WO2003000735A2 - Nucleic acids encoding olfactory receptors - Google Patents

Abstract

Nucleic acids encoding G protein-coupled receptors are disclosed, and methods of using same.

Description

NUCLEIC ACIDS ENCODING OLFACTORY RECEPTORS

RELATED APPLICATIONS This application claims the benefit of and priority to U.S Provisional

Application 60/301,095, filed June 26, 2001 and to U.S. Provisional Application 60/332,758, filed November 6, 2001, the entire teachings of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

G protein-coupled receptors ("GPCRs") are a superfamily of intrinsic transmembrane cell-surface receptors that mediate the transmission of extracellular signals into the cell to produce a cellular response. There are thought to be anywhere from 400 to over 1000 different members of this family. GPCRs are intrinsic membrane proteins, and operate by a common transduction mechanism. In their inactive state, the GPCRs bind to the G proteins. Upon activation, they stimulate guanine nucleotide exchange on the G proteins, resulting in the release of GDP and the binding of GTP. The G-protein then dissociates from the GPCR, and interacts with the adenylate cyclases, which catalyze the conversion of ATP into cAMP. The cAMP then acts as a second messenger. The G proteins can cause intracellular coupling of the GPCRs with various intracellular enzymes, ion channels and transporters.

GPCRs (and perforce, G proteins) are involved in an enormous range of biological processes, and have been found to regulate such processes as hydrolysis

+ 2+ ofplasma membrane phospholipids, the K and Ca ion channels, yeast mating signals, the signaling by cholera and pertussis toxins, and proliferation in some cancers (e.g., pituitary, adrenal, ovarian). The signal can be endogenous or exogenous or, in the case of rhodopsin receptors, the stimulus can be light. Many drugs bind to a GPCR and either produce a response or block the actions of the normal signal. The GPCR superfamily includes the cannabinoid and opioid receptors, chemokine, histamine, angiotensin, neurotensin, vasopressin, calcitonin, dopamine, glutamate and bombesin receptors, taste and odorant receptors, and many others.

SUMMARY OF THE INVENTION The present invention relates to human G protein-coupled receptor (GPCR) genes that are specifically ordorant or olfactory receptors, particularly nucleic acids comprismg GPCR genes, and the amino acids encoded by such nucleic acids. These sequences are shown in Tables I and II. In Tables I and II, each GPCR entry lists the name (e.g., "MOOSE01980"), the University of California at Santa Cruz contig designation from which the sequence was analyzed (e.g., "ctgl3103"), the exon locations (e.g., "25879000 . . 25879025...."), followed by the amino acid sequence and the nucleic acid sequence.

In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of SEQ 3D NOs:l-230 (odd numbers), as shown in Tables I and U, and the complements thereof. The invention further relates to a nucleic acid molecule which hybridizes under high stringency conditions to a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1-230 (odd numbers), as shown in Tables I and II, and the complements thereof. The invention additionally relates to isolated nucleic acid molecules (e.g. , cDNA molecules) encoding a GPCR polypeptide (e.g. , encoding a polypeptide selected from the group consisting of SEQ JD NOs: 1-230 (even numbers), as shown in Tables I and II).

The invention further provides a method for assaying a sample for the presence of a nucleic acid molecule comprising all or a portion of a GPCR in a sample, comprising contacting said sample with a second nucleic acid molecule comprising a nucleotide sequence encodmg a GPCR polypeptide (e.g., one of SEQ JD NOs: 1-230 (odd numbers), as shown in Tables I and II, or the complement of one of SEQ ID NOs: 1-230 (odd numbers); a nucleotide sequence encoding one of SEQ ID NOs:l-230 (even numbers), as shown in Tables I and JJ), or a fragment or derivative thereof, under conditions appropriate for selective hybridization. The invention additionally provides a method for assaying a sample for the level of expression of a GPCR polypeptide, or fragment or derivative thereof, comprising detecting (directly or indirectly) the level of expression of the GPCR polypeptide, fragment or derivative thereof.

The invention also relates to a vector comprising an isolated nucleic acid molecule of the invention operatively linked to a regulatory sequence, as well as to a recombinant host cell comprising the vector. The invention also provides a method for preparing a polypeptide encoded by an isolated nucleic acid molecule described herein (a GPCR polypeptide), comprising culturing a recombinant host cell of the invention under conditions suitable for expression of said nucleic acid molecule. The invention further provides an isolated polypeptide encoded by isolated nucleic acid molecules of the invention (e.g., GPCR polypeptide), as well as fragments or derivatives thereof. In a particular embodiment, the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ JD NOs: 1-230 (even numbers), as shown in Tables I and TJ. The invention also relates to an isolated polypeptide comprising an amino acid sequence which is greater than about 90 percent identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-230 (even numbers), preferably about 95, 96, 97, 98 and 99 percent identical.

The invention also relates to an antibody, or an antigen-binding fragment thereof, which selectively binds to a polypeptide of the invention, as well as to a method for assaying the presence of a polypeptide encoded by an isolated nucleic acid molecule of the invention in a sample, comprising contacting said sample with an antibody which specifically binds to the encoded polypeptide.

The invention further relates to methods of diagnosing a predisposition to a condition mediated by GPCRs. The methods of diagnosing such a predisposition in an individual include detecting the presence of a mutation in GPCR, as well as detecting alterations in expression of a GPCR polypeptide, such as the presence of different splicing variants of GPCR polypeptides. The alterations in expression can be quantitative, qualitative, or both quantitative and qualitative.

The invention additionally relates to an assay for identifying agents that alter (e.g., enhance or inhibit) the activity or expression of one or more GPCR polypeptides. For example, a cell, cellular fraction, or solution containing a GPCR polypeptide or a fragment or derivative thereof, can be contacted with an agent to be tested, and the level of GPCR polypeptide expression or activity can be assessed. The activity or expression of more than one GPCR polypeptides can be assessed concurrently (e.g., the cell, cellular fraction, or solution can contain more than one type of GPCR polypeptide, such as different splicing variants, and the levels of the different polypeptides or splicing variants can be assessed).

In another embodiment, the invention relates to assays to identify polypeptides that interact with one or more GPCR polypeptides. In a yeast two- hybrid system, for example, a first vector is used which includes a nucleic acid encoding a DNA binding domain and also an GPCR polypeptide, splicing variant, or fragment or derivative thereof, and a second vector is used which includes a nucleic acid encoding a transcription activation domain and also a nucleic acid encoding a polypeptide which potentially may interact with the GPCR polypeptide, splicing variant, or fragment or derivative thereof (e.g., a GPCR polypeptide binding agent or receptor). Incubation of yeast containing both the first vector and the second vector under appropriate conditions allows identification of polypeptides which interact with the GPCR polypeptide or fragment or derivative thereof, and thus can be agents which alter the activity of expression of an GPCR polypeptide.

Agents that enhance or inhibit GPCR polypeptide expression or activity are also included in the current invention, as are methods of altering (enhancing or inhibiting) GPCR polypeptide expression or activity by contacting a cell containing GPCR and/or polypeptide, or by contacting the GPCR polypeptide, with an agent that enhances or inhibits expression or activity of GPCR or polypeptide. Additionally, the invention pertains to pharmaceutical compositions comprising the nucleic acids of the invention, the polypeptides of the invention, and or the agents that alter activity of GPCR polypeptide. The invention further pertains to methods of treating conditions mediated by GPCRs, by administering GPCR therapeutic agents, such as nucleic acids of the invention, polypeptides of the invention, the agents that alter activity of GPCR polypeptide, or compositions comprising the nucleic acids, polypeptides, and/or the agents that alter activity of GPCR polypeptide. DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to nucleic acids comprising ordorant or olfactory receptors that are a subfamily of G protein-coupled receptors ("GPCRs"), and the amino acids encoded by those nucleic acids.

Odorant receptors are a large family of G-protein coupled receptors, typically expressed in the neurons of the olfactory epithelium. Odorant receptors are highly sensitive and selective, and provide a fast response through activation of G- proteins. Typically, the transmembrane regions II-VJJ delimit a hypervariable region that defines the ligand specificity.

These receptors are involved in the treatment of infections and various diseases and conditions, including, but not limited to, many diseases are associated with olfactory receptor chemosensory problems. The loss of the sense of smell and the sense of taste are the most common chemosensory complaints. A reduction in the ability to detect odors is known as hyposmia, distortion of normal smell, dysosmia and a complete loss of the ability to detect odors, anosmia. A reduction in the ability to taste sweet, sour, bitter and salty is known as hypogeusia. a distortion of normal taste, dysgeusia and a complete loss, ageusia. Abnormalities in a smell and taste function frequently accompany and even signal the existence of several diseases or unhealthy conditions, including obesity, diabetes, hypertension, malnutrition, and some degenerative diseases of the nervous system such as Parkinson's disease, Alzheimer's disease and Korsakoff s psychosis.

With the availability of complete genomic sequences for many organisms today, including Homo sapiens, it has become clear that there is a need for data mining techniques to extract the information in them, e.g., gene prediction programs. Of these, the most successful ones are those based on the comparison of known protein or protein-derived information, or those that use expressed sequence tags (ESTs) to predict gene location and structure. One such algorithm is Gene Wise. It bases its exon prediction on the use of

Hidden Markov Models (HMMs) of proteins to be compared against a genomic sequence, so that the translation of the sequence will match the model in a similar way to other HMM profile searches (Eddy, Curr. Opin. Struct. Biol. 6(3):361-5, 1996), and allowing the presence of long insertions as long as they include donor and acceptor site sequences at both ends.

To take advantage of the algorithm, the models for different protein families must be built so that they represent the full-length sequences instead of the most common features in them. This is a major difference with existing HMM databases such as Pfam (Sonnhammer et al., Proteins 28(3):405-20, 1997), in which each model is built to represent a family of proteins as broad as possible with minimum overlap between them. In the present approach, the sequences were subdivided in several families so that the similarity inside of a group of them was over 50%. Given this approach, there are several points of overlap between different families when analyzing a sequence, so the discrimination must be done after the search is completed. Several resources that include expert-supervised classifications are used to select the best groups of sequences, e.g. , the GPCR data base (Horn et al. , Nucleic Acids Res. 26(l):275-9, 1998), PKR (Smith et al, Trends Biochem. Sci. 22(l l):444-6, 1997), NuclearRdb (Horn et al, Nucleic Acids Res. 29:346-349, 2001), IOCH (Le Novere et al., Nucleic Acids Res. 27(l):340-2, 1999), Enzyme (Bairoch, Nucleic Acids Res. 28:304-305, 2000) and Swiss-Prot (Bairoch et al, Nucleic Acids Res. 28:45-48, 2000). When none is available, or the sequences included in some groups are too distantly related, the grouping must be done manually, using the ClustalW (Thompson et al, Nucleic Acids Res. 22:4673-4680, 1994) package to measure the distance between different sequences.

The present model was built from multiple sequence alignments of the different protein families obtained with DiAlign 2 (Morgenstem, Bioinformatics

15(3):211-8, 1999). DiAlign works based on segment-to-segment comparisons instead of arbitrary thresholds for gap opening and extension, which makes it ideally suited for building models that represent an entire, full-length sequence, since the alignments built this way have more match states that would be assigned as insertion states when using other alignment algorithms. The models were built using the standard HMMer package. To search for new genes, a genome-wide scan was done on the University of California at Santa Cruz sequences, using the GeneWise algorithm. It translates the genomic sequence on the fly to proteins and can therefore maintain a reading frame through insertions and deletions. The algorithm also rewards gaps in the genomic sequence relative to the model if they are encapsulated within introns, like splice structure.

For each superfamily of proteins, a classification was obtained in which the sequences are grouped by length and similarity. Each one of these groups was then used to build a HMM profile representing this group of sequences. This approach aims to have models that can represent the full length of the encoded proteins for a whole range of proteins, without being too specific for any one of them or being too general, as would be a HMM built for large groups of sequences. This classification was based either on existing expert-supervised classifications, or by retrieval of sequences and classification based on pairwise alignment distances. These models were then searched against the October 2000 Fixed Release

(and its subsequent corrections) and the April 2001Fixed Release for Tables I and IJ, respectively, of the Santa Cruz contigs using the Paracel GeneMatcherf Hardware Accelerator with the GeneWise algorithm. The sequences were chopped at 100 Kb with an overlap of 1 Kb. Each one of the superfamilies required between 3 and 6 days to complete and generate results. The results represent the coding regions of the complete final protein as it is found in the organism.

The cross-validation of the results was done in two steps. First, all of the hits with an E-value lower than 10^" that did not overlap with one another were selected, and in the event of overlapping, the one with lowest E-value was selected. After selecting all of those matches, the DNA sequences were compared against the

RefSeq database (Pruitt et al, Trends Genet. 16(l):44-47, 2000) using BLAST (Altschul et al, Nucleic Acids Res. 25:3389-3402, 1997).

Only approximately one third of the genes were 90% or more identical to an existing human RefSeq entry and/or mRNAs from GenBank. The differences are usually due to pickmg the wrong model for a certain sequence that appears as a hit more than once in different families, being a different valid splice variant, which can be tested by comparing to the EST database, or by addition of a small last exon to complete the match instead of accept an stop codon in a previous one. In all of such cases, the results are easily and quickly corrected by eye. Very rarely the algorithm will actually make a wrong prediction, which is consistent with the expected behaviour (Guigo et al, Genome Res. 10(10):1631-42, 2000). The full sequences of the olfactory GPCR genes and splice variants are shown in Tables I and JJ as SEQ JD NOs: 1-230 (odd numbers). The amino acids encoded by these nucleic acids are shown in Tables I and JJ as SEQ JD NOs: 1-230 (even numbers).

A number of the genes were found to be linked with markers known to be associated with human diseases genes. These are shown in Table HI. The diseases were linked to the HMM genes in the following manner: (1) the HMM gene models were compared to the consensus of the human genome sequence, located and the results kept in a relational database; (2) all possible markers (Sequence Tagged Sites (STS's)) (public or deCODE genetics) are also located in the same consensus using ePCR or BLAT and results kept in a relational database; and (3) LOD scores for diseases are linked to markers. A span of one LOD drop around the marker, was also given. A computer program takes each LOD peak and linlcs it to the consensus through the markerhit in the database. The database is then queried for all HMM genes within the span of one LOD drop or a minimum of 15 Mb in each direction from the marker. The output is the name of the peak marker and its distance to the HMM gene.

NUCLEIC ACIDS OF THE INVENTION

Accordingly, the invention pertains to isolated nucleic acid molecules comprising human GPCR genes. The term, "GPCR", as used herein, refers to an isolated nucleic acid molecule selected from the group shown in Tables I and II, and consisting of SEQ TD NOs:l-230 (odd numbers), and also to a portion or fragment of the isolated nucleic acid molecule (e.g., cDNA or the gene) that encodes GPCR polypeptide (e.g., apolypeptide selected from the group shown in Tables I and II, and consisting of SEQ ID NOs: 1-230 (even numbers)). In a preferred embodiment, the isolated nucleic acid molecule comprises a nucleic acid molecule selected from the group consisting of SEQ ID NOs: 1-230 (odd numbers) or the complement of such a nucleic acid molecule.

The isolated nucleic acid molecules of the present invention can be RNA, for example, mRNA, or DNA, such as cDNA and genomic DNA. DNA molecules can be double-stranded or single-stranded; single stranded RNA or DNA can be either the coding, or sense, strand or the non-coding, or antisense, strand. The nucleic acid molecule can include all or a portion of the coding sequence of the gene and can further comprise additional non-coding sequences such as introns and non-coding 3' and 5' sequences (including regulatory sequences, for example). Additionally, the nucleic acid molecule can be fused to a marker sequence, for example, a sequence that encodes a polypeptide to assist in isolation or purification of the polypeptide. Such sequences include, but are not limited to, those that encode a glutathione-S-transferase (GST) fusion protein and those that encode a hemagglutinin A (HA) polypeptide marker from influenza. An "isolated" nucleic acid molecule, as used herein, is one that is separated from nucleic acids which normally flank the gene or nucleotide sequence (as in genomic sequences) and/or has been completely or partially purified from other transcribed sequences (e.g., as in an RNA library). For example, an isolated nucleic acid of the invention may be substantially isolated with respect to the complex cellular milieu in which it naturally occurs, or culture medium when produced by recombinant techniques, or chemical precursors or other chemicals when chemically synthesized. In some instances, the isolated material will form part of a composition (for example, a crude extract containing other substances), buffer system or reagent mix. hi other circumstances, the material may be purified to essential homogeneity, for example as determined by PAGE or column chromatography such as HPLC.

Preferably, an isolated nucleic acid molecule comprises at least about 50, 80 or 90% (on a molar basis) of all macromolecular species present. With regard to genomic DNA, the term "isolated" also can refer to nucleic acid molecules which are separated from the chromosome with which the genomic DNA is naturally associated. For example, the isolated nucleic acid molecule can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotides which flank the nucleic acid molecule in the genomic DNA of the cell from which the nucleic acid molecule is derived. ^•

The nucleic acid molecule can be fused to other coding or regulatory sequences and still be considered isolated. Thus, recombinant DNA contained in a vector is included in the definition of "isolated" as used herein. Also, isolated nucleic acid molecules include recombinant DNA molecules in heterologous host cells, as well as partially or substantially purified DNA molecules in solution. "Isolated" nucleic acid molecules also encompass in vivo and in vitro RNA transcripts of the DNA molecules of the present invention. An isolated nucleic acid molecule or nucleotide sequence can include a nucleic acid molecule or nucleotide sequence that is synthesized chemically or by recombinant means. Therefore, recombinant DNA contained in a vector are included in the definition of "isolated" as used herein. Also, isolated nucleotide sequences include recombinant DNA molecules in heterologous organisms, as well as partially or substantially purified DNA molecules in solution. In vivo and in vitro RNA transcripts of the DNA molecules of the present invention are also encompassed by "isolated" nucleotide sequences. Such isolated nucleotide sequences are useful in the manufacture of the encoded polypeptide, as probes for isolating homologous sequences (e.g., from other mammalian species), for gene mapping (e.g., by in situ hybridization with chromosomes), or for detecting expression of the gene in tissue (e.g., human tissue), such as by Northern blot analysis.

The present invention also pertains to nucleic acid molecules which are not necessarily found in nature but which encode a GPCR polypeptide (e.g., a polypeptide having an amino acid sequence comprising an amino acid sequence selected from the group consisting of SEQ JD NOs: 1-230 (even numbers)), or another splicing variant of a GPCR polypeptide or polymorphic variant thereof. Thus, for example, DNA molecules which comprise a sequence that is different from the naturally-occurring nucleotide sequence but which, due to the degeneracy of the genetic code, encode a GPCR polypeptide of the present invention are also the subject of this invention. The invention also encompasses nucleotide sequences encoding portions (fragments), or encoding variant polypeptides such as analogues or derivatives of a GPCR polypeptide. Such variants can be nafrffally-occυrring, such as in the case of allelic variation or single nucleotide polymorphisms, or non- naturally-occurring, such as those induced by various mutagens and mutagenic processes. Intended variations include, but are not limited to, addition, deletion and substitution of one or more nucleotides that can result in conservative or non- conservative amino acid changes, including additions and deletions. Preferably the nucleotide (and/or resultant amino acid) changes are silent or conserved; that is, they do not alter the characteristics or activity of a GPCR polypeptide. In one preferred embodiment, the nucleotide sequences are fragments that comprise one or more polymorphic microsatellite markers. In another preferred embodiment, the nucleotide sequences are fragments that comprise one or more single nucleotide polymorphisms in a GPCR gene.

Other alterations of the nucleic acid molecules of the invention can include, for example, labeling, methylation, intemucleotide modifications such as uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoamidates, carbamates), charged linkages (e.g., phosphorothioates, phosphorodithioates), pendent moieties (e.g., polypeptides), intercalators (e.g., acridine, psoralen), chelators, alkylators, and modified linkages (e.g., alpha anomeric nucleic acids). Also included are synthetic molecules that mimic nucleic acid molecules in the ability to bind to a designated sequences via hydrogen bonding and other chemical interactions. Such molecules include, for example, those in which peptide linkages substitute for phosphate linkages in the backbone of the molecule.

The invention also pertains to nucleic acid molecules hybridize under high stringency hybridization conditions, such as for selective hybridization, to a nucleotide sequence described herein (e.g., nucleic acid molecules which specifically hybridize to a nucleotide sequence encoding polypeptides described herein, and, optionally, have an activity of the polypeptide). In one embodiment, the invention includes variants described herein which hybridize under high stringency hybridization conditions (e.g., for selective hybridization) to a nucleotide sequence comprising a nucleotide sequence selected from the group consistmg of SEQ ID NOs:l-230 (odd numbers). In another embodiment, the invention includes variants described herein which hybridize under high stringency hybridization conditions (e.g., for selective hybridization) to a nucleotide sequence encoding an amino acid sequence selected from the group consisting of SEQ TD NOs:l-230 (even numbers) or a polymorphic variant thereof. In a preferred embodiment, the variant that hybridizes under high stringency hybridizations has an activity of a GPCR.

Such nucleic acid molecules can be detected and/or isolated by specific hybridization (e.g., under high stringency conditions). "Specific hybridization" as used herein, refers to the ability of a first nucleic acid to hybridize to a second nucleic acid in a manner such that the first nucleic acid does not hybridize to any nucleic acid other than to the second nucleic acid (e.g., when the first nucleic acid has a higher similarity to the second nucleic acid than to any other nucleic acid in a sample wherem the hybridization is to be performed). "Stringency conditions" for hybridization is a term of art which refers to the incubation and wash conditions, e.g., conditions of temperature and buffer concentration, which permit hybridization of a particular nucleic acid to a second nucleic acid; the first nucleic acid may be perfectly (i.e., 100%) complementary to the second, or the first and second may share some degree of complementarity which is less than perfect (e.g. , 70%, 75%, 85%, 95%). For example, certain high stringency conditions can be used which distinguish perfectly complementary nucleic acids from those of less complementarity. "High stringency conditions", "moderate stringency conditions" and "low stringency conditions" for nucleic acid hybridizations are explained on pages 2.10.1-2.10.16 and pages 6.3.1-6.3.6 in Current Protocols in Molecular Biology (Ausubel, F.M. et al, "Current Protocols in Molecular Biology", John Wiley & Sons, 1998), the entire teachings of which are incorporated by reference herein). The exact conditions which determine the stringency of hybridization depend not only on ionic strength (e.g., 0.2X SSC, 0.1X SSC), temperature (e.g., room temperature, 42 ° C, 68 ° C) and the concentration of destabilizing agents such as formamide or denaturing agents such as SDS, but also on factors such as the length of the nucleic acid sequence, base composition, percent mismatch between hybridizing sequences and the frequency of occurrence of subsets of that sequence within other non-identical sequences. Thus, equivalent conditions can be determined by varying one or more of these parameters while maintaining a similar degree of identity or similarity between the two nucleic acid molecules. Typically, conditions are used such that sequences at least about 60%, at least about 70%, at least about 80%, at least about 90% or at least about 95% or more identical to each other remain hybridized to one another. By varying hybridization conditions from a level of stringency at which no hybridization occurs to a level at which hybridization is first observed, conditions which will allow a given sequence to hybridize (e.g., selectively) with the most similar sequences in the sample can be determined.

Exemplary conditions are described in Krause, M.H. and S.A. Aaronson, Methods in Enzymology 200:546-556, 1991, and in, Ausubel, et al., "Current Protocols in Molecular Biology", John Wiley & Sons, 1998, which describes the determination of washing conditions for moderate or low stringency conditions. Washing is the step in which conditions are usually set so as to determine a minimum level of complementarity of the hybrids. Generally, starting from the lowest temperature at which only homologous hybridization occurs, each °C by which the final wash temperature is reduced (holding SSC concentration constant) allows an increase by 1% in the maximum extent of mismatching among the sequences that hybridize. Generally, doubling the concentration of SSC results in an increase in T_m of ~ 17 °C. Using these guidelines, the washing temperature can be determined empirically for high, moderate or low stringency, depending on the level of mismatch sought.

For example, a low stringency wash can comprise washing in a solution containing 0.2X SSC/0.1% SDS for 10 minutes at room temperature; a moderate stringency wash can comprise washing in a prewarmed solution (42 °C) solution containing 0.2X SSC/0.1% SDS for 15 minutes at 42°C; and a high stringency wash can comprise washing in prewarmed (68 °C) solution containing 0.1X SSC/0.1%SDS for 15 minutes at 68°C. Furthermore, washes can be performed repeatedly or sequentially to obtain a desired result as known in the art. Equivalent conditions can be determined by varying one or more of the parameters given as an example, as known in the art, while maintaining a similar degree of identity or similarity between the target nucleic acid molecule and the primer or probe used. The percent identity of two nucleotide or amino acid sequences can be determined by aligning the sequences for optimal comparison purposes (e.g., gaps can be introduced in the sequence of a first sequence). The nucleotides or amino acids at corresponding positions are then compared, and the percent identity between the two sequences is a function of the number of identical positions shared by the sequences (i.e., % identity = # of identical positions/total # of positions x 100). In certain embodiments, the length of a sequence aligned for comparison purposes is at least 30%), preferably at least 40%, more preferably at least 60%, and even more preferably at least 70%, 80%, 90% or 95% of the length of the reference sequence. The actual comparison of the two sequences can be accomplished by well-known methods, for example, using a mathematical algorithm. A preferred, non-limiting example of such a mathematical algorithm is described in Karlin et άl., Proc. Natl. Acad. Sci. USA 90:5873-5877, 1993. Such an algorithm is incorporated into the NBLAST and XBLAST programs (version 2.0) as described in Altschul et al. ,

Nucleic Acids Res. 25 :389-3402, 1997. When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., NBLAST) can be used (see, e.g., http://www.ncbi.nlm.nih.gov). In one embodiment, parameters for sequence comparison can be set at score=100, wordlength=12, or can be varied (e.g., W=5 or W=20).

Another preferred, non-limiting example of a mathematical algorithm utilized for the comparison of sequences is the algorithm of Myers and Miller CABIOS 4(1): 1-1-17. 1998. Such an algorithm is incorporated into the ALIGN program (version 2.0) which is part of the GCG sequence alignment software package (Accelrys, Cambridge, UK). When utilizing the ALIGN program for comparing amino acid sequences, a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4 can be used. Additional algorithms for sequence analysis are known in the art and include ADVANCE and ADAM as described in Torellis and Robotti, Comput. Appl. Biosci. 10:3-5, 1994; and FASTA described in Pearson and Lipman Proc. Natl. Acad. Sci. USA 85:2444-8, 1988.

In another embodiment, the percent identity between two amino acid sequences can be accomplished using the GAP program in the GCG software package using either a BLOSUM63 matrix or a PAM250 matrix, and a gap weight of 12, 10, 8, 6, or 4 and a length weight of 2, 3, or 4. In yet another embodiment, the percent identity between two nucleic acid sequences can be accomplished using the

GAP program in the GCG software package, using a gap weight of 50 and a length weight of 3. The present invention also provides isolated nucleic acid molecules that contain a fragment or portion that hybridizes under highly stringent conditions to a nucleotide sequence comprising a nucleotide sequence selected from the group consisting of SEQ JD NOs: 1-230 (odd numbers), or the complement of such a sequence, and also provides isolated nucleic acid molecules that contain a fragment or portion that hybridizes under highly stringent conditions to a nucleotide sequence encoding an amino acid sequence selected SEQ JD NOs: 1-230 (even numbers), or polymorphic variant thereof. The nucleic acid fragments of the invention are at least about 15, preferably at least about 18, 20, 23 or 25 nucleotides, and can be 30, 40, 50, 100, 200 or more nucleotides in length. Longer fragments, for example, 30 or more nucleotides in length, which encode antigenic polypeptides described herein are particularly useful, such as for the generation of antibodies as described below.

In a related aspect, the nucleic acid fragments of the invention are used as probes or primers in assays such as those described herein. "Probes" or "primers" are oligonucleotides that hybridize in a base-specific manner to a complementary strand of nucleic acid molecules. Such probes and primers include polypeptide nucleic acids, as described in Nielsen et al., Science 254:1497-1500, 1991.

Typically, a probe or primer comprises a region of nucleotide sequence that hybridizes to at least about 15, typically about 20-25, and more typically about 40, 50 or 75, consecutive nucleotides of a nucleic acid molecule comprising a contiguous nucleotide sequence selected from the group consisting of SEQ ID NOs: 1-230 (odd numbers), or the complement of such a sequence, or a sequence encoding an amino acid sequence selected from SEQ ID NOs: 1-230 (even numbers), or polymorphic variant thereof. In preferred embodiments, a probe or primer comprises 100 or fewer nucleotides, preferably from 6 to 50 nucleotides, preferably from 12 to 30 nucleotides. In other embodiments, the probe or primer is at least 70% identical to the contiguous nucleotide sequence or to the complement of the contiguous nucleotide sequence, preferably at least 80% identical, more preferably at least 90%) identical, even more preferably at least 95% identical, or even capable of selectively hybridizing to the contiguous nucleotide sequence or to the complement of the contiguous nucleotide sequence. Often, the probe or primer further comprises a label, e.g., radioisotope, fluorescent compound, enzyme, or enzyme co-factor.

