24/98 87 RTA00000425F.J.1 1.1 M00001637C:H12 76667
2109 3/24/98 88 RTA00000424F.b.22.4 M00001530A:F1 1 72971
21 10 3/24/98 89 RTA00000527F.n.02.1 M00003986C:G 1 1 24190
21 1 1 3/24/98 90 RTA00000525F.a.03.1 M00004031 D:F05 36786
21 12 3/24/98 91 RTA00000527F.i.21.2 M00003855A:F01 37490
21 13 3/24/98 92 RTA00000424F.a.24.4 M00001448D:E1 1 73951
21 14 3/24/98 93 RTA00000522F.U 4.1 M00001652D:G02 74280
21 15 3/24/98 94 RTA00000522F.n.05.1 M00001655D:H 1 1 73260
21 16 3/24/98 95 RTA00000523F.C.18.1 M00003817C:A10 66179
21 17 3/24/98 96 RTA00000523F.b.l3.1 M00003809B:A03 66330
21 18 3/24/98 97 RTA00000522F.J.14.2 M00001651 C:D1 1 73123
21 19 3/24/98 98 RTA00000527F.p.l6.1 M00004030C:C02 23798
2120 3/24/98 99 RTA00000425F.C.20.1 M00001626D:A02 73581
2121 3/24/98 100 RTA00000424F.i.21.1 M00001596A:E07 73482
2122 3/24/98 101 RTA00000523F.J.19.1 M00003966B:D02 65910
2123 3/24/98 102 RTA00000522F.g. l 9.1 M00001595C:A01 781 19
2124 3/24/98 103 RTA00000424F.b.22.1 M00001530A:F 1 1 72971
2125 3/24/98 104 RTA00000527F.b. l 8.1 M00003810D:H09 37469
2126 3/24/98 105 RTA00000526F.d.01.1 M00004104B:A02 4468
2127 3/24/98 106 RTA00000424F.J.14.1 M00001592B:B02 7431 1
2128 3/24/98 107 RTA00000523F.n.20.1 M00005174D:H02 0
2129 3/24/98 108 RTA00000525F.e.l 6.1 M000041 17B:G01 36837
2130 3/24/98 109 RTA00000424F.a.01.4 M00001575A:D05 43214
2131 3/24/98 1 10 RTA00000522F.d.08.1 M00001578B:A06 74284
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
2132 3/24/98 1 1 1 RTA00000425F.d.08.1 M00001631 A:F06 74350
2133 3/24/98 1 12 RTA00000523F.il.12.1 M00005173C:A02 0
2134 ■ 3/24/98 1 13 RTA00000527F.g.07.1 M00003840C:C02 37488
2135 3/24/98 1 14 RTA00000524F.a.23.1 M0000521 1 C:E09 0
2136 3/24/98 1 15 RTA00000525F.b.05.1 M00004034C:F05 21 1 16
2137 3/24/98 1 16 RTA00000425F.n.05.1 M00001647D:G07 73965
2138 3/24/98 1 17 RTA00000523F.d. l 8.1 M00003822B:G01 64072
2139 3/24/98 1 18 RTA00000525F.a.02.1 M00004031 C:H10 37454
2140 3/24/98 1 19 RTA00000523F.p.06.1 M00005177D:F09 0
2141 3/24/98 120 RTA00000426F.h.09.1 M00003905B:G03 78797
2142 3/24/98 121 RTA00000427F.n.02.1 M00004900D:B 10 0
2143 3/24/98 122 RTA00000523F.O.12.1 M00005177A:B06 0
2144 3/24/98 123 RTA00000427F.g.05.1 M00004069C:C08 63138
2145 3/24/98 124 RTA00000424F.m.12.1 M00001586C:H07 77675
2146 3/24/98 125 RTA00000424F.a.01.1 M00001575A:D05 43214
2147 3/24/98 126 RTA00000527F.m.05.1 M00003985A:C01 17240
2148 3/24/98 127 RTA00000523F.n. l 0.1 M00005140D:G09 0
2149 3/24/98 128 RTA00000428F.C.02.1 M00005229D:H07 0
2150 3/24/98 129 RTA00000527F.p.l 8.1 M00004030D:B06 31635
2151 3/24/98 130 RTA00000427F.h. l2.1 M00004092C:D08 36894
2152 3/24/98 131 RTA00000523F.C.15.1 M00003813D:G06 36935
2153 3/24/98 132 RTA00000427F.U 7.1 M00004101A:F07 64965
2154 3/24/98 133 RTA00000425F.f.04.1 M00001607A:B06 24633
2155 3/24/98 134 RTA00000424F.C.14.3 M00001476D:A09 76614
2156 3/24/98 135 RTA00000522F.k. l 0.2 M00001652D:B09 77619
2157 3/24/98 136 RTA00000424F.m.22.1 M00001614C:E1 1 72943
2158 3/24/98 137 RTA00000527F.h.17.1 M00003848D:G02 37799
2159 3/24/98 138 RTA00000527F.C.22.1 M00003822B:G12 37496
2160 3/24/98 139 RTA00000425F. 22.1 M00001633C:E12 78123
2161 3/24/98 140 RTA00000424F.m. l4.1 M00001612D:D12 77491
2162 3/24/98 141 RTA00000522F.k. l 9.1 M00001653A:A05 32625
2163 3/24/98 142 RTA00000523F.U 8.1 M00003856B:C04 64463
2164 3/24/98 143 RTA00000425F.J.22.1 M00001633B:E03 73882
2165 3/24/98 144 RTA00000527F.g.23.1 M00003846C:F08 37538
2166 3/24/98 145 RTA00000426F.m.24.1 M00003981 A:A07 63943
2167 3/24/98 146 RTA00000527F.L17.2 M00003853B:C08 37539
2168 3/24/98 147 RTA00000425F.d.21.1 M00001631 B:H04 78920
2169 3/24/98 148 RTA00000427F.n.l 8.1 M00004891 D:C1 1 0
2170 3/24/98 149 RTA00000424F.d.04.3 M00001478A:F12 76505
2171 3/24/98 150 RTA00000424F.d.04.1 M00001478A:F12 76505
2172 3/24/98 151 RTA00000427F.C.12.1 M00003976B:H07 66995
2173 3/24/98 152 RTA00000425F.d.07.1 M00001631 A:F12 43197
2174 3/24/98 153 RTA00000527F.1.13.1 M00003983C:F10 36904
2175 3/24/98 154 RTA00000522F.h. l 3.1 M00001596C:F09 40823
2176 3/24/98 155 RTA00000424F.1.19.1 M00001609C:A 12 75454
2177 3/24/98 156 RTA00000525F.b.22.1 M00004037C:D07 16679
2178 3/24/98 157 RTA00000523F.g.l 0.1 M00003848B:E07 40694
2179 3/24/98 158 RTA00000427F.a.06.1 M00004036A:A 1 1 66550
2180 3/24/98 159 RTA00000525F.C.19.1 M00004040B:F07 38159
2181 3/24/98 160 RTA00000523F.f.06.1 M00003833D:H08 62871
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
2182 3/24/98 161 RTA00000424F.h. l0.1 M00001485C:G06 72925
2183 3/24/98 162 RTA00000522F.a.l 2.1 M00001567A:H05 33515
2184 3/24/98 163 RTA00000522F.h.01.1 M00001595C:E05 75010
2185 3/24/98 164 RTA00000523F.n.l 7.1 M00005174D:B02 0
2186 3/24/98 165 RTA00000425F.e.21.1 M00001629D:D10 77203
2187 3/24/98 166 RTA00000523F.f.07.1 M00003833D:H10 62799
2188 3/24/98 167 RTA00000424F.i.20.1 M00001596A:D01 44010
2189 3/24/98 168 RTA00000424F.J.12.1 M00001594C:E05 73827
2190 3/24/98 169 RTA00000425F.f.05.1 M00001607A:D10 24090
2191 3/24/98 170 RTA00000523F.d.l2.1 M00003822B:D08 64888
2192 3/24/98 171 RTA00000523F.e.l 0.1 M00003829A:F03 62878
2193 3/24/98 172 RTA00000425F.f. l l . l M00001656C:C04 79275
2194 3/24/98 173 RTA00000426F.m. l 8.1 M00003986D:G07 62974
2195 3/24/98 174 RTA00000424F.b.21.4 M00001530A:B02 24686
2196 3/24/98 175 RTA00000528F.d. l 8.1 M00001582C:E01 2684
2197 3/24/98 176 RTA00000522F.g. l 5.1 M00001595B:G07 76536
2198 3/24/98 177 RTA00000522F.il.12.1 M00001656A:H 12 741 17
2199 3/24/98 178 RTA00000428F.a.l 2.1 M00005179B:H02 0
2200 3/24/98 179 RTA00000424F.d.l0.3 M00001530D:A1 1 731 10
2201 3/24/98 180 RTA00000523F.k.02.1 M00004687A:C03 0
2202 3/24/98 181 RTA00000523F.b.06.1 M00003808A:F09 28736
2203 3/24/98 182 RTA00000524F.b.l 7.1 M00005214B:A06 0
2204 3/24/98 183 RTA00000527F.C.04.1 M00003813C:H08 23090
2205 3/24/98 184 RTA00000524F.b.l 8.1 M00005214B:D1 1 0
2206 3/24/98 185 RTA00000527F.h.21.1 M00003850C:G09 37630
2207 3/24/98 186 RTA00000425F.C.07.1 M00001585D:F03 76042
2208 3/24/98 187 RTA00000428F.b.23.1 M00005231 D:H10 0
2209 3/24/98 188 RTA00000525F.C.15.1 M00004040A:A07 7692
2210 3/24/98 189 RTA00000424F.d.22.3 M00001448B:G07 76189
221 1 3/24/98 190 RTA00000523F.h. l 2.1 M00003851C:D07 65745
2212 3/24/98 191 RTA00000522F.g.22.1 M00001595C:B12 77504
2213 3/24/98 192 RTA00000523F.m.02.1 M00005134D:H03 0
2214 3/24/98 193 RTA00000428F.b. l2.1 M00005231 C:B07 0
2215 3/24/98 194 RTA00000522F.J.12.2 M00001651 C:A04 74341
2216 3/24/98 195 RTA00000523F.i.08.1 M00003855A:C12 65099
2217 3/24/98 196 RTA00000523FT.12.1 M00003840A:C 10 63751
2218 3/24/98 197 RTA00000425F.J.20.1 M00001633B:A12 26760
2219 3/24/98 198 RTA00000523F.O.05.1 M00005175B:H04 0
2220 3/24/98 199 RTA00000427F.f.24.1 M00004076D:B09 64572
2221 3/24/98 200 RTA00000527F.a.l 3.1 M00003805D:E06 37740
2222 3/24/98 201 RTA00000427F.n.l 7.1 M00004891 D:A07 0
2223 3/24/98 202 RTA00000528F.J.1 1.1 M00001669B:C12 1070
2224 3/24/98 203 RTA00000427F.p.l 0.2 M00005102C:F09 0
2225 3/24/98 204 RTA00000424F.a.09.4 M00001575C:C 1 1 77833
2226 3/24/98 205 RTA00000426F.h.l2.1 M00003905C:F12 78093
2227 3/24/98 206 RTA00000525F.f.07.1 M000041 19A:A06 37500
2228 3/24/98 207 RTA00000424F.J.07.1 M00001596B:C 1 1 7921 1
2229 3/24/98 208 RTA00000424F.m.10.1 M00001586C:E06 34251
2230 3/24/98 209 RTA00000427F.g. l 6.1 M00004069A:E12 6301 1
2231 3/24/98 210 RTA00000522F.g.06.1 M00001594D:G 1 1 78221
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
2232 3/24/98 21 1 RTA00000424F.lι.03.1 M00001487C:G09 74447
2233 3/24/98 212 RTA00000424F.n.06.1 M00001613A:D02 74737
2234 3/24/98 213 RTA00000427F.C.22.1 M00003978A:E09 63990
2235 3/24/98 214 RTA00000424F. 12.1 M00001610C:B07 77666
2236 3/24/98 215 RTA00000425F.f.02.1 M00001 607A:A01 76982
2237 3/24/98 216 RTA00000427F.Ii.1 1 .1 M00004092C:B 12 26494
2238 3/24/98 217 RTA00000425F.J.16.1 M00001639D:F02 75631
2239 3/24/98 218 RTA00000427F.U 9.1 M00004102C:D01 64206
2240 3/24/98 219 RTA00000427F.f. l 7.1 M000041 15A:B 12 63803
2241 3/24/98 220 RTA00000522F.O.18.1 M00001669B:H06 76366
2242 3/24/98 221 RTA00000427F.J.22.1 M00004097D:B05 66367
2243 3/24/98 222 RTA00000426F.p. l 0.1 M00004033D:C05 65845
2244 3/24/98 223 RTA00000522F.m.02.1 M00001654C:G07 76834
2245 3/24/98 224 RTA00000527F. 09.1 M00003981 C:F05 213
2246 3/24/98 225 RTA00000527F.d.09.1 M00003824A:G 1 1 10848
2247 3/24/98 226 RTA00000425F.e. l 5.1 M00001608D:F1 1 75921
2248 3/24/98 227 RTA00000427F.U 1 .1 M00004097C:H08 26635
2249 3/24/98 228 RTA00000523F.O.14.1 M00005177A:H09 0
2250 3/24/98 229 RTA00000424F.n. l 3.1 M00001584D:B06 74942
2251 3/24/98 230 RTA00000424F.g. l 4.1 M00001572A:B06 74879
2252 3/24/98 23 1 RTA00000426F.e. l 7.1 M00003810C:B06 64089
2253 3/24/98 232 RTA00000527F.U 3.2 M00003852B:G04 2924
2254 3/24/98 233 RTA00000426F.f. l 3.1 M00003851 A:A06 65384
2255 3/24/98 234 RTA00000524F.C.16.1 M00005218D:G 10 0
2256 3/24/98 235 RTA00000427F.g. l 9.1 M00004087A:B05 6461 1
2257 3/24/98 236 RTA00000527F.O.01 .1 M00004027A:D06 19088
2258 3/24/98 237 RTA00000522F.C.01 .1 M00001576A:C 1 1 74938
2259 3/24/98 238 RTA00000522F.g. l 7.1 M00001595B:G 10 76486
2260 3/24/98 239 RTA00000523F.J.17.1 M00003966B:A04 63610
2261 3/24/98 240 RTA00000522F.11.14.1 M00001657C:C 1 1 73410
2262 3/24/98 241 RTA00000527F.O.12.1 M00004028B:G08 688
2263 3/24/98 242 RTA00000523F.e.20.1 M00003829D:F03 65164
2264 3/24/98 243 RTA00000424F.C.15.3 M00001476D:F12 73533
2265 3/24/98 244 RTA00000426F.p.09.1 M00004033D:B07 66665
2266 3/24/98 245 RTA00000522F.p.09.1 M00001670A:F09 75204
2267 3/24/98 246 RTA00000426F.m.21 .1 M00003983A:F06 64915
2268 3/24/98 247 RTA00000425F.J.21 .1 M00001633B:B 1 1 77373
2269 3/24/98 248 RTA00000527F.I.14.1 M00003983D:A09 14935
2270 3/24/98 249 RTA00000523F.h.21 .1 M00003853B:C 10 41440
2271 3/24/98 250 RTA00000427F.li.24. ] M00004091 B:H09 65193
2272 3/24/98 251 RTA00000425F.f.24.1 M00001656D:C04 40841
2273 3/24/98 252 RTA00000425F.m.03.1 M00001642D:G08 76045
2274 3/24/98 253 RTA00000426F.m.08.1 M00004030B:A 12 63781
2275 3/24/98 254 RTA00000523F.d.24.1 M00003824D:D08 64799
2276 3/24/98 255 RTA00000523F.C.14.1 M00003813D:C02 66015
2277 3/24/98 256 RTA00000523F.b.20.1 M00003809C:H07 66492
2278 3/24/98 257 RTA00000522F.h.07.1 M00001595D:C 1 1 75149
2279 3/24/98 258 RTA00000527F.g. l0.1 M00003845A:E12 37820
2280 3/24/98 259 RTA00000528F.m.04.1 M00003830D:H 1 1 10815
2281 3/24/98 260 RTA00000524F.b.02.1 M00005212A:A02 0
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
2282 3/24/98 261 RTA00000427F.i.22.1 M00004104D:B05 63199
2283 3/24/98 262 RTA00000424F. 03.1 M00001590D:B04 21289
2284 3/24/98 263 RTA00000527F.H.07.1 M00003986D:H 12 15939
2285 3/24/98 264 RTA00000425F.e.09.1 M00001608C:G04 75550
2286 3/24/98 265 RTA00000427F.h.02.1 M00004085B:G01 63652
2287 3/24/98 266 RTA00000426F.f. l 6.1 M00003813B:F02 65613
2288 3/24/98 267 RTA00000425F.i.21.1 M00001635B:B02 75305
2289 3/24/98 268 RTA00000427F. 19.1 M00004103B:B07 62851
2290 3/24/98 269 RTA00000427F.p.02.2 M00005100B:D02 0
2291 3/24/98 270 RTA00000426F.g. l 6.1 M00003814B:C01 41446
2292 3/24/98 271 RTA00000527F.1.05.1 M00003983A:D02 13016
2293 3/24/98 272 RTA00000426F.m.02.1 M00004034C:C06 66237
2294 3/24/98 273 RTA00000424F.a.02.4 M00001575A:D06 78806
2295 3/24/98 274 RTA00000523F.h.06.1 M00003851 B:D03 28745
2296 3/24/98 275 RTA00000522F.1.22.1 M00001654C:D10 75801
2297 3/24/98 276 RTA00000427F.li.19. ! M00004092D:B1 1 63047
2298 3/24/98 277 RTA00000427F.e.08.1 M00003974D:E01 47387
2299 3/24/98 278 RTA00000522F.g.21.1 M00001595C:A09 77310
2300 3/24/98 279 RTA00000528F.b.03.1 M00001455A:D10 2078
2301 3/24/98 280 RTA00000522F.g.20.1 M00001595C:A05 77688
2302 3/24/98 281 RTA00000527F. 20.1 M00003982B:H07 17148
2303 3/24/98 282 RTA00000427F.h.22.1 M00004108C:E01 64547
2304 3/24/98 283 RTA00000425F.k.20.1 M00001633C:A08 74048
2305 3/24/98 284 RTA00000524F.b. l9.1 M00005216B:D02 0
2306 3/24/98 285 RTA00000522F.b.07.1 M00001570D:E05 78634
2307 3/24/98 286 RTA00000426F.g.l9.1 M00003858B:G02 63672
2308 3/24/98 287 RTA00000525F.d.19. l M000041 14B:D09 36860
2309 3/24/98 288 RTA00000427F.1.04.1 M00005136D:C01 0
2310 3/24/98 289 RTA00000427F.d. l 0.1 M00003978C:A12 40685
231 1 3/24/98 290 RTA00000427F.1.03.1 M00005136D:B07 0
2312 3/24/98 291 RTA00000523F.O.23.1 M00005177C:G04 0
2313 3/24/98 292 RTA00000424F.a.05.4 M00001575B:C01 77976
2314 3/24/98 293 RTA00000525F.C.02.1 M00004038A:E05 14618
2315 3/24/98 294 RTA00000424F.a.05.1 M00001575B:C01 77976
2316 3/24/98 295 RTA00000522F.1.15.1 M00001654B:A01 74691
2317 3/24/98 296 RTA00000425F.e.02.1 M00001625C:F10 76143
2318 3/24/98 297 RTA00000525F.C.1 1.1 M00004039C:E02 37895
2319 3/24/98 298 RTA00000527F.e.08.1 M00003826B:B04 19015
2320 3/24/98 299 RTA00000522F.C.14.1 M00001577A:A03 75449
2321 3/24/98 300 RTA00000424F.m.08.1 M00001584A:A07 19402
2322 3/24/98 301 RTA00000527FT.18.1 M00003830D:B1 1 37577
2323 3/24/98 302 RTA00000427F.p.04.2 M00005100B:H07 0
2324 3/24/98 303 RTA00000522F.a.06.1 M00001567A:C1 1 73662
2325 3/24/98 304 RTA00000525F.d. l3.1 M000041 10C:E03 349
2326 3/24/98 305 RTA00000523F.n. l 6.1 M00005173D:H02 0
2327 3/24/98 306 RTA00000522F.d.23.1 M00001579D:F02 73868
2328 3/24/98 307 RTA00000427F.p.03.2 M00005100B:G1 1 0
2329 3/24/98 308 RTA00000424F.k.23.1 M00001614A:B 10 31061
2330 3/24/98 309 RTA00000523F.J.10.1 M00003860B:G09 63384
2331 3/24/98 310 RTA00000527F.p.08.1 M00004029C:F02 36013
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
2332 3/24/98 31 1 RTA00000428F.b.02.1 M00005214D:D 10 0
2333 3/24/98 312 RTA00000426F.f. l 7.1 M0000381 1 C:C02 66334
2334 3/24/98 313 RTA00000523F.J.21.1 M00003966C:A 12 36925
2335 3/24/98 3 14 RTA00000522F.e.09.1 M00001589D:A01 32599
2336 3/24/98 315 RTA00000427F.il.19.1 M00004891 D:E07 0
2337 3/24/98 316 RTA00000523F.h. l 6.1 M00003851 D:H 1 1 6603 1
2338 3/24/98 3 1 7 RTA00000428F.a.01.1 M00004897D:G05 0
2339 3/24/98 31 8 RTA00000523F.a.01 .1 M00001671 C:F1 1 74923
2340 3/24/98 319 RTA00000523F.p. l 5.1 M00005178B:H01 0
2341 3/24/98 320 RTA00000427F.J.06.1 M00004102D:B05 63676
2342 3/24/98 321 RTA00000424F.m.04.1 M00001609C:G05 7901 7
2343 3/24/98 322 RTA00000523F.U 7.1 M00003856B:A 12 65779
2344 3/24/98 323 RTA00000524F.C.12.1 M00005218B:D09 0
2345 3/24/98 324 RTA00000523F.O.09.1 M00005176A:C 12 0
2346 3/24/98 325 RTA00000525F.C.18.1 M00004040B:C05 24208
2347 3/24/98 326 RTA00000527F.e.09. 1 M00003826B:E1 1 37521
2348 3/24/98 327 RTA00000424F.J.08.1 M00001596B:D09 73972
2349 3/24/98 328 RTA00000523F.n.01 .1 M00005137A:E01 0
2350 3/24/98 329 RTA00000527F.C.09.1 M00003817C:G06 64859
2351 3/24/98 330 RTA00000523F.d.23.1 M00003824C:A 10 63633
2352 3/24/98 331 RTA00000528F.k. l 0.1 M00001678C:F09 1981
2353 3/24/98 332 RTA00000523F.C.03.1 M00003810B:B 1 1 36913
2354 3/24/98 333 RTA00000427F.k.21 .1 M00004090D:F12 62880
2355 3/24/98 334 RTA00000427F.n. l l . l M00004960B:A09 0
2356 3/24/98 335 RTA00000427F.d.09.1 M00003980C:F 12 66486
2357 3/24/98 336 RTA00000426F.ιι.17.1 M00004039D:B 10 66572
2358 3/24/98 337 RTA00000525F.e.08.1 M000041 15C:H04 24193
2359 3/24/98 338 RTA00000523F.e. l 5.1 M00003829C:E08 7919
2360 3/24/98 339 RTA00000426F.m.03.1 M00004034C:E08 66480
2361 3/24/98 340 RTA00000424F.h.06.1 M00001485C:D07 77552
2362 3/24/98 341 RTA00000425F.d.06.1 M0000163 1 A:D03 77660
2363 3/24/98 342 RTA00000427F.e. l 2.1 M00003959C:G06 62813
2364 3/24/98 343 RTA00000527F.C.1 1.1 M00003817D:D12 37484
2365 3/24/98 344 RTA00000425F.p. l 5.1 M00001638C:H07 31680
2366 3/24/98 345 RTA00000426F.n.23.1 M00004030C:A08 18176
2367 3/24/98 346 RTA00000522F.m.19.1 M00001655C:C07 41544
2368 3/24/98 347 RTA00000522F.a.05.1 M00001567A:C04 3261 1
2369 3/24/98 348 RTA00000427F.i.09.1 M00004097C:E03 65916
2370 3/24/98 349 RTA00000424F.J.09.1 M00001 596B:H05 74387
2371 3/24/98 350 RTA00000424F.n. l l . l M00001582C:C04 73874
2372 3/24/98 351 RTA00000523F.1.03.1 M00004927A:A02 0
2373 3/24/98 352 RTA00000527F.e. l 3.1 M00003826C:F05 37588
2374 3/24/98 353 RTA00000428F.3.18.1 M00005214C:A09 0
2375 3/24/98 354 RTA00000425F.J.19.1 M00001639D:G06 77925
2376 3/24/98 355 RTA00000522F.g. l 2. 1 M00001595A:E07 78783
2377 3/24/98 356 RTA00000523F.a.07.1 M00001693A:H06 75804
2378 3/24/98 357 RTA00000425F.e.19. l M00001629D:B10 73409
2379 3/24/98 358 RTA00000425F.il.19.1 M00001638B:C08 78324
2380 3/24/98 359 RTA00000523F.d.21 .1 M00003824B:C09 33424
2381 3/24/98 360 RTA00000523F.J.03.1 M00003860A:A08 64535
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
2382 3/24/98 361 RTA00000523F.p.08.1 M00005178A:A07 0
2383 3/24/98 362 RTA00000523F.p.09.1 M00005178A:A08 0
2384 3/24/98 363 RTA00000427F. 07.1 M00004099A:F1 1 63742
2385 3/24/98 364 RTA00000523F.m.07.1 M00005136A:D10 0
2386 3/24/98 365 RTA00000527F. 16.1 M00003982B:B06 1015
2387 3/24/98 366 RTA00000522F.a. l 7.1 M00001567C:B08 79032
2388 3/24/98 367 RTA00000527F.1.19.1 M00003983D:E08 36856
2389 3/24/98 368 RTA00000424F.U 1.1 M00001485D:A05 41569
2390 3/24/98 369 RTA00000524F.C.08.1 M00005217C:C01 0
2391 3/24/98 370 RTA00000424F.d.l9.3 M00001448B:A07 73180
2392 3/24/98 371 RTA00000522F.J.09.2 M00001650D:F1 1 78522
2393 3/24/98 372 RTA00000424F.m.24.1 M00001614C:G07 77045
2394 3/24/98 373 RTA00000522FJ.19.2 M00001652B:D06 76224
2395 3/24/98 374 RTA00000528F.f. l 0.1 M00001596C:G05 3600
2396 3/24/98 375 RTA00000427F.p. l 9.2 M00004895C:G05 0
2397 3/24/98 376 RTA00000525F.b.21.1 M00004037C:D04 9486
2398 3/24/98 377 RTA00000527F.J.12.2 M00003857C:E05 37503
2399 3/24/98 378 RTA00000522F.g.l l . l M00001595A:D12 75432
2400 3/24/98 379 RTA00000522F.k.02.2 M00001652C:B09 77622
2401 3/24/98 380 RTA00000427F.e. l3.1 M00003959D:A04 66080
2402 3/24/98 381 RTA00000426F.f.l 8.1 M00003854C:C02 63271
2403 3/24/98 382 RTA00000427F.a.l2.1 M00003982C:H 10 63377
2404 3/24/98 383 RTA00000424F.b.23.4 M00001530A:H05 77322
2405 3/24/98 384 RTA00000527F.p.03.1 M00004029B:A06 5940
2406 3/24/98 385 RTA00000426F.f.l2.1 M00003823C:C04 19096
2407 3/24/98 386 RTA00000523F.1.16.1 M00005134C:G04 0
2408 3/24/98 387 RTA00000427F.f.02.1 M000041 18D:A1 1 36822
2409 3/24/98 388 RTA00000526F.d.l 7.1 M00004235A:A12 2757
2410 3/24/98 389 RTA00000424F. 5.1 M00001596A:A02 78043
241 1 3/24/98 390 RTA00000524F.a.l l . l M00005210D:C09 0
2412 3/24/98 391 RTA00000522F.m.03.1 M00001654C:G09 79194
2413 3/24/98 392 RTA00000522F.a.20.1 M00001567C:E07 74070
2414 3/24/98 393 RTA00000424F.b.l 5.4 M00001539B:B10 74958
2415 3/24/98 394 RTA00000527F.g. l4.1 M00003845D:B02 37532
2416 3/24/98 395 RTA00000522F.d.06.1 M00001578B:A02 74809
2417 3/24/98 396 RTA00000528F.g.05.2 M00001615C:E07 3770
2418 3/24/98 397 RTA00000427F.e.l 0.1 M00003974D:H07 64599
2419 3/24/98 398 RTA00000527F.C.16.1 M00003821A:H09 22908
2420 3/24/98 399 RTA00000524F.C.07.1 M00005217A:G10 0
2421 3/24/98 400 RTA00000523F.f.l 7.1 M00003840B:E08 63984
2422 3/24/98 401 RTA00000525F.C.16.1 M00004040A:B04 38209
2423 3/24/98 402 RTA00000527F.p.24.1 M00004031 B:A06 36832
2424 3/24/98 403 RTA00000425F.11.17.1 M00001636A:H 12 78304
2425 3/24/98 404 RTA00000522F.b. l 8.1 M00001573B:A06 3460
2426 3/24/98 405 RTA00000425F.e.07.1 M00001608C:D02 75992
2427 3/24/98 406 RTA00000523F.O.07.1 M00005176A:A05 0
2428 3/24/98 407 RTA00000523F.h.08.1 M00003851 B:E01 62893
2429 3/24/98 408 RTA00000522F.O.10.1 M00001660D:E05 78798
2430 3/24/98 409 RTA00000425F.1.10.1 M00001638A:C08 26893
2431 3/24/98 410 RTA00000427F.f.l 6.1 M000041 19D:H06 64122
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority' Priority Appln Appln
2432 3/24/98 41 1 RTA00000424F.ιι.12.1 M00001582C:G02 41589
2433 3/24/98 412 RTA00000425F.U 1.1 M00001664B:F06 21716
2434 3/24/98 413 RTA00000425F.i. l 0.1 M00001664B:E08 78736
2435 3/24/98 414 RTA00000426F.m.l2.1 M00004030B:D08 63740
2436 3/24/98 415 RTA00000527F.g. l 2.1 M00003845C:D04 37746
2437 3/24/98 416 RTA00000527F.U2.2 M00003852B:D1 1 0
2438 3/24/98 417 RTA00000524F.b. l 0.1 M00005213C:A01 0
2439 3/24/98 418 RTA00000425F.U 8.1 M00001633A:G10 42255
2440 3/24/98 419 RTA00000428F.b.22.1 M00005231 D:B09 0
2441 3/24/98 420 RTA00000424F.J.13.1 M00001594C:H03 74485
2442 3/24/98 421 RTA00000523F.i. l 0.1 M00003855B:B09 64876
2443 3/24/98 422 RTA00000527F.f.03.1 M00003829A:B08 17788
2444 3/24/98 423 RTA00000427F.p.06.2 M00005102C:C01 0
2445 3/24/98 424 RTA00000424F. 0.1 M00001592D:H02 73232
2446 3/24/98 425 RTA00000522F.i.07.2 M00001649A:E10 78377
2447 3/24/98 426 RTA00000424F.k.21.1 M00001614A:A04 73197
2448 3/24/98 427 RTA00000522F.b.08.1 M00001570D:E06 26915
2449 3/24/98 428 RTA00000522F.1.08.1 M00001654A:E08 78781
2450 3/24/98 429 RTA00000525F.a.l4.1 M00004033B:C02 37566
2451 3/24/98 430 RTA00000424F.g.08.1 M00001482C:F09 74928
2452 3/24/98 431 RTA00000425F.I.09.1 M00001638A:B04 75251
2453 3/24/98 432 RTA00000522F.O.20.1 M00001669C:B09 74853
2454 3/24/98 433 RTA00000527F.J.04.2 M00003856A:G04 1 1809
2455 3/24/98 434 RTA00000522F.C.1 1.1 M00001576C:H02 31064
2456 3/24/98 435 RTA00000523F.C.13.1 M00003813D:B12 40668
2457 3/24/98 436 RTA00000427F.Ϊ.21.1 M00004102C:F03 65540
2458 3/24/98 437 RTA00000427F.n. l0.1 M00004960B:A08 0
2459 3/24/98 438 RTA00000522F.h.02.1 M00001595C:E09 74947
2460 3/24/98 439 RTA00000522F.g. l0.1 M00001595A:C07 74294
2461 3/24/98 440 RTA00000523F.O.22.1 M00005177C:B04 0
2462 3/24/98 441 RTA00000528F.g.22.2 M00001630C:F09 920
2463 3/24/98 442 RTA00000425F.d.l4.1 M00001629A:H09 13417
2464 3/24/98 443 RTA00000425F. 16.1 M00001640A:F05 75282
2465 3/24/98 444 RTA00000525F.b.09.1 M00004035B:F05 23472
2466 3/24/98 445 RTA00000522F.J.08.2 M00001650D:D10 76613
2467 3/24/98 446 RTA00000425FT.20.1 M00001653D:H07 74071
2468 3/24/98 447 RTA00000523F.f.l9.1 M00003840B:F05 34169
2469 3/24/98 448 RTA00000425F.J.18.1 M00001639D:G 12 75561
2470 3/24/98 449 RTA00000426F.m.04.1 M00004028A:B10 36865
2471 3/24/98 450 RTA00000527F.g.21.1 M00003846B:C05 36028
2472 3/24/98 451 RTA00000527F.i. l 5.2 M00003852C:F07 14235
2473 3/24/98 452 RTA00000525F.a.22.1 M00004033D:G06 36848
2474 3/24/98 453 RTA00000522F.p.22.1 M00001671 B:F02 73322
2475 3/24/98 454 RTA00000424F.d.l2.2 M00001530D:E06 74342
2476 3/24/98 455 RTA00000424F.g.24.1 M00001487C:A1 1 79156
2477 3/24/98 456 RTA00000427F.a.l 0.1 M00004038B:D01 65370
2478 3/24/98 457 RTA00000426F.h.20.1 M00003905A:H 1 1 23187
2479 3/24/98 458 RTA00000424F.d. l2.3 M00001530D:E06 74342
2480 3/24/98 459 RTA00000425F.C.03.1 M00001585D:B12 74643
2481 3/24/98 460 RTA00000523F.f. l 6.1 M00003840B:E07 26522
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
2482 3/24/98 461 RTA00000427F.f. l 5.1 M000041 19D:A07 66734
2483 3/24/98 462 RTA00000427F.p. l3.2 M00004695B:E04 0
2484 3/24/98 463 RTA00000523F.p. l 6.1 M00005179D:B03 0
2485 3/24/98 464 RTA00000522F.p. l 8.1 M00001671 A:H06 76376
2486 3/24/98 465 RTA00000528F.d.04.1 M00001570D:E07 2395
2487 3/24/98 466 RTA00000427F.d.06.1 M00003980B:C06 33446
2488 3/24/98 467 RTA00000528F.h.02.2 M00001632C:D08 1701
2489 3/24/98 468 RTA00000524F.a.l 8.1 M0000521 1 A:E09 0
2490 3/24/98 469 RTA00000522F.e.20.1 M00001590B:H10 26770
2491 3/24/98 470 RTA00000427F.p.24.2 M00004897D:F03 0
2492 3/24/98 471 RTA00000528F.C.1 1.1 M00001486D:D12 1701
2493 3/24/98 472 RTA00000522F.g. l 8.1 M00001595B:H 1 1 73226
2494 3/24/98 473 RTA00000523F.O.21.1 M00005177C:A01 0
2495 3/24/98 474 RTA00000522F.H.05.1 M00001595C:H1 1 73358
2496 3/24/98 475 RTA00000427F.i.06.1 M00004097B:D03 41450
2497 3/24/98 476 RTA00000425F.n. l 6.1 M00001636A:C02 18265
2498 3/24/98 477 RTA00000527F.1.21.1 M00003983D:H02 36439
2499 3/24/98 478 RTA00000527F.p.09.1 M00004029C:F05 7694
2500 3/24/98 479 RTA00000527F.1.23.1 M00003984A:B06 36018
2501 3/24/98 480 RTA00000424F.d. l 7.3 M00001455A:E1 1 73958
2502 3/24/98 481 RTA00000523F.J.02.1 M00003857A:H10 62853
2503 2/24/98 1 132 RTA000001 19A.C.12.1 M00001453A:D08 4882
2504 2/24/98 6 RTAOOOOO 1 19A.J.15.1 M00001460A:E1 1 79623
2505 2/24/98 1041 RTA00000403F.b.05.1 M00001455B:E07 74300
2506 2/24/98 994 RTA00000408F.b.04.2 M00001455A:F04 39933
2507 2/24/98 401 RTAOOOOO 132A.C.1 1.1 M00001454A:G03 87278
2508 2/24/98 535 RTAOOOOO 1 19A.g.7.1 M00001454A:F1 1 83580
2509 2/24/98 867 RTA00000339F.1.21.1 M00001455D:D1 1 9781
2510 2/24/98 62 RTA00000339F.n.l0.1 M00001453B:F08 13719
251 1 2/24/98 380 RTA00000403F.b. l9.1 M00001456B:A06 22327
2512 1/28/98 288 RTA00000181 AR.i.06.3 M00001452A:C07 191 19
2512 2/24/98 198 RTA00000339R.1.14.1 M00001452A:C07 191 19
2513 1/28/98 288 RTA00000181 AR.i.06.3 M00001452A:C07 191 19
2513 2/24/98 198 RTA00000339R.1.14.1 M00001452A:C07 191 19
2514 2/24/98 264 RTA00000345F.J.08.1 M00001451 B:A04 16731
2515 2/24/98 1 125 RTA000001 18A.n.5.1 M00001451 A:C 10 0
2516 2/24/98 229 RTA00000345F.L09.1 M00001450A:D08 27250
2517 2/24/98 670 RTA00000131 A.Ϊ.6.1 M00001450A:B08 0
2518 2/24/98 892 RTA00000339F.m.17.1 M00001453B:H12 20854
2519 2/24/98 1 123 RTA00000408F.C.23.1 M00001458C:D10 42261
2520 2/24/98 680 RTA00000345F.e.l ! . l M00001391 C:C04 4392
2521 2/24/98 644 RTAOOOOO 1 19A.J.9.1 M00001460A:B 12 82060
2522 2/24/98 972 RTA00000408F.d.l 5.1 M00001459B:C 1 1 78467
2523 2/24/98 1081 RTA00000403F.d.02.1 M00001458D:D01 39224
2524 2/24/98 23 1 RTA00000408F.d.06.1 M00001458D:C 1 1 78997
2525 2/24/98 663 RTA00000403F.b.l2.1 M00001455D:A06 78775
2526 2/24/98 856 RTA00000408F.d.02.1 M00001458D:A01 79169
2527 2/24/98 743 RTA00000345F.i.08.1 M00001449D:G10 0
2528 2/24/98 1 162 RTA00000408F.C.10.1 M00001458A:A1 1 18247
2529 2/24/98 841 RTAOOOOO 1 19A.i.8.1 M00001457A:G 12 82593
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
2530 2/24/98 677 RTAOOOOO 1 19A.li.24. ] M00001457A:C05 82266
2531 2/24/98 750 RTA00000403F.C.05.1 M00001456C:C 1 1 74935
2532 2/24/98 751 RTA00000422F.i.02.1 M00001456C:B12 76436
2533 2/24/98 920 RTA00000403F.b.24.1 M00001456B:G01 78838
2534 2/24/98 1251 RTA00000408F.d.03.1 M00001458D:A02 22768
2535 2/24/98 450 RTA000001 18A.a.23.1 M00001395A:H02 3500
2536 2/24/98 85 RTA00000339F.L22.1 M00001427C:D01 5556
2537 2/24/98 684 RTA00000339F.L20.1 M00001426D:D12 6662
2538 2/24/98 129 RTAOOOOO 1 18A.d.24.1 M00001416A:H02 81488
2539 2/24/98 397 RTAOOOOO 1 18A.d.17.1 M00001416A:D09 81921
2540 2/24/98 158 RTA00000348R.J.16.1 M00001410A:D07 7005
2541 2/24/98 1025 RTAOOOOO 1 18A.J.24.1 M00001450A:B03 18
2542 2/24/98 1005 RTA00000339F.e.l 7.1 M00001397D:G08 7568
2543 2/24/98 1040 RTA00000348R.O.12.1 M00001433C:F10 2263
2544 2/24/98 746 RTA00000345F.e.02.1 M00001395A:E03 0
2545 2/24/98 517 RTAOOOOO 1 18A.3.2.1 M00001395A:A 12 38067
2546 2/24/98 1065 RTA00000195R.a.06.1 M00001394A:E04 35265
2546 1/28/98 595 RTA00000195R.a.06.1 M00001394A:E04 35265
2547 1/28/98 595 RTAOOOOO 195R.3.06.1 M00001394A:E04 35265
2547 2/24/98 1065 RTA00000195R.3.06.1 M00001394A:E04 35265
2548 1/28/98 675 RTAOOOOO 179 AR.b.21.3 M00001392C:D05 4366
2548 2/24/98 1264 RTA00000345F.e.l3.1 M00001392C:D05 4366
2549 1/28/98 562 RTA00000196F.J.12.1 M00001396A:H03 19294
2550 2/24/98 1042 RTA00000339F.g.l 0.1 M00001400C:D02 6327
2551 2/24/98 706 RTA00000403F.3.09.1 M00001448B:H05 77820
2552 2/24/98 823 RTAOOOOO 1 19A.L 1.1 M00001460A:H 1 1 81282
2553 2/24/98 703 RTA00000339F.n.05.1 M00001449D:B01 39648
2554 2/24/98 787 RTA00000345F.i.24.1 M00001449C:C05 0
2555 2/24/98 68 RTA00000339F.n.03.1 M00001449B:B03 0
2556 2/24/98 440 RTA00000403F.3.18.1 M00001448D:F12 75726
2557 2/24/98 815 RTA00000403F.3.17.1 M00001448D:E12 13686
2558 2/24/98 275 RTA00000353R.J.24.1 M00001428B:D01 23089
2559 2/24/98 902 RTA00000403F.3.10.1 M00001448C:E1 1 73952
2560 2/24/98 1214 RTA00000339F.J.07.1 M00001428D:B10 5673
2561 2/24/98 378 RTA00000403F.a.07.1 M00001448B:F09 73559
2562 2/24/98 473 RTA00000403F.3.05.1 M00001448A:E1 1 18808
2563 2/24/98 128 RTA00000403F.3.04.1 M00001448A:B12 23529
2564 2/24/98 227 RTA00000347F.C.06.1 M00001444D:C01 18846
2565 2/24/98 35 RTA00000339F.U3.1 M00001434A:B 10 5970
2566 2/24/98 442 RTA00000347F.b.02.1 M00001450A:A02 39304
2567 2/24/98 288 RTA00000403F.3.1 1.1 00001448C:F10 73109
2568 2/24/98 853 RTA00000408F.J.13.2 M00001485B:D10 42275
2569 2/24/98 249 RTA000001 19A.J.10.1 M00001460A:C10 79646
2570 2/24/98 634 RTA00000418F.C.04.1 M00001487B:A1 1 41587
2571 2/24/98 1 10 RTA00000408F. 14.1 M00001486B:E12 73856
2572 2/24/98 894 RTA00000408F.k.l2.1 M00001486B:D07 77246
2573 2/24/98 395 RTA00000408F.J.19.2 M00001485C:C08 73752
2574 2/24/98 509 RTA00000349R.g.l 0.1 M00001495B:B08 5777
2575 2/24/98 426 RTA00000408F.J.15.2 M00001485B:F05 74759
2576 2/24/98 101 RTA00000121 A.m.2.1 M00001507A:A 1 1 81064
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
2577 2/24/98 330 RTA00000403F.i.04.1 M00001485B:D09 8930
2578 2/24/98 647 RTA00000418F.b.23.1 M00001485A:C05 28767
2579 2/24/98 569 RTA00000403F.h. l 8.1 M00001484C:A04 39241
2580 2/24/98 236 RTA00000403F.li.12.1 M00001483C:G09 15205
2581 2/24/98 707 RTA00000403F.h. l l . l M00001483B:D04 39219
2582 2/24/98 869 RTA00000403F.h.07.1 M00001482D:H 1 1 26856
2583 2/24/98 1 101 RTA00000408F.J.17.2 M00001485B:H03 78935
2584 2/24/98 344 RTA00000403F.m. l 5.2 M00001575D:D 12 26901
2585 2/24/98 768 RTA00000121 A.k.5.1 M00001507A:E04 1 7530
2586 2/24/98 1 1 74 RTA00000121 A. 22.1 M00001507A:C05 79523
2587 2/24/98 184 RTA00000133A.J.13.1 M00001507A:B02 16846
2588 2/24/98 1230 RTA00000399F.J.14.1 M00001578C:F05 16942
2589 2/24/98 304 RTA00000403F.n.18.2 M00001577D:H06 881 1
2590 2/24/98 938 RTA00000403F.i.23.1 M00001487B:E 10 1 1364
2591 2/24/98 1 131 RTA0000041 8F.e.20.1 M00001576C:G05 73741
2592 2/24/98 651 RTA00000403F.g. l l . l M00001481 A:H08 24238
2593 2/24/98 3 12 RTA00000399F.i.08.1 M00001575D:B 10 38927
2594 2/24/98 800 RTA00000403F.m. l 2.1 M00001575D:A02 16933
2595 2/24/98 1017 RTA00000418F.e.03.1 M00001573B:G08 73442
2596 2/24/98 269 RTA00000422F.e.08.1 M00001573A:E01 39020
2597 2/24/98 1247 RTA00000408F.O.13.1 M00001572A:B05 74895
2598 2/24/98 847 RTA00000403F.1.1 1.1 M00001571 D:F05 25073
2599 2/24/98 910 RTA0000041 8F.f.03.1 M00001577B:F10 7891 1
2600 2/24/98 244 RTA00000120A.g.23.1 M00001465A:E10 81 189
2601 2/24/98 1 189 RTA00000339F.O.18.1 M00001469B:B01 6641
2602 2/24/98 1266 RTA00000121 A.a.2.1 M00001468A:H 10 81843
2603 2/24/98 414 RTAOOOOO 120A.p.1 8.1 M00001468A:C05 6478
2604 2/24/98 96 RTAOOOOO 120A.n.19.3 M00001467A:H07 80004
2605 2/24/98 1231 RTAOOOOO 120A.ni.13.3 M00001467A:C10 80608
2606 2/24/98 134 RTA00000408F.i.08.2 M00001482A:H05 7581 1
2607 2/24/98 410 RTA00000120A.h.5.1 M00001465A:G06 80344
2608 2/24/98 403 RTA00000403F.d.22.1 M00001473A:A07 10692
2609 2/24/98 183 RTA00000120A.g. l 8.1 M00001465A:C 12 81255
2610 2/24/98 810 RTAOOOOO 120A.h.9.1 M00001465A:B12 80736
261 1 2/24/98 71 RTAOOOOO 120A.d.24.1 M00001464A:E10 5085
2612 2/24/98 490 RTA00000120A.d. l 5.1 00001464A:B02 80533
2613 2/24/98 736 RTA00000120A.C.7.1 M00001462A:D03 80985
2614 2/24/98 724 RTA000001 19A.m. l 7.1 M00001461 A:F05 79536
2615 2/24/98 1063 RTA00000132A.n.7.1 M00001466A:F08 0
2616 2/24/98 74 RTA00000408F.e.22.2 M00001476B:F08 26930
2617 1/28/98 656 RTAOOOOO 178AR.h.22.3 M00001376B:A08 19230
2617 1/28/98 657 RTAOOOOO 178AR.h.22.2 M00001376B:A08 19230
261 7 2/24/98 1 137 RTA00000345F.d.03.1 M00001376B:A08 19230
2618 2/24/98 1012 RTA00000403F.g.06.1 M00001480C:A05 10505
2619 2/24/98 419 RTA00000408F.h.08.1 M00001480A:D03 74575
2620 2/24/98 871 RTA00000403F.f.23.1 M00001479C:E01 39223
2621 2/24/98 638 RTA0000041 8F.b.09.1 M00001478B:H08 19700
2622 2/24/98 • 770 RTA00000421 F.f.05.1 M00001477B:E02 5266
2623 2/24/98 549 RTA00000121 A.h. l 8.1 M00001471 A:B04 16376
2624 2/24/98 660 RTA00000408F.e.24.2 M00001476C:C 1 1 75002
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
2625 2/24/98 144 RTA00000349R.f. l 5.1 M00001472A:D08 75097
2626 2/24/98 774 RTA00000403F.e.24.1 M00001476B:D10 16432
2627 2/24/98 268 RTA00000403F.e.23.1 M00001476A:D1 1 9626
2628 2/24/98 715 RTA00000418F.b.01.1 M00001475C:G 1 1 76040
2629 2/24/98 1073 RTA00000418F.a.l 0.1 M00001475B:C04 15245
2630 2/24/98 100 RTA00000339F.O.23.1 M00001473C:D09 7801
2631 2/24/98 756 RTA00000403F.g.l 3.1 M00001481 B:D09 38718
2632 2/24/98 915 RTA00000408F.f.l4.2 M00001476D:F03 73024
2633 1/28/98 389 RTA00000181 AR.k.2.2 M00001453C:A1 1 0
2633 1/28/98 286 RTA00000181 AR. 2.3 M00001453C:A1 1 0
2634 1/28/98 565 RTA00000191 AF.C.10.1 M00003989B:F1 1 40422
2635 1/28/98 449 RTA00000181 AF.m.22.3 M00001455D:F09 9283
2635 1/28/98 450 RTA00000181AF.m.21.3 M00001455D:F09 9283
2636 1/28/98 449 RTA00000181 AF.m.22.3 M00001455D:F09 9283
2636 1/28/98 450 RTA00000181 AF.m.21.3 M00001455D:F09 9283
2637 1/28/98 449 RTA00000181 AF.m.22.3 M00001455D:F09 9283
2637 1/28/98 450 RTAOOOOO 181 AF.m.21.3 M00001455D:F09 9283
2638 1/28/98 449 RTA00000181 AF.m.22.3 M00001455D:F09 9283
2638 1/28/98 450 RTAOOOOO 181 AF.m.21.3 M00001455D:F09 9283
2639 1/28/98 390 RTAOOOOO 197ART.07.1 M00001457C:C1 1 19261
2639 1/28/98 184 RTAOOOOO 197AFT.7.1 M00001457C:C1 1 19261
2640 1/28/98 598 RTA00000197F.e.l0.1 M00001454B:D08 13154
2641 1/28/98 184 RTAOOOOO 197AFT.7.1 M00001457C:C1 1 19261
2641 1/28/98 390 RTAOOOOO 197ART.07.1 M00001457C:C 1 1 19261
2642 1/28/98 286 RTA00000181AR. 2.3 M00001453C:A1 1 0
2642 1/28/98 389 RTAOOOOO 181 AR.k.2.2 M00001453C:A1 1 0
2643 1 /28/98 667 RTAOOOOO 197AF.d.16.1 M00001452A:E07 23505
2644 1/28/98 679 RTAOOOOO 197AF.d.1 1.1 M00001451 C:E01 27260
2645 1/28/98 664 RTA00000195R.a.23.1 M00001449C:H12 86432
2646 1/28/98 594 RTA00000181 AR.e.04.3 M00001448A:G09 1 1825
2647 1/28/98 405 RTAOOOOO 197AF.b.24.1 M00001446C:D09 23171
2648 1/28/98 572 RTA00000181 AF.1.16.2 M00001454D:E05 13532
2649 1 /28/98 590 RTAOOOOO 190AF.d.2.1 M00003906B:F12 2444
2650 1/28/98 675 RTAOOOOO 179AR.b.21.3 M00001392C:D05 4366
2650 2/24/98 1264 RTA00000345F.e.l 3.1 M00001392C:D05 4366
2651 1/28/98 486 RTAOOOOO 190AR.p.22.2 M00003979A:E1 1 16368
2652 1/28/98 701 RTAOOOOO 199AF.0.10.1 M00003974C:E04 0
2653 1/28/98 704 RTAOOOOO 190AF.0.12.1 M00003972D:C09 3438
2654 1 /28/98 469 RTAOOOOO 190AF.n.2.1 M00003963A:E03 5650
2655 1/28/98 612 RTA00000197AR.e.22.1 M00001456A:H02 78758
2656 1/28/98 640 RTA00000190AF.f.5.1 M00003909A:H04 5015
2657 1/28/98 539 RTAOOOOO 197AR.b.13.1 M00001445B:E04 9560
2658 1/28/98 431 RTA00000199AF. 15.1 M00003905C:G 10 8275
2659 1/28/98 747 RTAOOOOO! 90 AF.c.6.1 M00003904D:D10 4780
2660 1/28/98 584 RTAOOOOO 190AR.C.03.1 M00003904C:A08 0
2660 2/24/98 1069 RTA00000346F.L05.1 M00003904C:A08 0
2661 1/28/98 584 RTAOOOOO 190AR.C.03.1 M00003904C:A08 0
2661 2/24/98 1069 RTA00000346F.L05.1 M00003904C:A08 0
2662 1/28/98 577 RTAOOOOO 190 AF.a.24.2 M00003901 B:A05 0
2663 1/28/98 639 RTAOOOOO 199 AF.j.1.1 M00003881 C:G09 6006
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
2664 1/28/98 649 RTA00000190AR.1.19.2 M00003946A:H 10 . 88204
2665 1 /28/98 488 RTA00000179AR.1.22.4 M00001405B:E09 4314
2665 1/28/98 481 RTAOOOOO 179AR.1.22.2 M00001405B:E09 4314
2666 1/28/98 721 RTAOOOOO 180AF.C.4.1 M00001417B:C04 5415
2667 1/28/98 744 RTA00000196F.m.4.1 M00001413A:F03 7958
2668 1/28/98 569 RTA00000196AF.1.23.1 M00001412A:E04 12052
2669 1 /28/98 707 RTA00000179AF.p.15.1 M0000141 1 D:F05 5622
2670 1/28/98 599 RTA00000179AF.O.5.1 M00001408D:D04 6172
2671 1 /28/98 420 RTA00000181 AF.C.1 1.1 M00001445D:A06 4769
2672 1/28/98 500 RTAOOOOO 179AR.m.07.5 M00001405D:D1 1 0
2673 1 /28/98 609 RTA00000196AF.n.05.1 M00001418B:F07 12531
2673 2/24/98 1 120 RTA00000353R.1.23.1 M00001418B:F07 12531
2674 1 /28/98 481 RTA00000179AR.1.22.2 M00001405B:E09 4314
2674 1 /28/98 488 RTAOOOOO 179AR.I.22.4 M00001405B:E09 4314
2675 1 /28/98 481 RTA00000179AR.I.22.2 M00001405B:E09 4314
2675 1/28/98 488 RTAOOOOO 179 AR.1.22.4 M00001405B:E09 4314
2676 1/28/98 481 RTA00000179AR.1.22.2 M00001405B:E09 4314
2676 1/28/98 488 RTA00000179AR.1.22.4 M00001405B:E09 4314
2677 1/28/98 636 RTAOOOOO 196F. 20.1 M00001402B:F12 6324
2678 1/28/98 691 RTA00000195F.3.10.1 M00001401C:H03 6803
2679 2/24/98 161 RTA00000418F.n.22.1 M00001659D:B05 79062
2680 1/28/98 61 1 RTA00000196F.1.13.2 M00001408A:H04 0
2681 1/28/98 535 RTAOOOOO 196AF.il.19.1 M00001423D:D12 6881
2682 1/28/98 413 RTA00000200F.a.l2.1 M00004031 D:BO5 16751
2683 1/28/98 580 RTAOOOOO 197F.3.12.1 M00001438B:B09 7895
2684 1/28/98 681 RTAOOOOO 180AF.1.04.2 M00001432D:F05 1 1 159
2685 1/28/98 568 RTA00000196AF.p.01.2 M00001430A:A02 87143
2686 1/28/98 736 RTAOOOOO 196 AF.o.13.1 M00001428B:A09 0
2687 1/28/98 438 RTA00000180AR.g.03.4 M00001425A:C 1 1 9024
2687 1 /28/98 95 RTAOOOOO 180 AF.g.3.1 M00001425A:C1 1 9024
2688 1/28/98 514 RTA00000196AF.n.02.1 M00001417D:A04 39260
2689 1/28/98 741 RTAOOOOO 196AF.n.22.1 M00001424B:H04 9572
2690 1 /28/98 609 RTAOOOOO 196AF.n.05.1 M00001418B:F07 12531
2690 2/24/98 1 120 RTA00000353R.1.23.1 M00001418B:F07 12531
2691 1/28/98 462 RTAOOOOO 196AF.il.17.1 M00001423D:A09 12477
2692 1 /28/98 477 RTAOOOOO 180AR.e.22.2 M00001423A:G05 7714
2693 1/28/98 445 RTA00000196AF.n.l 3.1 M00001422C:F12 8396
2694 1 /28/98 696 RTAOOOOO 180AR.d.16.3 M00001419D:C 10 1 1393
2694 2/24/98 1 184 RTA00000345F.h.08.1 M00001419D:C 10 1 1393
2695 1 /28/98 696 RTAOOOOO 180AR.d.16.3 M00001419D:C 10 1 1393
2695 2/24/98 1 184 RTA00000345F.h.08.1 M00001419D:C 10 1 1393
2696 1 /28/98 541 RTAOOOOO 197AR.b.16.1 M00001445C:A08 0
2697 1/28/98 95 RTAOOO00180AF.g.3.1 M00001425A:C 1 1 9024
2697 1/28/98 438 RTAOOOOO 180AR.g.03.4 M00001425A:C 1 1 9024
2698 1 /28/98 536 RTAOOOOO 193 AR.a.2.3 M00004216D:D03 0
2699 1/28/98 588 RTA00000191 AF.b.4.1 M00003983C:F03 14936
2700 1/28/98 401 RTA00000195F.e.04.1 M00004465B:D04 6731
2701 2/24/98 91 RTA00000355R.e. l 5.1 M00004316A:G09 22639
2701 1/28/98 410 RTA00000201 F.a.20.1 M00004316A:G09 22639
2702 1/28/98 410 RTA00000201 F.a.20.1 M00004316A:G09 22639
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
2702 2/24/98 91 RTA00000355R.e. l 5.1 M00004316A:G09 22639
2703 1 /28/98 716 RTA00000200F.p.05.1 M00004285C:A08 3984
2704 2/24/98 434 RTA00000348R.b. l 6.1 M00001347B:H04 6510
2705 1/28/98 528 RTA00000200F.n.09.2 M00004249D:B08 12391
2706 2/24/98 575 RTA00000345F.a. l 8.1 M00001351 C:B06 5517
2707 1/28/98 658 RTAOOOOO 193 AF.a.1.1 M00004216D:C03 16501
2708 1/28/98 472 RTAOOOOO 192AF.p.17.1 M00004214C:H05 1 1451
2709 1/28/98 478 RTAOOOOO 192AR.o.24.2 M00004210B:B05 7191
2710 1/28/98 753 RTAOOOOO 192AF.0.17.1 M00004208D:B10 5275
271 1 1/28/98 563 RTAOOOOO 192AR.0.16.2 M00004208B:F05 9061
2712 1/28/98 730 RTAOOOOO 192 AF.o.1 1.1 M00004205D:F06 0
2713 1/28/98 624 RTA00000200F.O.15.1 M00004275A:B03 7866
2714 2/24/98 169 RTA00000347F.3.17.1 M00001366D:C06 16723
2715 1/28/98 656 RTAOOOOO 178AR.h.22.3 M00001376B:A08 19230
2715 1/28/98 657 RTAOOOO0178 AR.h.22.2 M00001376B:A08 19230
2715 2/24/98 1 137 RTA00000345F.d.03.1 M00001376B:A08 19230
2716 1/28/98 657 RTAOOOOO 1 78AR.h.22.2 M00001376B:A08 19230
2716 1/28/98 656 RTAOOOOO 178AR.h.22.3 M00001376B:A08 19230
2716 2/24/98 1 137 RTA00000345F.d.03.1 M00001376B:A08 19230
2717 1/28/98 522 RTA00000178AR.li.17.2 M00001376A:C05 23824
2717 2/24/98 1095 RTA00000345F.C.12.1 M00001376A:C05 23824
2718 1/28/98 522 RTA00000178AR.h.l 7.2 M00001376A:C05 23824
2718 2/24/98 1095 RTA00000345F.C.12.1 M00001376A:C05 23824
2719 2/24/98 1 155 RTA00000353R.h.04.1 M00001375B:C06 17123
2720 1/28/98 614 RTA00000201 F.f.03.1 M00004493B:D09 22633
2721 2/24/98 16 RTA00000399F.3.02.1 M00001366D:C 12 0
2722 1/28/98 436 RTA00000200AF.k.l l . l M00004197C:F03 9796
2722 1/28/98 501 RTA00000200R.k.l l . l M00004197C:F03 9796
2723 2/24/98 1 140 RTA00000339F.C.05.1 M00001365A:H10 3908
2724 2/24/98 322 RTA00000339F.C.24.1 M00001364B:B06 5516
2725 2/24/98 888 RTA00000339R.C.04.1 M00001362D:H01 1805
2726 1/28/98 33 RTAOOOOO 178AR.3.20.1 M00001362C:H1 1 945
2726 2/24/98 979 RTA00000345F.b.l 7.1 M00001362C:H 1 1 945
2727 1/28/98 33 RTA00000178AR.a.20.1 M00001362C:H 1 1 945
2727 2/24/98 979 RTA00000345F.b.l 7.1 M00001362C:H1 1 945
2728 2/24/98 1 173 RTA00000339R.b.07.1 M00001360A:G 10 6826
2729 2/24/98 973 RTA00000339F.b.22.1 M00001373D:B03 6867
2730 1/28/98 581 RTA00000191 AF.p.3.2 M00004104B:F1 1 17
2731 1/28/98 637 RTA00000200AF.g. l 5.1 M00004135B:G01 22898
2731 1/28/98 476 RTA00000200R.g. l 5.1 M00004135B:G01 22898
2732 1/28/98 637 RTA00000200AF.g.l 5.1 M00004135B:G01 22898
2732 1/28/98 476 RTA00000200R.g. l 5.1 M00004135B:G01 22898
2733 1/28/98 474 RTAOOOOO 192 AR.d.1.3 M00004130D:H01 14507
2734 1/28/98 735 RTAOOOOO 192 AF.b.1 1.1 M000041 17A:G01 40014
2735 1/28/98 726 RTA00000200R.f. l 0.1 M000041 1 1 D:B07 4
2736 1/28/98 752 RTAOOOOO 192AF.0.7.1 M00004204D:C03 5275
2737 1/28/98 516 RTA00000200AF.e.23.1 M00004107B:A06 14686
2738 1/28/98 685 RTA00000200F .9.1 M00004159C:F09 36756
2738 2/24/98 704 RTA00000355R.3.12.1 M00004159C:F09 36756
2739 1/28/98 417 RTA00000200R.d. l 6.1 M00004085A:B02 39875
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
2740 1 /28/98 454 RTA00000200R.d.04.1 M00004078A:A06 5506
2741 1/28/98 551 RTA00000200AR.C.24.1 M00004076D:D04 15972
2742 1/28/98 524 RTAOOOO0191 AF.j.24.1 M00004076B:G03 0
2743 2/24/98 1 166 RTA00000347F.h.01.1 M00004040A:G 12 12043
2743 1/28/98 684 RTA00000200AR.b. l l .l M00004040A:G12 12043
2744 2/24/98 1 166 RTA00000347F.h.01.1 M00004040A:G 12 12043
2744 1/28/98 684 RTA00000200AR.b.l l .l M00004040A:G 12 12043
2745 1/28/98 415 RTA00000200AF.f.09.1 M000041 1 1 C:E1 1 12863
2746 1/28/98 448 RTA00000200AF.J.9.1 M00004177C:A01 8608
2747 2/24/98 446 RTA00000133A.m.l9.2 M00001512A:G05 80167
2748 1/28/98 436 RTA00000200AF.k.1 1.1 M00004197C:F03 9796
2748 1/28/98 501 RTA00000200R.k. l l .1 M00004197C:F03 9796
2749 1/28/98 436 RTA00000200AF.k. l l . l M00004197C:F03 9796
2749 1/28/98 501 RTA00000200R.k. l l . l M00004197C:F03 9796
2750 1 /28/98 436 RTA00000200AF.k.l l . l M00004197C:F03 9796
2750 1/28/98 501 RTA00000200R. 1 1.1 M00004197C:F03 9796
2751 1/28/98 610 RTA00000200AF.k.2.1 M00004188D:G08 35924
2752 1/28/98 494 RTA00000200AF.k. l . l M00004188C:A09 40049
2752 1/28/98 194 RTA00000200R.k.01.1 M00004188C:A09 40049
2753 1/28/98 574 RTAOOOOO 192 AF.f.3.1 M00004146C:C 1 1 5257
2754 1/28/98 604 RTA00000200AF.J.15.1 M00004185D:E04 5849
2755 1/28/98 579 RTA00000200F.i.7.1 M00004157D:B03 22322
2756 1/28/98 634 RTAOOOOO 192 AF.j .6.1 M00004172C:D08 1 1494
2757 1/28/98 421 RTA00000200AF.i.21.1 M00004167D:A07 5316
2758 1/28/98 543 RTA00000200AF.i.l9.1 M00004167A:H03 14722
2759 1/28/98 483 RTA00000192AF.h.l9.1 M00004162C:A07 4642
2760 2/24/98 704 RTA00000355R.3.12.1 M00004159C:F09 36756
2760 1/28/98 685 RTA00000200F.i.9.1 M00004159C:F09 36756
2761 1/28/98 607 RTA00000200AF. 12.1 M00004198B:D02 7359
2762 1/28/98 494 RTA00000200AF.k.l . l M00004188C:A09 40049
2762 1/28/98 194 RTA00000200R.k.01.1 M00004188C:A09 40049
2763 2/24/98 554 RTA00000409F.i.03.1 M00001610A:E09 75968
2764 2/24/98 1228 RTA00000404F.h.l 0.1 M00001618A:A03 37148
2765 2/24/98 332 RTA00000409F.L24.1 M0000161 1 B:A09 76967
2766 2/24/98 1023 RTA00000404F.f.l2.1 M0000161 1B:A05 39209
2767 2/24/98 572 RTA00000422F.1.03.1 M00001610D:D05 39147
2768 2/24/98 497 RTA00000350R.f.21.1 M00001610C:E07 221 10
2769 2/24/98 557 RTA00000409F.J.05.1 M0000161 1 C:C12 74128
2770 2/24/98 223 RTA00000404F.e.22.1 M00001610A:H05 1 1344
2771 2/24/98 165 RTA00000409F.J.07.1 M0000161 1 C:H 1 1 75190
2772 2/24/98 959 RTA00000340F.g.20.1 M00001609D:G 10 4089
2773 2/24/98 737 RTA00000404F.e.l 5.1 M00001609B:C09 39101
2774 2/24/98 974 RTA00000340F.h.07.1 M00001608D:D1 1 19254
2775 2/24/98 857 RTA00000404F.e.09.1 M00001608B:A09 39121
2776 1/28/98 340 RTA00000185AF.n.8.1 M00001608B:A03 0
2776 2/24/98 75 RTA00000350R.i.22.1 M00001608B:A03 0
2777 1/28/98 340 RTA00000185AF.n.8.1 M00001608B:A03 0
2777 2/24/98 75 RTA00000350R.i.22.1 M00001608B:A03 0
2778 2/24/98 546 RTA00000409F.i.09.1 M00001610B:C07 75279
2779 2/24/98 374 RTA00000422F.m.04.1 M00001615B:A09 38702
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
2780 2/24/98 505 RTA00000121 A.O.3.1 M0000151 1A:A02 81437
2781 2/24/98 453 RTA00000130A.h.l 3.1 M00001617A:A01 80790
2782 2/24/98 163 RTA00000422F.1.23.1 M00001616D:C 1 1 4240
2783 2/24/98 889 RTA00000346F.b.l6.1 M00001615C:G05 16485
2784 2/24/98 203 RTA00000404F.g.21.1 M00001615C:A1 1 37947
2785 2/24/98 32 RTA00000409F.J.02.1 M0000161 1 B:E06 76417
2786 2/24/98 872 RTA00000409F.1.20.1 M00001615B:G01 74394
2787 2/24/98 978 RTA00000130A.e.20.1 M00001606A:H09 79502
2788 2/24/98 45 RTA00000409F.I.12.1 M00001615A:D06 26755
2789 2/24/98 182 RTA00000404F.g.l4.1 M00001614D:B08 8858
2790 2/24/98 912 RTA00000404F.g. l 3.1 M00001614C:E06 9436
2791 2/24/98 1 191 RTA00000340F.i.05.1 M00001614B:E08 0
2792 2/24/98 192 RTA00000421 F.k.l 5.1 M00001613D:B03 2222
2793 2/24/98 360 RTA00000409F.J.19.1 M00001613A:F03 73792
2794 2/24/98 57 RTA00000409F.1.21.1 M00001615B:G07 73143
2795 2/24/98 354 RTA00000404F.C.03.2 M00001592C:F1 1 39198