The nucleic acid molecules of the invention such as those described above can be identified and isolated using standard molecular biology techniques and the sequence information provided herein. For example, nucleic acid molecules can be amplified and isolated by the polymerase chain reaction using synthetic oligonucleotide primers designed based on one or more of the sequences selected from the group consisting of SEQ ID NOs: 1-230 (odd numbers), or the complement of such a sequence, or designed based on nucleotides based on sequences encoding one or more of the amino acid sequences provided herein. See generally PCR

Technology: Principles and Applications for DNA Amplification (ed. H.A. Erlich, Freeman Press, NY, NY, 1992); PCR Protocols: A Guide to Methods and Applications (Eds. Innis et al, Academic Press, San Diego, CA, 1990); Manila et al, Nucl. Acids Res. 19:4967, 1991; Eckert et al, PCR Methods and Applications 1:17, 1991; PCR (eds. McPherson et al, IRL Press, Oxford); and U.S. Patent

4,683,202. The nucleic acid molecules can be amplified using cDNA, mRNA or genomic DNA as a template, cloned into an appropriate vector and characterized by DNA sequence analysis.

Other suitable amplification methods include the ligase chain reaction (LCR) (see Wu and Wallace, Genomics 4:560, 1989, Landegren et al, Science 241 :1077, 1988, transcription amplification (Kwoh et al, Proc. Natl. Acad. Sci. USA 86:1173, 1989), and self-sustained sequence replication (Guatelli et al, Proc. Nat. Acad. Sci. USA 87:1874, 1990) and nucleic acid based sequence amplification (NASBA). The latter two amplification methods involve isothermal reactions based on isothermal transcription, which produce both single stranded RNA (ssRNA) and double stranded DNA (dsDNA) as the amplification products in a ratio of about 30 or 100 to 1, respectively.

The amplified DNA can be radiolabelled and used as a probe for screening a cDNA library derived from human cells, mRNA in zap express, ZJRLOX or other suitable vector. Corresponding clones can be isolated, DNA can obtained following in vivo excision, and the cloned insert can be sequenced in either or both orientations by art recognized methods to identify the correct reading frame encoding a polypeptide of the appropriate molecular weight. For example, the direct analysis of the nucleotide sequence of nucleic acid molecules of the present invention can be accomplished using well-known methods that are commercially available. See, for example, Sambrook et al, Molecular Cloning, A Laboratory Manual (2nd Ed., CSHP, New York 1989); Zyskind et al , Recombinant DNA Laboratory Manual, (Acad. Press, 1988)). Using these or similar methods, the polypeptide and the DNA encoding the polypeptide can be isolated, sequenced and further characterized.

Antisense nucleic acid molecules of the invention can be designed using the nucleotide sequences of one or more of SEQ JD NOs:l-230 (odd numbers) and/or the complement of one or more of SEQ JD NOs: 1 -230 (odd numbers), and/or a portion of one or more of SEQ ID NOs: 1-230 (odd numbers), or the complement of one or more of SEQ JD NOs: 1-230 (odd numbers) and/or a sequence encoding the amino acid sequences of one or more of SEQ ID NOs:l-230 (even numbers), or encoding a portion of one or more of SEQ ID NOs: 1-230 (even numbers), and constructed using chemical synthesis and enzymatic ligation reactions using procedures known in the art. For example, an antisense nucleic acid molecule (e.g., an antisense oligonucleotide) can be chemically synthesized using naturally occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids, e.g., phosphorothioate derivatives and acridine substituted nucleotides Gan be used. Alternatively, the antisense nucleic acid molecule can be produced biologically using an expression vector into which a nucleic acid molecule has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid molecule will be of an antisense orientation to a target nucleic acid of interest).

In general, the isolated nucleic acid sequences of the invention can be used as molecular weight markers on Southern gels, and as chromosome markers that are labeled to map related gene positions. The nucleic acid sequences can also be used to compare with endogenous DNA sequences in patients to identify one or more of the disorders described above, and as probes, such as to hybridize and discover related DNA sequences or to subtract out known sequences from a sample. The nucleic acid sequences can further be used to derive primers for genetic fingerprinting, to raise anti-polypeptide antibodies using DNA immunization techniques, and as an antigen to raise anti-DNA antibodies or elicit immune responses. Portions or fragments of the nucleotide sequences identified herein (and the corresponding complete gene sequences) can be used in numerous ways as polynucleotide reagents. For example, these sequences can be used to: (i) map their respective genes on a chromosome; and, thus, locate gene regions associated with genetic disease; (ii) identify an individual from a minute biological sample (tissue typing); and (iii) aid in forensic identification of a biological sample. Additionally, the nucleotide sequences of the invention can be used to identify and express recombinant polypeptides for analysis, characterization or therapeutic use, or as markers for tissues in which the corresponding polypeptide is expressed, either constitutively, during tissue differentiation, or in diseased states. The nucleic acid sequences can additionally be used as reagents in the screening and/or diagnostic assays described herein, and can also be included as components of kits (e.g., reagent kits) for use in the screening and/or diagnostic assays described herein.

Another aspect of the invention pertains to nucleic acid constructs containing a nucleic acid molecule selected from the group consisting of SEQ ID NOs: 1-230 (odd numbers) and the complements thereof (or a portion thereof). Yet another aspect of the invention pertains to nucleic acid constructs containing a nucleic acid molecule encoding an amino acid sequence of SEQ JD NOs: 1 -230 (even numbers) or polymorphic variant thereof. The constructs comprise a vector (e.g., an expression vector) into which a sequence of the invention has been inserted in a sense or antisense orientation. As used herein, the term "vector" refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a "plasmid", which refers to a circular double stranded

DNA loop into which additional DNA segments can be ligated. Another type of vector is a viral vector, wherein additional DNA segments can be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors, expression vectors, are capable of directing the expression of genes to which they are operably linked. In general, expression vectors of utility in recombinant DNA techniques are often in the form of plasmids. However, the invention is intended to include such otlier forms of expression vectors, such as viral vectors (e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses) that serve equivalent functions.

Preferred recombinant expression vectors of the invention comprise a nucleic acid molecule of the invention in a form suitable for expression of the nucleic acid molecule in a host cell. This means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, which is operably linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, "operably linked" or "operatively linked" is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner which allows for expression of the nucleotide sequence (e.g. , in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell). The term "regulatory sequence" is intended to include promoters, enhancers and other expression control elements (e.g., polyadenylation signals). Such regulatory sequences are described, for example, in Goeddel, "Gene Expression Technology", Methods in Enzymology 185, Academic Press, San Diego, CA (1990). Regulatory sequences include those which direct constitutive expression of a nucleotide sequence in many types of host cell and those which direct expression of the nucleotide sequence only in certain host cells (e.g., tissue-specific regulatory sequences). It will be appreciated by those skilled in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed and the level of expression of polypeptide desired. The expression vectors of the invention can be introduced into host cells to thereby produce polypeptides, including fusion polypeptides, encoded by nucleic acid molecules as described herein.

The recombinant expression vectors of the invention can be designed for expression of a polypeptide of the invention in prokaryotic or eukaryotic cells, e.g., bacterial cells such as E. coli, insect cells (using baculovirus expression vectors), yeast cells or mammalian cells. Suitable host cells are discussed further in Goeddel, supra. Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.

Another aspect of the invention pertains to host cells into which a recombinant expression vector of the invention has been introduced. The terms "host cell" and "recombinant host cell" are used interchangeably herein. It is understood that such terms refer not only to the particular subject cell but also to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein.

A host cell can be any prokaryotic or eukaryotic cell. For example, a nucleic acid molecule of the invention can be expressed in bacterial cells (e.g., E. coli), insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells). Other suitable host cells are known to those skilled in the art.

Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional transformation or transfection techniques. As used herein, the terms "transformation" and "transfection" are intended to refer to a variety of art-recognized techniques for introducing a foreign nucleic acid molecule (e.g., DNA) into a host cell, mcluding calcium phosphate or calcium chloride co-precipitation, DEAE-dextran-mediated transfection, lipofection, or electroporation. Suitable methods for fransforming or transfecting host cells can be found in Sambrook, et al. (supra), and other laboratory manuals. For stable transfection of mammalian cells, it is known that, depending upon the expression vector and transfection technique used, only a small fraction of cells may integrate the foreign DNA into their genome. In order to identify and select these integrants, a gene that encodes a selectable marker (e.g., for resistance to antibiotics) is generally introduced into the host cells along with the gene of interest. Preferred selectable markers include those that confer resistance to drugs, such as G418, hygromycin and methotrexate. Nucleic acid molecules encoding a selectable marker can be introduced into a host cell on the same vector as the nucleic acid molecule of the invention or can be introduced on a separate vector. Cells stably transfected with the introduced nucleic acid molecule can be identified by drug selection (e.g., cells that have incorporated the selectable marker gene will survive, while the other cells die).

A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (i. e. , express) a polypeptide of the invention. Accordingly, the invention further provides methods for producing a polypeptide using the host cells of the invention. In one embodiment, the method comprises culturing the host cell of invention (into which a recombinant expression vector encoding a polypeptide of the invention has been introduced) in a suitable medium such that the polypeptide is produced. In another embodiment, the method further comprises isolating the polypeptide from the medium or the host cell.

The host cells of the invention can also be used to produce nonhuman transgenic animals. For example, in one embodiment, a host cell of the invention is a fertilized oocyte or an embryonic stem cell into which a nucleic acid molecule of the invention has been introduced (e.g. , an exogenous GPCR gene, or an exogenous nucleic acid encoding a GPCR polypeptide). Such host cells can then be used to create non-human transgenic animals in which exogenous nucleotide sequences have been introduced into the genome or homologous recombinant animals in which endogenous nucleotide sequences have been altered. Such animals are useful for studying the function and/or activity of the nucleotide sequence and polypeptide encoded by the sequence and for identifying andor evaluating modulators of their activity. As used herein, a "transgenic animal" is a non-human animal, preferably a mammal, more preferably a rodent such as a rat or mouse, in which one or more of the cells of the animal includes a transgene. Other examples of transgenic animals include non-human primates, sheep, dogs, cows, goats, chickens and amphibians. A transgene is exogenous DNA which is integrated into the genome of a cell from which a transgenic animal develops and which remains in the genome of the mature animal, thereby directing the expression of an encoded gene product in one or more cell types or tissues of the transgenic animal. As used herein, an "homologous recombinant animal" is a non-human animal, preferably a mammal, more preferably a mouse, in which an endogenous gene has been altered by homologous recombination between the endogenous gene and an exogenous DNA molecule introduced into a cell of the animal, e.g., an embryonic cell of the animal, prior to development of the animal.

Methods for generating transgenic animals via embryo manipulation and microinjection, particularly animals such as mice, have become conventional in the art and are described, for example, in U.S. Patent Nos. 4,736,866 and 4,870,009, U.S. Pat. No. 4,873,191 and in Hogan, Manipulating the Mouse Embryo (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1986). Methods for constructing homologous recombination vectors and homologous recombinant animals are described further in Bradley (1991) Current Opinion in BioTechnology 2:823-829 and in PCT Publication Nos. WO 90/11354, WO 91/01140, WO 92/0968, and WO 93/04169. Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut et al. (1997) Nature 385:810-813 and PCT Publication Nos. WO 97/07668 and WO 97/07669.

POLYPEPTIDES OF THE VENTION

The present invention also pertains to isolated polypeptides encoded by GPCRs ("GPCR polypeptides") and fragments and variants thereof, as well as polypeptides encoded by nucleotide sequences described herein (e.g., other splicing variants). The term "polypeptide" refers to a polymer of amino acids, and not to a specific length; thus, peptides, oligopeptides and proteins are included within the definition of a polypeptide. As used herein, a polypeptide is said to be "isolated" or "purified" when it is substantially free of cellular material when it is isolated from recombinant and non-recombinant cells, or free of chemical precursors or other chemicals when it is chemically synthesized. A polypeptide, however, can be joined to another poly eptide with which it is not normally associated in a cell (e.g. , in a "fusion protein") and still be "isolated" or "purified."

The polypeptides of the invention can be purified to homogeneity. It is understood, however, that preparations in which the polypeptide is not purified to homogeneity are useful. The critical feature is that the preparation allows for the desired function of the polypeptide, even in the presence of considerable amounts of other components. Thus, the invention encompasses various degrees of purity. In one embodiment, the language "substantially free of cellular material" includes preparations of the polypeptide having less than about 30% (by dry weight) other proteins (i.e., contaminating protem), less than about 20% other proteins, less than about 10% other proteins, or less than about 5% other proteins.

When a polypeptide is recombinantly produced, it can also be substantially free of culture medium, i.e., culture medium represents less than about 20%, less than about 10%), or less than about 5% of the volume of the polypeptide preparation. The language "substantially free of chemical precursors or other chemicals" includes preparations of the polypeptide in which it is separated from chemical precursors or other chemicals that are involved in its synthesis. In one embodiment, the language "substantially free of chemical precursors or other chemicals" includes preparations of the polypeptide having less thamabout 30% (by dry weight) chemical precursors or other chemicals, less than about 20% chemical precursors or other chemicals, less than about 10% chemical precursors or other chemicals, or less than about 5% chemical precursors or other chemicals. In one embodiment, a polypeptide of the invention comprises an arriino acid sequence encoded by a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs:l-230 (odd numbers), or the complement of such a nucleic acid, or portions thereof, e.g. , SEQ ID NO: 1 -230 (even numbers), or a portion or polymorphic variant thereof. However, the polypeptides of the invention also encompass fragment and sequence variants. Variants include a substantially homologous polypeptide encoded by the same genetic locus in an organism, i.e., an allelic variant, as well as other splicing variants. Variants also encompass polypeptides derived from other genetic loci in an organism, but having substantial homology to a polypeptide encoded by a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1-230 (odd numbers), or a complement of such a sequence, or portions thereof, or having substantial homology to a polypeptide encoded by a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of nucleotide sequences encoding SEQ TD NOs: 1-230 (even numbers), or polymorphic variants thereof. Variants also include polypeptides substantially homologous or identical to these polypeptides but derived from another organism, i.e., an ortholog. Variants also include polypeptides that are substantially homologous or identical to these polypeptides that are produced by chemical synthesis. Variants also include polypeptides that are substantially homologous or identical to these polypeptides that are produced by recombinant methods.

As used herein, two polypeptides (or a region of the polypeptides) are substantially homologous or identical when the amino acid sequences are at least about 45-55%o, typically at least about 70-75%, more typically at least about 80-85%), and most typically greater than about 90% or more homologous or identical. A substantially homologous amino acid sequence, according to the present invention, will be encoded by a nucleic acid molecule hybridizing to one or more of SEQ 3D NOs: 1-230 (odd numbers), or portion thereof, under stringent conditions as more particularly described above, or will be encoded by a nucleic acid molecule hybridizing to a nucleic acid sequence encoding one of SEQ 3D NOs: 1-230 (even numbers), a portion thereof or polymorphic variant thereof, under stringent conditions as more particularly described thereof. To deteπnine the percent homology or identity of two amino acid sequences, or of two nucleic acid sequences, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in the sequence of one polypeptide or nucleic acid molecule for optimal alignment with the other polypeptide or nucleic acid molecule). The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in one sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the other sequence, then the molecules are homologous at that position. As used herein, amino acid or nucleic acid "homology" is equivalent to amino acid or nucleic acid "identity". The percent homology between the two sequences is a function of the number of identical positions shared by the sequences

(i.e., percent homology equals the number of identical positions/total number of positions times 100).

The invention also encompasses polypeptides having a lower degree of identity but having sufficient similarity so as to perform one or more of the same functions performed by a polypeptide encoded by a nucleic acid molecule of the invention. Similarity is determined by conserved amino acid substitution. Such substitutions are those that substitute a given amino acid in a polypeptide by another amino acid of like characteristics. Conservative substitutions are likely to be phenotypically silent. Typically seen as conservative substitutions are the replacements, one for another, among the aliphatic amino acids Ala, Val, Leu and He; interchange of the hydroxyl residues Ser and Thr, exchange of the acidic residues Asp and Glu, substitution between the amide residues Asn and Gin, exchange of the basic residues Lys and Arg and replacements among the aromatic residues Phe and Tyr. Guidance concerning which amino acid changes are likely to be phenotypically silent are found in Bowie et al, Science 247:1306-1310 (1990). A variant polypeptide can differ in amino acid sequence by one or more substitutions, deletions, insertions, inversions, fusions, and truncations or a combination of any of these. Further, variant polypeptides can be fully functional or can lack function in one or more activities. Fully functional variants typically contain only conservative variation or variation in non-critical residues or in non-critical regions. Functional variants can also contain 'substitution of similar amino acids that result in no change or an insignificant change in function.

Alternatively, such substitutions may positively or negatively affect function to some degree. Non-functional variants typically contain one or more non-conservative amino acid substitutions, deletions, insertions, inversions, or truncation or a substitution, insertion, inversion, or deletion in a critical residue or critical region.

Amino acids that are essential for function can be identified by methods known in the art, such as site-directed mutagenesis or alanme-scanning mutagenesis (Cunningham et al, Science 244:1081-1085 (1989)). The latter procedure introduces single alanine mutations at every residue in the molecule. The resulting mutant molecules are then tested for biological activity in vitro, or in vitro proliferative activity. Sites that are critical for polypeptide activity can also be determined by structural analysis such as crystallization, nuclear magnetic resonance or photoaffmity labeling (Smith et al, J. Mol. Biol. 224:899-904 (1992); de Vos et al, Science 255:306-312 (1992)). The mvention also includes polypeptide fragments of the polypeptides of the invention. Fragments can be derived from a polypeptide encoded by a nucleic acid molecule comprising one of SEQ 3D NOs: 1-230 (odd numbers), or a complement of such a nucleic acid (e.g., SEQ 3D NOs.T-230 (even numbers), or other variants). However, the invention also encompasses fragments of the variants of the polypeptides described herein. As used herein, a fragment comprises at least 6 contiguous amino acids. Useful fragments include those that retain one or more of the biological activities of the polypeptide as well as fragments that can be used as an immunogen to generate polypeptide-specific antibodies. Biologically active fragments (peptides which are, for example, 6, 9, 12, 15, 16, 20, 30, 35, 36, 37, 38, 39, 40, 50, 100 or more amino acids in length) can comprise a domain, segment, or motif that has been identified by analysis of the polypeptide sequence using well-known methods, e.g. , signal peptides, extracellular domains, one or more transmembrane segments or loops, hgand binding regions, zinc finger domains, DNA binding domains, acylation sites, glycosylation sites, or phosphorylation sites.

Fragments can be discrete (not fused to other amino acids or polypeptides) or can be within a larger polypeptide. Further, several fragments can be comprised within a single larger polypeptide. In one embodiment a fragment designed for expression in a host can have heterologous pre- and pro-polypeptide regions fused to the amino terminus of the polypeptide fragment and an additional region fused to the carboxyl terminus of the fragment. The invention thus provides chimeric or fusion polypeptides. These comprise a polypeptide of the invention operatively linked to a heterologous protein or polypeptide having an amino acid sequence not substantially homologous to the polypeptide. "Operatively linked" indicates that the polypeptide and the heterologous protein are fused in-frame. The heterologous protein can be fused to the N-terminus or C-terminus of the polypeptide. In one embodiment the fusion polypeptide does not affect function of the polypeptide r se. For example, the fusion polypeptide can be a GST-fusion polypeptide in which the polypeptide sequences are fused to the C-terminus of the GST sequences. Other types of fusion polypeptides include, but are not limited to, enzymatic fusion polypeptides, for example /3-galactosidase fusions, yeast two-hybrid GAL fusions, poly-His fusions and Ig fusions. Such fusion polypeptides, particularly poly-His fusions, can facilitate the purification of recombinant polypeptide. In certain host cells (e.g. , mammalian host cells), expression and/or secretion of a polypeptide can be increased by using a heterologous signal sequence. Therefore, in another embodiment, the fusion polypeptide contains a heterologous signal sequence at its N-terminus. EP-A-O 464 533 discloses fusion proteins comprising various portions of immunoglobulin constant regions. The Fc is useful in therapy and diagnosis and thus results, for example, in improved pharmacokinetic properties (EP-A 0232262). In drug discovery, for example, human protems have been fused with Fc portions for the purpose of high-throughput screening assays to identify antagonists. Bennett et al, J. Mol. Recog. 8:52-58 (1995) and Johanson et al, J. Biol. Chem.

270:16:9459-9471 (1995). Thus, this invention also encompasses soluble fusion polypeptides containing a polypeptide of the invention and various portions of the constant regions of heavy or light chains of immunoglobulins of various subclass (IgG, IgM, IgA, IgE). A chimeric or fusion polypeptide can be produced by standard recombinant

DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of nucleic acid fragments can be carried out using anchor primers which give rise to complementary overhangs between two consecutive nucleic acid fragments which can subsequently be annealed and re-amplified to generate a chimeric nucleic acid sequence (see Ausubel et al., Current Protocols in Molecular Biology, 1992). Moreover, many expression vectors are commercially available that afready encode a fusion moiety (e.g., a GST protein). A nucleic acid molecule encoding a polypeptide of the invention can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the polypeptide.

The isolated polypeptide can be purified from cells that naturally express it, purified from cells that have been altered to express it (recombinant), or synthesized using known protem synthesis methods. In one embodiment, the polypeptide is produced by recombinant DNA techniques. For example, a nucleic acid molecule encoding the polypeptide is cloned into an expression vector, the expression vector introduced into a host cell and the polypeptide expressed in the host cell. The polypeptide can then be isolated from the cells by an appropriate purification scheme using standard protein purification techniques.

In general, polypeptides of the present invention can be used as a molecular weight marker on SDS-PAGE gels or on molecular sieve gel filtration columns using art-recognized methods. The polypeptides of the present invention can be used to raise antibodies or to elicit an immune response. The polypeptides can also be used as a reagent, e.g., a labeled reagent, in assays to quantitatively determine levels of the polypeptide or a molecule to which it binds (e.g., a ligand) in biological fluids. The polypeptides can also be used as markers for cells or tissues in which the corresponding polypeptide is preferentially expressed, either constitutively, during tissue differentiation, or in a diseased state. The polypeptides can be used to isolate a corresponding binding agent, e.g., ligand, such as, for example, in an interaction trap assay, and to screen for peptide or small molecule antagonists or agonists of the binding interaction.

ANTIBODIES OF THE INVENTION

Polyclonal and/or monoclonal antibodies that specifically bind one form of the gene product but not to the other form of the gene product are also provided. Antibodies are also provided that bind a portion of either the variant or the reference gene product that contains the polymorphic site or sites. The invention provides antibodies to the polypeptides and polypeptide fragments of the mvention, e.g., having an amino acid sequence of one of SEQ 3D NOs: 1-230 (even numbers) or a portion thereof, or having an amino acid sequence encoded by a nucleic acid molecule comprising all or a portion of SEQ 3D NOs: 1-230 (odd numbers), or a complement or another variant or portion thereof. The term "antibody" as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e., molecules that contain an antigen binding site that specifically binds an antigen. A molecule that specifically binds to a polypeptide of the invention is a molecule that binds to that polypeptide or a fragment thereof, but does not substantially bind other molecules in a sample, e.g., a biological sample, which naturally contains the polypeptide. Examples of immunologically active portions of immunoglobulin molecules include F(ab) and F(ab')₂ fragments which can be generated by treating the antibody with an enzyme such as pepsin. The invention provides polyclonal and monoclonal antibodies that bind to a polypeptide of the invention. The term "monoclonal antibody" or "monoclonal antibody composition", as used herein, refers to a population of antibody molecules that contain only one species of an antigen binding site capable of immunoreacting with a particular epitope of a polypeptide of the invention. A monoclonal antibody composition thus typically displays a single binding affinity for a particular polypeptide of the invention with which it immunoreacts. Polyclonal antibodies can be prepared as described above by immunizing a suitable subject with a desired immunogen, e.g., polypeptide of the invention or fragment thereof. The antibody titer in the immunized subject can be monitored over time by standard techniques, such as with an enzyme linked immunosorbent assay (ELISA) using immobilized polypeptide. If desired, the antibody molecules directed against the polypeptide can be isolated from the mammal (e.g. , from the blood) and further purified by well-known techniques, such as protein A chromatography to obtain the IgG fraction. At an appropriate time after immunization, e.g., when the antibody titers are highest, antibody-producing cells can be obtained from the subject and used to prepare monoclonal antibodies by standard techniques, such as the hybridoma technique originally described by Kohler and Milstein (1975) Nature 256:495-497, the human B cell hybridoma technique (Kozbor et al. (1983) Immunol. Today 4:72), the EBV-hybridoma technique (Cole et al. (1985), Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96) or trioma techniques. The technology for producing hybridomas is well known (see generally Current Protocols in Immunology (1994)

Coligan et al. (eds.) John Wiley & Sons, Inc., New York, NY). Briefly, an immortal cell line (typically a myeloma) is fused to lymphocytes (typically splenocytes) from a mammal immunized with an immunogen as described above, and the culture supernatants of the resulting hybridoma cells are screened to identify a hybridoma producing a monoclonal antibody that binds a polypeptide of the invention.

Any of the many well known protocols used for fusing lymphocytes and immortalized cell lines can be applied for the purpose of generating a monoclonal antibody to a polypeptide of the invention (see, e.g., Current Protocols in Immunology, supra; Galfre et al, Nature 266:55052 (1977); R.H. Kenneth, in Monoclonal Antibodies: A New Dimension In Biological Analyses, Plenum Publishing Corp., New York, New York (1980); and Lerner, Yale J. Biol. Med. 54:387-402 (1981). Moreover, the ordinarily skilled worker will appreciate that there are many variations of such methods that also would be useful.

Alternative to preparing monoclonal antibody-secreting hybridomas, a monoclonal antibody to a polypeptide of the invention can be identified and isolated by screening a recombinant combinatorial immunoglobulin library (e.g., an antibody phage display library) with the polypeptide to thereby isolate immunoglobulin hbrary members that bind the polypeptide. Kits for generating and screening phage display libraries are commercially available (e.g., the Pharmacia Recombinant Phage Antibody System, Catalog No. 27-9400-01; and the Stratagene SurfZAP™ Phage Display Kit, Catalog No. 240612). Additionally, examples of methods and reagents particularly amenable for use in generating and screening antibody display library can be found in, for example, U.S. Patent No. 5,223,409; PCT Publication No. WO 92/18619; PCT Publication No. WO 91/17271; PCT Publication No. WO 92/20791; PCT Publication No. WO 92/15679; PCT Publication No. WO 93/01288; PCT Publication No. WO 92/01047; PCT Publication No. WO 92/09690; PCT Pubhcation No. WO 90/02809; Fuchs et al, Bio/Technology 9:1370-1372 (1991);

Hay et al, Hum. Antibod. Hybridomas 3:81-85 (1992); Huse et al, Science 246:1275-1281 (1989); Griffiths et al, EMBO J. 12:725-734 (1993).

Additionally, recombinant antibodies, such as chimeric and humanized monoclonal antibodies, comprising both human and non-human portions, which can be made using standard recombinant DNA techniques, are within the scope of the invention. Such chimeric and humanized monoclonal antibodies can be produced by recombinant DNA techniques known in the art.

In general, antibodies of the invention (e.g., a monoclonal antibody) can be used to isolate a polypeptide of the invention by standard techniques, such as affinity chromatography or immunoprecipitation. A polypeptide-specific antibody can facilitate the purification of natural polypeptide from cells and of recombinantly produced polypeptide expressed in host cells. Moreover, an antibody specific for a polypeptide of the invention can be used to detect the polypeptide (e.g., in a cellular lysate, cell supernatant, or tissue sample) in order to evaluate the abundance and pattern of expression of the polypeptide. Antibodies can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, /3-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include sfreptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhoda nine, dicWorofriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include I, I, S or H.

DIAGNOSTIC AND SCREEN3NG ASSAYS OF THE INVENTION

The present invention also pertains to a method of diagnosing or aiding in the diagnosis of a disease or condition associated with a GPCR gene or gene product in an individual. Diagnostic assays can be designed for assessing GPCR gene expression, or for assessing activity of GPCR polypeptides of the invention. In one embodiment, the assays are used in the context of a biological sample (e.g., blood, serum, cells, tissue) to thereby determine whether an individual is afflicted with a disease or condition associated with a GPCR, or a defect in a GPCR. The invention also provides for prognostic (or predictive) assays for determining whether an individual is susceptible to a disease of condition associated with a GPCR, e.g., if an individual is at risk for addiction to an opoid. For example, mutations in the gene can be assayed in a biological sample. Such assays can be used for prognostic or predictive purpose to thereby prophylactically treat an individual prior to the onset of symptoms associated with a susceptibility to a disease or condition associated with a GPCR. Another aspect of the invention pertains to assays for monitoring the influence of agents (e.g., drugs, compounds or other agents) on the gene expression or activity of polypeptides of the invention, as well as to assays for identifying agents that bind to a polypeptides. These and other assays and agents are described in further detail in the following sections.