2796 2/24/98 791 RTA00000399F.n. l 5.1 M00001594D:C03 3213
2797 2/24/98 921 RTA00000422F.J.02.1 M00001594D:B08 10368
2798 2/24/98 1 1 14 RTA00000340F.f.22.1 M00001594B:F12 1720
2799 2/24/98 966 RTA00000422F.k. l 5.1 M00001594A:G09 19253
2800 2/24/98 46 RTA00000404F.C.20.1 M00001594A:D08 39088
2801 2/24/98 955 RTA00000404F.e.06.1 M00001607D:F06 39315
2802 2/24/98 1 103 RTA00000346F.a.l6.1 M00001593A:B07 12082
2803 2/24/98 540 RTA00000418F.i. l 8.1 M00001595C:B05 78024
2804 2/24/98 1245 RTA00000422F.k.22.1 M00001592C:E05 4098
2805 2/24/98 693 RTA00000404F.b. l9.1 M00001592B:A04 39281
2806 2/24/98 1013 RTA00000404F.b.l8.1 M00001592A:H05 13669
2807 2/24/98 989 RTA00000418F.i.l2.1 M00001592A:E02 78971
2808 2/24/98 404 RTA00000404F.b. l l . l M00001591 D:F06 39079
2809 2/24/98 786 RTA00000404F.b.09.1 M00001591 D:C07 39166
2810 2/24/98 1 147 RTA00000404F.C.18.1 M00001594A:C01 38982
281 1 2/24/98 686 RTAOOOOO 129A. 21.1 M00001601 A:E12 82067
2812 2/24/98 101 1 RTA00000400F.C.04.1 M00001618A:F08 6445
2813 2/24/98 702 RTAOOOOO 130A.d.5.1 M00001605A:H03 82051
2814 2/24/98 425 RTAOOOOO 130A.b.5.1 M00001605A:E09 79579
2815 2/24/98 ' 458 RTAOOOOO 130A.a.19.1 M00001605A:A06 0
2816 2/24/98 51 RTAOOOOO 129A.n.21.1 M00001604A:C 1 1 79381
2817 2/24/98 804 RTAOOOOO 129A.n.24.1 M00001604A:C07 81409
2818 2/24/98 317 RTAOOOOO 195 AF.b.21.1 M00001595B:A09 39055
2818 1/28/98 602 RTAOOOOO 195 AF.b.21.1 M00001595B:A09 39055
2819 2/24/98 864 RTAOOOOO 129A.n.17.1 M00001604A:A09 7981 1
2820 2/24/98 317 RTAOOOOO 195 AF.b.21.1 M00001595B:A09 39055
2820 1/28/98 602 RTAOOOOO 195 AF.b.21.1 M00001595B:A09 39055
2821 2/24/98 875 RTA00000129A.k.22.1 M00001601 A:E02 79639
2822 2/24/98 406 RTA00000129A. 12.1 M00001601A:A06 79322
2823 2/24/98 179 RTA00000418F.i. l9.1 M00001596D:E03 79180
2824 2/24/98 759 RTA00000399F.O.06.1 M00001595D:G03 13574
2825 2/24/98 306 RTA00000404F.d.l3.1 M00001595D:A04 39036
2826 2/24/98 1055 RTA00000346F.a.04.1 M00001607B:C05 5382
2827 2/24/98 350 RTAOOOOO 129 A.p.3.1 M00001604A:B08 32644
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
2828 2/24/98 721 RTA00000422F. 14.1 M00001649D:A08 0
2829 2/24/98 391 RTAOOOOO 130A.li.16.1 M00001617A:A08 80761
2830 2/24/98 962 RTA00000404F.p.05.2 M00001652D:E09 1896
2831 2/24/98 65 RTA00000404F.p.04.2 M00001652D:E05 39069
2832 2/24/98 1108 RTA00000346F.C.16.1 M00001652B:G10 9579
2833 2/24/98 1200 RTA00000422F.k.l7.1 M00001652A:A01 38955
2834 2/24/98 1218 RTA00000418F.m.l8.1 M00001653B:G10 76479
2835 2/24/98 171 RTA00000404F.n.20.1 M00001650A:C11 26865
2836 2/24/98 180 RTA00000400F.J.19.1 M00001653C:D10 4086
2837 2/24/98 556 RTA00000400F.i.ll.l M00001649C:H10 2587
2838 2/24/98 848 RTA00000404F.ιι.18.2 M00001649C:E11 37169
2839 2/24/98 29 RTA00000404F.n.l6.2 M00001649C:D05 39095
2840 2/24/98 146 RTA00000404F.n.ll.2 M00001649A:E11 38001
2841 2/24/98 700 RTA00000350R.m.l4.1 M00001644C:B07 39171
2842 2/24/98 699 RTA00000340F.I.05.1 M00001644B:D06 38935
2843 2/24/98 479 RTA00000418F.rn.10.] M00001651A:H11 79110
2844 2/24/98 1169 RTA00000405F.b.08.1 M00001656B:E01 39182
2845 2/24/98 855 RTA00000423F.a.01.1 M00001659C:F10 39103
2846 2/24/98 363 RTA00000405F.C.11.1 M00001659A:D12 39068
2847 2/24/98 807 RTA00000418F.n.11.1 M00001658D:G12 78977
2848 2/24/98 795 RTA00000418F.n.07.1 M00001658B:A07 76316
2849 2/24/98 109 RTA00000422F.p.24.2 M00001658A:G09 5823
2850 2/24/98 696 RTA00000404F.p.l2.2 M00001653B:C06 0
2851 2/24/98 369 RTA00000410F.m.05.1 M00001657B:B04 74964
2852 2/24/98 1229 RTA00000422F.n.l4.1 M00001642C:G02 26787
2853 2/24/98 529 RTA00000422F.O.19.2 M00001655C:E01 13084
2854 2/24/98 327 RTA00000405F.a.ll.l M00001655A:B11 39124
2855 2/24/98 393 RTA00000418F.m.24.1 M00001654D:F12 77114
2856 2/24/98 381 RTA00000418F.m.23.1 M00001654D:F11 77195
2857 2/24/98 877 RTA00000418F.rn.22.! M00001654D:E12 74567
2858 2/24/98 166 RTA00000418F.m.l9.1 M00001654D:A03 8890
2859 2/24/98 291 RTA00000405F.C.01.1 M00001657D:A04 19236
2860 2/24/98 356 RTA00000409F.m.24.1 M00001620D:H02 3942
2861 2/24/98 717 RTA00000404F...22.1 M00001625C:G05 39082
2862 2/24/98 648 RTA00000340F.i.l3.1 M00001624B:B10 79299
2863 2/24/98 914 RTA00000138A.m.l5.1 M00001624A:A03 41603
2864 2/24/98 587 RTAOOOOO 130A.O.21.1 M00001623A:F04 80218
2865 2/24/98 22 RTA00000130A.m.l5.1 M00001622A:H12 81630
2866 2/24/98 767 RTAOOOOO 138A.p.10.1 M00001644A:H01 81625
2867 2/24/98 262 RTA00000409F.n.l4.1 M00001621B:G05 78190
2868 2/24/98 960 RTA00000404F.1.19.2 M00001639B:H01 16196
2869 2/24/98 608 RTA00000404F.U2.1 M00001620D:G11 39001
2870 2/24/98 342 RTA00000404F.i.02.1 M00001619D:D10 39015
2871 2/24/98 195 RTA00000404F.h.22.1 M00001619C:C07 18735
2872 2/24/98 214 RTA00000404F.h.l9.1 M00001619A:E05 8096
2873 2/24/98 52 RTA00000409F.m.l2.1 M00001618B:D09 73490
2874 2/24/98 769 RTA00000340F.i.l0.1 M00001618A:F10 38561
2875 2/24/98 383 RTA00000404F.U8.1 M00001621C:H12 21912
2876 2/24/98 256 RTA00000404F.1T1.03.2 M00001640A:H02 11799
2877 2/24/98 519 RTA00000404F.1.10.1 M00001638B:F10 23136
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
2878 2/24/98 646 RTA00000421 F.m. l 4.1 M00001642A:F03 3524
2879 2/24/98 659 RTA00000422F.m.24.1 M00001641 D:C04 39159
2880 2/24/98 701 RTA0000041 8F.I.1 1 .1 M00001641 C:H07 77158
2881 2/24/98 873 RTA00000418F.1.06.1 M00001641 C:F01 73317
2882 2/24/98 422 RTA00000418F.1.04.1 M00001641 C:D02 74140
2883 2/24/98 766 RTA00000404FJ.01 .1 M00001625D:G 10 26859
2884 2/24/98 20 RTA00000404F.m.04.2 M00001641 A:A1 1 22720
2885 2/24/98 346 RTA00000418F.J.08.1 M00001626C:C 1 1 73382
2886 2/24/98 141 RTA00000418F.k. l 9.1 M00001639C:C02 74932
2887 2/24/98 373 RTA00000418F. 18.1 M00001639C:A10 75385
2888 2/24/98 405 RTA00000418F.k. l 7.1 M00001639C:A09 75390
2889 2/24/98 63 RTA00000404F.1.20.2 M00001639B:H05 38638
2889 2/24/98 133 RTA00000404F.1.20.1 M00001639B:H05 38638
2890 2/24/98 133 RTA00000404F.1.20.1 M00001639B:H05 38638
2890 2/24/98 63 RTA00000404F.1.20.2 M00001639B:H05 38638
2891 2/24/98 1261 RTA00000404F.m. l 7.2 M00001643B:E05 0
2892 2/24/98 626 RTA00000410F.J.01 .1 M00001641 B:F 12 73399
2893 2/24/98 982 RTAOOOOO 126 A.p.23.2 M00001 552A:F06 80915
2894 2/24/98 196 RTA00000418F. 10.1 M00001639A:G07 74454
2895 2/24/98 765 RTA00000137A.J.15.4 M00001559A:C08 4213
2896 2/24/98 895 RTAOOOOO 137AJ.1 1 .4 M00001559A:A1 1 79752
2897 2/24/98 232 RTAOOOOO 128 A.b.20.1 M00001558A:G09 79761
2898 2/24/98 152 RTA00000127A.L20.1 M00001555A:B 12 81418
2899 2/24/98 78 RTA00000195AF.b. l 3.1 M00001560D:A03 12605
2899 1 /28/98 59 RTA00000195AF.b. l 3.1 M00001560D:A03 12605
2900 2/24/98 448 RTA00000127A.a.3.1 M00001552A:H10 13232
2901 2/24/98 801 RTAOOOOO 128 A.m.23.1 M00001561 A:D01 81441
2902 2/24/98 499 RTAOOOOO 126A.p.18.2 M00001552A:E10 80881
2903 2/24/98 1212 RTA00000349R.O.03.1 M00001551 D:H07 23006
2904 2/24/98 484 RTA00000126A.n. l 3.2 M00001551 A:H06 79735
2905 2/24/98 240 RTAOOOOO 126A.n.7.2 M0000155 1 A:D06 79557
2906 2/24/98 45 1 RTAOOOOO 126A.0.22.1 M00001551 A:A 1 1 81752
2907 2/24/98 513 RTAOOOOO 126A.k.7.2 M00001550A:E07 79866
2908 2/24/98 578 RTAOOOOO 127A.f.1 1 .1 M00001554A:A08 81463
2909 2/24/98 372 RTA00000408F.p.24.1 M00001579A:E03 74286
2910 2/24/98 985 RTA00000409F.a.08.1 M00001582D:B01 74978
291 1 2/24/98 685 RTAOOOOO 129A.a.13.2 M00001582A:A03 79780
2912 2/24/98 574 RTA00000403F.O.14.1 M00001579D:H09 38971
2913 2/24/98 601 RTA00000403F.O.13.1 M00001579D:F04 39049
2914 2/24/98 432 RTA0000041 8F.g.05.1 M00001579C:H06 73075
2915 1 /28/98 59 RTAOOOOO 195AF.b.13.1 M00001560D:A03 12605
2915 2/24/98 78 RTAOOOOO 195AF.b.13.1 M00001560D:A03 12605
2916 2/24/98 491 RTA0000041 8F.f.21 . 1 M00001579B:F04 75157
2917 2/24/98 612 RTA00000125A. 14.1 M00001545A:G05 79457
2918 1 /28/98 248 RTAOOOOO 198R.C.14.1 M00001578D:C04 39814
2918 2/24/98 778 RTA00000347F.e.05.1 M00001 578D:C04 39814
2919 1 /28/98 248 RTA00000198R.C.14.1 M00001578D:C04 39814
2919 2/24/98 778 RTA00000347F.e.05.1 M00001578D:C04 39814
2920 2/24/98 361 RTA00000422F.d. l 6.1 M00001570C:G03 39133
2921 2/24/98 173 RTA00000418F.d. l 3.1 M00001570A:H01 74309
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
2922 2/24/98 1 195 RTA00000422F.e.23.1 M00001567D:B03 19246
2923 2/24/98 1 168 RTA00000421 F.b.06.1 M00001567A:B09 21 13
2924 2/24/98 580 RTA00000403F.O.07.1 M00001579C:A01 39037
2925 2/24/98 53 1 RTA00000345F.n. l2.1 M00001528A:C04 7337
2926 2/24/98 154 RTA00000340F.b.21.1 M00001533D:A08 8001
2927 2/24/98 19 RTAOOOOO 123 A.k.23.1 M00001533A:G05 80313
2928 2/24/98 1265 RTA00000340F.d.07.1 M00001532D:A06 0
2929 2/24/98 1 124 RTAOOOOO 123 A.h.22.1 M00001532A:C01 17124
2930 2/24/98 1241 RTA00000408F.1.14.1 M00001530A:E10 12001
2931 2/24/98 534 RTAOOOOO 126A.g.7.1 M00001548A:H04 1902
2932 2/24/98 694 RTA00000418F.C.07.1 M00001529D:C05 73245
2933 2/24/98 1034 RTAOOOOO 124A.f.16.3 M00001536A:F1 1 47430
2934 2/24/98 790 RTA00000345F.n.08.1 M00001517A:B 1 1 0
2935 2/24/98 613 RTAOOOOO 122A.J .22.1 M00001 516A:F06 81 151
2936 2/24/98 885 RTAOOOOO 122AJ.17.1 M00001516A:D02 62736
2937 2/24/98 1262 RTAOOOOO 122A.h.4.1 M00001514A:G03 33576
2938 2/24/98 135 RTAOOOOO 122A.d.5.1 M00001513A:F05 81 155
2939 1/28/98 391 RTAOOOOO 179AF.e.20.3 M00001396A:C03 4009
2940 2/24/98 537 RTA00000408F.1.09.1 M00001530A:A09 75487
2941 2/24/98 683 RTA00000403F.J.21 .1 M00001540D:E02 24723
2942 2/24/98 343 RTA00000422F.g.21.1 M00001583A:F07 17232
2943 2/24/98 226 RTAOOOOO 125A.k.10.1 M00001545A:F02 81644
2944 2/24/98 763 RTA00000135A.m. l 8.1 M00001545A:C03 19255
2945 2/24/98 156 RTA00000125A.U .1 M00001545A:B12 0
2946 2/24/98 597 RTAOOOOO 135A.1.1 .2 M00001545A:B10 39426
2947 2/24/98 586 RTAOOOOO 125 A.g.24.1 M00001544A:F05 80397
2948 2/24/98 467 RTAOOOOO 123A.n.13.2 M00001534A:D03 39167
2949 2/24/98 830 RTA00000347F.b.08.1 M00001541 B:E05 17591
2950 2/24/98 997 RTA00000134A.1.9.1 M00001535A:D 10 81814
2951 2/24/98 371 RTA00000403F.J.17.1 M00001539D:B 10 38563
2952 2/24/98 33 RTA00000403F.J.15.1 M00001539B:G07 23840
2953 2/24/98 1209 RTA00000408F.n.05.2 M00001539A:H02 77883
2954 2/24/98 530 RTA00000408F.n.02.2 M00001539A:E01 76993
2955 2/24/98 1213 RTA00000135A.a.23.1 M00001537A:H05 27054
2956 2/24/98 347 RTA00000125A.n.4.1 M00001546A:D08 81984
2957 2/24/98 472 RTAOOOOO 135A.f.14.2 M00001542A:G 12 79969
2958 2/24/98 243 RTA00000410F.C.14.1 M00001634A:H05 77809
2959 2/24/98 919 RTA00000410F.d. l 8.1 M00001635D:D05 75458
2960 2/24/98 825 RTA00000404F.k.22.2 M00001635D:C 12 39084
2960 2/24/98 364 RTA00000404F. 22.1 M00001635D:C12 39084
2961 2/24/98 825 RTA00000404F.k.22.2 M00001635D:C 12 39084
2961 2/24/98 364 RTA00000404F. 22.1 M00001635D:C 12 39084
2962 2/24/98 595 RTA00000410F.d. l 0.1 M00001635B:H02 77561
2963 2/24/98 175 RTA00000410F.d.09.1 M00001635B:H01 76964
2964 2/24/98 206 RTA00000410F.b. l 5.1 M00001633C:F09 77100
2965 2/24/98 1083 RTA0000041 8F.J.20.1 M00001634D:D04 77101
2966 2/24/98 922 RTA00000410F.e.09.1 M00001636A:F08 76093
2967 2/24/98 1035 RTA00000404F.k. l 5.1 M00001634A:B04 18225
2968 2/24/98 1 167 RTA00000410F.C.06.1 M00001633D:H06 77784
2969 2/24/98 53 RTA00000410F.C.04.1 M00001633D:G09 74099
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
2970 2/24/98 567 RTA00000410F.C.02.1 M00001633D:D12 75055
2971 2/24/98 819 RTA00000410F.b.24.1 M00001633D:D09 75104
2972 2/24/98 666 RTA00000403F.O.19.1 M00001582D:F02 78615
2973 2/24/98 559 RTA00000418F.k.03.1 M00001634D:G 1 1 78901
2974 2/24/98 999 RTA00000418F. 04.1 M00001637A:A03 75864
2975 2/24/98 936 RTA00000121 A.n.23.1 M0000151 1 A:G01 26981
2976 2/24/98 201 RTA00000404F.I.09.1 M00001638B:E12 39176
2977 2/24/98 1 160 RTA00000400F.g.02.1 M00001638B:E03 1508
2978 2/24/98 827 RTA00000410F.f. l 2.1 M00001637C:E03 73883
2979 2/24/98 622 RTA00000404F.1.07.1 M00001637C:C06 10798
2980 2/24/98 365 RTA00000418F.k.07.1 M00001637A:F10 75067
2981 2/24/98 248 RTA00000404F. 24.1 M00001636A:C03 15256
2982 2/24/98 25 RTA00000418F. 05.1 M00001637A:A06 73021
2983 2/24/98 1 178 RTA00000400F.f. l l . l M00001636A:E07 4088
2984 2/24/98 1 180 RTA00000404F.1.05.1 M00001636D:F09 38671
2985 2/24/98 71 1 RTA00000404F.I.03.2 M00001636B:G 1 1 40272
2985 2/24/98 785 RTA00000404F.I.03.1 M00001636B:G 1 1 40272
2986 2/24/98 785 RTA00000404F.1.03.1 M00001636B:G1 1 40272
2986 2/24/98 71 1 RTA00000404F.1.03.2 M00001636B:G 1 1 40272
2987 2/24/98 71 1 RTA00000404F.1.03.2 M00001636B:G1 1 40272
2987 2/24/98 785 RTA00000404F.1.03.1 M00001636B:G1 1 40272
2988 2/24/98 71 1 RTA00000404F.1.03.2 M00001636B:G 1 1 40272
2988 2/24/98 785 RTA00000404F.I.03.1 M00001636B:G 1 1 40272
2989 2/24/98 1 106 RTA00000410F.b. l 7.1 M00001633C:H05 77458
2990 2/24/98 253 RTA00000400F.f.l 8.1 M00001637A:E10 3764
2991 2/24/98 562 RTA00000401 F.J.17.1 M00003901 B:C05 5483
2992 2/24/98 1082 RTA00000137A.O.22.1 M00001587A:D01 0
2993 2/24/98 594 RTAOOOOO 129A.C.18.2 M00001587A:B10 37216
2994 2/24/98 891 RTAOOOOO 137A.p.12.1 M00001587A:B01 80614
2995 2/24/98 131 RTA00000418F.g.22.1 M00001585B:F01 74837
2996 2/24/98 880 RTA00000418F.g.20.1 M00001585B:C03 74626
2997 2/24/98 742 RTA00000410F.b. l 8.1 M00001633C:H1 1 76701
2998 2/24/98 879 RTA00000409F.b. l9.1 M00001584D:H02 14479
2999 2/24/98 167 RTA00000399F.1.14.1 M00001590B:G08 3354
3000 2/24/98 1260 RTA00000422F.f.l 8.1 M00001583D:B08 24528
3000 2/24/98 1258 RTA00000403F.p.05.2 M00001583D:B08 24528
3001 2/24/98 1260 RTA00000422F.f.l 8.1 M00001583D:B08 24528
3001 2/24/98 1258 RTA00000403F.p.05.2 M00001583D:B08 24528
3002 2/24/98 1260 RTA00000422F.f. l 8.1 M00001583D:B08 24528
3002 2/24/98 1258 RTA00000403F.p.05.2 M00001583D:B08 24528
3003 2/24/98 1260 RTA00000422F.f. l 8.1 M00001583D:B08 24528
3003 2/24/98 1258 RTA00000403F.p.05.2 M00001583D:B08 24528
3004 2/24/98 67 RTA00000409F.a.22.1 M00001583B:F02 75200
3005 2/24/98 564 RTA00000418F.k.08.1 M00001639A:C03 18259
3006 1/28/98 282 RTAOOOOO 193AF.C.15.1 M00004248B:E08 3726
3007 2/24/98 242 RTA00000404F.J.08.1 M00001629B:B08 39066
3008 2/24/98 669 RTA00000410F.b. l 0.1 M00001633C:B09 74504
3009 2/24/98 725 RTA00000410F.b.07.1 M00001633C:A05 78916
3010 2/24/98 423 RTA00000410F.a.l 6.1 M00001633A:E06 73548
301 1 2/24/98 695 RTA00000418F.J.15.1 M00001632C:H07 74855
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
3012 2/24/98 901 RTA00000418F.J.14.1 M00001632C:B10 32623
3013 2/24/98 752 RTA00000410F.a.08.1 M00001632A:B 10 73324
3014 2/24/98 1007 RTA00000404F.a.01.1 M00001589B:B08 19251
3015 2/24/98 1093 RTA00000340F.U 5.1 M00001629C:E07 26815
3016 2/24/98 664 RTA00000404F.a.09.1 M00001589C:E06 38985
3017 2/24/98 1246 RTA00000418F.J.1 1.1 M00001626C:E04 73853
3018 2/24/98 174 RTA00000404F.b.02.1 M00001591 B:B12 38984
3019 2/24/98 1 142 RTA00000418F.i.06.1 M00001591 B:B06 75151
3020 2/24/98 740 RTA00000399F.I.19.1 M00001590D:G07 40145
3021 2/24/98 1098 RTA00000409F.d. l6.1 M00001590C:F10 76090
3022 2/24/98 591 RTA00000409F.a. l 6.1 M00001583A:A05 73990
3023 2/24/98 1 1 10 RTA00000404F.J.24.1 M00001631 D:G05 39067
3024 1/28/98 108 RTA00000183 AR.lι.23.2 M00001528A:F09 18957
3024 1/28/98 236 RTAOOOOO 183 AR.h.23.1 M00001528A:F09 18957
3024 1/28/98 129 RTAOOOOO 134A.d.10.1 M00001528A:F09 18957
3025 1/28/98 68 RTAOOOOO 184F.k.19.1 M00001558B:D08 8022
3025 1/28/98 63 RTAOOOOO 184AF.k.19.1 M00001558B:D08 8022
3026 1/28/98 269 RTA00000183AF.k.l3.1 M00001534B:C 12 0
3027 1/28/98 129 RTAOOOOO 134A.d.10.1 M00001528A:F09 18957
3027 1/28/98 108 RTAOOOOO 183 AR.h.23.2 M00001528A:F09 18957
3027 1/28/98 236 RTAOOOOO 183 AR.h.23.1 M00001528A:F09 18957
3028 1/28/98 129 RTAOOOOO 134A.d.10.1 M00001528A:F09 18957
3028 1/28/98 108 RTAOOOOO 183 AR.h.23.2 M00001528A:F09 18957
3028 1/28/98 236 RTAOOOOO 183 AR.h.23.1 M00001528A:F09 18957
3029 1/28/98 236 RTAOOOOO 183 AR.h.23.1 M00001528A:F09 18957
3029 1/28/98 108 RTA00000183AR.h.23.2 M00001528A:F09 18957
3029 1/28/98 129 RTA00000134A.d.l 0.1 M00001528A:F09 18957
3030 1/28/98 34 RTA00000197AF.n.8.1 M00001536D:A12 4101
3031 1/28/98 108 RTAOOOOO 183 AR.h.23.2 M00001528A:F09 18957
3031 1/28/98 129 RTA00000134A.d. l 0.1 M00001528A:F09 18957
3031 1/28/98 236 RTAOOOOO 183 AR.h.23.1 M00001528A:F09 18957
3032 1/28/98 106 RTAOOOOO 197AF.n.21.1 M00001540B:C09 0
3033 1/28/98 236 RTAOOOOO 183 AR.h.23.1 M00001528A:F09 18957
3033 1/28/98 129 RTA00000134A.d.l 0.1 M00001528A:F09 18957
3033 1/28/98 108 RTAOOOOO 183 AR.h.23.2 M00001528A:F09 18957
3034 1/28/98 108 RTAOOOOO 183 AR.h.23.2 M00001528A:F09 18957
3034 1/28/98 236 RTA00000183AR.h.23.1 M00001528A:F09 18957
3034 1/28/98 129 RTAOOOOO 134A.d.10.1 M00001528A:F09 18957
3035 1/28/98 129 RTAOOOOO 134A.d.10.1 M00001528A:F09 18957
3035 1/28/98 108 RTAOOOOO] 83AR.h.23.2 M00001528A:F09 18957
3035 1/28/98 236 RTA00000183 AR.h.23.1 M00001528A:F09 18957
3036 1/28/98 233 RTA00000197AF.1.8.1 M0000151 1 B:C06 39954
3037 1/28/98 323 RTA00000182AF.m.21.1 M00001490C:C 12 18699
3038 1/28/98 223 RTA00000197F.i.9.1 M00001488D:C 10 0
3039 1/28/98 236 RTA00000183AR.h.23.1 M00001528A:F09 18957
3039 1/28/98 108 RTA00000183AR.h.23.2 M00001528A:F09 18957
3039 1/28/98 129 RTAOOOOO 134A.d.10.1 M00001528A:F09 18957
3040 1/28/98 352 RTAOOOOO 197AF.p.3.1 M00001550A:A03 7239
3041 1/28/98 301 RTA0OOOO181 AR.i.l 9.3 M00001452C:B06 16970
3041 1/28/98 295 RTA00000181 AR.U 9.2 M00001452C:B06 16970
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
3042 1/28/98 68 RTAOOOOO 184F.k.19.1 M00001558B:D08 8022
3042 1/28/98 63 RTA00000184AF.k.l9.1 M00001558B:D08 8022
3043 1/28/98 63 RTAOOOOO 184AF.k.19.1 M00001558B:D08 8022
3043 1/28/98 68 RTAOOOOO 184F.k.19.1 M00001558B:D08 8022
3044 1/28/98 41 RTA00000184F.k.l2.1 M00001557D:D09 8761
3045 1/28/98 150 RTAOOOOO 184F.k.09.1 M00001557C:H07 7065
3046 1/28/98 82 RTA00000183AF.1.18.1 M00001535D:C01 3484
3047 1/28/98 338 RTAOOOOO 184AF.i.1.1 M00001554B:C07 0
3048 1/28/98 327 RTAOOOOO 182AF.L 1.3 M00001479B:A01 7033
3049 1/28/98 256 RTA00000184AR.e.l5.1 M00001549C:E06 16347
3050 1/28/98 99 RTAOOOOO 184AF.d.8.1 M00001548A:A08 4393
3051 1/28/98 355 RTAOOOOO 184AR.b.24.1 M00001546B:C05 5777
3052 1/28/98 322 RTAOOOOO 184AR.b.21.1 M00001546B:B02 39788
3053 1/28/98 97 RTAOOOOO 197AF.o.2.1 M00001541C:B07 5739
3054 1/28/98 313 RTA00000183AF.O.11.1 M00001540D:D02 0
3055 1/28/98 42 RTAOOOOO] 84F.J.21.1 M00001557A:D02 7065
3056 1/28/98 378 RTA00000181AF. 24.3 M00001454B:C12 7005
3056 1/28/98 119 RTA00000181AR. 24.2 M00001454B:C12 7005
3056 1/28/98 116 RTA00000181AR. 24.3 M00001454B:C12 7005
3057 1/28/98 134 RTAOOOOO 197F.e.11.1 M00001454B:G03 2306
3057 1/28/98 298 RTAOOOOO 197 AR.e.11.1 M00001454B:G03 2306
3058 1/28/98 134 RTAOOOOO 197F.e.11.1 M00001454B:G03 2306
3058 1/28/98 298 RTAOOOOO 197 AR.e.11.1 M00001454B:G03 2306
3059 1/28/98 134 RTAOOOOO 197F.e.11.1 M00001454B:GO3 2306
3059 1/28/98 298 RTAOOOOO 197AR.e.11.1 M00001454B:G03 2306
3060 1/28/98 116 RTA00000181AR.L24.3 M00001454B:C12 7005
3060 1/28/98 378 RTA00000181AF. 24.3 M00001454B:C12 7005
3060 1/28/98 119 RTA00000181AR. 24.2 M00001454B:C12 7005
3061 1/28/98 116 RTA00000181AR. 24.3 M00001454B:C12 7005
3061 1/28/98 378 RTA00000181AF. 24.3 M00001454B:C12 7005
3061 1/28/98 119 RTA00000181AR.k.24.2 M00001454B:C12 7005
3062 1/28/98 159 RTAOOOOO 182AF.1.12.1 M00001487A:A05 1027
3063 1/28/98 119 RTA00000181AR. 24.2 M00001454B:C12 7005
3063 1/28/98 116 RTA00000181AR. 24.3 M00001454B:C12 7005
3063 1/28/98 378 RTA00000181AF.k.24.3 M00001454B:C12 7005
3064 1/28/98 341 RTA00000181AF.1.06.2 M00001454C:C08 0
3065 1/28/98 116 RTA00000181AR. 24.3 M00001454B:C12 7005
3065 1/28/98 119 RTA00000181AR.k.24.2 M00001454B:C12 7005
3065 1/28/98 378 RTA00000181AF. 24.3 M00001454B:C12 7005
3066 1/28/98 378 RTA0000018 lAF.k.24.3 M00001454B:C12 7005
3066 1/28/98 116 RTA00000181AR. 24.3 M00001454B:C12 7005
3066 1/28/98 119 RTA00000181AR. 24.2 M00001454B:C12 7005
3067 1/28/98 378 RTA00000181AF. 24.3 M00001454B:C12 7005
3067 1/28/98 116 RTA00000181AR.k.24.3 M00001454B:C12 7005
3067 1/28/98 119 RTA00000181AR. 24.2 M00001454B:C12 7005
3068 1/28/98 378 RTA00000181AF.k.24.3 M00001454B:C12 7005
3068 1/28/98 116 RTA00000181AR. 24.3 M00001454B:C12 7005
3068 1/28/98 119 RTAOOOOO] 81 AR.k.24.2 M00001454B:C12 7005
3069 1/28/98 170 RTA00000197AF.d.23.1 M00001453A:E11 16130
3070 1/28/98 491 RTAOOOOO 196F. 11.1 M00001399C:H12 J)
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
3071 1/28/98 1 19 RTA00000181 AR.k.24.2 M00001454B:C12 7005
3071 1/28/98 378 RTA00000181 AF. 24.3 M00001454B:C 12 7005
3071 1/28/98 1 16 RTA00000181 AR. 24.3 M00001454B:C12 7005
3072 1/28/98 674 RTAOOOOO 197AR.e.24.1 M00001456B:F10 39250
3072 1/28/98 3 RTAOOOOO 197 AF.e.24.1 M00001456B:F10 39250
3073 2/24/98 78 RTA00000195AF.b. l3.1 M00001560D:A03 12605
3073 1/28/98 59 RTA00000195AF.b. l3.1 M00001560D:A03 12605
3074 1/28/98 189 RTAOOOOO 197AF.li.10.1 M00001476B:F10 15554
3075 1/28/98 46 RTAOOOOO 182AF.f.13.1 M00001470C:B10 8010
3076 1/28/98 200 RTA00000182AF.f.2.1 M00001469D:D02 4794
3077 1/28/98 325 RTA00000182AF.d. l 8.4 M00001467D:H05 37435
3078 1/28/98 45 RTA00000197AR.f.l2.1 M00001458C:E01 3513
3079 1/28/98 298 RTAOOOOO 197 AR.e.1 1.1 M00001454B:G03 2306
3079 1/28/98 134 RTA00000197F.e.l l .l M00001454B:G03 2306
3080 1/28/98 37 RTA00000181 AF.H.15.2 M00001457A:B07 86128
3081 1/28/98 7 RTAOOOOO 197AR.e.12.1 M00001454B:G07 22095
3082 1/28/98 674 RTAOOOOO 197AR.e.24.1 M00001456B:F10 39250
3082 1/28/98 j ^ RTAOOOOO 197 AF.e.24.1 M00001456B:F10 39250
3083 1/28/98 88 RTAOOOOO 197 AF.e.23.1 M00001456B:C09 37157
3084 1/28/98 243 RTA00000181 AF.m.15.3 M00001455D:A1 1 12081
3085 1/28/98 326 RTA00000197AR.e. l9.1 M00001455D:A09 8047
3086 1/28/98 293 RTA00000197AF.e. l3.1 M00001454C:F02 662
3087 1/28/98 380 RTAOOOOO 182 AF.k.24.1 M00001485D:B10 5625
3088 1/28/98 206 RTA00000181AF.O.04.2 M00001457C:C12 22205
3089 1/28/98 228 RTA00000187AR.h.l 5.2 M00001679A:A06 6660
3090 1/28/98 68 RTAOOOOO 184F. 19.1 M00001558B:D08 8022
3090 1/28/98 63 RTA00000184AF.k.19.1 M00001558B:D08 8022
3091 1/28/98 191 RTA00000187AF.p.23.1 M00003748B:F02 39804
3092 1/28/98 10 RTAOOOOO 198AF.n.16.1 M00001694C:H 10 3721
3093 1/28/98 219 RTAOOOOO 198AF.m.19.1 M00001680D:D02 40041
3093 1/28/98 32 RTAOOOOO 198R.m.19.1 M00001680D:D02 40041
3094 1/28/98 32 RTAOOOOO 198R.m.19.1 M00001680D:D02 40041
3094 1/28/98 219 RTA00000198AF.m. l 9.1 M00001680D:D02 40041
3095 1/28/98 317 RTA00000198AF.p.09.1 M00003761 D:E02 10473
3095 1/28/98 186 RTA00000198R.p.09.1 M00003761D:E02 10473
3096 1/28/98 219 RTA00000198AF.m. l9.1 M00001680D:D02 40041
3096 1/28/98 32 RTA00000198R.m. l 9.1 M00001680D:D02 40041
3097 1/28/98 64 RTA00000198AF.p.l2.1 M00003763D:E10 8878
3097 1/28/98 542 RTA00000198R.p.l 2.1 M00003763D:E10 8878
3098 1/28/98 364 RTAOOOOO 187 AF.g.13.1 M00001676C:C1 1 2991
3099 1/28/98 430 RTA00000198R.k.23.1 M00001661 B:C08 8995
3099 1/28/98 294 RTAOOOOO 198 AF.k.23.1 M00001661 B:C08 8995
3100 1/28/98 430 RTA00000198R.k.23.1 M00001661 B:C08 8995
3100 1/28/98 294 RTAOOOOO 198 AF.k.23.1 M00001661 B:C08 8995
3101 1/28/98 57 RTA00000198AF. 20.1 M00001660C:B12 22553
3102 1/28/98 368 RTA00000198AF. 8.1 M00001660A:C12 17432
3103 1/28/98 247 RTA00000198AF.k.08.1 M00001656C:G08 17436
3104 1/28/98 219 RTA00000198AF.m.l9.1 M00001680D:D02 40041
3104 1/28/98 32 RTA00000198R.m. l 9.1 M00001680D:D02 40041
3105 1/28/98 199 RTA00000199R.C.09.1 M00003800A:C09 16824
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
3105 1/28/98 66 RTA00000199F.C.09.2 M00003800A:C09 16824
3106 1/28/98 225 RTA00000189AF.b.5.1 M00003828A:E04 3784
3107 1/28/98 5 RTA00000195R.C.11.1 M00003811A:E03 66087
3108 1/28/98 284 RTAOOOOO 199F.d.10.2 M00003808C:B05 22049
3108 2/24/98 816 RTA00000354R.n.04.1 M00003808C:B05 22049
3109 1/28/98 284 RTAOOOOO 199F.d.10.2 M00003808C:B05 22049
3109 2/24/98 816 RTA00000354R.n.04.1 M00003808C:B05 22049
3110 1/28/98 2 RTA00000188AF.n.l5.1 M00003804A:H04 0
3111 1/28/98 317 RTAOOOOO 198 AF.p.09.1 M00003761D:E02 10473
3111 1/28/98 186 RTA00000198R.p.09.1 M00003761D:E02 10473
3112 1/28/98 199 RTAOOOOO 199R.C.09.1 M00003800A:C09 16824
3112 1/28/98 66 RTAOOOOO 199F.C.09.2 M00003800A:C09 16824
3113 1/28/98 487 RTA00000198F.i.8.1 M00001639A:F10 9807
3113 1/28/98 277 RTA00000198AR.i.08.1 M00001639A:F10 9807
3114 1/28/98 66 RTAOOOOO 199F.C.09.2 M00003800A:C09 16824
3114 1/28/98 199 RTAOOOOO 199R.C.09.1 M00003800A:C09 16824
3115 1/28/98 224 RTAOOOOO 188AF.m.11.1 M00003799A:D09 0
3116 1/28/98 58 RTA00000199F.b.01.2 M00003778A:D08 19118
3117 1/28/98 216 RTAOOOOO 188 AF.g.9.1 M00003774B:B08 4959
3118 1/28/98 201 RTAOOOOO 198AF.p.18.1 M00003769B:D03 23081
3119 1/28/98 542 RTAOOOOO 198R.p.12.1 M00003763D:E10 8878
3119 1/28/98 64 RTAOOOOO 198AF.p.12.1 M00003763D:E10 8878
3120 1/28/98 199 RTAOOOOO 199R.C.09.1 M00003800A:C09 16824
3120 1/28/98 66 RTA00000199F.C.09.2 M00003800A:C09 16824
3121 1/28/98 146 RTAOOOOO 185AF.a.19.2 M00001571C:H06 5749
3122 1/28/98 248 RTA00000198R.C.14.1 M00001578D:C04 39814
3122 2/24/98 778 RTA00000347F.e.05.1 M00001578D:C04 39814
3123 1/28/98 248 RTA00000198R.C.14.1 M00001578D:C04 39814
3123 2/24/98 778 RTA00000347F.e.05.1 M00001578D:C04 39814
3124 1/28/98 147 RTA00000185AF.C.24.2 M00001578B:E04 23001
3125 1/28/98 195 RTA00000198AF.C.10.1 M00001577B:H02 77149
3126 1/28/98 171 RTAOOOOO 198R.C.07.1 M00001575D:G05 19181
3126 1/28/98 525 RTAOOOOO 198AF.C.7.1 M00001575D:G05 19181
3127 1/28/98 172 RTAOOOOO 186AF.p.09.2 M00001655C:E04 6879
3128 1/28/98 230 RTA00000185AR.b.l8.1 M00001575B:C09 12171
3129 1/28/98 192 RTA00000185AF.m.7.1 M00001605C:D12 39804
3130 1/28/98 19 RTA00000185AF.a.8.1 M00001570D:A03 4868
3131 1/28/98 492 RTA00000198AF.b.8.1 M00001567C:H12 22636
3131 1/28/98 23 RTA00000198R.b.08.1 M00001567C:H12 22636
3132 1/28/98 23 RTAOOOOO 198R.b.08.1 M00001567C:H12 22636
3132 1/28/98 492 RTA00000198AF.b.8.1 M00001567C:H12 22636
3133 1/28/98 357 RTAOOOOO 184AF.0.15.1 M00001564D:C09 0
3134 1/28/98 30 RTA00000184AR.n.07.2 M00001561C:F06 0
3135 1/28/98 59 RTA00000195AF.b.l3.1 M00001560D:A03 12605
3135 2/24/98 78 RTA00000195AF.b.l3.1 M00001560D:A03 12605
3136 1/28/98 525 RTA00000198AF.C.7.1 M00001575D:G05 19181
3136 1/28/98 171 RTAOOOOO 198R.C.07.1 M00001575D:G05 19181
3137 1/28/98 303 RTAOOOOO 186AR.e.03.3 M00001623D:C10 22110
3138 1/28/98 295 RTA00000181AR.i.l9.2 M00001452C:B06 16970
3138 1/28/98 301 RTA00000181AR.i.l9.3 M00001452C:B06 16970
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
3 139 1/28/98 232 RTAOOOOO 186 AF.j .03.2 M00001638A:E07 0
3140 1/28/98 309 RTAOOOOO 198AF.li.12.1 M00001632C:A02 9503
3141 1/28/98 268 RTAOOOOO 186AF.h.01.2 M00001632A:F12 0
3142 1/28/98 267 RTAOOOOO 186AF.g.1 1.2 M00001630B:H09 5214
3143 1/28/98 83 RTAOOOOO 186AF.f.24.2 M00001629B:E06 0
3143 1/28/98 336 RTAOOOOO 186AF.f.24.1 M00001629B:E06 0
3144 1/28/98 222 RTA00000185AF.i.4.1 M00001594A:B12 13942
3145 1/28/98 217 RTAOOOOO 198 AF.h.3.1 M00001625D:C07 22562
3146 1/28/98 196 RTA00000198F.e. l 0.1 M00001599B:E09 9727
3147 1/28/98 372 RTAOOOOO 186 AF.d.23.1 M00001623B:G07 22187
3148 1/28/98 302 RTAOOOOO 186AF.d.1.2 M00001621 C:C08 40044
3149 1/28/98 262 RTA00000186AF.C.17.1 M00001619D:G05 8551
3150 1/28/98 358 RTA00000198AF.g.7.1 M00001616C:C09 13386
3151 1/28/98 166 RTAOOOOO 198 AF.f.21 .1 M00001614D.D09 22676
3152 1 /28/98 277 RTAOOOOO 198AR.i.08.1 M00001639A:F10 9807
3152 1/28/98 487 RTA00000198F.i.8.1 M00001639A:F10 9807
3153 1/28/98 336 RTAOOOOO 186AFT.24.1 M00001629B:E06 0
3153 1/28/98 83 RTAOOOOO 186AFT.24.2 M00001629B:E06 0
3154 1 /28/98 352 RTAOOOOO 197AF.p.3.1 M00001550A:A03 7239
3155 1/28/98 251 RTA00000192AF.ιι.13.1 M00004197D:H01 8210
3156 1/28/98 41 RTAOOOOO 184F.k.12.1 M00001557D:D09 8761
3157 1/28/98 731 RTAOOOOO 184F.k.02.1 M00001557B:H10 5192
3158 1/28/98 42 RTAOOOOO 184FJ.21.1 M00001557A:D02 7065
3159 1/28/98 42 RTAOOOOO 184F.J.21.1 M00001557A:D02 7065
3160 1/28/98 302 RTA00000186AF.d. l .2 M00001621 C:C08 40044
3161 1/28/98 560 RTA00000184AF.i.23.3 M00001556A:F1 1 1577
3162 1/28/98 558 RTAOOOOO 186AR.h.14.1 M00001632D:H07 0
3163 1/28/98 256 RTA00000184AR.e.l 5.1 M00001549C:E06 16347
3164 1/28/98 682 RTA00000125A.J.16.1 M00001544A:E06 0
3165 1/28/98 129 RTA00000134A.d. l 0.1 M00001528A:F09 18957
3165 1/28/98 108 RTA00000183AR.h.23.2 M00001528A:F09 18957
3165 1/28/98 236 RTAOOOOO 183 AR.h.23.1 M00001528A:F09 18957
3166 1/28/98 129 RTAOOOOO 134A.d.10.1 M00001528A:F09 18957
3166 1/28/98 108 RTA00000183 AR.h.23.2 M00001528A:F09 18957
3166 1/28/98 236 RTA00000183AR.h.23.1 M00001528A:F09 18957
3167 1/28/98 108 RTA00000183AR.h.23.2 M00001528A:F09 18957
3167 1/28/98 236 RTAOOOOO 183 AR.h.23.1 M00001528A:F09 18957
3167 1/28/98 129 RTAOOOOO 134A.d.10.1 M00001528A:F09 18957
3168 2/24/98 531 RTA00000345F.n. l2.1 M00001528A:C04 7337
3169 1/28/98 324 RTAOOOOO 184F.J.06.1 M00001556B:G02 1 1294
3170 2/24/98 604 RTA00000351 R.C.13.1 M00003747D:C05 1 1476
3171 1/28/98 301 RTA00000181 AR.i. l 9.3 M00001452C:B06 16970
3171 1/28/98 295 RTA00000181 AR.U9.2 M00001452C:B06 16970
3172 1/28/98 231 RTA00000192AF.1.13.2 M00004185C:C03 1 1443
3173 1/28/98 634 RTAOOOOO 192 AF.j .6.1 M00004172C:D08 1 1494
3174 1/28/98 165 RTAOOOOO 192 AF.g.23.1 M00004157C:A09 6455
3175 1/28/98 574 RTAOOOOO 192 AF.f.3.1 M00004146C:C 1 1 5257
3176 1/28/98 146 RTA00000185AF.a.l9.2 M00001571C:H06 5749
3177 1/28/98 651 RTAOOOOO 189AR.d.22.2 M00003844C:B 1 1 6539
3178 1/28/98 161 RTAOOOOO 183 AF.e.23.2 M00001506D:A09 0
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
3179 1 /28/98 475 RTAOOOOO 187 AR.m.3.3 M00001682C:B 12 17055
3180 2/24/98 39 RTA00000187AF.1.7.1 M00001680D:F08 10539
3181 1/28/98 228 RTAOOOOO 187AR.h.15.2 M00001679A:A06 6660
3182 2/24/98 465 RTA00000350R.p.l 8.1 M00001676B:F05 1 1460
3183 1/28/98 575 RTAOOOOO 186AF.1.12.2 M00001645A:C12 19267
3184 2/24/98 700 RTA00000350R.m. l4.1 M00001644C:B07 39171
3185 1/28/98 261 RTAOOOOO 192AF.a.24.1 M000041 14C:F1 1 13183
3186 1/28/98 236 RTA00000183AR.h.23.1 M00001528A:F09 18957
3186 1/28/98 108 RTA00000183 AR.h.23.2 M00001528A:F09 18957
3186 1/28/98 129 RTA00000134A.d. l 0.1 M00001528A:F09 18957
3187 1/28/98 398 RTA00000177AR.1.13.3 M00001353A:G 12 8078
3188 1 /28/98 645 RTA00000177AF.k.9.1 M00001352A:E02 16245
3189 1/28/98 283 RTA00000177AF.i.8.4 M00001350A:H01 7187
3190 1/28/98 361 RTAOOOOO 177AR.g.16.4 M00001347A:B 10 13576
3191 1/28/98 680 RTAOOOOO 177AFT 10.1 M00001345A:E01 6420
3192 1 /28/98 632 RTA00000183AR.g.03.1 M00001512D:G09 3956
3192 1/28/98 630 RTA00000183AR.g.03.2 M00001512D:G09 3956
3193 1/28/98 702 RTA00000177AR.b.8.5 M00001340B:A06 17062
3194 1/28/98 330 RTA00000177AR.m. l 7.4 M00001355B:G 10 14391
3194 1 /28/98 493 RTAOOOOO 177 AF.m.17.1 M00001355B:G 10 14391
3194 1/28/98 337 RTA00000177AR.m. l 7.3 M00001355B:G10 14391
3195 1/28/98 236 RTA00000183 AR.h.23.1 M00001528A:F09 18957
3195 1/28/98 129 RTA00000134A.d. l 0.1 M00001528A:F09 18957
3195 1/28/98 108 RTA00000183 AR.h.23.2 M00001528A:F09 18957
3196 1/28/98 129 RTAOOOOO 134A.d.10.1 M00001528A:F09 18957
3196 1/28/98 236 RTA000O0183AR.h.23.1 M00001528A:F09 18957
3196 1/28/98 108 RTA00000183 AR.h.23.2 M00001528A:F09 18957
3197 1/28/98 435 RTAOOOOO 182AR.C.22.1 M00001467A:D08 16283
3198 1/28/98 635 RTA00000181 AF.p.7.3 M00001460A:E01 38773
3199 1/28/98 362 RTAOOOOO 197 AR.c.24.1 M00001450A:B12 82498
3200 2/24/98 442 RTA00000347F.b.02.1 M00001450A:A02 39304
3201 1/28/98 265 RTA00000177AF.e. l4.1 M00001343D:H07 23255
3202 1/28/98 270 RTA00000178R.1.08.1 M00001383A:C03 39648
3203 1/28/98 472 RTAOOOOO 192AF.p.17.1 M00004214C:H05 1 1451
3204 1/28/98 603 RTAO0OO0183AR.d.l l .3 M00001504D:G06 6420
3205 1/28/98 519 RTAOOOOO 183 AF.a.24.2 M00001499B:A1 1 10539
3206 1/28/98 435 RTA00000182AR.C.22.1 M00001467A:D08 16283
3207 2/24/98 158 RTA00000348R.J.16.1 M00001410A:D07 7005
3208 1/28/98 41 1 RTA00000179AF.J.13.3 M00001400B:H06 0
3209 1/28/98 742 RTAOOOOO 177AF.m.1.1 M00001353D:D10 14929
3210 1/28/98 270 RTA00000178R.1.08.1 M00001383A:C03 39648
321 1 1/28/98 337 RTAO0OO0177AR.m. l 7.3 M00001355B:G10 14391
321 1 1/28/98 493 RTAOOOOO 177AF.m.17.1 M00001355B:G 10 14391
321 1 1/28/98 330 RTA00000177AR.m.17.4 M00001355B:G 10 14391
3212 1/28/98 297 RTAOOOOO 178 AF.f.9.3 M00001371 C:E09 7172
3213 1/28/98 33 RTAOOOOO 178AR.a.20.1 M00001362C:H 1 1 945
3213 2/24/98 979 RTA00000345F.b.l 7.1 M00001362C:H 1 1 945
3214 1/28/98 33 RTAOOOOO 178 AR.a.20.1 M00001362C:H 1 1 945
3214 2/24/98 979 RTA00000345F.b. l 7.1 M00001362C:H1 1 945
3215 1/28/98 466 RTAOOOOO 177AF.p.20.1 M00001361 A:A05 4141
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
3216 1/28/98 330 RTA00000177AR.m.l7.4 MOOOO1355B:G10 14391
3216 1/28/98 493 RTA00000177AF.m.l7.1 M00001355B:G10 14391
3216 1/28/98 337 RTA00000177AR.m.l7.3 M00001355B:G10 14391
3217 1/28/98 632 RTA00000183AR.g.03.1 M00001512D:G09 3956
3217 1/28/98 630 RTA00000183AR.g.03.2 M00001512D:G09 3956
3218 1/28/98 391 RTA00000179AF.e.20.3 M00001396A:C03 4009
3219 1/28/98 370 RTA00000179AF.C.15.3 M00001392D:H06 2995
3219 1/28/98 460 RTA00000179AF.C.15.1 M00001392D:H06 2995
3220 1/28/98 47 RTAOOOOO 192AF.m.12.1 M00004191D:B11 0
3221 1/28/98 438 RTAOOOOO 180 AR.g.03.4 M00001425A:C11 9024
3221 1/28/98 95 RTA00000180AF.g.3.1 M00001425A:C11 9024
3222 1/28/98 438 RTAOOOOO 180 AR.g.03.4 M00001425A:C11 9024
3222 1/28/98 95 RTAOOOOO 180 AF.g.3.1 M00001425A:C11 9024
3223 1/28/98 320 RTAOOOOO 196AF.m.13.1 M00001415B:E09 16290
3224 1/28/98 365 RTA00000196F.I.20.2 M00001410B:G05 22678
3225 1/28/98 80 RTA00000196AF.p.l3.2 M00001432A:E06 6125
3226 1/28/98 179 RTAOOOOO 179AF.f.20.3 M00001397B:B09 16154
3227 1/28/98 379 RTA00000180AF.1.06.2 M00001433A:G07 5625
3228 1/28/98 460 RTAOOOOO 179AF.C.15.1 M00001392D:H06 2995
3228 1/28/98 370 RTAOOOOO 179 AF.c.15.3 M00001392D:H06 2995
3229 1/28/98 107 RTA00000196R. 13.1 M00001390A:A09 9857
3230 1/28/98 120 RTAOOOOO 178AR.m.19.5 M00001384D:H07 0
3230 1/28/98 377 RTAOOOOO 178AF.m.19.1 M00001384D:H07 0
3231 1/28/98 120 RTAOOOOO 178AR.m.19.5 M00001384D:H07 0
3231 1/28/98 377 RTA00000178AF.m.l9.1 M00001384D:H07 0
3232 1/28/98 384 RTAOOOOO 196AF.h.17.1 M00001384C:F12 39215
3233 1/28/98 182 RTA00000196AF.h.l6.1 M00001384C:E03 39895
3234 1/28/98 105 RTAOOOOO 179AF.g.12.3 M00001398A:G03 36390
3235 1/28/98 252 RTA00000181AF.e.l8.3 M00001448D:C09 8
3235 1/28/98 253 RTA00000181AF.e.l7.3 M00001448D:C09 8
3236 1/28/98 301 RTA00000181AR.i.l9.3 M00001452C:B06 16970
3236 1/28/98 295 RTAOOOOO] 8 lAR.i.19.2 M00001452C:B06 16970
3237 1/28/98 288 RTA00000181AR.i.06.3 M00001452A:C07 19119
3237 2/24/98 198 RTA00000339R.1.14.1 M00001452A:C07 19119
3238 1/28/98 288 RTA00000181AR.i.06.3 M00001452A:C07 19119
3238 2/24/98 198 RTA00000339R.1.14.1 M00001452A:C07 19119
3239 1/28/98 109 RTA00000197AF.d.l2.1 M00001451D:C10 39546
3240 1/28/98 149 RTA00000181AR.h.06.3 M00001450D:D04 87226
3241 1/28/98 75 RTAOOOOO 180AR.h.19.2 M00001428A:H10 84182
3242 1/28/98 21 RTA00000131A.g.l9.2 M00001449A:G10 36535
3243 1/28/98 308 RTAOOOOO 178AF.J .20.1 M00001380C:E05 15066
3244 1/28/98 253 RTA00000181AF.e.l7.3 M00001448D:C09 8
3244 1/28/98 252 RTA00000181AF.e.l8.3 M00001448D:C09 8
3245 1/28/98 252 RTA00000181AF.e.l8.3 M00001448D:C09 8
3245 1/28/98 253 RTA00000181AF.e.l7.3 M00001448D:C09 8
3246 1/28/98 253 RTA00000181AF.e.l7.3 M00001448D:C09 8
3246 1/28/98 252 RTA00000181AF.e.l8.3 M00001448D:C09 8
3247 1/28/98 136 RTA00000197AF.C.10.1 M00001448B:F06 10400
3248 1/28/98 177 RTA00000197AF.C.3.1 M00001447C:C01 3145
3249 1/28/98 204 RTA00000180AR.O.5.2 M00001437D:C04 7848
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
3250 1/28/98 362 RTAOOOOO 197AR.C.24.1 M00001450A:B12 82498
3251 1/28/98 81 RTA00000196AF.b.l5.1 M00001347B:E01 5102
3252 1/28/98 342 RTAOOOOO 196AF.d.10.1 M00001354C:B06 22256
3253 1/28/98 113 RTAOOOOO 196AF.d.09.1 M00001354B:B10 16934
3254 1/28/98 463 RTA00000177AR. 23.4 M00001352D:D02 35550
3254 1/28/98 168 RTAOOOOO 177 AR.k.23.1 M00001352D:D02 35550
3255 1/28/98 463 RTA00000177 AR.k.23.4 M00001352D:D02 35550
3255 1/28/98 168 RTAOOOOO] 77AR.k.23.1 M00001352D:D02 35550
3256 1/28/98 135 RTA00000196AF.C.22.1 M00001352D:C05 22548
3257 1/28/98 270 RTA00000178R.1.08.1 M00001383A:C03 39648
3258 1/28/98 359 RTAOOOOO 196AF.b.17.1 M00001348A:D04 12193
3259 1/28/98 493 RTA00000177AF.m.l7.1 M00001355B:G10 14391
3259 1/28/98 337 RTA00000177AR.m.l7.3 M00001355B:G10 14391
3259 1/28/98 330 RTA00000177AR.m.l7.4 M00001355B:G10 14391
3260 1/28/98 361 RTA00000177AR.g.l6.4 M00001347A:B10 13576
3261 1/28/98 265 RTA00000177AF.e.l4.1 M00001343D:H07 23255
3262 1/28/98 56 RTAOOOOO 177AF.e.9.1 M00001343D:C04 37442
3263 1/28/98 48 RTAOOOOO 177 AR.a.23.5 M00001339D:G02 6995
3264 2/24/98 308 RTA00000353R.d.ll.l M00004692A:H08 0
3265 1/28/98 164 RTA00000193AR. 14.4 M00004307C:A06 9457
3266 1/28/98 283 RTA00000177AF.i.8.4 M00001350A:H01 7187
3267 1/28/98 15 RTAOOOOO 177AR.n.8.1 M00001356D:F06 4188
3267 1/28/98 89 RTAOOOOO 177AF.n.8.3 M00001356D:F06 4188
3268 1/28/98 383 RTAOOOOO 199FT.20.2 M00003847B:G03 0
3269 1/28/98 132 RTAOOOOO 178AFT.20.3 M00001372C:F07 39881
3270 1/28/98 296 RTAOOOOO 196AF.f.20.1 M00001371D:G01 22774
3271 1/28/98 297 RTAOOOOO 178 AF.f.9.3 M00001371C:E09 7172
3272 1/28/98 240 RTAOOOOO 178 AF.e.1.1 M00001369A:H12 2664
3273 1/28/98 16 RTAOOOOO 196AF.e.16.1 M00001363C:H02 39252
3274 1/28/98 112 RTA00000177AF.m.8.1 M00001354C:C10 8010
3275 1/28/98 154 RTA00000196F.e.7.1 M00001360D:E11 1039
3276 1/28/98 330 RTA00000177AR.m.l7.4 M00001355B:G10 14391
3276 1/28/98 493 RTA00000177AF.m.l7.1 M00001355B:G10 14391
3276 1/28/98 337 RTA00000177AR.m.l7.3 M00001355B:G10 14391
3277 1/28/98 89 RTAOOOOO 177AF.n.8.3 M00001356D:F06 4188
3277 1/28/98 15 RTAOOOOO 177AR.n.8.1 M00001356D:F06 4188
3278 1/28/98 493 RTAOOOOO 177 AF.m.17.1 M00001355B:G10 14391
3278 1/28/98 337 RTA00000177AR.m.l7.3 M00001355B:G10 14391
3278 1/28/98 330 RTA00000177AR.m.l7.4 M00001355B:G10 14391
3279 1/28/98 337 RTA00000177AR.m.l7.3 M00001355B:G10 14391
3279 1/28/98 330 RTA00000177AR.m.l7.4 M00001355B:G10 14391
3279 1/28/98 493 RTA00000177AF.m.l7.1 M00001355B:G10 14391
3280 1/28/98 330 RTAOOOOO 177AR.m.17.4 M00001355B:G10 14391
3280 1/28/98 493 RTAOOOOO 177AF.m.17.1 M00001355B:G10 14391
3280 1/28/98 337 RTAOOOOO 177AR.ni.17.3 M00001355B:G10 14391
3281 1/28/98 337 RTAOOOOO 177AR.ni.17.3 M00001355B:G10 14391
3281 1/28/98 493 RTAOOOOO 177 AF.m.17.1 M00001355B:G10 14391
3281 1/28/98 330 RTAOOOOO] 77AR.ni.17.4 M00001355B:G10 14391
3282 1/28/98 169 RTA00000196AF.g.24.1 M00001380C:F02 8685
3283 1/28/98 363 RTA00000196AF.e.l4.1 M00001362C:A10 12850
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
3284 1/28/98 92 RTAOOOOO 198AF.J.18.1 M00001653B:G07 22759
3284 1/28/98 433 RTA00000198RJ.18.1 M00001653B:G07 22759
3285 1/28/98 537 RTAOOOOO 188AF.g.14.1 M00003774C:D02 0
3286 1/28/98 434 RTAOOOOO 187AR.d.2.2 M00001664C:H 10 4892
3287 1/28/98 703 RTA00000198F.1.09.1 M00001664B:D06 361 1
3288 1/28/98 430 RTAOOOOO 198R. 23.1 M00001661 B:C08 8995
3288 1/28/98 294 RTA00000198AF. 23.1 M00001661 B:C08 8995
3289 1/28/98 294 RTA00000198AF. 23.1 M00001661 B:C08 8995
3289 1/28/98 430 RTAOOOOO 198R.L23.1 M00001661 B:C08 8995
3290 1/28/98 754 RTA00000187AF.1.1 1.1 M00001681A:F03 4482
3291 1/28/98 732 RTAOOOOO 186AF.p.01.2 M00001654D:G1 1 40440
3292 1/28/98 475 RTA00000187AR.m.3.3 M00001682C:B12 17055
3293 1/28/98 433 RTA00000198RJ.18.1 M00001653B:G07 22759
3293 1/28/98 92 RTA00000198AF.J.18.1 M00001653B:G07 22759
3294 1/28/98 555 RTAOOOOO 198AF.J.08.1 M00001651 B:A 1 1 10983
3295 1/28/98 399 RTA00000186AF.m. l 5.2 M00001649C:B10 40122
3296 1/28/98 575 RTAOOOOO 186AF.1.12.2 M00001645A:C 12 19267
3297 1/28/98 666 RTA00000198F.i.l 0.1 M00001640B:F03 12792
3298 1/28/98 654 RTAOOOOO 186AF.J.21.2 M00001639D:B07 22506
3299 1/28/98 670 RTA00000186AF.p.l 7.3 M00001656B:A07 38383
3300 1/28/98 393 RTA00000188AF.b.l4.1 M00003754D:D02 0
3301 1/28/98 422 RTA00000189AF.b.l2.1 M00003829B:G03 17233
3301 1/28/98 210 RTA00000189AR.b.l2.1 M00003829B:G03 17233
3302 1/28/98 587 RTAOOOOO 199F.a.3.1 M00003772D:E10 16617
3303 1/28/98 394 RTAOOOOO 198AF.p.22.1 M00003771A:G10 0
3304 1/28/98 542 RTAOOOOO 198R.p.12.1 M00003763D:E10 8878
3304 1/28/98 64 RTAOOOOO 198AF.p.12.1 M00003763D:E10 8878
3305 1/28/98 64 RTAOOOOO 198AF.p.12.1 M00003763D:E10 8878
3305 1/28/98 542 RTAOOOOO 198R.p.12.1 M00003763D:E10 8878
3306 1/28/98 465 RTA00000187AF. 20.1 M00001680B:C01 3648
3307 1/28/98 423 RTA00000188AR.b.17.1 M00003755A:B03 10662
3308 1/28/98 71 1 RTA00000198F. 2.1 M00001637B:E07 8076
3309 1/28/98 497 RTAOOOOO 198 AF.o.09.1 M00003751 B:A05 4310
3309 1/28/98 506 RTA00000198R.O.09.1 M00003751 B:A05 4310
3310 1/28/98 506 RTAOOOOO 198R.O.09.1 M00003751 B:A05 4310
3310 1/28/98 497 RTA00000198AF.O.09.1 M00003751 B:A05 4310
331 1 1/28/98 432 RTA00000198AF.O.05.1 M00003750A:D01 26702
331 1 1/28/98 49 RTA00000198R.O.05.1 M00003750A:D01 26702
3312 1/28/98 49 RTA00000198R.O.05.1 M00003750A:D01 26702
3312 1/28/98 432 RTA00000198AF.O.05.1 M00003750A:D01 26702
3313 1/28/98 585 RTAOOOOO! 98AF.n.18.1 M00001771 A:A07 16715
3314 1/28/98 527 RTA00000198R.m.23.1 M00001684B:G03 38469
3315 1/28/98 471 RTA00000188AF.e.2.1 M00003763B:H01 0
3316 1/28/98 171 RTAOOOOO] 98R.C.07.1 M00001575D:G05 19181
3316 1/28/98 525 RTA00000198AF.C.7.1 M00001575D:G05 19181
3317 1/28/98 557 RTA00000198AF.d.9.1 M00001587D:A10 8841
3318 1/28/98 523 RTA00000198AF.d.4.1 M00001586D:E02 22435
3319 1/28/98 441 RTA00000185AF.e.6.1 M00001583B:E 10 0
3320 1/28/98 439 RTA00000185AF.d. l 4.2 M00001579D:G07 8071
3321 1/28/98 561 RTAOOOOO 185AR.d.10.1 M00001579C:H 10 0
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
3322 1/28/98 277 RTAOOOOO 198AR.Ϊ.08.1 M00001639A:F10 9807
3322 1/28/98 487 RTAOOOOO 198F. 8.1 M00001639A:F10 9807
3323 1/28/98 525 RTAOOOOO 198AF.C.7.1 M00001575D:G05 19181
3323 1/28/98 171 RTA00000198R.C.07.1 M00001575D:G05 19181
3324 2/24/98 317 RTA00000195AF.b.21.1 M00001595B:A09 39055
3324 1/28/98 602 RTA00000195AF.b.21.1 M00001595B:A09 39055
3325 1/28/98 507 RTA00000198AF.C.5.1 M00001573D:F10 53802
3326 1/28/98 414 RTA00000185AR.b. l 5.1 M00001573D:F04 39813
3326 1/28/98 428 RTA00000185AF.b.l 5.2 M00001573D:F04 39813
3327 1/28/98 428 RTA00000185AF.b.l5.2 M00001573D:F04 39813
3327 1/28/98 414 RTA00000185AR.b. l 5.1 M00001573D:F04 39813
3328 1/28/98 414 RTAOOOOO 185AR.b.15.1 M00001573D:F04 39813
3328 1/28/98 428 RTA00000185AF.b.l 5.2 M00001573D:F04 39813
3329 1/28/98 428 RTAOOOOO 185AF.b.15.2 M00001573D:F04 39813
3329 1/28/98 414 RTA00000185AR.b.l 5.1 M00001573D:F04 39813
3330 1/28/98 392 RTA00000185AF.b.l l .2 M00001573C:D03 9024
3331 1/28/98 549 RTA00000198AF.C.16.1 M00001579C:B1 1 26801
3332 1/28/98 628 RTAOOOOO 198AF.g.16.1 M00001621 D:D03 6602
3333 1/28/98 616 RTA00000188AF.m.07.1 M00003798D:E03 23183
3334 1/28/98 489 RTAOOOOO 186 AF.h.22.1 M00001634B:C10 16485
3335 1/28/98 655 RTA00000186AF.g.8.2 M00001630B:A1 1 8065
3336 1/28/98 592 RTA00000186AF.e. l 8.1 M00001624C:A06 0
3337 1/28/98 713 RTAOOOOO 198 AF.g.21.1 M00001624A:F09 6273
3338 1/28/98 554 RTAOOOOO 186AR.e.07.4 M00001623D:G03 4175
3338 1/28/98 400 RTAOOOOO 186AR.e.07.3 M00001623D:G03 4175
3339 1/28/98 467 RTAOOOOO 195AF.b.19.1 M00001589A:D12 77678
3340 1/28/98 646 RTAOOOOO 186AF.d.24.1 M00001623C:H07 31 14
3341 1/28/98 740 RTA00000198AF.d.l 5.1 M00001590C:H08 5997
3342 1/28/98 504 RTA00000198AF.g.2.1 M00001615C:D02 16640
3343 1/28/98 470 RTA00000198AF.f.l 6.1 M00001614A:E06 0
3344 1/28/98 388 RTAOOOOO 185AF.ιι.17.1 M00001609B:A1 1 5336
3345 1/28/98 495 RTA00000185AF.J.21.1 M00001597A:E12 0
3346 2/24/98 317 RTAOOOOO 195 AF.b.21.1 M00001595B:A09 39055
3346 1/28/98 602 RTA00000195AF.b.21.1 M00001595B:A09 39055
3347 1/28/98 487 RTA00000198F.i.8.1 M00001639A:F10 9807
3347 1/28/98 277 RTAOOOOO 198AR. 08.1 M00001639A:F10 9807
3348 1/28/98 554 RTAOOOOO 186AR.e.07.4 M00001623D:G03 4175
3348 1/28/98 400 RTAOOOOO 186AR.e.07.3 M00001623D:G03 4175
3349 1/28/98 699 RTAOOOOO 178AF.a.12.1 M00001362B:H06 0
3350 1/28/98 416 RTA00000199F.a.5.1 M00003773B:G01 22134
3351 1/28/98 656 RTAOOOOO 178AR.h.22.3 M00001376B:A08 19230
3351 1/28/98 657 RTA00000178AR.h.22.2 M00001376B:A08 19230
3351 2/24/98 1 137 RTA00000345F.d.03.1 M00001376B:A08 19230
3352 1/28/98 656 RTA00000178AR.h.22.3 M00001376B:A08 19230
3352 1/28/98 657 RTAOOOOO 178AR.h.22.2 M00001376B:A08 19230
3352 2/24/98 1 137 RTA00000345F.d.03.1 M00001376B:A08 19230
3353 1/28/98 522 RTA00000178AR.h.l 7.2 M00001376A:C05 23824
3353 2/24/98 1095 RTAOO000345F.C.12.1 M00001376A:C05 23824
3354 1/28/98 522 RTAOO000178AR.h.l 7.2 M00001376A:C05 23824
3354 2/24/98 1095 RTA00000345F.C.12.1 M00001376A:C05 23824
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
3355 1/28/98 656 RTAOOOOO 178 AR.h.22.3 MO0001376B:A08 19230
3355 1/28/98 657 RTAOOOOO 178AR.h.22.2 M00001376B:A08 19230
3355 2/24/98 1 137 RTA00000345F.d.03.1 M00001376B:A08 19230
3356 1/28/98 566 RTA00000195F.a.4.1 M00001372C:G 12 20470
3357 1/28/98 657 RTAOOOOO 178AR.h.22.2 M00001376B:A08 19230
3357 1/28/98 656 RTAOOOOO 178AR.h.22.3 M00001376B:A08 19230
3357 2/24/98 1 137 RTA00000345F.d.03.1 M00001376B:A08 19230
3358 1/28/98 605 RTAOOOOO 196F.e.9.1 M00001361 A:H07 23300
3359 1/28/98 532 RTAOOOOO 177AF.o.4.1 M00001358C:C06 0
3360 1/28/98 493 RTAOOOOO 177AF.m.17.1 M00001355B:G10 14391
3360 1/28/98 330 RTAOOOOO 177AR.m.17.4 M00001355B:G 10 14391
3360 1/28/98 337 RTA00000177AR.m.l 7.3 M00001355B:G10 14391
3361 1/28/98 330 RTA00000177AR.m. l 7.4 M00001355B:G10 14391
3361 1/28/98 493 RTA00000177AF.ni.17.1 M00001355B:G 10 14391
3361 1/28/98 337 RTAOOOOO 177AR.m.17.3 M00001355B:G10 14391
3362 1/28/98 337 RTA00000177AR.m.l 7.3 M00001355B:G 10 14391
3362 1/28/98 493 RTAOOOOO 177AF.m.17.1 M00001355B:G 10 14391
3362 1/28/98 330 RTA00000177AR.m.l 7.4 M00001355B:G 10 14391
3363 1/28/98 742 RTAOOOOO 177AF.m.1.1 M00001353D:D10 14929
3364 1/28/98 547 RTA00000196AF.g.8.1 M00001375B:G 12 39665
3365 1/28/98 510 RTA00000178AF.n.23.1 M00001387B:E02 3298
3366 1/28/98 606 RTA00000179AR.e.01.4 M00001395A:C09 2493
3367 2/24/98 1065 RTA00000195 R.a.06.1 M00001394A:E04 35265
3367 1/28/98 595 RTA00000195R.a.06.1 M00001394A:E04 35265
3368 2/24/98 1065 RTA00000195R.a.06.1 M00001394A:E04 35265
3368 1/28/98 595 RTA00000195R.a.06.1 M00001394A:E04 35265
3369 1/28/98 370 RTA00000179AF.C.15.3 M00001392D:H06 2995
3369 1/28/98 460 RTA00000179AF.C.15.1 M00001392D:H06 2995
3370 1/28/98 370 RTAOOOOO 179AF.C.15.3 M00001392D:H06 2995
3370 1/28/98 460 RTA00000179AF.C.15.1 M00001392D:H06 2995
3371 1/28/98 657 RTA00000178AR.h.22.2 M00001376B:A08 19230
3371 1/28/98 656 RTAOOOOO 178AR.h.22.3 M00001376B:A08 19230
3371 2/24/98 1 137 RTA00000345F.d.03.1 M00001376B:A08 19230
3372 1/28/98 675 RTA00000179AR.b.21.3 M00001392C:D05 4366
3372 2/24/98 1264 RTA00000345F.e.l3.1 M00001392C:D05 4366
3373 1/28/98 168 RTA00000177AR.L23.1 M00001352D:D02 35550
3373 1/28/98 463 RTAOOOOO 177 AR.k.23.4 M00001352D:D02 35550
3374 1/28/98 652 RTA00000178AR.m.21.4 MO0001385A:F12 7861
3374 1/28/98 653 RTA00000178AR.m.21.5 M00001385A:F12 7861
3375 1/28/98 653 RTA00000178AR.m.21.5 M00001385A:F 12 7861
3375 1/28/98 652 RTA00000178AR.m.21 .4 M00001385A:F12 7861
3376 1/28/98 672 RTAOOOOO 196AF.h.09.1 M00001382B:F12 8015
3377 1/28/98 668 RTA00000178AF.i.l 7.1 M00001377C:E12 0
3378 1/28/98 746 RTA00000178AF.i.01.2 M00001376B:F03 4
3379 1/28/98 656 RTAOOOOO 178AR.h.22.3 M00001376B:A08 19230
3379 1/28/98 657 RTA00000178AR.h.22.2 M00001376B:A08 19230
3379 2/24/98 1 137 RTA00000345F.d.03.1 M00001376B:A08 19230
3380 1/28/98 675 RTAOOOOO 179 AR.b.21.3 M00001392C:D05 4366
3380 2/24/98 1264 RTA00000345F.e. l 3.1 M00001392C:D05 4366
3381 1/28/98 651 RTAOOOOO 189AR.d.22.2 M00003844C:B 1 1 6539
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
3382 1/28/98 444 RTA00000189AF.1.16.1 M00003879A:G05 0
3383 1/28/98 648 RTA00000199F.i.9.1 M00003878C:E04 7
3384 2/24/98 678 RTAOOOOO 195 AF.c.24.1 M00003860D:H07 0
3384 1/28/98 412 RTA00000195AF.C.24.1 M00003860D:H07 0
3385 1/28/98 412 RTAOOOOO 195 AF.c.24.1 M00003860D:H07 0
3385 2/24/98 678 RTA00000195 AF.c.24.1 M00003860D:H07 0
3386 1/28/98 484 RTAOOOOO 199F.g.20.2 M00003860D:A01 15767
3387 1/28/98 398 RTA00000177AR.1.13.3 M00001353A:G12 8078
3388 1/28/98 556 RTAOOOOO 199FT.17.2 M00003845D:B04 22905
3389 1/28/98 545 RTA00000196F.a.2.1 M00001338B:E02 3575
3390 1/28/98 406 RTAOOOOO 199F.f.09.2 M00003842B:D09 22907
3390 1/28/98 78 RTAOOOOO 199R.f.09.1 M00003842B:D09 22907
3391 1/28/98 78 RTAOOOOO 199R.f.09.1 M00003842B:D09 22907
3391 1/28/98 406 RTA00000199F.f.09.2 M00003842B:D09 22907
3392 1/28/98 692 RTA00000199F.e.4.1 M00003820B:C05 0
3393 1/28/98 458 RTA00000199R.d.l6.1 M00003812C:A05 24191
3394 1/28/98 755 RTAOOOOO 199F.C.21.2 M00003803C:D09 5070
3395 1/28/98 505 RTA00000188AF.11.03.1 M00003801B:B10 9443
3396 1/28/98 714 RTA00000199R.g.07.1 M00003853D:D03 0
3397 1/28/98 724 RTAOOOOO 177ART.15.4 M00001345B:E10 9062
3398 1/28/98 623 RTAOOOOO 198R.b.24.1 M00001571D:B11 19047
3398 1/28/98 748 RTAOOOOO 198 AF.b.24.1 M00001571D:B11 19047
3399 1/28/98 395 RTAOOOOO 196R.C.21.2 M00001352C:H10 0
3400 1/28/98 593 RTAOOOOO 196R.C.14.2 M00001352B:F04 23105
3400 1/28/98 485 RTAOOOOO 196AF.C.14.1 M00001352B:F04 23105
3401 1/28/98 485 RTA00000196AF.C.14.1 M00001352B:F04 23105
3401 1/28/98 593 RTA00000196R.C.14.2 M00001352B:F04 23105
3402 1/28/98 645 RTA00000177AF.L9.1 M00001352A:E02 16245
3403 1/28/98 576 RTAOOOOO 196AF.C.7.1 M00001350B:G11 0
3404 1/28/98 737 RTA00000189AR.m.9.1 M00003880B:C08 2917
3405 1/28/98 728 RTA00000177ART.17.4 M00001345C:B01 8594
3406 1/28/98 453 RTA00000199AF. 20.1 M00003881A:D09 9544
3407 1/28/98 440 RTAOOOOO 177AR .13.4 M00001345A:G11 10480
3408 1/28/98 680 RTAOOOOO 177AFT.10.1 M00001345A:E01 6420
3409 1/28/98 573 RTAOOOOO 196AF.b.7.1 M00001344A:G07 7774
3410 1/28/98 402 RTAOOOOO 177AF.b.21.4 M00001341A:F12 4443
3411 1/28/98 702 RTA00000177AR.b.8.5 M00001340B:A06 17062
3412 1/28/98 463 RTA00000177AR.k.23.4 M00001352D:D02 35550
3412 1/28/98 168 RTA00000177AR. 23.1 M00001352D:D02 35550
3413 1/28/98 600 RTAOOOOO 177AF.g.4.1 M00001346B:B07 4119
3414 1/28/98 280 RTAOOOOO 193AF.b.18.1 M00004233C:H09 7542
3415 1/28/98 748 RTAOOOOO 198 AF.b.24.1 M00001571D:B11 19047
3415 1/28/98 623 RTA00000198R.b.24.1 M00001571D-.B11 19047
3416 1/28/98 249 RTA00000200R.O.03.2 M00004257C:H06 22807
3416 1/28/98 178 RTA00000200F.O.03.1 M00004257C-.H06 22807
3416 1/28/98 85 RTA00000200R.O.03.1 M00004257C:H06 22807
3417 1/28/98 282 RTAOOOOO 193AF.C.15.1 M00004248B:E08 3726
3418 1/28/98 307 RTA00000200F.n.05.2 M00004246C:A09 18989
3418 1/28/98 319 RTA00000200F.n.05.1 M00004246C:A09 18989
3419 1/28/98 319 RTA00000200F.ii.05.! M00004246C:A09 18989
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority' Priority Appln Appln
3419 1/28/98 307 RTA00000200F.n.05.2 M00004246C:A09 18989
3420 1/28/98 85 RTA00000200R.O.03.1 M00004257C:H06 22807
3420 1/28/98 249 RTA00000200R.O.03.2 M00004257C:H06 22807
3420 1/28/98 178 RTA00000200F.O.03.1 M00004257C:H06 22807
3421 1/28/98 307 RTA00000200F.n.05.2 M00004246C:A09 18989
3421 1/28/98 319 RTA00000200F.n.05.1 M00004246C:A09 18989
3422 1/28/98 50 RTA00000201 R.a.02.1 M00004295B:D02 35362
3422 1/28/98 235 RTA00000201 AF.a.02.1 M00004295B:D02 35362
3423 1/28/98 251 RTAOOOOO 192AF.n.13.1 M00004197D:H01 8210
3424 1/28/98 47 RTAOOOOO 192 AF.m.12.1 M00004191 D:B1 1 0
3425 1/28/98 494 RTA00000200AF.k. l . l M00004188C:A09 40049
3425 1/28/98 194 RTA00000200R.k.01.1 M00004188C:A09 40049
3426 1/28/98 494 RTA00000200AF. 1.1 M00004188C:A09 40049
3426 1/28/98 194 RTA00000200R.k.01.1 M00004188C:A09 40049
3427 1/28/98 231 RTA00000192AF.I.13.2 M00004185C:C03 1 1443
3428 1/28/98 382 RTA00000200AF.J.6.1 M00004176B:E08 22902
3429 1/28/98 307 RTA00000200F.11.05.2 M00004246C:A09 18989
3429 1/28/98 319 RTA00000200F.n.05.1 M00004246C:A09 18989
3430 1/28/98 52 RTA00000201 R.b.02.1 M00004319D:G09 22660
3431 1/28/98 271 RTA00000201 F.d.02.1 M00004375A:H01 2599
3431 1/28/98 239 RTA00000201 R.d.02.1 M00004375A:II01 2599
3431 1/28/98 227 RTA00000201 R.d.02.2 M00004375A:H01 2599
3432 1/28/98 227 RTA00000201 R.d.02.2 M00004375A:H01 2599
3432 1/28/98 239 RTA00000201 R.d.02.1 M00004375A:H01 2599
3432 1/28/98 271 RTA00000201 F.d.02.1 M00004375A:H01 2599
3433 1/28/98 227 RTA00000201 R.d.02.2 M00004375A:H01 2599
3433 1/28/98 271 RTA00000201 F.d.02.1 M00004375A:H01 2599
3433 1/28/98 239 RTA00000201 R.d.02.1 M00004375A:H01 2599
3434 1/28/98 271 RTA00000201 F.d.02.1 M00004375A:H01 2599
3434 1/28/98 239 RTA00000201 R.d.02.1 M00004375A:H01 2599
3434 1/28/98 227 RTA00000201 R.d.02.2 M00004375A:H01 2599
3435 1/28/98 227 RTA00000201 R.d.02.2 M00004375A:H01 2599
3435 1/28/98 271 RTA00000201 F.d.02.1 M00004375A:H01 2599
3435 1/28/98 239 RTA00000201 R.d.02.1 M00004375A:H01 2599
3436 1/28/98 178 RTA00000200F.O.03.1 M00004257C:H06 22807
3436 1/28/98 249 RTA00000200R.O.03.2 M00004257C:H06 22807
3436 1/28/98 85 RTA00000200R.O.03.1 M00004257C:H06 22807
3437 1/28/98 273 RTA00000201 F.C.08.1 M00004353C:H07 0
3438 1/28/98 328 RTA00000200AF.g.09.1 M00004131 B:H09 22785
3438 1/28/98 26 RTA00000200R.g.09.1 M00004131 B:H09 22785
3439 2/24/98 571 RTA00000355R.e.l4.1 M00004314B:G07 16837
3439 1/28/98 343 RTA00000201 F.a.l 8.1 M00004314B:G07 16837
3440 1/28/98 343 RTA00000201 F.a.l 8.1 M00004314B:G07 16837
3440 2/24/98 571 RTA00000355R.e.l4.1 M00004314B:G07 16837
3441 1/28/98 164 RTAOOOOO 193AR.i.14.4 M00004307C:A06 9457
3442 1/28/98 50 RTA00000201 R.a.02.1 M00004295B:D02 35362
3442 1/28/98 235 RTA00000201AF.a.02.1 M00004295B:D02 35362
3443 1/28/98 235 RTA00000201AF.a.02.1 M00004295B:D02 35362
3443 1/28/98 50 RTA00000201 R.a.02.1 M00004295B:D02 35362
3444 1/28/98 50 RTA00000201 R.a.02.1 M00004295B:D02 35362
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
3444 1/28/98 235 RTA00000201 AF.a.02.1 M00004295B:D02 35362
3445 1/28/98 227 RTA00000201 R.d.02.2 M00004375A:H01 2599
3445 1 /28/98 271 RTA00000201 F.d.02.1 M00004375A:H01 2599
3445 1/28/98 239 RTA00000201 R.d.02.1 M00004375A:H01 2599
3446 1/28/98 13 RTA00000190AF.L5.1 M00003919A:A10 0
3447 1/28/98 72 RTA00000200F.a.6.1 M00004029B:F1 1 36952
3448 1/28/98 101 RTAOOOOO 191 AF.d.08.2 M00003997B:G07 970
3449 1/28/98 79 RTAOOOOO 199AF.p.4.1 M00003985C:F01 10282
3450 1/28/98 121 RTAOOOOO 199AF.0.16.1 M00003979A:F03 16721
3451 1/28/98 193 RTAOOOOO 199AF.n.3.1 M00003946D:C1 1 0
3452 1/28/98 165 RTAOOOOO 192 AF.g.23.1 M00004157C:A09 6455
3453 1/28/98 381 RTAOOOOO 199AF.ni.14.1 M00003938A:B04 10580
3454 1/28/98 123 RTAOOOOO 191 AF.k.6.1 M00004078B:A1 1 5451
3455 1/28/98 102 RTAOOOOO 199R.J.08.1 M00003884D:G07 37844
3456 1/28/98 86 RTA00000189AF.1.22.1 M00003879C:G 10 33333
3457 1 /28/98 148 RTAOOOOO 199F.li.17.2 M00003871 A:A05 36254
3458 1/28/98 143 RTA00000199R.h.09.1 M00003867C:H09 76020
3459 1/28/98 266 RTAOOOOO 199FT.21.2 M00003847C:E09 13344
3460 2/24/98 153 RTA00000422F.g.22.1 M00001585B:A06 22561
3461 1/28/98 292 RTAOOOOO 199AF.ni.18.1 M00003939C:F04 0
3462 1/28/98 275 RTA00000191 AF.O.17.2 M00004102A:H02 5957
3462 1/28/98 274 RTA00000191 AF.O.17.1 M00004102A:H02 5957
3463 1/28/98 239 RTA00000201 R.d.02.1 M00004375A:H01 2599
3463 1/28/98 271 RTA00000201 F.d.02.1 M00004375A:H01 2599
3463 1/28/98 227 RTA00000201 R.d.02.2 M00004375A:H01 2599
3464 1 /28/98 328 RTA00000200AF.g.09.1 M00004131 B:H09 22785
3464 1/28/98 26 RTA00000200R.g.09.1 M00004131 B:H09 22785
3465 1 /28/98 214 RTA00000200AF.f.22.1 M00004121 C:F06 16521
3466 1/28/98 160 RTAOOOOO 192 AF.b.20.1 M000041 18D:E08 0
3467 1 /28/98 98 RTA00000200AF.f.l4.1 M000041 15D:C08 22051
3467 1/28/98 100 RTA00000200R.f.l4.1 M000041 15D:C08 22051
3468 1/28/98 98 RTA00000200AFT.14.1 M000041 15D:C08 22051
3468 1/28/98 100 RTA00000200RT.14.1 M000041 15D:C08 22051
3469 1/28/98 305 RTA00000200AF.b. l 5.1 M00004040D:F01 10627
3470 1/28/98 98 RTA00000200AFT.14.1 M000041 15D:C08 22051
3470 1/28/98 100 RTA00000200RT.14.1 M000041 15D:C08 22051
3471 1/28/98 29 RTA00000200AF.b.l 9.1 M00004042D:H02 22847
3472 1/28/98 274 RTA00000191 AF.O.17.1 M00004102A:H02 5957
3472 1/28/98 275 RTAOOOOO 191 AF.o.17.2 M00004102A:H02 5957
3473 1/28/98 274 RTA00000191AF.O.17.1 M00004102A:H02 5957
3473 1/28/98 275 RTAOOOOO 191 AF.o.17.2 M00004102A:H02 5957
3474 1/28/98 275 RTAOOOOO 191 AF.o.17.2 M00004102A:H02 5957
3474 1/28/98 274 RTA00000191 AF.O.17.1 M00004102A:H02 5957
3475 1/28/98 226 RTAOOOOO 191 AR.o.09.4 M00004096A:G02 0
3476 1/28/98 40 RTA00000200AR.e.02.1 M00004090A:F09 36059
3477 1/28/98 175 RTA00000200F. 5.1 M00004156B:A12 22892
3478 1 /28/98 98 RTA00000200AF.f.l 4.1 M000041 15D:C08 22051
3478 1/28/98 100 RTA00000200R.f. l4.1 M000041 15D:C08 22051
3479 1/28/98 643 RTA00000184AF.C.9.1 M00001546C:G10 16245
3480 1/28/98 615 RTA00000197R.p.20.1 M00001554B:B07 22795
SEQ ID Filing SEQ ID Sequence Name Clone Nsme Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
3480 1/28/98 559 RTA00000197AF.p.20.1 M00001554B:B07 22795
3481 1/28/98 660 RTAOOOOO 197AF.p.16.1 M00001552D:G08 6013
3482 1/28/98 521 RTAOOOOO 197AF.p.12.1 M00001552B:G05 0
3483 1/28/98 403 RTA00000184AF.f.l3.1 M00001550D:H02 3784
3484 1/28/98 517 RTAOOOOO 184AF.e.14.1 M00001549C:D02 16347
3485 1/28/98 676 RTAOOOOO 197AR.m.14.1 M00001531B:E09 14879
3486 1/28/98 596 RTAOOOOO 184AF.d.9.1 M00001548A:B11 6515
3487 1/28/98 559 RTA00000197AF.p.20.1 M00001554B:B07 22795
3487 1/28/98 615 RTA00000197R.p.20.1 M00001554B:B07 22795
3488 1/28/98 729 RTAOOOOO 184AF.3.19.1 M00001544C:C06 2628
3489 1/28/98 682 RTA00000125A.J.16.1 M00001544A:E06 0
3490 1/28/98 723 RTAOOOOO 183 AF.p.24.1 M00001543C:F01 3116
3491 1/28/98 509 RTAOOOOO 183AF.p.17.1 M00001543A:H12 5158
3492 1/28/98 738 RTA00000183AF.O.8.1 M00001540C:B10 8927
3493 1/28/98 227 RTA00000201R.d.02.2 M00004375A:H01 2599
3493 1/28/98 271 RTA00000201F.d.02.1 M00004375A:H01 2599
3493 1/28/98 239 RTA00000201R.d.02.1 M00004375A:H01 2599
3494 1/28/98 502 RTAOOOOO 197AF.0.23.1 M00001549A:A09 12682
3495 1/28/98 468 RTA00000198AF.3.18.1 M00001561C:E11 0
3496 1/28/98 210 RTAOOOOO 189AR.b.12.1 M00003829B:G03 17233
3496 1/28/98 422 RTAOOOOO 189AF.b.12.1 M00003829B:G03 17233
3497 1/28/98 748 RTAOOOOO 198AF.b.24.1 M00001571D:B11 19047
3497 1/28/98 623 RTA00000198R.b.24.1 M00001571D:B11 19047
3498 1/28/98 397 RTAOOOOO 198AF.b.22.1 M00001571B:E03 38956
3499 1/28/98 571 RTAOOOOO 198AF.b.14.1 M00001569C:B06 801
3500 1/28/98 492 RTAOOOOO 198AF.b.8.1 M00001567C:H12 22636
3500 1/28/98 23 RTA00000198R.b.08.1 M00001567C:H12 22636
3501 1/28/98 492 RTAOOOOO 198AF.b.8.1 M00001567C:H12 22636
3501 1/28/98 23 RTA00000198R.b.08.1 M00001567C:H12 22636
3502 1/28/98 559 RTA00000197AF.p.20.1 M00001554B:B07 22795
3502 1/28/98 615 RTA00000197R.p.20.1 M00001554B:B07 22795
3503 1/28/98 727 RTA00000184AF.il.12.2 M00001561D:C11 3727
3504 1/28/98 559 RTA00000197AF.p.20.1 M00001554B:B07 22795
3504 1/28/98 615 RTA00000l97R.p.20.1 M00001554B:B07 22795
3505 1/28/98 641 RTA00000198F.3.10.1 M00001558A:E11 6695
3506 1/28/98 731 RTA00000184F.k.02.1 M00001557B:H10 5192
3507 1/28/98 597 RTA00000198F.a.4.1 M00001557A:F01 9635
3508 1/28/98 560 RTA00000184AF. 23.3 M00001556A:F11 1577
3509 1/28/98 601 RTA00000184AF.i.l0.2 M00001555A:B01 3744
3510 1/28/98 700 RTA00000183AF. 18.2 M00001529D:H02 40129
3511 1/28/98 437 RTAOOOOO 198R.3.23.1 M00001563B:D11 10700
3512 1/28/98 591 RTAOOOOO 197AF.h.1.1 M00001470A:H01 13075
3512 1/28/98 110 RTA00000197R.h.01.1 M00001470A:H01 13075
3513 1/28/98 259 RTAOOOOO 197 AF.j .4.1 M00001492D:A11 17209
3513 1/28/98 386 RTAOOOOO 197AR.J .04.1 M00001492D:A11 17209
3514 1/28/98 386 RTA00000197AR.J.04.1 M00001492D:A11 17209
3514 1/28/98 259 RTAOOOOO 197 AF.j .4.1 M00001492D:A11 17209
3515 1/28/98 644 RTAOOOOO 197F.i.12.1 M00001489B:A06 3605
3516 1/28/98 633 RTA00000197F.i.8.1 M00001488A:E01 6292
3517 1/28/98 546 RTA00000197F.i.6.1 M00001487C:D06 12149
SEQ ID Filing SEQ ID Sequence Nsme Clone Nsme Cluster
NO: D3te of NO: in ID
Priority Priority
Appln Appln
3518 1/28/98 650 RTAOOOOO 183AR.n.17.1 M00001539B:H06 9800
3519 1/28/98 513 RTA00000197AF.h. l4. ] M00001477B:F04 7045
3520 1/28/98 519 RTAOOOOO 183 AF.a.24.2 M00001499B:A1 1 10539
3521 1/28/98 1 10 RTAOOOOO 197R.h.01.1 M00001470A:H01 13075
3521 1/28/98 591 RTAOOOOO 197AF.h.1.1 M00001470A:H01 13075
3522 1/28/98 446 RTAOOOOO 182 AF.a.23.3 M00001463A:F06 9755
3523 1/28/98 739 RTA00000181 AF.p.l2.3 M00001460C:H02 22204
3524 1/28/98 635 RTA00000181 AF.p.7.3 M00001460A:E01 38773
3525 1/28/98 720 RTAOOOOO 197AFT.14.1 M00001459B:C09 3732
3526 1/28/98 623 RTAOOOOO 198R.b.24.1 M00001571 D:B1 1 19047
3526 1/28/98 748 RTAOOOOO 198 AF.b.24.1 M00001571 D:B1 1 19047
3527 1/28/98 419 RTAOOOOO 182AF.J .20.1 M00001483B:D03 4769
3528 1/28/98 632 RTA00000183AR.g.03.1 M00001512D:G09 3956
3528 1/28/98 630 RTAOOOOO 183 AR.g.03.2 M00001512D:G09 3956
3529 1/28/98 695 RTAOOOOO 197F.m.5.1 M00001528C:H04 10872
3530 1/28/98 479 RTA00000197R.1.22.1 M00001528A:C 1 1 6962
3530 1/28/98 665 RTAOOOOO 197AF.1.22.1 M00001528A:C 1 1 6962
3531 1/28/98 479 RTAOOOOO 197R.1.22.1 M00001528A:C 1 1 6962
3531 1/28/98 665 RTA00000197AF.1.22.1 M00001528A:C1 1 6962
3532 1/28/98 479 RTA00000197R.1.22.1 M00001528A:C1 1 6962
3532 1/28/98 665 RTAOOOOO 197AF.1.22.1 M00001528A:C1 1 6962
3533 1/28/98 479 RTA00000197R.1.22.1 M00001528A:C1 1 6962
3533 1/28/98 665 RTAOOOOO 197AF.1.22.1 M00001528A:C1 1 6962
3534 1/28/98 550 RTAOOOOO 183AF.g.14.1 M00001513D:A03 0
3535 1/28/98 404 RTAOOOOO 195 AF.b.6.1 M00001496C:G10 39490
3536 1/28/98 630 RTAOOOOO 183 AR.g.03.2 M00001512D:G09 3956
3536 1/28/98 632 RTAOOOOO 183 AR.g.03.1 M00001512D:G09 3956
3537 1/28/98 570 RTA00000183AF.3.19.2 M00001499A:A05 3788
3538 1/28/98 630 RTA00000183AR.g.03.2 M00001512D:G09 3956
3538 1/28/98 632 RTAOOOOO 183 AR.g.03.1 M00001512D:G09 3956
3539 1/28/98 603 RTAOOOOO 183 AR.d.1 1 .3 M00001504D:G06 6420
3540 1/28/98 715 RTA00000197AR.k. l l . l M00001500D:E10 53758
3541 1/28/98 503 RTAOOOOO 197AF.L9.1 M00001500C:C08 3138
3542 1/28/98 719 RTAOOOOO 183AF.b.12.1 M00001500A:B02 0
3543 1/28/98 271 RTA00000201 F.d.02.1 M00004375A:H01 2599
3543 1/28/98 239 RTA00000201 R.d.02.1 M00004375A:H01 2599
3543 1/28/98 227 RTA00000201 R.d.02.2 M00004375A:H01 2599
3544 1/28/98 630 RTAOOOOO 183 AR.g.03.2 M00001512D:G09 3956
3544 1/28/98 632 RTAOOOOO 183 AR.g.03.1 M00001512D:G09 3956
3545 3/24/98 15 RTA00000425F.J.14.1 M00001639D:C 12 73397
3546 3/24/98 1 1 1 RTA00000425F.d.08.1 M00001631 A:F06 74350
3547 3/24/98 152 RTA00000425F.d.07.1 M00001631 A:F12 43197
3548 3/24/98 147 RTA00000425F.d.21.1 M00001631 B:H04 78920
3549 3/24/98 77 RTA00000425F.U 7.1 M00001633A:F1 1 43213
3550 3/24/98 418 RTA00000425F.i.l 8.1 M00001633A:G 10 42255
3551 3/24/98 197 RTA00000425F.J.20.1 M00001633B:A12 26760
3552 3/24/98 143 RTA00000425F.J.22.1 M00001633B:E03 73882
3553 3/24/98 283 RTA00000425F.k.20.1 M00001633C:A08 74048
3554 3/24/98 139 RTA00000425F. 22.1 M00001633C:E12 78123
3555 2/24/98 870 RTA00000418F.n.24.1 M00001659D:C09 73153
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
3556 3/24/98 403 RTA00000425F.n. l 7.1 M00001636A:H 12 78304
3557 2/24/98 1 109 RTA00000422FT.22.1 M00001584A:G03 38703
3558 3/24/98 150 RTA00000424F.d.04.1 M00001478A:F12 76505
3558 3/24/98 149 RTA00000424F.d.04.3 M00001478A:F12 76505
3559 3/24/98 358 RTA00000425F.n. l 9.1 M00001638B:C08 78324
3560 3/24/98 165 RTA00000425F.e.21.1 M00001629D:D10 77203
3561 3/24/98 443 RTA00000425F.k. l 6.1 M00001640A:F05 75282
3562 3/24/98 252 RTA00000425F.IT1.03.1 M00001642D:G08 76045
3563 3/24/98 1 16 RTA00000425F.n.05.1 M00001647D:G07 73965
3564 3/24/98 425 RTA00000522F.L07.2 M00001649A:E10 78377
3565 ' 3/24/98 445 RTA00000522F.J.08.2 M00001650D:D10 76613
3566 3/24/98 371 RTA00000522F.J.09.2 M00001650D:F1 1 78522
3567 3/24/98 97 RTA00000522F.J.14.2 M00001651C:D1 1 73123
3568 3/24/98 69 RTA00000522F.J.15.2 M00001651 C:G12 76535
3569 3/24/98 373 RTA00000522F.J.19.2 M00001652B:D06 76224
3570 3/24/98 93 RTA00000522F. 14.1 M00001652D:G02 74280
3571 3/24/98 50 RTA00000522F.k. l 5.1 M00001652D:G06 76866
3572 3/24/98 141 RTA00000522F. 19.1 M00001653A:A05 32625
3573 3/24/98 409 RTA00000425F.1.10.1 M00001638A:C08 26893
3574 2/24/98 443 RTA00000414F.f. l 5.1 M00005260A:A12 0
3575 2/24/98 886 RTA00000420F.m. l 5.1 M00005235B:F10 0
3576 2/24/98 260 RTA00000414F.e.08.1 M00005236A:E04 0
3577 2/24/98 734 RTA00000414F.e.09.1 M00005236A:G10 0
3578 2/24/98 1077 RTA00000414F.e.l l .l M00005236B:A12 0
3579 2/24/98 970 RTA00000414F.e.l5.1 M00005236B:G03 0
3580 2/24/98 271 RTA00000414F.e.l6.1 M00005236B:H10 0
3581 2/24/98 58 RTA00000420F.m.l 8.1 M00005254D:A10 0
3582 2/24/98 289 RTA00000420F.n.08.1 M00005257A:H1 1 0
3583 2/24/98 1033 RTA00000414F.e.l 9.1 M00005257C:E05 0
3584 2/24/98 793 RTA00000414F.e.21.1 M00005257C:G01 0
3585 2/24/98 36 RTA00000414F.e.22.1 M00005257D:A06 0
3586 2/24/98 852 RTA00000414F.f.03.1 M00005257D:G07 0
3587 3/24/98 341 RTA00000425F.d.06.1 M00001631A:D03 77660
3588 2/24/98 961 RTA00000420F.n.21.2 M00005259B:D12 0
3589 3/24/98 441 RTA00000528F.g.22.2 M00001630C:F09 920
3590 2/24/98 940 RTA00000414FT.17.1 M00005260A:F04 0
3591 2/24/98 160 RTA00000414FT.19.1 M00005260B:E1 1 0
3592 3/24/98 140 RTA00000424F.m. l4.1 M00001612D:D12 77491
3593 3/24/98 34 RTA00000424F.m.l 5.1 M00001612D:F06 73759
3594 3/24/98 212 RTA00000424F.n.06.1 M00001613A:D02 74737
3595 3/24/98 308 RTA00000424F.k.23.1 M00001614A:B10 31061
3596 3/24/98 372 RTA00000424F.m.24.1 M00001614C:G07 77045
3597 3/24/98 396 RTA00000528F.g.05.2 M00001615C:E07 3770
3598 3/24/98 296 RTA00000425F.e.02.1 M00001625C:F10 76143
3599 3/24/98 99 RTA00000425F.C.20.1 M00001626D:A02 73581
3600 3/24/98 442 RTA00000425F.d. l4.1 M00001629A:H09 13417
3601 3/24/98 357 RTA00000425F.e. l 9.1 M00001629D:B10 73409
3602 2/24/98 210 RTA00000419F.p.24.1 M00004039B:E12 63477
3603 2/24/98 501 RTA00000414F.f.05.1 M00005257D:H 1 1 0
3604 2/24/98 561 RTA00000420F.e.10.1 M00004108D:G04 65899
SEQ ID Filing SEQ ID Sequence Name Clone Nsrne Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
3605 2/24/98 758 RTA00000407F.a.01.1 M00004039A:H 1 1 12501
3606 2/24/98 688 RTA00000413F.d.23.1 M00004090B:H06 66030
3607 2/24/98 124 RTA00000420F.d.05.1 M00004092B:E05 64432
3608 2/24/98 329 RTA00000413F.e.l 6.1 M00004093C:C02 63836
3609 2/24/98 359 RTA00000420F.d.l2.1 M00004096D:H03 64095
3610 2/24/98 429 RTA00000422F.C.17.1 M00004099D:F01 1360
361 1 2/24/98 630 RTA00000413F.f. l 9.1 M00004100B:C07 65189
3612 2/24/98 439 RTA00000413F.g.23.1 M00004103B:E09 40700
3613 2/24/98 3 RTA00000420F.d. l 8.1 M00004105C:B05 63074
3614 2/24/98 1064 RTA00000420F.d.l9.1 M00004105C:C08 43146
3615 2/24/98 671 RTA00000413F.h. l2.1 M00004107A:A12 66929
3616 2/24/98 507 RTA00000420F.e.02.1 M00004107B:D07 40259
3617 2/24/98 319 RTA00000420F.b.21.1 M00004088D:B10 65057
3618 2/24/98 931 RTA00000420F.e.09.1 M00004108D:E07 66325
3619 2/24/98 840 RTA00000420F.b.20.1 M00004088D:B05 0
3620 2/24/98 545 RTA00000420F.e.l 5.1 M000041 10A:A10 20190
3621 2/24/98 981 RTA00000420F.e.20.1 M000041 10B:A07 64762
3622 3/24/98 370 RTA00000424F.d.l9.3 M00001448B:A07 73180
3623 3/24/98 370 RTA00000424F.d. l9.3 M00001448B:A07 73180
3624 3/24/98 189 RTA00000424F.d.22.3 M00001448B:G07 76189
3625 3/24/98 189 RTA00000424F.d.22.3 M00001448B:G07 76189
3626 3/24/98 92 RTA00000424F.a.24.4 M00001448D:E1 1 73951
3627 3/24/98 92 RTA00000424F.a.24.4 M00001448D:E1 1 73951
3628 3/24/98 279 RTA00000528F.b.03.1 M00001455A:D10 2078
3629 3/24/98 279 RTA00000528F.b.03.1 M00001455A:D10 2078
3630 3/24/98 480 RTA00000424F.d.l 7.3 M00001455A:E1 1 73958
3631 3/24/98 480 RTA00000424F.d. l 7.3 M00001455A:E1 1 73958
3632 2/24/98 583 RTA00000406F.U 7.1 M00003904B:C03 37902
3633 2/24/98 590 RTA00000407F.b.22.1 M00004108B:B02 37487
3634 2/24/98 1075 RTA00000413F.b. l 7.1 M00004078A:F07 21704
3635 2/24/98 544 RTA00000420F.1.21.2 M00005232A:H12 0
3636 1/28/98 684 RTA00000200AR.b.l l . l M00004040A:G12 12043
3636 2/24/98 1 166 RTA00000347F.h.01.1 M00004040A:G12 12043
3637 1/28/98 684 RTA00000200AR.b. l l . l M00004040A:G12 12043
3637 2/24/98 1 166 RTA00000347F.h.01.1 M00004040A:G12 12043
3638 2/24/98 1087 RTA00000401 F.O.13.1 M00004040C:A01 3220
3639 2/24/98 1 14 RTA00000341 F.m.21.1 M00004051 D:E01 0
3640 2/24/98 81 1 RTA00000413F.a.l2.1 M00004072D:F09 63403
3641 2/24/98 714 RTA00000420F.a.08.1 M00004073A:D10 19473
3642 1/28/98 387 RTA00000191 AF.j.14.1 M00004073A:H 12 1002
3642 2/24/98 632 RTA00000191 AF.J.14.1 M00004073A:H12 1002
3643 1/28/98 387 RTA00000191 AF.J.14.1 M00004073A:H 12 1002
3643 2/24/98 632 RTAOOOOO 191 AF.j.14.1 M00004073A:H12 1002
3644 2/24/98 964 RTA00000423F.1.15.1 M00004075B:G09 1 1219
3645 2/24/98 355 RTA00000420F.3.19.1 M00004076A:D12 34192
3646 2/24/98 745 RTA00000413F.b.04.1 M00004076D:H07 66427
3647 2/24/98 64 RTA00000413F.d. l 8.1 M00004090B:B04 65305
3648 2/24/98 698 RTA00000413F.b.l6.1 M00004078A:E05 65126
3649 2/24/98 190 RTA00000419F.p.23.1 M00004039B:A05 64748
3650 2/24/98 903 RTA00000420F.a.21.1 M00004078B:C1 1 66241
SEQ ID Filing SEQ ID Sequence Name Clone Nsme Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
3651 2/24/98 588 RTA00000420F.3.23.1 M00004078B:F12 42158
3652 2/24/98 1 1 85 RTA00000413F.b.20.1 M00004079D:G08 66063
3653 2/24/98 619 RTA00000420F.b.04.1 M00004081 A:E02 63820
3654 2/24/98 988 RTA00000407F.a.22.1 M00004081 A:G01 15570
3655 2/24/98 705 RTA00000407F.3.23.1 M00004081 C:A10 23489
3656 2/24/98 282 RTA00000407F.3.24.1 M00004083A:E08 37560
3657 2/24/98 835 RTA00000413F.C.10.1 M00004083B:C01 65600
3658 2/24/98 598 RTA00000420F.b. l 8.1 M00004086D:G08 66136
3659 2/24/98 335 RTA00000413F.d.02.1 M00004087B:A12 661 72
3660 2/24/98 504 RTA00000413F.d.05.1 M00004087C:A01 64788
3661 2/24/98 76 RTA00000413F.d. l 6.1 M00004088C:F01 63331
3662 2/24/98 726 RTA00000420F.b. l 9.1 M00004088D:A1 1 36873
3663 2/24/98 521 RTA00000413F.b. l4.1 M00004078A:C 1 1 66591
3664 2/24/98 255 RTA00000419F.O.16.1 M00003989C:G05 62867
3665 2/24/98 665 RTA00000419F.p.20.1 M00004039A:C03 9458
3666 2/24/98 1234 RTA00000352R.C.20.1 M00003982A:B 12 7339
3667 2/24/98 247 RTA00000412F.J.17.1 M00003982C:G04 64071
3668 2/24/98 1 145 RTA00000423F. 21 .2 M00003984D:B08 37499
3669 2/24/98 993 RTA00000406F.O.05.1 M00003985B:G04 37894
3670 2/24/98 328 RTA00000423F. 19.2 M00003985D:E10 17615
3671 2/24/98 254 RTA00000341 F.1.15.1 M00003986B:A08 5294
3672 2/24/98 948 RTA00000419F.O.06.1 M00003986C:D09 64643
3673 2/24/98 661 RTA00000341 F.1.16.1 M00003986D:C08 8479
3674 2/24/98 1 1 7 RTA00000341 F.m. l3.1 M00003987B:E12 26502
3675 2/24/98 1210 RTA00000419F.O.09.1 M00003987B:F08 66396
3676 2/24/98 460 RTA00000341 F.J.12.1 M00003987C:G03 12195
3677 2/24/98 486 RTA00000346F.1.13.1 M00003980B:C 1 1 7542
3678 2/24/98 723 RTA00000419F.O.15.1 M00003989C:D03 32487
3679 2/24/98 897 RTA00000419F.n.24.1 M00003980A:F04 65995
3680 2/24/98 92 RTA00000412F.I.04.1 M00003989D:F12 66372
3681 2/24/98 1014 RTA00000412F.I.14.1 M00004029B:F01 62792
3682 2/24/98 348 RTA00000412F.1.19.1 M00004029C:C05 65825
3683 2/24/98 284 RTA00000412F.1.21.1 M00004029C:G 10 65183
3684 2/24/98 188 RTA00000406F.p.04.1 M00004030D:F 1 1 37458
3685 2/24/98 812 RTA00000412F.O.05.1 M00004034A:A01 63575
3686 2/24/98 91 1 RTA00000406F.p. l3.1 M00004034C:G02 8584
3687 2/24/98 230 RTA00000423F.k.01.1 M00004034D:E09 40426
3688 2/24/98 1076 RTA00000423F. 09.1 M00004035B:H09 26630
3689 2/24/98 941 RTA00000419F.p.08.1 M00004036D:B04 65560
3690 2/24/98 1 186 RTA00000419F.p. l 0.1 M00004036D:B09 41448
3691 2/24/98 42 RTA00000423F. 17.2 M00004038A:F02 37512
3692 2/24/98 934 RTA00000414F.e.01.1 M00005233D:H07 0
3693 2/24/98 37 RTA00000406F.O.15. 1 M00003988D:A08 37482
3694 2/24/98 1016 RTA00000406F.ii.12. ! M00003960A:G07 37517
3695 1 /28/98 584 RTAOOOOO 190 AR.c.03.1 M00003904C:A08 0
3695 2/24/98 1069 RTA00000346F. 05.1 M00003904C:A08 0
3696 1 /28/98 584 RTAOOOOO 190AR.C.03.1 M00003904C:A08 0
3696 2/24/98 1069 RTA00000346F. 05.1 M00003904C:A08 0
3697 2/24/98 489 RTA00000406F.J.19.1 M00003906A:F12 1685
3698 2/24/98 461 RTA00000412F.d. l 6.1 M00003906B:H06 26829
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
3699 2/24/98 558 RTA00000419F.m.04.1 M00003906C:C05 74367
3700 2/24/98 120 RTA00000401 F.m.02.1 M00003907A:F01 1573
3701 2/24/98 628 RTA00000412F.d. l 9.1 M00003907B:C03 75743
3702 2/24/98 792 RTA00000406F.k.l l . l M00003907B:D05 38715
3703 2/24/98 292 RTA00000423F.i.l 8.1 M00003918A:D08 14996
3704 2/24/98 1 192 RTA00000406F.m. l 7.1 M00003918A:F09 0
3705 2/24/98 9 RTA00000406F.n.02.1 M00003918C:H10 15051
3706 2/24/98 629 RTA00000352R.C.04.1 M00003924A:D08 71976
3707 2/24/98 438 RTAOOOOO 195R.d.09.1 M00003981 C:B04 8537
3708 2/24/98 433 RTA00000419F.n.02.1 M00003958B:H08 .65963
3709 2/24/98 147 RTA00000422F.C.02.1 M000041 18B:A03 2902
3710 2/24/98 649 RTA00000412F.g.03.1 M00003971 B:A10 64740
371 1 2/24/98 1 141 RTA00000347F.f.08.1 M00003972D:H02 5948
3712 2/24/98 252 RTA00000412F.g.24.1 M00003973C:C03 28741
3713 2/24/98 732 RTA00000412F.H.1 1.1 M00003974B:B 1 1 63175
3714 2/24/98 1 81 RTA00000412F.H.21.1 M00003974D:F02 64348
3715 2/24/98 345 RTA00000412F.h.23.2 M00003974D:H04 651 18
3716 2/24/98 148 RTA00000419F.11.04.1 M00003975C:F07 13102
371 7 2/24/98 31 1 RTA00000419F.n.09.1 M00003977C:A06 66070
3718 2/24/98 1044 RTA00000419F.n.1 1 .1 M00003977C:B03 66477
3719 2/24/98 652 RTA00000419F.n. l2.1 M00003977D:A03 66086
3720 2/24/98 452 RTA00000419F.n.l3.1 M00003977D:A06 66026
3721 2/24/98 796 RTA00000419F.n.l 5.1 M00003977D:D04 63484
3722 2/24/98 1249 RTA00000419F.n.l 7.1 M00003978D:G04 63186
3723 2/24/98 860 RTA00000419F.m.23.1 M00003958B:E1 1 64263
3724 2/24/98 713 RTA00000414F.b.l0.1 M00005212D:D09 0
3725 2/24/98 1002 RTA00000419F.p.l 8.1 M00004038D:G06 63002
3726 2/24/98 1048 RTA00000413F.O.07.2 M00005100A:C01 0
3727 2/24/98 508 RTA00000420F.i.20.1 M00005101 C:E12 0
3728 2/24/98 1001 RTA00000413F.p.07.2 M00005102C:D03 0
3729 2/24/98 88 RTA00000420F.L24.1 M00005134B:E08 0
3730 2/24/98 93 RTA00000413F.p.24.1 M00005139A:H03 0
3731 2/24/98 142 RTA00000420FJ.19.1 M00005140C:B 10 0
3732 2/24/98 833 RTA00000420FJ.20.1 M00005140D:C06 0
3733 2/24/98 316 RTA00000414F.a.02.1 M00005178D:H04 0
3734 2/24/98 1 100 RTA00000414F.a.l2.1 M00005210A:E06 0
3735 2/24/98 1 175 RTA00000414F.b.04.1 M00005212B:E01 0
3736 2/24/98 1236 RTA00000414F.b.06.1 M00005212C:C03 0
3737 2/24/98 747 RTA00000413F.n.24.1 M00004960C:E10 0
3738 2/24/98 207 RTA00000414F.b.08.1 M00005212C:H02 0
3739 2/24/98 935 RTA00000420F.i.07.1 M00004960A:B08 0
3740 2/24/98 741 RTA00000414F.b. l2.1 M00005212D:H01 0
3741 2/24/98 865 RTA00000414F.C.03.1 M00005216A:D09 0
3742 2/24/98 862 RTA00000414F.C.07.1 M00005216A:H01 0
3743 2/24/98 565 RTA00000420F.k.l 7.2 M00005217B:A06 0
3744 2/24/98 1226 RTA00000414F.C.12.1 M00005218A:F09 0
3745 2/24/98 512 RTA00000414F.C.16.1 M00005228A:B03 0
3746 2/24/98 817 RTA00000420F.1.08.2 M00005228C:C05 0
3747 2/24/98 573 RTA00000414F.C.23.1 M00005229B:G12 0
3748 2/24/98 1237 RTA00000414F.C.24.1 M00005229B:H04 0
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: D3te of NO: in ID Priority Priority Appln Appln
3749 2/24/98 727 RTA00000414F.d.02.1 M00005229B:H06 0
3750 2/24/98 566 RTA00000414F.d.05.1 M00005229D:H03 0
3751 2/24/98 307 RTA00000420F.I.12.2 M00005230B:H09 0
3752 3/24/98 149 RTA00000424F.d.04.3 M00001478A:F12 76505
3752 3/24/98 150 RTA00000424F.d.04.1 M00001478A:F12 76505
3753 2/24/98 946 RTA00000414F.b.07.1 M00005212C:D02 0
3754 1/28/98 343 RTA00000201 F.3.18.1 M00004314B:G07 16837
3754 2/24/98 571 RTA00000355R.e. l4.1 M00004314B:G07 16837
3755 2/24/98 481 RTA00000413F.i.23.1 M000041 18B:F01 63073
3756 2/24/98 1039 RTA00000407F.C.08.1 M000041 18D:B05 37549
3757 2/24/98 824 RTA00000420F.f.07.1 M000041 19A:C09 66312
3758 2/24/98 813 RTA00000346F.O.06.1 M00004136D:B02 4937
3759 2/24/98 1070 RTA00000346F.n.22.1 M00004137A:D06 0
3760 2/24/98 283 RTA00000346F.n.06.1 M00004139C:A12 12439
3761 2/24/98 368 RTA00000346F.O.08.1 M00004149C:B02 0
3762 2/24/98 704 RTA00000355R.3.12.1 M00004159C:F09 36756
3762 1/28/98 685 RTA00000200F.i.9.1 M00004159C:F09 36756
3763 1/28/98 685 RTA00000200F.Ϊ.9.1 M00004159C:F09 36756
3763 2/24/98 704 RTA00000355R.a. l2.1 M00004159C:F09 36756
3764 2/24/98 1254 RTA00000341 F.p. l l .l M00004159C:G12 0
3765 2/24/98 1 188 RTA00000341 F.O.18.1 M00004169D:B1 1 37189
3766 2/24/98 40 RTA00000352R.1.06.1 M00004187D:H06 40343
3767 2/24/98 456 RTA00000413F.O.06.1 M00005100A:B02 0
3768 2/24/98 882 RTA00000355R.C.03.1 M00004244C:G07 3986
3769 2/24/98 503 RTA00000420F.m.08.1 M00005233B:D04 0
3770 2/24/98 571 RTA00000355R.e.l4.1 M00004314B:G07 16837
3770 1/28/98 343 RTA00000201 F.3.18.1 M00004314B:G07 16837
3771 2/24/98 91 RTA00000355R.e.l5.1 M00004316A:G09 22639
3771 1/28/98 410 RTA00000201 F.3.20.1 M00004316A:G09 22639
3772 2/24/98 91 RTA00000355R.e. l 5.1 M00004316A:G09 22639
3772 1/28/98 410 RTA00000201 F.3.20.1 M00004316A:G09 22639
3773 2/24/98 1 135 RTA00000346F.O.16.1 M00004358D:C02 176
3774 2/24/98 220 RTA00000413F. 02.1 M00004690A:G08 0
3775 2/24/98 487 RTA00000420F.g.05.1 M00004891 B:D01 0
3776 2/24/98 102 RTA00000420F.g.06.1 M00004891 C:D04 0
3777 2/24/98 1238 RTA00000420F.g.09.1 M00004895B:E12 0
3778 2/24/98 18 RTA00000420F.g.l2.1 M00004895B:G04 0
3779 2/24/98 1 196 RTA00000413F.I.18.1 M00004895D:G07 0
3780 2/24/98 579 RTA00000413F.m.l 6.1 M00004898C:F03 0
3781 2/24/98 143 RTA00000420F.h.l3.1 M00004899D:G06 0
3782 2/24/98 909 RTA00000420F.i.04.1 M00004959D:H 12 0
3783 2/24/98 709 RTA00000352R.p.09.1 M00004228C:H03 16915
3784 3/24/98 221 RTA00000427F.J.22.1 M00004097D:B05 66367
3785 3/24/98 188 RTA00000525F.C.15.1 M00004040A:A07 7692
3786 3/24/98 401 RTA00000525F.C.16.1 M00004040A:B04 38209
3787 3/24/98 53 RTA00000525F.C.17.1 M00004040A:C08 38160
3788 3/24/98 325 RTA00000525F.C.18.1 M00004040B:C05 24208
3789 3/24/98 159 RTA00000525F.C.19.1 M00004040B:F07 38159
3790 3/24/98 209 RTA00000427F.g.l 6.1 M00004069A:E12 6301 1
3791 3/24/98 123 RTA00000427F.g.05.1 M00004069C:C08 63138
SEQ ID Filing SEQ ID Sequence Name Clone Nsme Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
3792 3/24/98 62 RTA00000427F.J.19.1 M00004077A:G 12 41395
3793 3/24/98 265 RTA00000427F.h.02.1 M00004085B:G01 63652
3794 3/24/98 235 RTA00000427F.g. l 9.1 M00004087A:B05 6461 1
3795 3/24/98 333 RTA00000427F.k.21.1 M00004090D:F12 62880
3796 3/24/98 130 RTA00000427F.h.l2.1 M00004092C:D08 36894
3797 3/24/98 243 RTA00000424F.C.15.3 M00001476D:F12 73533
3798 3/24/98 227 RTA00000427F.U 1.1 M00004097C:H08 26635
3799 3/24/98 456 RTA00000427F.a.l 0.1 M00004038B:D01 65370
3800 3/24/98 7 RTA00000523F.O.20.1 M00005177B:H02 0
3801 3/24/98 291 RTA00000523F.O.23.1 M00005177C:G04 0
3802 3/24/98 1 19 RTA00000523F.p.06.1 M00005177D:F09 0
3803 3/24/98 178 RTA00000428F.3.12.1 M00005179B:H02 0
3804 3/24/98 463 RTA00000523F.p. l 6.1 M00005179D:B03 0
3805 3/24/98 390 RTA00000524F.3.1 1.1 M00005210D:C09 0
3806 3/24/98 468 RTA00000524F.3.18.1 M0000521 1 A:E09 0
3807 3/24/98 1 14 RTA00000524F.3.23.1 M0000521 1 C:E09 0
3808 3/24/98 29 RTA00000524F.b.03.1 M00005212A:D10 0
3809 3/24/98 36 RTA00000428F.3.16.1 M00005212D:F08 0
3810 3/24/98 417 RTA00000524F.b. l 0.1 M00005213C:A01 0
381 1 3/24/98 182 RTA00000524F.b. l 7.1 M00005214B:A06 0
3812 3/24/98 348 RTA00000427F.i.09.1 M00004097C:E03 65916
3813 3/24/98 384 RTA00000527F.p.03.1 M00004029B:A06 5940
3814 3/24/98 84 RTA00000527F.L 18.1 M00003982B:C 10 1 1332
3815 3/24/98 48 RTA00000527F.k.21.1 M00003982B:H 10 36051
3816 3/24/98 271 RTA00000527F.1.05.1 M00003983A:D02 13016
3817 3/24/98 246 RTA00000426F.m.21.1 M00003983A:F06 64915
3818 3/24/98 16 RTA00000426F.m.22.1 M00003983A:G02 30002
3819 3/24/98 367 RTA00000527F.1.19.1 M00003983D:E08 36856
3820 3/24/98 477 RTA00000527F.1.21.1 M00003983D:H02 36439
3821 3/24/98 126 RTA00000527F.m.05.1 M00003985A:C01 17240
3822 3/24/98 89 RTA00000527F.n.02.1 M00003986C:G 1 1 24190
3823 3/24/98 263 RTA00000527F.n.07.1 M00003986D:H 12 15939
3824 3/24/98 49 RTA00000527F.n.22.1 M00004027A:A08 24175
3825 3/24/98 449 RTA00000426F.m.04.1 M00004028A:B10 36865
3826 3/24/98 336 RTA00000426F.n.l 7.1 M00004039D:B10 66572
3827 3/24/98 27 RTA00000527F.p.02.1 M00004029B:A01 36844
3828 3/24/98 297 RTA00000525F.C.1 1.1 M00004039C:E02 37895
3829 3/24/98 17 RTA00000527F.p.06.1 M00004029B:G10 1292
3830 3/24/98 310 RTA00000527F.p.08.1 M00004029C:F02 36013
3831 3/24/98 478 RTA00000527F.p.09.1 M00004029C:F05 7694
3832 3/24/98 253 RTA00000426F.m.08.1 M00004030B:A12 63781
3833 3/24/98 414 RTA00000426F.m. l 2.1 M00004030B:D08 63740
3834 3/24/98 345 RTA00000426F.n.23.1 M00004030C:A08 18176
3835 3/24/98 98 RTA00000527F.p.l6.1 M00004030C:C02 23798
3836 3/24/98 1 15 RTA00000525F.b.05.1 M00004034C:F05 21 1 16
3837 3/24/98 444 RTA00000525F.b.09.1 M00004035B:F05 23472
3838 3/24/98 158 RTA00000427F.3.06.1 M00004036A:A 1 1 66550
3839 3/24/98 376 RTA00000525F.D.21.1 M00004037C:D04 9486
3840 3/24/98 293 RTA00000525F.C.02.1 M00004038A:E05 14618
3841 3/24/98 138 RTA00000527F.C.22.1 M00003822B:G 12 37496
SEQ ID Filing SEQ ID Sequence Name Clone Nsme Cluster
NO: D3te of NO: in ID Priority Priority Appln Appln
3842 3/24/98 30 RTA00000426F.m.07.1 M00004028A:G03 63504
3843 3/24/98 322 RTA00000523F.i. l 7.1 M00003856B:A12 65779
3844 3/24/98 31 1 RTA00000428F.b.02.1 M00005214D:D10 0
3845 3/24/98 233 RTA00000426F.f.l 3.1 M00003851 A:A06 65384
3846 3/24/98 274 RTA00000523F.h.06.1 M00003851 B:D03 28745
3847 3/24/98 407 RTA00000523F.h.08.1 M00003851 B:E01 62893
3848 3/24/98 82 RTA00000523F.h. l 5.1 M00003851 C:F09 65137
3849 3/24/98 316 RTA00000523F.h. l 6.1 M00003851 D:H 1 1 66031
3850 3/24/98 232 RTA00000527F.i. l 3.2 M00003852B:G04 2924
3851 3/24/98 451 RTA00000527F.i.l 5.2 M00003852C:F07 14235
3852 3/24/98 249 RTA00000523F.h.21.1 M00003853B:C 10 41440
3853 3/24/98 72 RTA00000426F.f. l 9.1 M00003854C:C09 66701
3854 3/24/98 60 RTA00000523F.i.06.1 M00003855A:A01 66341
3855 3/24/98 91 RTA00000527F.i.21.2 M00003855A:F01 37490
3856 3/24/98 137 RTA00000527F.li.17.1 M00003848D:G02 37799
3857 3/24/98 433 RTA00000527F.J.04.2 M00003856A:G04 1 1809
3858 3/24/98 157 RTA00000523F.g. l 0.1 M00003848B:E07 40694
3859 3/24/98 75 RTA00000523F.i.22.1 M00003857A:E12 64688
3860 3/24/98 481 RTA00000523F.J.02.1 M00003857A:H10 62853
3861 3/24/98 377 RTA00000527F.J.12.2 M00003857C:E05 37503
3862 3/24/98 286 RTA00000426F.g.l 9.1 M00003858B:G02 63672
3863 3/24/98 71 RTA00000527F.J.20.2 M00003860D:E06 37603
3864 3/24/98 205 RTA00000426F.h.l2.1 M00003905C:F12 78093
3865 3/24/98 40 RTA00000426F.h.23.1 M0000391 1 A:D12 75964
3866 3/24/98 369 RTA00000524F.C.08.1 M00005217C:C01 0
3867 3/24/98 234 RTA00000524F.C.16.1 M00005218D:G10 0
3868 3/24/98 8 RTA00000428F.b.06.1 M00005228A:A09 0
3869 3/24/98 193 RTA00000428F.b.l2.1 M00005231 C:B07 0
3870 3/24/98 419 RTA00000428F.b.22.1 M00005231 D:B09 0
3871 2/24/98 486 RTA00000346F.1.13.1 M00003980B:C 1 1 7542
3872 3/24/98 421 RTA00000523F.i.l 0.1 M00003855B:B09 64876
3873 3/24/98 10 RTA00000527F.f.l2.1 M00003829D:D12 5945
3874 3/24/98 145 RTA00000426F.m.24.1 M00003981A:A07 63943
3875 3/24/98 39 RTA00000527F.C.23.1 M00003822C:A07 37742
3876 3/24/98 35 RTA00000426F.f.l l .l M00003823C:B01 63102
3877 3/24/98 385 RTA00000426F.f.l2.1 M00003823C:C04 19096
3878 3/24/98 2 RTA00000523F.d. l9.1 M00003824A:A06 26489
3879 3/24/98 225 RTA00000527F.d.09.1 M00003824A:G 1 1 10848
3880 3/24/98 359 RTA00000523F.d.21.1 M00003824B:C09 33424
3881 3/24/98 330 RTA00000523F.d.23.1 M00003824C:A10 63633
3882 3/24/98 254 RTA00000523F.d.24.1 M00003824D:D08 64799
3883 3/24/98 74 RTA00000527F.d. l9.1 M00003825B:F 10 486
3884 3/24/98 67 RTA00000527F.e.03.1 M00003825D:F01 25560
3885 3/24/98 352 RTA00000527F.e.l 3.1 M00003826C:F05 37588
3886 3/24/98 185 RTA00000527F.h.21.1 M00003850C:G09 37630
3887 3/24/98 338 RTA00000523F.e.l 5.1 M00003829C:E08 7919
3888 3/24/98 284 RTA00000524F.b.l9.1 M00005216B:D02 0
3889 3/24/98 242 RTA00000523F.e.20.1 M00003829D:F03 65164
3890 3/24/98 301 RTA00000527F.f. l 8.1 M00003830D:B 1 1 37577
3891 3/24/98 259 RTA00000528F.m.04.1 M00003830D:H 1 1 10815
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
3892 3/24/98 160 RTA00000523F.f.06.1 M00003833D:H08 62871
3893 3/24/98 166 RTA00000523F.f.07.1 M00003833D:H10 62799
3894 3/24/98 196 RTA00000523F.f. l2.1 M00003840A:C10 63751
3895 3/24/98 447 RTA00000523F.f. l9.1 M00003840B:F05 34169
3896 3/24/98 1 13 RTA00000527F.g.07.1 M00003840C:C02 37488
3897 3/24/98 45 RTA00000528F.m.12.1 M00003842D:F08 5768
3898 3/24/98 415 RTA00000527F.g. l2.1 M00003845C:D04 37746
3899 3/24/98 1 RTA00000527F.g. l 3.1 M00003845D:A04 36035
3900 3/24/98 450 RTA00000527F.g.21.1 M00003846B:C05 36028
3901 3/24/98 144 RTA00000527F.g.23.1 M00003846C:F08 37538
3902 3/24/98 422 RTA00000527F.f.03.1 M00003829A:B08 17788
3903 3/24/98 176 RTA00000522F.g.15.1 M00001595B:G07 76536
3904 3/24/98 264 RTA00000425F.e.09.1 M00001608C:G04 75550
3905 3/24/98 32 RTA00000424F.n.l4.1 M00001584D:C 1 1 73008
3906 3/24/98 459 RTA00000425F.C.03.1 M00001585D:B12 74643
3907 3/24/98 124 RTA00000424F.m.12.1 M00001586C:H07 77675
3908 3/24/98 314 RTA00000522F.e.09.1 M00001589D:A01 32599
3909 3/24/98 262 RTA00000424F.k.03.1 M00001590D:B04 21289
3910 3/24/98 106 RTA00000424FJ.14.1 M00001592B:B02 7431 1
391 1 3/24/98 424 RTA00000424F.k. l 0.1 M00001592D:H02 73232
3912 3/24/98 168 RTA00000424F.J.12.1 00001594C:E05 73827
3913 3/24/98 420 RTA00000424F.J.13.1 M00001594C:H03 74485
3914 3/24/98 210 RTA00000522F.g.06.1 M00001594D:G1 1 78221
3915 3/24/98 439 RTA00000522F.g. l 0.1 M00001595A:C07 74294
3916 3/24/98 300 RTA00000424F.m.08.1 M00001584A:A07 19402
3917 3/24/98 355 RTA00000522F.g.l2.1 M00001595A:E07 78783
3918 3/24/98 41 1 RTA00000424F.n.l2.1 M00001582C:G02 41589
3919 3/24/98 238 RTA00000522F.g. l 7.1 M00001595B:G10 76486
3920 3/24/98 472 RTA00000522F.g. l 8.1 M00001595B:H1 1 73226
3921 3/24/98 102 RTA00000522F.g.l 9.1 M00001595C:A01 781 19
3922 3/24/98 280 RTA00000522F.g.20.1 M00001595C:A05 77688
3923 3/24/98 191 RTA00000522F.g.22.1 M00001595C:B12 77504
3924 3/24/98 163 RTA00000522F.h.01.1 M00001595C:E05 75010
3925 3/24/98 438 RTA00000522F.h.02.1 M00001595C:E09 74947
3926 3/24/98 257 RTA00000522F.h.07.1 M00001595D:C 1 1 75149
3927 3/24/98 389 RTA00000424F.i.l 5.1 M00001596A:A02 78043
3928 3/24/98 167 RTA00000424F.i.20.1 M00001596A:D01 44010
3929 3/24/98 374 RTA00000528F.f.l 0.1 M00001596C:G05 3600
3930 3/24/98 215 RTA00000425F.f.02.1 M00001607A:A01 76982
3931 3/24/98 22 RTA00000527F.k. l 5.1 M00003982A:G03 22688
3932 3/24/98 378 RTA00000522F.g.l l . l M00001595A:D12 75432
3933 3/24/98 63 RTA00000522F.b.01.1 M00001570C:B02 75691
3934 3/24/98 430 RTA00000424F.g.08.1 M00001482C:F09 74928
3935 3/24/98 340 RTA00000424F.h.06.1 M00001485C:D07 77552
3936 3/24/98 161 RTA00000424F.li.10. ] M00001485C:G06 72925
3937 3/24/98 368 RTA00000424F.i.l l . l M00001485D:A05 41569
3938 3/24/98 455 RTA00000424F.g.24.1 M00001487C:A1 1 79156
3939 3/24/98 21 1 RTA00000424F.h.03.1 M00001487C:G09 74447
3940 3/24/98 174 RTA00000424F.b.21 .4 M00001530A:B02 24686
3941 3/24/98 383 RTA00000424F.b.23.4 M00001530A:H05 77322
SEQ ID Filing SEQ ID Sequence Name Clone Nsme Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
3942 3/24/98 179 RTA00000424F.d.l0.3 M00001530D:A1 1 731 10
3943 3/24/98 393 RTA00000424F.b.l 5.4 M00001539B:B10 74958
3944 3/24/98 347 RTA00000522F.a.05.1 M00001567A:C04 3261 1
3945 3/24/98 303 RTA00000522F.3.06.1 M00001567A:C1 1 73662
3946 3/24/98 229 RTA00000424F.n. l3.1 M00001584D:B06 74942
3947 3/24/98 392 RTA00000522F.a.20.1 M00001567C:E07 74070
3948 3/24/98 226 RTA00000425F.e.l 5.1 M00001608D:F1 1 75921
3949 3/24/98 285 RTA00000522F.b.07.1 M00001570D:E05 78634
3950 3/24/98 465 RTA00000528F.d.04.1 M00001570D:E07 2395
3951 3/24/98 404 RTA00000522F.b.l 8.1 M00001573B:A06 3460
3952 3/24/98 9 RTA00000522F.b.22.1 M00001573B:H12 75181
3953 3/24/98 109 RTA00000424F.a.01.4 M00001575A:D05 43214
3953 3/24/98 125 RTA00000424F.a.01.1 M00001575A:D05 43214
3954 3/24/98 125 RTA00000424F.a.01.1 M00001575A:D05 43214
3954 3/24/98 109 RTA00000424F.3.01.4 M00001575A:D05 43214
3955 3/24/98 294 RTA00000424F.a.05.1 M00001575B:C0 ! 77976
3955 3/24/98 292 RTA00000424F.a.05.4 M00001575B:C01 77976
3956 3/24/98 292 RTA00000424F.3.05.4 M00001575B:C01 77976
3956 3/24/98 294 RTA00000424F.3.05.1 M00001575B:C01 77976
3957 3/24/98 434 RTA00000522F.C.1 1.1 M00001576C:H02 31064
3958 3/24/98 299 RTA00000522F.C.14.1 M00001577A:A03 75449
3959 3/24/98 1 10 RTA00000522F.d.08.1 M00001578B:A06 74284
3960 3/24/98 306 RTA00000522F.d.23.1 M00001579D:F02 73868
3961 3/24/98 350 RTA00000424F.n.l l . l M00001582C:C04 73874
3962 3/24/98 366 RTA00000522F.3.17.1 M00001567C:B08 79032
3963 3/24/98 239 RTA00000523F.J.17.1 M00003966B:A04 63610
3964 3/24/98 405 RTA00000425F.e.07.1 M00001608C:D02 75992
3965 3/24/98 231 RTA00000426F.e.l 7.1 M00003810C:B06 64089
3966 3/24/98 104 RTA00000527F.b.l 8.1 M00003810D:H09 37469
3967 3/24/98 312 RTA00000426FT.17.1 M0000381 1 C:C02 66334
3968 3/24/98 266 RTA00000426F.f.l 6.1 M00003813B:F02 65613
3969 3/24/98 183 RTA00000527F.C.04.1 M00003813C:H08 23090
3970 3/24/98 435 RTA00000523F.C.13.1 M00003813D:B12 40668
3971 3/24/98 255 RTA00000523F.C.14.1 M00003813D:C02 66015
3972 3/24/98 131 RTA00000523F.C.15.1 M00003813D:G06 36935
3973 3/24/98 270 RTA00000426F.g.l 6.1 M00003814B:C01 41446
3974 3/24/98 95 RTA00000523F.C.18.1 M00003817C:A10 66179
3975 3/24/98 329 RTA00000527F.C.09.1 M00003817C:G06 64859
3976 3/24/98 65 RTA00000523F.C.01.1 M00003810A:A02 65710
3977 3/24/98 398 RTA00000527F.C.16.1 M00003821A:H09 22908
3978 3/24/98 96 RTAO00O0523F.b. l3.1 M00003809B:A03 66330
3979 3/24/98 313 RTA00000523F.J.21.1 M00003966C:A12 36925
3980 3/24/98 86 RTA00000523F. 01.1 M00003966C:F03 41437