DIAGNOSTIC ASSAYS

The nucleic acids, probes, primers, polypeptides and antibodies described herein can be used in methods of diagnosis of a susceptibility to a disease or condition associated with a GPCR, as well as in kits useful for diagnosis of a susceptibility to a disease or condition associated with a GPCR.

In one embodiment of the invention, diagnosis of a susceptibihty to a disease or condition associated with a GPCR is made by detecting a polymorphism in a GPCR as described herein. The polymorphism can be a mutation in a GPCR, such as the insertion or deletion of a single nucleotide, or of more than one nucleotide, resulting in a frame shift mutation; the change of at least one nucleotide, resulting in a change in the encoded amino acid; the change of at least one nucleotide, resulting in the generation of a premature stop codon; the deletion of several nucleotides, resulting in a deletion of one or more amino acids encoded by the nucleotides; the insertion of one or several nucleotides, such as by unequal recombination or gene conversion, resulting in an interruption of the coding sequence of the gene; duplication of all or apart of the gene; transposition of all or apart of the gene; or rearrangement df all or a part of the gene. More than one such mutation may be present in a single gene. Such sequence changes cause a mutation in the polypeptide encoded by a GPCR gene. For example, if the mutation is a frame shift mutation, the frame shift can result in a change in the encoded amino acids, and/or can result in the generation of a premature stop codon, causing generation of a truncated polypeptide. Alternatively, a polymorphism associated with a susceptibility to a disease or condition associated with a GPCR can be a synonymous mutation in one or more nucleotides (i.e., a mutation that does not result in a change in the polypeptide encoded by a GPCR gene). Such a polymorphism may alter splicing sites, affect the stability or transport of mRNA, or otherwise affect the transcription or translation of the gene. A GPCR gene that has any of the mutations described above is referred to herein as a "mutant gene." hi a first method of diagnosing a susceptibility to a susceptibility to a disease or condition associated with a GPCR, hybridization methods, such as Southern analysis, Northern analysis, or in situ hybridizations, can be used (see Current Protocols in Molecular Biology, Ausubel, F. et al, eds., John Wiley & Sons, including all supplements through 1999). For example, a biological sample from a test subject (a "test sample") of genomic DNA, RNA, or cDNA, is obtained from an individual suspected of having, being susceptible to or predisposed for, or carrying a defect for, a susceptibility to a disease or condition associated with a GPCR (the "test individual"). The individual can be an adult, child, or fetus. The test sample can be from any source which contains genomic DNA, such as a blood sample, sample of amniotic fluid, sample of cerebrospinal fluid, or tissue sample from skin, muscle, buccal or conjunctival mucosa, placenta, gastrointestinal tract or other organs. A test sample of DNA from fetal cells or tissue can be obtained by appropriate methods, such as by amniocentesis or chorionic villus sampling. The DNA, RNA, or cDNA sample is then examined to determine whether a polymorphism in a GPCR is present, and/or to determine which splicing variant(s) encoded by the GPCR is present. The presence of the polymorphism or splicing variant(s) can be indicated by hybridization of the gene in the genomic DNA, RNA, or cDNA to a nucleic acid probe. A "nucleic acid probe", as used herein, can be a DNA probe or an RNA probe; the nucleic acid probe can contain at least one polymorphism in a GPCR or contains a nucleic acid encoding a particular splicing variant of a GPCR. The probe can be any of the nucleic acid molecules described above (e.g., the gene, a fragment, a vector comprising the gene, a probe or primer, etc.).

To diagnose a susceptibility to a susceptibility to a disease or condition associated with a GPCR, a hybridization sample is formed by contacting the test sample containing a GPCR, with at least one nucleic acid probe. A preferred probe for detecting mRNA or genomic DNA is a labeled nucleic acid probe capable of hybridizing to mRNA or genomic DNA sequences described herein. The nucleic acid probe can be, for example, a full-length nucleic acid molecule, or a portion thereof, such as an oligonucleotide of at least 15, 30, 50, 100, 250 or 500 nucleotides in length and sufficient to specifically hybridize under stringent conditions to appropriate mRNA or genomic DNA. For example, the nucleic acid probe can be all or a portion of one of SEQ ID NOs: 1-230 (odd numbers), or the complement thereof, or a portion thereof; or can be a nucleic acid encoding a portion of one of SEQ ID NOs: 1-230 (even numbers). Other suitable probes for use in the diagnostic assays of the invention are described above (see e.g., probes and primers discussed under the heading, "Nucleic Acids of the Invention").

The hybridization sample is maintained under conditions that are sufficient to allow specific hybridization of the nucleic acid probe to a GPCR. "Specific hybridization", as used herein, indicates exact hybridization (e.g., with no mismatches). Specific hybridization can be performed under high stringency conditions or moderate stringency conditions, for example, as described above. In a particularly preferred embodiment, the hybridization conditions for specific hybridization are high stringency.

Specific hybridization, if present, is then detected using standard methods. If specific hybridization occurs between the nucleic acid probe and the GPCR in the test sample, then the GPCR has the polymorphism, or is the splicing variant, that is present in the nucleic acid probe. More than one nucleic acid probe can also be used concurrently in this method. Specific hybridization of any one of the nucleic acid probes is indicative of a polymorphism in the GPCR, or of the presence of a particular splicing variant encoding the GPCR and is therefore diagnostic for a susceptibility to a susceptibility to a disease or condition associated with a GPCR. In Northern analysis (see Current Protocols in Molecular Biology, Ausubel, F. et al, eds., John Wiley & Sons, supra) the hybridization methods described above are used to identify the presence of a polymorphism or a particular splicing variant, associated with a susceptibility to a susceptibility to a disease or condition associated with a GPCR. For Northern analysis, a test sample of RNA is obtained from the individual by appropriate means. Specific hybridization of a nucleic acid probe, as described above, to RNA from the individual is indicative of a polymorphism in a GPCR, or of the presence of a particular splicing variant encoded by a GPCR, and is therefore diagnostic for a susceptibility to a susceptibility to a disease or condition associated with a GPCR.

For representative examples of use of nucleic acid probes, see, for example, U.S. Patents No. 5,288,611 and 4,851,330. Alternatively, a peptide nucleic acid (PNA) probe can be used instead of a nucleic acid probe in the hybridization methods described above. PNA is a DNA mimic having a peptide-like, inorganic backbone, such as N-(2-aminoethyl)glycine units, with an organic base (A, G, C, T or U) attached to the glycine nitrogen via a methylene carbonyl linker (see, for example, Nielsen, P.E. et al, Bioconjugate Chemistry 5, American Chemical Society, p. 1 (1994). The PNA probe can be designed to specifically hybridize to a gene having a polymorphism associated with a susceptibility to a susceptibility to a disease or condition associated with a GPCR. Hybridization of the PNA probe to a GPCR is diagnostic for a susceptibility to a susceptibility to a disease or condition associated with a GPCR. In another method of the invention, mutation analysis by restriction digestion can be used to detect a mutant gene, or genes containing a polymorphism(s), if the mutation or polymorphism in the gene results in the creation or elimination of a restriction site. A test sample containing genomic DNA is obtained from the individual. Polymerase chain reaction (PCR) can be used to amplify a GPCR (and, if necessary, the flanking sequences) in the test sample of genomic DNA from the test individual. RFLP analysis is conducted as described (see Current Protocols in Molecular Biology, supra). The digestion pattern of the relevant DNA fragment indicates the presence or absence of the mutation or polymoφhism in the GPCR, and therefore indicates the presence or absence of this susceptibihty to a susceptibility to a disease or condition associated with a GPCR.

Sequence analysis can also be used to detect specific polymorphisms in a GPCR. A test sample of DNA or RNA is obtained from the test individual. PCR or other appropriate methods can be used to amplify the gene, and/or its flanking sequences, if desired. The sequence of a GPCR, or a fragment of the gene, or cDNA, or fragment of the cDNA, or mRNA, or fragment of the mRNA, is determined, using standard methods. The sequence of the gene, gene fragment, cDNA, cDNA fragment, mRNA, or mRNA fragment is compared with the known nucleic acid sequence of the gene, cDNA (e.g., one or more of SEQ ID NOs: 1-230 (odd numbers), or a complement thereof, or a nucleic acid sequence encoding one of SEQ ID NOs: 1-230 (even numbers) or a fragment thereof) or mRNA, as appropriate. The presence of a polymoφhism in the GPCR indicates that the individual has a susceptibility to a susceptibility to a disease or condition associated with a GPCR.

Allele-specific oligonucleotides can also be used to detect the presence of a polymoφhism in a GPCR, through the use of dot-blot hybridization of amplified oligonucleotides with allele-specific ohgonucleotide (ASO) probes (see, for example, Saiki, R. et al, Nature 324:163-166 (1986)). An "allele-specific oligonucleotide" (also referred to herein as an "allele-specific oligonucleotide probe") is an oligonucleotide of approximately 10-50 base pairs, preferably approximately 15-30 base pairs, that specifically hybridizes to a GPCR, and that contains a polymoφhism associated with a susceptibility to a susceptibihty to a disease or condition associated with a GPCR. An allele-specific oligonucleotide probe that is specific for particular polymoφhisms in a GPCR can be prepared, using standard methods (see Current Protocols in Molecular Biology, supra). To identify polymoφhisms in the gene that are associated with a susceptibility to a susceptibility to a disease or condition associated with a GPCR, a test sample of DNA is obtained from the individual. PCR can be used to amplify all or a fragment of a GPCR, and its flanking sequences. The DNA containing the amplified GPCR (or fragment of the gene) is dot-blotted, using standard methods (see Current Protocols in Molecular Biology, supra), and the blot is contacted with the oligonucleotide probe. The presence of specific hybridization of the probe to the amplified GPCR is then detected. Specific hybridization of an allele-specific oligonucleotide probe to DNA from the individual is indicative of a polymoφhism in the GPCR, and is therefore indicative of a susceptibility to a susceptibility to a disease or condition associated with a GPCR.

In another embodiment, arrays of oligonucleotide probes that are complementary to target nucleic acid sequence segments from an individual, can be used to identify polymoφhisms in a GPCR. For example, in one embodiment, an oligonucleotide array can be used. Ohgonucleotide arrays typically comprise a plurality of different oligonucleotide probes that are coupled to a surface of a substrate in different known locations. These oligonucleotide arrays, also described as "Genechips™," have been generally described in the art, for example, U.S. Pat. No. 5,143,854 and PCT patent publication Nos. WO 90/15070 and 92/10092. These arrays can generally be produced using mechanical synthesis methods or light directed synthesis methods which incoφorate a combination of photolithographic methods and solid phase oligonucleotide synthesis methods. See Fodor et al, Science 251:767-777 (1991), Pirrung et al, U.S. Pat. No. 5,143,854 (see also PCT Application No. WO 90/15070) and Fodor et al, PCT Publication No. WO 92/10092 and U.S. Pat. No. 5,424,186, the entire teachings of each of which are incoφorated by reference herein. Techniques for the synthesis of these arrays using mechanical synthesis methods are described in, e.g., U.S. Pat. Nos. 5,384,261, the entire teachings of which are incoφorated by reference herein.

Once an oligonucleotide aπay is prepared, a nucleic acid of interest is hybridized with the aπay and scanned for polymoφhisms. Hybridization and scanning are generally carried out by methods described herein and also in, e.g., Published PCT Apphcation Nos. WO 92/10092 and WO 95/11995, and U.S. Pat. No. 5,424,186, the entire teachings of which are incoφorated by reference herein. In brief, a target nucleic acid sequence which includes one or more previously identified polymoφhic markers is amplified by well known amphfication techniques, e.g., PCR. Typically, this involves the use of primer sequences that are complementary to the two strands of the target sequence both upstream and downstream from the polymoφhism. Asymmetric PCR techniques may also be used. Amplified target, generally incoφorating a label, is then hybridized with the array under appropriate conditions. Upon completion of hybridization and washing of the array, the aπay is scanned to determine the position on the array to which the target sequence hybridizes. The hybridization data obtained from the scan is typically in the form of fluorescence intensities as a function of location on the array. Although primarily described in terms of a single detection block, e.g. , for detection of a single polymoφhism, arrays can include multiple detection blocks, and thus be capable of analyzing multiple, specific polymoφhisms. In alternate arrangements, it will generally be understood that detection blocks may be grouped within a single aπay or in multiple, separate aπays so that varying, optimal conditions may be used during the hybridization of the target to the aπay. For example, it may often be desirable to provide for the detection of those polymoφhisms that fall within G-C rich stretches of a genomic sequence, separately from those falling in A-T rich segments. This allows for the separate optimization of hybridization conditions for each situation.

Additional description of use of oligonucleotide aπays for detection of polymoφhisms can be found, for example, in U.S. Patents 5,858,659 and 5,837,832, the entire teachings of which are incoφorated by reference herein. Other methods of nucleic acid analysis can be used to detect polymoφhisms in a GPCR or variants encoding by a GPCR. Representative methods include direct manual sequencing (Church and Gilbert, Proc. Natl. Acad. Sci. USA 81:1991-1995 (1988); Sanger, F. et al. Proc. Natl. Acad. Sci. USA 74:5463-5467 (1977); Beavis et al, U.S. Pat. No. 5,288,644); automated fluorescent sequencing; single-stranded conformation polymoφhism assays (SSCP); clamped denaturing gel electrophoresis (CDGE); denaturing gradient gel electrophoresis (DGGE) (Sheffield, V.C. et al. Proc. Natl. Acad. Sci. USA 86:232-236 (1989)), mobility shift analysis (Orita, M. et al, Proc. Natl Acad. Sci. USA 86:2766-2770 (1989)), restriction enzyme analysis (Flavell et al, Cell 15:25 (1978); Geever, et al, Proc. Natl. Acad. Sci USA 78:5081 (1981)); heteroduplex analysis; chemical mismatch cleavage (CMC) (Cotton et al, Proc. Natl. Acad. Sci USA 85:4397-4401 (1985)); RNase protection assays (Myers, R.M. et al, Science 230:1242 (1985)); use of polypeptides which recognize nucleotide mismatches, such as E. coli mutS protein; allele-specific PCR, for example. In another embodiment of the invention, diagnosis of a susceptibility to a susceptibihty to a disease or condition associated with a GPCR can also be made by examining expression and/όr composition of a GPCR polypeptide, by a variety of methods, including enzyme linked immunosorbent assays (ELISAs), Western blots, ήnmunoprecipitations and immunofluorescence. A test sample from an individual is assessed for the presence of an alteration in the expression and/or an alteration in composition of the polypeptide encoded by a GPCR, or for the presence of a particular variant encoded by a GPCR. An alteration in expression of a polypeptide encoded by a GPCR can be, for example, an alteration in the quantitative polypeptide expression (i.e., the amount of polypeptide produced); an alteration in the composition of a polypeptide encoded by a GPCR is an alteration in the qualitative polypeptide expression (e.g., expression of a mutant GPCR polypeptide or of a different splicing variant). In a prefeπed embodiment, diagnosis of a susceptibility to a susceptibility to a disease or condition associated with a GPCR is made by detecting a particular splicing variant encoded by that GPCR, or a particular pattern of splicing variants.

Both such alterations (quantitative and qualitative) can also be present. An "alteration" in the polypeptide expression or composition, as used herein, refers to an alteration in expression or composition in a test sample, as compared with the expression or composition of polypeptide by a GPCR in a control sample. A control sample is a sample that coπesponds to the test sample (e.g., is from the same type of cells), and is from an individual who is not affected by a susceptibility to a disease or condition associated with a GPCR. An alteration in the expression or composition of the polypeptide in the test sample, as compared with the control sample, is indicative of a susceptibility to a susceptibility to a disease or condition associated with a GPCR. Similarly, the presence of one or more different splicing variants in the test sample, or the presence of significantly different amounts of different splicing variants in the test sample, as compared with the control sample, is indicative of a susceptibility to a susceptibility to a disease or condition associated with a GPCR. Various means of examining expression or composition of the polypeptide encoded by a GPCR can be used, including speetroscopy, colorimetry, electrophoresis, isoelectric focusing, and immunoassays (e.g., David et al. , U.S. Pat. No. 4,376,110) such as immunoblotting (see also Current Protocols in Molecular

Biology, particularly Chapter 10). For example, in one embodiment, an antibody capable of binding to the polypeptide (e.g., as described above), preferably an antibody with a detectable label, can be used. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., Fab or F(ab')₂) can be used. The term "labeled", with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labehng include detection of a primary antibody using a fluorescently labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently labeled streptavidin.

Western blotting analysis, using an antibody as described above that specifically binds to a polypeptide encoded by a mutant GPCR, or an antibody that specifically binds to a polypeptide encoded by a non-mutant gene, or an antibody that specifically binds to a particular splicing variant encoded by a GPCR, can be used to identify the presence in a test sample of a particular splicing variant or of a polypeptide encoded by a polymoφhic or mutant GPCR, or the absence in a test sample of a particular splicing variant or of a polypeptide encoded by a non- polymoφhic or non-mutant gene. The presence of a polypeptide encoded by a polymoφhic or mutant gene, or the absence of a polypeptide encoded by a non- polymoφhic or non-mutant gene, is diagnostic for a susceptibility to a susceptibility to a disease or condition associated with a GPCR, as is the presence (or absence) of particular splicing variants encoded by the GPCR gene.

In one embodiment of this method, the level or amount of polypeptide encoded by a GPCR in a test sample is compared with the level or amount of the polypeptide encoded by the GPCR in a control sample. A level or amount of the polypeptide in the test sample that is higher or lower than the level or amount of the polypeptide in the control sample, such that the difference is statistically significant, is indicative of an alteration in the expression of the polypeptide encoded by the GPCR, and is diagnostic for a susceptibility to a susceptibility to a disease or condition associated with that GPCR. Alternatively, the composition of the polypeptide encoded by a GPCR in a test sample is compared with the composition of the polypeptide encoded by the GPCR in a control sample (e.g., the presence of different splicing variants). A difference in the composition of the polypeptide in the test sample, as compared with the composition of the polypeptide in the control sample, is diagnostic for a susceptibility to a susceptibility to a disease or condition associated with that GPCR. In another embodiment, both the level or amount and the composition of the polypeptide can be assessed in the test sample and in the control sample. A difference in the amount or level of the polypeptide in the test sample, compared to the control sample; a difference in composition in the test sample, compared to the control sample; or both a difference in the amount or level, and a difference in the composition, is indicative of a susceptibility to a susceptibihty to a disease or condition associated with that GPCR.

Kits (e.g., reagent kits) useful in the methods of diagnosis comprise components useful in any of the methods described herein, including for example, hybridization probes or primers as decribed herein (e.g., labeled probes or primers), reagents for detection of labeled molecules, restriction enzymes (e.g., for RFLP analysis), allele-specific oligonucleotides, antibodies which bind to mutant or to non-mutant (native) GPCR polypeptide, means for amplification of nucleic acids comprising a GPCR, or means for analyzing the nucleic acid sequence of a GPCR or for analyzing the amino acid sequence of a GPCR polypeptide, etc.

SCREENING ASSAYS AND AGENTS IDENTIFIED THEREBY

The invention provides methods (also refeπed to herein as "screening assays") for identifying the presence of a nucleotide that hybridizes to a nucleic acid of the invention, as well as for identifying the presence of a polypeptide encoded by a nucleic acid of the invention. 3n one embodiment, the presence (or absence) of a nucleic acid molecule of interest (e.g. , a nucleic acid that has significant homology with a nucleic acid of the invention) in a sample can be assessed by contacting the sample with a nucleic acid comprising a nucleic acid of the invention (e.g. , a nucleic acid having the sequence of one of SEQ 3D NOs:l-230 (odd numbers), or the complement thereof, or a nucleic acid encoding an amino acid having the sequence of one of SEQ ID NOs:l-230 (even numbers), or a fragment or variant of such nucleic acids), under stringent conditions as described above, and then assessing the sample for the presence (or absence) of hybridization. In a prefeπed embodiment, high stringency conditions are conditions appropriate for selective hybridization. In another embodiment, a sample containing the nucleic acid molecule of interest is contacted with a nucleic acid containing a contiguous nucleotide sequence (e.g., a primer or a probe as described above) that is at least partially complementary to a part of the nucleic acid molecule of interest (e.g., a GPCR nucleic acid), and the contacted sample is assessed for the presence or absence of hybridization. In a prefeπed embodiment, the nucleic acid containing a contiguous nucleotide sequence is completely complementary to a part of the nucleic acid molecule of interest. In any of these embodiments, all or a portion of the nucleic acid of interest can be subjected to amplification prior to performing the hybridization.

In another embodiment, the presence (or absence) of a polypeptide of interest, such as a polypeptide of the invention or a fragment or variant thereof, in a sample can be assessed by contacting the sample with an antibody that specifically hybridizes to the polypeptide of interest (e.g., an antibody such as those described above), and then assessing the sample for the presence (or absence) of binding of the antibody to the polypeptide of interest.

In another embodiment, the invention provides methods for identifying agents (e.g., fusion proteins, polypeptides, peptidomimetics, prodrugs, other receptors associated with GPCRs, binding agents, antibodies, small molecules or other drugs, or ribozymes which alter (e.g. , increase or decrease) the activity of the polypeptides described herein, or which otherwise interact with the polypeptides herein. For example, such agents can be agents which bind to polypeptides described herein (e.g., GPCR binding agents); which have a stimulatory or inhibitory effect on, for example, activity of polypeptides of the invention; or which change (e.g., enhance or inhibit) the ability of the polypeptides of the invention to interact with GPCR binding agents (e.g., G-proteins, other receptors associated with GPCRs, or other binding agents); or which alter posttranslational processing of the GPCR polypeptide (e.g., agents that alter proteolytic processing to direct the polypeptide from where it is normally synthesized to another location in the cell, such as the cell surface; agents that alter proteolytic processing such that more polypeptide is released from the cell, etc.

In one embodiment, the invention provides assays for screening candidate or test agents that bind to or modulate the activity of polypeptides described herein (or biologically active portion(s) thereof), as well as agents identifiable by the assays. Test agents can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including: biological libraries; spatially addressable parallel sohd phase or solution phase libraries; synthetic library methods requiring deconvolution; the 'one-bead one-compound' library method; and synthetic library methods using affinity chromatography selection. The biological library approach is limited to polypeptide libraries, while the other four approaches are applicable to polypeptide, non-peptide oligomer or small molecule libraries of compounds (Lam, K.S., Anticancer Drug Des. 12:145 (1997)).

In one embodiment, to identify agents which alter the activity of a GPCR polypeptide, a cell, cell lysate, or solution containing or expressing a GPCR polypeptide (e.g., one of SEQ 3D NOs: 1-230 (even numbers), or another splicing variant encoded by a GPCR), or a fragment or derivative thereof (as described above), can be contacted with an agent to be tested; alternatively, the polypeptide can be contacted directly with the agent to be tested. The level (amount) of GPCR activity is assessed (e.g., the level (amount) of GPCR activity is measured, either directly or indirectly), and is compared with the level of activity in a control (i.e., the level of activity of the GPCR polypeptide or active fragment or derivative thereof in the absence of the agent to be tested). If the level of the activity in the presence of the agent differs, by an amount that is statistically significant, from the level of the activity in the absence of the agent, then the agent is an agent that alters the activity of a GPCR polypeptide. An increase in the level of GPCR activity relative to a control, indicates that the agent is an agent that enhances (is an agonist of) GPCR activity. Similarly, a decrease in the level of GPCR activity relative to a control, indicates that the agent is an agent that inhibits (is an antagonist of) GPCR activity. In another embodiment, the level of activity of a GPCR polypeptide or derivative or fragment thereof in the presence of the agent to be tested, is compared with a control level that has previously been established. A level of the activity in the presence of the agent that differs from the control level by an amount that is statistically significant indicates that the agent alters GPCR activity.

The present invention also relates to an assay for identifying agents which alter the expression of a GPCR gene (e.g., antisense nucleic acids, fusion proteins, polypeptides, peptidomimetics, prodrugs, other receptors associated with GPCRs, G- proteins, binding agents, antibodies, small molecules or other drugs, or ribozymes) which alter (e.g., increase or decrease) expression (e.g., transcription or translation) of the gene or which otherwise interact with the nucleic acids described herein, as well as agents identifiable by the assays. For example, a solution containing a nucleic acid encoding a GPCR polypeptide (e.g., a GPCR gene) can be contacted with an agent to be tested. The solution can comprise, for example, cells containing the nucleic acid or cell lysate containing the nucleic acid; alternatively, the solution can be another solution which comprises elements necessary for transcription translation of the nucleic acid. Cells not suspended in solution can also be employed, if desired. The level and/or pattern of GPCR expression (e.g., the level and/or pattern of mRNA or of protein expressed, such as the level and/or pattern of different splicing variants) is assessed, and is compared with the level and/or pattern of expression in a control (i e. , the level and/or pattern of the GPCR expression in the absence of the agent to be tested). If the level and/or pattern in the presence of the agent differs, by an amount or in a manner that is statistically significant, from the level and/or pattern in the absence of the agent, then the agent is an agent that alters the expression of GPCR. Enhancement of GPCR expression indicates that the agent is an agonist of GPCR activity. Similarly, inhibition of GPCR expression indicates that the agent is an antagonist of GPCR activity. In another embodiment, the level and/or pattern of GPCR polypeptide(s) (e.g., different splicing variants) in the presence of the agent to be tested, is compared with a control level and/or pattern that has previously been established. A level and/or pattern in the presence of the agent that differs from the control level and/or pattern by an amount or in a manner that is statistically significant indicates that the agent alters GPCR expression. h another embodiment of the invention, agents which alter the expression of a GPCR gene or which otherwise interact with the nucleic acids described herein, can be identified using a cell, cell lysate, or solution containing a nucleic acid encoding the promoter region of the GPCR gene operably linked to a reporter gene. After contact with an agent to be tested, the level of expression of the reporter gene (e.g., the level of mRNA or of protein expressed) is assessed, and is compared with the level of expression in a confrol (i.e., the level of the expression of the reporter gene in the absence of the agent to be tested). If the level in the presence of the agent differs, by an amount or in a manner that is statistically significant, from the level in the absence of the agent, then the agent is an agent that alters the expression of the GPCR, as indicated by its ability to alter expression of a gene that is operably linked to the GPCR gene promoter. Enhancement of the expression of the reporter indicates that the agent is an agonist of GPCR activity. Similarly, inhibition of the expression of the reporter indicates that the agent is an antagonist of GPCR activity. In another embodiment, the level of expression of the reporter in the presence of the agent to be tested, is compared with a control level that has previously been established. A level in the presence of the agent that differs from the control level by an amount or in a manner that is statistically significant indicates that the agent alters expression. Agents which alter the amounts of different splicing variants encoded by a

GPCR (e.g., an agent which enhances activity of a first splicing variant, and which inhibits activity of a second splicing variant), as well as agents which are agonists of activity of a first splicing variant and antagonists of activity of a second splicing variant, can easily be identified using these methods described above. In other embodiments of the invention, assays can be used to assess the impact of a test agent on the activity of a polypeptide in relation to a GPCR binding agent. For example, a cell that expresses a compound that interacts with a GPCR (herein refeπed to as a "GPCR binding agent", which can be a polypeptide or other molecule that interacts with a GPCR, such as a G-protein) is contacted with a GPCR in the presence of a test agent, and the ability of the test agent to alter the interaction between the GPCR and the GPCR binding agent is determined. Alternatively, a cell lysate or a solution containing the GPCR binding agent, can be used. An agent which binds to the GPCR or the GPCR binding agent can alter the interaction by interfering with, or enhancing the ability of the GPCR to bind to, associate with, or otherwise interact with the GPCR binding agent. Determining the ability of the test agent to bind to a GPCR or a GPCR binding agent can be accomplished, for example, by coupling the test agent with a radioisotope or enzymatic label such that binding of the test agent to the polypeptide can be determined by detecting the labeled with 1, ³ S, C or H, either directly or indirectly, and the radioisotope detected by direct counting of radioemmission or by scintillation counting.