3981 3/24/98 26 RTA00000427F.b.23.1 M00003973D:F08 64297
3982 3/24/98 277 RTA00000427F.e.08.1 M00003974D:E01 47387
3983 3/24/98 397 RTA00000427F.e.l 0.1 M00003974D:H07 64599
3984 3/24/98 31 RTA00000427F.C.10.1 M00003976B:E06 65478
3985 3/24/98 151 RTA00000427F.C.12.1 M00003976B:H07 66995
3986 3/24/98 57 RTA00000427F.C.20.1 M00003978A:E01 26527
3987 3/24/98 213 RTA00000427F.C.22.1 M00003978A:E09 63990
SEQ ID Filing SEQ ID Sequence Nsme Clone Nsme Cluster
NO: Dste of NO: in ID Priority Priority Appln Appln
3988 3/24/98 289 RTA00000427F.d. l 0.1 M00003978C:A 12 40685
3989 3/24/98 28 RTA00000427F.d.08.1 M00003980C:E12 63967
3990 3/24/98 335 RTA00000427F.d.09.1 M00003980C:F12 66486
3991 3/24/98 267 RTA00000425F.i.21 .1 M00001635B:B02 75305
3992 3/24/98 343 RTA00000527F.C.1 1 .1 M0000381 7D:D12 37484
3993 3/24/98 251 RTA00000425F.f.24.1 M00001656D:C04 40841
3994 3/24/98 155 RTA00000424F.I.19.1 M00001609C:A 12 75454
3995 3/24/98 321 RTA00000424F.m.04.1 M00001609C:G05 79017
3996 3/24/98 214 RTA00000424F.U 2.1 M00001610C:B07 77666
3997 3/24/98 446 RTA00000425F.f.20.1 M00001653D:H07 74071
3998 3/24/98 428 RTA00000522F.1.08.1 M00001654A:E08 78781
3999 3/24/98 295 RTA00000522F.1.15.1 M00001654B:A01 74691
4000 3/24/98 275 RTA00000522F.1.22.1 M00001654C:D10 75801
4001 3/24/98 223 RTA00000522F.m.02.1 M00001654C:G07 76834
4002 3/24/98 391 RTA00000522F.m.03.1 M00001654C:G09 79194
4003 3/24/98 346 RTA00000522F.m. l 9.1 M00001655C:C07 41544
4004 3/24/98 51 RTA00000522F.n.02.1 M00001655D:E08 74959
4005 3/24/98 94 RTA00000522F.n.05.1 M00001655D:H 1 1 73260
4006 3/24/98 332 RTA00000523F.C.03.1 M00003810B:B1 1 36913
4007 3/24/98 172 RTA00000425F.f. l l . l M00001656C:C04 79275
4008 3/24/98 58 RTA00000527F.L06.1 M00003981 B:B12 12469
4009 3/24/98 240 RTA00000522F.n. l4.1 M00001657C:C 1 1 73410
4010 3/24/98 56 RTA00000522F.n. l 6.1 M00001657D:A10 26769
401 1 3/24/98 20 RTA00000522F.O.06.1 M00001659D:A09 26860
4012 3/24/98 38 RTA00000528F.i.22.1 M00001661 D:D05 2478
4013 3/24/98 413 RTA00000425F.U 0.1 M00001664B:E08 78736
4014 3/24/98 412 RTA00000425F.i. l l . l M00001664B:F06 21716
4015 3/24/98 202 RTA00000528F.J.1 1 .1 M00001669B:C 12 1070
4016 3/24/98 432 RTA00000522F.O.20.1 M00001669C:B09 74853
4017 3/24/98 245 RTA00000522F.p.09.1 M00001670A:F09 75204
4018 3/24/98 33 1 RTA00000528F.L 10.1 M00001678C:F09 1981
4019 3/24/98 356 RTA00000523F.3.07.1 M00001693A:H06 75804
4020 3/24/98 200 RTA00000527F.3.13.1 M00003805D:E06 37740
4021 3/24/98 14 RTA00000523F.b.02.1 M00003806C:A06 65163
4022 3/24/98 1 77 RTA00000522F.n. l2.1 M00001656A:H 12 741 17
4023 2/24/98 1 158 RTA00000405F.O.03.1 M00003829C:H05 37575
4024 2/24/98 1 1 81 RTA00000346FT.14.1 M00003800B:F03 16998
4025 2/24/98 610 RTA00000419F.d.07.1 M00003820B:D10 21421
4026 2/24/98 1227 RTA0000041 1 F.g.05.1 M00003822D:B 10 64664
4027 2/24/98 412 RTA0000041 1 F.g.06.1 M00003822D:C06 66065
4028 2/24/98 21 RTA0000041 1 F.g.08.1 M00003822D:D04 45815
4029 2/24/98 1208 RTA00000347F.e.24.1 M00003823B:F07 8188
4030 2/24/98 502 RTA00000341 F.d.08.1 M00003824C:D07 0
4031 2/24/98 528 RTA00000405F.n. l 6.1 M00003825B:B 10 21503
4032 2/24/98 15 RTA00000419F.C.19.1 M00003820A:A08 64346
4033 2/24/98 637 RTA00000419F.d. l 4.1 M00003828A:D05 64945
4034 2/24/98 81 RTA00000419F.C.16.1 M00003819D:B01 65254
4035 2/24/98 754 RTA00000419F.e.02.1 M00003830C:A03 65010
4036 2/24/98 430 RTA00000419F.e.04.1 M00003831 C:G05 62963
4037 2/24/98 541 RTA0000041 1 F.h. l 5.1 M00003832A:A09 65160
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
4038 2/24/98 1079 RTA00000419F.e.l0.1 M00003833B:B03 63225
4039 2/24/98 577 RTA00000419F.e.ll.l M00003833B:C12 36780
4040 2/24/98 1220 RTA00000419F.e.23.1 M00003834B:G04 65772
4041 2/24/98 691 RTA00000354R.n.08.1 M00003835A:A09 8802
4042 2/24/98 536 RTA00000411F.i.02.1 M00003835B:H11 66975
4043 2/24/98 421 RTA00000419F.f.l0.1 M00003835D:G06 66193
4044 2/24/98 1150 RTA00000411F.g.24.1 M00003825B:B11 65233
4045 2/24/98 533 RTA00000423F.e.ll.l M00003809B:E10 2566
4046 2/24/98 520 RTA00000406F.C.20.1 M00003871D:G06 38578
4047 2/24/98 41 RTA00000419F.b.l2.1 M00003806B:C09 63148
4048 2/24/98 917 RTA00000423F.e.21.1 M00003806B:G05 66961
4049 2/24/98 326 RTA00000419F.b.l5.1 M00003806D:D11 43969
4050 2/24/98 297 RTA00000419F.b.l8.1 M00003808D:D08 67034
4051 2/24/98 139 RTA00000419F.b.l9.1 M00003809A:C01 65534
4052 2/24/98 1021 RTA00000419F.b.21.1 M00003809A:F01 65366
4053 2/24/98 1152 RTA00000405F.m.07.1 M00003809B:B02 37733
4054 2/24/98 310 RTA00000419F.d.06.1 M00003820B:D07 65496
4055 2/24/98 120 RTA00000401F.m.02.1 M00003907A:F01 1573
4056 2/24/98 69 RTA00000405F.O.18.1 M00003839A:D07 11016
4057 2/24/98 482 RTA00000411F.e.24.1 M00O03813A:B02 64781
4058 2/24/98 50 RTA00000411F.f.02.1 M00003813A:D08 63386
4059 2/24/98 602 RTA00000411F.f.06.1 M00003813B:E09 64186
4060 2/24/98 761 RTA00000411F.f.l4.1 M00003814B:C12 62984
4061 2/24/98 674 RTA00000411F.f.l7.1 M00003814B:F12 65661
4062 2/24/98 1164 RTA00000405F.m.21.1 M00003815C:C06 24218
4063 2/24/98 951 RTA00000419F.C.04.1 M00003815C:D12 63749
4064 2/24/98 471 RTA00000419F.C.11.1 M00003817B:C04 65504
4065 2/24/98 1047 RTA00000419F.C.14.1 M00003819B:G01 65727
4066 2/24/98 1178 RTA00000400F.f.ll.l M00001636A:E07 4088
4067 2/24/98 89 RTA00000406F.C.08.1 M00003870C:A10 22387
4068 2/24/98 94 RTA00000406F.3.23.1 M00003867B:D10 38712
4069 2/24/98 1038 RTA00000406F.b.01.1 M00003867B:G07 39006
4070 2/24/98 783 RTA00000406F.b.02.1 M00003867B:G08 38744
4071 2/24/98 563 RTA00000406F.b.08.1 M00003867D:A06 18258
4072 2/24/98 1072 RTA00000419F.J.03.1 M00003868B:G06 77578
4073 2/24/98 846 RTA00000419F.J.11.1 M00003868C:C07 73183
4074 2/24/98 17 RTA00000411 F.m.15.1 M00003868D:B09 78014
4075 2/24/98 589 RTA00000411F.m.l8.1 M00003868D:D09 75629
4076 2/24/98 971 RTA00000411F.i.ll.l M00003837C:E05 66849
4077 2/24/98 794 RTA00000406F.C.06.1 M00003870C:A01 37924
4078 2/24/98 788 RTA00000419F.i.04.1 M00003860B:F11 65791
4079 2/24/98 883 RTA00000406F.C.09.1 M00003870C:E10 5671
4080 2/24/98 918 RTA00000419F.J.22.1 M00003871A:A02 73525
4081 2/24/98 757 RTA00000423F.h.l3.1 M00003871A:B09 14398
4082 2/24/98 208 RTA00000419F.J.23.1 M00003871A:C11 74470
4083 2/24/98 1127 RTA00000401F.g.22.1 M00003871A:G09 1147
4084 2/24/98 1205 RTA00000419F.k.05.1 M00003871C:E04 11757
4085 2/24/98 522 RTA00000406F.C.18.1 M00003871C:F12 14368
4086 2/24/98 459 RTA00000419F.k.06.1 M00003871D:A10 78493
4087 2/24/98 965 RTA00000411F.n.06.1 M00003871D:E11 73886
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: D3te of NO: in ID Priority Priority Appln Appln
4088 2/24/98 457 RTA00000411F.m.l9.1 M00003868D:D11 74924
4089 2/24/98 145 RTA00000419F.g.l2.1 M00003842C:G03 66171
4090 2/24/98 633 RTA00000341F.d.02.1 M00003797A:G03 4706
4091 2/24/98 1026 RTA00000419F.f.l8.1 M00003839D:E11 64047
4092 2/24/98 524 RTA00000419F.f.23.1 M00003840D:H10 65002
4093 2/24/98 204 RTA00000351R.k.l9.1 M00003841B:E03 936
4094 2/24/98 968 RTA00000419F.f.24.1 M00003841B:E06 18717
4095 2/24/98 209 RTA00000411F.J.02.1 M00003841C:D07 65310
4096 2/24/98 1118 RTA00000411F.J.03.1 M00003841C:F01 66263
4097 2/24/98 470 RTA00000411F.J.06.1 M00003841C:H08 63545
4098 2/24/98 1153 RTA00000411F.J.07.1 M00003841C:H11 66963
4099 1/28/98 412 RTAOOOOO 195 AF.c.24.1 M00003860D:H07 0
4099 2/24/98 678 RTA00000195AF.C.24.1 M00003860D:H07 0
4100 2/24/98 777 RTA00000419F.g.02.1 M00003842A:A03 62839
4101 2/24/98 678 RTAOOOOO 195 AF.c.24.1 M00003860D:H07 0
4101 1/28/98 412 RTAOOOOO 195 AF.c.24.1 M00003860D:H07 0
4102 2/24/98 799 RTA00000411F.J.15.1 M00003843A:E04 66871
4103 2/24/98 932 RTA00000405F.p.03.1 M00003844A:A11 11346
4104 2/24/98 266 RTA00000419F.g.l5.1 M00003844D:A07 32519
4105 2/24/98 547 RTA00000419F.h.02.1 M00003845D:G08 63985
4106 2/24/98 290 RTA00000411F.k.l6.1 M00003852C:B06 64759
4107 2/24/98 23 RTA00000411F.k.20.1 M00003854B:A07 64973
4108 2/24/98 1138 RTA00000411F.k.21.1 M00003854B:D04 65349
4109 2/24/98 1000 RTA00000351R.J.21.1 M00003859D:C05 31604
4110 2/24/98 980 RTA00000411F.i.l3.1 M00003837C:F10 66138
4111 2/24/98 112 RTA00000422F.C.11.1 M00003841D:A04 2643
4112 2/24/98 905 RTA00000405F.g.21.2 M00001673B:F07 38966
4112 2/24/98 906 RTA00000405F.g.21.1 M00001673B:F07 38966
4113 2/24/98 294 RTA00000405F.1.17.1 M00003805A:F02 17225
4114 2/24/98 105 RTA00000346F.d.08.1 M00001671A:A10 39955
4115 2/24/98 1190 RTA00000405F.g.02.2 M00001671B:G05 10567
4116 2/24/98 280 RTA00000418F.p.l5.1 M00001671C:C11 31066
4117 2/24/98 1151 RTA00000405F.g.l8.2 M00001672D:E08 5255
4118 2/24/98 66 RTA00000405F.g.l9.2 M00001673A:G08 37150
4119 2/24/98 1239 RTA00000340F.O.22.1 M00001673B:B07 7356
4120 2/24/98 906 RTA00000405F.g.21.1 M00001673B:F07 38966
4120 2/24/98 905 RTA00000405F.g.21.2 M00001673B:F07 38966
4121 2/24/98 893 RTA00000418F.p.l0.1 M00001669D:F05 75323
4122 2/24/98 906 RTA00000405F.g.21.1 M00001673B:F07 38966
4122 2/24/98 905 RTA00000405F.g.21.2 M00001673B:F07 38966
4123 2/24/98 808 RTA00000418F.p.08.1 M00001669D:D06 73983
4124 2/24/98 469 RTA00000405F.g.24.1 M00001673D.-D06 39076
4125 2/24/98 1094 RTA00000405F.h.03.2 M00001673D:F10 20633
4126 2/24/98 803 RTA00000405F.h.05.2 M00001674A:G07 75706
4127 2/24/98 667 RTA00000405F.h.07.2 M00001674A:G11 4984
4128 2/24/98 276 RTA00000423F.a.l8.1 M00001675A:G10 26761
4129 2/24/98 1050 RTA00000405F.f.05.2 M00001669C:D09 14359
4129 2/24/98 1049 RTA00000405FT.05.1 M00001669C:D09 14359
4130 2/24/98 1050 RTA00000405F.f.05.2 M00001669C:D09 14359
4130 2/24/98 1049 RTA00000405F.f.05.1 M00001669C:D09 14359
SEQ ID Filing SEQ ID Sequence Name Clone Nsme Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4131 2/24/98 104 RTA00000421F.n.03.1 M00001675C:A04 1638
4132 2/24/98 388 RTA00000411F.3.07.1 M00001675C:C03 74547
4133 2/24/98 906 RTA00000405F.g.21.1 M00001673B:F07 38966
4133 2/24/98 905 RTA00000405F.g.21.2 M00001673B:F07 38966
4134 2/24/98 222 RTA00000405F.e.09.1 M00001663C:F12 38978
4135 2/24/98 518 RTA00000410F.m.l8.1 M00001660B:A09 76365
4136 2/24/98 218 RTA00000346F.e.l3.1 M00001660B:D03 74653
4137 2/24/98 427 RTA00000410F.m.20.1 M00001660B:E03 74285
4138 2/24/98 1099 RTA00000400F.m.l6.1 M00001660B:E04 3307
4139 2/24/98 775 RTA00000405F.C.22.1 M00001660C:B06 39053
4140 2/24/98 28 RTA00000422F.p.06.2 M00001661A:B11 39282
4141 2/24/98 108 RTA00000418F.O.18.1 M00001661B:F06 78676
4142 2/24/98 954 RTA00000410F.n.05.l M00001662A:C07 77830
4143 2/24/98 1182 RTA00000346F.d.21.1 M00001670B:G12 6641
4144 2/24/98 1043 RTA00000423F.b.l7.1 M00001662B:F06 8200
4145 2/24/98 447 RTA00000423F.b.04.3 M00001675D:E10 6311
4146 2/24/98 305 RTA00000418F.p.06.1 M00001664A:F08 32628
4147 2/24/98 1116 RTA00000410F.O.04.1 M00001664D:F04 79018
4148 2/24/98 320 RTA00000422F.p.07.2 M00001661A:E06 39024
4149 2/24/98 197 RTA00000410F.O.05.1 M00001669A:B02 75262
4150 2/24/98 738 RTA00000422F.n.20.1 M00001669B:B12 38676
4151 2/24/98 495 RTA00000400F.O.21.1 M00001669C:C08 16259
4152 2/24/98 1050 RTA00000405F.f.05.2 M00001669C:D09 14359
4152 2/24/98 1049 RTA00000405F.f.05.1 M00001669C:D09 14359
4153 2/24/98 1049 RTA00000405F.f.05.1 M00001669C:D09 14359
4153 2/24/98 1050 RTA00000405F.f.05.2 M00001669C:D09 14359
4154 2/24/98 492 RTA00000340F.O.18.1 M00001669D:C03 4261
4155 2/24/98 61 RTA00000410F.n.07.1 M00001662A:G01 78823
4156 2/24/98 299 RTA00000405F.1.15.1 M00001694A:E03 19575
4157 2/24/98 475 RTA00000411F.d.05.1 M00001681C:A08 75812
4158 2/24/98 692 RTA00000411F.d.l0.1 M00001681D:C12 76445
4159 2/24/98 336 RTA00000340F.n.l3.1 M00001688D:B10 17055
4160 2/24/98 270 RTA00000411F.d.l5.1 M00001692A:B06 74890
4161 2/24/98 969 RTA00000411F.d.l8.1 M00001692A:G06 76063
4162 2/24/98 927 RTA00000411F.d.21.1 M00001692B:E01 74794
4163 2/24/98 1133 RTA00000405F.1.03.1 M00001692D:B01 38580
4164 2/24/98 576 RTA00000401F.d.l5.2 M00001693C:C12 5297
4165 2/24/98 1059 RTA00000405F.h.21.2 M00001675C:D12 39072
4166 2/24/98 780 RTA00000405F.1.11.1 M00001693D:E08 2055
4167 2/24/98 933 RTA00000419F.3.18.1 M00001680A:B02 78484
4168 2/24/98 631 RTA00000411F.e.03.1 M00001694D:C12 73648
4169 2/24/98 585 RTA00000340R.O.12.1 M00003746C:E02 53732
4170 2/24/98 604 RTA00000351R.C.13.1 M00003747D:C05 11476
4171 2/24/98 187 RTA00000351R.g.ll.l M00003779D:E08 3077
4172 2/24/98 1060 RTA00000346F.g.02.1 M00003792A:B10 6901
4173 2/24/98 690 RTA00000341F.b.05.1 M00003793D:A11 0
4174 2/24/98 86 RTA00000346F.g.22.1 M00003794D:G03 6371
4175 2/24/98 1051 RTA00000346F.h.24.1 M00003797A:C11 4379
4176 2/24/98 377 RTA00000346F.i.01.1 M00003797A:D06 22260
4177 2/24/98 963 RTA00000405F.1.07.1 M00001693C:E09 38636
SEQ ID Filing SEQ ID Sequence Name Clone Nsme Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
4178 2/24/98 121 RTA00000418F.p.l9.1 M00001677D:B01 78544
4179 2/24/98 781 RTA00000423F.f.09.1 M00003808C:A05 64823
4180 2/24/98 1028 RTA00000346F.d.l2.1 M00001676B:B09 11777
4181 2/24/98 82 RTA00000411F.b.03.1 M00001676B:E01 23634
4182 2/24/98 465 RTA00000350R.p.l8.1 M00001676B:F05 11460
4183 2/24/98 56 RTA00000411F.b.06.1 M00001676C:A04 77884
4184 2/24/98 789 RTA00000423F.b.l3.1 M00001676C:E07 20619
4185 2/24/98 267 RTA00000423F.a.l9.1 M00001676D:A02 21396
4186 2/24/98 836 RTA00000411F.b.l7.1 M00001676D:B02 72893
4187 2/24/98 370 RTA00000405F.i.20.1 M00001677A:G11 38532
4188 2/24/98 39 RTAOOOOO 187AF.1.7.1 M00001680D:F08 10539
4189 2/24/98 389 RTA00000411F.C.02.1 M00001677B:B04 72852
4190 2/24/98 1004 RTA00000419F.a.24.1 M00001680B:D02 79290
4191 2/24/98 958 RTA00000195AF.C.8.1 M00001678B:H01 0
4191 1/28/98 520 RTA00000195AF.C.8.1 M00001678B:H01 0
4192 2/24/98 958 RTA00000195AF.C.8.1 M00001678B:H01 0
4192 1/28/98 520 RTA00000195AF.C.8.1 M00001678B:H01 0
4193 2/24/98 500 RTA00000411F.C.10.1 M00001678D:B11 73117
4194 2/24/98 323 RTA00000421F.n.l9.1 M00001679A:D10 16409
4195 2/24/98 309 RTA00000340F.n.01.1 M00001679A:G06 39081
4196 2/24/98 337 RTA00000340F.p.04.1 M00001679D:B02 78533
4197 1/28/98 238 RTAOOOOO 187AR.L 12.1 M00001679D:F02 78415
4197 2/24/98 407 RTA00000340R.m.07.1 M00001679D:F02 78415
4198 1/28/98 238 RTAOOOOO 187AR.L 12.1 M00001679D:F02 78415
4198 2/24/98 407 RTA00000340R.m.07.1 M00001679D:F02 78415
4199 2/24/98 387 RTA00000411F.3.15.1 M00001675D:B08 73812
4200 2/24/98 48 RTA00000411F.b.24.1 M00001677B:A12 30041
4201 2/24/98 234 RTA00000195AF.d.4.1 M00003881D:D06 22766
4201 1/28/98 185 RTA00000195AF.d.4.1 M00003881D:D06 22766
4202 2/24/98 130 RTA00000406F.f.l2.1 M00003879A:C11 21895
4203 2/24/98 953 RTA00000406F.f.05.1 M00003878C:F06 22961
4204 2/24/98 138 RTA00000406F.f.03.1 M00003878C:D08 38687
4205 2/24/98 673 RTA00000406F.d.09.1 M00003875B:F12 38591
4206 2/24/98 136 RTA00000419F.I.12.1 M00003901C:B01 75710
4207 2/24/98 300 RTA00000406F.g.17.1 M00003881B:F10 37979
4208 2/24/98 2 RTA00000406F.d.l6.1 M00003875C:G02 15040
4209 2/24/98 1207 RTA00000401F.J.21.1 M00003901B:F10 0
4210 2/24/98 494 RTA00000419F. 2.1 M00003876C:F02 0
4211 2/24/98 515 RTA00000419F.1.03.1 M00003879A:D02 79060
4212 2/24/98 26 RTA00000423F.h.l8.1 M00003876C:D02 37972
4213 2/24/98 49 RTA00000406F.d.l2.1 M00003875C:A01 38575
4214 2/24/98 986 RTA00000406F.d.24.1 M00003876B:C05 37997
4215 2/24/98 150 RTA00000419F.L19.1 M00003877C:G12 75447
4216 2/24/98 538 RTA00000423F.g.04.1 M00003903D:C12 23012
4217 2/24/98 1046 RTA00000346F.J.06.1 M00003879A:A02 5767
4218 2/24/98 868 RTA00000406F.i.08.1 M00003903C:E12 37946
4219 2/24/98 409 RTA00000406F.f.ll.1 M00003879A:B08 38601
4220 2/24/98 924 RTA00000354R.m.02.1 M00003890B:C08 12766
4221 2/24/98 543 RTA00000419F.k.24.1 M00003878C:G08 75596
4222 1/28/98 185 RTA00000195AF.d.4.1 M00003881D:D06 22766
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
4222 2/24/98 234 RTAOOOOO 195 AF.d.4.1 M00003881 D:D06 22766
4223 2/24/98 382 RTA00000341 F.li.10.1 M00003901 B:G 1 1 0
4224 2/24/98 550 RTA0000041 1 F.n.20.1 M00003875C:A09 75816
4225 2/24/98 614 RTA00000406F.U 3.1 M00003904A:C04 37904
4226 2/24/98 13 RTA00000406F.f. l 8.1 M00003879B:G02 38587
4227 2/24/98 1256 RTA00000401 F. 19.1 M00003903D:D10 799
4228 2/24/98 185 RTA00000423F.J.05.1 M00003903C:C05 37958
4229 2/24/98 1 77 RTA00000406F.i.l 2.1 M00003903D:H1 1 39080
4230 2/24/98 802 RTA00000406F.g.03.1 M00003880B:D1 1 38690
4231 2/24/98 34 RTA0000041 1 F.11.1 1.1 M00003875A:B01 77276
4232 2/24/98 498 RTA00000406F.e. l 5.1 M00003877C:A1 1 39074
4233 2/24/98 929 RTA0000041 1 F.n.09.1 M00003875A:A07 78962
4234 2/24/98 984 RTA00000406F.g.08.1 M00003880C:H03 37963
4235 2/24/98 818 RTA00000406F.h.05.1 M00003901 B:C03 38542
4236 2/24/98 592 RTA00000421 F.p.l 8.1 M00003877B:H 10 750
4237 2/24/98 313 RTA00000406F.g.07.1 M00003880C:E1 1 37925
4238 1/28/98 324 RTA00000184F.J.06.1 M00001556B:G02 1 1294
4239 2/24/98 773 RTA00000406F.h.03.1 M00003901 B:A09 38585
4240 3/24/98 244 RTA00000426F.p.09.1 M00004033D:B07 66665
4241 3/24/98 222 RTA00000426F.p. l0.1 M00004033D:C05 65845
4242 1/28/98 181 RTA00000198AF.d.2.1 M00001585A:F07 0
4243 1/28/98 77 RTA00000197AF.n.2.1 M00001535A:D02 6229
4244 2/24/98 844 RTA0000041 1 F.3.09.1 M00001675C:F01 78629
4245 2/24/98 352 RTA0000041 1 F.a. l 0.1 M00001675C:G01 73073
4246 3/24/98 272 RTA00000426F.m.02.1 M00004034C:C06 66237
4247 3/24/98 429 RTA00000525F.a. l4.1 M00004033B:C02 37566
4248 2/24/98 1 18 RTA00000408F.h.03.1 M00001479D:H03 78382
4249 3/24/98 156 RTA00000525F.b.22.1 M00004037C:D07 16679
4250 2/24/98 70 RTA00000409F.m. l3.1 M00001618B:E05 0
4251 2/24/98 1 198 RTA00000412F.f.l 0.2 M00003959A:A03 65405
4252 2/24/98 1 139 RTA00000404F.h.20.1 M00001619B:A09 15564
4253 3/24/98 41 RTA00000525F.b. l 7.1 M00004037B:A04 24715
4254 3/24/98 452 RTA00000525F.3.22.1 M00004033D:G06 36848
4255 2/24/98 1019 RTA00000403F.g.03.1 M00001479D:G06 23537
4256 2/24/98 532 RTA00000403F.3.24.1 M00001455B:A09 24128
4257 3/24/98 5 RTA00000426F.p.04.1 M00004029B:H08 34149
4258 3/24/98 43 RTA00000527F.p.07.1 M00004029C:B03 23343
4259 2/24/98 562 RTA00000401 F.J.17.1 M00003901 B:C05 5483
4260 2/24/98 303 RTA00000130A.h.22.1 M00001617A:D06 80933
4261 2/24/98 1201 RTA00000409F.m.02.1 M00001616C:A1 1 9157
4262 3/24/98 241 RTA00000527F.O.12.1 M00004028B:G08 688
4263 2/24/98 1 170 RTA00000409F.1.24.1 M00001616C:A02 73174
4264 2/24/98 1 76 RTA00000403F.b. l 0.1 M00001455C:G07 73268
4265 1/28/98 131 RTA00000185AF.d. l l .2 M00001579D:C03 6539
4265 1/28/98 626 RTAOOOOO 185 AR.d.1 1.1 M00001579D:C03 6539
4266 1/28/98 190 RTAOOOOO 134A.C.7.1 M00001528A:A01 5175
4266 1/28/98 176 RTAOOOOO 183AF.h.19.1 M00001528A:A01 5175
4267 3/24/98 90 RTA00000525F.3.03.1 M00004031 D:F05 36786
4268 3/24/98 236 RTA00000527F.O.01.1 M00004027A:D06 19088
4269 3/24/98 339 RTA00000426F.m.03.1 M00004034C:E08 66480
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4270 1/28/98 183 RTAOOOOO 198AF.C.17.1 M00001579C:E08 6923
4271 3/24/98 44 RTA00000527F.p. l 7.1 M00004030C:D12 17223
4272 3/24/98 129 RTA00000527F.p. l 8.1 M00004030D:B06 31635
4273 3/24/98 402 RTA00000527F.p.24.1 M00004031 B:A06 36832
4274 3/24/98 1 18 RTA00000525F.a.02.1 M00004031 C:H 10 37454
4275 1/28/98 353 RTAOOOOO] 98F.a.9.1 M00001557D:C08 0
4276 2/24/98 1250 RTA00000403F.f.l 5.1 M00001477D:F10 22768
4277 1/28/98 13 1 RTA00000185AF.d. l l .2 M00001579D:C03 6539
4277 1/28/98 626 RTAOOOOO 185 AR.d.1 1.1 M00001579D:C03 6539
4278 2/24/98 428 RTA00000422F.f.l4.1 M00001478B:D07 2036
4279 1/28/98 209 RTAOOOOO 182AF.C.5.1 M00001464D:F06 6397
4279 1 /28/98 304 RTA00000182AR.C.5.1 M00001464D:F06 6397
4280 2/24/98 205 RTA00000138A.n.4.1 M00001624A:G 1 1 21920
4281 2/24/98 251 RTAOOOOO 1 19A.Ϊ.9.1 M00001457A:G03 0
4282 3/24/98 250 RTA00000427F.h.24.1 M00004091 B:H09 65193
4283 1/28/98 61 RTAOOOOO 197AF.h.1 1.1 M00001476D:G03 22264
4284 3/24/98 216 RTA00000427F.h. l l . l M00004092C:B 12 26494
4285 1/28/98 1 10 RTAOOOOO 197R.h.01.1 M00001470A:H01 13075
4285 1/28/98 591 RTAOOOOO 197AF.h.1.1 M00001470A:H01 13075
4286 1/28/98 1 10 RTAOOOOO 197R.h.01.1 M00001470A:H01 13075
4286 1/28/98 591 RTAOOOOO 197AF.li.1.1 M00001470A:H01 13075
4287 3/24/98 276 RTA00000427F.h.l9.1 M00004092D:B1 1 63047
4288 1/28/98 335 RTAOOOOO 182AF.e.3.2 M00001468B:H06 0
4289 3/24/98 475 RTA00000427F.i.06.1 M00004097B:D03 41450
4290 2/24/98 286 RTA00000404F.i.l9.1 M00001625B:C10 38698
4291 1/28/98 209 RTAOOOOO 182AF.C.5.1 M00001464D:F06 6397
4291 1/28/98 304 RTA00000182AR.C.5.1 M00001464D:F06 6397
4292 2/24/98 1 165 RTA00000408F.C.08.1 M00001456D:G 1 1 73473
4293 1/28/98 304 RTA00000182AR.C.5.1 M00001464D:F06 6397
4293 1/28/98 209 RTA00000182AF.C.5.1 M00001464D:F06 6397
4294 1/28/98 138 RTAOOOOO 182AF.a.3.3 M00001462B:A10 0
4295 1/28/98 36 RTA00000181 AF.p.4.3 M00001460A:A03 40392
4296 2/24/98 523 RTA00000418F.J.09.1 M00001626C:D12 76352
4297 2/24/98 296 RTA00000347F.d.06.1 M00001457C:F02 39122
4298 1/28/98 390 RTAOOOOO 197AR.f.07.1 M00001457C:C1 1 19261
4298 1/28/98 184 RTAOOOOO 197 AF.f.7.1 M00001457C:C1 1 19261
4299 1/28/98 184 RTAOOOOO 197 AF.f.7.1 M00001457C:C1 1 19261
4299 1/28/98 390 RTAOOOOO 197AR.f.07.1 M00001457C:C1 1 19261
4300 1/28/98 133 RTA00000181 AR.n.20.3 M00001457B:E03 0
4301 3/24/98 132 RTA00000427F. 17.1 M00004101 A:F07 64965
4302 3/24/98 218 RTA00000427F.i. l9.1 M00004102C:D01 64206
4303 3/24/98 436 RTA00000427F.i.21.1 M00004102C:F03 65540
4304 1/28/98 209 RTA00000182AF.C.5.1 M00001464D:F06 6397
4304 1/28/98 304 RTAOOOOO 182AR.C.5.1 M00001464D:F06 6397
4305 1/28/98 176 RTAOOOOO 183AF.h.19.1 M00001528A:A01 5175
4305 1/28/98 190 RTAOOOOO 134A.C.7.1 M00001528A:A01 5175
4306 1/28/98 12 RTA00000183AF.i.l 5.2 M00001529B:C04 2642
4306 2/24/98 379 RTA00000349R.J.07.1 M00001529B:C04 2642
4307 2/24/98 1 156 RTA00000408FT.10.2 M00001476D:C05 75309
4308 2/24/98 366 RTA00000403F.C.10.1 M00001456D:F05 75261
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4309 2/24/98 353 RTA00000409F.n.17.1 M00001621 C:C10 76725
4310 2/24/98 526 RTA0000041 1 F.a.05.1 M00001675B:H03 76699
431 1 2/24/98 90 RTA0000041 1 F.a.02.1 M00001675B:E02 78537
4312 2/24/98 952 RTA0000041 1 F.a.01.1 M00001675B:D02 74524
4313 2/24/98 392 RTA00000410F.p.23.1 M00001675B:C01 73948
4314 2/24/98 238 RTA00000340F.J.12.1 M00001624A:B06 3277
4315 1/28/98 176 RTAOOOOO 183AF.h.19.1 M00001528A:A01 5175
4315 1/28/98 190 RTAOOOOO 134A.C.7.1 M00001528A:A01 5175
4316 2/24/98 298 RTA00000406F.h.07.1 M00003901 B:H04 38003
4317 1/28/98 190 RTA00000134A.C.7.1 M00001528A:A01 5175
4317 1/28/98 176 RTAOOOOO 183AF.h.19.1 M00001528A:A01 5175
4318 1/28/98 12 RTA00000183AF.U 5.2 M00001529B:C04 2642
4318 2/24/98 379 RTA00000349R.J.07.1 M00001529B:C04 2642
4319 1/28/98 122 RTAOOOOO 197AF.1.15.1 M00001517B:G08 4947
4320 3/24/98 199 RTA00000427F.f.24.1 M00004076D:B09 64572
4321 1/28/98 161 RTA00000183AF.e.23.2 M00001506D:A09 0
4322 1/28/98 17 RTA00000183 AR.e.14.2 M00001506B:D09 17437
4323 1/28/98 346 RTAOOOOO 197 AR.k.22.1 M00001505C:H01 1 1394
4324 1/28/98 125 RTA00000197AF.k.l5.1 M00001504D:D1 1 22750
4325 1/28/98 212 RTAOOOOO 197 AF.j.9.1 M00001494B:C01 13236
4326 1/28/98 314 RTA00000182AF.O.5.1 M00001493B:D09 5007
4327 1/28/98 386 RTAOOOOO 197AR.J.04.1 M00001492D:A1 1 17209
4327 1/28/98 259 RTA00000197AF.J.4.1 M00001492D:A1 1 17209
4328 1/28/98 259 RTAOOOOO 197AF.J .4.1 M00001492D:A1 1 17209
4328 1/28/98 386 RTAOOOOO 197 AR.j .04.1 M00001492D:A1 1 17209
4329 1/28/98 94 RTAOOOOO 195 AF.b.4.1 M00001490C:D07 0
4330 1/28/98 336 RTAOOOOO 186AFT.24.1 M00001629B:E06 0
4330 1/28/98 83 RTAOOOOO 186AFT.24.2 M00001629B:E06 0
4331 2/24/98 1037 RTA00000339F.1.12.1 M00001450A:G1 1 771 1
4332 1/28/98 432 RTA00000198AF.O.05.1 M00003750A:D01 26702
4332 1/28/98 49 RTA00000198R.O.05.1 M00003750A:D01 26702
4333 2/24/98 468 RTA00000423F.C.19.1 M00001680B:E10 40472
4334 2/24/98 1009 RTA00000399F.O.24.1 M00001607D:A1 1 2272
4335 1/28/98 281 RTAOOOOO 188AF.n.10.1 M00003802D:B1 1 10283
4336 1/28/98 157 RTAOOOOO 188 AF.n.01.1 M00003801A:B10 36412
4337 2/24/98 842 RTA00000401 F.n.23.1 M00003982A:B06 1552
4338 2/24/98 1216 RTA00000404F.e.07.1 M00001608A:D03 9034
4339 2/24/98 1045 RTA00000408F.J.05.2 M00001483C:G06 73878
4340 2/24/98 483 RTA00000406F.g.22.1 M00003881 D:C 12 38590
4341 1/28/98 310 RTA00000188AF.m.08.1 M00003798D:H08 22155
4342 1/28/98 1 18 RTAOOOOO 199F.b.24.2 M00003794A:B03 0
4343 1/28/98 218 RTA00000188AF.O.18.1 M0000381 1 D:A12 13678
4344 3/24/98 380 RTA00000427F.e.l3.1 M00003959D:A04 66080
4345 1/28/98 315 RTA00000199R.d.23.1 M00003815D:H09 37477
4346 1/28/98 140 RTAOOOOO 199F.a.2.1 M00003772A:D07 12674
4347 3/24/98 101 RTA00000523F.J.19.1 M00003966B:D02 65910
4348 1/28/98 278 RTA00000198AF-P- 16.1 M00003768A:E02 71877
4349 2/24/98 514 RTA00000404F.e. l 3.1 M00001608D:E09 12046
4350 1/28/98 508 RTA00000187AF.i.l4.2 M00001679B:H07 19406
4350 2/24/98 928 RTA00000340F.m.04.1 M00001679B:H07 19406
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
4351 1/28/98 317 RTA00000198AF.p.09.1 M00003761 D:E02 10473
4351 1 /28/98 186 RTAOOOOO 198R.p.09.1 M00003761 D:E02 10473
4352 1/28/98 317 RTAOOOOO 198 AF.p.09.1 M00003761 D:E02 10473
4352 1/28/98 186 RTAOOOOO 198R-P-09.1 M00003761 D:E02 10473
4353 3/24/98 66 RTA00000427F.b.l 5.1 M00003971 C:F09 66891
4354 1 /28/98 508 RTA00000187AF.U4.2 M00001679B:H07 19406
4354 2/24/98 928 RTA00000340F.m.04.1 M00001679B:H07 19406
4355 1 /28/98 144 RTAOOOOO 198 AF.o.18.1 M00003755A:A09 13018
4356 3/24/98 248 RTA00000527F.I.14.1 M00003983D:A09 14935
4357 1/28/98 347 RTA00000199F.b.03.2 M00003779B:E12 38340
4358 1 /28/98 272 RTAOOOOO 199F.g.08.2 M00003853D:G08 0
4359 1/28/98 263 RTAOOOOO] 90AF.n.6.1 M00003965A:B1 1 0
4360 2/24/98 1 183 RTA00000346F.J.21.1 M00003879D:A08 3095
4361 2/24/98 553 RTA00000408F.J.12.2 M00001485B:C03 18226
4362 3/24/98 181 RTA00000523F.b.06.1 M00003808A:F09 28736
4363 1 /28/98 246 RTAOOOOO 199AF.1.4.1 M0000391 1 D:B04 4410
4364 1 /28/98 51 RTAOOOOO 199R.k.07.1 M00003901 C:A03 12973
4365 1/28/98 62 RTAOOOOO 190AF.a.18.2 M00003900D:B 10 0
4366 1/28/98 1 17 RTAOOOOO 199AF.J.18.1 M00003889D:B09 5140
4367 1/28/98 255 RTAOOOOO 199 AF.j.17.1 M00003889A:D10 5121
4368 1/28/98 180 RTA00000199AF.J.12.1 M00003887A:A06 22461
4369 3/24/98 256 RTA00000523F.b.20.1 M00003809C:H07 66492
4370 2/24/98 603 RTA00000399F.O.19.1 M00001607A:F1 1 2594
4371 2/24/98 510 RTA00000131A.g.l6.2 M00001449A:F01 0
4372 1/28/98 49 RTA00000198R.O.05.1 M00003750A:D01 26702
4372 1/28/98 432 RTAOOOOO 198AF.O.05.1 M00003750A:D01 26702
4373 2/24/98 424 RTA00000138A.e.l3.1 M00001605A:E06 79608
4374 1/28/98 90 RTAOOOOO 199F.f.15.2 M00003845A:H12 8772
4375 1/28/98 244 RTAOOOOO 199F.f.12.2 M00003844C:A08 8131
4376 1/28/98 78 RTA00000199R.f.09.1 M00003842B:D09 22907
4376 1/28/98 406 RTAOOOOO 199FT.09.2 M00003842B:D09 22907
4377 1/28/98 406 RTAOOOOO 199F.f.09.2 M00003842B:D09 22907
4377 1/28/98 78 RTAOOOOO 199RT.09.1 M00003842B:D09 22907
4378 1/28/98 44 RTAOOOOO 199F .08.2 M00003841 D:E03 12445
4379 1/28/98 39 RTAOOOOO 189AR.b.19.1 M00003832B:E01 5294
4379 2/24/98 239 RTA00000346F.J.02.1 M00003832B:E01 5294
4380 1/28/98 39 RTAOOOOO 189AR.b.19.1 M00003832B:E01 5294
4380 2/24/98 239 RTA00000346F.J.02.1 M00003832B:E01 5294
4381 2/24/98 1 161 RTA00000346F.m.05.1 M00003983B:C08 5644
4382 2/24/98 887 RTA00000339F.p.06.1 M00001484A:A10 4880
4383 3/24/98 46 RTA00000523F.C.09.1 M00003813C:D08 47389
4384 2/24/98 1206 RTA00000418F.b.20.1 M00001484D:G05 73560
4385 1 /28/98 336 RTAOOOOO 186AF.f.24.1 M00001629B:E06 0
4385 1/28/98 83 RTAOOOOO 186AFT.24.2 M00001629B:E06 0
4386 1/28/98 1 1 1 RTAOOOOO 198 AF.o.12.1 M00003751 D:B02 22038
4387 3/24/98 365 RTA00000527F.U 6.1 M00003982B:B06 1015
4388 2/24/98 1 1 13 RTA00000418F.p.21.1 M00001677D:F03 78068
4389 3/24/98 281 RTA00000527F.k.20.1 M00003982B:H07 17148
4390 1/28/98 360 RTA00000198F.i.5.1 M00001638A:D10 39989
4391 1/28/98 55 RTAOOOOO 186AF.i.21.1 M00001636C:H09 6033
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4392 1/28/98 316 RTAOOOOO 198AF.h.24.1 M00001636C:C01 8390
4393 1/28/98 208 RTAOOOOO 198AF.h.22.1 M00001635C:A03 22366
4394 2/24/98 1031 RTA00000404F.g.08.1 M00001613D:H 10 38980
4395 3/24/98 382 RTA00000427F.a. l2.1 M00003982C:H 10 63377
4396 2/24/98 916 RTA00000418F.p.20.1 M00001677D:B07 78023
4397 1/28/98 91 RTAOOOOO 198 AF.j.19.1 M00001653C:F12 38914
4398 2/24/98 858 RTA00000341 F.e.20.1 M00003891 D:B 10 67422
4399 1/28/98 354 RTA00000198R.k.03.1 M00001655A:F06 22765
4399 1/28/98 158 RTA00000198AF.k.03.1 M00001655A:F06 22765
4400 3/24/98 219 RTA00000427F.f.l 7.1 M000041 15A:B12 63803
4401 3/24/98 153 RTA00000527F.1.13.1 M00003983C:F10 36904
4402 3/24/98 320 RTA00000427F.J.06.1 M00004102D:B05 63676
4403 2/24/98 762 RTA0000041 1 F.C.04.1 M00001677B:E06 76858
4404 2/24/98 957 RTA0000041 1 F.C.03.1 M00001677B:B06 79280
4405 3/24/98 479 RTA00000527F.1.23.1 M00003984A:B06 36018
4406 1/28/98 329 RTAOOOOO 186AF.b.9.1 M00001616C:F07 0
4407 2/24/98 1 1 15 RTA00000340F.i.08.1 M00001615B:F07 12005
4408 2/24/98 1022 RTA00000401 F.J.15.1 M00003901 A:C09 3061
4409 1/28/98 4 RTAOOOOO 198RT.04.1 M00001607D:F07 5023
4410 3/24/98 173 RTA00000426F.m. l 8.1 M00003986D:G07 62974
441 1 2/24/98 616 RTA00000423F.C.1 1.1 M00001677D:B02 0
4412 1/28/98 345 RTA00000187AF.h.21.1 M00001679A:F01 39171
4413 2/24/98 621 RTA00000408F.i.l 8.2 M00001482C:D02 74410
4414 1/28/98 344 RTA00000198AF.O.02.1 M00003748A:B07 68756
4415 2/24/98 257 RTA0000041 1 F.C.17.1 M00001678D:G03 77664
4416 2/24/98 944 RTA00000422F.L24.1 M00001610C:E06 391 18
4417 2/24/98 876 RTA00000423F.d.l6.1 M00001678D:C1 1 39173
4418 2/24/98 1 144 RTA00000345F.J.09.1 M00001451 B:F01 13
4419 1/28/98 242 RTAOOOOO 198 AF.m.17.1 M00001679D:F06 77992
4419 1/28/98 260 RTA00000198R.m. l 7.1 M00001679D:F06 77992
4420 1/28/98 260 RTAOOOOO 198R.m.17.1 M00001679D:F06 77992
4420 1/28/98 242 RTAOOOOO 198AF.ni.17.1 M00001679D:F06 77992
4421 1/28/98 242 RTAOOOOO 198AF.m.17.1 M00001679D:F06 77992
4421 1/28/98 260 RTAOOOOO 198R.m.17.1 M00001679D:F06 77992
4422 1/28/98 260 RTA00000198R.m. l 7. l M00001679D:F06 77992
4422 1/28/98 242 RTAOOOOO 198AF.m.17.1 M00001679D:F06 77992
4423 1/28/98 238 RTA0000O187AR. 12.1 M00001679D:F02 78415
4423 2/24/98 407 RTA00000340R.m.07.1 M00001679D:F02 78415
4424 1/28/98 276 RTA00000198AF.J.15.1 M00001653B:E09 4369
4425 1/28/98 65 RTAOOOOO 198 AF.m.16.1 M00001679D:D05 51
4426 1/28/98 257 RTAOOOOO 198AF.e.20.1 M00001604C:E09 9810
4427 2/24/98 820 RTA00000423F.d. l l . l M00001678C:C06 38950
4428 3/24/98 466 RTA00000427F.d.06.1 M00003980B:C06 33446
4429 2/24/98 455 RTA00000399F.d.23.1 M00001481 B:A07 3310
4430 2/24/98 851 RTA00000423F.d.07.1 M00001678B:B12 0
4431 1/28/98 142 RTAOOOOO 198AF. 19.1 M00001660B:C04 75879
4432 2/24/98 485 RTA00000419F.a.02.1 M00001678A:F05 77993
4433 3/24/98 224 RTA00000527F.k.09.1 M00003981C:F05 213
4434 2/24/98 1032 RTA00000423F.C.13.1 M00001678A:A1 1 39059
4435 1/28/98 354 RTAOOOOO 198R. 03.1 M00001655A.-F06 22765
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4435 1/28/98 158 RTAOOOOO 198 AF.k.03.1 M00001655A:F06 22765
4436 1/28/98 354 RTA00000198R. 03.1 M00001655A:F06 22765
4436 1 /28/98 158 RTA00000198AF.k.03.1 M00001655A:F06 22765
4437 1/28/98 158 RTA00000198AF.k.03.1 M00001655A:F06 22765
4437 1/28/98 354 RTA00000198R.k.03.1 M00001655A:F06 22765
4438 1/28/98 238 RTAOOOOO 187AR.L 12.1 M00001679D:F02 78415
4438 2/24/98 407 RTA00000340R.m.07.1 M00001679D:F02 78415
4439 1/28/98 669 RTA00000192AF.C.2.1 M00004121 B:G01 0
4440 3/24/98 394 RTA00000527F.g. l 4.1 M00003845D:B02 37532
4441 1/28/98 608 RTAOOOOO] 92AF.p.8.1 M00004212B:C07 2379
4441 2/24/98 653 RTA00000352R.m. l2.1 M00004212B:C07 2379
4442 1/28/98 608 RTA00000192AF.p.8.1 M00004212B:C07 2379
4442 2/24/98 653 RTA00000352R.m.l2.1 M00004212B:C07 2379
4443 1/28/98 730 RTAOOOOO 192 AF.o.1 1.1 M00004205D:F06 0
4444 2/24/98 1 157 RTA00000422F.m. l 8.1 M00001647B:E04 23829
4445 2/24/98 1 187 RTA00000120A.C.19.1 M00001464A:B03 81016
4446 2/24/98 913 RTA00000120A.C.20.1 M00001464A:B07 43235
4447 1/28/98 589 RTA00000192AF.1.1.1 M00004183C:D07 16392
4448 2/24/98 640 RTA00000405F.f.02.1 M00001669B.-G02 38665
4449 1/28/98 27 RTAOOOOO 192AF.i.12.1 M00004169C:C12 5319
4450 2/24/98 681 RTA00000120A.C.24.1 M00001464A:D03 34278
4451 2/24/98 265 RTA00000340F. 16.1 M00001647B:C09 13157
4452 1/28/98 70 RTAOOOOO 192 AF.e.3.1 M00004138B:H02 13272
4453 3/24/98 171 RTAO0O00523F.e.l 0.1 M00003829A:F03 62878
4454 2/24/98 1 134 RTA00000418F.m.02.1 M00001650A:A12 74550
4455 1/28/98 618 RTA00000192AF.a.l4.1 M000041 1 1D:A08 6874
4456 1/28/98 457 RTA00000191AR.1.7.2 M00004081 C:D12 14391
4457 2/24/98 596 RTA00000351 R.L03.1 M00003846B:D06 6874
4458 3/24/98 460 RTA00000523F.f. l 6.1 M00003840B:E07 26522
4459 3/24/98 400 RTA00000523F.f. l 7.1 M00003840B:E08 63984
4460 2/24/98 1 129 RTA00000401 F.m.07.1 M00003907D:F1 1 2893
4461 2/24/98 132 RTA00000418F.m.05.1 M00001650B:C 10 73600
4462 1/28/98 482 RTA00000187AF.J.7.1 M00001679C:F01 78091
4463 2/24/98 1 107 RTA00000419F.1.22.1 M00003903D:C06 78444
4464 2/24/98 609 RTA00000404F.O.10.2 M00001651 B:B12 16785
4465 1/28/98 376 RTA00000177AF.m.l 8.3 M00001355B:G1 1 0
4465 1/28/98 375 RTA00000177AF.m.l 8.1 M00001355B:G 1 1 0
4466 2/24/98 186 RTA00000132A.k.6.1 M00001464A:E07 81284
4467 1/28/98 18 RTA00000196AF.C.17.1 M00001352C:F06 39602
4468 3/24/98 282 RTA00000427F.h.22.1 M00004108C:E01 64547
4469 2/24/98 859 RTA00000419F.m.22.1 M00003914A:G09 75600
4470 3/24/98 33 RTA00000524F.b.21.1 M00005216C:B09 0
4471 3/24/98 170 RTA00000523F.d. l2.1 M00003822B:D08 64888
4472 3/24/98 1 17 RTA00000523F.d.l 8.1 M00003822B:G01 64072
4473 2/24/98 739 RTA00000423F.h.20.1 M00003914A:G06 38639
4474 2/24/98 527 RTA00000419F.m.21 .1 M00003914A:E04 77947
4475 2/24/98 237 RTAOOOOO 1 19AJ.22. I M00001460A:F07 80336
4476 2/24/98 349 RTA00000404F.m.l 0.2 M00001641 D:E02 779
4477 2/24/98 462 RTAOOOOO 1 19A.J.23.1 M00001460A:G07 79835
4478 2/24/98 1263 RTA00000341 F. 22.1 M0000391 1 A:F10 7825
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4479 3/24/98 47 RTA00000523F.e.l8.1 M00003829D:A11 62898
4480 1/28/98 152 RTA00000196AF.C.20.1 M00001352C:H02 8934
4481 3/24/98 13 RTA00000528F.m.l6.1 M00003845D:C03 4468
4482 1/28/98 14 RTAOOOOO 196R.C.11.2 M00001352A:E12 13658
4483 2/24/98 641 RTA00000410F.J.20.1 M00001642D:G10 73601
4484 1/28/98 141 RTAOOOOO 196AF.C.6.1 M00001350A:D06 23148
4485 1/28/98 25 RTA00000196AF.C.1.1 M00001349C:C05 8171
4486 2/24/98 436 RTAOOOOO 119A.m.15.1 M00001461A:E05 80989
4487 1/28/98 9 RTAOOOOO 177 AF.g.22.1 M00001347C:G08 7031
4488 2/24/98 162 RTA00000406F.I.08.1 M00003908D:D12 39016
4489 2/24/98 1056 RTA00000419F.rn.18.] M00003908C:G09 76014
4490 1/28/98 73 RTAOOOOO 177 AF.e.21.3 M00001344A:H07 4306
4491 3/24/98 326 RTA00000527F.e.09.1 M00003826B:E11 37521
4492 2/24/98 900 RTA00000419F.m.l3.1 M00003908A:F12 79052
4493 2/24/98 441 RTA00000404F.m.20.2 M00001647A:H08 39144
4494 2/24/98 1217 RTA00000410F.J.17.1 M00001642D:F02 72912
4495 3/24/98 309 RTA00000523F.J.10.1 M00003860B:G09 63384
4496 2/24/98 385 RTA00000418F.m.l4.1 M00001651B:E06 75711
4497 2/24/98 1121 RTA00000120A.m.10.3 M00001467A:B03 81376
4498 1/28/98 617 RTAOOOOO 179AF.d.13.3 M00001394A:F01 6583
4499 2/24/98 1242 RTA00000405F.d.l0.1 M00001661C:F11 39000
4500 3/24/98 19 RTA00000527F.J.02.2 M00003856A:B07 4896
4501 2/24/98 645 RTA00000422F.p.l2.2 M00001661C:F10 9840
4502 3/24/98 142 RTA00000523F.i.l8.1 M00003856B:C04 64463
4503 2/24/98 376 RTA00000400F.L22.1 M00001656A:B07 2512
4504 1/28/98 532 RTA00000177AF.O.4.1 M00001358C:C06 0
4505 2/24/98 1128 RTA00000423F.a.02.3 M00001656B:A08 39210
4506 2/24/98 1143 RTA00000423F.a.03.1 M00001656B:D05 26796
4507 2/24/98 408 RTA00000405F.d.l4.1 M00001662A:C12 35209
4508 3/24/98 360 RTA00000523F.J.03.1 M00003860A:A08 64535
4509 1/28/98 409 RTAOOOOO 180AF.d.1.3 M00001418D:B06 8526
4510 2/24/98 784 RTA00000418F.O.14.1 M00001661B:B05 33524
4511 3/24/98 120 RTA00000426F.h.09.1 M00003905B:G03 78797
4512 1/28/98 706 RTA00000177AF.i.6.4 M00001350A:B08 0
4513 3/24/98 4 RTA00000426F.h.ll.l M00003905B:H05 75479
4514 2/24/98 697 RTA00000412F.d.l4.1 M00003905D:C08 76757
4515 2/24/98 908 RTA00000423F.g.03.1 M00003905C:G11 38007
4516 3/24/98 342 RTA00000427F.e.l2.1 M00003959C:G06 62813
4517 2/24/98 97 RTA00000403F.e.01.1 M00001473A:C11 38965
4518 2/24/98 555 RTA00000133A.d.22.1 M00001469A:G11 11797
4519 2/24/98 454 RTA00000418F.n.19.1 M00001659C:F02 28761
4520 2/24/98 562 RTA00000401F.J.17.1 M00003901B:C05 5483
4521 2/24/98 1215 RTA00000422F.O.08.2 M00001659D:D03 26832
4522 2/24/98 635 RTA00000418F.O.17.1 M00001661B:F03 79069
4523 3/24/98 190 RTA00000523F.li.12.1 M00003851C:D07 65745
4524 1/28/98 267 RTAOOOOO 186 AF.g.11.2 M00001630B:HO9 5214
4525 2/24/98 238 RTA00000340F.J.12.1 M00001624A:B06 3277
4526 2/24/98 331 RTA00000404F.O.18.2 M00001651C:C05 39110
4527 1/28/98 626 RTAOOOOO 185 AR.d.11.1 M00001579D:C03 6539
4527 1/28/98 131 RTA00000185AF.d.ll.2 M00001579D:C03 6539
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4528 1/28/98 626 RTAOOOOO 185 AR.d.1 1.1 M00001579D:C03 6539
4528 1/28/98 131 RTAOOOOO 185 AF.d.1 1.2 M00001579D:C03 6539
4529 1/28/98 147 RTAOOOOO 185 AF.c.24.2 M00001578B:E04 23001
4530 2/24/98 164 RTA00000345F. 06.1 M00001475A:A12 0
4531 2/24/98 61 1 RTA00000404F.p.02.2 M00001652D:A06 39097
4532 2/24/98 274 RTA00000405F.e.08.1 M00001663C:F10 37916
4533 2/24/98 755 RTA00000423F.d.l 7.1 M00001663A:C1 1 20630
4534 2/24/98 126 RTA00000422F.J.20.1 M00001653A.-G07 22388
4535 3/24/98 195 RTA00000523F .08.1 M00003855A:C12 65099
4536 3/24/98 83 RTA00000527F.i.05.2 M00003851C:B06 37481
4537 1/28/98 375 RTAOOOOO 177AF.ni.18.1 M00001355B:G1 1 0
4537 1/28/98 376 RTAOOOOO 177AF.m.18.3 M00001355B:G1 1 0
4538 2/24/98 763 RTAOOOOO 135 A.m.18.1 M00001545A:C03 19255
4539 2/24/98 362 RTA00000418F.m.16.1 M00001653B:E06 74986
4540 2/24/98 287 RTA00000410F.n.09.1 M00001662C:A04 1 1736
4541 3/24/98 416 RTA00000527F.i.l2.2 M00003852B:D1 1 0
4542 2/24/98 662 RTA00000339F.O.07.1 M00001473D:G01 2566
4543 2/24/98 949 RTA00000340R.J.07.1 M00001654C:D05 38954
4544 3/24/98 146 RTA00000527F.U 7.2 M00003853B:C08 37539
4545 2/24/98 939 RTA00000405F.a.03.1 M00001654C:E04 39065
4546 3/24/98 42 RTA00000527F.U9.2 M00003853C:C06 38089
4547 3/24/98 381 RTA00000426F.f.l 8.1 M00003854C:C02 63271
4548 2/24/98 656 RTA00000403F.e.08.1 M00001473D:B1 1 19126
4549 3/24/98 37 RTA00000426FT.20.1 M00003854C:F01 65134
4550 2/24/98 733 RTA00000405F.d. l 8.1 M00001662C:B02 10494
4551 1/28/98 334 RTAOOOOO 181 AR.b.21.3 M00001444C:D05 3266
4551 1/28/98 321 RTAOOOOO 181 AR.b.21.1 M00001444C:D05 3266
4552 3/24/98 198 RTA00000523F.O.05.1 M00005175B:H04 0
4553 3/24/98 302 RTA00000427F.p.04.2 M00005100B:H07 0
4554 3/24/98 203 RTA00000427F.p. l 0.2 M00005102C:F09 0
4555 1/28/98 331 RTA00000197AR.C.20.1 M00001449D:A06 16282
4556 3/24/98 6 RTA00000523F.1.10.1 M00005134B:E01 0
4557 1/28/98 174 RTA00000181 AF.e.22.3 M00001448D:F09 3442
4558 3/24/98 79 RTA00000523F.1.15.1 M00005134C:E1 1 0
4559 3/24/98 386 RTA00000523F.1.16.1 M00005134C:G04 0
4560 3/24/98 76 RTA00000523F.1.18.1 M00005134D:A06 0
4561 3/24/98 192 RTA00000523F.m.02.1 M00005134D:H03 0
4562 3/24/98 290 RTA00000427F.1.03.1 M00005136D:B07 0
4563 3/24/98 269 RTA00000427F.p.02.2 M00005100B:D02 0
4564 1/28/98 321 RTAOOOOO 181 AR.b.21.1 M00001444C:D05 3266
4564 1/28/98 334 RTAOOOOO 181 AR.b.21.3 M00001444C:D05 3266
4565 3/24/98 334 RTA00000427F.ii.1 1.1 M00004960B:A09 0
4566 1/28/98 334 RTA00000181 AR.b.21.3 M00001444C:D05 3266
4566 1/28/98 321 RTAOOOOO 181 AR.b.21.1 M00001444C:D05 3266
4567 1/28/98 334 RTAOOOOO 1 81 AR.b.21.3 M00001444C:D05 3266
4567 1/28/98 321 RTAOOOOO 181 AR.b.21.1 M00001444C:D05 3266
4568 3/24/98 328 RTA00000523F.n.01.1 M00005137A:E01 0
4569 1/28/98 356 RTA00000180AF.1.12.2 M00001433B:H1 1 0
4570 3/24/98 68 RTA00000523F.n.04.1 M00005138B:D12 0
4571 3/24/98 127 RTA00000523F.n. l 0.1 M00005140D:G09 0
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4572 1/28/98 187 RTAOOOOO 180AR.J.04.4 M00001429C:G12 22300
4573 3/24/98 1 12 RTA00000523F.n.l2.1 M00005173C:A02 0
4574 3/24/98 305 RTA00000523F.H.16.1 M00005173D:H02 0
4575 3/24/98 164 RTA00000523F.n. l 7.1 M00005174D:B02 0
4576 3/24/98 107 RTA00000523F.n.20.1 M00005174D:H02 0
4577 2/24/98 898 RTA00000418F.1.03.1 M00001641C:C06 79058
4578 3/24/98 288 RTA00000427F.1.04.1 M00005136D:C01 0
4579 3/24/98 462 RTA00000427F.p.l3.2 M00004695B:E04 0
4580 1/28/98 137 RTA00000181 AF.m.4.3 M00001455A:E09 13238
4581 1/28/98 20 RTA00000181AF.1.14.2 M00001454D:D06 2364
4582 3/24/98 105 RTA00000526F.d.01.1 M00004104B:A02 4468
4583 3/24/98 261 RTA00000427F.L22.1 M00004104D:B05 63199
4584 3/24/98 81 RTA00000427F.J.07.1 M00004105A:B10 64819
4585 3/24/98 287 RTA00000525F.d. l9.1 M000041 14B:D09 36860
4586 1/28/98 31 1 RTAOOOOO 191 AR.j.4.2 M00004071 D:A10 5198
4587 3/24/98 337 RTA00O00525F.e.08.1 M000041 15C:H04 24193
4588 3/24/98 206 RTA00000525FT.07.1 M000041 19A:A06 37500
4589 3/24/98 461 RTA00000427F.f. l 5.1 M000041 19D:A07 66734
4590 3/24/98 410 RTA00000427F.f.l 6.1 M000041 19D:H06 64122
4591 3/24/98 307 RTA00000427F.p.03.2 M00005100B:G1 1 0
4592 3/24/98 180 RTA00000523F.k.02.1 M00004687A:C03 0
4593 1/28/98 1 15 RTAOOOOO 179 AR.o.20.3 M00001409D:F1 1 2409
4594 3/24/98 315 RTA00000427F.n. l9.1 M00004891 D:E07 0
4595 3/24/98 375 RTA00000427F.p. l9.2 M00004895C:G05 0
4596 3/24/98 470 RTA00000427F.p.24.2 M00004897D:F03 0
4597 1/28/98 155 RTA00000197F.e.8.1 M00001454A:C1 1 3135
4598 1/28/98 286 RTA00000181AR. 2.3 M00001453C:A1 1 0
4598 1/28/98 389 RTA00000181 AR. 2.2 M00001453C:A1 1 0
4599 1/28/98 286 RTA00000181AR.k.2.3 M00001453C:A1 1 0
4599 1/28/98 389 RTA00000181AR.k.2.2 M00001453C:A 1 1 0
4600 1/28/98 285 RTA00000181 AR.J.14.3 M00001453B:E10 5399
4601 3/24/98 317 RTA00000428F.a.01.1 M00004897D:G05 0
4602 3/24/98 85 RTA00000427F.m.21 .1 M00004900C:E1 1 0
4603 3/24/98 121 RTA00000427F.n.02.1 M00004900D:B10 0
4604 3/24/98 78 RTA00000427F.O.05.1 M00004958B:D01 0
4605 3/24/98 437 RTA00000427F.n. l0.1 M00004960B:A08 0
4606 3/24/98 388 RTA00000526F.d.l 7.1 M00004235A:A12 2757
4607 1 /28/98 299 RTA00000196AF.f.5.1 M00001366D:G02 1 1937
4608 1/28/98 369 RTA00000196F.m.3.1 M00001413A:F02 10453
4609 3/24/98 319 RTA00000523F.p.l5.1 M00005178B:H01 0
4610 1/28/98 374 RTAOOOOO 178AF.1.1 1.1 M00001383A:G04 23286
461 1 2/24/98 1090 RTA00000405F.g.22.1 M00001673C:A02 527
4612 1/28/98 127 RTA00000178AF.k. l 8.1 M00001382A:F04 9755
4613 1/28/98 104 RTA00000196R.h.03.1 M00001381 A:D02 6636
4614 2/24/98 642 RTA00000341 F.li.19.1 M00003916C:C05 0
4615 2/24/98 655 RTA00000351 R.p. l4.1 M00003915C:H04 13166
4616 1/28/98 145 RTA00000178AF.h.24.1 M00001376B:C06 6745
4617 2/24/98 224 RTA00000341 F.g.21.1 M00003914C:F09 8823
4618 2/24/98 301 RTA00000401 F.m.23.1 M00003914C:C02 2801
4619 2/24/98 133 RTA00000404F.1.20.1 M00001639B:H05 38638
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4619 2/24/98 63 RTA00000404F.1.20.2 M00001639B:H05 38638
4620 2/24/98 542 RTA00000410F.U 9.1 M00001641 B:C 10 78988
4621 2/24/98 63 RTA00000404F.1.20.2 M00001639B:H05 38638
4621 2/24/98 133 RTA00000404F.1.20.1 M00001639B:H05 38638
4622 2/24/98 600 RTA00000406F.m.04.1 M00003914B:A1 1 14959
4623 1/28/98 33 RTA00000178AR.a.20.1 M00001362C:H1 1 945
4623 2/24/98 979 RTA00000345F.b. l 7.1 M00001362C:H1 1 945
4624 1/28/98 33 RTAOOOOO 178 AR.a.20.1 M00001362C:H 1 1 945
4624 2/24/98 979 RTA00000345F.b. l 7.1 M00001362C:H1 1 945
4625 3/24/98 73 RTA00000524F.b. l2.1 M00005213C:G01 0
4626 1/28/98 J /j RTA00000196F.e.l 2.1 M00001361 C:H1 1 10147
4627 2/24/98 1233 RTA00000418F.1.02.1 M00001641 C:C05 39316
4628 3/24/98 184 RTA00000524F.b. l 8.1 M00005214B:D1 1 0
4629 3/24/98 353 RTA00000428F.a.l 8.1 M00005214C:A09 0
4630 1/28/98 89 RTA00000177AF.n.8.3 M00001356D:F06 4188
4630 1/28/98 15 RTA00000177AR.n.8.1 M00001356D:F06 4188
4631 1/28/98 89 RTAOOOOO 177AF.n.8.3 M00001356D:F06 4188
4631 1/28/98 15 RTAOOOOO 177AR.n.8.1 M00001356D:F06 4188
4632 1/28/98 375 RTA00000177AF.m. l 8.1 M00001355B:G1 1 0
4632 1/28/98 376 RTAOOOOO 177 AF.m.18.3 M00001355B:G1 1 0
4633 1/28/98 375 RTAOOOOO 177AF.m.18.1 M00001355B:G1 1 0
4633 1/28/98 376 RTAOOOOO 177AF.ni.18.3 M00001355B:G1 1 0
4634 2/24/98 682 RTA00000410F.i.l 7.1 M00001641 B:B01 78147
4635 1/28/98 367 RTA00000196F.i.24.1 M00001392C:D10 4233
4636 1/28/98 264 RTA00000179AF.k.3.3 M00001401A:H07 0
4637 1/28/98 333 RTA00000196F.k. l 5.1 M00001400A:F06 8320
4638 1/28/98 38 RTAOOOOO 196R. 07.1 M00001399C:D09 22443
4638 1/28/98 289 RTA00000196F. 07.1 M00001399C:D09 22443
4639 1/28/98 38 RTAOOOOO 196R. 07.1 M00001399C:D09 22443
4639 1/28/98 289 RTA00000196F.k.07.1 M00001399C:D09 22443
4640 1/28/98 289 RTA00000196F. 07.1 M00001399C:D09 22443
4640 1/28/98 38 RTA00000196R.k.07.1 M00001399C:D09 22443
4641 1/28/98 38 RTA00000196R.k.07.1 M00001399C:D09 22443
4641 1/28/98 289 RTAOOOOO 196F. 07.1 M00001399C:D09 22443
4642 3/24/98 324 RTA00000523F.O.09.1 M00005176A:C12 0