Alternatively, test agents can be enzymatically labeled with, for example, horseradish peroxidase, alkaline phosphatase, or luciferase, and the enzymatic label detected by determination of conversion of an appropriate substrate to product. It is also within the scope of this invention to determine the ability of a test agent to interact with the polypeptide without the labeling of any of the interactants. For example, a microphysiometer can be used to detect the interaction of a test agent with a GPCR or a GPCR binding agent without the labeling of either the test agent, GPCR, or the GPCR binding agent. McConnell, H.M. et al, Science 257:1906-1912 (1992). As used herein, a "microphysiometer" (e.g., Cytosensor™) is an analytical histrument that measures the rate at which a cell acidifies its environment using a light-addressable potentiometric sensor (LAPS). Changes in this acidification rate can be used as an indicator of the interaction between ligand and polypeptide. Thus, these receptors can be used to screen for compounds that are agonists for use in treating a susceptibility to a disease or condition associated with a GPCR or antagonists for studying a susceptibility to a disease or condition associated with a GPCR. Drugs could be designed to regulate GPCR activation that in turn can be used to regulate signaling pathways and transcription events of genes downstream. hi another embodiment of the mvention, assays can be used to identify polypeptides that interact with one or more GPCR polypeptides, as described herein. For example, a yeast two-hybrid system such as that described by Fields and Song (Fields, S. and Song, O., Nature 340:245-246 (1989)) can be used to identify polypeptides that interact with one or more GPCR polypeptides. In such a yeast two-hybrid system, vectors are constructed based on the flexibility of a transcription factor which has two functional domains (a DNA binding domain and a transcription activation domain). If the two domains are separated but fused to two different proteins that interact with one another, transcriptional activation can be achieved, and transcription of specific markers (e.g., nutritional markers such as His and Ade, or color markers such as lacZ) can be used to identify the presence of interaction and transcriptional activation. For example, in the methods of the invention, a first vector is used which includes a nucleic acid encoding a DNA binding domain and also a GPCR polypeptide, splicing variant, or fragment or derivative thereof, and a second vector is used which includes a nucleic acid encoding a transcription activation domain and also a nucleic acid encoding a polypeptide which potentially may interact with the GPCR polypeptide, splicing variant, or fragment or derivative thereof (e.g., a GPCR polypeptide binding agent or G-protein). Incubation of yeast containing the first vector and the second vector under appropriate conditions (e.g., mating conditions such as used in the Matchmaker™ system from Clontech (Palo Alto, California, USA)) allows identification of colonies which express the markers of interest. These colonies can be examined to identify the polypeptide(s) that interact with the GPCR polypeptide or fragment or derivative thereof. Such polypeptides may be useful as agents that alter the activity of expression of a GPCR polypeptide, as described above. In more than one embodiment of the above assay methods of the present invention, it may be desirable to immobilize either GPCR, the GPCR binding agent, or other components of the assay on a solid support, in order to facilitate separation of complexed from uncomplexed forms of one or both of the polypeptides, as well as to accommodate automation of the assay. Binding of a test agent to the polypeptide, or interaction of the polypeptide with a binding agent in the presence and absence of a test agent, can be accomplished in any vessel suitable for containing the reactants. Examples of such vessels include microtitre plates, test tubes, and micro-centrifuge tubes. In one embodiment, a fusion protein (e.g., a glutathione-S-transferase fusion protein) can be provided which adds a domain that allows GPCR or a GPCR binding agent to be bound to a matrix or other solid support. .

In another embodiment, modulators of expression of nucleic acid molecules of the invention are identified in a method wherein a cell, cell lysate, or solution containing a nucleic acid encodmg a GPCR is contacted with a test agent and the expression of appropriate mRNA or polypeptide (e.g. , splicing variant(s)) in the cell, cell lysate, or solution, is determined. The level of expression of appropriate mRNA or polypeptide(s) in the presence of the test agent is compared to the level of expression of RNA or polypeptide(s) in the absence of the test agent. The test agent can then be identified as a modulator of expression based on this comparison. For example, when expression of mRNA or polypeptide is greater (statistically significantly greater) in the presence of the test agent than in its absence, the test agent is identified as a stimulator or enhancer of the mRNA or polypeptide expression. Alternatively, when expression of the mRNA or polypeptide is less (statistically significantly less) in the presence of the test agent than in its absence, the test agent is identified as an inhibitor of the mRNA or polypeptide expression. The level of mRNA or polypeptide expression in the cells can be determined by methods described herein for detecting mRNA or polypeptide.

This invention further pertains to novel agents identified by the above-described screening assays. Accordingly, it is within the scope of this invention to further use an agent identified as described herein in an appropriate animal model. For example, an agent identified as described herein (e.g., a test agent that is a modulating agent, an antisense nucleic acid molecule, a specific antibody, or a polypeptide-binding agent) can be used in an animal model to determine the efficacy, toxicity, or side effects of treatment with such an agent. Alternatively, an agent identified as described herein can be used in an animal model to determine the mechanism of action of such an agent. Furthermore, this invention pertains to uses of novel agents identified by the above-described screening assays for treatments as described herein, hi addition, an agent identified as described herein can be used to alter activity of a polypeptide encoded by a GPCR, or to alter expression of a GPCR, by contacting the polypeptide or the gene (or contacting a cell comprising the polypeptide or the gene) with the agent identified as described herein.

PHARMACEUTICAL COMPOSITIONS

The present invention also pertains to pharmaceutical compositions comprising nucleic acids described herein, particularly nucleotides encoding the polypeptides described herein; comprising polypeptides described herein (e.g. , one or more of SEQ ID NOs: 1-230 (even numbers)); and/or comprising other splicing variants encoded by a GPCR; and/or an agent that alters (e.g., enhances or inhibits) GPCR gene expression or GPCR polypeptide activity as described herein. For instance, a polypeptide, protein (e.g., a G-protein), an agent that alters GPCR gene expression, or a GPCR binding agent or binding partner, fragment, fusion protein or prodrug thereof, or a nucleotide or nucleic acid construct (vector) comprising a nucleotide of the present invention, or an agent that alters GPCR polypeptide activity, can be formulated with a physiologically acceptable carrier or excipient to prepare a pharmaceutical composition. The carrier and composition can be sterile. The fonnulation should suit the mode of administration.

Suitable pharmaceutically acceptable carriers include but are not limited to water, salt solutions (e.g., NaCl), saline, buffered saline, alcohols, glycerol, ethanol, gum arabic, vegetable oils, benzyl alcohols, polyethylene glycols, gelatin, carbohydrates such as lactose, amylose or starch, dextrose, magnesium stearate, talc, silicic acid, viscous paraffin, perfume oil, fatty acid esters, hydroxymethylcellulose, polyvinyl pyrolidone, etc., as well as combinations thereof. The pharmaceutical preparations can, if desired, be mixed with auxiliary agents, e.g. , lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, flavoring and/or aromatic substances and the like which do not deleteriously react with the active agents.

The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. The composition can be a liquid solution, suspension, emulsion, tablet, pill, capsule, sustained release formulation, or powder. The composition can be formulated as a suppository, with traditional binders and carriers such as triglycerides. Oral formulation can include standard carriers such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, polyvinyl pyrolhdone, sodium saccharine, cellulose, magnesium carbonate, etc.

Methods of introduction of these compositions include, but are not limited to, intradermal, intramuscular, intraperitoneal, intraocular, intravenous, subcutaneous, topical, oral and intranasal. Other suitable methods of introduction can also include gene therapy (as described below), rechargeable or biodegradable devices, particle acceleration devises ("gene guns") and slow release polymeric devices. The pharmaceutical compositions of this invention can also be administered as part of a combinatorial therapy with other agents.

The composition can be formulated in accordance with the routine procedures as a pharmaceutical composition adapted for administration to human beings. For example, compositions for intravenous administration typically are solutions in sterile isotonic aqueous buffer. Where necessary, the composition may also include a solubilizing agent and a local anesthetic to ease pain at the site of the injection. Generally, the ingredients are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampule or sachette indicat- ing the quantity of active agent. Where the composition is to be adnύnistered by infusion, it can be dispensed with an infusion bottle containing sterile pharmaceutical grade water, saline or dextrose/water. Where the composition is administered by injection, an ampule of sterile water for injection or saline can be provided so that the ingredients may be mixed prior to administration. For topical application, nonsprayable forms, viscous to semi-solid or solid forms comprising a carrier compatible with topical application and having a dynamic viscosity preferably greater than water, can be employed. Suitable formulations include but are not limited to solutions, suspensions, emulsions, creams, ointments, powders, enemas, lotions, sols, liniments, salves, aerosols, etc., which are, if desired, sterihzed or mixed with auxiliary agents, e.g. , preservatives, stabilizers, wetting agents, buffers or salts for influencing osmotic pressure, etc. The agent may be incoφorated into a cosmetic formulation. For topical application, also suitable are sprayable aerosol preparations wherein the active ingredient, preferably in combination with a solid or liquid inert carrier material, is packaged in a squeeze bottle or in admixture with a pressurized volatile, normally gaseous propellant, e.g. , pressurized air.

Agents described herein can be formulated as neutral or salt forms. Pharmaceutically acceptable salts include those formed with free amino groups such as those derived from hydrochloric, phosphoric, acetic, oxalic, tartaric acids, etc., and those formed with free carboxyl groups such as those derived from sodium, potassium, ammonium, calcium, ferric hydroxides, isopropylamine, triethylamine, 2-ethylamino ethanol, histidine, procaine, etc.

The agents are administered in a therapeutically effective amount. The amount of agents which will be therapeutically effective in the freatment of a particular disorder or condition will depend on the nature of the disorder or condition, and can be determined by standard clinical techniques. In addition, in vitro or in vivo assays may optionally be employed to help identify optimal dosage ranges. The precise dose to be employed in the formulation will also depend on the route of administration, and the seriousness of the symptoms of a susceptibility to a disease or condition associated with a GPCR, and should be decided according to the judgment of a practitioner and each patient's circumstances. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems.

The invention also provides a pharmaceutical pack or kit comprising one or more containers filled with one or more of the ingredients of the pharmaceutical compositions of the invention. Optionally associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use of sale for human administration. The pack or kit can be labeled with information regarding mode of administration, sequence of drug administration (e.g., separately, sequentially or concuπently), or the like. The pack or kit may also include means for reminding the patient to talce the therapy. The pack or kit can be a single unit dosage of the combination therapy or it can be a plurality of unit dosages. In particular, the agents can be separated, mixed together in any combination, present in a single vial or tablet. Agents assembled in a blister pack or other dispensing means is prefeπed. For the pmpose of this invention, unit dosage is intended to mean a dosage that is dependent on the individual pharmacodynamics of each agent and administered in FDA approved dosages in standard time courses.

METHODS OF THERAPY The present invention also pertains to methods of treatment (prophylactic and/or therapeutic) for a susceptibility to a disease or condition associated with a GPCR, using a GPCR therapeutic agent. A "GPCR therapeutic agent" is an agent that alters (e.g., enhances or inhibits) GPCR polypeptide activity and/or GPCR gene expression, as described herein (e.g., a GPCR agonist or antagonist). GPCR therapeutic agents can alter GPCR polypeptide activity or gene expression by a variety of means, such as, for example, by providing additional GPCR polypeptide or by upregulating the transcription or translation of the GPCR gene; by altering posttranslational processing of the GPCR polypeptide; by altering transcription of GPCR splicing variants; or by interfering with GPCR polypeptide activity (e.g., by binding to a GPCR polypeptide), or by downregulating the transcription or translation of a GPCR gene. Representative GPCR therapeutic agents include the following: nucleic acids or fragments or derivatives thereof described herein, particularly nucleotides encoding the polypeptides described herein and vectors comprising such nucleic acids (e.g., a gene, cDNA, and or mRNA, such as a nucleic acid encoding a GPCR polypeptide or active fragment or derivative thereof, or an oligonucleotide; for example, one of SEQ ID NOs : 1 -230 (odd numbers), or a complement thereof, or a nucleic acid encoding one of SEQ JD NOs: 1-230 (even numbers), or fragments or derivatives thereof); polypeptides described herein (e.g., one or more of SEQ JD NOs:l-230 (even numbers), and/or other splicing variants encoded by a GPCR, or fragments or derivatives thereof); other polypeptides (e.g., G-proteins); GPCRbmding agents; peptidomimetics; fusion proteins or prodrugs thereof; antibodies (e.g., an antibody to a mutant GPCR polypeptide, or an antibody to a non-mutant GPCR polypeptide, or an antibody to a particular splicing variant encoded by a GPCR, as described above); ribozymes; other small molecules; and other agents that alter (e.g., enhance or inhibit) GPCR gene expression or polypeptide activity, or that regulate transcription of GPCR splicing variants (e.g., agents that affect which splicing variants are expressed, or that affect the amount of each splicing variant that is expressed. More than one GPCR therapeutic agent can be used concurrently, if desired.

A GPCR therapeutic agent that is a nucleic acid is used in the treatment of a susceptibility to a disease or condition associated with a GPCR. The term, "treatment" as used herein, refers not only to ameliorating symptoms associated with the disease, but also preventing or delaying the onset of the disease, and also lessening the severity or frequency of symptoms of the disease. The therapy is designed to alter (e.g., inhibit or enhance), replace or supplement activity of a GPCR polypeptide in an individual. For example, a GPCR therapeutic agent can be administered in order to upregulate or increase the expression or availability of the GPCR gene or of specific splicing variants of GPCR, or, conversely, to downregulate or decrease the expression or availability of the GPCR gene or specific splicing variants of the GPCR. Upregulation or increasing expression or availabihty of a native GPCR gene or of a particular splicing variant could interfere with or compensate for the expression or activity of a defective gene or another splicing variant; downregulation or decreasing expression or availability of a native GPCR gene or of a particular splicing variant could minimize the expression or activity of a defective gene or the particular splicing variant and thereby minimize the impact of the defective gene or the particular splicing variant.

The GPCR therapeutic agent(s) are administered in a therapeutically effective amount (i.e., an amount that is sufficient to treat the disease, such as by ameliorating symptoms associated with the disease, preventing or delaying the onset of the disease, and/or also lessening the severity or frequency of symptoms of the disease). The amount which will be therapeutically effective in the treatment of a particular individual's disorder or condition will depend on the symptoms and severity of the disease, and can be determined by standard clinical techniques. In addition, in vitro or in vivo assays may optionally be employed to help identify optimal dosage ranges. The precise dose to be employed in the formulation will also depend on the route of administration, and the seriousness of the disease or disorder, and should be decided according to the judgment of a practitioner and each patient's circumstances. Effective doses maybe extrapolated from dose-response curves derived from in vitro or animal model test systems.

In one embodiment, a nucleic acid of the invention (e.g., a nucleic acid encoding a GPCR polypeptide, such as one of SEQ 3D NOs: 1-230 (odd numbers), or a complement thereof; or another nucleic acid that encodes a GPCR polypeptide or a splicing variant, derivative or fragment thereof, such as a nucleic acid encoding one of SEQ ID NOs: 1-230 (even numbers)) can be used, either alone or in a pharmaceutical composition as described above. For example, a GPCR or a cDNA encoding a GPCR polypeptide, either by itself or included within a vector, can be introduced into cells (either in vitro or in vivo) such that the cells produce native GPCR polypeptide. If necessary, cells that have been transformed with the gene or cDNA or a vector comprising the gene or cDNA can be introduced (or re- introduced) into an individual affected with the disease. Thus, cells which, in nature, lack native GPCR expression and activity, or have mutant GPCR expression and activity, or have expression of a disease-associated GPCR splicing variant, can be engineered to express the GPCR polypeptide or an active fragment of the GPCR polypeptide (or a different variant of the GPCR polypeptide). In a prefeπed embodiment, nucleic acid encoding a GPCR polypeptide, or an active fragment or derivative thereof, can be introduced into an expression vector, such as a viral vector, and the vector can be introduced into appropriate cells in an animal. Other gene transfer systems, including viral and nonviral fransfer systems, can be used. Alternatively, nonviral gene transfer methods, such as calcium phosphate coprecipitation, mechanical techniques (e.g., microinjection); membrane fusion- mediated transfer via liposomes; or direct DNA uptake, can also be used.

Alternatively, in another embodiment of the invention, a nucleic acid of the invention; a nucleic acid complementary to a nucleic acid of the invention; or a portion of such a nucleic acid (e.g., an oligonucleotide as described below), can be used in "antisense" therapy, in which a nucleic acid (e.g., an oligonucleotide) which specifically hybridizes to the mRNA and/or genomic DNA of a GPCR is administered or generated in situ. The antisense nucleic acid that specifically hybridizes to the mRNA and/or DNA inhibits expression of the GPCR polypeptide, e.g., by inhibiting translation and/or transcription. Binding of the antisense nucleic acid can be by conventional base pair complementarity, or, for example, in the case of binding to DNA duplexes, through specific interaction in the major groove of the double hehx. An antisense construct of the present invention can be delivered, for example, as an expression plasmid as described above.. When the plasmid is transcribed in the cell, it produces RNA which is complementary to a portion of the mRNA and/or DNA which encodes the GPCR polypeptide. Alternatively, the antisense construct can be an oligonucleotide probe which is generated ex vivo and introduced into cells; it then inhibits expression by hybridizing with the mRNA and/or genomic DNA of the GPCR. In one embodiment, the ohgonucleotide probes are modified oligonucleotides which are resistant to endogenous nucleases, e.g. exonucleases and/or endonucleases, thereby rendering them stable in vivo. Exemplary nucleic acid molecules for use as antisense oligonucleotides are phosphoramidate, phosphothioate and methylphosphonate analogs of DNA (see also U.S. Pat. Nos. 5,176,996; 5,264,564; and 5,256,775). Additionally, general approaches to constructing oligomers useful in antisense therapy are also described, for example, by Van der Krol et al, (Biotechniques 6:958-976 (1988)); and Stein et al. (Cancer Res. 48:2659-2668 (1988)). With respect to antisense DNA, oligodeoxyribonucleotides derived from the translation initiation site are prefeπed. To perform antisense therapy, oligonucleotides (mRNA, cDNA or DNA) are designed that are complementary to mRNA encoding the GPCR. The antisense oligonucleotides bind to GPCR mRNA transcripts and prevent translation. Absolute complementarity, although prefeπed, is not required. A sequence "complementary" to a portion of an RNA, as refeπed to herein, indicates that a sequence has sufficient complementarity to be able to hybridize with the RNA, forming a stable duplex; in the case of double-stranded antisense nucleic acids, a single strand of the duplex DNA may thus be tested, or triplex formation may be assayed. The ability to hybridize will depend on both the degree of complementarity and the length of the antisense nucleic acid, as described in detail above. Generally, the longer the hybridizing nucleic acid, the more base mismatches with an RNA it may contain and still form a stable duplex (or triplex, as the case may be). One skilled in the art can ascertain a tolerable degree of mismatch by use of standard procedures.

The oligonucleotides used in antisense therapy can be DNA, RNA, or chimeric mixtures or derivatives or modified versions thereof, single-stranded or double-stranded. The oligonucleotides can be modified at the base moiety, sugar moiety, or phosphate backbone, for example, to improve stability of the molecule, hybridization, etc. The oligonucleotides can include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger et al, Proc. Natl. Acad. Sci. USA 86:6553-6556 (1989); Lemaifre et al, Proc. Natl. Acad Sci. USA 84:648-652 (1987); PCT Intemational Publication No. WO 88/09810) or the blood-brain barrier

(see, e.g., PCT International Publication No. WO 89/10134), or hybridization-triggered cleavage agents (see, e.g., 3£rol et al, Bio/Techniques 6:958-976 (1988)) or intercalating agents. (See, e.g., Zon, Pharm. Res. 5:539-549 (1988)). To this end, the oligonucleotide may be conjugated to another molecule (e.g., a peptide, hybridization triggered cross-linking agent, transport agent, hybridization-triggered cleavage agent). The antisense molecules are delivered to cells that express GPCR in vivo. A number of methods can be used for delivering antisense DNA or RNA to cells; e.g., antisense molecules can be injected directly into the tissue site, or modified antisense molecules, designed to target the desired cells (e.g., antisense linked to peptides or antibodies that specifically bind receptors or antigens expressed on the target cell surface) can be administered systemically. Alternatively, in a prefeπed embodiment, a recombinant DNA construct is utihzed in which the antisense oligonucleotide is placed under the control of a strong promoter (e.g., pol III or pol II). The use of such a construct to transfect target cells in the patient results in the transcription of sufficient amounts of single stranded RNAs that will form complementary base pairs with the endogenous GPCR transcripts and thereby prevent translation of the GPCR mRNA. For example, a vector can be introduced in vivo such that it is taken up by a cell and directs the transcription of an antisense RNA. Such a vector can remain episomal or become chromosomally integrated, as long as it can be transcribed to produce the deshed antisense RNA. Such vectors can be constracted by recombinant DNA technology methods standard in the art and described above. For example, a plasmid, cosmid, YAC or viral vector can be used to prepare the recombinant DNA construct that can be introduced directly into the tissue site. Alternatively, viral vectors can be used which selectively infect the desired tissue, in which case administration may be accomplished by another route (e.g. , systemically).

Endogenous GPCR expression can also be reduced by inactivating or "knocking out" GPCR or its promoter using targeted homologous recombination (e.g., see Smithies et al, Nature 317:230-234 (1985); Thomas & Capecchi, Cell 51:503-512 (1987); Thompson et al, Cell 5:313-321 (1989)). For example, a mutant, non-functional GPCR (or a completely unrelated DNA sequence) flanked by

DNA homologous to the endogenous GPCR (either the coding regions or regulatory regions of GPCR) can be used, with or without a selectable marker and/or a negative selectable marker, to transfect cells that express the GPCR in vivo. Insertion of the DNA construct, via targeted homologous recombination, results in inactivation of the GPCR. The recombinant DNA constructs can be directly administered or targeted to the required site in vivo using appropriate vectors, as described above. Alternatively, expression of non-mutant GPCRs can be increased using a similar method: targeted homologous recombination can be used to insert a DNA construct comprising a non-mutant, functional GPCR, e.g., a gene having one of SEQ ID NOs: 1-230 (odd numbers), or the complement thereof, or a portion thereof, in place of a mutant GPCR in the cell, as described above. In another embodiment, targeted homologous recombination can be used to insert a DNA construct comprising a nucleic acid that encodes a GPCR polypeptide variant that differs from that present in the cell.

Alternatively, endogenous GPCR expression can be reduced by targeting deoxyribonucleotide sequences complementary to the regulatory region of a GPCR (i. e. , the GPCR promoter and/or enhancers) to form triple helical structures that prevent transcription of the GPCR in target cells in the body. (See generally, Helene, C, Anticancer Drug Des. 6(6):569-84 (1991); Helene, C, et al, Ann. N.Y. Acad. Sci. 660:27-36 (1992); and Maher, L. J., Bioassays 14(12):807-15 (1992)). Likewise, the antisense constructs described herein, by antagonizing the normal biological activity of one of the GPCR proteins, can be used in the manipulation of tissue, e.g., tissue differentiation, both in vivo and for ex vivo tissue cultures. Furthermore, the anti-sense techniques (e.g., microinjection of antisense molecules, or transfection with plasmids whose transcripts are anti-sense with regard to a GPCR mRNA or gene sequence) can be used to investigate the role of one or GPCR in developmental events, as well as the normal cellular function of the GPCRs in adult tissue. Such techniques can be utilized in cell culture, but can also be used in the creation of transgenic animals.

In yet another embodiment of the invention, other GPCR therapeutic agents as described herein can also be used in the treatment or prevention of a susceptibility to a disease or condition associated with a GPCR. The therapeutic agents can be delivered in a composition, as described above, or by themselves. They can be administered systemically, or can be targeted to a particular tissue. The therapeutic agents can be produced by a variety of means, including chemical synthesis; recombinant production; in vivo production (e.g., a transgenic animal, such as U.S.

Pat. No. 4,873,316 to Meade et al), for example, and can be isolated using standard means such as those described herein. A combination of any of the above methods of freatment (e.g. , administration of non-mutant GPCR polypeptide in conjunction with antisense therapy targeting mutant GPCR mRNA; administration of a first splicing variant encoded by a GPCR in conjunction with antisense therapy targeting a second splicing encoded by a

GPCR), can also be used. The teachings of all publications cited herein are incoφorated herein by reference in their entirety.

While this invention has been particularly shown and described with references to prefeπed embodiments thereof, it will be understood by those skilled the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.

Table l

MOOSE01980 ctgl3103 25879000..25879025, 25958335..25959244

MENQSSISEFFLRGISAPPEQQQSLFGIFLCMYLVTLTGNLLIIL AIGSDLIJLHTPMYFFLANLSFVDMGLTSSTVTKMLVNIQTRHHTISY TGCLTQMYFFLMFGDLDSFFLAAMAYDRYVAICHPLCYSTVMRPQV CALMLALCWVLTMVALTHTFLMARLSFCVTGEIAHFFCDITPVLKLS CSDTH31NEI^MWVLGGTVL3VPFLC1VTSYTHIVPAILRVRTRGGVGK AFSTCSSHLC CVFYGTLFSAYLCPPSIASEEKDIAAAAMYTIVTPM LNPFIYSL3 KDIV[KGALK3^FiπiElKKHKKW (SEQ ID NO: 2) atggaaaaccaatccagcatttctgaatttttcctccgaggaatatcagcgcctccagagcaacagc agtccctcttcggaattttcctgtgtatgtatcttgtcaccttgactgggaacctgctcatcatcctggccattggct ctgacctgcacctccacacccccatgtactttttcttggccaacctgtcttttgttgacatgggtttaacgtcctcca cagttaccaagatgctggtgaatatacagactcggcatcacaccatctcctatacgggttgcctcacgcaaatg tatttctttctgatgtttggtgatctagacagcttcttcctggctgccatggcgtatgaccgctatgtggccatttgc caccccctctgctactccacagtcatgaggccccaagtctgtgccctaatgcttgcattgtgctgggtcctcacc aatatcgttgccctgactcacacgttcctcatggctcggttgtccttctgtgtgactggggaaattgctcactttttc tgtgacatcactcctgtcctgaagctgtcatgttctgacacccacatcaacgagatgatggtttttgtcttgggag gcaccgtactcatcgtcccctttttatgcattgtcacctcctacatccacattgtgccagctatcctgagggtccg aacccgtggtggggtgggcaaggccttttccacctgcagttcccacctctgcgttgtttgtgtgttctatgggac cctcttcagtgcctacctgtgtcctccctccattgcctctgaagagaaggacattgcagcagctgcaatgtacac catagtgactcccatgttgaacccctttatctatagcctaaggaacaaggacatgaagggggccctaaagagg ctcttcaaaagaagaaagaaacacaaaaagtgg (SEQ ID NO:l)

MOOSE01981 ctgl5907 32670285..32670410, 32712477..32713295

MNWENESSPKEFE LGFSDRAWLQMPLFVVLLISYTITIFGNVS IMMVCILDPKLHTPMYFFLTNLS ILDLCYTTTTVPHMLVNIGCNKKTI SYAGCVAHLI3FLALGATECLLLAVMSFDRYVAVCRPLFIYVVIMNY V\ CL31MAAFSWLIGFGNSVLQSSLTLNMPRCGHQEVDHFFCEVPAL L3N_JSCADTKPIEAELFFFSVLILL3PVTLJLISYGFJAQAVL3DRSAEGRQ 3 FGTCGSIJMIVΎSLFYGTAΓΏVIYLQPPSSTSKDWGKMFLTLFYTVI TPSLWLrmj EODMKDALKKLMRFIJHKSTKI (SEQ ID NO: 4) atgaattgggaaaatgagagctccccaaaagagtttatactacttggcttctcagatagggcttggct acaaatgcccctttttgtggtcctgttaatatcatacacaatcaccatatttggcaatgtgtccatcatgatggtgtg cattctggatcccaaacttcatactcccatgtatttctttctcactaatctctccatcttagatctctgctataccacaa ctacagtccctcatatgttggtaaatattggttgcaacaaaaagaccatcagctatgctggctgtgtggcccacc tcatcatcttcctggccctaggtgctacagagtgtctccttctggctgttatgtcctttgacagatatgtggctgttt gcagacccctccactatgtagtcatcatgaattattggttctgcctaaggatggcagccttctcatggctcattgg tttcggcaactcagtgctgcagtcttccttgactcttaacatgccacgctgtggtcaccaggaagtggaccactt tttctgtgaggtgcctgcacttctcaagttgtcatgtgctgacacaaagcctattgaggctgagctcttcttctttag tgtactaattcttctaattccagtgacattgatcctcatctcctatggcttcatagctcaagcagtattaaaaatcag gtcagcagaaggacggcaaaaagcatttgggacatgtgggtcccacatgattgtggtgtccctcttttatggaa cagccatttatatgtatcttcaaccaccttcatccacctctaaggactggggaaagatgttcctcaccctcttttac accgtcatcactccaagtctcaacccgctcatttacaccttaagaaataaggacatgaaggatgccctgaaga aactgatgagatttcaccacaaatctacaaaaata (SEQ ID NO: 3) MOOSE01984 ctgl8147 116224..116906, 166266..166527