4643 3/24/98 122 RTA00000523F.O.12.1 M00005177A:B06 0
4644 1/28/98 167 RTAOOOOO 179AF.d.22.3 M00001394C:C1 1 7955
4645 1/28/98 351 RTA00000179AF.C.22.1 M00001393B:B09 22515
4645 1/28/98 459 RTA00000179AF.C.22.3 M00001393B:B09 22515
4646 1/28/98 351 RTAOOOOO 179AF.C.22.1 M00001393B:B09 22515
4646 1/28/98 459 RTA00000179AF.C.22.3 M00001393B:B09 22515
4647 3/24/98 361 RTA00000523F.p.08.1 M00005178A:A07 0
4648 1/28/98 43 RTA00000179AF.C.14.3 M00001392D:H04 0
4649 3/24/98 268 RTA00000427F. 19.1 M00004103B:B07 62851
4650 3/24/98 473 RTA00000523F.O.21.1 M00005177C:A01 0
4651 1/28/98 60 RTA00000196AR.i.l2.3 M00001389D:G1 1 38800
4651 1/28/98 128 RTAOOOOO 196F.i.12.1 M00001389D:G1 1 38800
4652 1/28/98 128 RTA00000196F 12.1 M00001389D:G1 1 38800
4652 1/28/98 60 RTA00000196AR.U2.3 M00001389D:G1 1 38800
4653 1/28/98 60 RTA00000196AR.i.l2.3 M00001389D:G 1 1 38800
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID
Priority Priority
Appln Appln
4653 1/28/98 128 RTAOOOOO 196F.i.12.1 M00001389D:G 1 1 38800
4654 1/28/98 60 RTAOOOOO 196AR.i.12.3 M00001389D:G 1 1 38800
4654 1/28/98 128 RTAOOOOO 196F.L 12.1 M00001389D:G 1 1 38800
4655 1/28/98 28 RTAOOOOO 178AR.O.01.5 M00001387B:H07 0
4656 1/28/98 279 RTAOOOOO 196 AF.h.24.1 M00001386A:D1 1 7308
4657 1/28/98 130 RTA00000196AF.h.23.1 M00001386A:C02 13357
4658 1/28/98 254 RTA00000178AF.n.2.1 M00001385C:H1 1 17083
4659 1/28/98 74 RTAOOOOO 196AF.h.20.1 M00001385B:F10 0
4660 1/28/98 377 RTA00000178AF.m. l 9.1 M00001384D:H07 0
4660 1/28/98 120 RTA00000178AR.m.l9.5 M00001384D:H07 0
4661 1/28/98 377 RTA00000178AF.m. l 9.1 M00001384D:H07 0
4661 1 /28/98 120 RTA00000178AR.m.19.5 M00001384D:H07 0
4662 3/24/98 228 RTA00000523F.O.14.1 M00005177A:H09 0
4663 1/28/98 567 RTA00000177AR.m. l3.1 M00001355A:C12 4175
4663 1/28/98 538 RTA00000177AR.m. l 3.3 M00001355A:C12 4175
4663 1/28/98 533 RTA00000177AR.rn.13-4 M00001355A:C12 4175
4664 1/28/98 51 1 RTAOOOOO 196AF.g.10.1 M00001376B:A02 12498
4665 1/28/98 620 RTA00000201 R.g.08.1 M00004692A:E07 0
4665 1/28/98 619 RTA00000201 F.g.08.1 M00004692A:E07 0
4665 1/28/98 621 RTA00000201 R.g.08.2 M00004692A:E07 0
4666 3/24/98 194 RTA00000522F.J.12.2 M00001651C:A04 74341
4667 2/24/98 79 RTA00000419F.g.08.1 M00003842C:D1 1 66700
4668 1/28/98 619 RTA00000201 F.g.08.1 M00004692A:E07 0
4668 1/28/98 620 RTA00000201 R.g.08.1 M00004692A:E07 0
4668 1/28/98 621 RTA00000201 R.g.08.2 M00004692A:E07 0
4669 1/28/98 529 RTAOOOOO 178AF.b.13.1 M00001364A:E1 1 31 14
4670 2/24/98 1 1 1 RTAOOOOO 128A.J.20.1 M00001560A:F03 9900
4671 3/24/98 379 RTA00000522F. 02.2 M00001652C:B09 77622
4672 3/24/98 135 RTA00000522F. 10.2 M00001652D:B09 77619
4673 2/24/98 1 197 RTA00000128A.J.10.1 M00001560A:H06 80085
4674 2/24/98 140 RTA00000128A.J.6.2 M00001560A:H10 5316
4675 3/24/98 247 RTA00000425F.J.21.1 M00001633B:B1 1 77373
4676 1/28/98 538 RTAOOOOO 177AR.m.13.3 M00001355A:C12 4175
4676 1/28/98 567 RTAOOOOO 177 AR.m.13.1 M00001355A:C12 4175
4676 1/28/98 533 RTA00000177AR.m.l3.4 M00001355A:C12 4175
4677 2/24/98 729 RTA00000403F.m.20.1 M00001576A:F1 1 707
4677 2/24/98 437 RTA00000403F.m.20.2 M00001576A:F1 1 707
4678 1/28/98 533 RTAOOOOO 177AR.m.13.4 M00001355A:C12 4175
4678 1/28/98 538 RTAOOOOO 177AR.ni.13.3 M00001355A:C12 4175
4678 1/28/98 567 RTA00000177AR.m.13.1 M00001355A:C12 4175
4679 1/28/98 533 RTA00000177AR.m. l 3.4 M00001355A:C12 4175
4679 1/28/98 538 RTAOOOOO 177 AR.m.13.3 M00001355A:C 12 4175
4679 1/28/98 567 RTAOOOOO 177AR.m.13.1 M00001355A:C12 4175
4680 1/28/98 538 RTAOOOOO 177AR.m.13.3 M00001355A:C12 4175
4680 1/28/98 567 RTA00000177AR.rn.13- l M00001355A:C12 41 75
4680 1 /28/98 533 RTAOOOOO 177AR.ni.13.4 M00001355A:C12 4175
4681 1/28/98 533 RTA00000177AR.m.13.4 M00001355A:C12 4175
4681 1/28/98 538 RTA00000177AR.m. l3.3 M00001355A:C12 4175
4681 1/28/98 567 RTAOOOOO 177AR.ni.13.1 M00001355A:C12 4175
4682 1/28/98 620 RTA00000201 R.g.08.1 M00004692A:E07 0
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4682 1/28/98 621 RTA00000201 R.g.08.2 M00004692A:E07 0
4682 1/28/98 619 RTA00000201 F.g.08.1 M00004692A:E07 0
4683 2/24/98 845 RTA00000348R.b.04.1 M00001342B:E01 1890
4684 2/24/98 1088 RTA00000339R.b.02.1 M00001344B:F12 0
4684 2/24/98 1 149 RTA00000339F.b.02.1 M00001344B:F12 0
4685 2/24/98 618 RTA00000423F.1.04.1 M00004039B:G08 14320
4686 2/24/98 1235 RTA0000041 1 F.J.04.1 M00003841C:F03 66219
4687 2/24/98 415 RTA00000340R.f.05.1 M00001569B:G1 1 3202
4688 2/24/98 1088 RTA00000339R.b.02.1 M00001344B:F12 0
4688 2/24/98 1 149 RTA00000339F.b.02.1 M00001344B:F12 0
4689 2/24/98 1067 RTA0000041 1 F.J.1 1.1 M00003841 D:F06 66154
4690 1/28/98 429 RTA00000196F.i. l 9.1 M00001390C:C1 1 39498
4690 2/24/98 925 RTA00000353R.h.l0.1 M00001390C:C1 1 39498
4691 1/28/98 508 RTA00000187AF.i.l4.2 M00001679B:H07 19406
4691 2/24/98 928 RTA00000340F.m.04.1 M00001679B:H07 19406
4692 2/24/98 10 RTA00000350R.C.12.1 M00001550D:A04 9728
4693 1/28/98 553 RTA00000201 F.b.22.1 M00004344B:H04 35728
4694 1/28/98 459 RTA00000179AF.C.22.3 M00001393B:B09 22515
4694 1/28/98 351 RTAOOOOO 179AF.C.22.1 M00001393B:B09 22515
4695 1/28/98 351 RTAOOOOO 179AF.C.22.1 M00001393B:B09 22515
4695 1/28/98 459 RTAOOOOO 179AF.C.22.3 M00001393B:B09 22515
4696 2/24/98 235 RTA00000126A.O.23.1 M00001551A:B10 6268
4697 2/24/98 942 RTAOOOOO 126A.n.6.2 M00001551A:D04 79917
4698 2/24/98 228 RTA0000041 1 F.k. l9.1 M00003852D:E08 64200
4699 1/28/98 638 RTA00000193AF.1.05.2 M00004348A:A02 2815
4700 3/24/98 431 RTA00000425F.1.09.1 M00001638A:B04 75251
4701 1/28/98 540 RTAOOOOO 179AF.b.10.3 M00001391 D:D10 0
4702 2/24/98 390 RTA00000355R.a. l4.1 M00004187D:G09 10207
4703 1/28/98 429 RTAOOOOO 196F.i.19.1 M00001390C:C1 1 39498
4703 2/24/98 925 RTA00000353R.h. l 0.1 M00001390C:C1 1 39498
4704 2/24/98 930 RTAOOOOO 127A.h.22.2 M00001554A:E04 13155
4705 2/24/98 1 193 RTA0000041 1 F.k. l 4.1 M00003851 A:C10 63987
4706 1/28/98 694 RTA00000201 R.C.19.1 M00004370A:G05 22357
4707 3/24/98 80 RTA00000425F.p.l2.1 M00001638C:G01 73219
4708 3/24/98 344 RTA00000425F.p. l5.1 M00001638C:H07 31680
4709 1/28/98 743 RTA00000178AF.k.9.1 M00001381 B:F06 16342
4710 2/24/98 202 RTA00000419F.g.22.1 M00003845D:A09 64515
471 1 1/28/98 749 RTA00000178AR.U3.4 M00001377B:H01 0
4712 3/24/98 217 RTA00000425F.J.16.1 M00001639D:F02 75631
4713 3/24/98 448 RTA00000425F.J.18.1 M00001639D:G 12 75561
4714 1/28/98 385 RTA00000201 F.C.24.1 M00004374D:E10 35731
4715 2/24/98 904 RTA00000127A.e.6.1 M00001553A:E07 5885
4716 2/24/98 620 RTA00000420F.a.07.1 M00004072C:F08 63405
4717 1/28/98 396 RTAOOOOO 179AR.b.02.3 M00001391 B:G12 0
4718 2/24/98 463 RTA00000403F.O.22.1 M00001583A:D01 25076
4718 2/24/98 1084 RTA00000403F.O.22.2 M00001583A:D01 25076
4719 2/24/98 1225 RTA00000346F.J.13.1 M00003841 C:E04 5337
4720 2/24/98 1221 RTA00000403F.O.17.1 M00001582D:A02 23085
4721 2/24/98 878 RTA00000413F.C.12.1 M00004083B:G03 65334
4722 2/24/98 764 RTA00000413F.C.17.1 M00004085B:B05 36831
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4723 2/24/98 398 RTA00000407F.b.04.1 M00004086D:B09 63221
4724 2/24/98 1 179 RTA00000341 F.O.12.1 M00004144A:F04 2883
4725 2/24/98 7 RTA00000413F.d. l2.1 M00004088C:A 12 66467
4726 2/24/98 881 RTA00000413F.d. l 5.1 M00004088C:E04 64943
4727 2/24/98 463 RTA00000403F.O.22.1 M00001583A:D01 25076
4727 2/24/98 1084 RTA00000403F.O.22.2 M00001583A:D01 25076
4728 2/24/98 1084 RTA00000403F.O.22.2 M00001583A:D01 25076
4728 2/24/98 463 RTA00000403F.O.22.1 M00001583A:D01 25076
4729 1/28/98 506 RTAOOOOO 198R.O.09.1 M00003751 B:A05 4310
4729 1/28/98 497 RTAOOOOO 198AF.O.09.1 M00003751 B:A05 4310
4730 2/24/98 1015 RTA00000129A.b.6.2 M00001582A:H01 391 1 1
4731 2/24/98 866 RTA00000407F.b.08.1 M00004088D:B03 37513
4732 2/24/98 943 RTA00000413F.C.03.1 M00004081 D:H09 64527
4733 2/24/98 463 RTA00000403F.O.22.1 M00001583A:D01 25076
4733 2/24/98 1084 RTA00000403F.O.22.2 M00001583A:D01 25076
4734 1 /28/98 490 RTAOOOOO 198AF.11.05.1 M00001687A:G01 24157
4735 2/24/98 798 RTA00000420F.C.04.1 M00004089A:B08 65007
4736 2/24/98 850 RTA00000420F.C.07.1 M00004089A:E02 65555
4737 2/24/98 199 RTA00000403F.m.l3.2 M00001575D:A10 39077
4738 1/28/98 424 RTAOOOOO 187 AR.j .24.1 M00001679D:B05 78356
4738 1/28/98 418 RTAOOOOO 187 AR.k.01.1 M00001679D:B05 78356
4739 1/28/98 424 RTAOOOOO 187 AR.j .24.1 M00001679D:B05 78356
4739 1/28/98 418 RTAOOOOO 187 AR.k.01.1 M00001679D:B05 78356
4740 1/28/98 418 RTAOOOOO 187 AR.k.01.1 M00001679D:B05 78356
4740 1/28/98 424 RTAOOOOO 187 AR.j .24.1 M00001679D:B05 78356
4741 1/28/98 424 RTAOOOOO 187 AR.j .24.1 M00001679D:B05 78356
4741 1/28/98 418 RTAOOOOO 187 AR.k.01.1 M00001679D:B05 78356
4742 1/28/98 482 RTA00000187AF.J.7.1 M00001679C:F01 78091
4743 1/28/98 693 RTAOOOOO 198F.m.12.1 M00001679C:D05 4
4744 3/24/98 23 RTA00000522F.p.07.1 M00001670A:C1 1 76888
4745 1/28/98 497 RTAOOOOO 198 AF.o.09.1 M00003751 B:A05 4310
4745 1/28/98 506 RTAOOOOO 198R.O.09.1 M00003751 B:A05 4310
4746 1/28/98 642 RTAOOOOO 189AF.i.14.1 M00003868B:G 1 1 0
4747 2/24/98 1 1 19 RTAOOOOO 126A.k.24.1 M00001550A:F07 39428
4748 2/24/98 654 RTA00000421 F.a.05.1 M00001570C:G06 5278
4749 2/24/98 1 146 RTA00000347F.h.02.1 M00004072D:H 12 562
4750 2/24/98 137 RTA00000339R.a.06.1 M00001346A:E04 58694
4751 2/24/98 729 RTA00000403F.m.20.1 M00001576A:F1 1 707
4751 2/24/98 437 RTA00000403F.m.20.2 M00001576A:F1 1 707
4752 2/24/98 627 RTA00000408F.p.21.1 M00001579A:C03 77930
4753 2/24/98 735 RTA00000420F.3.1 1.1 M00004073C:D04 66460
4754 2/24/98 525 RTA00000348R.d.24.1 M00001349B:G05 5774
4755 2/24/98 624 RTA00000420F.a. l 6.1 M00004075D:C10 63345
4756 2/24/98 437 RTA00000403F.m.20.2 M00001576A:F1 1 707
4756 2/24/98 729 RTA00000403F.m.20.1 M00001576A:F1 1 707
4757 2/24/98 437 RTA00000403F.m.20.2 M00001576A:F1 1 707
4757 2/24/98 729 RTA00000403F.m.20.1 M00001576A:F1 1 707
4758 1/28/98 499 RTAOOOOO 199F.b.22.2 M00003791C:E09 17018
4759 2/24/98 843 RTA00000418F.g.03.1 M00001579C:E06 78737
4760 2/24/98 956 RTA00000423F.1.06.1 M00004062A:H06 38136
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: D3te of NO: in ID Priority Priority Appln Appln
4761 2/24/98 826 RTA00000422F.e.07.1 M00001579C:G05 38964
4761 2/24/98 832 RTA00000403F.O.10.2 M00001579C:G05 38964
4762 2/24/98 826 RTA00000422F.e.07.1 M00001579C:G05 38964
4762 2/24/98 832 RTA00000403F.O.10.2 M00001579C:G05 38964
4763 2/24/98 826 RTA00000422F.e.07.1 M00001579C:G05 38964
4763 2/24/98 832 RTA00000403F.O.10.2 M00001579C:G05 38964
4764 2/24/98 826 RTA00000422F.e.07.1 M00001579C:G05 38964
4764 2/24/98 832 RTA00000403F.O.10.2 M00001579C:G05 38964
4765 2/24/98 1 159 RTA00000413F.b. l 8.1 M00004078C:F04 39873
4766 2/24/98 1 122 RTA00000419F.f.l 6.1 M00003839D:E02 64679
4767 2/24/98 1053 RTA00000413F.b.24.1 M00004080A:F01 651 17
4768 2/24/98 1052 RTA00000420F.b.02.1 M00004081 A:A08 64013
4769 2/24/98 157 RTA00000339F.a.23.1 M00001361 B:C07 4022
4770 1/28/98 452 RTAOOOOO 199F.d.19.2 M00003813D:H 12 6707
4771 2/24/98 480 RTA0000041 1F.U 5.1 M00003837C:G08 31612
4772 2/24/98 125 RTA00000403F.m.18.1 M00001576A:B09 39185
4773 2/24/98 548 RTA00000413F.b. l2.1 M00004077B:H 1 1 64932
4774 2/24/98 814 RTA00000408F.1.24.1 M00001530B:G09 34263
4775 1/28/98 688 RTA00000193AF.g.3.1 M00004050D:A06 5567
4776 1/28/98 451 RTA00000200AF.b.20.1 M00004043A:D02 40403
4777 1/28/98 456 RTA00000200AF.b.l2.1 M00004040B:F10 22053
4778 2/24/98 849 RTAOOOOO 122A.n.16.1 M00001517A:G08 80553
4779 1/28/98 12 RTA00000183AF.L15.2 M00001529B:C04 2642
4779 2/24/98 379 RTA00000349R.J.07.1 M00001529B:C04 2642
4780 1/28/98 12 RTA00000183AF.U 5.2 M00001529B:C04 2642
4780 2/24/98 379 RTA00000349R.J.07.1 M00001529B:C04 2642
4781 1/28/98 512 RTA00000191AF.C.3.1 M00003987D:D06 3549
4782 2/24/98 431 RTA00000399F.J.15.1 M00001578C:G06 1261
4783 1/28/98 586 RTAOOOOO 199R.0.1 1.1 M00003976C:A10 23172
4784 1/28/98 496 RTAOOOO0190 AF.p.3.1 M00003975B:F03 2378
4785 2/24/98 340 RTA00000408F.1.13.1 M00001530A:B12 4423
4786 1/28/98 617 RTAOOOOO 179 AF.d.13.3 M00001394A:F01 6583
4787 2/24/98 779 RTA00000408F.1.16.1 M00001530A:F 12 73468
4788 1/28/98 387 RTA00000191AF.J.14.1 M00004073A:H12 1002
4788 2/24/98 632 RTAOOOOO 191 AF.j.14.1 M00004073A:H12 1002
4789 1/28/98 464 RTA00000199AF.I.14.1 M00003917A:D02 22865
4790 2/24/98 668 RTA00000408F.m.05.2 M00001530C:G10 23384
4791 2/24/98 1066 RTAOOOOO 123 A.f.2.1 M00001531 A:H03 80379
4792 2/24/98 213 RTAOOOOO 123 A.f.3.1 M00001531 A:H07 44017
4793 2/24/98 43 RTA00000420F.g.04.1 M00004891 B:B 12 0
4794 2/24/98 302 RTA00000356R.f l 8.1 M00004692A:H 10 0
4795 2/24/98 308 RTA00000353R.d.l l . l M00004692A:H08 0
4796 2/24/98 975 RTA0000041 1 F.n.02.1 M00003870B:F04 78049
4797 1/28/98 722 RTA00000199R.J.24.1 M00003895C:A10 0
4798 2/24/98 643 RTA00000420F.1.14.2 M00005230D:F06 0
4799 1/28/98 480 RTA00000181AF.O.08.2 M00001457C:H 12 849
4800 1/28/98 518 RTAOOOOO 199AF.n.22.1 M00003971A:A06 23064
4801 1/28/98 618 RTAOOOOO 192AF.a.14.1 M000041 1 1 D:A08 6874
4802 2/24/98 937 RTA00000121A.n.l 5.1 M0000151 1 A:G08 40849
4803 2/24/98 821 RTA00000420F.h.16.1 M00004927A:E06 0
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4804 2/24/98 658 RTA00000121 A.n.2.1 M0000151 1 A:A05 33585
4805 2/24/98 551 RTA00000340F.b.05.1 M00001513A:G07 0
4806 2/24/98 172 RTA00000420F.i.l 7.1 M00005101 C:B09 0
4807 2/24/98 1224 RTA00000122A.h.24.1 M00001514A:A12 48
4808 1/28/98 631 RTA00000200AF.h. l9.2 M00004151 D:E03 0
4809 2/24/98 80 RTAOOOOO 122A.g.16.1 M00001514A:B04 81366
4810 2/24/98 809 RTA00000420F.i.23.1 M00005134A:D1 1 0
481 1 2/24/98 650 RTA00000122A.g.l 7.1 M00001514A:B08 32655
4812 2/24/98 73 RTA00000413F.p. l 5.2 M00005136D:D06 0
4813 1/28/98 425 RTA00000200AF.C.16.1 M00004064D:A1 1 23433
4814 2/24/98 60 RTA00000413F.p. l 7.2 M00005136D:G06 0
4815 1/28/98 387 RTA00000191AF.J.14.1 M00004073A:H12 1002
4815 2/24/98 632 RTA00000191 AF.J.14.1 M00004073A:H 12 1002
4816 2/24/98 837 RTA00000420F.h.'θl .1 M00004897C:D06 0
4817 2/24/98 123 RTAOOOOO 122A.J.18.1 M00001516A:D05 81317
4818 2/24/98 77 RTA00000420F.J.22.1 M00005173B:F01 0
4819 1/28/98 734 RTA00000200AF.d.21.1 M00004087C:D03 0
4820 1/28/98 733 RTA00000200AF.d.20.1 M00004087A:G08 26600
4821 2/24/98 1003 RTA00000420F.k.08.2 M00005176C:C09 0
4822 1/28/98 442 RTA00000191 AF.1.9.1 M00004081 C:H06 0
4823 1/28/98 457 RTA00000191 AR.I.7.2 M00004081 C:D12 14391
4824 2/24/98 552 RTA0000041 1 F.n.l2.1 M00003875A:C04 73308
4825 2/24/98 782 RTA00000419F.k.03.1 M00003871C:B05 40822
4826 2/24/98 839 RTA00000414F.b.01.1 M00005212B:A02 0
4827 1/28/98 674 RTA00000197AR.e.24.1 M00001456B:F10 39250
4827 1/28/98 3 RTA00000197AF.e.24.1 M00001456B:F10 39250
4828 1/28/98 669 RTA00000192AF.C.2.1 M00004121B:G01 0
4829 1/28/98 718 RTA00000196F.1.14.2 M00001408B:G06 23144
4830 2/24/98 1259 RTA00000420F.1.19.2 M00005231 A:H04 0
4831 1/28/98 717 RTA00000200F.O.10.2 M00004269B:C08 36432
4832 2/24/98 107 RTA00000125A.g. l 6.1 M00001544A:C09 21497
4833 1/28/98 697 RTAOOOOO 193 AF.e.21.1 M00004271 B:B06 0
4834 2/24/98 829 RTA0000041 1 F.m.l l .l M00003867A:D12 73196
4835 1/28/98 409 RTAOOOOO 180AF.d.1.3 M00001418D:B06 8526
4836 3/24/98 426 RTA00000424F.k.21.1 M00001614A:A04 73197
4837 2/24/98 874 RTA00000346F.O.22.1 M00004300C:H09 7381
4838 3/24/98 136 RTA00000424F.m.22.1 M00001614C:E1 1 72943
4839 2/24/98 636 RTA00000418F.e.21.1 M00001577B:A03 74773
4840 2/24/98 1202 RTA00000347F.h.l0.1 M00004206A:E02 22779
4841 2/24/98 1030 RTA00000125A.C.17.1 M00001542A:E04 80619
4842 2/24/98 753 RTA00000345F.O.13.1 M00001546B:F12 1 1500
4843 2/24/98 221 RTA00000414F.f. l3.1 M00005259D:H08 0
4844 2/24/98 193 RTA00000347F.b. l0.1 M00001546C:C07 8044
4845 2/24/98 1 104 RTAOOOOO 126A.b.10.1 M00001547A:F06 0
4846 2/24/98 1 177 RTA00000126A.b.9.1 M00001547A:F1 1 81279
4847 2/24/98 923 RTAOOOOO 126A.d.19.1 M00001548A:G01 79474
4848 2/24/98 98 RTA0000041 1 F.1.03.1 M00003854D:A12 62702
4849 2/24/98 625 RTAOOOOO 126 A.h.22.2 M00001549A:F01 0
4850 1/28/98 710 RTAO0000196AF.1.3.1 M00001405B:D07 20864
4851 2/24/98 1 102 RTAOOOOO 126A.J.15.2 M00001549A:H1 1 40425
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4852 3/24/98 467 RTA00000528F.h.02.2 M00001632C:D08 1701
4853 1/28/98 41 1 RTAOOOOO 179 AF.j.13.3 M00001400B:H06 0
4854 2/24/98 1 126 RTAOOOOO 136A.h.6.1 M00001550A:D09 81620
4855 1/28/98 712 RTA00000201 F.b.21.1 M00004341 B:G03 9071
4856 2/24/98 1257 RTA00000419F.h.21.1 M0O0O3856C:B08 64828
4857 2/24/98 194 RTAOOOOO 124A.k.5.1 M00001538A:F12 80252
4858 1/28/98 508 RTA00000187AF.i. l4.2 M00001679B:H07 19406
4858 2/24/98 928 RTA00000340F.m.04.1 M00001679B:H07 19406
4859 1/28/98 3 RTAOOOOO 197 AF.e.24.1 M00001456B:F10 39250
4859 1/28/98 674 RTA00000197AR.e.24.1 M00001456B:F10 39250
4860 2/24/98 606 RTA00000420F.1.20.2 M00005232A:C10 0
4861 2/24/98 30 RTA0000041 1 F.m.24.1 M00003870B:B08 77568
4862 2/24/98 31 RTAOOOOO 134A.J.10.1 M00001534A:G06 81383
4863 2/24/98 1 136 RTA00000406F.C.05.1 M00003870A:H01 22077
4864 2/24/98 41 1 RTA00000420F.m. l 2.1 M00005234D:B04 0
4865 2/24/98 1086 RTA00000403F.n.22.2 M00001578B:B05 26775
4865 2/24/98 1085 RTA00000403F.n.22.1 M00001578B:B05 26775
4866 2/24/98 1018 RTA00000413F.J.21.1 M0O004688A:A02 0
4867 2/24/98 657 RTAOOOOO 124A.L20.1 M00001538A:C08 80913
4868 2/24/98 718 RTAOOOOO 124A.k.23.1 M00001538A:D03 81350
4869 2/24/98 1092 RTAOOOOO 125 A.c.2.1 M00001542A:F06 40148
4870 2/24/98 615 RTA00000135A.b.23.1 M00001538A:D12 35241
4871 2/24/98 639 RTA00000414F.d.09.1 M00005231 C:B01 0
4872 2/24/98 1086 RTA00000403F.n.22.2 M00001578B:B05 26775
4872 2/24/98 1085 RTA00000403F.n.22.1 M00001578B:B05 26775
4873 2/24/98 99 RTA00000420F.m. l 9.1 M00005254D:B08 0
4874 2/24/98 1085 RTA00000403F.n.22.1 M00001578B:B05 26775
4874 2/24/98 1086 RTA00000403F.n.22.2 M00001578B:B05 26775
4875 2/24/98 1086 RTA00000403F.n.22.2 M00001578B:B05 26775
4875 2/24/98 1085 RTA00000403F.n.22.1 M00001578B:B05 26775
4876 1/28/98 725 RTAOOOOO 197AF.b.1.1 M00001441 D:E04 12134
4877 2/24/98 215 RTA00000403F.J.18.1 M00001539D:E10 5790
4878 2/24/98 1010 RTA00000408F.n. l 6.2 M00001540C:B03 73720
4879 2/24/98 1074 RTA00000423F.h. l l . l M00003867C:E1 1 38977
4880 2/24/98 27 RTA00000420F.n.l9.2 M00005259B:C01 0
4881 1/28/98 578 RTAOOOOO 180AF.g.17.1 M00001426A:A09 16653
4882 2/24/98 1 172 RTA00000423F.h.03.1 M00003875D:D09 37903
4883 2/24/98 1008 RTA00000414F.f.07.1 M00005259C:B05 0
4884 2/24/98 582 RTA00000414F.e.l4.1 M00005236B:F10 0
4885 1/28/98 178 RTA00000200F.O.03.1 M00004257C:H06 22807
4885 1/28/98 249 RTA00000200R.O.03.2 M00004257C:H06 22807
4885 1/28/98 85 RTA00000200R.O.03.1 M00004257C:H06 22807
4886 2/24/98 1223 RTA00000347F.a.14.1 M00001429D:F1 1 7421
4887 2/24/98 488 RTA00000339F.k.23.1 M00001429D:H12 0
4888 3/24/98 100 RTA00000424F.i.21.1 M00001596A:E07 73482
4889 3/24/98 64 RTA00000424F.i.24.1 M00001596A:G06 79101
4890 3/24/98 207 RTA00000424F.J.07.1 M00001596B:C1 1 7921 1
4891 3/24/98 327 RTA00000424F.J.08.1 M00001596B:D09 73972
4892 3/24/98 349 RTA00000424F.J.09.1 M00001596B:H05 74387
4893 3/24/98 154 RTA00000522F.h. l3.1 M00001596C:F09 40823
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4894 2/24/98 1252 RTA00000400F.g.08.1 M00001639A:C1 1 1275
4895 2/24/98 261 RTA00000341 F.b.06.1 M00003794A:E12 17008
4896 1/28/98 312 RTA00000193AF.h.2.1 M00004290A:B03 3273
4897 1/28/98 590 RTA00000190AF.d.2.1 M00003906B:F12 2444
4898 1/28/98 213 RTA00000200F.O.04.1 M00004260D:C12 12514
4899 2/24/98 333 RTA00000399F.f. l l .l M00001487C:F01 40167
4900 1/28/98 249 RTA00000200R.O.03.2 M00004257C:H06 22807
4900 1/28/98 178 RTA00000200F.O.03.1 M00004257C:H06 22807
4900 1 /28/98 85 RTA00000200R.O.03.1 M00004257C:H06 22807
4901 1 /28/98 85 RTA00000200R.O.03.1 M00004257C:H06 22807
4901 1/28/98 178 RTA00000200F.O.03.1 M00004257C:H06 22807
4901 1/28/98 249 RTA00000200R.O.03.2 M00004257C:H06 22807
4902 1/28/98 85 RTA00000200R.O.03.1 M00004257C:H06 22807
4902 1/28/98 249 RTA00000200R.O.03.2 M00004257C:H06 22807
4902 1 /28/98 178 RTA00000200F.O.03.1 M00004257C:H06 22807
4903 1 /28/98 249 RTA00000200R.O.03.2 M00004257C:H06 22807
4903 1 /28/98 85 RTA00000200R.O.03.1 M00004257C:H06 22807
4903 1/28/98 178 RTA00000200F.O.03.1 M00004257C:H06 22807
4904 1/28/98 249 RTA00000200R.O.03.2 M00004257C:H06 22807
4904 1/28/98 85 RTA00000200R.O.03.1 M00004257C:H06 22807
4904 1/28/98 178 RTA00000200F.O.03.1 M00004257C:H06 22807
4905 3/24/98 133 RTA00000425F.f.04.1 M00001607A:B06 24633
4906 3/24/98 169 RTA00000425F.f.05.1 M00001607A:D10 24090
4907 2/24/98 44 RTA00000418F. 14.1 M00001639A:H06 76133
4908 2/24/98 1204 RTA00000419F.I.02.1 M00003879A:C01 75736
4909 2/24/98 748 RTA00000346F. l l . l M00003793C:D09 38528
4910 2/24/98 4 RTA00000339F.i.20.1 M00001438D:C06 4356
491 1 1/28/98 93 RTA00000200F.O.1 1.1 M00004270A:F1 1 0
4912 1/28/98 435 RTAOOOOO 182 AR.c.22.1 M00001467A:D08 16283
4913 1/28/98 683 RTAOOOOO 187 AR.j .01.1 M00001679C:D01 79028
4914 3/24/98 469 RTA00000522F.e.20.1 M00001590B:H10 26770
4915 1 /28/98 172 RTAOOOOO 186AF.p.09.2 M00001655C:E04 6879
4916 2/24/98 806 RTA00000345F.f.08.1 M00001413B:H09 0
4917 1/28/98 677 RTA00000197AF.i.19.1 M00001490B:H1 1 39554
4918 1/28/98 443 RTAOOOOO 197AR.i.17.1 M00001490A:E1 1 3516
4919 2/24/98 863 RTA00000406F.p.08.1 M00004032C:B02 37573
4920 3/24/98 55 RTA00000528F.e.23.1 M00001593B:D10 19242
4921 2/24/98 121 1 RTA00000399F.f. l4.1 M00001487D:C 1 1 1 1483
4922 1/28/98 609 RTA00000196AF.n.05.1 M00001418B:F07 12531
4922 2/24/98 1 120 RTA00000353R.1.23.1 M00001418B:F07 12531
4923 1/28/98 609 RTA00000196AF.n.05.1 M00001418B:F07 12531
4923 2/24/98 1 120 RTA00000353R.I.23.1 M00001418B:F07 12531
4924 3/24/98 474 RTA00000522F.h.05.1 M00001595C:H1 1 73358
4925 1/28/98 284 RTAOOOOO 199F.d.10.2 M00003808C:B05 22049
4925 2/24/98 816 RTA00000354R.n.04.1 M00003808C:B05 22049
4926 2/24/98 1 1 12 RTA00000418F.C.05.1 M00001487B:F02 76475
4927 1/28/98 687 RTA00000197AF.g.4.1 M00001464B:B03 8821
4928 2/24/98 990 RTA00000121 A.h. l9.1 M00001471A:D04 80334
4929 1/28/98 696 RTAOOOOO 180 AR.d.16.3 M00001419D:C 10 1 1393
4929 2/24/98 1 184 RTA00000345F.h.08.1 M00001419D:C 10 1 1393
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4930 1/28/98 751 RTAOOOOO 179AF.C.4.3 M00001392D:B 1 1 0
4931 1/28/98 696 RTAOOOOO 180AR.d.16.3 M00001419D:C 10 1 1393
4931 2/24/98 1 184 RTA00000345F.h.08.1 M00001419D:C 10 1 1393
4932 1/28/98 162 RTA00000201 F.e.l 5.1 M00004444B:D1 1 9960
4933 1/28/98 126 RTA00000201 F.d. l6.1 M00004388B:A08 0
4934 1/28/98 332 RTAOOOOO 193 AR.n.04.3 M00004375C:D01 9850
4935 2/24/98 838 RTA00000408F. 19.1 M00001487C:G03 77593
4936 2/24/98 1 13 RTA00000401 F.e.02.1 M00003805B:C04 0
4937 3/24/98 278 RTA00000522F.g.21.1 M00001595C:A09 77310
4938 3/24/98 54 RTA00000425F.f. l 9.1 M00001653D:G07 32635
4939 2/24/98 976 RTA00000419F.b.l 7.1 M00003808D:D04 63261
4940 2/24/98 59 RTA00000346F.J.08.1 M00003879B:A06 39951
4941 2/24/98 151 RTA00000341 F.C.21.1 M00003789C:F06 7899
4942 1/28/98 67 RTA00000200AF.g.07.1 M00004128B:G01 0
4943 2/24/98 324 RTA00000340F.p. l 7.1 M00003750C:H05 0
4944 2/24/98 476 RTA00000345F.h.01.1 M00001441 B:D1 1 10834
4945 2/24/98 245 RTA00000195AF.d.20.1 M000041 17A:D1 1 37574
4945 1/28/98 87 RTAOOOOO 195 AF.d.20.1 M000041 17A:D1 1 37574
4946 2/24/98 245 RTAOOOOO 195 AF.d.20.1 M000041 17A:D1 1 37574
4946 1/28/98 87 RTAOOOOO 195 AF.d.20.1 M000041 17A:D1 1 37574
4947 2/24/98 991 RTA00000419F.b.l0.1 M00001694C:G04 78566
4948 2/24/98 14 RTA00000419F.b.09.1 M00001694C:F12 78128
4949 1/28/98 261 RTA00000192AF.a.24.1 M000041 14C:F1 1 13183
4950 1/28/98 24 RTA00000200AF.f.l l . l M000041 1 1 D:D1 1 0
4951 3/24/98 408 RTA00000522F.O.10.1 M00001660D:E05 78798
4952 1/28/98 328 RTA00000200AF.g.09.1 M00004131 B:H09 22785
4952 1/28/98 26 RTA00000200R.g.09.1 M00004131 B:H09 22785
4953 2/24/98 861 RTA00000419F.b.06.1 M00001694B:B08 76728
4954 3/24/98 24 RTA00000522F.n.08.1 M00001656A:D10 76343
4955 2/24/98 760 RTA00000423F.d.04.1 M00001694A:B 12 1 1307
4956 3/24/98 220 RTA00000522F.O.18.1 M00001669B:H06 76366
4957 2/24/98 279 RTA00000418F.L21.1 M00001596D:E10 78728
4958 1/28/98 84 RTA00000191 AF.li.14. ! M00004056B:D09 13553
4959 1/28/98 284 RTA00000199F.d.l0.2 M00003808C:B05 22049
4959 2/24/98 816 RTA00O00354R.n.04.1 M00003808C:B05 22049
4960 2/24/98 217 RTA00000399F.O.17.1 M00001599D:A09 1 106
4961 1/28/98 287 RTA00000200AF.b.07.1 M00004039C:C01 17125
4961 1/28/98 173 RTA00000200AR.b.07.1 M00004039C:C01 17125
4962 1/28/98 287 RTA00000200AF.b.07.1 M00004039C:C01 17125
4962 1/28/98 173 RTA00000200AR.b.07.1 M00004039C:C01 17125
4963 1/28/98 287 RTA00000200AF.b.07.1 M00004039C:C01 17125
4963 1/28/98 173 RTA00000200AR.b.07.1 M00004039C:C01 17125
4964 1/28/98 287 RTA00000200AF.b.07.1 M00004039C:C01 17125
4964 1/28/98 173 RTA00000200AR.b.07.1 M00004039C:C01 17125
4965 3/24/98 464 RTA00000522F.p.l 8.1 M00001671 A:H06 76376
4966 3/24/98 453 RTA00000522F.p.22.1 M00001671 B:F02 73322
4967 2/24/98 54 RTA00000399F.O.01.1 M00001595C:E01 3055
4968 2/24/98 1219 RTA00000347F.e.20.1 M00003771 B:E05 3991 1
4969 2/24/98 825 RTA00000404F. 22.2 M00001635D:C12 39084
4969 2/24/98 364 RTA00000404F. 22.1 M00001635D:C 12 39084
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
4970 1/28/98 241 RTA00000200AF.I.17.1 M00004217C:D03 12771
4970 1/28/98 151 RTA00000200R.1.17.1 M00004217C:D03 12771
4970 1/28/98 202 RTA00000200R.I.17.2 M00004217C:D03 12771
4971 1/28/98 241 RTA00000200AF.I.17.1 M00004217C:D03 12771
4971 1/28/98 151 RTA00000200R.1.17.1 M00004217C:D03 12771
4971 1/28/98 202 RTA00000200R.1.17.2 M00004217C:D03 12771
4972 1/28/98 241 RTA00000200AF.1.17.1 M00004217C:D03 12771
4972 1/28/98 202 RTA00000200R.1.17.2 M00004217C:D03 12771
4972 1/28/98 151 RTA00000200R.1.17.1 M00004217C:D03 12771
4973 1/28/98 241 RTA00000200AF.I.17.1 M00004217C:D03 12771
4973 1/28/98 202 RTA00000200R.1.17.2 M00004217C:D03 12771
4973 1 /28/98 151 RTA00000200R.1.17.1 M00004217C:D03 12771
4974 1/28/98 241 RTA00000200AF.1.17.1 M00004217C:D03 12771
4974 1/28/98 202 RTA00000200R.I.17.2 M00004217C:D03 12771
4974 1/28/98 151 RTA00000200R.1.17.1 M00004217C:D03 12771
4975 1/28/98 241 RTA00000200AF.1.17.1 M0000421 7C:D03 12771
4975 1/28/98 151 RTA00000200R.1.17.1 M0000421 7C:D03 12771
4975 1/28/98 202 RTA00000200R.1.17.2 M00004217C:D03 12771
4976 1/28/98 241 RTA00000200AF.1.17.1 M00004217C:D03 12771
4976 1/28/98 151 RTA00000200R.1.17.1 M00004217C:D03 12771
4976 1/28/98 202 RTA00000200R.1.17.2 M00004217C:D03 12771
4977 1/28/98 241 RTA00000200AF.1.17.1 M00004217C:D03 12771
4977 1/28/98 151 RTA00000200R.1.17.1 M 00004217C:D03 12771
4977 1/28/98 202 RTA00000200R.1.17.2 M00004217C:D03 12771
4978 1/28/98 241 RTA00000200AF.1.17.1 M00004217C:D03 12771
4978 1/28/98 151 RTA00000200R.I.17.1 M00004217C:D03 12771
4978 1/28/98 202 RTA00000200R.I.17.2 M00004217C:D03 12771
4979 1/28/98 366 RTAOOOOO 192 AF.o.19.1 M00004208D:H08 3549
4980 1/28/98 328 RTA00000200AF.g.09.1 M00004131 B:H09 22785
4980 1/28/98 26 RTA00000200R.g.09.1 M00004131 B:H09 22785
4981 1/28/98 245 RTA00000200AF. 7.1 M00004193C:G1 1 0
4982 2/24/98 1036 RTA00000339F.k.08.1 M00001439B:A10 8133
4983 2/24/98 72 RTA00000347F.a.08.1 M00001592C:G04 3135
4984 2/24/98 1 163 RTA00000341 F.b. l4.1 M00003763A:C01 5992
4985 2/24/98 278 RTA00000404F.C.10.1 M00001593B:E1 1 23534
4986 1/28/98 250 RTA00000192AF.J.21.1 M00004176D:B12 2289
4987 2/24/98 51 1 RTA00000341 F.b. l3.1 M00003762B:H09 0
4988 1/28/98 27 RTA00000192AF.i. l2.1 M00004169C:C 12 5319
4989 2/24/98 416 RTA00000404F.C.19.1 M00001594A:D06 39026
4990 2/24/98 351 RTA00000340F.p.20.1 M00003752B:C02 17008
4991 1/28/98 215 RTA00000192AR.e. l 4.3 M00004142A:D08 3300
4992 1/28/98 163 RTA00000192AR.e. l3.3 M00004142A:B12 9457
4993 1/28/98 318 RTA00000200AF.g.l 7.1 M00004138A:H09 0
4994 2/24/98 1 105 RTA00000340F.p. l 8.1 M00003751 C:A04 287
4995 2/24/98 1080 RTA00000351 R.g.06.1 M00003771 D:G05 0
4996 2/24/98 478 RTA00000418F.h.08.1 M00001589B:E07 76401
4997 2/24/98 584 RTA00000418F.d.22.1 M00001573B:C06 75324
4998 2/24/98 493 RTAOOOOO 129A.d.1.2 M00001587A:F05 80058
4999 2/24/98 402 RTA00000420F.e. l 6.1 M000041 10A:E04 63639
5000 2/24/98 1006 RTA00000129A.e. l4.1 M00001587A:F08 80053
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
5001 2/24/98 285 RTA00000413F.i.02.1 M000041 10D:A10 65857
5002 1/28/98 659 RTAOOOOO 185 AR.k.23.2 M00001601 A:E09 0
5003 2/24/98 122 RTA00000420F.f.06.1 M000041 15D:D08 64812
5004 2/24/98 245 RTAOOOOO 195 AF.d.20.1 M000041 17A:D1 1 37574
5004 1/28/98 87 RTA00000195AF.d.20.1 M000041 17A:D1 1 37574
5005 1/28/98 87 RTA00000195AF.d.20.1 M000041 17A:D1 1 37574
5005 2/24/98 245 RTAOOOOO 195 AF.d.20.1 M000041 17A:D1 1 37574
5006 2/24/98 720 RTAOOOOO 129A.d.2.4 M00001587A:G06 801 19
5007 2/24/98 687 RTA00000350R.g.l0.1 M00001587C:C10 9026
5008 3/24/98 18 RTA00000522F.e. l 6.1 M00001590A:C08 75283
5009 1/28/98 447 RTA00000198AF.d.8.1 M00001587A:H03 0
5010 1/28/98 554 RTAOOOOO 186AR.e.07.4 M00001623D:G03 4175
5010 1/28/98 400 RTAOOOOO 186AR.e.07.3 M00001623D:G03 4175
501 1 1/28/98 526 RTAOOOOO 185 AF.e.20.1 M00001585A:D06 5865
5012 2/24/98 1 RTA00000404F.a.02.1 M00001589B:E12 9738
5013 1/28/98 530 RTAOOOOO 185 AF.d.24.2 M00001582D:F05 0
5014 2/24/98 1096 RTA00000421 F.a.06.1 M00001589C:A1 1 2385
5015 1/28/98 131 RTAOOOOO 185 AF.d.1 1.2 M00001579D:C03 6539
5015 1/28/98 626 RTAOOOOO 185 AR.d.1 1.1 M00001579D:C03 6539
5016 1/28/98 626 RTAOOOOO 185 AR.d.1 1.1 M00001579D:C03 6539
5016 1/28/98 131 RTAOOOOO 185 AF.d.1 1.2 M00001579D:C03 6539
5017 2/24/98 1020 RTA00000412F.p.06.1 M00004038B:H10 65485
5018 1/28/98 671 RTA00000185AR.d.08.1 M00001579C:E09 6562
5019 2/24/98 1240 RTA00000404F.a.l 8.1 M00001590B:B02 36267
5020 2/24/98 1 15 RTA00000418F.h. l9.1 M00001590B:C05 0
5021 2/24/98 21 1 RTA00000404F.a.l9.1 M00001590B:C07 38624
5022 1/28/98 455 RTAOOOOO 198AF.d.12.1 M00001589A:C01 21 142
5023 1/28/98 622 RTAOOOOO 186AR.m.14.2 M00001649B:G 12 9800
5024 2/24/98 958 RTAOOOOO 195 AF.c.8.1 M00001678B:H01 0
5024 1/28/98 520 RTAOOOOO 195 AF.c.8.1 M00001678B:H01 0
5025 1/28/98 520 RTAOOOOO 195 AF.c.8.1 M00001678B:H01 0
5025 2/24/98 958 RTAOOOOO 195 AF.c.8.1 M00001678B:H01 0
5026 1/28/98 690 RTAOOOOO 198R.1.21.1 M00001673A:A04 19194
5027 2/24/98 772 RTA00000413F.e.04.1 M00004090C:C07 64176
5028 2/24/98 834 RTA00000407F.b. l l . l M00004090C:C 10 0
5029 2/24/98 1 154 RTA00000403F.m.09.2 M00001575B:G01 26814
5030 2/24/98 1203 RTA00000413F.e.l 0.1 M00004092C:B03 31033
5031 2/24/98 12 RTA00000339F.b.l 7.1 M00001366D:E12 10020
5032 2/24/98 947 RTA00000347F.g.08.1 M00004096B:F05 23121
5033 1/28/98 39 RTAOOOOO 189AR.b.19.1 M00003832B:E01 5294
5033 2/24/98 239 RTA00000346F.J.02.1 M00003832B:E01 5294
5034 1/28/98 39 RTAOOOOO 189AR.b.19.1 M00003832B:E01 5294
5034 2/24/98 239 RTA00000346F.J.02.1 M00003832B:E01 5294
5035 2/24/98 560 RTA00000419F.d. l 6.1 M00003828B:E07 64357
5036 2/24/98 568 RTA00000403F.m.03.1 M00001573D:D10 39179
5037 2/24/98 191 RTA00000419F.d. l 7.1 M00003828B:F09 64353
5038 2/24/98 607 RTA00000420F.d.l6.1 M00004103D:F10 64485
5039 2/24/98 1 130 RTA00000354R.p.01.1 M00004104C:H12 0
5040 2/24/98 710 RTA00000413F.g.24.1 M00004104D:A04 65481
5041 2/24/98 24 RTA00000423F.1.09.1 M000041 18A:H08 9752
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
5042 2/24/98 896 RTA00000423F.I.20.1 M00004105C:E09 12580
5043 2/24/98 1078 RTA00000423F.f.03.1 M00003829C:D10 63852
5044 1/28/98 558 RTAOOOOOl 86AR.h.14.1 M00001632D:H07 0
5045 2/24/98 155 RTA00000413F.h. l3.1 M00004107A:D01 65190
5046 2/24/98 926 RTA00000399F. 20.1 M00001585C:D10 3003
5047 2/24/98 1 194 RTA00000420F.e.05.1 M00004107D:E12 63908
5048 1/28/98 400 RTAOOOOO 186AR.e.07.3 M00001623D:G03 4175
5048 1/28/98 554 RTAOOOOOl 86AR.e.07.4 M00001623D:G03 4175
5049 2/24/98 570 RTA00000405F.n.l3.1 M00003824A:G10 23810
5050 2/24/98 334 RTA00000408F.p.05.1 M00001575B:B02 9649
5051 2/24/98 1029 RTA0000041 1 F.f.04.1 M00003813A:G04 64526
5052 3/24/98 134 RTA00000424F.C.14.3 M00001476D:A09 76614
5053 2/24/98 396 RTA00000406F.e.21.1 M00003877D:G05 9090
5054 3/24/98 230 RTA00000424F.g.l4.1 M00001572A:B06 74879
5055 2/24/98 617 RTA00000423F.f.23.1 M00003816C:E09 15390
5056 2/24/98 5 RTA00000408F.O.12.2 M00001572A:A10 78578
5057 2/24/98 689 RTA00000419F.p.03.1 M00004035A:G10 1937
5058 3/24/98 273 RTA00000424F.a.02.4 M00001575A:D06 78806
5059 2/24/98 241 RTA00000339F.d.l3.1 M00001395C:F1 1 0
5060 3/24/98 237 RTA00000522F.C.01.1 M00001576A:C 1 1 74938
5061 1/28/98 745 RTAOOOOOl 83 AF.m.1 1.1 M00001536D:G02 8927
5062 1/28/98 408 RTA00000183AR.1.15.1 M00001535C:E01 39383
5063 2/24/98 464 RTA00000195AF.C.12.1 M00003818B:G12 37582
5063 1/28/98 300 RTA00000195AF.C.12.1 M00003818B:G12 37582
5064 1/28/98 647 RTA00000197F.m.l l .l M00001530B:D10 16488
5065 2/24/98 464 RTAOOOOO 195AF.C.12.1 M00003818B:G 12 37582
5065 1/28/98 300 RTA00000195AF.C.12.1 M00003818B:G 12 37582
5066 3/24/98 395 RTA00000522F.d.06.1 M00001578B:A02 74809
5067 2/24/98 516 RTA00000339F.f.20.1 M00001399A:C03 6494
5068 2/24/98 890 RTA00000418F.J.19.1 M00001634D:D02 78399
5069 2/24/98 435 RTA00000340F.b.02.1 M00001503C:G05 10185
5070 3/24/98 175 RTA00000528F.d.l 8.1 M00001582C:E01 2684
5071 2/24/98 168 RTA0000041 1 F.e.22.1 M00003812B:D07 63638
5072 2/24/98 1071 RTA00000404F.k.l 8.2 M00001635A:C06 5475
5073 2/24/98 189 RTA00000347F.a.l3.1 M00001402D:F02 22446
5074 2/24/98 825 RTA00000404F.k.22.2 M00001635D:C12 39084
5074 2/24/98 364 RTA00000404F.k.22.1 M00001635D:C12 39084
5075 3/24/98 25 RTA00000425F.C.06.1 M00001585D:D1 1 78041
5076 3/24/98 186 RTA00000425F.C.07.1 M00001585D:F03 76042
5077 3/24/98 208 RTA00000424F.m. l 0.1 M00001586C:E06 34251
5078 2/24/98 420 RTA00000422F.b.l 6.1 M00003813B:A1 1 17045
5079 3/24/98 103 RTA00000424F.b.22.1 M00001530A:F1 1 72971
5079 3/24/98 88 RTA00000424F.b.22.4 M00001530A:F1 1 72971
5080 3/24/98 318 RTA00000523F.a.01.1 M00001671C:F1 1 74923
5081 2/24/98 676 RTA0000041 1 F.g.21 .1 M00003823D:G05 64500
5082 3/24/98 RTA00000528F.b.23.1 M00001479C:F10 1605
5083 2/24/98 1244 RTA00000418F.h.23.1 M00001591 A:B08 75153
5084 2/24/98 321 RTA00000339F.C.21.1 M00001389C:A08 5325
5085 1/28/98 429 RTAOOOOO 196F.i.19.1 M00001390C:C 1 1 39498
5085 2/24/98 925 RTA00000353R.h. l 0.1 M00001390C:C 1 1 39498
SEQ ID Filing SEQ ID Sequence Name Clone Nsme Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
5086 1/28/98 429 RTA00000196F.U9.1 M00001390C:C11 39498
5086 2/24/98 925 RTA00000353R.li.10.1 M00001390C:C11 39498
5087 3/24/98 471 RTA00000528F.C.11.1 M00001486D:D12 1701
5088 2/24/98 103 RTA00000418F.J.12.1 M00001626C:G08 73316
5089 2/24/98 1148 RTA00000345F.d.23.1 M0000I390D:E03 5862
5090 2/24/98 87 RTA00000403F.1.20.1 M00001573A:A06 18267
5091 3/24/98 427 RTA00000522F.b.08.1 M00001570D:E06 26915
5092 1/28/98 661 RTAOOOOO 198R.b.04.1 M00001565A:H09 0
5093 2/24/98 200 RTA00000339F.C.02.1 M00001381C:B08 12975
5094 2/24/98 1243 RTA00000404F.J.19.1 M00001630D:H10 0
5095 1/28/98 750 RTAOOOOO 198AF.a.19.1 M00001561D:C05 0
5096 2/24/98 418 RTA00000410F.a.01.1 M00001631D:B10 73354
5097 3/24/98 458 RTA00000424F.d.l2.3 M00001530D:E06 74342
5097 3/24/98 454 RTA00000424F.d.l2.2 M00001530D:E06 74342
5098 3/24/98 458 RTA00000424F.d.l2.3 M00001530D:E06 74342
5098 3/24/98 454 RTA00000424F.d.l2.2 M00001530D:E06 74342
5099 2/24/98 159 RTA00000348R.J.17.1 M00001391D:C06 2641
5100 2/24/98 539 RTA00000346F.m.l5.1 M00004037B:C04 13553
5101 2/24/98 170 RTA00000422F.n.08.1 M00001632B:E05 38655
5102 3/24/98 162 RTA00000522F.3.12.1 M00001567A:H05 33515
5103 2/24/98 315 RTA00000419F.p.l2.1 M00004037A:E04 13767
5104 2/24/98 119 RTA00000423F.k.05.1 M00004036D:F02 37472
5105 3/24/98 12 RTA00000522F.3.23.1 M00001570C:A05 38613
5106 3/24/98 103 RTA00000424F.b.22.1 M00001530A:F11 72971
5106 3/24/98 88 RTA00000424F.b.22.4 M00001530A:F11 72971
5107 2/24/98 21 RTA00000411F.g.08.1 M00003822D:D04 45815
5108 1/28/98 35 RTAOOOOOl 91 AF.n.17.1 M00004091B:D11 7848
5109 3/24/98 39 RTA00000527F.C.23.1 M00003822C:A07 37742
5110 1/28/98 43 RTAOOOOOl 79AF.C.14.3 M00001392D:H04 0
5111 2/24/98 54 RTA00000399F.O.01.1 M00001595C:E01 3055
5112 2/24/98 63 RTA00000404F.1.20.2 M00001639B:H05 38638
5113 1/28/98 82 RTAOOOOOl 83AF.1.18.1 M00001535D:C01 3484
5114 3/24/98 84 RTA00000527F.k.l8.1 M00003982B:C10 11332
5115 1/28/98 99 RTAOOOOO 184AF.d.8.1 M00001548A:A08 4393
5116 2/24/98 99 RTA00000420F.m.l9.1 M00005254D:B08 0
5117 2/24/98 100 RTA00000339F.O.23.1 M00001473C:D09 7801
5118 2/24/98 104 RTA00000421F.n.03.1 M00001675C:A04 1638
5119 2/24/98 105 RTA00000346F.d.08.1 M00001671A:A10 39955
5120 2/24/98 114 RTA00000341F.I11.21.1 M00004051D:E01 0
5121 1/28/98 137 RTAOOOOOl 8 lAF.m.4.3 M00001455A:E09 13238
5122 1/28/98 162 RTA00000201F.e.l5.1 M00004444B:D11 9960
5123 1/28/98 170 RTA00000197AF.d.23.1 M00001453A:E11 16130
5124 1/28/98 206 RTAOOOOOl 81 AF.o.04.2 M00001457C:C12 22205
5125 1/28/98 209 RTAOOOOOl 82AF.C.5.1 M00001464D:F06 6397
5126 2/24/98 215 RTA00000403F.J.18.1 M00001539D:E10 5790
5127 2/24/98 219 RTA00000419F.C.18.1 M00003819D:B11 41394
5128 1/28/98 229 RTAOOOOOl 98 AF.g.3.1 M00001615C:F03 0
5129 1/28/98 230 RTAOOOOOl 85AR.b.18.1 M00001575B:C09 12171
5130 3/24/98 245 RTA00000522F.p.09.1 M00001670A:F09 75204
5131 2/24/98 258 RTA00000406F. 15.1 M00003907C:C04 38549
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
5132 1/28/98 262 RTAOOOOO 186AF.C.17.1 M00001619D:G05 8551
5133 1/28/98 269 RTA00000183AF.U 3.1 M00001534B:C 12 0
5134 1/28/98 276 RTAOOOOO 198AF.J.15.1 M00001653B:E09 4369
5135 2/24/98 281 RTA0000041 1 F.I.13.1 M00003857C:C09 431 14
5136 1/28/98 284 RTAOOOOO 199F.d.10.2 M00003808C:B05 22049
5137 1/28/98 292 RTAOOOOOl 99AF.m.18.1 M00003939C:F04 0
5138 1/28/98 297 RTAOOOOOl 78 AF.f.9.3 M00001371C:E09 7172
5139 2/24/98 301 RTA00000401 F.m.23.1 M00003914C:C02 2801
5140 1/28/98 302 RTAOOOOO 186AF.d.1.2 M00001621 C:C08 40044
5141 1/28/98 315 RTAOOOOOl 99R.d.23.1 M00003815D:H09 37477
5142 2/24/98 315 RTA00000419F.p. l2.1 M00004037A:E04 13767
5143 1/28/98 321 RTAOOOOOl 81 AR.b.21.1 M00001444C:D05 3266
5144 3/24/98 323 RTA00000524F.C.12.1 M00005218B:D09 0
5145 1/28/98 329 RTAOOOOO 186AF.b.9.1 M00001616C:F07 0
5146 1/28/98 334 RTAOOOOOl 81 AR.b.21.3 M00001444C:D05 3266
5147 2/24/98 334 RTA00000408F.p.05.1 M00001575B:B02 9649
5148 1/28/98 335 RTAOOOOOl 82AF.e.3.2 M00001468B:H06 0
5149 1/28/98 336 RTAOOOOO 186AF.f.24.1 M00001629B:E06 0
5150 2/24/98 341 RTA00000412F.g.20.2 M00003972C:F08 25018
5151 2/24/98 343 RTA00000422F.g.21.1 M00001583A:F07 17232
5152 1/28/98 347 RTAOOOOO 199F.b.03.2 M00003779B:E12 38340
5153 2/24/98 354 RTA00000404F.C.03.2 M00001592C:F1 1 39198
5154 1/28/98 361 RTAOOOOO 177AR.g.16.4 M00001347A:B10 13576
5155 1/28/98 364 RTAOOOOOl 87AF.g.13.1 M00001676C:C 1 1 2991
5156 2/24/98 377 RTA00000346F.Ϊ.01.1 M00003797A:D06 22260
5157 2/24/98 389 RTA0000041 1 F.C.02.1 M00001677B:B04 72852
5158 2/24/98 403 RTA00000403F.d.22.1 M00001473A:A07 10692
5159 1/28/98 407 RTAOOOOOl 78 AF.e.20.1 M00001370D:E12 3135
5160 1/28/98 422 RTAOOOOOl 89AF.b.12.1 M00003829B:G03 17233
5161 2/24/98 429 RTA00000422F.C.17.1 M00004099D:F01 1360
5162 2/24/98 431 RTA00000399F.J.15.1 M00001578C:G06 1261
5163 1/28/98 439 RTAOOOOO 185 AF.d.14.2 M00001579D:G07 8071
5164 2/24/98 448 RTAOOOOO 127A.3.3.1 M00001552A:H 10 13232
5165 2/24/98 450 RTAOOOOOl 18A.3.23.1 M00001395A:H02 3500
5166 1/28/98 451 RTA00000200AF.b.20.1 M00004043A:D02 40403
5167 2/24/98 455 RTA00000399F.d.23.1 M00001481 B:A07 3310
5168 1/28/98 475 RTAOOOOO 187AR.m.3.3 M00001682C:B 12 17055
5169 3/24/98 475 RTA00000427F.i.06.1 M00004097B:D03 41450
5170 3/24/98 477 RTA00000527F.1.21.1 M00003983D:H02 36439
5171 1/28/98 480 RTAOOOOOl 81 AF.o.08.2 M00001457C:H12 849
5172 3/24/98 480 RTA00000424F.d.l 7.3 M00001455A:E1 1 73958
5173 3/24/98 481 RTA00000523F.J.02.1 M00003857A:H 10 62853
5174 1/28/98 483 RTA00000192AF.h.l 9.1 M00004162C:A07 4642
5175 2/24/98 489 RTA00000406F.J.19.1 M00003906A:F12 1685
5176 1/28/98 501 RTA00000200R.k.l l . l M00004197C:F03 9796
5177 2/24/98 502 RTA00000341 F.d.08.1 M00003824C:D07 0
5178 2/24/98 508 RTA00000420F.i.20.1 M00005101 C:E12 0
5179 1/28/98 510 RTAOOOOOl 78AF.n.23.1 M00001387B:E02 3298
5180 1/28/98 51 1 RTAOOOOOl 96AF.g.10.1 M00001376B:A02 12498
5181 2/24/98 519 RTA00000404F.1.10.1 M00001638B:F10 23136
SEQ ID Filing SEQ ID Sequence Name Clone Name Cluster
NO: Date of NO: in ID Priority Priority Appln Appln
5182 2/24/98 524 RTA00000419F.f.23.1 M00003840D:H 10 65002
5183 1/28/98 525 RTA00000198AF.C.7.1 M00001575D:G05 19181
5184 1/28/98 526 RTAOOOOO 185 AF.e.20.1 M00001585A:D06 5865
5185 1/28/98 527 RTAOOOOO 198R.m.23.1 M00001684B:G03 38469
5186 1/28/98 529 RTA00000178AF.b.l 3.1 M00001364A:E1 1 31 14
5187 1/28/98 530 RTAOOOOOl 85 AF.d.24.2 M00001582D:F05 0
5188 1/28/98 540 RTAOOOOOl 79AF.b.10.3 M00001391D:D10 0
5189 1/28/98 541 RTAOOOOO 197AR.b.16.1 M00001445C:A08 0
5190 1/28/98 545 RTAOOOOOl 96F.3.2.1 M00001338B:E02 3575
5191 2/24/98 547 RTA00000419F.h.02.1 M00003845D:G08 63985
5192 1/28/98 548 RTAOOOOOl 79 AF.f.23.3 M00001397B:G03 35258
5193 1/28/98 550 RTAOOOOOl 83AF.g.14.1 M00001513D:A03 0
5194 2/24/98 555 RTA00000133A.d.22.1 M00001469A:G1 1 1 1797
5195 1/28/98 569 RTAOOOOOl 96AF.I.23.1 M00001412A:E04 12052
5196 1/28/98 570 RTA00000183AF.3.19.2 M00001499A:A05 3788
5197 1/28/98 574 RTAOOOOO 192 AF.O.1 M00004146C:C 1 1 5257
5198 1/28/98 575 RTA00000186AF.1.12.2 M00001645A:C 12 19267
5199 1/28/98 576 RTAOOOOO 196AF.C.7.1 M00001350B:G1 I 0
5200 2/24/98 579 RTA00000413F.m. l 6.1 M00004898C:F03 0
5201 1/28/98 580 RTAOOOOO 197F.3.12.1 M00001438B:B09 7895
5202 2/24/98 580 RTA00000403F.O.07.1 M00001579C:A01 39037
5203 2/24/98 584 RTA00000418F.d.22.1 M00001573B:C06 75324
5204 1/28/98 585 RTAOOOOO 198AF.n.18.1 M00001771A:A07 16715
5205 1/28/98 601 RTAOOOOOl 84AF.i.l 0.2 M00001555A:B01 3744
5206 1/28/98 607 RTA00000200AF.k. l2.1 M00004198B:D02 7359
5207 1/28/98 613 RTAOOOOO 177AF. 18.4 M00001352C:A05 53729
5208 1/28/98 640 RTAOOOOOl 90 AF.f.5.1 M00003909A:H04 5015
5209 2/24/98 645 RTA00000422F.p.l2.2 M00001661 C:F10 9840
5210 1/28/98 654 RTAOOOOO 186AF.J.21.2 M00001639D:B07 22506
521 1 1/28/98 680 RTAOOOOOl 77AF.f.10.1 M00001345A:E01 6420
5212 1/28/98 699 RTAOOOOO 178AF.a.12.1 M00001362B:H06 0
5213 1/28/98 703 RTA00000198F.1.09.1 M00001664B:D06 361 1
5214 1/28/98 704 RTAOOOOO 190AF.0.12.1 M00003972D:C09 3438
5215 1/28/98 723 RTAOOOOOl 83 AF.p.24.1 M00001543C:F01 3116
5216 2/24/98 733 RTA00000405F.d. l 8.1 M00001662C:B02 10494
5217 1/28/98 739 RTAOOOOOl 8 lAF.p.12.3 M00001460C:H02 22204
5218 1/28/98 742 RTAOOOOO 177AF.m.1.1 M00001353D:D10 14929
5219 2/24/98 774 RTA00000403F.e.24.1 M00001476B:D10 16432
5220 2/24/98 775 RTA00000405F.C.22.1 M00001660C:B06 39053
5221 2/24/98 790 RTA00000345F.n.08.1 M00001517A:B 1 1 0
5222 2/24/98 816 RTA00000354R.n.04.1 M00003808C:B05 22049
5223 2/24/98 829 RTA0000041 1 F.m. l l . l M00003867A:D12 73196
5224 2/24/98 851 RTA00000423F.d.07.1 M00001678B:B12 0
5225 2/24/98 871 RTA00000403F.f.23.1 M00001479C:E01 39223
5226 2/24/98 877 RTA00000418F.m.22.1 M00001654D:E12 74567
5227 2/24/98 914 RTAOOOOO 138A.m.15.1 M00001624A:A03 41603
5228 2/24/98 923 RTAOOOOO 126A.d.19.1 M00001548A:G01 79474
5229 2/24/98 924 RTA00000354R.m.02.1 M00003890B:C08 12766
5230 2/24/98 940 RTA00000414F.f.l 7.1 M00005260A:F04 0
5231 2/24/98 1005 RTA00000339F.e.l 7.1 M00001397D:G08 7568
SEQ ID Filing SEQ ID Sequence Nβme Clone Nsme Cluster
NO: Dste of NO: in ID Priority Priority Appln Appln
5232 2/24/98 1013 RTA00000404F.b. l 8.1 M00001592A:H05 13669
5233 2/24/98 1037 RTA00000339F.1.12.1 M00001450A:G 1 1 771 1
5234 2/24/98 1055 RTA00000346F.3.04.1 M00001607B:C05 5382
5235 2/24/98 1070 RTA00000346F.n.22.1 M00004137A:D06 0
5236 2/24/98 1096 RTA00000421 F.3.06.1 M00001589C:A1 1 2385
5237 2/24/98 1 125 RTAOOOOOl 18A.H.5.1 M00001451A:C10 0
5238 2/24/98 1 128 RTA00000423F.3.02.3 M00001656B:A08 39210
5239 2/24/98 1 129 RTA00000401 F.m.07.1 M00003907D:F 1 1 2893
5240 2/24/98 1 136 RTA00000406F.C.05.1 M00003870A:H01 22077
5241 2/24/98 1 142 RTA00000418F.i.06.1 M00001591 B:B06 75151
5242 2/24/98 1 145 RTA00000423F.k.21.2 M00003984D:B08 37499
5243 2/24/98 1 149 RTA00000339F.b.02.1 M00001344B:F12 0
5244 2/24/98 1 166 RTA00000347F.h.01.1 M00004040A:G12 12043
5245 2/24/98 1 177 RTAOOOOOl 26A.b.9.1 M00001547A:F1 1 81279
5246 2/24/98 1 187 RTA00000120A.C.19.1 M00001464A:B03 81016
5247 2/24/98 1203 RTA00000413F.e. I 0.1 M00004092C:B03 31033
5248 2/24/98 1205 RTA00000419F.k.05.1 M00003871 C:E04 1 1757
5249 2/24/98 1230 RTA00000399F.J.14.1 M00001578C:F05 16942
5250 2/24/98 1233 RTA00000418F.I.02.1 M00001641 C:C05 39316
5251 2/24/98 1248 RTA00000419F.O.07.1 M00003986C:E09 14059
5252 2/24/98 1261 RTA00000404F.m. l 7.2 M00001643B:E05 0
Table 3 Polynucleotides encoding gene products of a protein family or having a known functional domain(s).