MEAGNQTGFLEF3LLGLSEDPELQPF3FGLFLSMYLVTVLGNLLI3LAIS SDSHLHTPMYFFLSNLSWVDICFSTCIWID^VNIQTENKAISYMDCLTQVY FSIVIFFPILDTLLLTVMAYDI^VAVCHPLHYMIIMNPHLCGLLVFVTWLLGV MTSLLMSLMMHLIFCKDFEIPIIFFCELTYILQLACSDTFLNSTLIYFMTGVLG VFPLLGIIFSYSIΠASSIRI TMSSTEGKYJ. AFSTCGSHLCVVSLFYGTGLGVYL SSAVTHSSQSSSMASVMYAMVTPMLNPFIYSLRNKDVKGALGRLLSRAASC LLR (SEQ ID NO: 6) atggaagcaggaaaccaaacaggatttttagagtttatccttctcggactctctgaggatccagaactacagcc gttcatatttgggctgttcctgtccatgtacctggtgacggtgctgggaaacctgctcatcatcctggccatcagctctgact cccacctccacacccccatgtacttcttcctctccaacctgtcctgggttgacatctgtttcagcacttgcatcgtccccaag atgctggtgaacatccagaccgagaacaaagccatctcctacatggactgcctcacacaggtctatttctccatgttttttcc tattctggacacgctactcctgaccgtgatggcctatgaccggtttgtggctgtctgccaccctctgcactatatgatcatcat gaacccccacctctgtggcctcctggtttttgtcacctggctcattggtgtcatgacatccctcctccatatttctctgatgatg catctaatcttctgtaaagattttgaaattccacattttttctgcgaactgacgtacatcctccagctggcctgctctgatacctt cctgaacagcacgttgatatactttatgacgggtgtgctgggcgtttttcccctccttgggatcattttctcttattcacgaattg cttcatccataaggaagataatgtcctccaccgagggcaagtacaaagccttttccacctgtggatctcacctctgtgtggt ctccttgttctatggaacaggacttggggtctatctcagttctgctgtgacccattcttcccagagcagctccatggcctcag tgatgtacgccatggtcacccccatgctgaaccccttcatctacagcctgaggaacaaggatgtgaagggggccctggg gagactccttagcagggcagcctcttgtctcttacgg (SEQ ID NO: 5)

MOOSE01987 ctgl5944 1720461..1721241, 1821742..1821917

MASGNLTWVTEFILVGVSDDPELQIPLFLVFLVLYLLTVAGNLGΠTL TSVDPQLQTPJLQFFMYYFLSNLSFLDISCSTAITPKMLANFLASRKSISPYGC ALQMFFFASFADAECLILAAMAYDRYAAICNPLLYTTLMSRRVCVCF3VLA YFSGSTTSLVHVCLTFI^SFCGSNIVNHFFCDIPPLLALSCTDTQ3NQLLLFAL CSFIQTSTFW3FISYFC3LITVLSIKSSGGRSKTFSTCASHLIAVTLFYGALLFM YLQPTTSYSLDTDKVVAVFYTVWPMFNPΠYSFRNEDVKNALKKLLERIGY SNEW (SEQ ID NO: 8) atggcttcaggaaatctcacatgggtgacggagttcattcttgtgggagtctcagatgatccggagctccagat tcccctcttcctggtcttcctggtgctctatttgctgaccgtggcagggaacctgggcatcatcaccctcaccagtgttgacc ctcaacttcaaacccccatccttcaaattcccatgtattattttcttagcaacttatctttcttagacatcagctgttctacagcaa tcactcctaaaatgctggcaaacttcttggcatccaggaaaagcatctctccttatgggtgtgcactacaaatgtttttcttcg cttcttttgctgatgctgagtgccttatcctggcagcaatggcttatgaccgctatgcagccatctgcaacccactgctctata ctacactgatgtctaggagagtctgtgtctgcttcattgtgttggcatatttcagtggaagtacaacatcactggtccatgtgt gcctcacattcaggctgtcattttgtggctccaatatcgtcaatcattttttctgtgatatcccacctcttctggctttatcatgtac agacactcagatcaaccagcttctgctctttgctttgtgcagcttcatccagaccagcacttttgtggtaatatttatttcttactt ctgcatcctcatcactgtgttgagcatcaagtcctcaggtggcagaagcaaaacattctccacttgtgcttcccacctcata gcagtcaccttattctatggagcgctcctgtttatgtacttacagcccaccactagctattccctagacactgataaggtggt ggcagtgttttatactgttgtatttcccatgtttaatccaataatttatagtttcagaaacaaggatgtgaaaaatgctctcaaaa agctattagaaagaattggatattcaaatgaatgg (SEQ ID NO: 7)

MOOSE01989 ctgl590729556418..29557338, 29640738..29640758

MI^WVNDSΠQEFJLLGFSDRPWLEFPLLVVFLISYTVTIFGNLTΠLVSR LDTKLHTPMYFFLTNLSLLDLCYTTCTVPQMLVNLCSTRKVIS YRGCVAQLF IFLALGATEYLLLAVMSFDRFVAICRPLHYSVIMHQRLCLQLAAASWVTGFS NSVWLSTLTLQLPLCDPYVTDHFLCEVPALLI LSCVETTANEAELFLVSELFH LIPLTL3XISYAF3VI^VLRIQSAEGRQ3$AFGTCGSFILIVVSLFYSTAVSVYLQ PPSPSSIH)QGKMVSLFYGIIAPMLNPLIYTL3^NKEVKEGFKRLVARRRSSSPN (SEQ ID NO: 10) atgaattgggtaaatgacagcatcatacaggagtttattctgctgggtttctcagatcgaccttggctggagtttc cactccttgtggtcttcttgatttcttacactgtgaccatctttggcaatctgaccattattctagtgtcacgcctggacaccaaa cttcatacccccatgtatttttttcttaccaatctatcactcctggatctttgttacaccacatgtacagtcccacaaatgctagta aatttatgcagcatcaggaaagtaatcagttatcgtggctgtgtagcccagcttttcatatttctggccttgggggctactgaa tatcttctcctggccgtcatgtcctttgataggtttgtagctatttgtcggcctctccattactcagttatcatgcaccagagact ctgcctccagttggcagctgcatcctgggttactggttttagtaactcagtgtggttgtctaccctgactctccagctgccact ctgtgacccctatgtgatagatcactttctctgtgaagtccctgcactgctcaagttatcttgtgttgagacaacagcaaatga ggctgaactattccttgtcagtgagctcttccatctaatacccctgacactcatccttatatcatatgcttttattgtccgagcag tattgaggatacagtctgctgaaggtcgacaaaaagcatttgggacatgtggttcccatctaattgtggtgtctcttttttatag tacagccgtctctgtgtacctgcaaccaccttcgcccagctccaaggaccaaggaaagatggtttctctcttctatggaatc attgcacccatgctgaatccccttatatatacacttaggaacaaggaggtaaaggaaggctttaaaaggttggttgcaaga aggagatcatcaagcccaaat (SEQ ID NO: 9)

MOOSE01990 ctgl3517 1551578..1551604, 1690079..1690511, 1820877..1821358

MAAENSSFVTQFILAGLTDQPGVQIPLFFLFLGFYVVTWGNLGLITLI RLNSHLHTPMYFFLYNLSF3DFCYSSVITPKMLMSFVLKKNSISYAGCMTQL FFFLFFVVSESFILSAMAYDRYVAICNPLLYMVTMSPQVCFLLLLGVYGMGF AGAMAHTAAMMKLSFCKSHJJNHYFCDVLPLLNLSCSNTHLNELLLFIIAGF NTLVPTLAVAVSYAFILYSJLHTRSSEGRSKAFGTCSSHLMAVVJFFGSITFMY FKPPSSNSLDQEKVSSVFYTTV3PI^LNPLIYSL3^KDVKI ϋLI KVLCWKFWP GQS (SEQ ID NO: 12) atggctgctgagaattcctccttcgtgacacagtttatcctcgcaggcttaactgaccaaccgggagtccagat ccccctcttcttcctgtttctaggcttctacgtggtcactgtggtggggaacctgggcttgataaccctgataaggctcaact ctcacttgcacacccctatgtacttcttcctctataacttgtccttcatagatttctgctattccagtgttatcactcccaaaatgc tgatgagctttgtcttaaagaagaacagcatctcctacgcagggtgtatgactcagctcttcttctttcttttctttgttgtctctg agtccttcatcctgtcagcaatggcgtatgaccgctatgtggccatctgtaacccactgttgtacatggtcaccatgtctccc caggtgtgttttctccttttgttgggtgtctatgggatggggtttgctggggccatggcccacacagctgccatgatgaaact gtccttttgcaaatcccacattatcaaccattacttctgtgatgttcttcccctcctcaatctctcctgctccaacacacacctca atgagcttctactttttatcattgcggggtttaacaccttggtgcccaccctagctgttgctgtctcctatgccttcatcctctac agcatccttcacatccgctcctcagagggccggtccaaagcttttggaacatgcagctctcatctcatggctgtggtgatct tctttgggtccattaccttcatgtatttcaagcccccttcaagtaactccctggaccaggagaaggtgtcctctgtgttctaca ccacggtgatccccatgctgaaccctttaatatacagtctgaggaataaggatgtgaagaaagcattaaggaaggtcttat gttggaagttctggccagggcaatca (SEQ TD NO: 11)

MOOSE01991 ctgl6359 766137..766709, 919485..919856, 94258O..942609

MEIO iXTVVREFVLLGLPSSAEQQHLLSVLFLCMYLATTLGNMLIIA TIGFDSITLHSPMYFFLSNLAFVDICFTSTTVPQMVVN3LTGTKTISFAGCLTQL FFFVSFVNMDSLLLCVMAYDRYVAICIJPLIJYTAI MNLCLCVQLVAGLWLV TYLHALLHTVLIAQLSFCASNI3IJHFFCDLNPLLQLSCSDMPL3MQLACVDTS LNEMEMYLASFVFVVLPLGLILVSYGH3A3^VLK3RSAEGI^KAFNTCSSHV AVVSLFYGS3IFMYLQPAKSTSIJEQGKFIALFYTVVTPALNPLIYTLRNTEVK SALRHMMGKFVITKLW (SEQ ID NO: 14) atggaaaaaagaaatctaacagttgtcagggaattcgtccttctgggacttcctagctcagcagagcagcagc acctcctgtctgtgctctttctctgtatgtatttagccaccaccttggggaacatgctcatcattgcgacgattggctttgactct cacctccattcccctatgtacttcttccttagtaacttggcctttgttgacatctgctttacgtcgactacagtcccccaaatggt agtgaatatcttgactggcaccaagactatctcttttgcaggctgcctcacccagctcttcttcttcgtttcttttgtgaatatgg acagcctccttctgtgtgtgatggcgtatgatagatatgtggcgatttgccaccccttacattacaccgccagaatgaacct gtgcctttgtgtccagctagtggctggactgtggcttgttacttacctccacgccctcctgcatactgtcctaatagcacagc tgtccttctgtgcctccaatatcatccatcatttcttctgtgatctcaatcctctcctgcagctctcttgctctgacatgcccctca ttatgcaactggcttgtgtggataccagcctcaatgagatggagatgtacctggccagctttgtctttgttgtcctgcctctgg ggctcatcctggtctcttacggccacattgcccgggccgtgttgaagatcaggtcagcagaagggcggagaaaggcatt caacacctgttcttcccacgtggctgtggtgtctctgttttacgggagcatcatcttcatgtatctccagccagccaagagca cctcccatgagcagggcaagttcatagctctgttctacaccgtagtcactcctgcgctgaacccacttatttacaccctgag gaacacggaggtgaagagcgccctccggcacatgatgggtaaatttgtaatcacaaaattgtgg (SEQ ID NO:13)

MOOSE01992 ctgl59442380342..2381089, 2437225..2437421

MEDKNQTVVTEFLLLGLTDHPYQI IVLFFMFLFVYLITLGGNLGMIT LIWJDPIILHTPMYFFLRIJFHLSFVDTCFSSVVSPI^MLTDFFVI IIKAISFLGCA LQQWFFGFFVAADCFLLESMAYDCYVAICNPLLYSVAMSQRLCIQLVVGPY VIGLMNTMTHTTNAFCLPFCGPIWINPI^CDMSPLLSLVCADTRLNKLAVFI VAGAVGWSGLTJDISYJYJUMAILRIRSADGRCKTFSTCSSHLTAVFISYGTLF FIYVJJPSATFSLDLNKVVSVFYTAVTPMLNPLr^SLi VKDAIHRTVTQRK FCKA (SEQ ID NO : 16) atggaagataagaaccagacagtagtgactgaatttctcttattgggcctcacagatcatccctatcagaagatt gttctcttcttcatgtttctctttgtttatcttatcaccctgggaggtaacttggggatgatcactctcatatggattgatcccaga ctccacactcctatgtacttttttcttaggcacttccacctgtcctttgtggacacctgcttctcctcagttgtgagccccaagat gctcactgacttclfrgtgaagaggaaagccatttctttccttggctgtgctttgcagcagtggttctttgggttctttgtggca gcagactgtttcctcttggagtccatggcctatgactgctatgtggccatctgtaacccattgttatactcagttgctatgtccc agaggctctgcatccagctagtggtgggtccctatgtcattggactcatgaataccatgactcacacaacaaatgcattttg tctccctttttgtggccctaatgtcatcaatcctttcttctgtgatatgtcccccttactttcccttgtatgtgctgataccaggctc aataagttggcagttttcatcgtggctggagctgtgggagtcttcagtggtctgactatcctgatttcctacatttacatcctca tggccatcctgaggatccgctctgctgatgggaggtgcaaaaccttttctacttgctcttctcacctgacagctgttttcatct cgtatggtacccttttctttatttatgtacatcccagtgcaaccttctccctggatctcaataaagtagtgtctgtgttttacacag cagtgattcctatgttgaacccacttatctacagcttgagaaacaaggaagtcaaagatgccatccacaggactgtcactc agaggaagttttgcaaggcc (SEQ ID NO: 15)

MOOSE02000 ctgl4877 55693..55722, 232653..233561 MK3^KNFTEVSEF3FLGFSSFG3 QITLFVVFLTVYILTLVANIJIVTπCI

DHHLHTPMYFFLSMLASSETVYTLVIVPRMLLSLIFHNQPISLAGCATQMFFF VILATNNCFLLTAMGYDRYVAICRPLRYTVIMSKGLCAQLVCGSFGIGLTM AVL3TVTAMFNLPFCGTVVD3JFFCD3YPVMI^SCroTTII^JJNYGVSSFVJFVP IGLIFISYVLVISSILQIASAEGJ^ KTFATCVSHLTVV3VHCGCAS3AYL3π⁾KSE SSffi3α)LVLSVTYTπTPLLNPVVYSL3 NKEVKDALCRVLCLIIKπTS W (SEQ ID NO: 18) atgaagagaaagaacttcacagaagtgtcagaattcattttcttgggattttctagctttggaaagcatcagataa ccctctttgtggttttcctaactgtctacattttaactctggttgctaacatcatcattgtgactatcatctgcattgaccatcatct ccacactcccatgtatttcttcctaagcatgctggctagttcagagacggtgtacacactggtcattgtgccacgaatgctttt gagcctcatttttcataaccaacctatctccttggcaggctgtgctacacaaatgttcttttttgttatcttggccactaataattg cttcctgcttactgcaatggggtatgaccgctatgtggccatctgcagacccctgagatacactgtcatcatgagcaaggg actatgtgcccagctggtgtgtgggtcctttggcattggtctgactatggcagttctccatgtgacagccatgttcaatttgcc gttctgtggcacagtggtagaccacttcttttgtgacatttacccagtcatgaaactttcttgcattgataccactatcaatgag ataataaattatggtgtaagttcatttgtgatttttgtgcccataggcctgatatttatctcctatgtccttgtcatctcttccatcct tcaaattgcctcagctgagggccggaagaagacctttgccacctgtgtctcccacctcactgtggttattgtccactgtggc tgtgcctccattgcctacctcaagccgaagtcagaaagttcaatagaaaaagaccttgttctctcagtgacgtacaccatca tcactcccttgctgaaccctgttgtttacagtctgagaaacaaggaggtaaaggatgccctatgcagagttctctgtctgca caagattattaccagctgg (SEQ ID NO: 17) MOOSE02003 ctgl3517 1950134..1951056, 1975668..1975683

MAAGNHSTVTEFILKGLTKRADLQLPLFLLFLGIYLVTIVGNLGMITLI CLNSQLHTPMYYFLSNLSLMDLCYSSVITPKMLVNFVSEKNΠSYAGCMSQL YFFLWVIAECYMLTVMAYDRYVAJC3JPLLYNIIMSHHTCLLLVAVVYAIGL IGSTIETGLMLI LPYCEHLISHYFCDILPLMKLSCSSTYDVEMTVFFSAGFNJI VTSLTVLVSYTFILSSILGISTTEGRSKAFSTCSSHLAAVGMFYGSTAFMYLK PSTISSLTQENVASVFYTTVIPMLNPLIYSLRNKEVKAAVQKTLRGKXIITHRW

(SEQ ID NO: 20) atggctgcaggaaatcactctacagtgacagagttcattctcaagggtttaacgaagagagcagacctccagc tccccctctttctcctcttcctcgggatctacttggtcaccatcgtggggaacctgggcatgatcactctaatttgtctgaactc tcagctgcacacccccatgtactactttctcagcaatctgtcactcatggatctctgctactcctccgtcattacccctaagat gctggtgaactttgtgtcagagaaaaacatcatctcctacgcagggtgcatgtcacagctctacttcttccttgtttttgtcatt gctgagtgttacatgctgacagtgatggcctacgaccgctatgttgccatctgccaccctttgctttacaacatcattatgtct catcacacctgcctgctgctggtggctgtggtctacgccatcggactcattggctccacaatagaaactggcctcatgttaa aactgccctattgtgagcacctcatcagtcactacttctgtgacatcctccctctcatgaagctgtcctgctctagcacctatg atgttgagatgacagtcttcttttcggctggattcaacatcatagtcacgagcttaacagttcttgtttcttacaccttcattctct ccagcatcctcggcatcagcaccacagaggggagatccaaagccttcagcacctgcagctcccaccttgcagccgtgg gaatgttctatggatcaactgcattcatgtacttaaaaccctccacaatcagttccttgacccaggagaatgtggcctctgtg ttctacaccacggtaatccccatgttgaatcccctaatctacagcctgaggaacaaggaagtaaaggctgccgtgcagaa aacgctgaggggtaaactcattcatcataggtgg (SEQ ID NO: 19)

MOOSE02005 ctgl3657 1700549..1700902, 1802976..1803502,

1973146..1973212

MESGNQSTVTEF3FTGFPQLQDAFQLLFFS3FLATYLLTLLENLLULAI HSDGQLHKPMYFFLSHLSFLEMWYVTVISPKMLVDFLSHDKSISFNGCMTQ

LYFFVTFVCTEYILLAIMAFDRYVAICNPLRYPV3MTNQLCGTLAGGCWFCG LMTAM3K WIAQLHYCGMPQ3NHYFCDISPLLNVSCEDASQAEMMV3FFLS ILVLLVPLVLTFISYIFIVSTILiαSSVEGQCI AFATCASHLTWWHYGCASFI YLl^TSLYSSDiαDI^VAVTYTVITPLLNPLVYTL3^NKEVKMALIlKVLGRCL NSKTV (SEQ ID NO: 22) atggagagcggaaaccaatcaacagtgactgaatttatcttcactggattccctcagcttcaggatgccttcca gcttctctttttctccattttcctggcaacctatctgctgacactgctggagaatcttcttatcatcttagctatccacagtgatgg gcagctgcataagcccatgtacttcttcttgagccacctctccttcctggagatgtggtatgtcacagtcatcagccccaag atgcttgttgacttcctcagtcatgacaagagtatttccttcaatggctgcatgactcaactttacttttttgtgacctttgtctgc actgagtacatccttcttgctatcatggcctttgaccgctatgtagccatttgtaatccactacgctacccagtcatcatgacc aaccagctctgtggcacactggctggaggatgctggttctgtggactcatgactgccatgattaagatggtttttatagcac aacttcactactgtggcatgcctcagatcaatcactacttttgtgatatctctccactccttaacgtctcctgtgaggatgcctc acaggctgagatgatggtcatctttttcctcagcattctggtattgctggttccccttgtgttgatattcatctcctacatcttcat agtttccaccatcctcaagatctcctcagtggaaggacagtgcaaagccttcgccacctgtgcttcccacctcacagtggt cgtcgtccactatggctgtgcttcctttatctacttgaggcccacatccctgtactcttcagataaggaccggctcgtggcag tgacttatactgtgattactccactactcaacccccttgtctatacactgagaaataaagaagtaaagatggctctgagaaag gttctgggtagatgcttaaattccaaaactgta (SEQ ID NO: 21)

MOOSE02012 ctgl2559 8951547..8952461. 9093750..9093773 MGDNITS3REFLLLGFPVGPRIQMLLFGLFSLFYVFTLLGNGT3LGLISL

DS3^3JAPMYFFLSFiUAVVD]AYACNTVP3^MLVNLLI3PAiα^jISFAGFiMMQTF

LFSTFAVTECLLLWMSYDLYVAICHPLRYLAJMTWRVCITLAVTSWTTGVL LSL3IJLVLLLPLPFCILPQI ΗFFCE3LAVLKXACADTITINENMVLAGAISGLV GPLSTIVVSYMCILCAILQIQSREVQREAFRTCFSFΓLCVIGLVYGTAIIMYVGP RYGNPI^QKKYLLLFHSLFNPMLNPLICSLRNSEVKNTLKRVLGRS QWCKS Q (SEQ ID NO: 24) atgggagacaatataacatccatcagagagttcctcctactgggatttcccgttggcccaaggattcagatgct cctctttgggctcttctccctgttctacgtcttcaccctgctggggaacgggaccatactggggctcatctcactggactcca gactgcacgcccccatgtacttcttcctctcacacctggcggtcgtcgacatcgcctacgcctgcaacacggtgccccgg atgctggtgaacctcctgcatccagccaagcccatctcctttgcgggccgcatgatgcagacctttctgttttccacttttgct gtcacagaatgtctcctcctggtggtgatgtcctatgatctgtacgtggccatctgccaccccctccgatatttggccatcat gacctggagagtctgcatcaccctcgcggtgacttcctggaccactggagtccttttatccttgattcatcttgtgttacttcta cctttacccttctgtaggccccagaaaatttatcactttttttgtgaaatcttggctgttctcaaacttgcctgtgcagataccca catcaatgagaacatggtcttggccggagcaatttctgggctggtgggacccttgtccacaattgtagtttcatatatgtgca tcctctgtgctatccttcagatccaatcaagggaagttcagaggaaagccttccgcacctgcttctcccacctctgtgtgatt ggactcgtttatggcacagccattatcatgtatgttggacccagatatgggaaccccaaggagcagaagaaatatctcctg ctgtttcacagcctctttaatcccatgctcaatccccttatctgtagtcttaggaactcagaagtgaagaatactttgaagaga gtgctgggaaggagccaatggtgtaagtcccag (SEQ ID NO: 23) MOOSE02013 ctgl3103 7556019..7556060, 7752122..7753039

MEWΕNQTIXVEFFLKGHSV33P3^ELLFFVL 3MYVVILLGNGTLILISI LDPHLHTPMYFFLGNLSFLDICYTTTSJPSTLVSFLSERKTISFSGCAVQMFLG

LAMGTTECVLLGMMAFDRYVAICNPLRYPTJMSI<NAYVPMAVGSWFAG3V NSAVQTTFVVQLPFCPVKLWINITFSCEILAVIVIKXACADISGNEFLMLVATILF TLMPLLLIVISYSLΠSSILKFFLSSEGRSK.AFSTCSAHLTVVJJFYGTILFMYMI P KSKETLNSDDLDATDKΠSIVIFYGVMTPMMNPLIYSLI NIΦVKEALCRLFRS GFHSQYN (SEQ ID NO: 26) atggaatgggaaaaccaaaccattctggtggaattttttctgaagggacattctgttcacccaaggcttgagtta ctcttttttgtgctaatcttcataatgtatgtggtcatccttctggggaatggtactctcattttaatcagcatcttggaccctcac cttcacacccctatgtacttctttctggggaacctctccttcttggacatctgctacaccaccacctctattccctccacactag tgagcttcctttcagaaagaaagaccatttccttttctggctgtgcagtgcagatgttccttggcttggccatggggacaaca gagtgtgtgcttctgggcatgatggcctttgaccgctatgtggctatctgcaaccctctgagatatcccatcatcatgagca agaatgcctatgtacccatggctgttgggtcctggtttgcagggattgtcaactctgcagtacaaactacatttgtagtacaa ttgcctttctgcaggaagaatgtcatcaatcatttctcatgtgaaattctagctgtcatgaagttggcctgtgctgacatctcag gcaatgagttcctcatgcttgtggccacaatattgttcacattgatgccactgctcttgatagttatctcttactcattaatcattt ccagcatcctcaagattcactcctctgaggggagaagcaaagctttctctacctgctcagcccatctgactgtggtcataat attctatgggaccatcctcttcatgtatatgaagcccaagtctaaagagacacttaattcagatgacttggatgctaccgaca aaattatatccatgttctatggggtgatgactcccatgatgaatcctttaatctacagtcttagaaacaaggatgtgaaagag gcactctgcaggctgttcaggagtggatttcattcccagtacaac (SEQ ID NO: 25)

MOOSE02014 ctg53 48293..48490, 296652..297358, 314735..314759

NHSRVTEFVLLGLSSSRELQPFLFLTFSLLYLATLLGNFLΠLTVTSDSR LHTPMYFLLANLSFIDIWYISST NMLVNTLSEIKTISFSGCFLQFYFFFSLGT TECFFLSVMAYDRYLAICRPLFΓYPSJMTGKFCTJLVCVCWVGGFLCYPVPIVL ISQLPFCGPNΠDHLVCDPGPLFALACISAPSTELICYTFNSMΠFGPFLSILGSYT

LVTRAVLC3PSGAGRTKAFSTCGSHLMVVSLFYGTLMVMYVSPTSGNPAGM

QKΠTLVYTAMTPFLNPLIYSLP^UKDMKDALKRVLGRRQWPSSI (SEQ ID

NO: 28) aatcattctcggg^gacagaatttgtgttgctgggactgtctagttcaagggagctccaacctttcttgtttcttaca ttttcactactttatctagcaattctgttgggcaactttctcatcatcctcactgtgacctcagattcccgccttcacacccccat gtactttctgcttgcaaacctgtcatttatagacatctggtacatttcctccactgtcccaaacatgctagtcaatatcctctctg agattaaaaccatctccttctctggttgcttcctgcaattctatttctttttttcactgggtacaacagagtgtttctttttatcagtta tggcttatgatcggtacctggccatctgtcgtccattacactacccctccatcatgactgggaagttctgtataattctggtct gtgtatgctgggtaggcggatttctctgctatccagtccctattgttcttatctcccaacttcccttctgtgggcccaacatcatt gaccacttggtgtgtgacccaggcccattgtttgcactggcctgcatctctgctccttccactgagcttatctgttacaccttc aactcgatgattatctttgggcccttcctctccatcttgggatcttacactctggtcatcagagctgtgctttgtattccctctgg tgctggtcgaactaaagctttctccacatgtgggtcccacctaatggtggtgtctctattctatggaacccttatggtgatgta tgtgagcccaacatcagggaacccagcaggaatgcagaagatcatcactctggtatacacagcaatgactccattcttaa atccccttatctatagtcttcgaaacaaagacatgaaagatgctctaaagagagtcctgggcaggagacagtggccttcct ctatc (SEQ ID NO: 27)

MOOSE02016 ctgl3657 2010295..2010336, 2020876..2021775

MDTGNWSQVAEFΠLGFPHLQGVQIYLFLLLLLIYLMTVLGNLLIFLV VCLDS3^LHTPMTYHFVSILSFSELGYTAAT3P3IAV LANLFSEKKTISFSGCLLQIY FFHSLGATECYLLTAMAYDRYLAICRPLHYPTLMTPTLCAEIAIGCWLGGLA GPVVEISLISIILPFCGPNRIQHVFCDFPPVLSLACTDTSTNVLVDFVINSCKIL ATFLLILCSYVQΠCTVLI ^>SAAGKR3^ISTCASHLTVVL3FYGSILSMYVRL KKSYSLDYDQALAVVYSVLTPFLNPFIYSLHN3^Π EAWKKYICILRQPATE M (SEQ ID NO: 30) atggacacagggaactggagccaggtagcagaattcatcatcttgggcttcccccatctccagggtgtccag atttatctcttcctcttgttgcttctcatttacctcatgactgtgttgggaaacctgctgatattcctggtggtctgcctggactcc cggcttcacacacccatgtaccactttgtcagcattctctccttctcagagcttggctatacagctgccaccatccctaagat gctggcaaacttgttcagtgagaaaaagaccatttcattctctgggtgtctcctgcagatctatttctttcactcccttggagc gactgagtgctatctcctgacagctatggcctacgataggtatttagccatctgccggcccctccactacccaaccctcatg accccaacactttgtgcagagattgccattggctgttggttgggaggcttggctgggccagtagttgaaatttccttgatttc acgcctcccattctgtggccccaatcgcattcagcacgtcttttgtgacttccctcctgtgctgagtttggcttgcactgatac gtctacaaatgtcctagtagattttgttataaattcctgcaagatcctagccaccttcctgctgatcctctgctcctatgtgcag atcatctgcacagtgctcagaattccctcagctgccggcaagaggaaggccatctccacgtgtgcctcccacctcactgt ggttctcatcttctatgggagcatcctttccatgtatgtgcggctgaagaagagctactcactggactatgaccaggccctg gcagtggtctactcagtgctcacacccttcctcaaccccttcatctacagcttgcacaacaaggagatcaaggaggcttgg aaaaagtacatctgcaggaggcagccagccacggaaatg (SEQ ID NO: 29)

MOOSE02017 ctgl4667 1151783..1151789, 1152941..1153872

MGSFNTSFEDGFILVGFSDWPQLEPILFVFIFIFYSLTLFGNTΠIALSWL DLRLHTPMYFFLSHLSLLDLCFTTSTVPQLL3NLCGVDRTITRGGCVAQLFIY LALGSTECVLLVVMAFDRYAAVCRPLHYMA3M3JPHLCQTLAIASWGAGFV NSLIQTGLA-MAMPLCGH3Π_JNHFFCEMPVFLKLACADTEGTEAKMFVARVIV VAWAALILGSYVΗIAHAVURVKSTAGRRKAFGTCGSHLLVVFLFYGSAIYT YLQSIHNYSEREGIΠ^VALFYTΠTPILNPLIYTLRNKDVKGALWKVLWRGRD SGQW (SEQ ID NO: 32) atgggaagtttcaacaccagttttgaagatggcttcattttggtgggattctcagattggccgcaactggagccc atcctgtttgtctttatttttattttctactccctaactctctttggcaacaccatcatcatcgctctctcctggctagaccttcggct gcacacacctatgtacttctttctctctcatctgtccctcctggacctctgcttcaccaccagcaccgtgccccagctcctgat caacctttgcggggtggaccgcaccatcacccgtggagggtgtgtggctcagctcttcatctacctagccctgggctcca cagagtgtgtgctcctggtggtgatggcctttgaccgctatgctgctgtctgtcgtccactccactacatggccatcatgca cccccatctctgccagaccctggctatcgcctcctggggtgcgggtttcgtgaactctctgatccagacaggtctcgcaat ggccatgcctctctgtggccatcgactgaatcacttcttctgtgagatgcctgtatttctgaagttggcttgtgcggacacag aaggaacagaggccaagatgtttgtggcccgagtcatagtcgtggctgttcctgcagcacttattctaggctcctatgtgc acattgctcatgcagtgctgagggtgaagtcaacggctgggcgcagaaaggcttttgggacttgtgggtcccacctccta gtagttttccttttttatggctcagccatctacacatatctccaatccatccacaattattctgagcgtgagggaaaatttgttgc ccttttttatactataattacccccattctcaatcctctcatttatacactaagaaacaaggacgtgaagggggctctgtggaa agtactatggaggggcagggactcagggcagtgg (SEQ ID NO: 31) MOOSE02019 ctg53 1139348..1139380, 1231694..1232602

MKGANLSQGMEFELLGLTTDPQLQRLLFWFLGMYTATLLGNLVMF

LLIIJVSATLHTPMYSLLKSLSFLDFCYSSTVVPQTLVNFLAXRKVISYFGCMT

QMFFYAGFATSECYLIAAMAYDRYAAICNPLLYSTIMSPEVCASLIVGSYSA GFLNSLFFLTGCJFSLKFCGAHVVTHFFCDGPPILSLSCVDTSLCEILLFIFAGFN

LLSCTLTILISYFLILNTILKMSSAQGRFKAFSTCASHLTAICLFFGTTLFMYLR PRSSYSLTQDRTVAVIYTVV3PVLNPLMYSLRM DV30 AL1KLLKKLFISFPD (SEQ ID NO: 34) atgaaaggggcaaacctgagccaagggatggagtttgagctcttgggcctcaccactgacccccagctcca gaggctgctcttcgtggtgttcctgggcatgtacacagccactctgctggggaacctggtcatgttcctcctgatccatgtg agtgccaccctgcacacacccatgtactccctcctgaagagcctctccttcttggatttctgctactcctccacggttgtgcc ccagaccctggtgaacttcttggccaagaggaaagtgatctcttattttggctgcatgactcagatgttcttctatgcgggttt tgccaccagtgagtgctatctcatcgctgccatggcctatgaccgctatgccgctatttgtaaccccctgctctactcaacc atcatgtctcctgaggtctgtgcctcgctgattgtgggctcctacagtgcaggattcctcaattctcttatccacactggctgt atctttagtctgaaattctgcggtgctcatgtcgtcactcacttcttctgtgatgggccacccatcctgtccttgtcttgtgtaga cacctcactgtgtgagatcctgctcttcatttttgctggtttcaaccttttgagctgcaccctcaccatcttgatctcctacttctt aattctcaacaccatcctgaaaatgagctcggcccagggcaggtttaaggcattttccacctgtgcatcccacctcactgc catctgcctcttctttggcacaacactttttatgtacctgcgccccaggtccagctactccttgacccaggaccgcacagttg ctgtcatctacacagtggtgatcccagtgctgaaccccctcatgtactctttgagaaacaaggatgtgaagaaagctttaat aaagcttttaaagaaattgtttataagctttccagat (SEQ ID NO: 33)

MOOSE02020 ctgl59442581969..2582449, 2606297..2606721,

2726123..2726158

MGRGNSTEVTEFHLLGFGVQHEFQHVLFΓVLLLIYVTSLIGNIGMILLI KTDS3^QTPLVRYFFPQ3JLAFVDICYTSAITPΪCMLQSFTEENNLITFRGCVIQFL

VYATFATSDCYLLAIMAMDCYVAICKPLRYPMIMSQTVΎIQLVAGSYΠGSI NASVHTGFTCSLSFCKSNS3NHFFCDWPILALSCSNVDINIMLLVVFVGSNLI FTGLVVTFSYTYIMATILK-MSSSAGRKXSFSTCASHLTAVT3FYGTLSYMYLQ SHSNNSQENMKVAF3EYGTV3PML1^L3YSL3^NKEVKEALKIILLWSECCVSQ N (SEQ ID NO: 36) atgggtcgaggaaacagcactgaagtgactgaattccatcttctgggatttggtgtccaacacgaatttcagca tgtccttttcattgtacttcttcttatctatgtgacctccctgataggaaatattggaatgatcttactcatcaagaccgattccag acttcaaacacccatgtacttlutccacaacatttggcttttgttgatatctgttatacttctgctatcactcccaagatgctcca aagcttcacagaagaaaataatttgataacatttcggggctgtgtgatacaattcttagtttatgcaacatttgcaaccagtga ctgttacctcctagctattatggcaatggattgttatgttgccatctgtaagccccttcgctatcccatgatcatgtcccaaaca gtctacatccaactcgtagctggctcatatattataggctcaataaatgcctctgtacatacaggttttacatgttcactgtcctt ctgcaagtccaatagcatcaatcactltttctgtgatgttccccctattcttgctctttcatgctccaatgttgacatcaacatcat gctacttgttgtc1fr:gtgggatctaacttgatattcactgggttggtcgtcatcttttcctacatctacatcatggccaccatcct gaaaatgtcttctagtgcaggaaggaaaaaatccttctcaacatgtgcttcccacctgaccgcagtcaccattttctatggg acactctcttacatgtatttgcagtctcattctaataattcccaggaaaatatgaaagtggcctttatattttatggcacagttatt cccatgttaaatcctttaatctatagcttgagaaataaggaagtaaaagaagctttaaaaagactactatggtctgaatgttgt gtctcccaaaat (SEQ ID NO: 35)

MOOSE02023 ctgl5944 3691512..3691544, 3844394.3845284, 3904316..3904339

IVΠLEGNLTSVTEFVMMGFAG3HEAHLLFFILFLTMYLFTLVENLAΠLV

VGLDHRLRRPMYFFLTHLSCLEIWYTSVTVPKMLAGFIGVDGGKNISYAGC

LSQLFIFTFLGATECFLLAAMAYDRYVAICMPLHYGAFVSWGTC3RLAAAC

WLVGFLTPTLPIYLLSQLTFCGPNVIDHFSCDASPLLALSCSDVTWI ETVDFL VSLAVLLASSM OAVSYGNIV VTLLHIRSAAERWKAFSTCAAHLTVVSLFY GTLFFMYVQTKVTSSIN3^NKVVSWYSVVTPMLNPLIYSL3 KEVKGALGRT LSQKKKKKKN (SEQ ID NO: 38) atgttagaaggaaatctcaccagcgtaactgaatttgtcatgatgggctttgctggcatccatgaagcacacctc ctcttcttcatactcttcctcaccatgtacctgttcaccttggtggagaatttggccatcattttagtggtgggtttggaccacc gactacggagacccatgtatttcttcctgacacacttgtcctgccttgaaatctggtacacttctgttacagtgcccaagatg ctggctggttttattggggtggatggtggcaagaatatctcttatgctggttgcctatcccagctcttcatcttcacctttcttgg ggcaactgagtgtttcctactggctgccatggcctatgatcgttatgtggccatttgtatgcctctccactatggggcttttgt gtcctggggcacctgcatccgtctggcagctgcctgttggctggtaggtttcctcacacccatcttgccaatctacctcttgt ctcagctaacattttgtggcccaaatgtcattgaccatttctcctgtgatgcctcacccttgctagccttgtcgtgctcagatgt cacttggaaggagactgtggatttcctggtgtctctggctgtgctactggcctcctctatggtcattgctgtgtcctatggcaa catcgtctggacactgctgcacatccgctcagctgctgagcgctggaaggccttctctacctgtgcagctcacctgactgt ggtgagcctcttctatggcactcttttctttatgtatgtccagaccaaggtgacctcctccatcaacttcaacaaggtggtatct gtcttctactctgttgtcacgcccatgctcaatcctctcatctacagtcttaggaacaaggaagtgaagggagctctgggtc gaactctgtctcaaaaaaaaaaaaaaaaaaaaaat (SEQ ID NO: 37)

MOOSE02024 ctgl5285 7036487..7036516, 7045683..7046006,

7131678..7132265

MKNRTMFGEFJDLGLTNQPELQVMIFIFLFLTYMLSILGNLTΠTLTLLD PHLQTPMYFFLRNFSFLEISFTSFJPRFLTSMTTGNKVISFAGCLTQYFFAIFL GATEFYLLASMS YDRYVAICKPLHYLTIMSSRVCIQLVFCSWLGGFLAILPPΠ

LMTQVDFCVSNILNHYYCDYGPLVELACSDTSLLELMISVMTATIVF3MIPFS LIVTSYTRILGAILAMASTQSRRKVFSTCSSHLLVVSLFFGTASITYIRPQAGSS VTTDRV SLFYTVITPMLNPIIYTLRl^IΦVRliAL3 HLLPL3 KWLRIW (SEQ ID NO: 40) atgaaaaacagaaccatgtttggtgagtttattctactgggccttacaaatcaacctgaactccaagtgatgatat tcatctttctgttcctcacctacatgctaagtatcctaggaaatctgactattatcaccctcaccttactagacccccacctcca gacccccatgtatttcttcctccggaatttctccttcttagaaatttccttcacatccatttttattcccagatttctgaccagcatg acaacaggaaataaagttatcagctttgctggctgcttgactcagtattluttgctatatttcttggagctaccgagttttacct cctggcctccatgtcttatgatcgttatgtggccatctgcaaacccttgcattacctgactattatgagcagcagagtctgcat acaactagtgttctgctcctggttggggggattcctagcaatcttaccaccaatcatcctgatgacccaggtagatttctgtg tctccaacattctgaatcactattactgtgactatgggcctctcgtggagcttgcctgctcagacacaagcctcttagaactg atgatctccgtgatgacagccaccatagtcttcattatgatccccttctctctgattgtcacctcttacatccgcatcctgggtg ccatcctagcaatggcctccacccagagccgccgcaaggtcttctccacctgctcctcccatctgctcgtggtctctctctt ctttggaacagccagcatcacctacatccggccgcaggcaggctcctctgttaccacagaccgcgtcctcagtctcttcta cacagtcatcacacccatgctcaaccccatcatctacacccttcggaacaaggacgtgaggagggccctgcgacacttg ctgcctttgagaaagtggttgagaatatgg (SEQ ID NO: 39)

Table π

MOOSE06786 ctgl8433 219426..220365,

MKSWNNT3JLEFLLLGISEEPELQAFLFGLFLSMYLVTVLGNLLI3LATI SDSHLHTPMY3^LSNLSFVDICFVSTT K LVMQTHNKVITYAGCITQMCF FLLFVGLDNJ^LLTVMAYDI^VAICHPLHYMV3MNPQLCGLLVLASWIMSVL NSMLQSLMVLPLPFCTJJMEIPJJFFCEINQVVHLACSDTFLNDΓV^IYFAVALL GGGPLTGTUYSYSK3VSSIRAISSAQGKYKAFSTCASHLSVVSLFYGTCLGVY LSSAATIJNSHTGAAASVIVRY^'TVVTPMLNPFR SLI^KHJJ GAMKTFFRGKQN RI AI (SEQ ID NO: 42) atgaaatcatggaacaatacaataattttagaatttcttctcctgggaatttcagaggaaccagaattgcaggcct tcctctttgggctgttcctgtccatgtacctggtcactgtgctcgggaacctgctcatcatcctggccacaatctcagactcc cacctccacacccccatgtacttcttcctctccaacctgtccttcgtagacatctgttttgtctctaccactgtcccgaagatgc tggtgaacatccagacacacaacaaagtcatcacctatgcaggctgcatcacccagatgtgctttttcttactctttgtagga ttggataacttccttctgaccgtgatggcctatgaccggtttgtggccatctgtcaccctctgcactacatggtcattatgaac cctcaactctgtggactgctggttctggcatcctggatcatgagtgttctgaattccatgttacaaagcttaatggtgttgcca ctgcccttttgtacacacatggaaatccctcattttttctgtgaaattaatcaggtggtccaccttgcctgttctgacacctttctt aatgacatagtgatgtattttgcagtagcgctgctgggcggtggtcccctcactgggatcctgtactcttactctaagatagt ttcctccatacgtgcaatctcatcagctcaggggaagtataaggcattttccacctgtgcatctcacctctcagttgtctcctt attttatggtacatgcttaggggtgtaccttagttctgctgccacccacaattcacacacaggtgctgcagcctcagtgatgt acactgtggtcacccccatgctgaaccccttcatctacagtctgaggaataaacacataaagggtgctatgaaaacattctt cagaggaaagcaaaatagaaaggctatt (SEQ ID NO: 41)

MOOSE06791 ctgl5907 32399000..32399533, 32422271..32422654,

32470431..32470448, MLNTTSVTEFLLLGVTDIQELQPFLFVVFLTIYFISVAGNGAILMTVISD

PI^HSPMYFFLGNLSCLDICYSSVTLPK^ΛQNFLSAIIKAISFLGCISQLFΓFFH FLGSTEAMLLAVMAFD3^VAICIΠ^,LRYTV3MNPQLCTQIVLAITIWMIGFFILAL LHSLMTSPXNFCGSNRIYHFFCDIQPVLQLVCGDTSLNELQIJLATALLILCPF GLILGSYGI ,VTIEI^IPSVAGRRKAFSTCSSFRL3 ^SLFYGTALFIYIRPI ASY DPATDPLVSLFYA TP3LNPIIYSLIWTEVKAALKRTIQKTAFHSSW (SEQ

ID NO: 44) atgctgaatacaacctcagtcactgaatttctccttttgggagtgacagacattcaagaactgcagccttttctctt cgttgttttccttaccatctacttcatcagtgtggctgggaatggagccattctgatgattgtcatctctgatcctagactccatt cccctatgtatttcttcctgggaaacctgtcctgcctggacatctgctactccagcgtaacactgccaaaaatgctgcagaa cttcctctctgcacacaaagcaatttctttcttgggatgcataagccaactccatttcttccacttcctgggcagcacagagg ccatgttgttggccgtgatggcatttgaccgctttgtggctatttgcaagccacttcgctacactgtcattatgaaccctcagc tctgtacccagatggccatcacaatctggatgattggttttttccatgccctgctgcactccctaatgacctctcgcttgaactt ctgtggttctaaccgtatctatcacttcttctgtgatatccagcctgtcctgcagctggtatgtggagacacctcgcttaatga actgcagattatcctggcaacagccctcctcatcctctgcccctttggcctcatcctgggctcctacgggcgtatcctcgtta ccatcttccggatcccatctgttgcgggccgccgcaaggccttctccacctgctcctcccacctgatcgtggtctccctctt ctatggcaccgcactctttatctatattcgccctaaggccagctacgatccggccactgaccctctggtgtccctcttctatg ctgtggtcacccccatcctcaaccccatcatctacagcctgcggaacacagaggtcaaagctgccctaaagagaaccat ccagaaaacggcatttcacagcagttgg (SEQ ID NO: 43) MOOSE06792 ctgl5907 32026075..32026200, 32068267..32069085,

MNWENESSPI^F3LLGFSD3^WLQMPLFVVLLISYTITIFGNVSTMMV C3LDPKLHTPlvrYFFLTNLS3LDLCYTTTTW3JMLVMGCNKKTISYAGCVAHL IJFLALGATECLLLAVMSFDRYVAVCRPLFiYVVIMNYWFCLRMAAFSWLIG FGNSVLQSSLTLNMPRCGHQEVDHFFCEVPALLKLSCADTia'IEAELFFFSVL ILL3J? VTLILIS YGFIAQAVLKIRS AEGRQI AFGTCGSITMIVVSLFYGTAIYMY

LQPPSSTSKDWGKMFLTLFYTVITPSLNPLIYTL3^N30DMIO ALKJJ,MRFHH KSTKI (SEQ ID NO: 46) atgaattgggaaaatgagagctccccaaaagagtttatactacttggcttctcagatagggcttggctacaaatg ccccttlttgtggtcctgttaatatcatacacaatcaccatatttggcaatgtgtccatcatgatggt aacttcatactcccatgtatttctttctcactaatctctccatcttagatctctgctataccacaactacagtccctcatatgttggt aaatattggttgcaacaaaaagaccatcagctatgctggctgtgtggcccacctcatcatcttcctggccctaggtgctaca gagtgtctccttctggctgttatgtcctttgacagatatgtggctgtttgcagacccctccactatgtagtcatcatgaattattg gttctgcctaaggatggcagccttctcatggctcattggtttcggcaactcagtgctgcagtcttccttgactcttaacatgcc acgctgtggtcaccaggaagtggaccactttttctgtgaggtgcctgcacttctcaagttgtcatgtgctgacacaaagcct attgaggctgagctcttcttctttagtgtactaattcttctaattccagtgacattgatcctcatctcctatggcttcatagctcaa gcagtattaaaaatcaggtcagcagaaggacggcaaaaagcatttgggacatgtgggtcccacatgattgtggtgtccct cttttatggaacagccatttatatgtatcttcaaccaccttcatccacctctaaggactggggaaagatgttcctcaccctcttt tacaccgtcatcactccaagtctcaacccgctcatttacaccttaagaaataaggacatgaaggatgccctgaagaaactg atgagatttcaccacaaatctacaaaaata (SEQ ID NO: 45)

MOOSE06799 ctgl3103 26750090..26750116, 26765948.-26766852,

26824997..26825006,

MEGMNQTTVSDFLLLGLSEWPEEQPLLFGIFLGMYLVTMVGNLLΠL AISSDPHLHTPMYFFLANLSLTDACFTSASIPKMLANIHTQSQΠSYSGCLAQL YFLLMFGGLDNCLLAVMAYDRYVAJCQPLHYSTSMSPQLCALMLGVCWVL TNCPADMHTLLLTRVAFCAQI^3P3JFYCDPSALLiα_JACSDT3ϊVNELMπTMG LLFLTVPLLL3VFSYVIOFWAVFVISSPGGRWKAFSTCGSHLTVVLLFYGSLM GVYLLPPSTYSTETiESRAAVLYMVITPTLN FIYSLRNRDMI^ALGKXF3J3^KF DSKRI (SEQ ID NO: 48) atggagggaatgaaccaaaccactgtttcagacttcctccttctaggactctctgagtggccagaggagcagc ctcttctgtttggcatcttccttggcatgtacctggtcaccatggtggggaacctgctcattatcctggccatcagctctgacc cacacctccatactcccatgtacttctttctggccaacctgtcattaactgatgcctgtttcacttctgcctccatccccaaaat gctggccaacattcatacccagagtcagatcatctcgtattctgggtgtcttgcacagctatatttcctccttatgtttggtggc cttgacaactgcctgctggctgtgatggcatatgaccgctatgtggccatctgccaaccactccattacagcacatctatga gtccccagctctgtgcactaatgctgggtgtgtgctgggtgctaaccaactgtcctgccctgatgcacacactgttgctgac ccgcgtggctttctgtgcccagaaagccatccctcatttctattgtgatcctagtgctctcctgaagcttgcctgctcagatac ccatgtaaacgagctgatgatcatcaccatgggcttgctgttcctcactgttcccctcctgctgatcgtcttctcctatgtccg cattttctgggctgtgtttgtcatctcatctcctggagggagatggaaggccttctctacctgtggttctcatctcacggtggtt ctgctcttctatgggtctcttatgggtgtgtatttacttcctccatcaacttactctacagagagggaaagtagggctgctgttc tctatatggtgattattcccacgctaaacccattcatttatagcttgaggaacagagacatgaaggaggctttgggtaaacttt ttcacagaaaatttgatagtaaaaggata (SEQ ID NO: 47)

MOOSE06800 ctgl3103 26713968..26714879, 26718054..26718080,

GRVNQTTVSDFLLLGLSEWPEEQPLLFGTFLGMYLVTMVGNLLHLAI SSDPIJLHTPMYFFLANLSLTDACFTSASIPI MLANIHTQSQΠSYSGCLAQLYF

LLMFGGLDNCLLAVMAYDRYVAICQPLHYSTSMSPQLCALMLGVCWVLT NCPALMHTLLLTRVAFCAQKA3PITFYCDPSALL3Α ACSDTIRVNELMΠTMGL LFLTWLLLIV SYVRFFWAVFVISSPGGRWKAFSTCGSHLTVVLLFYGSLMG VYLLPPSTYSTEMSRAAVLYIVLVIIPTLOTFJYSLRNI^MI^AXGKLFCRAFS FSSL (SEQ ID NO: 50) ggcagagtgaaccaaaccactgtttcagacttcctccttctaggactctctgagtggccagaggagcagcctc ttctgtttggcatcttccttggcatgtacctggtcaccatggtggggaacctgctcattatcctggccatcagctctgaccca cacctccatactcccatgtacttctttctggccaacctgtcattaactgatgcctgtttcacttctgcctccatccccaaaatgc tggccaacattcatacccagagtcagatcatctcgtattctgggtgtcttgcacagctatatttcctccttatgtttggtggcctt gacaactgcctgctggctgtgatggcatatgaccgctatgtggccatctgccaaccactccattacagcacatctatgagt ccccagctctgtgcactaatgctgggtgtgtgctgggtgctaaccaactgtcctgccctgatgcacacactgttgctgacc cgcgtggctttctgtgcccagaaagccatccctcatttctattgtgatcctagtgctctcctgaagcttgcctgctcagatacc catgtaaacgagctgatgatcatcaccatgggcttgctgttcctcactgttcccctcctgctgatcgtcttctcctatgtccgc attttctgggctgtgtttgtcatctcatctcctggagggagatggaaggccttctctacctgtggttctcatctcacggtggttc tgctcttctatgggtctcttatgggtgtgtatttacttcctccatcaacttactctacagagagggaaagtagggctgctgttct ctatatggtgattattcccacgctaaacccattcatttatagcttgaggaacagagacatgaaggaggctttgggtaaactttt ttgcagagcttttagtttctcatcatta (SEQ ID NO: 49)

MOOSE06803 ctgl5907 30939074..30939994, 30982809..30982829,

5 MNWVNDSΠQEFILLGFSDRPWLEFPLLVVFLISYTVTIFGNLTΠLVSR

LDTKXHTPMYFFLTNLSLLDLCYTTCTVPQMLVNLCSIRKVISYRGCVAQLF LAUGATEYLLLAVMSFD3^VAIC3^L!JYSVIMHQRLCLQLAAASWVTGFS NSVWLSTLTLQLPLCDPYVTDHFLCEVPALLI LSCVETTANEAELFLVSELFH LIPLTL3LISYAFIVILAVLI QSAEGRQKAFGTCGSHLIVVSLFYSTAVSVYLQ l o PPSPSSKDQGKMVSLFYGΠAPMLNPLIYTLRNI^VKEGFKRLVARRSFCSST

(SEQ ID NO: 52) atgaattgggtaaatgacagcatcatacaggagtttattctgctgggtttctcagatcgaccttggctggagtttc cactccttgtggtcttcttgatttcttacactgtgaccatctttggcaatctgaccattattctagtgtcacgcctggacaccaaa cttcatacccccatgtatttttttcttaccaatctatcactcctggatctttgttacaccacatgtacagtcccacaaatgctagta

15 aatttatgcagcatcaggaaagtaatcagttatcgtggctgtgtagcccagcttttcatatttctggccttgggggctactgaa tatcttctcctggccgtcatgtcctttgataggtttgtagctatttgtcggcctctccattactcagttatcatgcaccagagact ctgcctccagttggcagctgcatcctgggttactggttttagtaactcagtgtggttgtctaccctgactctccagctgccact ctgtgacccctatgtgatagatcactttctctgtgaagtccctgcactgctcaagttatcttgtgttgagacaacagcaaatga ggctgaactattccttgtcagtgagctcttccatctaatacccctgacactcatccttatatcatatgcttttattgtccgagcag 0 tattgaggatacagtctgctgaaggtcgacaaaaagcatttgggacatgtggttcccatctaattgtggtgtctcttttttatag tacagccgtctctgtgtacctgcaaccaccttcgcccagctccaaggaccaaggaaagatggtttctctcttctatggaatc attgcacccatgctgaatccccttatatatacacttaggaacaaggaggtaaaggaaggctttaaaaggttggttgcaaga cgttctttctgctcatccacc (SEQ ID NO: 51) 5 MOOSE06809 ctg4256 15356000..15356015, 15362637..15363562,

MGLGNESSLMDFILLGFSDHPRLEAVLFVFVLFFYLLTLVGNFTIΠISY

LDPPLHTPMYFFLSNLSLLDICFTTSLAPQTLVNLQPVPKKTITYGGCVAQLYI SLALGSTECILLADMALDRYIAVCKPLIJYVV3MNPRLCQQLASISWLSGLAS SL3IIATFTLQLPLCGNIJRLDHFICEVPALLI LACVDTTVNELVLFVVSVLFV 0 VIPPALISISYGFITQAVLR3KSVEAR3Ϊ3^AJ^?STCSS3JLTVV3IFYGTITYVYLQPS DSYAQDQGIO?ISLFYTlvrVTPTLNPI3YTLJ^NKDMKEALIlKLLSGKLISKQN (SEQ ID NO: 54) atgggattgggcaatgagagttccctaatggatttcatccttctaggcttctcagaccaccctcgtctggaggct gttctctttgtatttgtccttttcttctacctcctgacccttgtgggaaacttcaccataatcatcatctcatatctggatccccctc 5 ttcataccccaatgtacttttttctcagcaacctctctttactggacatctgcttcactactagccttgctcctcagaccttagtta acttgcaaagaccaaagaagacgatcacttacggtggttgtgtggcgcaactctatatttctctggcactgggctccactg aatgtatcctcttggctgacatggccttggatcggtacattgctgtctgcaaacccctccactatgtagtcatcatgaaccca cggctttgccaacagctggcatctatctcctggctcagtggtttggctagttccctaatccatgcaacttttaccttgcaattg cctctctgtggcaaccataggctggaccattttatttgcgaagtaccagctcttctcaagttggcttgtgtggacaccactgt 0 caatgaattggtgctttttgttgttagtgttctgtttgttgtcattccaccagcactcatctccatctcctatggcttcataactcaa gctgtgctgaggatcaaatcagtagaggcaaggcacaaagccttcagcacctgctcctcccaccttacagtggtgattat attctatggcaccataatctacgtgtacctgcaacctagtgacagctatgcccaggaccaagggaagtttatctccctcttct acaccatggtgacccccactttaaatcctatcatctatactttaaggaacaaggatatgaaagaggctctgaggaaacttct ctcgggaaaattgatctctaaacagaat (SEQ ID NO: 53) 5