SEQ ID Validation Sequence Biological Start Stop Score Direction
NO: Activity (Profile)
3920 393.ElO.spό: 148957 7tm_l 531 710 9520 for
2667 172.F10.sp6: 133946 7tm_2 45 724 8708 rev
2758 177.C6.sp6:134733 7tm_2 41 697 9828 rev
2933 184.C7.sp6: 135556 7tm_2 3 834 8987 for
3129 121.E12.sp6: 131940 7tm_2 245 1324 9550 rev
3365 172.A7.sp6: 133883 7tm_2 94 761 8743 rev
3418 123.F9.sp6:132333 7tm_2 203 585 8785 rev
3419 123.F9.sp6: 132333 7tm_2 203 585 8785 rev
3597 394.G2.sp6: 149165 7tm_2 73 793 9209 for
3648 370.C5.sp6:141726 7tm_2 76 770 9269 for
3686 370.Bl .sp6:141710 7tm_2 89 662 8791 for
3695 368.A12.sp6:141322 7tm_2 121 719 9015 rev
3696 368.A12.sp6: 141322 7tm_2 121 719 9015 rev
4172 219.C10.sp6:139007 7tm_2 46 774 11394 rev
4216 368.Dl l .sp6: 141357 7tm_2 66 775 9384 rev
4228 368.Al l.sp6:141321 7tm_2 7 1079 9097 for
4441 99.F7.sp6: 131296 7tm_2 534 1265 10956 rev
4442 99.F7.sp6:131296 7tm_2 534 1265 10956 rev
4482 100.D2.sp6:131459 7tm_2 122 1404 9296 rev
4495 395.B12.sp6:149307 7tm_2 79 1432 10427 rev
4525 90.B4.sp6: 130874 7tm_2 4 691 9435 for
4616 100.D5.sp6:131462 7tm_2 655 1349 9255 for
4653 100.D7.sp6:131464 7tm_2 357 1346 11461 rev
4654 100.D7.sp6:131464 7tm_2 357 1346 11461 rev
4658 100.H6.sp6:131511 7tm_2 119 1035 10001 rev
4659 100.G6.sp6:131499 7tm_2 363 1 188 9901 rev
4660 100.F6.sp6: 131487 7tm_2 50 1 127 8799 for
4661 100.F6.sp6:131487 7tm_2 50 1127 8799 for
4710 367.H9.sp6:141210 7tm 2 143 1266 11883 rev
4755 370.F4.sp6:141761 7tm_2 78 704 8942 for
4856 367.Hl l.sp6:141212 7tm_2 176 1227 9975 rev
4885 123.E10.sp6: 132322 7tm_2 210 691 9071 rev
4900 123.ElO.spό: 132322 7tm_2 210 691 9071 rev
4901 123.E10.sp6: 132322 7tm 2 210 691 9071 rev
2656 176.Hl l .sp6: 134606 ANK 207 290 4450 for
2555 180.C9.sp6:135947 asp 156 670 6710 for
3632 368.Hl l.sp6:141405 asp 136 1226 6880 rev
4205 368.B5.sp6:141327 asp 309 806 6073 for
4251 369.D6.sp6: 141546 asp 434 1332 6263 rev
4253 396.F9.sp6: 149544 asp 97 1 106 5999 rev
4261 216.G10.sp6: 139247 asp 74 703 6188 rev
4365 122.H12.sp6:132168 asp 152 1040 6183 rev
4498 80.H6.sp6: 130297 asp 61 418 5944 rev
4664 172.E5.sp6:133929 asp 219 976 6434 for
4718 185.D9.sp6:135762 asp 31 872 5944 rev
4733 185.D9.sp6: 135762 asp 31 872 5944 rev
4746 176.B10.sp6: 134533 asp 253 1446 6079 rev
SEQ ID Validation Sequence Biological Start Stop Score Direction
NO: Activity (Profile) 1
4822 177.F3.sp6: 134766 asp 0 894 6336 rev
4854 184.Fl l .sp6: 135596 asp 61 737 6416 rev
4856 367.Hl l .sp6:141212 asp 81 1187 6182 rev
4929 180.E6.sp6: 135968 asp 81 706 6150 for
4931 180.E6.sp6: 135968 asp 81 706 6150 for
2723 180.F2.sp6: 135976 ATPases 135 627 1 1664 for
2842 217.Hl l.sp6: 139452 ATPases 2 701 5972 for
3019 216.Bl .sp6: 139178 ATPases 170 616 6150 for
3046 121.B8.sp6:131900 ATPases 13 635 5867 rev
3190 80.D2.sp6: 130245 ATPases 13 386 6068 for
3290 176.C6.sp6:134541 ATPases 85 579 5883 for
3670 369.C10.sp6:141538 ATPases 329 730 6206 for
3998 394.H8.sp6: 149183 ATPases 21 571 5954 rev
4119 218.Fl l .sp6: 138852 ATPases 313 816 6057 for
4159 219.A7.sp6:138980 ATPases 88 662 6145 for
4223 368.F9.sp6: 141379 ATPases 178 648 5937 for
4384 181.Gl l.sp6: 135354 ATPases 362 769 5900 rev
4473 369.B4.sp6:141520 ATPases 4 412 14130 for
4540 218.C8.sp6:138813 ATPases 12 576 5782 rev
4560 404.G6.sp6: 162933 ATPases 86 605 6001 rev
4689 367.H8.sp6:141209 ATPases 17 476 5905 rev
4785 184.E5.sp6:135578 ATPases 184 632 5943 for
4792 184.C6.sp6: 135555 ATPases 333 813 5773 for
4847 184.Bl l.sp6: 135548 ATPases 14 498 6140 for
5041 377.Cl.sp6:141918 ATPases 4 655 5933 for
3404 176.F10.sp6:134581 Bcl-2 69 356 16419 for
4036 367.F5.sp6:141182 bromodomain 40 210 8810 for
4489 369.D3.sp6:141543 bromodomain 63 230 10270 for
3408 172.El .sp6:133925 BZIP 146 298 4066 for
3951 393.G5.sp6:148976 BZIP 1 16 304 5931 for
4850 172.E9.sp6:133933 BZIP 91 260 4366 for
3618 370.B12.sp6: 141721 cyclin 1 18 324 8980 for
3895 395.G6.sp6: 149361 cyclin 11 281 6930 for
4536 395.G8.sp6: 149363 cyclin 12 279 5950 for
4455 99.F5.sp6: 131294 Cys-protease 72 348 18479 for
4684 180.Dl .sp6:135951 Cys-protease 38 992 10103 rev
4688 180.Dl .sp6: 135951 Cys-protease 38 992 10103 rev
4801 177.E4.sp6:134755 Cys-protease 48 326 19999 for
4659 100.G6.sp6:131499 DAG_PE_bind 605 702 6290 rev
4821 377.C8.sp6:141925 Dead box helic 172 828 7867 rev
5083 216.Al .sp6:139166 Dead box helic 44 589 26532 for
2734 177.G4.sp6:134779 EFhand 79 153 3780 for
2893 185.Al .sp6:135718 EFhand 287 358 2580 rev
3775 377.A5.sp6:141898 EFhand 477 563 3010 for
4056 367.B7.sp6:141 136 EFhand 225 272 2500 rev
4152 218.B10.sp6:138803 EFhand 40 1 14 2640 rev
4153 218.B10.sp6: 138803 EFhand 40 1 14 2640 rev
4154 218.C10.sp6:138815 EFhand 39 113 2640 rev
4905 393.H12.sp6:148995 EFhand 145 231 4640 for
4943 219.A9.sp6:138982 EFhand 685 750 2550 rev
SEQ ID Validation Sequence Biological Start : Stop Score Direction
NO: Activity (Profile)
2849 218.B5.sp6: 138798 Ets_Nterm 340 531 10400 for
2728 180.A2.sp6:135916 FNtypell 291 423 6400 rev
3018 216.Cl .sp6:139190 FNtypell 501 634 6460 for
4496 218.Gl .sp6: 138854 FNtypell 20 141 6180 rev
4914 393.H8.sp6: 148991 FNtypell 448 576 61 10 for
2504 181.C3.sp6:135298 G-alpha 66 715 8084 rev
3290 176.C6.sp6: 134541 G-alpha 62 690 9062 for
4288 121.B4.sp6:131896 G-alpha 46 447 21415 for
4444 217.D12.sp6:139405 G-alpha 15 702 40404 for
4562 404.B7.sp6: 162874 G-alpha 120 682 8424 for
2503 180.Al l .sp6:135925 helicase C 165 479 4494 for
4469 369.C4.sp6: 141532 helicase C 559 756 3732 rev
5020 185.D12.sp6:135765 helicase C 381 534 5000 for
4241 396.H8.sp6: 149567 homeobox 80 230 5170 for
2550 180.E5.sp6: 135967 mkk 342 612 5791 for
3407 172.Fl.sp6: 133937 mkk 94 669 5688 rev
3451 123.A2.sp6: 132266 mkk 26 378 7889 for
3600 394.B3.sp6: 149106 mkk 32 782 9544 for
3646 370.H4.sp6: 141785 mkk 18 307 9394 for
3680 369.Gl l .sp6:141587 mkk 182 725 5375 for
4175 219.H10.sp6:139067 mkk 280 723 15454 for
4205 368.B5.sp6: 141327 mkk 249 725 5502 for
4278 181.C9.sp6:135304 mkk 168 880 5551 rev
4322 121.F6.sp6:131946 mkk 111 730 5399 for
4777 177.E2.sp6:134753 mkk 288 636 5720 rev
4482 100.D2.sp6:131459 PDEase 849 1 195 5945 for
2578 181.Hl l.sp6:135366 protkinase 116 710 5531 for
2712 177.G7.sp6:134782 protkinase 6 511 5445 for
2835 218.Cl.sp6: 138806 protkinase 127 747 5492 for
2843 218.El .sp6:138830 protkinase 64 726 5592 rev
2971 217.F4.sp6: 139421 protkinase 83 702 5818 rev
3009 217.A4.sp6: 139361 protkinase 57 682 5395 rev
3084 121.E2.sp6:131930 protkinase 69 658 5593 rev
3226 100.D8.sp6:131465 protkinase 174 620 5453 for
3274 100.C3.sp6:131448 protkinase 228 736 5616 for
3356 172.B5.sp6:133893 protkinase 148 715 5381 for
3377 172.B6.sp6:133894 protkinase 119 775 5616 for
3451 123.A2.sp6: 132266 protkinase 24 384 9797 for
3600 394.B3.sp6:149106 protkinase 357 780 11395 for
3635 377.Gl l .sp6:141976 protkinase 117 739 5992 for
3646 370.H4.sp6: 141785 protkinase 24 275 8338 for
3665 370.F2.sp6:141759 protkinase 33 800 5658 for
3669 369.B 10.sp6: 141526 protkinase 1 482 5504 rev
3700 369.D2.sp6: 141542 protkinase 28 661 5428 for
3710 369.G6.sp6:141582 protkinase 71 631 5751 for
3791 396.Cl l .sp6:149510 protkinase 27 709 5793 rev
3905 393.H7.sp6:148990 protkinase 88 680 5470 rev
3919 393.D10.sp6:148945 protkinase 72 594 5617 for
4044 367.G4.sp6: 141 193 protkinase 30 699 5439 for
4072 368.B2.sp6:141324 protkinase 44 800 5556 for
SEQ ID ' Validation Sequence Biological Starl t Stop Score Direction
NO: Activity (Profile)
41 17 218.Dl l .sp6: 138828 protkinase 38 781 6423 for
4175 219.H10.sp6:139067 protkinase 277 717 15720 for
4373 216.E5.sp6: 139218 protkinase 1 15 710 5537 for
4569 100.C10.sp6:131455 protkinase 56 783 5556 rev
4755 370.F4.sp6: 141761 protkinase 39 803 5635 for
4760 370.F3.sp6: 141760 protkinase 188 775 5771 for
4807 184.H3.sp6:135612 protkinase 23 699 5515 for
5059 180.B5.sp6: 135931 protkinase 182 671 5718 rev
5102 393.F4.sp6: 148963 protkinase 28 650 5345 for
3671 369.D10.sp6:141550 ras 12 332 9802 for
3936 393. A3. sp6: 148902 Thioredox 0 263 5887 rev
3927 393.Fl l .sp6: 148970 TNFR_c6 151 261 6445 for
2956 184.E10.sp6:135583 transmembrane4 19 483 8339 rev
2981 217.E6.sp6:139411 transmembrane4 83 728 8417 for
3836 396.C9.sp6: 149508 transmembrane4 300 924 9444 rev
4038 367.A6.sp6: 141123 transmembrane4 32 495 8407 rev
4364 123.Al .sp6:132265 transmembrane4 1289 1548 8114 rev
4406 122.Cl.sp6: 132097 transmembrane4 6 535 8122 for
4431 122.E4.sp6:132124 transmembrane4 10 530 8829 for
4441 99.F7.sp6: 131296 transmembrane4 613 1253 9443 rev
4442 99.F7.sp6: 131296 transmembrane4 613 1253 9443 rev
4653 100.D7.sp6:131464 transmembrane4 335 1207 8255 rev
4654 100.D7.sp6: 131464 transmembrane4 335 1207 8255 rev
4710 367.H9.sp6.T41210 transmembrane4 398 1 130 8352 rev
4944 180.H7.sp6: 136005 transmembrane4 356 983 8356 rev
3381 176.D9.sp6: 134556 trypsin 164 764 9670 rev
4684 180.Dl.sp6:135951 trypsin 371 1229 10479 rev
4688 180.Dl .sp6: 135951 trypsin 371 1229 10479 rev
2754 177.H6.sp6: 134793 WD domain 345 437 6510 for
3046 121.B8.sp6:131900 WD domain 98 193 6400 for
3227 100.B10.sp6:131443 WD domain 544 642 6590 for
4243 121.A8.sp6:131888 WD domain 93 188 6400 for
5046 185.F10.sp6: 135787 WD_domain 382 480 5880 for
3129 121.E12.sp6:131940 Wnt_dev_sign 101 821 12160 rev
3173 99.G6.sp6:131307 Wnt dev sign 49 880 12334 rev
3390 176.C9.sp6: 134544 Wnt_dev_sign 249 854 1 1038 rev
3391 176.C9.sp6: 134544 Wnt_dev_sign 249 854 11038 rev
3656 370.G6.sp6:141775 Wnt_dev_sign 211 785 1 1490 rev
3836 396.C9.sp6: 149508 Wnt_dev_sign 282 1017 12318 rev
4253 396.F9.sp6: 149544 Wnt_dev_sign 482 1298 11217 rev
4330 122.A2.sp6: 132074 Wnt_dev_sign 94 933 12383 rev
4359 123.B2.sp6:132278 Wnt_dev_sign 538 1435 11785 for
4364 123.Al.sp6:132265 Wnt_dev_sign 760 1544 12660 rev
4375 122.G10.sp6: 132154 Wnt_dev_sign 29 884 1 1603 rev
4385 122.A2.sp6: 132074 Wnt_dev_sign 94 933 12383 rev
4409 121.F12.sp6: 131952 Wnt_dev_sign 9 734 11 167 rev
4441 99.F7.sp6: 131296 Wnt_dev_sign 560 1399 13749 rev
4442 99.F7.sp6: 131296 Wnt_dev_sign 560 1399 13749 rev
4535 395.F10.sp6: 149353 Wnt_dev_sign 100 907 1 1535 rev
4586 123.A4.sp6: 132268 Wnt_dey_sign 80 1 122 1 1249 rev
SEQ ID Validation Sequence Biological Start ; Stop Score Direction NO: Activity (Profile)
4605 404.D5.sp6: 162896 Wnt_dev_sign 31 816 11304 rev
4653 100.D7.sp6: 131464 Wnt_dev_sign 467 1314 11882 rev
4654 100.D7.sp6: 131464 Wnt_dev_sign 467 1314 1 1882 rev 4665 177.B l l .sp6: 134726 Wnt_dev_sign 137 1266 12708 rev 4668 177.B l l .sp6: 134726 Wnt_dev_sign 137 1266 12708 rev 4682 177.B l l .sp6: 134726 Wnt_dev_sign 137 1266 12708 rev 4710 367.H9.sp6: 141210 Wnt dev sign 692 1481 12886 rev 4718 185.D9.sp6: 135762 Wnt_dev_sign 129 890 11145 rev 4724 377.D2.sp6: 141931 Wnt_dev_sign 400 1227 1 1044 rev 4733 185.D9.sp6: 135762 Wnt_dev_sign 129 890 11145 rev 4856 367.Hl l .sp6: 141212 Wnt_dev_sign 295 1669 13366 rev 4866 377.D4.sp6: 141933 Wnt_dev_sign 549 1380 14522 rev 4925 219.B12.sp6: 138997 Wnt dev sign 312 1214 13188 rev 4959 219.B12.sp6: 138997 Wnt dev sign 312 1214 13188 rev 3409 172.Dl.sp6: 133913 Y_phosphatase 476 804 6932 for
3418 123.F9.sp6:132333 Y_phosphatase 28 439 6096 rev
3419 123.F9.sp6: 132333 Y_phosphatase 28 439 6096 rev 3657 370.H6.sp6:141787 Y_phosphatase 148 554 6481 for 3804 404.B10.sp6:162877 Y_phosphatase 104 466 6446 rev 3806 404.D10.sp6: 162901 Y_phosphatase 9 614 6516 for 3974 395.F2.sp6: 149345 Y_phosphatase 164 645 6093 rev 4238 121.E9.sp6:131937 Y_phosphatase 240 777 6147 rev 4263 216.F10.sp6: 139235 Y_phosphatase 21 504 6342 for 4343 122.E9.sp6:132129 Y_phosphatase 381 807 6036 rev 4363 123.Bl.sp6:132277 Y_phosphatase 61 510 6229 rev 4434 219.F4.sp6:139037 Y_phosphatase 2 261 10353 for 4473 369.B4.sp6:141520 Y_phosphatase 231 768 6110 rev 4629 404.Ell.sp6:162914 Y_phosphatase 580 920 6005 rev 5094 217.A3.sp6:139360 Y_phosphatase 263 622 6222 rev 2738 177.A6.sp6: 134709 Zincfιng_C2H2 65 127 4380 for 2760 177.A6.sp6: 134709 Zincfing_C2H2 65 127 4380 for 2832 218.B2.sp6:138795 Zincfmg C2H2 94 156 4940 for 3736 377.H8.sp6: 141985 Zincfmg_C2H2 495 557 4850 for
3762 377.G2.sp6: 141967 Zincfmg_C2H2 52 1 14 4380 for
3763 377.G2.sp6: 141967 Zincfing_C2H2 52 1 14 4380 for 4794 377.G4.sp6: 141969 Zincfϊng_C2H2 247 308 3930 for 5090 185.C4.sp6: 135745 Zincfing_C2H2 238 300 4540 for 3774 377.E4.sp6:141945 Zincfing_C3HC4 128 244 9335 for 4477 18l.E3.sp6:135322 Zincfmg C3HC4 321 445 8221 for
Table 19. Polynucleotides Specifically Expressed in Colon
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 lib 20
ID clones clones clones clones clones clones clones clones
NO:
3 RTAOOOOO 197 AF.e.24.1 39250 2 0 0 0 0 0 0 0
7 RTAOOOOO 197AR.e.12.1 22095 3 0 0 0 0 0 0 0
16 RTAOOOOO 196AF.e.16.1 39252 2 0 0 0 0 0 0 0
18 RTAOOOOO 196AF.C.17.1 39602 2 0 0 0 0 0 0 0
21 RTA00000131A.g.l9.2 36535 2 0 0 0 0 0 0 0
22 RTAOOOOO 187AR.0.10.2 8984 4 3 0 0 0 2 0 0
23 RTAOOOOO 198R.b.08.1 22636 3 0 0 0 0 0 0 0
26 RTA00000200R.g.09.1 22785 3 0 0 0 0 0 0 0
29 RTA00000200AF.b.l9.1 22847 3 0 0 0 0 0 0 0
31 RTA00000200F.m.l5.1 22601 3 0 0 0 1 0 0 0
37 RTA00000181AF.n.l5.2 86128 1 0 0 0 0 0 0 0
38 RTAOOOOO 196R.k.07.1 22443 2 0 0 0 0 0 0 1
40 RTA00000200AR.e.02.1 36059 2 0 0 0 1 1 1 0
48 RTAOOOOOl 77 AR.a.23.5 6995 4 2 0 0 0 0 0 0
49 RTAOOOOO 198R.O.05.1 26702 2 0 0 0 0 0 0 0
50 RTA00000201R.a.02.1 35362 2 0 0 0 0 0 0 0
61 RTAOOOOO 197AF. 1 1.1 22264 3 0 0 0 0 0 0 0
66 RTAOOOOO 199F.C.09.2 16824 3 1 0 0 0 0 0 0
75 RTAOOOOO 180AR. 19.2 84182 1 0 0 0 0 0 0 0
78 RTAOOOOO 199RT.09.1 22907 3 0 0 0 0 0 0 0
79 RTAOOOOO 199AF.p.4.1 10282 3 3 0 0 0 0 0 0
85 RTA00000200R.O.03.1 22807 3 0 0 0 0 0 0 0
86 RTAOOOOO 189AF.1.22.1 33333 1 1 0 0 0 0 0 0
87 RTAOOOOO 195 AF.d.20.1 37574 2 0 0 0 0 0 0 0
92 RTAOOOOO 198AF.J.18.1 22759 3 0 0 0 0 0 0 0
95 RTAOOOOO 180AF.g.3.1 9024 5 2 0 0 0 0 0 0
102 RTAOOOOO 199R.J.08.1 37844 2 0 0 0 0 0 0 0
103 RTAOOOOO 199F.e.10.1 22906 3 0 0 0 0 0 1 0
105 RTAOOOOO 179AF.g.12.3 36390 2 0 0 0 0 0 0 0
108 RTAOOOOO 183 AR.h.23.2 18957 3 0 0 0 0 0 0 0
109 RTAOOOOO 197 AF.d.12.1 39546 2 0 0 0 0 0 0 0
116 RTAOOOOOl 81 AR.k.24.3 7005 8 2 0 0 0 0 0 0
1 19 RTAOOOOOl 81 AR.k.24.2 7005 8 2 0 0 0 0 0 0
124 RTAOOOOO 199AR.m.06.1 1 199112222 3 0 0 0 0 0 0 0
129 RTAOOOOO 134A.d.10.1 18957 3 0 0 0 0 0 0 0
137 RTAOOOOOl 81 AF.m.4.3 13238 4 1 0 0 0 0 0 0
141 RTAOOOOO 196AF.C.6.1 23148 3 0 0 0 0 0 0 0
142 RTAOOOOO 198AF. 19.1 75879 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib 1 lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 Iii
ID clones clones clones clones clones clones clones cl
NO:
143 RTAOOOOO 199R.h.09.1 76020 1 0 0 0 0 0 0 0
144 RTAOOOOO 198AF.0.18.1 13018 4 0 0 0 1 0 0 0
148 RTAOOOOO 199F.h.17.2 36254 2 0 0 0 0 0 0 0
149 RTAOOOOOl 81 AR.h.06.3 87226 1 0 0 0 0 0 0 0
166 RTAOOOOO 198AF.f.21.1 22676 3 0 0 0 0 0 0 0
173 RTA00000200AR.b.07.1 17125 4 0 0 0 0 0 0 0
178 RTA00000200F.O.03.1 22807 3 0 0 0 0 0 0 0
180 RTA00000199AF.J.12.1 22461 3 0 0 0 0 0 0 0
185 RTAOOOOOl 95 AF.d.4.1 22766 3 0 0 0 0 0 0 0
194 RTA00000200R.k.01.1 40049 2 0 0 0 0 0 0 0
195 RTAOOOOO 198AF.C.10.1 77149 1 0 0 0 0 0 0 0
198 RTAOOOOO 197AR.e.07.1 86969 1 0 0 0 0 0 0 0
199 RTAOOOOO 199R.C.09.1 16824 3 1 0 0 0 0 0 0
206 RTA00000181AF.O.04.2 22205 3 0 0 0 0 0 0 0
207 RTAOOOOO 199AF.1.19.1 22460 3 0 0 0 0 0 0 0
208 RTAOOOOO 198AF.h.22.1 22366 2 1 0 0 0 0 0 0
211 RTAOOOOO 199 AF.m.15.1 10101 3 0 0 0 0 0 0 0
212 RTA00000197AF.J.9.1 13236 4 1 0 0 0 0 0 0
230 RTAOOOOO 185AR.b.18.1 12171 3 2 0 0 0 0 0 0
235 RTA00000201AF.a.02.1 35362 2 0 0 0 0 0 0 0
236 RTAOOOOO 183 AR.h.23.1 18957 3 0 0 0 0 0 0 0
238 RTAOOOOO 187AR.k.12.1 78415 1 0 0 0 0 0 0 0
242 RTA00000198AF.m.l7.1 77992 1 0 0 0 0 0 0 0
243 RTA00000181AF.m.l5.3 12081 4 0 0 0 0 0 0 0
248 RTAOOOOO 198R.C.14.1 39814 2 0 0 0 0 0 0 0
249 RTA00000200R.O.03.2 22807 3 0 0 0 0 0 0 0
251 RTA00000192AF.n.l3.1 8210 2 6 0 0 0 0 0 0
256 RTAOOOOO 184AR.e.15.1 16347 4 0 0 0 0 0 0 0
260 RTAOOOOO 198R.m.17.1 77992 1 0 0 0 0 0 0 0
270 RTA00000178R.1.08.1 39648 2 0 0 0 0 0 0 0
278 RTAOOOOO 198AF.p.16.1 71877 1 0 0 0 0 0 0 0
280 RTA00000193AF.b.l 8.1 7542 8 0 0 2 1 0 1 0
284 RTA00000199F.d.l0.2 22049 3 0 0 0 0 0 0 0
287 RTA00000200AF.b.07.1 17125 4 0 0 0 0 0 0 0
288 RTAOOOOOl 81 AR.i.06.3 19119 3 0 0 0 0 0 0 0
289 RTAOOOOOl 96F. 07.1 22443 2 0 0 0 0 0 0 1
294 RTAOOOOO 198AF. 23.1 8995 2 5 0 0 0 0 0 0
296 RTAOOOOO 196AFT.20.1 22774 3 0 0 0 0 0 0 0
300 RTAOOOOO 195AF.C.12.1 37582 2 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI
ID clones clones clones clones clones clones clones cl
NO:
302 RTAOOOOOl 86AF.d.1.2 40044 2 0 0 1 0 0 0 0
307 RTA00000200F.n.05.2 18989 3 0 0 0 0 0 0 0
308 RTAOOOOO 178 AF.j .20.1 15066 4 0 0 0 0 0 0 0
310 RTAOOOOO 188AF.m.08.1 22155 3 0 0 0 0 0 0 0
315 RTAOOOOO 199R.d.23.1 37477 2 0 0 0 0 0 0 0
319 RTA00000200F.n.05.1 18989 3 0 0 0 0 0 0 0
320 RTAOOOOO 196AF.m.13.1 16290 4 0 0 0 0 0 0 0
325 RTAOOOOO 182AF.d.18.4 37435 2 0 0 0 0 0 0 0
328 RTA00000200AF.g.09.1 22785 3 0 0 0 0 0 0 0
330 RTAOOOOO 177AR.m.17.4 14391 3 1 0 0 0 0 0 0
331 RTAOOOOO 197AR.C.20.1 16282 4 0 0 0 0 0 0 0
337 RTAOOOOO 177AR.m.17.3 14391 3 1 0 0 0 0 0 0
342 RTAOOOOO 196AF.d.10.1 22256 3 0 0 0 0 0 0 0
343 RTA00000201F.a.l8.1 16837 2 2 0 0 0 0 0 0
344 RTAOOOOOl 98 AF.o.02.1 68756 1 0 0 0 0 0 0 0
345 RTAOOOOO 187AF.h.21.1 39171 2 0 0 0 0 0 0 0
347 RTAOOOOO 199F.b.03.2 38340 2 0 0 0 0 0 0 0
358 RTAOOOOOl 98 AF.g.7.1 13386 3 2 0 0 0 0 0 0
362 RTAOOOOO 197AR.C.24.1 82498 1 0 0 0 0 0 0 0
371 RTAOOOOO 197F.e.7.1 86969 1 0 0 0 0 0 0 0
378 RTAOOOOOl 8 lAF.k.24.3 7005 8 2 0 0 0 0 0 0
382 RTA00000200AF.J.6.1 22902 3 0 0 0 0 0 0 0
384 RTAOOOOO 196AF.h.17.1 39215 2 0 0 0 0 0 0 0
392 RTAOOOOO 185AF.D.11.2 9024 5 2 0 0 0 0 0 0
397 RTAOOOOO 198AF.b.22.1 38956 2 0 0 0 0 0 0 0
399 RTAOOOOO 186AF.IΗ.15.2 40122 2 0 0 0 0 0 0 0
406 RTAOOOOO 199FT.09.2 22907 3 0 0 0 0 0 0 0
408 RTAOOOOO 183AR.1.15.1 39383 2 0 0 0 0 0 0 0
413 RTA00000200F.a.l2.1 16751 4 0 0 0 0 0 0 0
416 RTAOOOOO 199F.a.5.1 22134 3 0 0 0 0 0 0 0
418 RTAOOOOO 187AR. 01.1 78356 1 0 0 0 0 0 0 0
424 RTAOOOOO 187AR.J.24.1 78356 1 0 0 0 0 0 0 0 426 RTAOOOOO 199AF.0.19.1 36927 2 0 0 0 0 0 0 0
429 RTAOOOOO 196F.Ϊ.19.1 39498 2 0 0 0 0 0 0 0
430 RTAOOOOO 198R. 23.1 8995 2 5 0 0 0 0 0 0
432 RTA00000198AF.O.05.1 26702 2 0 0 0 0 0 0 0
433 RTAOOOOO 198RJ.18.1 22759 3 0 0 0 0 0 0 0 435 RTAOOOOO 182AR.C.22.1 16283 3 0 0 0 0 0 0 0
438 RTAOOOOO 180AR.g.03.4 9024 5 2 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 lib 20
ID clones clones clones clones clones clones clones clones
NO:
451 RTA00000200AF.b.20.1 40403 0 0 0 0 0 0 0
455 RTAOOOOO 198AF.d.12.1 21142 1 0 0 0 0 0 0
456 RTA00000200AF.b.l2.1 22053 0 0 0 0 0 0 0
457 RTA00000191AR.1.7.2 14391 1 0 0 0 0 0 0
461 RTA00000190AF.e.l3.1 38961 0 0 0 0 0 0 0
462 RTAOOOOO 196AF.n.17.1 12477 1 0 0 0 0 0 0 467 RTAOOOOO 195AF.b.19.1 77678 1 0 0 0 0 0 0 0
475 RTAOOOOO 187AR.m.3.3 17055 4 0 0 0 0 0 0 0
476 RTA00000200R.g.l5.1 22898 0 0 0 0 0 0 0 482 RTAOOOOO 187AF.J.7.1 78091 0 0 0 0 0 0 0
485 RTAOOOOO 196AF.C.14.1 23105 0 0 0 0 0 0 0
486 RTAOOOOO 190AR.p.22.2 16368 0 0 0 0 0 0 0
492 RTAOOOOO 198AF.D.8.1 22636 0 0 0 0 0 0 0
493 RTAOOOOO 177AF.m.17.1 14391 1 0 0 0 0 0 0
494 RTA0000O200AF.k.l.l 40049 0 0 0 0 0 0 0
498 RTAOOOOO 190AF.h.12.1 12977 0 0 0 0 0 0 0
499 RTAOOOOO 199F.b.22.2 17018 0 0 0 0 0 0 0 508 RTAOOOOO 187AFX 14.2 19406 1 0 0 0 0 0 0 511 RTAOOOOO 196AF.g.10.1 12498 1 1 0 0 0 0 0 517 RTA00000184AF.e.l4.1 16347 0 0 0 0 0 0 0 522 RTAOOOOO 178AR. 17.2 23824 1 0 0 0 0 0 0 531 RTAOOOOO 195F.a.3.1 27179 0 0 0 0 0 0 0 544 RTA00000196F.J.13.1 23170 0 0 0 0 0 0 0 547 RTAOOOOO 196AF.g.8.1 39665 0 0 0 0 0 0 0 549 RTAOOOOO 198AF.C.16.1 26801 0 0 0 0 0 0 0 553 RTA00000201F.b.22.1 35728 0 0 0 0 0 0 1 559 RTAOOOOOl 97 AF.p.20.1 22795 0 0 0 0 0 0 0 563 RTAOOOOO 192AR.0.16.2 9061 2 0 0 0 0 0 0 565 RTA00000191AF.C.10.1 40422 0 0 0 0 0 0 0 568 RTAOOOOO 196AF.p.01.2 87143 0 0 0 0 0 0 0 578 RTAOOOOO 180AF.g.17.1 16653 1 0 0 0 0 0 0 583 RTAOOOOO 190AR.h.12.2 12977 0 0 0 0 0 0 0
585 RTAOOOOO 198AF.n.18.1 16715 1 0 0 0 0 0 0
586 RTAOOOOO 199R.0.11.1 23172 0 0 0 0 0 0 0
588 RTA00000191AF.b.4.1 14936 0 0 0 0 0 0 0
589 RTAOOOOO 192AF.1.1.1 16392 0 0 0 0 0 0 0 593 RTAOOOOO 196R.C.14.2 23105 0 0 0 0 0 0 0 595 RTAOOOOOl 95R.a.06.1 35265 0 1 0 0 0 0 0 602 RTAOOOOO 195 AF.b.21.1 39055 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib 1 lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 lit
ID clones clones clones clones clones clones clones cl
NO:
612 RTAOOOOO 197AR.e.22.1 78758 1 0 0 0 0 0 0 0
615 RTAOOOOO 197R.p.20.1 22795 3 0 0 0 0 0 0 0
618 RTAOOOOO 192AF.a.14.1 6874 6 3 0 0 1 0 0 0
623 RTAOOOOO 198R.b.24.1 19047 3 0 0 0 0 0 0 0
627 RTAOOOOO 199F.h.15.2 22269 3 0 0 0 0 0 0 0
628 RTAOOOOO 198AF.g.16.1 6602 1 1 0 0 0 0 0 0
634 RTAOOOOO 192AF.J.6.1 1 1494 4 0 0 0 0 0 0 0
635 RTAOOOOOl 8 lAF.p.7.3 38773 2 0 0 0 0 0 0 0
637 RTA00000200AF.g.l 5.1 22898 3 0 0 0 0 0 0 0
643 RTAOOOOO 184AF.C.9.1 16245 4 0 0 0 0 0 0 0
645 RTAOOOOO 177AF. 9.1 16245 4 0 0 0 0 0 0 0
649 RTAOOOOO 190AR.1.19.2 88204 1 0 0 0 0 0 0 0
662 RTA00000201R.a.l5.1 57347 1 0 0 0 0 0 0 0
664 RTA00000195R.a.23.1 86432 1 0 0 0 0 0 0 0
670 RTAOOOOO 186AF.p.17.3 38383 2 0 0 0 0 0 0 0
674 RTAOOOOO 197AR.e.24.1 39250 2 0 0 0 0 0 0 0
683 RTAOOOOO 187 AR.j.01.1 79028 1 0 0 0 0 0 0 0
686 RTA00000201F.f.07.1 511 16 1 0 0 0 0 0 0 0
694 RTA00000201R.C.19.1 22357 2 1 0 0 0 0 0 0
702 RTAOOOOO 177AR.b.8.5 17062 3 0 0 0 0 0 0 0
712 RTA00000201F.b.21.1 9071 3 4 0 0 0 0 0 0
717 RTA00000200F.O.10.2 36432 2 0 0 0 0 0 0 0
718 RTAOOOOO 196F.1.14.2 23144 3 0 0 0 0 0 0 0
725 RTAOOOOOl 97 AF.b.1.1 12134 1 1 0 0 0 0 0 0
733 RTA00000200AF.d.20.1 26600 2 0 0 0 0 0 0 0
743 RTAOOOOOl 78 AF.k.9.1 16342 3 0 0 0 0 0 0 0
748 RTAOOOOO 198 AF.b.24.1 19047 3 0 0 0 0 0 0 0
757 RTA00000406F.d.l6.1 15040 2 2 0 0 0 0 0 0
760 RTA00000408F.O.12.2 78578 1 0 0 0 0 0 0 0
761 RTAOOOOOl 19AJ.15.1 79623 1 0 0 0 0 0 0 0
762 RTA00000413F.d.l2.1 66467 1 0 0 0 0 0 0 0
763 RTA00000423F112.1 91 18 4 3 0 0 0 0 0 0
766 RTA00000411F.k.05.1 64777 1 0 0 0 0 0 0 0
769 RTA00000419F.b.09.1 78128 1 0 0 0 0 0 0 0
772 RTA0000041 1F.m. l5.1 78014 1 0 0 0 0 0 0 0
774 RTAOOOOO 123 A.k.23.1 80313 1 0 0 0 0 0 0 0
777 RTA00000130A.m.l5.1 81630 1 0 0 0 0 0 0 0
778 RTA0000041 1F.k.20.1 64973 1 0 0 0 0 0 0 0
780 RTA00000418F.k.05.1 73021 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI
ID clones clones clones clones clones clones clones cl
NO:
781 RTA00000423F.h.l8.1 37972 2 0 0 0 0 0 0 0
783 RTA00000422F.p.06.2 39282 2 0 0 0 0 0 0 0
784 RTA00000404F.n.l 6.2 39095 2 0 0 0 0 0 0 0
785 RTA00000411F.m.24.1 77568 1 0 0 0 0 0 0 0
786 RTA00000134A.J.10.1 81383 1 0 0 0 0 0 0 0
787 RTA00000409F.J.02.1 76417 1 0 0 0 0 0 0 0
788 RTA00000403F .15.1 23840 2 1 0 0 0 0 0 0
789 RTA00000411F.H.11.1 77276 1 0 0 0 0 0 0 0
790 RTA00000339F.Ϊ.13.1 5970 6 4 0 0 0 0 0 0
792 RTA00000406F.O.15.1 37482 2 0 0 0 0 0 0 0
793 RTA00000412F.g.04.2 64457 1 0 0 0 0 0 0 0
795 RTA00000352R.1.06.1 40343 2 0 0 0 0 0 0 0
796 RTA00000419F.b.l2.1 63148 1 0 0 0 0 0 0 0
797 RTA00000423F.k.l 7.2 37512 2 0 0 0 0 0 0 0
799 RTA00000418F.k.l4.1 76133 1 0 0 0 0 1 0 0
800 RTA00000409F.1.12.1 26755 1 0 0 0 0 0 0 0
801 RTA00000404F.C.20.1 39088 2 0 0 0 0 0 1 0
802 RTA00000423F.g.09.1 38958 2 0 0 0 0 0 0 0
804 RTA00000406F.d.l2.1 38575 2 0 0 0 0 0 0 0
805 RTA00000411F.f.02.1 63386 1 0 0 0 0 0 0 0
806 RTAOOOOO 129A.n.21.1 79381 1 0 0 0 0 0 0 0
807 RTA00000409F.m.l2.1 73490 1 0 0 0 0 0 0 0
808 RTA00000410F.C.04.1 74099 1 0 0 0 0 0 0 0
810 RTA00000406F.m.09.1 26891 2 0 0 0 0 0 0 0
81 1 RTA0000041 1F.b.06.1 77884 1 0 0 0 0 0 0 0
812 RTA00000409F.1.21.1 73143 1 0 0 0 0 0 0 0
818 RTA00000404F.1.20.2 38638 2 0 0 0 0 0 0 0
819 RTA00000413F.d.l8.1 65305 1 0 0 0 0 0 0 0
820 RTA00000404F.p.04.2 39069 2 0 0 0 0 0 0 0
821 RTA00000405F.g.l9.2 37150 2 0 0 0 0 0 0 0
822 RTA00000409F.a.22.1 75200 1 0 0 0 0 0 0 0
824 RTA00000405F.O.18.1 11016 4 2 0 0 0 0 0 0
829 RTA00000408F.e.22.2 26930 1 0 0 0 0 0 0 0
831 RTA00000413F.d.l6.1 63331 1 0 0 0 0 0 0 0
834 RTA00000419F.g.08.1 66700 1 0 0 0 0 0 0 0
835 RTA00000122A.g. l6.1 81366 1 0 0 0 0 0 0 0
836 RTA00000419F.C.16.1 65254 1 0 0 0 0 0 0 0
837 RTA0000041 1F.b.03.1 23634 1 2 0 0 0 0 0 0
842 RTA00000403F.1.20.1 18267 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl 845 RTA0000041 1 F.a.02.1 78537 1 0 0 0 0 0 0 0
847 RTA00000412F.1.04.1 66372 1 0 0 0 0 0 0 0
849 RTA00000406F.a.23.1 38712 2 0 0 0 0 0 0 0
851 RTAOOOOO 120A.n.19.3 80004 1 0 0 0 0 0 0 0
852 RTA00000403F.e.01.1 38965 2 0 0 0 0 0 0 0
853 RTA00000411F.1.03.1 62702 1 0 0 0 0 0 0 0
856 RTAOOOOOl 21 A.m.2.1 81064 1 0 0 0 0 0 0 0
858 RTA00000418F.J.12.1 73316 1 0 0 0 0 ' 0 0 0
862 RTAOOOOO 125A.g.16.1 21497 2 1 0 0 0 0 0 0
863 RTA00000418F.O.18.1 78676 1 0 0 0 0 0 0 0
865 RTA00000408F. 14.1 73856 1 0 0 0 0 0 0 0
871 RTA00000403F.O.15.1 39140 2 0 0 0 0 0 0 0
872 RTA00000341F.m.l3.1 26502 1 0 0 0 0 0 0 0
873 RTA00000408F.h.03.1 78382 1 0 0 0 0 0 0 0
874 RTA00000423F.k.05.1 37472 2 0 0 0 0 0 0 0
876 RTA00000418F.p. l9.1 78544 1 0 0 0 0 0 0 0
877 RTA00000420F.f.06.1 64812 1 0 0 0 0 0 0 0
878 RTAOOOOO 122A.J.18.1 81317 1 0 0 0 0 0 0 0
879 RTA00000420F.d.05.1 64432 1 0 0 0 0 0 0 0
880 RTA00000403F.m. l8.1 39185 2 0 0 0 0 0 0 0
882 RTA00000411F.J.05.1 40709 1 1 0 0 0 0 0 0
883 RTA00000403F.a.04.1 23529 2 1 0 0 0 0 0 0
885 RTA00000406F.f.l2.1 21895 2 1 0 0 0 0 0 0
886 RTA00000418F.g.22.1 74837 1 0 0 0 0 0 0 0
888 RTA00000404F.1.20.1 38638 2 0 0 0 0 0 0 0
889 RTA00000408F.L08.2 75811 1 0 0 0 0 0 0 0
890 RTAOOOOO 122A.d.5.1 81 155 1 0 0 0 0 0 0 0
894 RTA00000419F.b.l9.1 65534 1 0 0 0 0 0 0 0
896 RTA00000418F. 19.1 74932 1 0 0 0 0 0 0 0
900 RTA00000419F.g.l2.1 66171 1 0 0 0 0 0 0 0
901 RTA00000404F.n. l l.2 38001 2 0 0 0 0 0 0 0
904 RTA00000419F.O.24.1 65092 1 0 0 0 0 0 0 0
905 RTA00000419F.k. l9.1 75447 1 0 0 0 0 0 0 0
907 RTAOOOOO 127A.i.20.1 81418 1 0 0 0 0 0 0 0
908 RTA00000422F.g.22.1 22561 3 0 0 0 0 0 0 0
910 RTA00000413F.h. l3.1 65190 1 0 0 0 0 0 0 0
913 RTA00000348R.J.16.1 7005 8 2 0 0 0 0 0 0
916 RTA00000418F.n.22.1 79062 1 0 0 0 0 0 0 0
917 RTA00000406F.1.08.1 39016 2 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl
X INl/UV.
920 RTA00000409F.J.07.1 75190 1 0 0 0 0 0 0 0
923 RTA0000041 1F.e.22.1 63638 1 0 0 0 0 0 0 0
924 RTA00000347F.a.l7.1 16723 3 1 0 0 0 0 0 0
926 RTA00000404F.n.20.1 26865 2 0 0 0 0 0 0 0
929 RTA00000404F.b.02.1 38984 2 0 0 0 0 0 0 0
931 RTA00000403F.b.l0.1 73268 1 0 0 0 0 0 0 0
932 RTA00000406F.U2.1 39080 2 0 0 0 0 0 0 0
933 RTA00000406F.h.08.1 16228 2 2 0 0 0 0 0 0
934 RTA00000418F.L19.1 79180 1 0 0 0 0 0 0 0
936 RTA00000412F.h.21.1 64348 1 0 0 0 0 0 0 0
938 RTAOOOOO 120A.g.18.1 81255 1 0 0 0 0 0 0 0
940 RTA00000423FJ.05.1 37958 2 0 0 0 0 0 0 0
941 RTAOOOOO 132A. 6.1 81284 1 0 0 0 0 0 0 0
943 RTA00000406F.p.04.1 37458 2 0 0 0 0 0 0 0
944 RTA00000347F.a.l3.1 22446 3 0 0 0 0 0 0 0
945 RTA00000419F.p.23.1 64748 1 0 0 0 0 0 0 0
946 RTA00000419F.d.l7.1 64353 1 0 0 0 0 0 0 0
949 RTAOOOOO 124A.k.5.1 80252 1 0 0 0 0 0 0 0
950 RTA00000404F.h.22.1 18735 2 1 0 0 0 0 1 0
952 RTA00000410F.O.05.1 75262 1 0 0 0 0 0 0 0
953 RTA00000339R.1.14.1 19119 3 0 0 0 0 0 0 0
954 RTA00000403F.m.l3.2 39077 2 0 0 0 0 0 0 0
957 RTA00000419F.g.22.1 64515 1 0 0 0 0 0 0 0
958 RTA00000404F.g.21.1 37947 2 0 0 0 0 0 0 0
960 RTA00000138A.n.4.1 21920 2 1 0 0 0 0 0 0
961 RTA00000410F.b.l5.1 77100 1 0 0 0 0 0 0 0
963 RTA00000419F.J.23.1 74470 1 0 0 0 0 0 0 0
964 RTA0000041 1FJ.02.1 65310 1 0 0 0 0 0 0 0
965 RTA00000419F.p.24.1 63477 1 0 0 0 0 0 0 0
966 RTA00000404F.a.l9.1 38624 2 0 0 0 0 0 0 0
973 RTA00000346F.e.l3.1 74653 1 0 0 0 0 0 0 0
974 RTA00000419F.C.18.1 41394 1 1 0 0 0 0 0 0
978 RTA00000404F.e.22.1 1 1344 3 3 0 0 0 0 0 0
981 RTA00000125A.k. l0.1 81644 1 0 0 0 0 0 0 0
982 RTA00000347F.C.06.1 18846 2 1 0 0 0 0 0 0
983 RTA0000041 1F.k.l9.1 64200 1 0 0 0 0 0 0 0
984 RTA00000345F.Ϊ.09.1 27250 2 0 0 0 0 0 0 0
985 RTA00000423F.k.01.1 40426 2 0 0 0 0 0 0 0
986 RTA00000408F.d.06.1 78997 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI
ID clones clones clones clones clones clones clones cl X INTUV.
987 RTAOOOOO 128A.b.20.1 79761 1 0 0 0 0 0 0 0
989 RTAOOOOOl 95 AF.d.4.1 22766 3 0 0 0 0 0 0 0
991 RTA00000403F.h. l2.1 15205 2 1 0 0 0 0 0 0
992 RTAOOOOOl 19A.J.22.1 80336 1 0 0 0 0 0 0 0
995 RTAOOOOO 126A.n.7.2 79557 1 0 0 1 0 0 0 0
997 RTA00000404FJ.08.1 39066 2 0 0 0 0 0 0 0
998 RTA00000410F.C.14.1 77809 1 0 0 0 0 0 0 0
999 RTAOOOOO 120A.g.23.1 81 189 1 0 0 0 0 0 0 0
1000 RTAOOOOO 195 AF.d.20.1 37574 2 0 0 0 0 0 0 0
1002 RTA00000412F.J.17.1 64071 1 0 0 0 0 0 0 0
1004 RTAOOOOOl 19A.J.10.1 79646 1 0 0 0 0 0 0 0
1010 RTA00000419F.O.16.1 62867 1 0 0 0 0 0 0 0
1012 RTA00000411F.C.17.1 77664 1 0 0 0 0 0 0 0
1013 RTA00000406F. 15.1 38549 2 0 0 0 0 0 0 0
1014 RTA00000406F.a.02.1 37744 2 0 0 0 0 0 0 0
1016 RTA00000341F.b.06.1 17008 4 0 0 0 0 0 0 0
1017 RTA00000409F.n.l4.1 78190 1 0 0 0 0 0 0 0
1019 RTA00000345FJ.08.1 16731 3 1 0 0 0 0 0 0
1021 RTA00000419F.g.l5.1 32519 1 1 0 0 0 0 0 0
1022 RTA00000423F.3.19.1 21396 1 2 0 0 0 0 0 0
1024 RTA00000422F.e.08.1 39020 2 0 0 0 0 0 0 0
1025 RTA00000411F.d.l5.1 74890 1 0 0 0 0 0 0 0
1027 RTA00000411F.1.15.1 66704 1 0 0 0 0 0 0 0
1029 RTA00000405F.e.08.1 37916 2 0 0 0 1 0 0 0
1030 RTA00000353R .24.1 23089 3 0 0 0 0 0 0 0
1032 RTA00000418F.O.06.1 75930 1 0 0 0 0 0 0 0
1033 RTA00000404F.C.10.1 23534 2 1 0 0 0 0 0 0
1034 RTA00000418F.i.21.1 78728 1 0 0 0 0 0 0 0
1036 RTA00000411F.1.13.1 43114 1 1 0 0 0 0 0 0
1037 RTA00000407F.a.24.1 37560 2 0 0 0 0 0 0 0
1038 RTA00000346F.n.06.1 12439 4 0 0 0 0 0 0 0
1039 RTA00000412F.1.21.1 65183 1 0 0 0 0 0 0 0
1040 RTA00000413F.i.02.1 65857 1 0 0 0 0 0 0 0
1041 RTA00000404F.i. l9.1 38698 2 0 0 0 0 0 0 0
1043 RTA00000403F.a.l l .l 73109 1 0 0 0 0 0 0 0
1045 RTA0000041 1F.k. l6.1 64759 1 0 0 0 0 0 1 0
1046 RTA00000405F.C.01.1 19236 2 0 0 0 0 0 0 0
1047 RTA00000423F.i.l8.1 14996 4 0 0 0 0 0 0 0
1050 RTA00000406F.a.07.1 26607 2 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib 1 lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl NO: 1051 RTA00000347F.d.06.1 39122 2 0 0 0 0 0 0 0
1052 RTA00000419F.b.l 8.1 67034 1 0 0 0 0 0 0 0
1053 RTA00000406F.h.07.1 38003 2 0 0 0 0 0 0 0
1054 RTA00000405F.1.15.1 19575 2 1 0 0 0 0 0 0
1055 RTA00000406F.g.l7.1 37979 2 0 0 0 0 0 0 0
1058 RTAOOOOO 130A.h.22.1 80933 1 0 0 0 0 0 0 0
1061 RTA00000404F.d.l3.1 39036 2 0 0 0 0 0 0 0
1064 RTA00000340F.n.01.1 39081 2 0 0 0 0 0 0 0
1065 RTA00000419F.d.06.1 65496 1 0 0 0 0 0 0 0
1066 RTA00000419F.n.09.1 66070 1 0 0 0 0 0 0 0
1067 RTA00000399F.i.08.1 38927 2 0 0 0 0 0 0 0
1069 RTA00000423F.g.l3.1 38028 2 0 0 0 0 0 0 0
1072 RTAOOOOO 195 AF.b.21.1 39055 2 0 0 0 0 0 0 0
1073 RTA00000403F.h.05.1 39096 2 0 0 0 0 0 0 0
1075 RTA00000422F.p.07.2 39024 2 0 0 1 0 0 0 0
1078 RTA00000421F.n.l9.1 16409 3 1 0 0 0 0 0 0
1080 RTA00000345F. 21.1 40204 2 0 0 0 0 0 0 0
1082 RTA00000405F.a.l l .l 39124 2 0 0 0 0 0 0 0
1084 RTA00000413F.e.l6.1 63836 1 0 0 0 0 0 0 0
1086 RTA00000404F.O.18.2 39110 2 0 0 0 0 0 0 0
1087 RTA00000409F.i.24.1 76967 1 0 0 0 0 0 0 0
1091 RTA00000340F.n.l3.1 17055 4 0 0 0 0 0 0 0
1092 RTA00000340F.p.04.1 78533 1 0 0 0 0 0 0 0
1093 RTA00000411F.C.05.1 73368 1 0 0 0 0 0 0 0
1097 RTA00000404F.i.02.1 39015 2 0 0 0 0 0 0 0
1099 RTA00000403F.m. l5.2 26901 2 0 0 0 0 0 0 0
1100 RTA00000412F.h.23.2 651 18 1 0 0 0 0 0 0 0
1101 RTA00000418F.J.08.1 73382 1 0 0 0 0 0 0 0
1102 RTAOOOOOl 25 A.n.4.1 81984 1 0 0 0 0 0 0 0
1103 RTA00000412F.1.19.1 65825 1 0 0 0 0 0 0 0
1 105 RTAOOOOO 129A.p.3.1 32644 1 1 0 0 0 0 0 0
1 106 RTA00000340F.p.20.1 17008 4 0 0 0 0 0 0 0
1 107 RTA00000411F.a. l0.1 73073 1 0 0 0 0 0 0 0
1 108 RTA00000409F.n.l7.1 76725 1 0 0 0 0 0 0 0
1 109 RTA00000404F.C.03.2 39198 2 0 0 0 0 0 0 0
1 1 10 RTA00000420F.a.l9.1 34192 1 1 0 0 0 0 0 0
1 1 14 RTA00000420F.d.l2.1 64095 1 0 0 0 0 0 0 0
1 115 RTA00000409F .19.1 73792 1 0 0 0 0 0 0 0
1116 RTA00000422F.d.l6.1 39133 2 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl NO: 1 1 17 RTA00000418F.m. l6.1 74986 1 0 0 0 0 0 0 0
1 1 18 RTA00000405F.C.1 1.1 39068 2 0 0 0 0 0 0 0
1 1 19 RTA00000404F. 22.1 39084 2 0 0 0 0 0 0 0
1 120 RTA00000418F. 07.1 75067 1 0 0 0 0 0 0 0
1 121 RTA00000403F.C.10.1 75261 1 0 0 0 0 0 0 0
1124 RTA00000410F.m.05.1 74964 1 0 0 0 0 0 0 0
1125 RTA00000405F.L20.1 38532 2 0 0 0 0 0 0 0
1127 RTA00000408F.p.24.1 74286 1 0 0 0 0 0 0 0
1 128 RTA00000418F.k. l 8.1 75385 1 0 0 0 0 0 0 0
1 129 RTA00000422F.m.04.1 38702 2 0 0 0 0 0 0 0
1 133 RTA00000403F.a.07.1 73559 1 0 0 0 0 0 0 0
1 135 RTA00000403F.b.l9.1 22327 2 1 0 0 0 0 0 0
1 136 RTA00000418F.m.23.1 77195 1 0 0 0 0 0 0 0
1138 RTA00000404F.U 8.1 21912 2 1 0 0 0 0 0 0
1139 RTA00000422F.i.l4.1 39300 2 0 0 0 0 0 0 0
1140 RTA00000418F.m.l4.1 7571 1 1 0 0 1 0 0 0 0
1141 RTA00000406F.O.12.1 37459 2 0 0 0 0 0 0 0
1143 RTA00000411F.a.07.1 74547 1 0 0 0 0 0 0 0
1144 RTA00000411F.C.02.1 72852 1 0 0 0 0 0 0 0
1146 RTAOOOOO 130A.h.16.1 80761 1 0 0 0 0 0 0 0
1147 RTA00000410F.p.23.1 73948 1 0 0 0 0 0 0 0
1148 RTA00000418F.m.24.1 77114 1 0 0 0 0 0 0 0
1150 RTA00000408F.J.19.2 73752 1 0 0 0 0 0 0 0
1152 RTAOOOOOl 18A.d.17.1 81921 1 0 0 0 0 0 0 0
1 153 RTA00000407F.b.04.1 63221 1 0 0 0 0 0 0 0
1154 RTA00000411F.e.07.1 65008 1 0 0 0 0 0 0 0
1156 RTAOOOOO 132A.C.11.1 87278 1 0 0 0 0 0 0 0
1157 RTA00000420F.e. l6.1 63639 1 0 0 0 0 0 0 0
1159 RTA00000404F.b.l l.l 39079 2 0 0 0 0 0 0 0
1160 RTA00000418F.k. l7.1 75390 1 0 0 0 0 0 0 0
1 161 RTAOOOOO 129A.k.12.1 79322 1 0 0 0 0 0 0 0
1162 RTA00000340R.m.07.1 78415 1 0 0 0 0 0 0 0
1 163 RTA00000405F.d. l4.1 35209 2 0 0 0 0 0 1 0
1164 RTA00000406F.f.l l .l 38601 2 0 0 0 0 0 0 0
1 165 RTAOOOOO 120A.h.5.1 80344 1 0 0 0 0 0 0 0
1167 RTA00000411F.g.06.1 66065 1 0 0 0 0 0 0 0
1 168 RTA00000408F.d.l6.1 76318 1 0 0 0 0 0 0 0
1 171 RTA00000404F.C.19.1 39026 2 0 0 0 0 0 0 1
1173 RTA00000410F.a.01.1 73354 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI
ID clones clones clones clones clones clones clones cl
NO:
1174 RTA00000408F.h.08.1 74575 1 0 0 0 0 0 0 0
1 175 RTA00000422F.b. l6.1 17045 4 0 0 0 0 0 0 0
1 176 RTA00000419F.f. l0.1 66193 1 0 0 0 0 0 0 0
1 177 RTA00000418F.1.04.1 74140 1 0 0 0 0 0 0 0
1178 RTA00000410F.3.16.1 73548 1 0 0 0 0 0 0 0
1 179 RTAOOOOO 138A.e.13.1 79608 1 0 0 0 0 0 0 0
1180 RTAO0O0013OA.b.5.1 79579 1 0 0 0 0 0 0 0
1 181 RTA00000408F.J.15.2 74759 1 0 0 0 0 0 0 0
1182 RTA00000410F.m.20.1 74285 1 0 0 0 0 0 0 0
1 185 RTA00000419F.e.04.1 62963 1 0 0 0 0 0 0 0
1 187 RTA00000418F.g.05.1 73075 1 0 0 0 0 0 0 0
1 188 RTA00000419F.n.02.1 65963 1 0 0 0 0 0 0 0
1 191 RTAOOOOOl 19A.m.l 5.1 80989 1 0 0 0 0 0 0 0
1 194 RTA00000413F.g.23.1 40700 1 1 0 0 0 0 0 0
1 195 RTA00000403F.a. l8.1 75726 1 0 0 0 0 0 0 0
1 196 RTA00000404F.m.20.2 39144 2 0 0 0 0 0 0 0
1 199 RTA00000419F.h.04.1 65034 1 0 0 0 0 0 0 0
1200 RTA00000408F.d.l2.1 75782 1 0 0 0 0 0 0 0
1201 RTA00000133A.m.l9.2 80167 1 0 0 0 0 0 0 0
1206 RTAOOOOO 126A.o.22.1 81752 1 0 0 0 0 0 0 0
1207 RTA00000419F.n. l3.1 66026 1 0 0 0 0 0 0 0
1208 RTAOOOOO 130A.h.13.1 80790 1 0 0 0 0 0 0 0
1212 RTA00000411F.m.l9.1 74924 1 0 0 0 0 0 0 0
1214 RTA00000419F. 06.1 78493 1 0 0 0 0 0 0 0
1216 RTA00000412F.d.l6.1 26829 1 0 0 0 0 0 0 0
1217 RTAOOOOOl 19A.J.23.1 79835 1 0 0 0 0 0 0 0
1219 RTAOOOOO 195AF.C.12.1 37582 2 0 0 0 0 0 0 0
1223 RTA00000423F.C.19.1 40472 2 0 0 0 0 0 0 0
1224 RTA00000405F.g.24.1 39076 2 0 0 0 0 0 0 0
1226 RTA00000419F.C.1 1.1 65504 1 0 0 0 0 0 0 0
1227 RTAOOOOO 135A.f.14.2 79969 1 0 0 0 0 0 0 0
1228 RTA00000403F.a.05.1 18808 1 1 0 0 0 0 0 0
1229 RTA00000405F.e.l7.1 38662 2 0 0 0 0 0 0 0
1230 RTA0000041 1F.d.05.1 75812 1 0 0 0 0 0 0 0
1232 RTA00000418F.d.03.1 76824 1 0 0 0 0 0 0 0
1233 RTA00000418F.h.08.1 76401 1 0 0 0 0 0 0 0
1234 RTA00000418F.m.l0.1 791 10 1 0 0 0 0 0 0 0
1235 RTA00000411 F.i. l5.1 31612 1 1 0 0 0 0 0 0
1236 RTA00000413F.i.23.1 63073 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI
ID clones clones clones clones clones clones clones cl X JNTΓUV.