MOOSE06813 ctgl3103 26845545..26846093, 26908345..26908738,

MGRNNLTI^SEFILLGLSS3^PEDQKPLFAVFLP3YLITVIGNLLIILAJRS DTRLQTPMYFFLSILSFVDICYVTVπPK-MLVNFLSETKTISYGECLTQMYFFL AFGNTDSYLLAAMATORYVAICNPFHYITIMSHRCCVLLLVLSFCIPHFHSLL 0 HILLTNQL3FCASNVIFiHFFCDDQPPVLKXSCSDTSSSQMVVMTETLAVIVTP FLCT3PSYLQI3NTVL3^IPSAAGKWKAFSTCGSHLTVVVLFYGSVIYNYFRPLS MΥSVMKGRVATVMYTVVTPMLNPFrϊ^'SLi KDMKRGLKKLRHI^FTJJRK N (SEQ ID NO: 56) atgggaagaaataacctaacaagaccctctgaattcatcctccttggactctcctctcgacctgaggatcagaa gccgctctttgctgtgttcctccccatctaccttatcacagtgataggaaacctgcttatcatcctggccatccgctcagaca ctcgtctccagacgcccatgtacttctttctaagcatcctgtcttttgttgacatttgctatgtgacagtcattatccctaagatg ctggtgaacttcttatcagagacaaagaccatctcttacggtgagtgtctgacccagatgtactttttcttagcctttggaaac acagacagttacctgctagcagccatggccattgaccgctatgtggccatatgtaatcccttccactacatcaccattatga gtcacagatgctgtgtcctgcttctggttctctccttctgcattccacattttcactccctcctgcacattcttctgactaatcagc tcatcttctgtgcctccaatgtcatccatcactttttctgcgatgatcaaccacctgtgctaaagctctcctgctctgacacatc ctccagccagatggtggtgatgactgagaccttagctgtcattgtgacccccttcctgtgtaccatcttctcctacctgcaaa tcatcgtcactgtgctcagaatcccctctgcagccgggaagtggaaggccttctctacctgtggctcccacctcactgtagt ggtcctgttctatgggagtgtcatctatgtctattttaggcctctgtccatgtactcagtgatgaagggccgggtagccacag ttatgtacacagtagtgacacccatgctgaaccctttcatctacagcctgaggaacaaagatatgaaaaggggtttgaaga aattaagacacagagaatttactcatagaaagaac (SEQ ID NO: 55)

MOOSE06815 ctgl3517 1607901..1607927, 1667204..1668118,

MTMENYSMAAQFVLDGLTQQAELQLPLFLLFLGIYWTVVGNLGMI LLIAVSPLLHTPMYYFLSSLSFVDFCYSSVITPKMLVNFLGKKNTILYSECMV QLFFFVWVVAEGYLLTAMAYDRYVAICSPLLYNAIMSSWVCSLLVLAAFF LGFLSALTHTSAMM3Π_JSFCKSHΠNIIYFCDVLPLLNLSCSNTHLNELLLFΠA GFNTLWTLAVAVSYAFILYSILH3RSSEGRSKAFGTCSSHLMAVVIFFGSITF MYFKPPSSNSLDQEKVSSVFYTTVIPMLNPLIYSL3 NΩDVKJ .L^VL3^RIIR QPSRW (SEQ ID NO: 58) atgaccatggaaaattattctatggcagctcagtttgtcttagatggtttaacacagcaagcagagctccagctg cccctcttcctcctgttcctgggaatctatgtggtcacagtagtgggcaacctgggcatgattctcctgattgcagtcagccc tctacttcacacccccatgtactatttcctcagcagcttgtccttcgtcgatttctgctattcctctgtcattactcccaaaatgct ggtgaacttcctaggaaagaagaatacaatcctttactctgagtgcatggtccagctctttttctttgtggtctttgtggtggct gagggttacctcctgactgccatggcatatgatcgctatgttgccatctgtagcccactgctttataatgcgatcatgtcctca tgggtctgctcactgctagtgctggctgccttcttcttgggctttctctctgccttgactcatacaagtgccatgatgaaactgt ccttttgcaaatcccacattatcaaccattacttctgtgatgttcttcccctcctcaatctctcctgctccaacacacacctcaat gagcttctactttttatcattgcggggtttaacaccttggtgcccaccctagctgttgctgtctcctatgccttcatcctctacag catccttcacatccgctcctcagagggccggtccaaagcttttggaacatgcagctctcatctcatggctgtggtgatcttct ttgggtccattaccttcatgtatttcaagcccccttcaagtaactccctggaccaggagaaggtgtcctctgtgttctacacc acggtgatccccatgctgaaccctttaatatacagtctgaggaataaggatgtgaagaaagcattaaggaaggtcttaagg aggaggagacagcctagcagatgg (SEQ ID NO: 57)

MOOSE06820 ctgl5944 3168536..3168548, 3217166..3218091, RGRNQTEVTEFLLLGLSDNPDLQGVLFALFLLIYMAJ^MVGNLGMΓV

L3KJDLCLHTPMYFFLSSLSFVDASYSSSVTPIOVJLVNLMAENKAISFHGCAA QFYFFGSFLGTECFLLAMMAYDRYAAΓWNPLLYPVLVSGRICFLLIATSFLA

GCGNAAfflTGMTFI^SFCGSNRII^ FYCDTPPLL3π_JSCSDTIJFNGlV3MAFSS FIVISCVM LISYLCIFIAVLKMPSLEGRHKAFSTCASYLMAVTIFFGTILFMY LRPTSSYSMEQDK SWYTVlT?VLNPLrcSLKNia)VK^ PN (SEQ ID NO: 60) cgaggcagaaatcaaacagaagtaacagaatttctcctcttaggactttccgacaatccagatctacaaggagt cctctttgcattgtttctgttgatctatatggcaaacatggtgggcaarttggggatgattgtattgattaagattgatctctgtct ccacacccccatgtatttctttctcagtagcctctcttttgtagatgcctcttactcttcttccgtcactcccaagatgctggtga acctcatggctgagaataaggccatttcttttcatggatgtgctgcccagttctacttctttggctccttcctggggactgagt gcttcctgttggccatgatggcatatgaccgctatgcagccatttggaaccccctgctctacccagttctcgtgtctgggag aatttgctttttgctaatagctacctccttcttagcaggttgtggaaatgcagccatacatacagggatgacttttaggttgtcc ttttgtggttctaataggatcaaccatttctactgtgacaccccgccactgctcaaactctcttgctctgatacccacttcaatg gcattgtgatcatggcattctcaagttttattgtcatcagctgtgttatgattgtcctcatttcctacctgtgtatcttcattgccgt cttgaagatgccttcgttagagggcaggcacaaagccttctccacctgtgcctcttacctcatggctgtcaccatattctttg gaacaatcctcttcatgtacttgcgccctacatctagctactcaatggagcaagacaaggttgtctctgtcttttatacagtaa taatccctgtgctaaatcccctcatctatagtttaaaaaataaggatgtaaaaaaggccctaaagaagatcttatggaaaca catcttgcacagcccaaat (SEQ ID NO: 59) MOOSE06827 ctgl3103 26933654..26934554, 26941304..26941347,

MEIKNYSSSTSGFILLGLSSNPQLQKPLFAIFLIMYLLAAVGNVLΠPAI

YSDPI^HTPMYFFLSNLSFMDICFTTVΓV KMLVNFLSETKVISYVGCLAQM

YFFMAFGNTDSYLLASMA3DRLVAICNPLHYDVVIVKP3 CLLMLLGSCSIS

HLHSLFRVLLMSRLSFCASH3I3ΠIFFCDTQPVLIΑ,SCSDTSSSQMVVMTETLA VWTPFLCIJFSYLI IVTVLRIPSAAGKWKAFSTCGSHLTAVALFYGSIIYVY

F: PLSϊvreSVVrøRVATVMYT TPI\tfLNPFIYSLRN^ EHSP (SEQ ID NO: 62) atggagataaagaactacagcagcagcacctcaggcttcatcctcctgggcctctcttccaaccctcagctgc agaaacctctctttgccatcttcctcatcatgtacctgctcgctgcggtggggaatgtgctcatcatcccggccatctactct gaccccaggctccacacccctatgtacttttttctcagcaacttgtctttcatggatatctgcttcacaacagtcatagtgccta agatgctggtgaattttctatcagagacaaaggttatctcctatgtgggctgcctggcccagatgtacttctttatggcatttg ggaacactgacagctacctgctggcctctatggccatcgaccggctggtggccatctgcaaccccttacactatgatgtg gttatgaaaccacggcattgcctgctcatgctattgggttcttgcagcatctcccacctacattccctgttccgcgtgctactt atgtctcgcttgtctttctgtgcctctcacatcattaagcactttttctgtgacacccagcctgtgctaaagctctcctgctctga cacatcctccagccagatggtggtgatgactgagaccttagctgtcattgtgacccccttcctgtgtatcatcttctcctacct gcgaatcatggtcactgtgctcagaatcccctctgcagccgggaagtggaaggccttctctacctgtggctcccacctca ctgcagtagcccttttctatgggagtattatttatgtctattttaggcccctgtccatgtactcagtggttagggaccgggtagc cacagttatgtacacagtagtgacacccatgctgaaccctttcatctacagcctgaggaacaaagatatgaagagggaga tcaagaagaaactctcaaaacgaacaaaggaacactccccc (SEQ ID NO: 61)

MOOSE06828 ctgl4877 4363377..4363409, 4364445..4365350,

MKRKNFTEVSEFJFLGFSSFGKHQITLFVVFLTVYILTLVANTΠVTΠCI DIJHLHTPMYFFLSMLASSETVYTLVIWPMLLSLIFHNQPISLAGCATQMFFF

VILATNNCFLLTAMGYDRYVAICRPLRYTVIMSKGLCAQLVCGSFGIGLTM AVLIJVTAMFNLPFCGTVVDHFFCDr PVMKLSCIDTTINEJJNYGVS SFVTFVP

IGLIFISYVLVISSTLQIASAEGRKKTFATCVSHLTVVIVHCGCASIAYLKPKSE SSffiKDLVLSVTYTIITPLLNPVVYSLRNKEVKDALCRVLSKRHRYGNJ (SEQ ID NO: 64) atgaagagaaagaacttcacagaagtgtcagaattcattttcttgggattttctagctttggaaagcatcagataa ccctctftgtggttttcctaactgtctacattttaactctggttgctaacatcatcattgtgactatcatctgcattgaccatcatct ccacactcccatgtatttcttcctaagcatgctggctagttcagagacggtgtacacactggtcattgtgccacgaatgctttt gagcctcatttttcataaccaacctatctccttggcaggctgtgctacacaaatgttcttttttgttatcttggccactaataattg cttcctgcttactgcaatggggtatgaccgctatgtggccatctgcagacccctgagatacactgtcatcatgagcaaggg actatgtgcccagctggtgtgtgggtcctttggcattggtctgactatggcagttctccatgtgacagccatgttcaatttgcc gttctgtggcacagtggtagaccacttcttttgtgacatttacccagtcatgaaactttcttgcattgataccactatcaatgag ataataaattatggtgtaagttcatttgtgatttttgtgcccataggcctgatatttatctcctatgtccttgtcatctcttccatcct tcaaattgcctcagctgagggccggaagaagacctttgccacctgtgtctcccacctcactgtggttattgtccactgtggc tgtgcctccattgcctacctcaagccgaagtcagaaagttcaatagaaaaagaccttgttctctcagtgacgtacaccatca tcactcccttgctgaaccctgttgtttacagtctgagaaacaaggaggtaaaggatgccctatgcagagtactttctaagag acacaggtatggaaacatc (SEQ ID NO: 63) MOOSE06832 ctgl3517 2024387..2025309, 2050457..2050472,

MAAGNHSTVTEFILKGLTKRADLQLPLFLLFLGIYLVTIVGNLGMITLI CLNSQLHTPMYYFLSNLSLMDLCYSSVITPKMLVNFVSEKNΠSYAGCMSQL YFFLWVLABCYMLTVMAYDRYVAICIJPLLYNIIMSHHTCLLLVAVVYAIGL IGSTIETGLMLKLPYCEHLISHYFCDILPLMKLSCSSTYDVEMTVFFSAGFNΠ VTSLTVLVSYTFILSSILGISTTEGRSKAFSTCSSHLAAVGMFYGSTAFMYLK PSTISSLTQENVASVFYTTVIPMLNPLIΎSLRNKEVKAAVQKTLRGKLSPHSW

(SEQ ID NO: 66) atggctgcaggaaatcactctacagtgacagagttcattctcaagggtttaacgaagagagcagacctccagc tccccctctttctcctcttcctcgggatctacttggtcaccatcgtggggaacctgggcatgatcactctaatttgtctgaactc tcagctgcacacccccatgtactactttctcagcaatctgtcactcatggatctctgctactcctccgtcattacccctaagat gctggtgaactttgtgtcagagaaaaacatcatctcctacgcagggtgcatgtcacagctctacttcttccttgtttttgtcatt gctgagtgttacatgctgacagtgatggcctacgaccgctatgttgccatctgccaccctttgctttacaacatcattatgtct catcacacctgcctgctgctggtggctgtggtctacgccatcggactcattggctccacaatagaaactggcctcatgttaa aactgccctattgtgagcacctcatcagtcactacttctgtgacatcctccctctcatgaagctgtcctgctctagcacctatg atgttgagatgacagtcttcttttcggctggattcaacatcatagtcacgagcttaacagttcttgtttcttacaccttcattctct ccagcatcctcggcatcagcaccacagaggggagatccaaagccttcagcacctgcagctcccaccttgcagccgtgg gaatgttctatggatcaactgcattcatgtacttaaaaccctccacaatcagttccttgacccaggagaatgtggcctctgtg ttctacaccacggtaatccccatgttgaatcccctaatctacagcctgaggaacaaggaagtaaaggctgccgtgcagaa aacgctgaggggtaaactgagcccgcattcctgg (SEQ ID NO: 65)

MOOSE06837 ctgl5944 5082071..5082579, 5123054..5123489,

MENNTEVSEFILLGLTNAPELQVPLF3MFTLIYLITLTGNLGM3ILILLD SHLHTPMYFFLSNLSLAGIGYSSAVTPKVLTGLLIED3 S YSACAAQMFFCA

VFATVENYLLSSMAYDRYAAVCNPLHYTTTMTTRVCACLAIGFTGSYICGL FQSSIHVAFTFHLSFCHSNVVNHFFCD3PPLLAXSCSDIYAHEIVLFILAAFNIF FTLLIJLNSYVF]F3AJLR]ymSAEGQKKVFSTCAYHLTTVS3FYGTITFMYLQPS SGHSMDTDKISSVFYTMV3PMLNPLVYSLPvNI EVQSAFKVVIGKAKSSLGL (SEQ ID NO: 68) atggagaataatacagaggtgagtgaattcatcctgcttggtctaaccaatgccccagaactacaggttcccct ctttatcatgtttaccctcatctacctcatcactctgactgggaacctggggatgatcatattaatcctgctggactctcatctc cacactcccatgtacttttttctcagtaacctgtctcttgcaggcattggttactcctcagctgtcactccaaaggttttaactgg gttgcttatagaagacaaagccatctcctacagtgcctgtgctgctcagatgttcttttgtgcagtctttgccactgtggaaaa ttacctcttgtcctcaatggcctatgaccgctacgcagcagtgtgtaaccccctacattataccaccaccatgacaacacgt gtgtgtgcttgtctggctataggcttcactggctcctacatctgtggactctttcaatcctccatccatgttgcttttactttccat ctctccttctgtcattctaatgtggttaatcactlfrutgtgatattccaccactcttagctctttcttgctctgatatttacgcacat gagattgtgctcttcatattggcagcatttaatatcttlttcactctcttga gaggatgcattcagctgagggacaaaagaaggtcttttccacctgtgcctatcacctcactactgtttccatcttctatggga caatcacctttatgtacttacagccaagttctggtcattccatggacacagacaaaatctcatctgtgttctacaccatggtca tccccatgcttaaccctctagtctatagcctgaggaacaaagaagtccagagtgcattcaaggtggttattggaaaagcaa agtcttcattgggctta (SEQ ID NO: 67)

MOOSE06838 ctgl5944 6676490..6676496, 6679052..6679971, 6713800..6713814,

MESWNSSSVTMFILLGFTDHPELQALLFVTFLGIYLTTLAWNLALIFLI RGDTHLHTPIVlYFFLSNLSFroiCYSSAVAPNMLTDFFWEQKTISFVGCAAQF FFFVGMGLSECLLLTAMAYDRYAAISSPLLYPT TQGLCT3RMVVGAYVGG FLSSLIQASSIFRLIJFCGPlNαTNHFFCDLPPVLALSCSDTFLSQVVNFLVVVTV GGTSFLQLLISYGYIVSAVL3πPSAEGRWI ACNTCASIJLMVVTLLFGTALFV YL3y^>SSSYLLGRDKVVS YSLVIPMLl^L3YSLRNKEiKDAUWKVLE3iKKIP SPW (SEQ ID NO: 70) atggaatcctggaacagctcatcagtgaccatgttcatcctcctgggattcacagaccatccagaactccagg ccctcctctttgtgaccttcctgggcatctatcttaccaccctggcctggaacctggccctcatttttctgatcagaggtgaca cccatctgcacacacccatgtacttcttcctaagcaacttatctttcattgacatctgctactcttctgctgtggctcccaatatg ctcactgacttcttctgggagcagaagaccatatcatttgtgggctgtgctgctcagttttttttctttgtcggcatgggtctgtc tgagtgcctcctcctgactgctatggcatacgaccgatatgcagccatctccagcccccttctctaccccactatcatgacc cagggcctctgtacacgcatggtggttggggcatatgttggtggcttcctgagctccctgatccaggccagctccatattta ggcttcacttttgcggacccaacatcatcaaccacttcttctgcgacctcccaccagtcctggctctgtcttgctctgacacc ttcctcagtcaagtggtgaatttcctcgtggtggtcactgtcggaggaacatcgttcctccaactccttatctcctatggttac atagtgtctgcggtcctgaagatcccttcagcagagggccgatggaaagcctgcaacacgtgtgcctcgcatctgatggt ggtgactctgctgtttgggacagcccttttcgtgtacttgcgacccagctccagctacttgctaggcagggacaaggtggt gtctgttttctattcattggtgatccccatgctgaaccctctcatttacagtttgaggaacaaagagatcaaggatgccctgtg gaaggtgttggaaaggaagaaaattccttcaccctgg (SEQ ID NO: 69)

MOOSE06839 ctg4256 15048207..15049148,

MDGTNGSTQTHFILLGFSDRPHLERILFVVILIAYLLTLVGNTTΠLVSR LDPHLHTPMYFFLAHLSFLDLSFTTSSFFQLLYNLNGCDKTISYMGCALQLFL FLGLGGVECLLLAVMAYDRCVAICKPLHYMVIMNPRLCRGLVSVTWGCGV ANSLAMSPVTLRLPRCGHHEVDHFLMMPALIRMACVSTVAIEGTVFVLKK GVVLSPLWILLSYSYIVRAVLQIRSASGRQKAFGTCGSHLTVVSLFYGNJJY MYMQPGASSSQDQGMFLMLFYNWTPLLNPLIYTL3^NREVKGALGRLLLGK RELGKE (SEQ ID NO: 72) atggatggaaccaatggcagcacccaaacccatttcatcctactgggattctctgaccgaccccatctggaga ggatcctctttgtggtcatcctgatcgcgtacctcctgaccctcgtaggcaacaccaccatcatcctggtgtcccggctgga cccccacctccacacccccatgtacttcttcctcgcccacctttccttcctggacctcagtttcaccaccagctccatccccc agctgctctacaaccttaatggatgtgacaagaccatcagctacatgggctgtgccatccagctcttcctgttcctgggtct gggtggtgtggagtgcctgcttctggctgtcatggcctatgaccggtgtgtggctatctgcaagcccctgcactacatggt gatcatgaaccccaggctctgccggggcttggtgtcagtgacctggggctgtggggtggccaactccttggccatgtctc ctgtgaccctgcgcttaccccgctgtgggcaccacgaggtggaccacttcctgcgtgagatgcccgccctgatccggat ggcctgcgtcagcactgtggccatcgaaggcaccgtctttgtcctgaaaaaaggtgttgtgctgtcccccttggtgtttatc ctgctctcttacagctacattgtgagggctgtgttacaaattcggtcagcatcaggaaggcagaaggccttcggcacctgc ggctcccatctcactgtggtctcccttttctatggaaacatcatctacatgtacatgcagccaggagccagttcttcccagga ccagggcatgttcctcatgctcttctacaacattgtcacccccctcctcaatcctctcatctacaccctc'agaaacagagag gtgaagggggcactgggaaggttgcttctggggaagagagagctaggaaaggag (SEQ ID NO: 71)

MOOSE06841 ctgl59442976120..2976989, 3039328..3039399,

MSRRNYTELTEFVLLGLTSIiPELIlAPCFGVFLVIYLVTVLGNLGLITLI KIDT3n.HTPMYYFLSHLAFVDLCYSSAJTP3asJMVNFVVE3 NTIPFHACATQL GCFLTFMITECFLLASMAYDCYVAICSPLHYSTLMSRRVCIQLVAVPYIYSFL

VALFHTVITF3^TYCGPNL3NTJFYCDDLPFLALSCSDT33MKEIL3FAFAGFDM ISSSS3VLTSYJFIIAAILRmSTQGQIJ3^^STCGSHMVTVTIFYGTLIFMYLQPK SNHSLDTDKMAS YTVVIPMLNPLrYSL3 NIffiVKDASKKALDKGCENLQI (SEQ ID NO: 74) atgtccagaagaaactatactgaactgacagaatttgttctcttgggtctaacaagccgtccagagctgcgagc cccgtgctttggggtgtttttagttatctatctggtcacagtgctgggcaatcttgggttgattactttaatcaagattgatactc gactccacacacctatgtactatttcctcagccacctggcctttgttgacctttgttactcctctgctattacaccgaagatgat ggtgaattttgttgtggaacgcaacaccattcctttccatgcttgtgcaacccaactgggttgttttctcaccttcatgatcact gagtgtttccttctagcctccatggcctacgattgctatgtcgccatctgtagtcccctgcattattcaacactgatgtcaaga agagtctgcattcaactggtggcagttccatatatatacagcttcctggttgccctcttccacaccgttatcactttccgtctga cttactgtggcccaaacttaattaaccatttctattgtgatgacctccccttcttagctctgtcctgctcagacacacacatgaa ggaaattctgatatttgcctttgctggctttgatatgatctcttcctcttccattgtcctcacctcctacatctttattattgccgcta tcctaaggatccgctctactcaggggcaacacaaagccatttccacctgtggctcccatatggtgactgtcactattttctat ggcacactgatctttatgtacctacagcccaaatcaaatcactccttggacacagacaagatggcttctgtattttacacagt ggtgatccccatgttaaaccccctaatctatagtctaaggaacaaagaagtgaaagatgcctcaaagaaagccttggata aaggttgtgaaaacttacagata (SEQ ID NO: 73)

MOOSE06843 ctgl3517 1713448..1713473, 1723011..1723498,

1781840..1782270, MTLRNSSSVTEF3LVGLSEQPELQLPLFLLFLGIYVFTWGNLGLITLIG

INPSLHTPMYFFLFNLSFIDLCYSCVFTPI MLNDFVSESIISYVGCMTQLFFFC FFVNSECYVLVSMAYDRYVAICNPLLYMVTMSPRVCFLLILMFGSYLMAFS GAMAHTGCML3^TFCDANT3DITYFCDILPLLQLSCTSTYINELVVFTVVGINI ΓV TVTIFISYGFILSSILHISSKΈGRSKAFSTCSSHIJAVSLFFGSGAFMYLNPSS AGSMDKI^ SSVFYTNVWMLNPLIΎSLRNKDVKFALRKALRRR

(SEQ ID NO: 76) atgactctgagaaacagctcctcagtgactgagtttatccttgtgggattatcagaacagccagagctccagct ccctcttttccttctattcttagggatctatgtgttcactgtggtgggcaacttgggcttgatcaccttaattgggataaatccta gccttcacacccccatgtactttttcctcttcaacttgtcctttatagatctctgttattcctgtgtgtttacccccaaaatgctgaa tgactttgtttcagaaagtatcatctcttatgtgggatgtatgactcagctatt^ gttggtatcaatggcctatgatcgctatgtggccatctgcaaccccctgctctacatggtcaccatgtccccaagggtctgc tttctgctgatccttatgtttggttcctatttgatggccttttctggtgccatggcccacactggatgcatgctgagactgacttt ctgtgatgcgaacaccatcgatcactacttctgtgacatcctccctctgctccagctctcctgcaccagcacctacatcaat gagctggtggttttcactgtggttggcatcaacatcattgtgcccactgttaccatctttatctcttatggtttcatcctctccag catcctccatatcagttccaaggagggcaggtccaaagctttcagcacttgcagttcccatataattgctgtttctctgttcttt ggatcaggtgcatttatgtatctcaacccatcttctgctgggtccatggataagagaaaattatcttctgtcttttatacaaatgt ggttcccatgttgaaccccttaatctacagcctgaggaacaaagatgttaaatttgccctaagaaaagccctgagacgaag gcataagttatctgatatt (SEQ ID NO: 75) MOOSE06844 ctgl5907 32272575..32273514,

MWINNQSSLDDFILLGFSDRPWLETPLSVIFLVAYΓFSLFGNISIILVSH LDPQLDSPMYFFVSNLSFLDLCYTTSTVPQMLVNLRGPEKTISYGGCVAQLY MLALGSTECILLALMAFDRYAAICIΑ^>LHΫPV3 NIJRRCIHMAAGTWISGFAN

SLVQSTLTVVAPRCGQRVLDHFFCEVPALLI XACIDIRVNEMELNVLGALLL LMPLTLILGTYVFIAQAVMRICS AESRWKAFNTCASHLLVVSLFYFTAISMY VQPPSSYSIJDRGKIMALFYGWTPTLNPFIYTLRNEDVKAALRRSLTKEFWTK TR (SEQ ID NO: 78) atgtggatcaacaatcaaagctcgctagatgattttatcctattgggattttctgaccgtccctggctagagacac ccctctctgtaatctttctggtggcctacatcttttccctatttggaaatatctccattatcctagtttcccatctggatccccagc ttgacagtcccatgtacttttttgtctctaatctatcctttctggacctctgctataccaccagcactgtcccacagatgctggtc aacctccggggaccagaaaagaccattagctatgggggttgtgttgcccaactctatatatttttggccctgggttctactg aatgcatacttctagccatcatggcctttgaccgttacgctgccatatgcaagccccttcactacccagtcatcatgaaccat agacgctgtatccacatggctgctggcacttggatcagtggctttgctaactcccttgtccagtccactctcacagtggtgg ccccaagatgtggacagagggtgttggaccatttcttctgtgaagttccagcccttttgaaactagcctgtattgatattcgtg tgaatgaaatggagctcaatgtactaggcgctttgcttctcctgatgccactcaccctcatcctgggcacttatgtgttcattg ctcaggcagtaatgagaatctgctctgctgaaagtcgctggaaggctttcaatacctgtgcctcacatttgctggtggtctc cctcttctacttcacagccatcagtatgtatgtccagcctccctctagctattctcatgaccgggggaagatcatggctctctt ttatggcattgtcacacccaccctcaacccattcatctacacattgagaaacaaggatgtgaaagctgccctgagaaggtc actgactaaagagttttggattaagacaaga (SEQ ID NO: 77) MOOSE06845 ctgl59442844959..2844965, 2848633..2849564,

MGIIRNNTNVPDFILTGLSDSEEVQMALFILFLLIYLITMLGNVGMILΠ RLDLQLHTPMYFFLTHLSF3DLSYSTVITPKTLANLLTSNYISFMGCFAQMFF

FVFLGAAECFLLSSMAYDRYVAICSPLRYPVIMSI RLCCALVTGPYVISFINS FVNVVWMSI LHFCDSNNV3 FFCDTSPILALSCMDTYDm3 fflILAGSTLM VSLITISASYVS3XSTIL30NSTSGKQKALSTCASHLLGVTIFYGTMIFTYLKPR KSYSLGI^QVAS YTIVIPMLNPLIYSLRNKEVKNALrRVMQRRQDSSQW (SEQ ID NO: 80) atgggtagaagaaataacacaaatgtgcctgacttcatccttacgggactgtcagattctgaagaggtccagat ggccctctttatactatttctcctgatatacctaattactatgctgggcaatgtggggatgatattgataatccgcctggacctc cagcttcacactcccatgtattttttccttactcacttgtcatttattgacctcagttactcaactgtcatcacacctaaaacctta gcgaacttactgacttccaactatatttccttcatgggctgctttgcccagatgttcttttttgtcttcttgggagctgctgaatgt tttcttctctcatcaatggcctatgatcgctacgtagctatctgcagtcctctacgttacccagttattatgtccaaaaggctgt gttgcgctcttgtcactgggccctatgtgattagctttatcaactcctttgtcaatgtggtttggatgagcagactgcatttctg cgactcaaatgtagttcgtcacthttctgcgacacgtctccaattttagctctgtcctgcatggacacatacgacattgaaat catgatacacattttagctggttccaccctgatggtgtcccttatcacaatatctgcatcctatgtgtccattctctctaccatcc tgaaaattaattccacttcaggaaagcagaaagctttgtctacttgtgcctctcatctcttgggagtcaccatcttttatggaac tatgatttttacttatttaaaaccaagaaagtcttattctttgggaagggatcaagtggcttctgttttfratacta atgctgaatccactcatttatagtcttagaaacaaagaagttaaaaatgctctcattagagtcatgcagagaagacaggact ccagtcagtgg (SEQ ID NO: 79)