1237 RTA0000041 1F.e.24.1 64781 1 0 0 0 0 0 0 0
1238 RTA00000406F.g.22.1 38590 2 0 0 0 0 0 0 0
1239 RTA00000126A.n.l3.2 79735 1 0 0 0 0 0 0 0
1240 RTA00000419F.a.02.1 77993 1 0 0 0 0 0 0 0
1241 RTA00000346F.1.13.1 7542 8 0 0 2 1 0 1 0
1245 RTA00000120A.d.l5.1 80533 1 0 0 0 0 0 0 0
1246 RTA00000418F.f.21.1 75157 1 0 0 0 0 0 0 0
1248 RTAOOOOO 129A.d.1.2 80058 1 0 0 0 0 0 0 0
1251 RTA00000419F.m.20.1 76720 1 0 0 0 0 0 0 0
1253 RTA00000406F.e.l5.1 39074 2 0 0 0 0 0 0 0
1255 RTA00000411F.C.10.1 73117 1 0 0 0 0 0 0 0
1259 RTA00000413F.d.05.1 64788 1 0 0 0 0 0 0 0
1260 RTAOOOOO 121 A.o.3.1 81437 1 0 0 0 0 0 0 0
1262 RTA00000420F.e.02.1 40259 2 0 0 0 0 0 0 0
1268 RTAOOOOO 126A.k.7.2 79866 1 0 0 0 0 0 0 0
1270 RTA00000419F.1.03.1 79060 1 0 0 0 0 0 0 0
1272 RTAOOOOOl 18A.a.2.1 38067 2 0 0 0 0 0 0 0
1273 RTA00000410F.m.l8.1 76365 1 0 0 0 0 0 0 0
1275 RTA00000406F.C.20.1 38578 2 0 0 0 0 0 0 0
1276 RTA00000413F.b.l4.1 66591 1 0 0 0 0 0 0 0
1277 RTA00000406F.C.18.1 14368 2 0 0 0 0 0 0 0
1278 RTA00000418F.J.09.1 76352 1 0 0 0 0 0 0 0
1279 RTA00000419FT.23.1 65002 1 0 0 0 0 0 0 0
1281 RTA00000411F.a.05.1 76699 1 0 0 0 0 0 0 0
1282 RTA00000419F.m.21.1 77947 1 0 0 0 0 0 0 0
1283 RTA00000405F.n.l6.1 21503 2 1 1 0 0 0 0 0
1284 RTA00000422F.O.19.2 13084 3 2 0 0 0 0 0 0
1285 RTA00000408F.n.02.2 76993 1 0 0 0 0 0 0 0
1290 RTAOOOOOl 19A.g.7.1 83580 1 0 0 0 0 0 0 0
1291 RTA00000411F.i.02.1 66975 1 0 0 0 0 0 0 0
1292 RTA00000408F.1.09.1 75487 1 0 0 0 0 0 0 0
1293 RTA00000423F.g.04.1 23012 2 1 0 0 0 0 0 0
1295 RTA00000418F.L 18.1 78024 1 0 0 0 0 0 0 0
1296 RTA00000411F.h.l5.1 65160 1 0 0 0 0 0 0 0
1297 RTA00000410F.i. l9.1 78988 1 0 0 0 0 0 0 0
1298 RTA00000419F. 24.1 75596 1 0 0 0 0 0 0 0
1301 RTA00000409F.i.09.1 75279 1 0 0 0 0 0 0 0
1302 RTA00000419F.h.02.1 63985 1 0 0 0 0 0 0 0
1303 RTA00000413F.b.l2.1 64932 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib 1 lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl NO: 1304 RTA00000121A.h.l 8.1 16376 4 0 0 0 0 0 0 0
1305 RTA0000041 1F.n.20.1 75816 1 0 0 0 0 0 0 0
1307 RTA0000041 1F.n.l2.1 73308 1 0 0 0 0 0 0 0
1308 RTA00000408FJ.12.2 18226 1 0 0 0 0 0 0 0
1309 RTA00000409F.L03.1 75968 1 0 0 0 0 0 0 0
1312 RTA00000409F .05.1 74128 1 0 0 0 0 0 0 0
1313 RTA00000419F.m.04.1 74367 1 0 0 0 0 0 0 0
1314 RTA00000418F.k.03.1 78901 1 0 0 0 0 0 0 0
1315 RTA00000419F.d.l6.1 64357 1 0 0 0 0 0 0 0
1316 RTA00000420F.e.l0.1 65899 1 0 0 0 0 0 0 0
1319 RTA00000418F.k.08.1 18259 1 0 0 0 0 0 0 0
1322 RTA00000410F.C.02.1 75055 1 0 0 0 0 0 0 0
1324 RTA00000403F.h.l8.1 39241 2 0 0 0 0 0 0 0
1325 RTA00000405F.n.l3.1 23810 2 1 0 0 0 0 0 0
1326 RTA00000355R.e.l4.1 16837 2 2 0 0 0 0 0 0
1327 RTA00000422F.1.03.1 39147 2 0 0 0 0 0 0 0
1329 RTA00000403F.O.14.1 38971 2 0 0 0 0 0 0 0
1333 RTAOOOOO 127A.f.1 1.1 81463 1 0 0 0 0 0 0 0
1335 RTA00000403F.O.07.1 39037 2 0 0 0 0 0 0 0
1336 RTA00000403F.d.l9.1 39243 2 0 0 0 0 0 0 0
1338 RTA00000406F.i.l7.1 37902 2 0 0 0 0 0 0 0
1339 RTA00000418F.d.22.1 75324 1 0 0 0 0 0 0 0
1340 RTA00000340R.O.12.1 53732 1 0 0 0 0 0 0 0
1341 RTAOOOOO 125A.g.24.1 80397 1 0 0 0 0 0 0 0
1342 RTAOOOOO 130A.O.21.1 80218 1 0 0 0 0 0 0 0
1343 RTA00000420F.3.23.1 42158 1 1 0 0 0 0 0 0
1344 RTA00000411F.m.l8.1 75629 1 0 0 0 0 0 0 0
1345 RTA00000407F.b.22.1 37487 2 0 0 0 0 0 0 0
1346 RTA00000409F.3.16.1 73990 1 0 0 0 0 0 0 0
1348 RTA00000341F.k.l2.1 62985 1 0 0 0 0 0 0 0
1349 RTAOOOOO 129A.C.18.2 37216 2 0 0 0 0 0 0 0
1350 RTA00000410F.d.l0.1 77561 1 0 0 0 0 0 0 0
1351 RTA00000351R.i.03.1 6874 6 3 0 0 1 0 0 0
1352 RTAOOOOOl 35 A.l.1.2 39426 2 0 0 0 0 0 0 0
1353 RTA00000420F.b. l 8.1 66136 1 0 0 0 0 0 0 0
1356 RTA00000403F.O.13.1 39049 2 0 0 0 0 0 0 0
1357 RTA00000411F.f.06.1 64186 1 0 0 0 0 0 0 0
1359 RTA00000351R.C.13.1 1 1476 6 0 0 0 0 0 0 0
1362 RTA00000420F.d.l6.1 64485 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib 1 lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl NO: 1363 RTA00000404F.U2.1 39001 2 0 0 0 0 0 0 0
1364 RTA00000404F.O.10.2 16785 2 2 0 0 0 0 0 0
1365 RTA00000419F.d.07.1 21421 1 2 0 0 0 0 0 0
1366 RTA00000404F.p.02.2 39097 2 0 1 0 0 0 0 0
1367 RTAOOOOO 125A.k.14.1 79457 1 0 0 0 0 0 0 0
1368 RTAOOOOO 122A.J.22.1 81151 1 0 0 0 0 0 0 0
1369 RTA00000406F.L 13.1 37904 2 0 0 0 0 0 0 0
1370 RTAOOOOOl 35 A.b.23.1 35241 2 0 0 0 0 0 0 0
1373 RTA00000423F.1.04.1 14320 2 0 0 0 0 0 0 0
1374 RTA00000420F.b.04.1 63820 1 0 0 0 0 0 0 0
1376 RTA00000408F. 8.2 74410 1 0 0 0 0 0 0 0
1378 RTA00000341F.J.05.1 36177 2 0 0 0 0 0 0 0
1379 RTA00000420F.a. l6.1 63345 1 0 0 0 0 0 0 0
1381 RTA00000410F .01.1 73399 1 0 0 0 0 0 0 0
1382 RTA00000408F.p.21.1 77930 1 0 0 0 0 0 0 0
1383 RTA00000412F.d.l9.1 75743 1 0 0 0 0 0 0 0
1384 RTA00000352R.C.04.1 71976 1 0 0 0 0 0 0 0
1385 RTA00000413FT.19.1 65189 1 0 0 0 0 0 0 0
1386 RTA00000411F.e.03.1 73648 1 0 0 0 0 0 0 0
1389 RTA00000418F.C.04.1 41587 1 1 0 0 0 0 0 0
1390 RTA00000418F.O.17.1 79069 1 0 0 0 0 0 0 0
1391 RTA00000418F.e.21.1 74773 1 0 0 0 0 0 0 0
1392 RTA00000419F.d.l4.1 64945 1 0 0 0 0 0 0 0
1396 RTA00000410F.J.20.1 73601 1 0 0 0 0 0 0 0
1399 RTAOOOOOl 19A.j.9.1 82060 1 0 0 0 0 0 0 0
1403 RTA00000340F.i. l3.1 79299 1 0 0 0 0 0 0 0
1404 RTA00000412F.g.03.1 64740 1 0 0 0 0 0 0 0
1405 RTAOOOOO 122A.g.17.1 32655 1 1 0 0 0 0 0 0
1407 RTA00000419F.n.l2.1 66086 1 0 0 0 0 0 0 0
1410 RTA00000351R.p. l4.1 13166 2 3 0 0 0 0 0 0
141 1 RTA00000403F.e.08.1 19126 3 0 0 0 0 0 0 0
1412 RTAOOOOO 124A.k.20.1 80913 1 0 0 0 0 0 0 0
1413 RTA00000121A.n.2.1 33585 1 1 0 0 0 0 0 0
1414 RTA00000422F.m.24.1 39159 2 0 1 0 1 1 2 2
1415 RTA00000408F.e.24.2 75002 1 0 0 0 0 0 0 0
1418 RTA00000403F.b. l2.1 78775 1 0 0 0 0 0 0 0
1419 RTA00000404F.a.09.1 38985 2 0 0 0 0 0 0 0
1421 RTA00000403F.O.19.1 78615 1 0 0 0 0 0 0 0
1424 RTA00000410F.b.l0.1 74504 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib 1 lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl
NO: 1426 RTA00000413F.h. l2.1 66929 1 0 0 0 0 0 0 0
1427 RTA00000406F. 14.1 38651 2 0 0 0 0 0 0 0
1429 RTA0000041 1F.f. l7.1 65661 1 0 0 0 0 0 0 0
1430 RTA0000041 1F.k. l0.1 64506 1 0 0 0 0 0 0 0
1431 RTA0000041 1F.g.21.1 64500 1 0 0 0 0 0 0 0
1432 RTAOOOOOl 19A.h.24.1 82266 1 0 0 0 0 0 0 0
1434 RTA00000408F.m.22.2 72949 1 0 0 0 0 0 0 0
1437 RTA00000410F.i. l7.1 78147 1 0 0 0 0 0 0 0
1440 RTA00000129A.3.13.2 79780 1 0 0 0 0 0 0 0
1441 RTAOOOOO 129A. 21.1 82067 1 0 0 0 0 0 0 0
1442 RTA00000350R.g. l0.1 9026 7 0 0 1 0 0 0 0
1443 RTA00000413F.d.23.1 66030 1 0 0 0 0 0 0 0
1447 RTA0000041 1F.d.l0.1 76445 1 0 0 0 0 0 0 0
1448 RTA00000404F.b.l9.1 39281 2 0 0 0 0 0 0 0
1449 RTA00000418F.C.07.1 73245 1 0 0 0 0 0 0 0
1450 RTA00000418FJ.15.1 74855 1 0 0 0 0 1 0 0
1453 RTA00000413F.b. l6.1 65126 1 0 0 0 0 0 0 0
1455 RTA00000350R.m.l4.1 39171 2 0 0 0 0 0 0 0
1456 RTA00000418F.1.11.1 77158 1 0 0 0 0 0 0 0
1457 RTAOOOOO 130A.d.5.1 82051 1 0 0 0 0 0 0 0
1458 RTA00000339F.n.05.1 39648 2 0 0 0 0 0 0 0
1460 RTA00000407F.a.23.1 23489 2 1 0 0 0 0 0 0
1462 RTA00000403F.h.l l .l 39219 2 0 0 0 0 0 0 0
1463 RTA00000406F.J.13.1 38688 2 0 0 0 0 0 0 0
1464 RTA00000352R.p.09.1 16915 4 0 0 0 0 0 0 0
1465 RTA00000413F.g.24.1 65481 1 0 0 0 0 0 0 0
1469 RTA00000420F.a.08.1 19473 1 2 0 0 0 0 0 0
1472 RTA00000404F.i.22.1 39082 2 0 0 0 0 0 0 0
1473 RTA00000124A.k.23.1 81350 1 0 0 0 0 0 0 0
1474 RTA00000404F.e.l l.l 38991 2 0 0 0 0 0 0 0
1475 RTAOOOOO 129A.d.2.4 801 19 1 0 0 0 0 0 0 0
1478 RTA00000419F.O.15.1 32487 1 1 0 0 0 0 0 0
1479 RTAOOOOOl 19A.m.17.1 79536 1 0 0 0 0 0 0 0
1480 RTA00000410F.b.07.1 78916 1 0 0 0 0 0 0 0
1481 RTA00000420F.b.l9.1 36873 2 0 0 0 0 0 0 0
1483 RTA0000041 1F.b.21.1 10051 1 0 0 0 0 0 0 0
1485 RTA00000356R.C.16.1 16915 4 0 0 0 0 0 0 0
1487 RTA00000412F.h.l l .l 63175 1 0 0 0 0 0 0 0
1490 RTA00000420F.a. l l .l 66460 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl
X NTfUV.
1491 RTAOOOOO 120A.C.7.1 80985 1 0 0 1 0 0 0 0
1492 RTA00000404F.e.l5.1 39101 2 0 0 0 0 0 0 0
1493 RTA00000422F.n.20.1 38676 2 0 0 0 0 0 1 0
1494 RTA00000423F.h.20.1 38639 2 0 0 0 0 0 0 0
1497 RTA00000410F.b.l 8.1 76701 1 0 0 0 0 0 0 0
1499 RTA00000423F.g.l5.1 35173 2 0 0 0 0 0 0 0
1500 RTA00000413F.b.04.1 66427 1 0 0 0 0 0 0 0
1503 RTA00000346F.f. l l .l 38528 2 0 0 0 0 0 0 0
1506 RTA00000422F.L02.1 76436 1 0 0 0 0 0 0 0
1507 RTA00000410F.a.08.1 73324 1 0 0 0 0 0 0 0
1509 RTA00000419F.e.02.1 65010 1 0 0 0 0 0 0 0
151 1 RTA00000403F.g.l3.1 38718 2 0 0 0 0 0 0 0
1513 RTA00000407F.a.01.1 12501 3 1 0 0 0 0 0 0
1516 RTA00000411F.f.l4.1 62984 1 0 0 0 0 0 0 0
1517 RTA0000041 1F.C.04.1 76858 1 0 0 0 0 0 0 0
1518 RTA00000135A.m.l8.1 19255 2 0 0 0 0 0 0 0
1519 RTA00000413F.C.17.1 36831 2 0 0 0 0 0 0 0
1521 RTA00000404F .01.1 26859 2 0 0 0 0 0 0 0
1522 RTA00000138A.p.l0.1 81625 1 0 0 0 0 0 0 0
1526 RTA00000423F.h.07.1 37933 2 0 0 0 0 0 0 0
1527 RTA00000413F.e.04.1 64176 1 0 0 0 0 0 0 0
1528 RTA00000406F.h.03.1 38585 2 0 0 0 0 0 0 0
1529 RTA00000403F.e.24.1 16432 2 2 0 0 0 0 0 0
1531 RTA00000403F.i.l l .l 23535 2 1 0 0 0 0 0 0
1532 RTA00000419F.g.02.1 62839 1 0 0 0 0 0 0 0
1533 RTA00000347F.e.05.1 39814 2 0 0 0 0 0 0 0
1534 RTA00000408F.1.16.1 73468 1 0 0 0 0 0 0 0
1536 RTA00000423F.f.09.1 64823 1 0 0 0 0 0 0 0
1537 RTA00000419F.k.03.1 40822 1 1 0 0 0 0 0 0
1538 RTA00000406F.b.02.1 38744 2 0 0 0 0 0 0 0
1539 RTA00000418F.O.14.1 33524 1 1 0 0 0 0 0 0
1541 RTA00000404F.b.09.1 39166 2 0 0 0 0 0 0 0
1547 RTA00000406F.k.l l .l 38715 2 0 0 0 0 0 0 0
1549 RTA00000406F.C.06.1 37924 2 0 0 0 0 0 0 0
1550 RTA00000418F.n.07.1 76316 1 0 0 0 0 0 0 0
1551 RTA00000419F.n. l5.1 63484 1 0 0 0 0 0 0 0
1552 RTA00000408F.n.06.2 76642 1 0 0 0 0 0 0 0
1553 RTA00000420F.C.04.1 65007 1 0 0 0 0 0 0 0
1554 RTA00000411F.J.15.1 66871 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib 1 lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl NO: 1556 RTAOOOOO 128A.m.23.1 81441 1 0 0 0 0 0 0 0
1557 RTA00000406F.g.03.1 38690 2 0 0 0 0 0 0 0
1558 RTA00000405F.h.05.2 75706 1 0 0 0 0 0 0 0
1559 RTAOOOOO 129A.n.24.1 81409 1 0 0 0 0 0 0 0
1562 RTA00000418F.n. l l .l 78977 1 0 0 0 0 0 0 0
1565 RTAOOOOO 120A.h.9.1 80736 1 0 0 0 0 0 0 0
1566 RTA00000413F.3.12.1 63403 1 0 0 0 0 0 0 0
1567 RTA00000412F.O.05.1 63575 1 0 0 0 0 0 0 0
1571 RTA00000354R.n.04.1 22049 3 0 0 0 0 0 0 0
1573 RTA00000406F.h.05.1 38542 2 0 0 0 0 0 0 0
1574 RTA00000410F.b.24.1 75104 1 0 0 0 0 0 0 0
1575 RTA00000423F.d. l l .l 38950 2 0 0 0 0 0 0 0
1578 RTAOOOOOl 19A. 1.1 81282 1 0 0 0 0 0 0 0
1579 RTA00000420F.f.07.1 66312 1 0 0 0 0 0 0 0
1580 RTA00000404F. 22.2 39084 2 0 0 0 0 0 0 0
1581 RTA00000422F.e.07.1 38964 2 0 0 0 0 0 0 0
1582 RTA00000410F.f.l2.1 73883 1 0 0 0 0 0 0 0
1584 RTA00000411F.m.l l .l 73196 1 0 0 0 0 0 0 0
1587 RTA00000403F.O.10.2 38964 2 0 0 0 0 0 0 0
1590 RTA00000413F.C.10.1 65600 1 0 0 0 0 0 0 0
1591 RTA00000411F.b.l7.1 72893 1 0 0 0 0 0 0 0
1593 RTA00000408F. 19.1 77593 1 0 0 0 0 0 0 0
1596 RTAOOOOOl 19A.L8.1 82593 1 0 0 0 0 0 0 0
1598 RTA00000418F.g.03.1 78737 1 0 0 0 0 0 0 0
1599 RTA0000041 1F.a.09.1 78629 1 0 0 0 0 0 0 0
1601 RTA00000419F.J.1 1.1 73183 1 0 0 0 0 0 0 0
1603 RTA00000404F.n.l 8.2 37169 2 0 0 0 0 0 0 0
1604 RTAOOOOO 122A.n.16.1 80553 1 0 0 0 0 0 0 0
1605 RTA00000420F.C.07.1 65555 1 0 0 0 0 0 0 0
1608 RTA00000408FJ.13.2 42275 1 1 0 0 0 0 0 0
1610 RTA00000423F.a.01.1 39103 2 0 0 0 0 0 0 0
1613 RTA00000341F.e.20.1 67422 1 0 0 0 0 0 0 0
1614 RTA00000419F.m.22.1 75600 1 0 0 0 0 0 0 0
1615 RTA00000419F.m.23.1 64263 1 0 0 0 0 0 0 0
1616 RTA00000419F.b.06.1 76728 1 0 0 0 0 0 0 0
1618 RTA00000406F.p.08.1 37573 2 0 0 0 0 0 0 2
1619 RTAOOOOO 129A.n.17.1 79811 1 0 0 0 0 0 0 0
1621 RTA00000407F.b.08.1 37513 2 0 0 0 0 0 0 0
1623 RTA00000406F.i.08.1 37946 2 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl
NO: 1624 RTA00000403F.h.07.1 26856 2 0 0 0 0 0 0 0
1625 RTA00000418F.n.24.1 73153 1 0 0 0 0 0 0 0
1627 RTA00000409F.1.20.1 74394 1 0 0 0 0 0 0 0
1628 RTA00000418F.1.06.1 73317 1 0 0 0 0 0 0 0
1629 RTA00000346F.O.22.1 7381 2 6 0 0 0 0 0 0
1630 RTAOOOOO 129A.k.22.1 79639 1 0 0 0 0 0 0 0
1632 RTA00000418F.m.22.1 74567 1 0 0 0 0 0 0 0
1633 RTA00000413F.C.12.1 65334 1 0 0 0 0 0 0 0
1635 RTA00000418F.g.20.1 74626 1 0 0 0 0 0 0 0
1636 RTA00000413F.d.l5.1 64943 1 0 0 0 0 0 0 0
1639 RTA00000412F.C.10.1 76372 1 0 0 0 0 0 0 0
1640 RTA00000122A.J.17.1 62736 1 0 0 0 0 0 0 0
1645 RTA00000418F.J.19.1 78399 1 0 0 0 0 0 0 0
1646 RTA00000137A.p. l2.1 80614 1 0 0 0 0 0 0 0
1648 RTA00000418F.p.l0.1 75323 1 0 0 0 0 0 0 0
1649 RTA00000408F.k.l2.1 77246 1 0 0 0 0 0 0 0
1650 RTA00000137A.J.1 1.4 79752 1 0 0 0 0 0 0 0
1652 RTA00000419F.n.24.1 65995 1 0 0 0 0 0 0 0
1653 RTA00000418F.1.03.1 79058 1 0 0 0 0 0 0 0
1655 RTA00000419F.m.l3.1 79052 1 0 0 0 0 0 0 0
1656 RTA00000418F.J.14.1 32623 1 1 0 0 0 0 0 0
1657 RTA00000403F.a.l0.1 73952 1 0 0 0 0 0 0 0
1658 RTA00000420F.a.21.1 66241 1 0 0 0 0 0 0 0
1659 RTAOOOOO 127A.e.6.1 5885 4 2 0 0 0 0 0 0
1660 RTA00000405F.g.21.2 38966 2 0 0 0 0 0 0 0
1661 RTA00000405F.g.21.1 38966 2 0 0 0 0 0 0 0
1662 RTA00000419F.m.06.1 75749 1 0 0 0 0 0 0 0
1663 RTA00000423F.g.03.1 38007 2 0 0 0 0 0 0 0
1665 RTA00000418F.f.03.1 7891 1 1 0 0 0 0 0 0 0
1668 RTAOOOOO 120A.C.20.1 43235 1 1 0 0 0 1 0 0
1669 RTA00000138A.m.l5.1 41603 1 1 0 0 0 0 0 0
1670 RTA00000408F.f.l4.2 73024 1 0 0 0 0 0 0 0
1671 RTA00000418F.p.20.1 78023 1 0 0 0 0 0 0 0
1672 RTA00000423F.e.21.1 66961 1 0 0 0 0 0 0 0
1673 RTA00000419F.J.22.1 73525 1 0 0 0 0 0 0 0
1674 RTA00000410F.d.l8.1 75458 1 0 0 0 0 0 0 0
1675 RTA00000403F.b.24.1 78838 1 0 0 0 0 0 0 0
1677 RTA00000410F.e.09.1 76093 1 0 0 0 0 0 0 0
1680 RTA00000353R.h. l0.1 39498 2 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI
ID clones clones clones clones clones clones clones cl 1682 RTA0000041 1F.d.21.1 74794 1 0 0 0 0 0 0 0
1683 RTA00000340F.m.04.1 19406 2 1 0 0 0 0 0 0
1684 RTA0000041 1F.n.09.1 78962 1 0 0 0 0 0 0 0
1685 RTAOOOOO 127A.h.22.2 13155 2 3 0 0 0 0 0 0
1686 RTA00000420F.e.09.1 66325 1 0 0 0 0 0 0 0
1687 RTA00000405F.p.03.1 1 1346 3 3 0 0 0 0 0 0
1688 RTA00000419F.a.l 8.1 78484 1 0 0 0 0 0 0 0
1691 RTAOOOOOl 21 A.n.23.1 26981 2 0 0 0 0 0 0 0
1692 RTA00000121A.n.l5.1 40849 1 1 0 0 0 0 0 0
1693 RTA00000403F.L23.1 1 1364 4 2 0 0 0 0 0 0
1694 RTA00000405F.3.03.1 39065 2 0 0 0 0 0 0 0
1696 RTA00000419F.p.08.1 65560 1 0 0 0 0 0 0 0
1697 RTAOOOOO 126A.n.6.2 79917 1 0 0 0 0 0 0 0
1698 RTA00000413F.C.03.1 64527 1 0 0 1 0 0 0 0
1699 RTA00000422F.k.24.1 39118 2 0 0 0 0 0 0 0
1700 RTA00000412F.C.17.1 75620 1 0 0 0 0 0 0 0
1702 RTA00000347F.g.08.1 23121 3 0 0 0 0 0 0 0
1703 RTA00000419F.O.06.1 64643 1 0 0 0 0 0 0 0
1704 RTA00000340R.J.07.1 38954 2 0 0 0 0 0 0 0
1705 RTA00000423F.J.02.1 38617 2 0 0 0 0 0 0 0
1706 RTA00000419F.C.04.1 63749 1 0 0 0 0 0 0 0
1707 RTA00000411F.a.01.1 74524 1 0 0 0 0 0 0 0
1708 RTA00000406F.f.05.1 22961 2 1 0 0 0 0 1 0
1709 RTA00000410F.n.05.1 77830 1 0 0 0 0 0 0 0
1710 RTA00000404F.e.06.1 39315 2 0 0 0 0 0 0 0
1712 RTA00000411F.C.03.1 79280 1 0 0 0 0 0 0 0
1718 RTA00000405F.1.07.1 38636 2 0 0 0 0 0 0 0
1720 RTA00000411F.n.06.1 73886 1 0 0 0 0 0 0 0
1721 RTA00000422F.k.l5.1 19253 2 0 0 0 0 0 0 0
1722 RTA00000406F.h. l6.1 38618 2 0 0 0 0 0 0 0
1723 RTA00000419FT.24.1 18717 1 1 0 0 0 0 0 0
1724 RTA00000411F.d.l8.1 76063 1 0 0 0 0 0 0 0
1727 RTA00000408F.d. l5.1 78467 1 0 0 0 0 0 0 0
1728 RTA00000339F.b.22.1 6867 7 3 0 0 0 0 0 0
1730 RTA00000411F.n.02.1 78049 1 0 0 0 0 0 0 0
1731 RTA00000419F.b. l7.1 63261 1 0 0 0 0 0 0 0
1733 RTAOOOOO 130A.e.20.1 79502 1 0 0 0 0 0 0 0
1735 RTA00000411F 13.1 66138 1 0 0 0 0 0 0 0
1736 RTA00000420F.e.20.1 64762 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI
ID clones clones clones clones clones clones clones cl
NO:
1737 RTAOOOOO 126A.p.23.2 80915 1 0 0 0 0 0 0 0
1739 RTA00000406F.g.08.1 37963 2 0 0 0 0 0 0 0
1740 RTA00000409F.a.08.1 74978 1 0 0 0 0 0 0 0
1741 RTA00000406F.d.24.1 37997 2 0 0 0 0 0 0 0
1744 RTA00000418F. 2.1 78971 1 0 0 0 0 0 0 0
1745 RTA00000121A.h.l9.1 80334 1 0 0 0 0 0 0 0
1746 RTA00000419F.b.l0.1 78566 1 0 0 0 0 0 0 0
1747 RTA00000406F.m.l0.1 38004 2 0 0 0 0 0 0 0
1748 RTA00000406F.O.05.1 37894 2 0 0 0 0 0 0 0
1749 RTA00000408F.b.04.2 39933 2 0 0 0 0 0 0 0
1750 RTA0000041 1F.k.04.1 65407 1 0 0 0 0 0 0 0
1752 RTA00000134A.1.9.1 81814 1 0 0 0 0 0 0 0
1754 RTA00000418F. 04.1 75864 1 0 0 0 0 0 0 0
1757 RTA00000419F.p.l8.1 63002 1 0 0 0 0 0 0 0
1759 RTA00000419F.a.24.1 79290 1 0 0 0 0 0 0 0
1761 RTAOOOOO 129A.e.14.1 80053 1 0 0 0 0 0 0 0
1762 RTA00000404F.a.01.1 19251 2 0 0 0 0 0 0 0
1765 RTA00000408F.n.l6.2 73720 1 0 0 0 0 0 0 0
1769 RTA00000412F.1.14.1 62792 1 0 0 0 0 0 0 0
1770 RTAOOOOO 129A.b.6.2 39111 2 0 0 0 0 0 0 0
1771 RTA00000406F.n.l2.1 37517 2 0 0 0 0 0 0 0
1772 RTA00000418F.e.03.1 73442 1 0 0 0 0 0 0 0
1774 RTA00000403F.g.03.1 23537 2 1 0 0 0 0 0 0
1775 RTA00000412F.p.06.1 65485 1 0 0 0 0 0 0 0
1776 RTA00000419F.b.21.1 65366 1 0 0 0 0 0 0 0
1779 RTA00000351R.J.16.1 64773 1 0 0 0 0 0 0 0
1781 RTA00000419F.f.l8.1 64047 1 0 0 0 0 0 0 0
1782 RTA00000423F.i.l6.1 38604 2 0 0 0 0 0 0 0
1784 RTA0000041 1F.f.04.1 64526 1 0 0 0 0 0 0 0
1785 RTAOOOOO 125A.C.17.1 80619 1 0 0 0 0 0 0 0
1786 RTA00000404F.g.08.1 38980 2 0 0 0 0 0 0 0
1787 RTA00000423F.C.13.1 39059 2 0 0 0 0 0 0 0
1790 RTA00000404F. 15.1 18225 2 0 0 0 0 0 0 0
1792 RTA00000339F.1.12.1 771 1 4 1 0 0 0 0 0 0
1793 RTA00000406F.b.01.1 39006 2 0 0 0 0 0 0 0
1794 RTA00000407F.C.08.1 37549 2 0 0 0 0 0 0 0
1796 RTA00000403F.b.05.1 74300 1 0 0 0 0 0 0 0
1800 RTA00000408F.J.05.2 73878 1 0 0 0 0 0 0 0
1802 RTA00000419F.C.14.1 65727 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI
ID clones clones clones clones clones clones clones cl
NO:
1806 RTA00000346F.h.24.1 4379 9 2 0 0 0 0 0 0
1807 RTA00000420F.b.02.1 64013 1 0 0 0 0 0 0 0
1808 RTA00000413F.b.24.1 651 17 1 0 0 0 0 0 0 0
1809 RTA00000412F.d.08.1 75328 1 0 0 0 0 0 0 0
181 1 RTA00000419F.m.l8.1 76014 1 0 0 0 0 0 0 0
1812 RTA00000419F.1.24.1 74628 1 0 0 0 0 0 0 0
1813 RTA00000408F.C.06.1 78619 1 0 0 0 0 0 0 0
1814 RTA00000405F.h.21.2 39072 2 0 0 0 0 0 0 0
1816 RTA00000405F.g.05.2 38987 2 0 0 0 0 0 0 0
1817 RTA00000411F.f.20.1 63501 1 0 0 0 0 0 0 0
1819 RTA00000420F.d. l9.1 43146 1 1 0 0 0 0 0 0
1820 RTAOOOOO 195R.a.06.1 35265 2 0 1 0 0 0 0 0
1821 RTAOOOOOl 23 A.f.2.1 80379 1 0 0 0 0 0 0 0
1822 RTA0000041 1FJ.11.1 66154 1 0 0 0 0 0 0 0
1827 RTA00000419F.J.03.1 77578 1 0 0 0 0 0 0 0
1829 RTA00000423F.h.l l .l 38977 2 0 0 0 0 0 0 0
1830 RTA00000413F.b.l7.1 21704 1 2 0 0 0 0 0 0
1833 RTA00000423FT.03.1 63852 1 0 0 0 0 0 0 0
1834 RTA00000419F.e.l0.1 63225 1 0 0 0 0 0 0 0
1836 RTA00000403F.d.02.1 39224 2 0 0 0 0 0 0 0
1838 RTA00000418FJ.20.1 77101 1 0 0 0 0 0 0 0
1846 RTA00000356R.h.05.1 35052 2 0 1 0 0 0 0 0
1848 RTA00000340F.Ϊ.15.1 26815 1 0 0 0 0 0 0 0
1850 RTA00000345F.C.12.1 23824 2 1 0 0 0 0 0 0
1852 RTA00000412F.O.03.1 65039 1 0 0 0 0 0 0 0
1853 RTA00000409F.d.l6.1 76090 1 0 0 0 0 0 0 0
1856 RTA00000408F.J.17.2 78935 1 0 0 0 0 0 0 0
1857 RTA00000126AJ.15.2 40425 2 0 0 0 0 0 0 0
1861 RTA00000410F.b.l7.1 77458 1 0 0 0 0 0 0 0
1862 RTA00000419F.1.22.1 78444 1 0 0 0 0 0 0 0
1864 RTA00000422F.f.22.1 38703 2 0 0 0 0 0 0 0
1867 RTA00000418F.C.05.1 76475 1 0 0 0 0 0 0 0
1868 RTA00000418F.p.21.1 78068 1 0 0 0 0 0 0 0
1870 RTA00000340F.i.08.1 12005 2 1 0 0 0 0 0 0
1871 RTA00000410F.O.04.1 79018 1 0 0 0 0 0 0 0
1872 RTA00000411F.1.16.1 16122 1 3 0 0 0 0 0 0
1873 RTA0000041 1FJ.03.1 66263 1 0 0 0 0 0 0 0
1874 RTAOOOOO 126A. 24.1 39428 2 0 0 0 0 0 0 0
1876 RTAOOOOO 120A.m.10.3 81376 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl
NO: 1877 RTA00000419F.f. l 6.1 64679 1 0 0 0 0 0 0 0
1878 RTA00000408F.C.23.1 42261 1 1 0 0 0 0 0 0
1881 RTAOOOOO 136A.h.6.1 81620 1 0 0 0 0 0 0 0
1886 RTA00000418F.e.20.1 73741 1 0 0 0 0 0 0 0
1888 RTA00000405F.1.03.1 38580 2 0 0 0 0 0 0 0
1889 RTA00000418F.m.02.1 74550 1 0 0 0 0 0 0 0
1891 RTA00000406F.C.05.1 22077 3 0 1 0 0 0 0 0
1893 RTA0000041 1F. 21.1 65349 1 0 0 0 0 0 0 0
1897 RTA00000418F.L06.1 75151 1 0 0 0 0 0 0 0
1898 RTA00000423F.a.03.1 26796 2 0 0 0 0 0 0 0
1900 RTA00O00423F.k.21.2 37499 2 0 0 0 0 0 0 0
1902 RTA00000404F.C.18.1 38982 2 0 0 0 0 0 0 0
1905 RTA00000411F.g.24.1 65233 1 0 0 0 0 0 0 0
1907 RTA00000405F.m.07.1 37733 2 0 0 0 0 0 0 0
1908 RTA0000041 1F.J.07.1 66963 1 0 0 0 0 0 0 0
1910 RTA00000353R.h.04.1 17123 4 0 0 0 0 0 0 0
191 1 RTA00000408F.f. l0.2 75309 1 0 0 0 0 0 0 0
1913 RTA00000405F.O.03.1 37575 2 0 0 0 0 0 0 0
1914 RTA00000413F.b. l 8.1 39873 2 0 0 0 0 0 0 0
1920 RTA00000408F.C.08.1 73473 1 0 0 0 0 0 0 0
1922 RTA00000410F.C.06.1 77784 1 0 0 0 1 0 0 0
1924 RTA00000405F.b.08.1 39182 2 0 0 0 0 0 0 0
1925 RTA00000409F.1.24.1 73174 1 0 0 0 0 0 0 0
1926 RTA00000406F.J.06.1 38952 2 0 0 0 0 0 0 0
1927 RTA00000423F.h.03.1 37903 2 0 0 0 0 0 0 0
1929 RTAOOOOOl 21 A.k.22.1 79523 1 0 0 0 0 0 0 0
1931 RTA0000041 1 F.m.06.1 24195 2 1 0 0 0 0 0 0
1932 RTAOOOOO 126A.b.9.1 81279 1 0 0 0 0 0 0 0
1935 RTA00000404F.1.05.1 38671 2 0 0 0 0 0 0 0
1941 RTA00000419F.p. l0.1 41448 1 1 0 0 0 0 0 0
1942 RTAOOOOO 120A.C.19.1 81016 1 0 0 0 0 0 0 0
1948 RTA0000041 1 F. 14.1 63987 1 0 0 0 0 0 0 0
1949 RTA00000420F.e.05.1 63908 1 0 0 0 0 0 0 0
1952 RTA00000128A.J.10.1 80085 1 0 0 0 0 0 0 0
1953 RTA00000412F.f. l 0.2 65405 1 0 0 0 0 0 0 0
1955 RTA00000422F. 17.1 38955 2 0 0 0 0 0 0 0
1957 RTA00000347F.h. l 0.1 22779 3 0 0 0 0 0 0 0
1959 RTA00000419F.1.02.1 75736 1 0 0 0 0 0 0 0
1961 RTA00000418F.b.20.1 73560 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl NO: 1964 RTA00000408F.n.05.2 77883 1 0 0 0 0 0 0 0
1965 RTA00000419F.O.09.1 66396 1 0 0 0 0 0 0 0
1970 RTA00000422F.O.08.2 26832 2 0 0 0 0 0 0 0
1973 RTA00000418F.m. l8.1 76479 1 0 0 0 0 0 0 0
1974 RTA00000347F.e.20.1 3991 1 2 0 0 0 0 0 0 0
1975 RTA00000419F.e.23.1 65772 1 0 0 0 0 0 0 0
1982 RTA00000411F.g.05.1 64664 1 0 0 0 0 0 0 0
1983 RTA00000404F.h.l0.1 37148 2 0 0 0 0 0 0 0
1984 RTA00000422F.n.l4.1 26787 2 0 0 0 0 0 0 0
1986 RTAOOOOO 120A.m.13.3 80608 1 0 0 0 0 0 0 0
1987 RTA00000412F.i.03.1 65617 1 0 0 0 0 0 0 0
1988 RTA00000418F.1.02.1 39316 2 0 0 0 0 0 0 0
1990 RTA0000041 1F.J.04.1 66219 1 0 0 0 0 0 0 0
1995 RTA00000404F.3.18.1 36267 2 0 0 0 0 0 0 0
1996 RTA00000408F.1.14.1 12001 2 3 0 0 0 0 0 0
1997 RTA00000405F.d.l0.1 39000 2 0 0 0 0 0 0 0
1999 RTA00000418F.h.23.1 75153 1 0 0 0 0 0 0 0
2001 RTA00000418F.J.1 1.1 73853 1 0 0 0 0 0 0 0
2002 RTA00000408F.O.13.1 74895 1 0 0 0 0 0 0 0
2003 RTA00000419F.O.07.1 14059 1 0 0 0 0 0 0 0
2004 RTA00000419F.n.l7.1 63186 1 0 0 0 0 0 0 0
2005 RTA00000403F.f.l5.1 22768 3 0 0 0 0 0 0 0
2006 RTA00000408F.d.03.1 22768 3 0 0 0 0 0 0 0
2008 RTA00000346F.f.02.1 62757 1 0 0 0 0 0 0 0
2010 RTA00000413F.i.21.1 64066 1 0 0 0 0 0 0 0
2012 RTA00000419F.h.21.1 64828 1 0 0 0 0 0 0 0
2021 RTA00000121A.3.2.1 81843 1 0 0 0 0 0 0 0
2022 RTA00000527F.g.l3.1 36035 2 0 0 0 0 0 0 0
2025 RTA00000426F.h.l l .l 75479 1 0 0 0 0 0 0 0
2030 RTA00000522F.b.22.1 75181 1 0 0 0 0 0 0 0
2033 RTA00000522F.3.23.1 38613 2 0 0 0 0 0 0 0
2035 RTA00000523F.b.02.1 65163 1 0 0 0 0 0 0 0
2036 RTA00000425F.J.14.1 73397 1 0 0 0 0 0 0 0
2039 RTA00000522F.e.l6.1 75283 1 0 0 0 0 0 0 0
2042 RTA00000523F.h.l7.1 65586 1 0 0 0 0 0 0 0
2044 RTA00000522F.p.07.1 76888 1 0 0 0 0 0 0 0
2045 RTA00000522F.n.08.1 76343 1 0 0 0 0 0 0 0
2046 RTA00000425F.C.06.1 78041 1 0 0 0 0 0 0 0
2047 RTA00000427F.b.23.1 64297 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib 1 lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl
2048 RTA00000527F.p.02.1 36844 2 0 0 0 0 0 0 0
2049 RTA00000427F.d.08.1 63967 1 0 0 0 0 0 0 0
2051 RTA00000426F.m.07.1 63504 1 0 0 0 0 0 0 0
2052 RTA00000427F.C.10.1 65478 1 0 0 0 0 0 0 0
2055 RTA00000424F.m.l5.1 73759 1 0 0 0 0 0 0 0
2056 RTA00000426F.f.l l .l 63102 1 0 0 0 0 0 0 0
2058 RTA00000426F.f.20.1 65134 1 0 0 0 0 0 0 0
2063 RTA00000527F.i.l9.2 38089 2 0 0 0 0 0 0 0
2068 RTA00000523F.e.l8.1 62898 1 0 0 0 0 0 0 0
2069 RTA00000527F.k.21.1 36051 2 0 0 0 0 0 0 0
2072 RTA00000522F.n.02.1 74959 1 0 0 0 0 0 0 0
2075 RTA00000425F.f.l9.1 32635 1 1 0 0 0 0 0 0
2076 RTA00000528F.e.23.1 19242 3 0 0 0 0 0 0 0
2077 RTA00000522F.n.l6.1 26769 1 0 0 0 0 0 0 0
2078 RTA00000427F.C.20.1 26527 1 0 0 0 0 0 0 0
2079 RTA00000527F.k.06.1 12469 3 1 0 0 0 0 0 0
2081 RTA00000523F.i.06.1 66341 1 0 0 0 0 0 0 0
2082 RTA00000427F.f.21.1 36853 2 0 0 0 0 0 0 0
2083 RTA00000427F.J.19.1 41395 1 1 0 0 0 0 0 0
2084 RTA00000522F.b.01.1 75691 1 0 0 0 0 0 0 0
2085 RTA00000424F.i.24.1 79101 1 0 0 0 0 0 0 0
2086 RTA00000523F.C.01.1 65710 1 0 0 0 0 0 0 0
2087 RTA00000427F.b.l5.1 66891 1 0 0 0 0 0 0 0
2090 RTA00000522F.J.15.2 76535 1 0 0 0 0 0 0 0
2093 RTA00000426F.f.l9.1 66701 1 0 1 0 0 0 0 0
2096 RTA00000523F.i.22.1 64688 1 0 0 0 0 0 0 0
2098 RTA00000425F.i.l7.1 43213 1 1 0 0 0 0 0 0
2101 RTA00000425F.p. l2.1 73219 1 0 0 0 0 0 0 0
2102 RTA00000427F.J.07.1 64819 1 0 0 0 0 0 0 0
2104 RTA00000527F.i.05.2 37481 2 0 0 0 0 0 0 0
2107 RTA00000523F.k.01.1 41437 1 1 0 0 0 0 0 0
2108 RTA00000425F.J.1 1.1 76667 1 0 0 0 0 0 0 0
2109 RTA00000424F.b.22.4 72971 1 0 0 0 0 0 0 0
211 1 RTA00000525F.3.03.1 36786 2 0 0 0 0 0 0 0
2112 RTA00000527F.i.21.2 37490 2 0 0 0 0 0 0 0
2113 RTA00000424F.3.24.4 73951 1 0 0 0 0 0 0 0
2114 RTA00000522F.k.l4.1 74280 1 0 0 0 0 0 0 0
2115 RTA00000522F.n.05.1 73260 1 0 0 0 0 0 0 0
2116 RTA00000523F.C.18.1 66179 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 lit
ID clones clones clones clones clones clones clones cl
NO:
21 17 RTA00000523F.b. l3.1 66330 1 0 0 0 0 0 0 0
21 19 RTA00000527F.p. l6.1 23798 2 1 0 0 0 0 0 0
2120 RTA00000425F.C.20.1 73581 1 0 0 0 0 0 0 0
2121 RTA00000424F.L21.1 73482 1 0 0 0 0 0 0 0
2122 RTA00000523F.J.19.1 65910 1 0 0 0 0 0 0 0
2124 RTA00000424F.b.22.1 72971 1 0 0 0 0 0 0 0
2125 RTA00000527F.b.l 8.1 37469 2 0 0 0 0 0 0 0
2129 RTA00000525F.e.l6.1 36837 2 0 0 0 0 0 0 0
2131 RTA00000522F.d.08.1 74284 1 0 0 0 0 0 0 0
2134 RTA00000527F.g.07.1 37488 2 0 0 0 0 0 0 0
2136 RTA00000525F.b.05.1 21 116 2 1 0 0 0 0 0 0
2137 RTA00000425F.n.05.1 73965 1 0 0 0 0 0 0 0
2138 RTA00000523F.d. l8.1 64072 1 0 0 0 0 0 0 0
2139 RTA00000525F.a.02.1 37454 2 0 0 0 0 0 0 0
2141 RTA00000426F.h.09.1 78797 1 0 0 0 0 0 0 0
2144 RTA00000427F.g.05.1 63138 1 0 0 0 0 0 0 0
2145 RTA00000424F.m.l2.1 77675 1 0 0 0 0 0 0 0
2151 RTA00000427F.h.l2.1 36894 2 0 0 0 0 0 0 0
2152 RTA00000523F.C.15.1 36935 2 0 0 0 0 0 0 0
2153 RTA00000427F. 17.1 64965 1 0 0 0 0 0 0 0
2155 RTA00000424F.C.14.3 76614 1 0 0 0 0 0 0 0
2156 RTA00000522F.k.l0.2 77619 1 0 0 0 0 0 0 0
2157 RTA00000424F.m.22.1 72943 1 0 0 0 0 0 0 0
2158 RTA00000527F.h. l7.1 37799 2 0 0 0 0 0 0 0
2159 RTA00000527F.C.22.1 37496 2 0 0 0 0 0 0 0
2160 RTA00000425F. 22.1 78123 1 0 0 0 0 0 0 0
2161 RTA00000424F.m. l4.1 77491 1 0 0 0 0 0 0 0
2162 RTA00000522F.k.l9.1 32625 1 1 0 0 0 0 0 0
2163 RTA00000523F.L18.1 64463 1 0 0 0 0 0 0 0
2164 RTA00000425F .22.1 73882 1 0 0 0 0 0 0 0
2165 RTA00000527F.g.23.1 37538 2 0 0 0 0 0 0 0
2166 RTA00000426F.m.24.1 63943 1 0 0 0 0 0 0 0
2168 RTA00000425F.d.21.1 78920 1 0 0 0 0 0 0 0
2170 RTA00000424F.d.04.3 76505 1 0 0 0 0 0 0 0
2171 RTA00000424F.d.04.1 76505 1 0 0 0 0 0 0 0
2172 RTA00000427F.C.12.1 66995 1 0 0 0 0 0 0 0
2174 RTA00000527F.il 3.1 36904 2 0 0 0 0 0 0 0
2175 RTA00000522F.h.l3.1 40823 1 1 0 0 0 0 0 0
2176 RTA00000424F.1.19.1 75454 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl
X JNTfUV.
2179 RTA00000427F.a.06.1 66550 1 0 0 0 0 0 0 0
2180 RTA00000525F.C.19.1 38159 2 0 0 0 0 0 0 0
2181 RTA00000523F.f.06.1 62871 1 0 0 0 0 0 0 0
2182 RTA00000424F.h. l0.1 72925 1 0 0 0 0 0 0 0
2183 RTA00000522F.a.l2.1 33515 1 1 0 0 0 0 0 0
2184 RTA00000522F.h.01.1 75010 1 0 0 0 0 0 0 0
2186 RTA00000425F.e.21.1 77203 1 0 0 0 0 0 0 0
2187 RTA00000523FT.07.1 62799 1 0 0 0 0 0 0 0
2189 RTA00000424F.J.12.1 73827 1 0 0 0 0 0 0 0
2191 RTA00000523F.d.l2.1 64888 1 0 0 0 0 0 0 0
2192 RTA00000523F.e. l0.1 62878 1 0 0 0 0 0 0 0
2193 RTA00000425F.f.l l .l 79275 1 0 0 0 0 0 0 0
2194 RTA00000426F.m. l 8.1 62974 1 0 0 0 0 0 0 0
2197 RTA00000522F.g.l5.1 76536 1 0 0 0 0 0 0 0
2198 RTA00000522F.n.l2.1 74117 1 0 0 0 0 0 0 0
2200 RTA00000424F.d.l0.3 731 10 1 0 0 0 0 0 0 0
2204 RTA00000527F.C.04.1 23090 3 0 0 0 0 0 0 0
2206 RTA00000527F.h.21.1 37630 2 0 0 0 0 0 0 0
2207 RTA00000425F.C.07.1 76042 1 0 0 0 0 0 0 0
2209 RTA00000525F.C.15.1 7692 2 0 0 0 0 0 0 0
2210 RTA00000424F.d.22.3 76189 1 0 0 0 0 0 0 0
221 1 RTA00000523F.h.l2.1 65745 1 0 0 0 0 0 0 0
2212 RTA00000522F.g.22.1 77504 1 0 0 0 0 0 0 0
2215 RTA00000522F.J.12.2 74341 1 0 0 0 0 0 0 0
2216 RTA00000523F.i.08.1 65099 1 0 0 0 0 0 0 0
2218 RTA00000425F .20.1 26760 1 0 0 0 0 0 0 0
2220 RTA00000427F.f.24.1 64572 1 0 0 0 0 0 0 0
2221 RTA00000527F.3.13.1 37740 2 0 0 0 0 0 0 0
2225 RTA00000424F.3.09.4 77833 1 0 0 0 0 0 0 0
2227 RTA00000525F.f.07.1 37500 2 0 0 0 0 0 0 0
2228 RTA00000424F.J.07.1 7921 1 1 0 0 0 0 0 0 0
2229 RTA00000424F.m.l0.1 34251 1 1 0 0 0 0 0 0
2231 RTA00000522F.g.06.1 78221 1 0 0 0 0 0 0 0
2232 RTA00000424F.h.03.1 74447 1 0 0 0 0 0 0 0
2233 RTA00000424F.n.06.1 74737 1 0 0 0 0 0 0 0
2234 RTA00000427F.C.22.1 63990 1 0 0 0 0 0 0 0
2235 RTA00000424F. 12.1 77666 1 0 0 0 0 0 0 0
2236 RTA00000425FT.02.1 76982 1 0 0 0 0 0 0 0
2237 RTA00000427F.h. l l .l 26494 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 lit
ID clones clones clones clones clones clones clones cl(
NO:
2238 RTA00000425FJ.16.1 75631 1 0 0 0 0 0 0 0
2240 RTA00000427F.f.l7.1 63803 1 0 0 0 0 0 0 0
2241 RTA00000522F.O.18.1 76366 1 0 0 0 0 0 0 0
2242 RTA00000427F .22.1 66367 1 0 0 0 0 0 0 0
2243 RTA00000426F.p.l0.1 65845 1 0 0 0 0 0 0 0
2244 RTA00000522F.m.02.1 76834 1 0 0 0 0 0 0 0
2247 RTA00000425F.e. l5.1 75921 1 0 0 0 0 0 0 0
2250 RTA00000424F.n.l3.1 74942 1 0 0 0 0 0 0 0
2251 RTA00000424F.g.l4.1 74879 1 0 0 0 0 0 0 0
2252 RTA00000426F.e.l7.1 64089 1 0 0 0 0 0 0 0
2256 RTA00000427F.g. l9.1 6461 1 1 0 0 0 0 0 0 0
2258 RTA00000522F.C.01.1 74938 1 0 0 0 0 0 0 0
2259 RTA00000522F.g.l7.1 76486 1 0 0 0 0 0 0 0
2260 RTA00000523F.J.17.1 63610 1 0 0 0 0 0 0 0
2261 RTA00000522F.n.l4.1 73410 1 0 0 0 0 0 1 0
2263 RTA00000523F.e.20.1 65164 1 0 0 0 0 0 0 0
2264 RTA00000424F.C.15.3 73533 1 0 0 0 0 0 0 0
2265 RTA00000426F.p.09.1 66665 1 0 0 0 0 0 0 0
2266 RTA00000522F.p.09.1 75204 1 0 0 0 0 0 0 0
2267 RTA00000426F.m.21.1 64915 1 0 0 0 0 0 0 0
2268 RTA00000425F.J.21.1 77373 1 0 0 0 0 0 0 0
2270 RTA00000523F.h.21.1 41440 1 1 0 0 0 0 0 0
2271 RTA00000427F.h.24.1 65193 1 0 0 0 0 0 0 0
2272 RTA00000425F.f.24.1 40841 1 1 0 0 0 0 0 0
2273 RTA00000425F.m.03.1 76045 1 0 0 0 0 0 0 0
2274 RTA00000426F.m.08.1 63781 1 0 0 0 0 0 0 0
2275 RTA00000523F.d.24.1 64799 1 0 0 0 0 0 0 0
2276 RTA00000523F.C.14.1 66015 1 0 0 0 0 0 0 0
2277 RTA00000523F.b.20.1 66492 1 0 0 0 0 0 0 0
2278 RTA00000522F.h.07.1 75149 1 0 0 0 0 0 0 0
2279 RTA00000527F.g.l0.1 37820 2 0 0 0 0 0 0 0
2282 RTA00000427F.i.22.1 63199 1 0 0 0 0 0 0 0
2284 RTA00000527F.n.07.1 15939 2 2 0 0 0 0 0 0
2285 RTA00000425F.e.09.1 75550 1 0 0 0 0 0 0 0
2286 RTA00000427F.h.02.1 63652 1 0 0 0 0 0 0 0
2287 RTA00000426F.f.16.1 65613 1 0 0 0 0 0 0 0
2288 RTA00000425F.i.21.1 75305 1 0 0 0 0 0 0 0
2289 RTA00000427F.k. l9.1 62851 1 0 0 0 0 0 0 0
2291 RTA00000426F.g. l6.1 41446 1 1 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 li'
ID clones clones clones clones clones clones clones cl
NO:
2292 RTA00000527F.1.05.1 13016 4 0 0 1 1 0 0 0
2293 RTA00000426F.m.02.1 66237 1 0 0 0 0 0 0 0
2296 RTA00000522F.1.22.1 75801 1 0 0 0 0 0 0 0
2297 RTA00000427F.h. l9.1 63047 1 0 0 0 0 0 0 0
2299 RTA00000522F.g.21.1 77310 1 0 0 0 0 0 0 0
2301 RTA00000522F.g.20.1 77688 1 0 0 0 0 0 0 0
2304 RTA00000425F. 20.1 74048 1 0 0 0 0 0 0 0
2306 RTA00000522F.b.07.1 78634 1 0 0 0 0 0 0 0
2307 RTA00000426F.g.l9.1 63672 1 0 0 0 0 0 0 0
2308 RTA00000525F.d. l9.1 36860 2 0 0 0 0 0 0 0
2310 RTA00000427F.d.l0.1 40685 1 1 0 0 0 0 0 0
2313 RTA00000424F.3.05.4 77976 1 0 0 0 0 0 0 0
2315 RTA00000424F.3.05.1 77976 1 0 0 0 0 0 0 0
2316 RTA00000522F.1.15.1 74691 1 0 0 0 0 0 0 0
2317 RTA00000425F.e.02.1 76143 1 0 0 0 0 0 0 0
2318 RTA00000525F.C.1 1.1 37895 2 0 0 0 0 0 0 0
2320 RTA00000522F.C.14.1 75449 1 0 0 0 0 0 0 0
2321 RTA00000424F.m.08.1 19402 1 2 0 0 0 0 0 0
2322 RTA00000527F.f.l8.1 37577 2 0 0 0 0 0 0 0
2324 RTA00000522F.a.06.1 73662 1 0 0 0 0 0 0 0
2327 RTA00000522F.d.23.1 73868 1 0 0 0 0 0 0 0
2330 RTA00000523F .10.1 63384 1 0 0 0 0 0 0 0
2331 RTA00000527F.p.08.1 36013 2 0 0 0 0 0 0 0
2333 RTA00000426F.f.l7.1 66334 1 0 0 0 0 0 0 0
2334 RTA00000523FJ.21.1 36925 2 0 0 0 0 0 0 0
2339 RTA00000523F.3.01.1 74923 1 0 0 0 0 0 0 0
2341 RTA00000427FJ.06.1 63676 1 0 0 0 0 0 0 0
2342 RTA00000424F.m.04.1 79017 1 0 0 0 0 0 0 0
2343 RTA00000523F.U7.1 65779 1 0 0 0 0 0 0 0
2346 RTA00000525F.C.18.1 24208 2 1 0 0 0 0 0 0
2347 RTA00000527F.e.09.1 37521 2 0 0 0 0 0 0 0
2348 RTA00000424F .08.1 73972 1 0 0 0 0 0 0 0
2350 RTA00000527F.C.09.1 64859 1 0 0 0 0 0 0 0
2353 RTA00000523F.C.03.1 36913 2 0 0 0 0 0 0 0
2354 RTA00000427F.k.21.1 62880 1 0 0 0 0 0 0 0
2356 RTA00000427F.d.09.1 66486 1 0 0 0 0 0 0 0
2357 RTA00000426F.n. l7.1 66572 1 0 0 0 0 0 0 0
2360 RTA00000426F.m.03.1 66480 1 0 0 0 0 0 0 0
2361 RTA00000424F.h.06.1 77552 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib 1 lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl
X INI fU"V.
2362 RTA00000425F.d.06.1 77660 1 0 0 0 0 0 0 0
2363 RTA00000427F.e. l2.1 62813 1 0 0 0 0 0 0 0
2366 RTA00000426F.n.23.1 18176 1 0 0 0 0 0 0 0
2367 RTA00000522F.m. l9.1 41544 1 1 0 0 0 0 0 0
2368 RTA00000522F.a.05.1 32611 1 1 0 0 0 0 0 0
2369 RTA00000427F.L09.1 65916 1 0 0 0 0 0 0 0
2370 RTA00000424F .09.1 74387 1 0 0 0 0 0 0 0
2371 RTA00000424F.n.l l .l 73874 1 0 0 0 0 0 0 0
2373 RTA00000527F.e.l3.1 37588 2 0 0 0 0 0 0 0
2375 RTA00000425F.J.19.1 77925 1 0 0 0 0 0 0 0
2376 RTA00000522F.g. l2.1 78783 1 0 0 0 0 0 0 0
2377 RTA00000523F.a.07.1 75804 1 0 0 0 0 0 0 0
2378 RTA00000425F.e. l 9.1 73409 1 0 0 0 0 0 0 0
2379 RTA00000425F.n.l9.1 78324 1 0 0 0 0 0 0 0
2384 RTA00000427F. 07.1 63742 1 0 0 0 0 0 0 0
2387 RTA00000522F.a.l7.1 79032 1 0 0 0 0 0 0 0
2388 RTA00000527F.1.19.1 36856 2 0 0 0 0 0 0 0
2389 RTA00000424F.L1 1.1 41569 1 1 0 0 0 0 0 0
2391 RTA00000424F.d.l9.3 73180 1 0 0 0 0 0 0 0
2392 RTA00000522F.J.09.2 78522 1 0 0 0 0 0 0 0
2393 RTA00000424F.m.24.1 77045 1 0 0 0 0 0 0 0
2394 RTA00000522F.J.19.2 76224 1 0 0 0 0 0 0 0
2398 RTA00000527F.J.12.2 37503 2 0 0 0 0 0 0 0
2399 RTA00000522F.g. l l .l 75432 1 0 0 0 0 0 0 0
2400 RTA00000522F.k.02.2 77622 1 0 0 0 0 0 0 0
2401 RTA00000427F.e. l3.1 66080 1 0 0 0 0 0 0 0
2402 RTA00000426F.f.l8.1 63271 1 0 0 0 0 0 0 0
2403 RTA00000427F.a.l2.1 63377 1 0 0 0 0 0 0 0
2404 RTA00000424F.b.23.4 77322 1 0 0 0 0 0 0 0
2408 RTA00000427F.f.02.1 36822 2 0 0 0 0 0 0 0
2410 RTA00000424F.i. l5.1 78043 1 0 0 0 0 0 0 0
2412 RTA00000522F.m.03.1 79194 1 0 0 0 0 0 0 0
2413 RTA00000522F.a.20.1 74070 1 0 0 0 0 0 0 0
2414 RTA00000424F.b.l5.4 74958 1 0 0 0 0 0 0 0
2415 RTA00000527F.g.l4.1 37532 2 0 0 0 0 0 0 0
2416 RTA00000522F.d.06.1 74809 1 0 0 0 0 0 0 0
2418 RTA00000427F.e. l0.1 64599 1 0 0 0 0 0 0 0
2419 RTA00000527F.C.16.1 22908 3 0 0 0 0 0 0 0
2421 RTA00000523F.f.l7.1 63984 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI
ID clones clones clones clones clones clones clones cl
NO:
2423 RTA00000527F.p.24.1 36832 2 0 0 0 0 0 0 0
2424 RTA00000425F.n. l7.1 78304 1 0 0 0 0 0 0 0
2426 RTA00000425F.e.07.1 75992 1 0 0 0 0 0 0 0
2428 RTA00000523F.h.08.1 62893 1 0 0 0 0 0 0 0
2429 RTA00000522F.O.10.1 78798 1 0 0 0 0 0 0 0
2430 RTA00000425F.1.10.1 26893 1 0 0 0 0 0 0 0
2431 RTA00000427F.f.l6.1 64122 1 0 0 0 0 0 0 0
2434 RTA00000425F.i.l0.1 78736 1 0 0 0 0 0 0 0
2435 RTA00000426F.m.l2.1 63740 1 0 0 0 0 0 0 0
2436 RTA00000527F.g.l2.1 37746 2 0 0 0 0 0 0 0
2439 RTA00000425F.i.l8.1 42255 1 1 0 0 0 0 0 0
2441 RTA00000424FJ.13.1 74485 1 0 0 0 0 0 0 0
2445 RTA00000424F.k.l0.1 73232 1 0 0 0 0 0 0 0
2446 RTA00000522F.i.07.2 78377 1 0 0 0 0 0 0 0
2448 RTA00000522F.b.08.1 26915 1 0 0 0 0 0 0 0
2449 RTA00000522F.1.08.1 78781 1 0 0 0 0 0 0 0
2450 RTA00000525F.3.14.1 37566 2 0 0 0 0 0 0 0
2451 RTA00000424F.g.08.1 74928 1 0 0 0 0 0 0 0
2452 RTA00000425F.1.09.1 75251 1 0 0 0 0 0 0 0
2453 RTA00000522F.O.20.1 74853 1 0 0 0 0 0 0 0
2454 RTA00000527F.J.04.2 1 1809 3 1 0 0 0 0 0 0
2456 RTA00000523F.C.13.1 40668 1 1 0 0 0 0 0 0
2457 RTA00000427F.L21.1 65540 1 0 0 0 0 0 0 0
2459 RTA00000522F.h.02.1 74947 1 0 0 0 0 0 0 0
2460 RTA00000522F.g.l0.1 74294 1 0 0 0 0 0 0 0
2464 RTA00000425F.k.l6.1 75282 1 0 0 0 0 0 0 0
2465 RTA00000525F.b.09.1 23472 2 1 0 0 0 0 0 0
2466 RTA00000522F.J.08.2 76613 1 0 0 0 0 0 0 0
2468 RTA00000523FT.19.1 34169 1 1 0 0 0 0 0 0
2469 RTA00000425F.J.18.1 75561 1 0 0 0 0 1 0 0
2470 RTA00000426F.m.04.1 36865 2 0 0 0 0 0 0 0
2471 RTA00000527F.g.21.1 36028 2 0 0 0 0 0 0 0
2473 RTA00000525F.3.22.1 36848 2 0 0 0 0 0 0 0
2474 RTA00000522F.p.22.1 73322 1 0 0 0 0 0 0 0
2475 RTA00000424F.d.l2.2 74342 1 0 0 0 0 0 0 0
2476 RTA00000424F.g.24.1 79156 1 0 0 0 0 0 0 0
2477 RTA00000427F.a.l0.1 65370 1 0 0 0 0 0 0 0
2478 RTA00000426F.h.20.1 23187 3 0 0 0 0 0 0 0
2479 RTA00000424F.d.l2.3 74342 1 0 0 0 0 0 0 0
SEQ Sequence Name cluster lib l lib 2 lib 15 lib 16 lib 17 lib 18 lib 19 HI ID clones clones clones clones clones clones clones cl NO: 2480 RTA00000425F.C.03.1 74643 1 0 0 0 0 0 0 0
2481 RTA00000523F.f.l6.1 26522 1 0 0 0 0 0 0 0
2482 RTA00000427F.f.l5.1 66734 1 0 0 0 0 0 0 0
2485 RTA00000522F.p. l 8.1 76376 1 0 0 0 0 0 0 0
2493 RTA00000522F.g. l 8.1 73226 1 0 0 0 0 0 0 0
2495 RTA00000522F.h.05.1 73358 1 0 0 0 0 0 0 0
2497 RTA00000425F.n.l6.1 18265 1 0 0 0 0 0 0 0
2498 RTA00000527F.1.21.1 36439 2 0 0 0 0 0 0 0
2501 RTA00000424F.d.l7.3 73958 1 0 0 0 0 0 0 0
2502 RTA00000523FJ.02.1 62853 1 0 0 0 0 0 0 0
Table 21. Clones Deposited on January 22, 1999 cDN A Library Ref No. cDNA ES17 cDNA ESl δ CDNA ES19 ATCC Accession No. ATCC No. ATCC No. ATCC No.
Clone Names in M00001368A:D07 M00001594A:D06 M00003906A:F04 Library M00003917A:D02 M00001613D:H10 M00003908A:F12
M00001673A:A04 M00001596D:E10 M00003914A:G09
M00003868B:G1 1 M00001592C:G04 M00003915C:H04
M00003917C:D03 M00001599D:A09 M00003905D:B08
M00003791C:E09 M00001619B:A09 M00003908C:G09
M00003870A:C05 M00001593B:E1 1 M00003914B:A1 1
M00003922A:D02 M00001605A:E06 M00003916C:C05
M00003861C:H02 M00001608A:D03 M00003959A:A03
M00003931B:A1 1 M00001616C:A02 M00003905D:C08
M00001679D:B05 M00001617A:D06 M00003908D:D12
M00001679C:D05 M00001595C:E01 M00003901B:H04
M00001687A:G01 M00001616C:A1 1 M00004031A:E01
M00003945A:E09 M00001608C:E1 1 M00004029C:C12
M00003908A:H09 M00001610C:E06 M0000391 1A:F10
M00001649B:G12 M00001612B:D1 1 M00003914C:F09
M00003813D:H12 M00001618B:E05 M00003963D:B05
M00004087C:D03 M00001621C:C10 M00003986C:E09
M00004269B:C08 M00001647A:H08 M00004031A:F07
M00004348A:A02 M00001631D:B10 M00003907C:C02
M00001679C:D01 M00001608D:E09 M0000391 1B:F08
M00001490A:E1 1 M00001641B:C10 M00003914C:H05
M00001387A:E10 M00001641D:E02 M00003918C:C12
M00001397B:G03 M00001630D:H10 M00003914C:C02
M00001441D:E04 M00001585C:D10 M00003914A:E04
M00001352C:G09 M00001560A:H10 M00003903B:D03
M00001370D:A12 M00001573B:C06 M00003905A:F09
M00001387B:A06 M00001660C:D1 1 M00003867C:E1 1
M00001397C:A10 M00001641C:C05 M00003870B:B08
M00001536D:G02 M00001578B:B05 M00003879D:A08
M00003895C:A10 M00001587C:C10 M00003891D:B10
M00001464B:B03 M00001590B:C07 M00003901C:A08
M00004370A:G05 M00001554A:E04 M00003903C:C04
M00001490B:H1 1 M00001570C:G06 M00003905A:F10
M00001530B:D10 M00001576A:B09 M00003906C:D06
M00001579C:E09 M00001582A:H01 M00003907D:A12
M00001587A:H03 M00001582B:E12 M00003905C:G1 1
M00001457C:H12 M00001615B:F07 M00003914D:D10
M00001535C:E01 M00001571C:A04 M00003972A:G09
M00001561D:C05 M00001573D:D10 M00003975D:C06
M00001589A:C01 M00001576A:F1 1 M00003905C:B02
M00001664D:G07 M00001579C:G05 M00003907D:F1 1
M00001565A:H09 M00001582D:A02 M00003914A:G06
M00001381C:B08 M00001589B:E07 M00003914D:E03
M00001395C:F1 1 M00001575B:B02 M00003972C:F08
M00001429D:F1 1 M00001578C:G06 M00003976C:D06
M00001449A:F01 M00001591A:B08 M00003907C:C04
M00001391C:H02 M00001607A:F1 1 M00003905B:C06
M00001429D:H12 M00001579C:E06 M00004088C:A12
M00001450A:G1 1 M00001661C:F1 1 M00004103C:D04
M00001344B:F12 M00001650B:C10 M00004107A:D01
cDN A Library Ref No. cDNA ES17 cDNA ES18 CDNA ES19 ATCC Accession No. ATCC No. ATCC No. ATCC No.
M00001391D:C06 M00001654C:E04 M000041 10A:E04
M00003971A:A06 M00001656B:A08 M00004062A:H06
M00001346A:E04 M00001662C:B02 M00004075D:C10
M00001455C:G07 M00001656B:D05 M00004081D:H09
M00001402D:F02 M00001661C:F10 M00004089A:B08
M00001438D:C06 M00001663A:C1 1 M00004103D:F10
M00001349B:G05 M00001669A:C10 M00004107B:B04
M00001389C:A08 M00001651B:B12 M00004032C:B02
M00001439B:A10 M00001653B:E06 M00004078C:F04
M00001455B:A09 M00001659C:F02 M00004038B:H10
M00001441B:D1 1 M00001661B:F03 M00004089A:E02
M00001453A:B01 M00001663C:F10 M00004096B:F05
M00001456D:E08 M00001669A:G12 M00004104C:H12
M00001399A:C03 M00001674D:C10 M000041 10D:A10
M00004496C:H03 M00001651B:E06 M00004036D:F02
M00004135D:G02 M00001651C:C05 M00004088C:E04
M00004692A:E07 M00001657C:C07 M00004104D:A04
M00004374D:E10 M00001662A:C12 M00004107D:E12
M00004405D:C04 M00001663D:C06 M000041 15D:D08
M00004312B:H07 M00001590B:C05 M00003846A:D03
M00003976C:A10 M00001483C:G06 M00004072C:F08
M00004043A:D02 M00001653A:G07 M00004039B:G08
M00004081C:H06 M00001625B:C10 M00003986D:D02
M00004050D:A06 M00001626C:D12 M00003914A:B07
M00001361B:C07 M00001634D:D02 M00003914D:B02
M00004341B:G03 M00001641C:C06 M00003971 B:B07
M00001342B.Ε01 M00001642D:F02 M00003978C:A03
M00004064D:A1 1 M00001647B:E04 M00003983B:C08
M00004087A:G08 M00001632B:E05 M00004033D:D07
M00004344B:H04 M00001639A:C1 1 M00004072D:H12
M00004497A:H03 M00001642D:G10 M00004077B:H1 1
M00001338C:E10 M00001624A:G1 1 M00004080A:F01
M00001366D:E12 M00001626C:G08 M00004092C:B03
M00001390D:E03 M00001672D:D04 M00004037B:C04
M00001413B:H09 M00001639A:H06 M00004073C:D04
M00004271B:B06 M00001662C:A04 M00004081A:A08
M00004151D:E03 M00001641B:B01 M00004085B:B05
M00001660B:C04 M00001673C:A02 M00004090C:C07
M00003802D:B1 1 M00001650A:A12 M00004086D:B09
M00001579C:E08 M00001659D:D03 M00004088D:B03
M00001557D:C08 M00001661B:B05 M00004090C:C10
M00003779B:E12 M00001671D:E10 M00004102C:D09
M00001638A:D10 M00001652D:A06 M00004105C:E09
M00003794A:B03 M00001654C:D05 M00004035A:G10
M00001616C:F07 M00001656A:B07 M00003906A:H07
M00001679A:F01 M00001647B:C09 M00004083B:G03
M00001604C:E09 M00001635A:C06 M00001675B:E02
M00001653B:E09 M00001482D:A04 M00003793C:D09
M00001585A:F07 M00001485C:B10 M00003762B:H09
M0000381 1D:A12 M00001457D:A07 M00001694C:F12
M00001653C:F12 M00001461A:E05 M00001678D:C1 1
M00001679D:F06 M00001477A:G07 M00001677D:B07
cDNA Library Ref No. cDNA ES17 CDNA ES18 CDNA ES19 ATCC Accession No. ATCC No. ATCC No. ATCC No.
M00003751D:B02 M00001479D:H03 M00001677B:A02
M00003801A:B10 M00001482C:D02 M00001675B:H03
M00003844C:A08 M00001484D:G05 M00003808D:D04
M00001636C:C01 M00001459B:D03 M00003752B:C02
M00001669C:B01 M00001464B:C1 1 M00003819D:B1 1
M00003755A:A09 M0000151 1A:A05 M00001677D:B02
M00003798D:H08 M00001477B:C02 M00001694C:G04
M00001444C:D05 M00001471A:D04 M00003789C:F06
M00004040B.-F10 M00001485C:H10 M00001678C:C06
M00001355A:C12 M00001485D.-E05 M00001675B:D02
M00001401A:H07 M00001487C:G03 M00003750C:H05
M00001393B:B09 M00001514A:B04 M00001694A:B12
M00001409D:F1 1 M00001530C:G10 M00001677B:H06
M00001387B:H07 M00001534A:G06 M00001675C:G01
M00001394C:C1 1 M00001539A:C12 M00001675B:C01
M00001344A:H07 M00001547A:F11 M00003857B:F07
M00001490C:D07 M00001550D:A04 M00003812B:D07
M00001352C:F06 M00001460A:F07 M00001694B:B08
M00001476D:G03 M00001472C:A01 M00001677B:E06
M00001399C:D09 M00001481B:A07 M00004037A:E04
M00001347C:G08 M00001456D:F05 M00003870A:H01
M00001453D:G12 M00001456D:G1 1 M00003842C:D1 1
M00001382A:F04 M00001477D:F10 M00003828B:F09
M00001392D:H04 M00001481A:G06 M00003856C.H09
M00001429C:G12 M00001464A:B03 M00003851A:C10
M00001454A:C1 1 M00001469A:G1 1 M00003841C:E04
M00001517B:G08 M00001478B:D07 M00003837C:G08
M00001535A:D02 M00001473A:C1 1 M00003828B:E07
M00001352A:E12 M00001457A:G03 M00003772C:B12
M00001381B:F06 M00001669B:G02 M00001677D:F03
M000041 17A:D1 1 M00001479D:G06 M00001678B:B12
M00004217C:D03 M00001473D:B1 1 M00001678D:G03
M00004270A:F1 1 M00001475A:A12 M00001675C:F01
M00003996A:A06 M00001460A:G07 M00003809A:H04
M00004056B:D09 M00001464A:D03 M00003771D:G05
M00004142A:B12 M00001473D:G01 M00001678A:F05
M00001396D:B03 M00001476D:C05 M00001677B:B06
M00001370D:E12 M00001484A:A10 M00003794A:E12
M00001390C:C1 1 M00001457C:F02 M00003771B:E05
M00003989A:H1 1 M00001459B:A12 M00001678A:A1 1
M00001426A:A09 M00001464A.Ε07 M00003805B:C04
M00004498D:D05 M00001467A:B03 M00001680B:E10
M00001391B:G12 M00001514A:B08 M00001679B:H07
M00001391D:D10 M00001464A:B07 M00003904D:B12
M00001376B:A02 M00001579A:C03 M00003856C:B08
M00001405B:D07 M00001517A:G08 M00003858D:G06
M00001368A:A03 M00001530B:G09 M00003870B:F04
M00001392D:B1 1 M00001538A:F12 M00003871C-.B05
M00003900D:B10 M00001540C:B03 M00003875A:C04
M00001494B:C01 M00001547A:F06 M00003901B:A09
M00001352C:A05 M00001550A:F07 M00003901C.-D03
M00001408B:G06 M00001567B:G1 1 M00003904C:B06
cDNA Library Ref No. CDNA ES17 CDNA ES18 CDNA ES19 ATCC Accession No. ATCC No. ATCC No. ATCC No.
M00004252C:E03 M00001572A:A10 M00003901C:F09
M00003901C:A03 M00001575B:G01 M00003904D:B10
M00004071D:A10 M00001487D:C1 1 M00003850D:H1 1
M00001377B:H01 M00001577B:A03 M00003902B:D06
M00003939A:A02 M00001539D:E10 M00003879A:C01
M00004250D:D10 M00001587A:F05 M00003877D:G05
M00004290A:B03 M00001560A:F03 M00003881D:C12
M00003911D:B04 M00001569B:G11 M00003903A:H09
M00004128B:G01 M00001573A:A06 M00003905A:A06
M00004142A:D08 M00001575D:A10 M00003875D.-D09
M00003977A:E04 M00001583A:D01 M00003879B:A06
M00004236C:D10 M00001587A:F08 M00003823D:G05
M00004388B:A08 M00001590B:B02 M00003763A:C01
M00004409B:A1 1 M00001553A:E07 M00003903B:C02
M00003965A:B1 1 M00001560A:H06 M00003905A:E07
M00003988A:E10 M00001589C:A1 1 M00003867A:D12
M00004138A:H09 M00001538A:C08 M00003857C:C09
M00003933C:D06 M00001531A:H03 M00003829C:D10
M00004193C:G1 1 M00001548A:G01 M00003839D:E02
M00004039C:C01 M00001531A:H07 M00003841C:F03
M00003924B:D04 M00001542A:E04 M00003903D:C06
M00004375C:D01 M00001487A:F10 M00003852D:E08
M00001503C:G05 M00003845D:A09
M0000151 1A:G08 M00003824A:G10
M00001539A:H12 M00003841C.F06
M00001542A:F06 M00003848A:C09
M00001549A:F01 M00003857C:F11
M00001514A:A12 M00003816C:C01
M00001516A:D05 M00003843A:E08
M00001546C:C07 M00003850A:F06
M00001549A:H1 1 M00003813B:A1 1
M00001538A:D03 M00003855C:F10
M00001544A:C09 M00003850D:B05
M00001546B:F12 M00003841D:F06
M00001550A:D09 M00003858B:G05
M00001487B:F02 M00003854D:A12
M00001513A:G07 M00003857C:G01
M00001530A:F12 M00003816C:E09
M00001538A:D12 M00003813A:G04
M00001587A:G06 M00003850D:A05
M00001551A:D04
M00001485B:C03
Table 22. Clones Deposited on January 22, 1999 cDNA Ref No.; cDNA Ref ES20 cDNA Ref No. ES27 cDNA Ref ES28 ATCC Accession No. ATCC No. ATCC No. ATCC No. Clone Nsmes in M00004891D:A07 M00001623B:G07 M00001550D:H02 Library M000041 18B:C1 1 M00001619D:G05 M00001549C:D02
M00004105A:B10 M00001616C:C09 M00001549A:A09
M00004099A:F1 1 M00001615C:F03 M00001548A:B1 1
M00004037C:D07 M00001614D:D09 M00001546C:G10
M00004033D:C05 M00001608B:A03 M00001544C:C06
M00003983D:A09 M00001607D:F07 M00003820B:C05
M00004029B:H08 M00001623D:C10 M00001543A:H12
M00004927A:A02 M00001599B:E09 M00001540C:B10
M00003983C:F10 M00001632C:C09 M00001552B:G05
M00003980B:C06 M00001605C:D12 M00001543C:F01
M00004033D:B07 M00001625D:C07 M00001552D:G08
M00004034C:E08 M00001629B:E06 M00001554B:B07
M00005100B:H07 M00001594A:B12 M00001555A:B01
M00005136A:D10 M00001632C:A02 M00001557A:F01
M00005173D:H02 M00001567C:H12 M00001558A:E1 1
M00004891D:C1 1 M00001635C:A03 M00001561C:E1 1
M00004101A:F07 M00001636C:H09 M00001571D:B11
M00003982B:B06 M00001638A:E07 M00001563B:D1 1
M00004108C:E01 M00001639A:F10 M00001569C:B06
M00005136D:B07 M00001656C:G08 M00001539B:H06
M000041 18D:A11 M00001632A:F12 M00001571B:E03
M00005102C:C01 M00001557A:D02 M00001561D:C1 1
M00005177C:A01 M00001529B:C04 M00001487C:D06
M00004927C:H1 1 M00001534B:C12 M00001454B:D08
M00005174D:B02 M00001535D:C01 M00003772D:E10
M00004027A:D06 M00001536D:A12 M00001573C:D03
M00005217A:G10 M00001540B:C09 M00001454D:E05
M00003984A:B06 M00001540D:D02 M00001455D:F09
M00003851C:D07 M00001541C:B07 M00001457C:C1 1
M00003959C:G06 M00001546B:B02 M00001459B:C09
M00005100B:G1 1 M00001575B:C09 M00001460A:E01
M00005213C:G01 M00001554B:C07 M00001460C:H02
M00003982B:H07 M00001578D:C04 M00001456A:H02
M00004029C:B03 M00001557C:H07 M00001477B:F04
M00004033D:G06 M00001558B:D08 M00003845D:B04
M00004091B:H09 M00001560D:A03 M00001488A:E01
M00003959D:A04 M00001561C:F06 M00001492D:A1 1
M00004030D:B06 M00001564D:C09 M00001496C:G10
M00004034C:C06 M00003748B:F02 M00001499A:A05
M00004030C:D12 M00001570D:A03 M00001500A:B02
M00003982C:H10 M00001660C:B12 M00001500D:E10
M00003971C:F09 M00001577B:H02 M00001513D:A03
M00004031B:A06 M00001548A:A08 M00001528A:C1 1
M00003966B:D02 M00003868B:D12 M00001528C:H04
M00004028B:G08 M00001718D:F07 M00001531B:E09
M00004031C:H10 M00003829C:A1 1 M00001463A:F06
M00004076D:B09 M00003832B:E01 M00003755A:B03
cDNA Ref No.; cDNA Ref ES20 cDNA Ref No. ES27 cDNA Ref ES28 ATCC Accession No. ATCC No. ATCC No. ATCC No.
M00004092D:B 1 1 M00003842B:D09 M00001653B:G07
M00003981C:F05 M00003845A:H12 M00001654D:G11
M00004031 D:F05 M00003847B:G03 M00001656B:A07
M00004097B:D03 M00003847C:E09 M00001664B:D06
M00003986D:G07 M00003853D:G08 M00001664C:H10
M00004033B:C02 M00003828A:E04 M00001680B:C01
M00004037B:A04 M00003867C:H09 M00001681A:F03
M00004092C:B12 M00003822A:F02 M00001684B:G03
M00005140D:G09 M00003868C:H10 M00001771A:A07
M00004897D:G05 M00003871A:A05 M00003774C:D02
M00004960B:D12 M00003879C:G10 M00003754D:D02
M00005134C:G04 M00003880C:F10 M00001640B:F03
M00005139A:F01 M00003881D:D06 M00003763B:H01
M00005176A:C12 M00003884D:G07 M00003812C:A05
M00005178A:A07 M00003887A:A06 M00003803C:D09
M00005212A:A02 M00003889A:D10 M00003801B:B10
M00005229D:H07 M00003889D:B09 M00003798D:E03
M000041 15C:H04 M00003858D:F12 M00003773B:G01
M00004687A:C03 M00003774B:B08 M00003771A:G10
M00004900C:E11 M00001680D:D02 M00001452A:E07
M00004695B:E04 M00001528A:F09 M00004029B:F1 1
M00005134D:A06 M00003748A:B07 M00003751B:A05
M00004103B:B07 M00001655A:F06 M00001609B:A1 1
M00005177A:B06 M00003750A:D01 M00001573D:F10
M00005178A:A08 M00003761D:E02 M00001579C:B1 1
M00004104D:B05 M00003763D:E10 M00001579C:H10
M000041 17B:G01 M00003768A:E02 M00001579D:G07
M00004900D:B10 M00003829B:G03 M00001583B:E10
M00005134D:H03 M00003772A:D07 M00001586D:E02
M00005173C:A02 M00001661B:C08 M00001587D:A10
M00005177A:H09 M00003778A:D08 M00001589A:D12
M00005178B:H01 M00003799A:D09 M00001590C:H08
M00005216C:B09 M00003800A:C09 M00001651B:A1 1
M00003826B:E11 M00003804A:H04 M00001597A:E12
M00001596A:G06 M00003806D:G05 M00001649C:B10
M00005100B:D02 M00003808C:B05 M00001614A:E06
M00005137A:E01 M0000381 1A:E03 M00001615C:D02
M000041 19A:A06 M00003815D:H09 M00001621D:D03
M00004891 D:E07 M00003818B:G12 M00001623D:G03
M00004958B:D01 M00003769B:D03 M00001624A:F09
M00005102C:F09 M00001390A:A09 M00001624C:A06
M00005136D:C01 M00001432A:E06 M00001630B:A1 1
M00005174D:H02 M00001381A:D02 M00001634B:C10
M00005177C:B04 M00001383A:G04 M00001639D:B07
M00005218B:D09 M00001384C:E03 M00001573D:F04
M00004102C:F03 M00001384C:F12 M00001595B:A09
M000041 14B:D09 M00001384D:H07 M00004156B:A12
M000041 19D:A07 M00001385B:F10 M00004319D:G09
M00004895C:G05 M00001385C:H1 1 M00004096A:G02
M00004235A:A12 M00001386A:C02 M00004101C:G08
cDNA Ref No.; cDNA Ref ES20 cDNA Ref No. ES27 cDNA Ref ES28 ATCC Accession No. ATCC No. ATCC No. ATCC No.
M00005134B:E01 M00001372C:F07 M00004102A:H02
M000041 15C:G03 M00001389D:G1 1 M00004108A:A09
M00005175B:H04 M00001371D:G01 M000041 1 1D:D1 1
M00005214B:D11 M00001392C:D10 M00004115D:C08
M00004102D:B05 M00001392D:H06 M000041 18D:E08
M000041 15A:B12 M00001397B:B09 M00004121C:F06
M000041 19D:H06 M00001398A:G03 M00004131B:H09
M00004897D:F03 M00001400A:F06 M00004141D:A09
M00004960B:A09 M00001410B:G05 M00004090A:F09
M00005134C:E1 1 M00001413A:F02 M00004146A:C08
M00005138B:D12 M00001415B:E09 M00004078B:A1 1
M00005176A:A05 M00001425A:C1 1 M00004176B:E08
M00005214C:A09 M00001386A:D1 1 M00004188C:A09
M00004102C:D01 M00001354C:B06 M00004233C:H09
M00004960B:A08 M00001339D:G02 M00004241D:F1 1
M00001476D:A09 M00001660A:C 12 M00004246C:A09
M00001572A:B06 M00001528A:A01 M00004247C:C 12
M00005217D:F12 M00001343D:C04 M00004248B:E08
M00005233A:G08 M00001347B:E01 M00004257C:H06
M00005236B:F10 M00001348A:D04 M00004260D:C12
M00005259B:C01 M00001349C:C05 M00004295B:D02
M00005254D:B08 M00001350A:D06 M00004040D:F01
M00005259C:B05 M00001352D:C05 M00004142D:E10
M00001575A:D06 M00001380C:E05 M00003853D:D03
M00005259D:H08 M00001354B:B10 M00003860D:H07
M00003813C:D08 M00001380C:F02 M00003878C:E04
M00001530D:E06 M00001354C:C10 M00003879A:G05
M00004891 B:B12 M00001355B:G1 1 M00003880B:C08
M00001596B:C1 1 M00001356D:F06 M00003881A:D09
M00004300C:H09 M00001360D:E1 1 M00003881C:G09
M00001486D:D12 M00001361C:H1 1 M00003901B:A05
M00001585D:F03 M00001362C:A10 M00003904D:D10
M00001596B:D09 M00001363C:H02 M00003905C:G10
M00001570D:E06 M00001366D:G02 M00003906B:F12
M00001582C:E01 M00001369A:H12 M00003909A:H04
M00001586C:E06 M00001352D:D02 M00004091B:D1 1
M00001593B:D10 M00001485D:B10 M00003963A:E03
M00001595C:H1 1 M00001457B:E03 M00004353C:H07
M00001596B:H05 M00001457C:C12 M00003919A:A10
M00001576A:C11 M00001458C:E01 M00003938A:B04
M00001596C:F09 M00001462B:A10 M00003939C:F04
M00001567A:H05 M00001464D:F06 M00003946D:C1 1
M00001585D:D1 1 M00001467D:H05 M00003979A:F03
M00004688A:A02 M00001468B:H06 M00003985C:F01
M00004927A:E06 M00001505C:H01 M00003997B:G07
M00005229D:H09 M00001470A:H01 M00003860D:A01
M000041 17B:A12 M00001457A:B07 M00004035A:A04
M00004187D:G09 M00001479B:A01 M00004042D:H02
M00005173B:F01 M00001469D:D02 M00004073B:B01
M00005218A:G05 M00001487A:A05 M00003946A:H10
cDNA Ref No.: cDNA Ref ES20 cDNA Ref No. ES27 cDNA Ref ES28 ATCC Accession No. ATCC No. ATCC No. ATCC No.
M000041 18A:H08 M00001352C:H02 M00001423D:A09
M00005134A:D1 1 M00001488D:C 10 M00004314B:G07
M00005176C:C09 M00001490C:C12 M00001405D:D1 1
M00005230D:F06 M00001493B:D09 M00001408A:H04
M00005234D:B04 M00001504D:D1 1 M00001408D:D04
M00005101C:E09 M00001376B:C06 M0000141 1D:F05
M00004206A:E02 M00001506B:D09 M00001412A:E04
M00001570C:A05 M0000151 1 B:C06 M00001413A:F03
M00005231A:H04 M00001476B:F10 M00001417B:C04
M00005235A:A03 M00001450D:D04 M00001417D:A04
M000041 18B:B04 M00001433A:G07 M00001418B:F07
M00005136D:D06 M00001470C:B 10 M00001419D:C10
M00005231C:B01 M00001437D:C04 M00001402B:F12
M00004153B:B03 M00001447C:C01 M00001423A:G05
M00004897C:D06 M00001448B:F06 M00001401C:H03
M00005136D:G06 M00001449D:A06 M00001423D:D12
M00005212B:A02 M00001433B:H1 1 M00001424B:H04
M00005232A:C 10 M00001451D:C 10 M00001428B:A09
M00004692A:H10 M00001452A:C07 M00001430A:A02
M00005101C:B09 M00001453C:A1 1 M00001432D:F05
M00004144A:F04 M00001456B:C09 M00001438B:B09
M00003852B:D1 1 M00001454B:G03 M00001445B:E04
M00001660D:E05 M00001454B:G07 M00001445C:A08
M00003808A:F09 M00001454C:C08 M00001446C:D09
M00001656A:D10 M00001454C:F02 M00001448A:G09
M00001671A:H06 M00001454D:D06 M00001449C:H12
M00003809C:H07 M00001456B:F10 M00001422C:F12
M00003853C:C06 M00001455D:A09 M00001352C:H10
M00003860A:A08 M00001455D:A1 1 M00004375A:H01
M00003822B:D08 M00001448D:F09 M00004380B:A05
M00003845A:E12 M00004444B:D1 1
M00003854C:C02 M00001338B:E02
M00003860B:G09 M00001341A:F12
M00003822B:G01 M00001344A:G07
M00001670A:C1 1 M00001345A:G1 1
M00003852A:B03 M00001345B.Ε10
M00003829D:A1 1 M00001345C:B01
M00003854C:F01 M00001346B:B07
M00003856B:C04 M00001405B:E09
M00003905A:H1 1 M00001352B:F04
M00001530A:F1 1 M00001451C:E01
M00003840B:E07 M00001361A:H07
M00003905B:G03 M00001362B:H06
M00003840B:E08 M00001372C:G12
M00003855A:C12 M00001375B:G12
M00003905B:H05 M00001376A:C05
M00003826B:B04 M00001376B:A08
M00003851C:B06 M00001377C:E12
M00003853B:C08 M00001382B:F12 00003829A:F03 M00001385A:F12
cDNA Ref No.: cDNA Ref ES20 cDNA Ref No. ES27 cDNA Ref ES28 ATCC Accession No. ATCC No. ATCC No. ATCC No.
M00001638C:G01 M00001394A:E04
M00003845D:B02 M00001395A:C09
M00001653D:G07 M00001396A:H03
M00001578B:A02 M00001350B:G1 1
M00001590B:H10
M00001595C:A09
M00001596A:E07
M00001607A:B06
M00001607A:D10
M00001652C:B09
M00001671B:F02
M00001632C:D08
M00001638C:H07
M00001652D:B09
M00001614C:E1 1
M00001633B:B1 1
M00001651C:A04
M00001639D:G12
M00001671C:F1 1
M00001638A:B04
M00001637C:H12
M00001669B:H06
M00001639D:F02
M00001590A:C08
M00001636A:C02
M00001614A:A04
M00001639D:G06
Table 23. Library Deposited on January 22, 1999 cDNA Ref No.; cDNA Library Ref ES29 cDNA Library Ref ES30 ATCC Accession No. ATCC No. ATCC No. Clone Names in M00001449D:B01 M00001594D:B08 Library M00001476D:F03 M00001593A:B07
M00001456C:B12 M00001594A:C01
M00001469B:B01 M00001594A:D08
M00001471A:B04 M00001594A:G09
M00001472A:D08 M00001595C:B05
M00001473A:A07 M00001594B:F12
M00001473C:D09 M00001596D:E03
M00001475B:C04 M00001594D:C03
M00001475C:G1 1 M00001592C:F11
M00001476A:D1 1 M00001590D:G07
M00001476B:D10 M00001595D:A04
M00001468A:C05 M00001595D:G03
M00001476C:C1 1 M00001601A:A06
M00001467A:H07 M00001590C:F10
M00001477B:E02 M00001589B:B08
M00001478B:H08 M00001589C:E06
M00001479C:E01 M0000161 1B:A05
M00001480A:D03 M00001601A:E02
M00001480C:A05 M00001587A:D01
M00001481A:H08 M00001591B:B12
M00001481B:D09 M00001590B:G08
M00001482A:H05 M00001592C:E05
M00001482D:H1 1 M00001591B:B06
M00001483C:G09 M00001591D:C07
M00001485A:C05 M00001591D:F06
M00001476B:F08 M00001592A:E02
M00001460A:E1 1 M00001592A:H05
M00001456C:C 1 1 M00001592B:A04
M00001457A:C05 M00001587A:B10
M00001457A:G12 M00001609D:G10
M00001458A:A1 1 M00005231D:B09
M00001458C:D10 M00001614B:E08
M00001458D:A01 M00005217C:C01
M00001458D:A02 M00001587A:B01
M00001458D:C11 M00001613D:B03
M00001458D:D01 M00001613A:F03
M00001459B:C1 1 M0000161 1C:H1 1
M00001468A:H10 M0000161 1C:C12
M00001460A:C10 M0000161 1B:E06
M00001485B:F05 M0000161 1B:A09
M00001460A:H1 1 M00001610D:D05
M00001461A:F05 M00001610B:C07
M00001462A:D03 M00001610C:E07
M00001464A:B02 M00001610A.Ε09
M00001464A:E10 M00001601A:E12
M00001465A:B12 M00001609B:C09
M00001465A:C12 M00001608D:D1 1
M00001465A:E10 M00001608B:A09
cDNA Ref No.; cDNA Library Ref ES29 cDNA Library Ref ES30 ATCC Accession No. ATCC No. ATCC No.
M00001465A:G06 M00001607D:F06
M00001466A:F08 M00001607B:C05
M00001467A:C10 M00001606A:H09
M00001460A:B12 M00001605A:H03
M00001545A:B12 M00001605A:E09
M00001535A:D10 M00001605A:A06
M00001536A:F1 1 M00001604A:C1 1
M00001537A:H05 M00001604A:C07
M00001539A:E01 M00001604A:B08
M00001539A:H02 M00001604A:A09
M00001539B:G07 M00001610A:H05
M00001539D:B10 M00005214B.Α06
M00001540D:E02 M00005228A:A09
M00001541B:E05 M00001567A:B09
M00001542A:G12 M00001561A:D01
M00001485B:D09 M00001559A:C08
M00001545A:B10 M00001559A:A1 1
M00001533A:G05 M00001558A:G09
M00001545A:F02 M00001555A:B12
M00001545A:G05 M00001554A:A08
M00001546A:D08 M00001552A:H10
M00001548A.Η04 M00001552A:F06
M00001550A:E07 M00005231C:B07
M00001551A:A1 1 M00005218D:G10
M00001551A:D06 M00001570A:H01
M00001551A:H06 M00005214D:D10
M00001551D:H07 M00001570C:G03
M00001552A:E10 M00005213C:A01
M00001450A:B08 M00005212D:F08
M00001544A:F05 M00005212A:D10
M00001512A:G05 M0000521 1C:E09
M00001483B:D04 M0000521 1A:E09
M00001485B:H03 M00005210D:C09
M00001485C:C08 M00005179D:B03
M00001486B:D07 M00005179B:H02
M00001486B:E12 M00005177D:F09
M00001487B:A1 1 M00005177C:G04
M00001487B:E10 M00005177B.-H02
M00001507A:A1 1 M00001614D:B08
M00001507A:B02 M00001615A:D06
M00001507A:C05 M00005216B:D02
M00001507A:E04 M00001579C:A01
M00001534A:D03 M00001585B:C03
M0000151 1A:G01 M00001585B:A06
M00001533D:A08 M00001584D:H02
M00001513A:F05 M00001584A:G03
M00001514A:G03 M00001583D:B08
M00001516A:D02 M00001583B:F02
M00001516A:F06 M00001583A:F07
M00001517A:B1 1 M00001583A:A05
cDNA Ref No.; cDNA Library Ref ES29 cDNA Library Ref ES30 ATCC Accession No. ATCC No. ATCC No.
M00001529D:C05 M00001582D:F02
M00001530A:A09 M00001582D:B01
M00001530A:E10 M00001582A:A03
M00001532A:C01 M00001579D:H09
M00001532D:A06 M00001567D:B03
M00001485B:D10 M00001579C:H06
M0000151 1A:A02 M00001585B:F01
M00004249D:B08 M00001579B:F04
M00004185D:E04 M00001579A:E03
M00004188D:G08 M00001578C:F05
M00004197C:F03 M00001577D:H06
M00004198B:D02 M00001577B:F10
M00004204D:C03 M00001576C:G05
M00004208B:F05 M00001575D:D12
M00004208D:B10 M00001575D:B10
M00004210B:B05 M00001575D:A02
M00001362D:H01 M00001573B:G08
M00004216D:D03 M00001573A:E01
M00004167A:H03 M00001572A:B05
M00004275A:B03 M00001571D:F05
M00004285C:A08 M00001579D:F04
M00004316A:G09 M00001636A:F08
M00004465B:D04 M00001643B:E05
M00004493B:D09 M00001642C:G02
M00001347B:H04 M00001642A:F03
M00001351C:B06 M00001641D:C04
M00001360A:G10 M00001641C:H07
M00004216D:C03 M00001641C:F01
M00004076D:D04 M00001641C:D02
M00001484C:A04 M00001641B:F12
M00001456B:G01 M00001634A:B04
M00003972D:C09 M00001636B:G1 1
M00003974C:E04 M00001649C:D05
M00003979A:E11 M00001636A:C03
M00003983C:F03 M00001635D:D05
M00003989B:F1 1 M00001635D:C12
M00004031D:B05 M00001635B:H02
M00004177C:A01 M00001635B:H01
M00004076B:G03 M00001634D:G1 1
M00004167D:A07 M00001634D:D04
M00004078A:A06 M00001634A:H05
M00004085A:B02 M00001641A:A1 1
M00004107B:A06 M00001638B:E12
M0000411 1C:E1 1 M00001640A:H02
M00004130D:H01 M00001614C:E06
M00004157D:B03 M00001636D:F09
M00004159C:F09 M00001637A:A03
M00004162C:A07 M00001637A:A06
M00004135B:G01 M00001637A:E10
M00004040A:G12 M00001637A:F10
cDNA Ref No.; cDNA Library Ref ES29 cDNA Library Ref ES30 ATCC Accession No. ATCC No. ATCC No.
M00001453B:H12 M00001637C:C06
M00001448A:E11 M00001644A.H01
M00001448B:F09 M00001638B:E03
M00001448B:H05 M00001649A:E1 1
M00001448C:E11 M00001638B:F10
M00001448C:F10 M00001639A:C03
M00001448D:F12 M00001639A:G07
M00001449B:B03 M00001639B:H01
M00001449C:C05 M00001639B:H05
M00001449D:G10 M00001639C:A09
M00001448A:B12 M00001639C:C02
M00001453A:D08 M00001649C:E1 1
M00001451B:A04 M00001649C:H10
M00001454A:F11 M00001637C:E03
M00001454A:G03 M00001617A:A08
M00001455A:F04 M00001622A:H12
M00001455B:E07 M00001621C:H12
M00001455D:A06 M00001621B:G05
M00001364B:B06 M00001620D:H02
M00004117A:G01 M00001620D:G11
M00001455D:D1 1 M00001619D:D10
M00001456B:A06 M00001619C:C07
M00001451A:C10 M00001619A:E05
M00001395A:E03 M00001623A:F04
M00001366D:C06 M00001618A:A03
M00001365A:H10 M00001618B:D09
M00001366D:C12 M00001617A:A01
M00001373D:B03 M00001616D:C1 1
M00001453B:F08 M00001615C.-G05
M00001444D:C01 M00001615C:A1 1
M00001375B:C06 M00001615B:G07
M00001392C:D05 M00001633D:H06
M00001395A:A12 M00001639C:A10
M00001395A:H02 M00001615B:A09
M00001397D:G08 M00001615B:G01
M00001434A:B10 M00001618A:F10
M00001416A:D09 M00001632C:H07
M00001433C:F10 M00001633D:D12
M00001416A:H02 M00001633D.-D09
M00001428D:B10 M00001618A:F08
M00001428B:D01 M00001633D:G09
M00001426D:D12 M00001624A:A03
M00001400C:D02 M00001633C:F09
M00001427C:D01 M00001633C:H05
M00001633C:B09
M00001633A:E06
M00001633C:H1 1
M00001632C:B10
M00001625D:G10
M00001631 D:G05
cDNA RefNo.; cDNA Library Ref ES29 cDNA Library Ref ES30
ATCC Accession No. ATCC No. ATCC No.
M00001629C:E07 M00001629B:B08 M00001626C:E04 M00001626C:C11 M00001632A:B10 M00001624B:B10 M00001633C:A05 M00001625C:G05
Table 24. Clones Deposited on January 22, 1999 cDNA Ref No.; cDNA RefES31 cDNA Ref No. ES32 cDNA Ref ES33 ATCC Accession No. ATCC No. ATCC No. ATCC No. Clone Names in M00003843A:E04 M00003906A:F12 M00005254D:A10 Library M00003842C:G03 M00003906B:H06 M00005260B:E1 1
M00003842A:A03 M00003906C:C05 M00005260A:F04
M00003841D:A04 M00003907A:F01 M00005260A:A12
M00003841B:E06 M00003907B:C03 M00005259B:D12
M00003841C:H1 1 M00003907B:D05 M00005257D:H1 1
M00003844A:A1 1 M00003918A:D08 M00005257D:G07
M00003841C:F01 M00003918A:F09 M00005257D:A06
M00003841C:H08 M00003918C:H10 M00005257C:G01
M00003841C.-D07 M00003924A:D08 M00005257A:H1 1
M00003844D:A07 M00003958B:E1 1 M00005236B:H10
M00003845D:G08 M00003958B:H08 M00005236B:G03
M00003852C:B06 M00003960A:G07 M00005257C:E05
M00003854B:A07 M00003971B:A10 M00001608C:D02
M00003854B:D04 M00003972D:H02 M00001608C:G04
M00003859D:C05 M00003973C:C03 M00001608D:F1 1
M00003860B:F1 1 M00003974B:B1 1 M00001609C:A12
M00003867B:G07 M00003974D:F02 M00001609C:G05
M00003867B:G08 M00003974D:H04 M00001610C:B07
M00003841B:E03 M00003975C:F07 M00001612D:D12
M00003822D:B10 M00003977C:A06 M00001612D:F06
M00003867D:A06 M00003977C:B03 M00001613A:D02
M00003868B:G06 M00003977D:A03 M00001614A:B10
M00003867B:D10 M00003977D:A06 M00001614C:G07
M00003831C:G05 M00003977D:D04 M00001615C:E07
M00003901C:B01 M00003978D:G04 M00001625C:F10
M00003868C:C07 M00003980A:F04 M00001626D:A02
M00003820A:A08 M00003980B:C1 1 M00001629A:H09
M00003820B:D07 M00003981C:B04 M00001629D:B10
M00003820B:D10 M00003982A:B12 M00001629D:D10
M00003822D:C06 M00003982C:G04 M00001630C:F09
M00003823B:F07 M00003984D:B08 M00001631A:D03
M00003824C:D07 M00003985B:G04 M00001631A:F06
M00003825B:B10 M00003985D:E10 M00001631A:F12
M00003825B:B1 1 M00003986B:A08 M00001631B:H04
M00003828A:D05 M00003986C:D09 M00001633A:F1 1
M00003822D:D04 M00003986D:C08 M00001633A:G10
M00003830C:A03 M00003987B:E12 M00001633B:A12
M00003840D:H10 M00003987B:F08 M00001633B:E03
M00003832A:A09 M00003987C:G03 M00001633C:A08
M00003833B:B03 M00003988D:A08 M00001633C:E12
M00003833B:C12 M00003989C:D03 M00001635B:B02
M00003834B:G04 M00003989C:G05 M00001636A:H12
M00003835A:A09 M00003989D:F12 M00001638A:C08
M00003835B:H1 1 M00004029B:F01 M00001638B:C08
M00003835D:G06 M00004029C:C05 M00001639D:C12
M00003837C:E05 M00004029C:G 10 M00001640A:F05
M00003837C:F10 M00004030D:F1 1 M00001642D:G08
cDNA Ref No.; cDNA Ref ES31 cDNA Ref No. ES32 cDNA Ref ES33 ATCC Accession No. ATCC No. ATCC No. ATCC No.
M00003839A:D07 M00004034A:A01 M00001647D:G07
M00003839D:E1 1 M00004034C:G02 M00001649A:E10
M00003829C:H05 M00004034D:E09 M00001650D:D10
M00003901 B:C03 M00004035B:H09 M00001650D:F1 1
M00003878C:F06 M00004036D:B04 M00001651C:D1 1
M00003878C:G08 M00004036D:B09 M00001651C:G12
M00003879A:A02 M00004038A:F02 M00001652B:D06
M00003879A:B08 M00004038D:G06 M00001652D:G02
M00003879A:C1 1 M00004039A:C03 M00001652D:G06
M00003879A:D02 M00004039A:H1 1 M00001653A:A05
M00003879B:G02 M00004039B:A05 M00001653D:H07
M00003880B:D1 1 M00004039B:E12 M00001654A:E08
M00003880C:E1 1 M00004040C:A01 M00001654B:A01
M00003880C:H03 M00004051D:E01 M00001654C:D10
M00003901B:F10 M00004072D:F09 M00001654C:G07
M00003890B:C08 M00004073A:D10 M00001654C:G09
M00003877C:A1 1 M00004075B:G09 M00001655C:C07
M00003819D:B01 M00004076A:D12 M00001655D:E08
M00003901B:G1 1 M00004076D:H07 M00001655D:H1 1
M00001692A:G06 M00004078A:C1 1 M00001656A:H12
M00003903C:C05 M00004078A:E05 M00001656C:C04
M00003903C:E12 M00004078A:F07 M00001656D:C04
M00003903D:C12 M00004078B:C1 1 M00001657C:C11
M00003903D:D10 M00004078B:F12 M00001657D:A10
M00003903D:H1 1 M00004079D:G08 M00001659D:A09
M00003904A:C04 M00004081A:E02 M00001661D:D05
M00003904B:C03 M00004081A:G01 M00001664B:E08
M00003904C:A08 M00004081C:A10 M00001664B:F06
M00003881B:F10 M00004083A:E08 M00001669B:C12
M00003871D:G06 M00004083B:C01 M00001669C:B09
M00003868D:D09 M00004086D:G08 M00001670A:F09
M00003868D:D1 1 M00004087B:A12 M00001678C:F09
M00003870C:A01 M00004087C:A01 M00001693A:H06
M00003870C:A10 M00004088C:F01 M00003805D:E06
M00003870C:E10 M00004088D:A1 1 M00003806C:A06
M00003871A:A02 M00004088D:B05 M00003809B:A03
M00003871A.B09 M00004088D:B10 M00003810A:A02
M00003871A:C1 1 M00004090B:B04 M00003810B:B1 1
M00003871A:G09 M00004090B:H06 M00003810C:B06
M00003871C:E04 M00004092B:E05 M00003810D:H09
M00003871C:F12 M00004093C:C02 M0000381 1C:C02
M00003878C:D08 M00004096D:H03 M00003813B:F02
M00003871D:E1 1 M00004099D:F01 M00003813C:H08
M00003877C:G12 M00004100B:C07 M00003813D:B12
M00003875A:A07 M00004103B:E09 M00003813D:C02
M00003875A:B01 M00004105C:B05 M00003813D:G06
M00003875B:F12 M00004105C:C08 M00003814B:C01
M00003875C:A01 M00004107A:A12 M00003817C:A10
M00003875C:A09 M00004107B:D07 M00003817C:G06
M00003875C:G02 M00004108B:B02 M00003817D:D12
cDNA Ref No.; cDNA Ref ES31 cDNA Ref No. ES32 cDNA Ref ES33 ATCC Accession No. ATCC No. ATCC No. ATCC No.
M00003876B:C05 M00004108D:E07 M00003821A:H09
M00003876C:D02 M00004108D:G04 M00003822B:G12
M00003876C:F02 M000041 10A:A10 M00003822C:A07
M00003877B:H10 M000041 10B:A07 M00003823C:B01
M00003868D:B09 M000041 18B:A03 M00003823C:C04
M00003871D:A10 M000041 18B:F01 M00003824A:G1 1
M00001669D:D06 M000041 18D:B05 M00003824B:C09
M00001661A:B1 1 M00004119A:C09 M00003824C.Α10
M00001661B:F06 M00004136D:B02 M00003824D:D08
M00001662A:C07 M00004137A:D06 M00003825B:F10
M00001662A:G01 M00004139C:A12 M00003825D:F01
M00001662B:F06 M00004149C:B02 M00003826C:F05
M00001663C:F12 M00004159C:G12 M00003829A:B08
M00001664A:F08 M00004169D:B1 1 M00003829C:E08
M00001664D:F04 M00004187D:H06 M00003829D:D12
M00001661A:E06 M00004228C.Η03 M00003829D:F03
M00001669A:B02 M00004244C:G07 M00003830D:B1 1
M00001669B:B12 M00004358D:C02 M00003830D:H1 1
M00001669C:C08 M00004690A:G08 M00003833D:H08
M00001675A:G10 M00004891B:D01 M00003833D:H10
M00001669D:C03 M00004891C:D04 M00003840A:C10
M00001660B:E03 M00004895B:E12 M00003840B:F05
M00001669D:F05 M00004895B:G04 M00003840C:C02
M00001670B:G12 M00004895D:G07 M00003845C:D04
M00001671A:A10 M00004898C:F03 M00003845D:A04
M00001671B:G05 M00004899D:G06 M00003846B:C05
M00001671C:C1 1 M00004959D:H12 M00003846C:F08
M00001672D:E08 M00004960A:B08 M00003848B:E07
M00001673A:G08 M00004960C:E10 M00003848D:G02
M00001673B:B07 M00005100A:B02 M00003850C:G09
M00001673B:F07 M00005100A:C01 M00003851A:A06
M00001673D:D06 M00005101C:E12 M00003851B:D03
M00001673D:F10 M00005102C:D03 M00003851B:E01
M00001674A:G07 M00005134B:E08 M00003851C:F09
M00001692D:B01 M00005139A:H03 M00003851D:H1 1
M00001669C:D09 M00005140C:B10 M00003852B:G04
M00001655C:E01 M00005140D:C06 M00003852C:F07
M00001649D:A08 M00005178D:H04 M00003853B:C10
M00001650A:C1 1 M00005210A:E06 M00003854C:C09
M00001651A:H1 1 M00005212B:E01 M00003855A:A01
M00001652A:A01 M00005212C:C03 M00003855A:F01
M00001652B:G10 M00005212C:D02 M00003855B:B09
M00001652D:E05 M00005212C:H02 M00003856A:G04
M00001652D:E09 M00005212D:D09 M00003856B:A12
M00001653B:C06 M00005212D:H01 M00003857A:E12
M00001653B:G10 M00005216A:D09 M00003857A:H10
M00001653C:D10 M00005216A:H01 M00003857C:E05
M00001654D:A03 M00005217B:A06 M00003858B:G02
M00001654D:E12 M00005218A:F09 M00003860D:E06
M00001654D:F1 1 M00005228A:B03 M00003905C:F12
cDNA Ref No.; cDNA Ref ES31 cDNA Ref No. ES32 cDNA Ref ES33 ATCC Accession No. ATCC No. ATCC No. ATCC No.
M00001660C:B06 M00005228C:C05 M0000391 1A:D12
M00001658D:G12 M00005229B:G12 M00003966B:A04
M00001675C:A04 M00005229B:H04 M00003966C:A12
M00001660B:D03 M00005229B:H06 M00003966C:F03
M00001660B:A09 M00005229D:H03 M00003973D:F08
M00001659D:C09 M00005230B:H09 M00003974D:E01
M00001659D:B05 M00005232A:H12 M00003974D-.H07
M00001654D:F12 M00005233B:D04 M00003976B:E06
M00001659A:D12 M00005233D:H07 M00003976B:H07
M00001655A:B1 1 M00005235B:F10 M00003978A:E01
M00001658B:A07 M00005236A:E04 M00003978A:E09
M00001658A:G09 M00005236A:G10 M00003978C:A12
M00001657D:A04 M00005236B:A12 M00003980C:E12
M00001657B:B04 M00001448B:A07 M00003980C:F12
M00001656B:E01 M00001448B:G07 M00003981A:A07
M00001660B:E04 M00001448D:E1 1 M00003981B:B12
M00001659C:F10 M00001455A:D10 M00003982A:G03
M00003808C:A05 M00001455A:E1 1 M00003982B:C10
M00001694D:C 12 M00001476D:F12 M00003982B:H10
M00003746C:E02 M00001478A:F12 M00003983A:D02
M00003779D:E08 M00001482C:F09 M00003983A:F06
M00003792A:B10 M00001485C:D07 M00003983A:G02
M00003793D:A11 M00001485C:G06 M00003983D:E08
M00003794D:G03 M00001485D:A05 M00003983D:H02
M00003797A:C1 1 M00001487C:A1 1 M00003985A:C01
M00003797A:D06 M00001487C:G09 M00003986C:G1 1
M00003797A:G03 M00001530A:B02 M00003986D:H12
M00003800B:F03 M00001530A:H05 M00004027A:A08
M00003805A:F02 M00001530D:A1 1 M00004028A:B10
M00003806B:C09 M00001539B:B10 M00004028A:G03
M00001674A:G1 1 M00001567A:C04 M00004029B:A01
M00003806D:D1 1 M00001567A:C1 1 M00004029B:A06
M00001693D:E08 M00001567C:B08 M00004029B:G10
M00003808D:D08 M00001567C:E07 M00004029C:F02
M00003809A:C01 M00001570C:B02 M00004029C:F05
M00003809A:F01 M00001570D:E05 M00004030B:A12
M00003809B:B02 M00001570D:E07 M00004030B:D08
M00003809B:E10 M00001573B:A06 M00004030C:A08
M00003813A:B02 M00001573B:H12 M00004030C:C02
M00003813A:D08 M00001575A:D05 M00004034C:F05
M00003813B:E09 M00001575B:C01 M00004035B:F05
M00003814B:C12 M00001576C:H02 M00004036A:A1 1
M00003814B:F12 M00001577A:A03 M00004037C:D04
M00003815C:C06 M00001578B:A06 M00004038A:E05
M00003815C:D12 M00001579D:F02 M00004038B:D01
M00003817B:C04 M00001582C:C04 M00004039C:E02
M00003806B:G05 M00001582C:G02 M00004039D:B10
M00001679A:D10 M00001584A:A07 M00004040A:A07
M00001675C:C03 M00001584D:B06 M00004040A:B04
M00001675C:D12 M00001584D:C1 1 M00004040A:C08
cDNA Ref No.: cDNA Ref ES31 cDNA Ref No. ES32 cDNA Ref ES33 ATCC Accession No. ATCC No. ATCC No. ATCC No.
M00001675D:E10 M00001585D:B12 M00004040B:C05
M00001676B:B09 M00001586C:H07 M00004040B:F07
M00001676B:E01 M00001589D:A01 M00004069A:E12
M00001676C:A04 M00001590D:B04 M00004069C:C08
M00001676C:E07 M00001592B:B02 M00004077A:G12
M00001676D:A02 M00001592D:H02 M00004085B:G01
M00001676D:B02 M00001594C:E05 M00004087A:B05
M00001677A:G1 1 M00001594C:H03 M00004090D:F12
M00001677B:A12 M00001594D:G1 1 M00004092C:D08
M00001677B:B04 M00001595A:C07 M00004097C:E03
M00001677D:B01 M00001595A:D12 M00004097C:H08
M00001678D:B1 1 M00001595A:E07 M00004097D:B05
M00001681C:A08 M00001595B:G07
M00003819B:G01 M00001595B:G10
M00001693C:E09 M00001595B:H1 1
M00001693C:C12 M00001595C:A01
M00001692B:E01 M00001595C:A05
M00001692A:B06 M00001595C:B12
M00001678B:H01 M00001595C:E05
M00001681D:C12 M00001595C:E09
M00001694A:E03 M00001595D:C1 1
M00001680B:D02 M00001596A:A02
M00001680A:B02 M00001596A:D01
M00001679D:F02 M00001596C:G05
M00001679D:B02 M00001607A:A01
M00001679A:G06
Claims
1. A library of polynucleotides, the library comprising the sequence information of at least one of SEQ ID NOS: 1-3544, 3546-4510, 4512-4725, 4727-4748, and 4750-5252.
2. The library of claim 1, wherein the library is provided on a nucleic acid array.
3. The library of claim 1, wherein the library is provided in a computer-readable format.
4. The library of claim 1, wherein the library comprises a differentially expressed polynucleotide comprising a sequence selected from the group consisting of SEQ ID NOS:65, 174, 203, 252, 253, 387, 419, 420, 491, 552, 560, 581, 590, 648, 693, 726, 746, 990, 1095, 1124, 1205, 1354, 1387, 1780, 1899, 1915, 1979, 2007, 2024, 2245, and 2325.
5. The library of claim 1, wherein the library comprises a polynucleotide differentially expressed in a human breast cancer cell, where the polynucleotide comprises a sequence selected from the group consisting of SEQ ID NOS: 15, 36, 44, 45, 89, 146, 154, 159, 165, 174, 172, 183, 203, 261, 364, 366, 387, 419, 420, 496, 503, 510, 512, 529, 552, 560, 564, 570, 590, 606, 644, 646, 693, 707, 711, 726, 746, 754, 756, 875, 902, 921, 942, 990, 1095, 1104, 1122, 1131, 1142, 1170, 1184, 1205, 1286, 1289, 1354, 1387, 1435, 1535, 1751, 1764, 1777, 1795, 1860, 1869, 1882, 1890, 1915, 1933, 1934, 1979, 1980, 2007, 2023, 2040, 2059, 2223, 2245, 2300, 2325, 2409, 2462, 2486, 2488, and 2492.
6. The library of claim 1, wherein the library comprises a polynucleotide differentially expressed in a human colon cancer cell, where the polynucleotide comprises a sequence selected from the group consisting of SEQ ID NOS:33, 65, 228, 250, 252, 253, 280, 282, 355, 370, 387, 443, 460, 491, 545, 560, 581, 603, 680, 693, 703, 704, 716, 726, 746, 752, 753, 1095, 1104, 1205, 1241, 1264, 1354, 1387, 1401, 1442, 1514, 1734, 1742, 1780, 1851, 1899, 1915, 1954, 2024, 2066, 2262, and 2325.
7. The library of claim 1, wherein the library comprises a polynucleotide differentially expressed in a human lung cancer cell, where the polynucleotide comprises a sequence selected from the group consisting of SEQ ID NOS: 10, 54, 65, 171, 174, 203, 252, 253, 254, 285, 419, 420, 466, , 491, 525, 526, 552, 571, 574, 590, 693, 700, 726, 742, 746, 861, 990, 922, 1088, 1288, 1355, 1417, 1422, 1444, 1454, 1570, 1597, 1979, 2007, 2024, 2034, 2038, 2126, and 2245.
8. The library of claim 1, wherein the library comprises a polynucleotide differentially expressed in a human cancer cell, where the polynucleotide comprises a sequence selected from the group consisting of SEQ ID NOS:648 andl 899.
9. An isolated polynucleotide comprising a nucleotide sequence having at least 90% sequence identity to an identifying sequence of SEQ ID NOS: 1-3544, 3546-4510, 4512-4725, 4727-4748, and 4750-5252, or a degenerate variant or fragment thereof.
10. The polynucleotide ofclaim 9, wherein the polynucleotide comprises a sequence ofone of SEQ ID NOS:2503, 2504, 2550, 2555, 2578, 2656, 2667, 2712, 2723, 2728, 2738, 2734, 2754, 2758, 2760, 2832, 2835, 2842, 2843, 2849, 2893, 2933, 2956, 2971, 2981, 3009, 3018, 3019, 3046, 3084, 3190, 3129, 3173, 3226, 3227, 3274, 3290, 3356, 3365, 3377, 3381, 3390, 3391, 3404, 3407, 3408, 3409, 3418, 3419, 3451, 3597, 3600, 3618, 3632, 3635, 3646, 3648, 3657, 3665, 3669, 3670, 3671, 3656, 3680, 3686, 3695, 3696, 3700, 3710, 3736, 3762, 3763, 3774, 3775, 3791, 3804, 3806, 3836, 3895, 3905, 3919, 3920, 3927, 3936, 3951, 3974, 3998, 4036, 4038, 4044, 4056, 4072, 4117, 4119, 4152, 4153, 4154, 4172, 4175, 4159, 4175, 4205, 4216, 4223, 4228, 4238, 4241, 4243, 4251, 4253, 4261, 4263,4278, 4288, 4322, 4330, 4343, 4359, 4363, 4364, 4365, 4373, 4375, 4384, 4385, 4406, 4409, 4431, 4434, 4441, 4442, 4444, 4455, 4469, 4473, 4477, 4482, 4489, 4495, 4496, 4498, 4525, 4535, 4536, 4540, 4560, 4616, 4562, 4586, 4605, 4629, 4653, 4654, 4658, 4659, 4660, 4661, 4664, 4665, 4668, 4684, 4682, 4688, 4689, 4710, 4718, 4733, 4724, 4733, 4746, 4755, 4760, 4710, 4777, 4785, 4792, 4794, 4801, 4807, 4821, 4822, 4847, 4850, 4854, 4856, 4866, 4885, 4900, 4901, 4905, 4914, 4925, 4929, 4931, 4943, 4944, 4959, 5111, 5020, 5041, 5046, 5059, 5083, 5090, 5094, 5102, 5125, 5174, 5197, 5208, 5217, 5237, 5239, 5241, 5243, 5248, and 5252.
11. A recombinant host cell containing the polynucleotide of claim 9.
12. An isolated polypeptide encoded by the polynucleotide of claim 9.
13. An antibody that specifically binds a polypeptide of claim 12.
14. A vector comprising the polynucleotide of claim 9.
15. A polynucleotide comprising the nucleotide sequence of an insert contained in a clone deposited as ATCC accession number xx, xx, xx, xx, xx, xx, xx, xx, or xx.
16. A method of detecting differentially expressed genes correlated with a cancerous state of a mammalian cell, the method comprising the step of: detecting at least one differentially expressed gene product in a test sample derived from a cell suspected of being cancerous, where the gene product is encoded by a gene corresponding to a sequence ofat least one of SEQ ID NOS: 10, 15, 33, 36, 44, 45, 54, 65, 89, 146, 154, 159, 165, 171, 172, 174, 183, 203, 228, 250, 252, 253, 254, 261, 280, 282, 285, 355, 364, 366, 370, 387, 419, 420, 443, 460, 466, 491, 496, 503, 510, 512, 525, 526, 529, 545, 552, 560, 564, 570, 571, 574, 581, 590, 603, 606, 644, 646, 648, 680, 693, 700, 703, 704, 707, 711, 716, 726, 742, 746, 752, 753, 754, 756, 861, 875, 902, 921, 922, 942, 990, 1088, 1095, 1104, 1122, 1131, 1142, 1170, 1184, 1205, 1286, 1288, 1289, 1354, 1355, 1387, 1417, 1435, 1444, 1454, 1535, 1570, 1597, 1734, 1742, 1751, 1764, 1777, 1780, 1795, 1860, 1869, 1882, 1890, 1899, 1915, 1933, 1934, 1954, 1979, 1980, 2007, 2023, 2024, 2034, 2040, 2059, 2126, 2223, 2245, 2262, 2300, 2325, 2409, 2486, 2462, 2488, 2492, 1241, 1264, 1401, 1422, 1442, 1514, 1851, 1915, 2007, 2024, 2038, 2066, and 2245; wherein detection of the differentially expressed gene product is correlated with a cancerous state of the cell from which the test sample was derived.
17. The method of claim 16, wherein said detecting step is by hybridization of the test sample to a reference array, wherein the reference array comprises an identifying sequence of at least one of SEQ ID NOS: 65, 174, 203, 252, 253, 387, 419, 420, 491, 552, 560, 581, 590, 648, 693, 726, 746, 990, 1095, 1124, 1205, 1354, 1387, 1780, 1899, 1915, 1979, 2007, 2024, 2325, and 2245.
18. The method of claim 16, wherein the cell is a breast tissue derived cell, and the differentially expressed gene product is encoded by a gene corresponding to a sequence of at least one of SEQ ID NOS:36, 44, 45, 89, 146, 154, 159, 165, 172, 174, 183, 203, 261, 364, 366, 387, 419, 420, 496, 503, 510, 512, 529, 552, 560,564, 570, 590, 606, 644, 646, 693, 707, 711, 726, 746, 754, 756, 875, 902, 921, 942, 990, 1095, 1104, 1122, 1131, 1142, 1170, 1184, 1205, 1286, 1289, 1354, 1387, 1435, 1535, 1751, 1764, 1777, 1795, 1860, 1869, 1882, 1890, 1915, 1933, 1934, 1979, 1980, 2007, 2023, 2040, 2059, 2223, 2245, 2300, 2325, 2409, 2462, 2486, 2488, and 2492.
19. The method of claim 16, wherein the cell is a colon tissue derived cell, and the differentially expressed gene product is encoded by a gene corresponding to a sequence of at least one of SEQ ID NOS:33, 65, 228, 250, 252, 253, 280, 282, 355, 370, 387, 443, 460, 491, 545, 560, 581, 603, 680, 693, 703, 704, 716, 726, 746, 752, 753, 1095, 1104, 1205, 1241, 1264, 1354, 1387, 1401, 1442, 1514, 1734, 1742, 1780, 1851, 1899, 1915, 1954, 2024, 2066, 2262, and 2325.
20. The method of claim 16, wherein the cell is a lung tissue derived cell, and the differentially expressed gene product is encoded by a gene corresponding to a sequence of at least one of SEQ ID NOS: 10, 54, 65, 171, 174, 203, 252, 253, 254, 285, 419, 420, 466, 491, 525, 526, 552, 571, 574, 590, 693, 700, 726, 742, 746, 861, 922, 990, 1088, 1288, 1355, 1417, 1422, 1444, 1454, 1570, 1597, 1979, 2007, 2024, 2034, 2038, 2126, and 2245.
21. The method of claim 16, wherein the differentially expressed gene product is encoded by a gene corresponding to a sequence ofat least one of SEQ ID NOS:648 and 1899.
Applications Claiming Priority (15)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US7291098P | 1998-01-28 | 1998-01-28 | |
US72910P | 1998-01-28 | ||
US7595498P | 1998-02-24 | 1998-02-24 | |
US75954P | 1998-02-24 | ||
US8011498P | 1998-03-31 | 1998-03-31 | |
US80114P | 1998-03-31 | ||
US8051598P | 1998-04-03 | 1998-04-03 | |
US8066698P | 1998-04-03 | 1998-04-03 | |
US80666P | 1998-04-03 | ||
US80515P | 1998-04-03 | ||
US10523498P | 1998-10-21 | 1998-10-21 | |
US105234P | 1998-10-21 | ||
US10587798P | 1998-10-27 | 1998-10-27 | |
US105877P | 1998-10-27 | ||
PCT/US1999/001619 WO1999038972A2 (en) | 1998-01-28 | 1999-01-28 | Human genes and gene expression products ii |
Publications (1)
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EP1053319A2 true EP1053319A2 (en) | 2000-11-22 |
Family
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EP99904288A Withdrawn EP1053319A2 (en) | 1998-01-28 | 1999-01-28 | Human genes and gene expression products ii |
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EP (1) | EP1053319A2 (en) |
JP (1) | JP2002519000A (en) |
WO (1) | WO1999038972A2 (en) |
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1999
- 1999-01-28 EP EP99904288A patent/EP1053319A2/en not_active Withdrawn
- 1999-01-28 WO PCT/US1999/001619 patent/WO1999038972A2/en not_active Application Discontinuation
- 1999-01-28 JP JP2000556580A patent/JP2002519000A/en not_active Withdrawn
Non-Patent Citations (1)
Title |
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See references of WO9938972A3 * |
Also Published As
Publication number | Publication date |
---|---|
WO1999038972A8 (en) | 2000-04-06 |
WO1999038972A9 (en) | 2001-05-17 |
WO1999038972A2 (en) | 1999-08-05 |
WO1999038972A3 (en) | 1999-12-23 |
JP2002519000A (en) | 2002-07-02 |
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