MOOSE06848 ctgl5944 3080567..3080584, 3085575..3085701,

3152600..3153396,

MLSPNHTIVTEFILLGLTDDPVLEKILFGVFLAIYLITLAGNLCMILLIR TNSQLQTPMYFFLGHLSFVDICYSSNVTPNML3TNFLSEQKTISYAGCFTQCL

LF3ALVITEFYFLASMALDRYVAICSPLIJYSSRMS3ζNICISLVTVPYMYGFLN GLSQTLLTFHLSFCGSLEINHFYCADPPLMLACSDTRV3ααVIAMFVVAGFTL SSSLFJJLLSYLFIFAAIFRIRSAEGRIJIAFSTCASTJLTWTLFYGTLFCIV1YVRPP SEKSVEQSKVJAVFYTFVSPMLNPIJYSLRNKDVKQAFWKLIRRNQICFLW (SEQ ID NO: 82) atgttgtccccaaaccacaccatagtgacagaattcattctcttaggactgacagacgacccagtgctagagaa gatcctgtttggggtgttcctggcgatctacctaatcacactggcaggcaacctgtgcatgatcctgctgatcaggaccaat tcccaactgcaaacacccatgtatttcttccttggtcacctctcctttgtagacatttgctattcttccaatgttactccaaatatg ctgcacaatttcctctcagaacagaagaccatctcctacgctggatgcttcacacagtgtcttctcttcatcgccctagtgat cactgagttttacttccttgcttcaatggcattggatcgctatgtagccatttgcagccctttacattacagttccaggatgtcc aagaacatttgcatctctctggtcactgtgccttacatgtatggcttccttaatgggctctctcagacactgctgacctttcact tatccttctgtggctcccttgaaatcaatcatttctactgcgctgatcctcctcttatcatgctggcctgctctgacacccgtgtc aaaaagatggcaatgtttgtagttgcaggclfractctctcaagctctctcttcatcattcttctgtcctatcttttcatttttgcag cgatcttcaggatccgttctgctgaaggcaggcacaaagccttttctacgtgtgcttcccacctgacaatagtcactttgtttt atggaaccctcttctgcatgtacgtaaggcctccatcagagaagtcagtggaacagtccaaagtcattgctgttttctacact tttgtaagccctatgttgaaccccatcatctatagtttgaggaacaaggatgtgaaacaagctttttggaaactgatcagaag aaaccagatttgttttctctgg (SEQ ID NO: 81)

MOOSE06850 ctgl8037 4716900..4717012, 4725887..4726711, 4748336..4748345,

MGGNQTSITEFLLLGFPIGPRIQMLLFGLFSLFYTPILLTLMGNGIILGLI YLDS3^HTPMYVFLSHLAIVDMSYASSTW3ΩV[LA1^VMHKKVISFAPCILQ TFLYLAFAITECLILVMMCYDRYVAICHPLQYTLIMNWRVCTVLASTCWIFS FLLALVHITLTDRLPFCGPQKJNIΪFFCQJMSVFKLACADTIILNQVVLFAGSAFI LVGPLCLVLVSYLHILVAILMQSGEG3 3^KAFSTCSSIJLCVVGLFFGSAIVMY IvlAPKSSHSQERRKLSLFYSLFl^ILNPLIYSLIWAEVKGALE lVLWKQRSIS YW (SEQ ID NO: 84) atggggggaaatcagacttccatcacagagttcctcctactgggatttcccattggcccaaggattcagatgct cctctttgggctcttctccctgttctacatcttcattctcttaaccctgatgggaaatgggattatcctggggctcatctacttgg actctagactgcacacacccatgtatgtcttcctgtcacacctggccattgtggacatgtcctatgcctcgagtactgtccct aagatgctagcaaatcttgtgatgcacaaaaaagtcatctcctttgctccttgcatacttcagacttttttgtatttggcgtttgct attacagagtgtctgattttggtgatgatgtgctatgatcggtatgtggcaatctgtcaccccttgcaatacaccctcattatga actggagagtgtgcactgtcctggcctcaacttgctggatatttagctttctcttggctctggtccatattactcttattctgagg ctgcctttttgtggcccacaaaagatcaaccactttttctgtcaaatcatgtccgtattcaaattggcctgtgctgacactagg ctcaaccaggtggtcctatttgcgggttctgcgttcatcttagtggggccgctctgcctggtgctggtctcctacttgcacat cctggtggccatcttgaggatccagtctggggagggccgcagaaaggccttctctacctgctcctcccacctctgcgtgg tggggcttttctttggcagcgccattgtcatgtacatggcccccaagtcaagccattctcaagaacggaggaagatcctttc cctgttttacagccttttcaacccgatcctgaaccccctcatctacagccttaggaatgcagaggtgaaaggggctctaaa gagagtcctttggaaacagagatcaataagttattgg (SEQ ID NO: 83)

MOOSE06860 ctgl5944 2680355..2680361, 2682467..2683101,

2712158..2712469,

MAGNNFTEVTVFILSGFANHPELQVSLFLMFLFIYLFTVLGNLGLITLI RMDSQLHTPMYFFLSNLAFmiFYSSTVTPI ALVl^QSNRRSISFVGCFVQMY FFMFCFVTLGTAECYLLSSMAYDRYAAICSPLFIYTVIMPKRLCLALITGPYVI

GFMDSFVNVVSMSRLIJFCDSNimHFFCDTSPILALSCTDTDNTEMLIFIIAGS TLMVSLITISASYVSILSTILKJNSTSGKQKAFSTCVSHLLGVTIFYGTMIFTYL KPRKSYSLGRDQVAP YTJVIPMLNPLIYSLRNREVKNALIRVMQRRQDSR KW (SEQ ID NO: 86) atggctggcaacaatttcactgaggttaccgtcttcatcctctctggatttgcaaatcaccctgaattacaagtca gtcttttcttgatgtttctcttcatttatctattcactgttttgggaaacctgggactgatcacgttaatcagaatggattctcagct tcacacccctatgtactttttcctgagcaatttagcatttattgacatattttactcctctactgtaacacctaaggcattggtgaa tttccaatccaatcggagatccatctcctttgttggctgctttgttcaaatgtacttttttatgttctgttttgtcttcttgggtactgc tgaatgttatcttctctcctcaatggcctatgatcgctatgcagcgatctgcagtcctctacactacacagttattatgcccaaa aggctctgcctcgctctcatcactgggccttatgtgattggctttatggactcctttgtcaatgtggtttccatgagcagattgc atttctgtgactcaaacataattcatcactttttctgtgacacttccccaattttagctctgtcctgcactgacacagacaacact gaaatgctgatattcattatcgctggttccaccctgatggtgtcccttatcacaatatctgcatcctatgtgtccattctctctac catcctgaaaattaattccacttcaggaaagcagaaagctttctctacttgcgtctctcatctcttgggagtcaccatcttctat ggaactatgatttttacttacttaaagccaagaaagtcttattccttgggaagagatcaagtggctcctgtgttttatactattgt gattcccatgctgaatccactcatttatagtcttagaaacagagaagtgaaaaatgctctcattagagtcatgcagagaaga caggactccagaaaatgg (SEQ ID NO: 85)

MOOSE06861 ctgl3517 1596125..1597057,

MAAENHSFVTKFJLVGLTEKSELQLPLFLVFLGIYVVTVLGNLGMITL IGLSSJJLHTPMYCFLSSLSFJDFCHSTVITPKMLVNFVTEKNΠSYPECMTQLY

FFLVFAJAECFfMLAAMAYDGYVAICSPLLYSiπSNKACFSLILVVYVIGLICA SAHIGCMFRVQFCKFDVINir FCDLISIUiaSCSSTYINELLILIFSGINILVPSL TILSSYJEπASILJilRYTEGRSKAFSTCSSHISAVSVFFGSAAFMYLQPSSVSSM DQGKVSSWYT WMLNPL3YSL3 .ΩDVHVAL3aKTLGKRTFL (SEQ D3 NO: 88) atggcagcagaaaaccattcttttgtgactaagtttattctggttgggctaacagagaagtcagagctacagctg cccctcttcctcgtcttcctgggaatctatgtagtcacagtgctggggaacctgggcatgatcacactgattgggctcagtt ctcacctgcacacacctatgtactgtttcctcagcagtctgtccttcattgacttctgccattccactgtcattacccctaagat gctggtgaactttgtgacagagaagaacatcatctcctaccctgaatgcatgactcagctctacttcttcctcgtttttgctatt gcagagtgtcacatgttggctgcaatggcatatgacggctacgtggccatctgtagccccttgctgtacagcatcatcatat ccaataaggcttgcttttctctgattttagtggtgtatgtaataggcctgatttgtgcgtcagctcatataggctgtatgtttagg gttcaattctgcaaatttgatgtgatcaaccattatttctgtgatcttatttctatcttgaagctctcctgttctagtacttacatta gagttactgattttaatctttagtggaattaacatccttgtccccagcctgaccatcctcagctcttacatcttcatcattgccag catcctccgcattcgctacactgagggcaggtccaaagccttcagcacttgcagctcccacatctcggctgtttctgttttct ttgggtctgcagcattcatgtacctgcagccatcatctgtcagctccatggaccaggggaaagtgtcctctgtgttttatact attgttgtgcccatgctgaaccccctgatctacagcctgaggaataaagatgtccacgttgccctgaagaaaacgctagg gaaaagaacattctta (SEQ ID NO: 87)

MOOSE06863 ctgl3517 1850676..1851026, 1878547..1879134, MTLRNSSSVTEFILVGLSEQPELQLPLFLLFLGIYVFTWGNLGLITLIG

INPSLHTPMYFFLFNLSF3DLCYSCVFTPKMLNDFVSESIISYVGCMTQLFFFC FFVNSECYVLVSMAYDRYVAICNPLLYMVTMSPRVCFLLMFGSYVVGFAG AMAHTGSMLRLTFCDSNV3DHYLCDVLPLLQLSCTSTHVSELVVVL3VVG3N 3 WSCT3LISYW3YTSILHIKSTQGRSKAFSTCSSHVIALSLFFGSAAFMYRKY SSGSMEQGKVSS YTNVWMLISPLΓY LRNIΦVKVA^

(SEQ ID NO: 90) atgactctgagaaacagctcctcagtgactgagtttatccttgtgggattatcagaacagccagagctccagct ccctcttttccttctattcttagggatctatgtgttcactgtggtgggcaacttgggcttgatcaccttaattgggataaatccta gccttcacacccccatgtactttttcctcttcaacttgtcctttatagatctctgttattcctgtgtgtttacccccaaaatgctgaa tgactttgtttcagaaagtatcatctcttatgtgggatgtatgactcagctatttttcttctgtttcttt gttggtatcaatggcctatgatcgctatgtggccatctgcaaccccctgctctacatggtcaccatgtccccaagggtctgc tttctgctgatgtttggttcctatgtggtagggtttgctggggccatggcccacactggaagcatgctgcgactgaccttctg tgattccaacgtcattgaccattatctgtgtgacgttctccccctcttgcagctctcctgcaccagcacccatgtcagtgagct ggtggttgttctcattgttgtgggtattaatatcatggtacccagttgtaccatcctcatttcttatgttttcattgtcactagcattc ttcatatcaaatccactcaaggaagatcaaaagccttcagtacttgtagctctcatgtcattgctctgtctctgttttttgggtca gcggcattcatgtatattaaatattcttctggatctatggagcagggaaaagtttcttctgttttctacactaatgtggtgcccat gctcaatcctctcatctacagtttgaggaacaaggatgtcaaagttgcactgaggaaagctctgattaaaattcagagaag aaatatattc (SEQ TD NO: 89) MOOSE06866 ctgl5944 2354182..2355090, 2359348..2359383,

MGKENCTTVAEFILLGLSDVPELRVCLFLLFLLIYGVTLLANLGMJAL IQVSSRLHTPIvEYFFLSHLSSVDFCYSSIIWiαiLANJEMΦKAISFLGCMVQF YLFCTCWTEVFLLAVMAYDRFVAICNPLLYTVTMSWKVRVELASCCYFC

GTVCSLIHLCLALIΠPFYRSNVINHFFCDLPPVLSLACSDITVNETLLFLVATL NESVTMIILTSYLLILTTILKMGSAEGRHKAFSTCASHLTAITVFHGTVLSIYC RPSSGNSGDADKVAT YTVVJPMLNSVIYSLRNIΦVKEALRKCVVWRKRI MSSK (SEQ ID NO: 92) atgggcaaggaaaactgcaccactgtggctgagttcattctccttggactatcagatgtccctgagttgagagt ctgcctcttcctgctgttccttctcatctatggagtcacgttgttagccaacctgggcatgattgcactgattcaggtcagctct cggctccacacccccatgtactttttcctcagccacttgtcctctgtagatttctgctactcctcaataattgtgccaaaaatgtt ggctaatatctttaacaaggacaaagccatctccttcctagggtgcatggtgcaattctacttgttttgcacttgtgtggtcact gaggtcttcctgctggccgtgatggcctatgaccgctttgtggccatctgtaaccctttgctatacacagtcaccatgtcttg gaaggtgcgtgtggagctggcttcttgctgctacttctg gggacggtgtgttctctgattcatttgtgcttagctcttaggatc cccttctatagatctaatgtgattaaccactttttctgtgatctacctcctgtcttaagtcttgcttgctctgatatcactgtgaatg agacactgctgttcctggtggccactttgaatgagagtgttaccatcatgatcatcctcacctcctacctgctaattctcacca ccatcctgaagatgggctctgcagagggcaggcacaaagccttctccacctgtgcttcccacctcacagctatcactgtct tccatggaacagtcctttccatttattgcaggcccagttcaggcaatagtggagatgctgacaaagtggccaccgtgttcta cacagtcgtgattcctatgctgaactctgtgatctacagcctgagaaataaagatgtgaaagaagctctcagaaaatgtgtg gtgtggaggaagaggattatgtccagcaaa (SEQ ID NO: 91) MOOSE06868 ctgl59442805857..2805868, 2810804..2811415,

2834798..2835118,

MDQGNKTEVTMFILTGFTDDFELQVFLFLLFFAIYLFTLIGNLGLWL VffiDSWLHNPMYYFLSVLSFLDACYSTVVTPKMLVNFLAKNKSISFIGCATQ MLLFVTFGTTECFLLAAMAYDHYVAJYNPLLYSVSMSPRVYVPLITASYVA GIL3JATmiVATFSLSFCGSNBIRHVFCDMPPLLAISCSDTHTNQLLLFYFVGSI EIJYTILlVLISYGF]LLAILEMQSAEGI 3^WSTCGAJJLTGVT3YHGT3XFlvr^ RPSSSYTSDNDMIVSIΪΥTT^ (SEQ ID NO: 94) atggatcaagggaacaagactgaagtcaccatgtttatattgacaggcttcacagatgattttgagctgcaagtc ttcctatttttactattttttgcaatctatctctttaccttgataggcaatttagggctggttgtgttggtcattgaggattcctggct ccacaaccccatgtattattttcttagtgttttatcattcttggatgcttgctattctacagttgtcactccaaaaatgttggtcaat ttcctggcaaaaaataaatccatttcatttatcggatgtgcaacacagatgcttctttttgttacttttggaactacagaatgtttt ctcttggctgcaatggcttatgatcactatgtagccatctacaaccctctcctgtattcagtgagcatgtcacccagagtctat gtgccactcatcactgcttcctacgttgctggcattttacatgctactatacatatagtggctacatttagcctgtccttctgtgg atccaatgaaattaggcatgtcttttgtgatatgcctcctctccttgctatttcttgttctgacactcacacaaaccagcttctact cttctactttgtgggttctattgagataatagtcactatcctgattgtcctgatctcctatggttttattctgttggccattctgaag atgcagtctgctgaagggaggagaaaagtcttctctacatgtggagctcacctaactggagtgacaatttatcatgggaca atcctcttcatgtatgtgagaccaagttccagctacacttcggacaatgacatgatagtgtcaatattttataccattgtgattc ccatgctgaatcccatcatctacagtttgcggaacaaagatgtaaaggaggcaatcaaaagattgcttgtgagaaattggtt cataaataagtta (SEQ ID NO: 93)

MOOSE06874 ctgl3103 7821645..7821689, 7841845..7842762,

MEWENQTJLVEFFLKGHSVHPRLELLFFVLTFIMYVVILLGNGTLILISI LDPHLHTPMYFFLGNLSFLDICYTTTSFF STLVSFLSERKTISFSGCAVQMFLG

LAMGTTECVLLGMMAFDRYVAICNPLRYPJJMSI NAYVPMAVGSWFAG1V NSAVQTTFVVQLPFCRKNVINHFSCEILAVMKLACADISGNEFLMLVATILF TLMPLLLIVISYSLΠSSILIΑHSSEGRSKAFSTCSAHLTVVIIFYGTILFMYMKP KSKETLNSDDLDATDKΠSMFYGVMTPMMNPLΓ^SLPNKDVKEAFIKCLLY VKTLCCSD (SEQ ID NO: 96) atggaatgggaaaaccaaaccattctggtggaattttttctgaagggacattctgttcacccaaggcttgagtta ctcttttttgtgctaatcttcataatgtatgtggtcatccttctggggaatggtactctcattttaatcagcatcttggaccctcac cttcacacccctatgtacttctttctggggaacctctccttcttggacatctgctacaccaccacctctattccctccacactag tgagcttcctttcagaaagaaagaccatttccttttctggctgtgcagtgcagatgttccttggcttggccatggggacaaca gagtgtgtgcttctgggcatgatggcctttgaccgctatgtggctatctgcaaccctctgagatatcccatcatcatgagca agaatgcctatgtacccatggctgttgggtcctggtttgcagggattgtcaactctgcagtacaaactacatttgtagtacaa ttgcctttctgcaggaagaatgtcatcaatcatttctcatgtgaaattctagctgtcatgaagttggcctgtgctgacatctcag gcaatgagttcctcatgcttgtggccacaatattgttcacattgatgccactgctcttgatagttatctcttactcattaatcattt ccagcatcctcaagattcactcctctgaggggagaagcaaagctttctctacctgctcagcccatctgactgtggtcataat attctatgggaccatcctcttcatgtatatgaagcccaagtctaaagagacacttaattcagatgacttggatgctaccgaca aaattatatccatgttctatggggtgatgactcccatgatgaatcctttaatctacagtcttagaaacaaggatgtgaaagag gcattcattaagtgtcttctttatgtgaagacactttgttgctcagac (SEQ ID NO: 95)

MOOSE06875 ctgl4877 3368510..3369409, 3379949..3379990, MDTGNWSQVAEFIILGFPFiLQGVQIYLFLLLLLIYLMTVLGNLLIFLV

VCLDSI^HTPMYHFVSILSFSELGYTAATJPKMLANLFSEKKTISFSGCLLQIY FFHSLGATECYLLTAMAYDRYLAICRPLHYPTLMTPTLCAEIAIGC LGGLA GPVVEISLISRLPFCGPNRIQIJVFCDFPPVLSLACTDTSTNVLVDFVINSCKIL ATFLLILCSYVQπCTVL3 ^>SAAGK3^3^ISTCASHLTVVL3PYGSILSIvrϊNRL EXSYSLDYDQALAVVYSVLTPFLNPFIYSLHI^J^J AWKKYICRRQPATE M (SEQ ID NO: 98) atggacacagggaactggagccaggtagcagaattcatcatcttgggcttcccccatctccagggtgtccag atttatctcttcctcttgttgcttctcatttacctcatgactgtgttgggaaacctgctgatattcctggtggtctgcctggactcc cggcttcacacacccatgtaccactttgtcagcattctctccttctcagagcttggctatacagctgccaccatccctaagat gctggcaaacttgttcagtgagaaaaagaccatttcattctctgggtgtctcctgcagatctatttctttcactcccttggagc gactgagtgctatctcctgacagctatggcctacgataggtatttagccatctgccggcccctccactacccaaccctcatg accccaacactttgtgcagagattgccattggctgttggttgggaggcttggctgggccagtagttgaaatttccttgatttc acgcctcccattctgtggccccaatcgcattcagcacgtcttttgtgacttccctcctgtgctgagtttggcttgcactgatac gtctacaaatgtcctagtagattttgttataaattcctgcaagatcctagccaccttcctgctgatcctctgctcctatgtgcag atcatctgcacagtgctcagaattccctcagctgccggcaagaggaaggccatctccacgtgtgcctcccacctcactgt ggttctcatcttctatgggagcatcctttccatgtatgtgcggctgaagaagagctactcactggactatgaccaggccctg gcagtggtctactcagtgctcacacccttcctcaaccccttcatctacagcttgcacaacaaggagatcaaggaggcttgg aaaaagtacatctgcaggaggcagccagccacggaaatg (SEQ ID NO: 97) MOOSE06877 ctgl83 49657.-49676, 57650..58571,

MSGENVTKVSTFILVGLPTAPGLQYLLFLLFLLTYLFVLVENLAΠLIV WSSTSLHIIPMYYFLSSMSFLEIWYVSDITPK-MLEGFLLQQKRISFVGCMTQL

YFFSSLVCTECVLLASMAYDRYVAICHPLRYHVLVTPGLCLQLVGFSFVSGF TISMTKVCFISSVTFCGSNVLNHFFCDISPILKLACTDFSTAELVDFILAFIILVF PLLATILSYWHITLAVLRIPSATGCWRAFSTCASHLTWTVFYTALLFMYVR PQAJDSQSSN30,ISAVYTVVTPI3NPL3YCL3^N3^Fi AXIQ ALGLG3ΪWLIIP W (SEQ DD NO: 100) atgagtggggagaatgtcaccaaggtcagcaccttcatcctggtgggcctccccacggccccagggctgca gtacctgctcttcctcctcttcctgctcacctacctctttgtcctggtggagaacctggccatcatcctcatcgtctggagcag cacctccctccacaggcccatgtactactttctgagctccatgtctttcctggagatctggtacgtgtctgacatcaccccca agatgctggagggcttcctcctccagcagaaacgcatctctttcgtcgggtgcatgacgcagctctacttcttcagctccct ggtgtgcaccgagtgtgtgcttctggcctccatggcctacgaccgctacgtggccatctgccacccgctgcgctaccacg tccttgtgaccccggggctgtgcctccagctggtgggcttctcctttgtgagtggcttcaccatctccatgatcaaggtctgt tttatctccagcgtcacgttctgtggctccaacgtcttgaaccacttcttctgtgacatttcccccatcctcaagctggcctgc acggacttctccactgcagagctggtggatttcatcctggccttcatcatcctggtgtttccgctcctggccaccatactgtc atattggcacatcaccctggctgtcctgcgcatcccctcggccaccggctgctggagagccttctctacctgcgcctctca cctcaccgtggtcaccgtcttctatacagccttgcttttcatgtatgtccggccccaagccattgattcccagagctccaaca agctcatctctgccgtgtacactgttgtcacgccaataattaaccctttgatttactgcctgaggaacaaggaatttaaggac gccttgaaaaaggccttgggcttgggtcattggctccatccctgg (SEQ ID NO: 99)

MOOSE06878 ctgl4667 1179150..1179156, 1180308..1181239,

MGSFNTSFEDGFILVGFSDWPQLEPILFVFIF3FYSLTLFGNT3IIALSWL DLRLHTPMYFFLSHLSLLDLCFTTSTVPQLL3NLCGVDRTITRGGCVAQLFIY LALGSTECVLLVVMAFDRYAAVCI^LHYMAJMHPHLCQTLAIASWGAGFV NSLIQTGLAIVtAMPLCGIJT^NHFFCEMPWLjaACADTEGTEAKMFVARVIV VAWAALIUGSYVHIA3JAVLRVKSTAGRRI AFGTCGSHLLVVFLFYGSAIYT YLQSIHNYSE3^G3π^?VALFYTπTPILNPL3YTL3^NKDVKGALWKVLWRGRD SGQW (SEQ ID NO: 102) atgggaagtttcaacaccagttttgaagatggcttcattttggtgggattctcagattggccgcaactggagccc atcctgtttgtctttatttttattttctactccctaactctctttggcaacaccatcatcatcgctctctcctggctagaccttcggct gcacacacctatgtacttctttctctctcatctgtccctcctggacctctgcttcaccaccagcaccgtgccccagctcctgat caacctttgcggggtggaccgcaccatcacccgtggagggtgtgtggctcagctcttcatctacctagccctgggctcca cagagtgtgtgctcctggtggtgatggcctttgaccgctatgctgctgtctgtcgtccactccactacatggccatcatgca cccccatctctgccagaccctggctatcgcctcctggggtgcgggtttcgtgaactctctgatccagacaggtctcgcaat ggccatgcctctctgtggccatcgactgaatcacttcttctgtgagatgcctgtatttctgaagttggcttgtgcggacacag aaggaacagaggccaagatgtttgtggcccgagtcatagtcgtggctgttcctgcagcacttattctaggctcctatgtgc acattgctcatgcagtgctgagggtgaagtcaacggctgggcgcagaaaggcttttgggacttgtgggtcccacctccta gtagtlfrccl ttttatggctcagccatctacacatatctccaatccatccacaattattctgagcgtgagggaaaatttgttgc ccttttttatactataattacccccattctcaatcctctcatttatacactaagaaacaaggacgtgaagggggctctgtggaa agtactatggaggggcagggactcagggcagtgg (SEQ ID NO: 101)

MOOSE06882 ctg4256 15474228..15474921, 15514483..15514700,

15525055..15525087,

MDTGNKTLPQDFLLLGFPGSQTLQLSLFMLFLVMY3LTVSGNVAILM LVSTSHQLHTPMYFFLSNLSFLEIWYTTAAVPKALAILLGRSQTISFTSCLLQ IVΓYFVFSLGCTEYFLLAAMAYDRCLAICYPLIΓYGAIMSSLLSAQLALGSWVC GFVA3AWTAXISGLSFCGP31AINIIFFCDIAPWIALACTNTQAVELVAFVIAV VVILSSCLITFVSYVYΠSTILR3PSAFFIGE^KAFSTCSSHLTVVTLYYSPVIYTYI RPASSYTFERDKVVAALYTLVTPTLNPI\^VYSFQNI^MQAG3 KLLHSKENY HQS (SEQ ID NO: 104) atggacacaggcaacaaaactctgccccaggactttctcttactgggctttcctggttctcaaactcttcagctct ctctctttatgctttttctggtgatgtacatcctcacagttagtggtaatgtggctatcttgatgttggtgagcacctcccatcag ttgcatacccccatgtacttctttctgagcaacctctccttcctggagatttggtataccacagcagcagtgcccaaagcact ggccatcctactggggagaagtcagaccatatcatttacaagctgtcttttgcagatgtactttgttttctcattaggctgcac agagtacttcctcctggcagccatggcttatgaccgctgtcttgccatctgctatcctttacactacggagccatcatgagta gcctgctctcagcgcagctggccctgggctcctgggtgtgtggtttcgtggccattgcagtgcccacagccctcatcagt ggcctgtccttctgtggcccccgtgccatcaaccacttcttctgtgacattgcaccctggattgccctggcctgcaccaaca cacaggcagtagagcttgtggcctttgtgattgctgttgtggttatcctgagttcatgcctcatcacctttgtctcctatgtgta catcatcagcaccatcctcaggatcccctctgccatagaaggcaagaggaaggccttctcaacatgctcatctcatctcac agtggtgaccctttactattctcctgtaatctacacctatatccgccctgcttccagctatacatttgaaagagacaaggtggt agctgcactctatactcttgtgactcccacattaaacccgatggtgtacagcttccagaatagggagatgcaggcaggaat taggaagcttctgcacagcaaaagaaactatcatcagagt (SEQ DD NO: 103)

MOOSE06887 ctgl5944 6600325..6601250, 6608365..6608383, MTGGGMTEITYFJULGFSDFPRΠKVLFTIFLVIYITSLAWNLSLIVLIR

MDSHLHTPMYFFLSNLSFIDVCYISSTVPKMLSNLLQEQQTITFVGCΠQYFIF STMGLSESCLMTAMAYDRYAAICNPLLYSSIMSPTLCVWMVLGAYMTGLT ASLFQIGALLQLIIFCGSNV3RHFFCDMPQLLILSCTDTFFVQVMTAILTMFFG IASALVMISYGYLGIS3]VIJΑTSAKGRSJ^AFNTCASIJLTAVSLFYTSGIFVYLSS SSGGSSSFD3^AS YTVV3PMLNPLLYSLI N3^3JN)AL3^J^Q353INWGSSNW

(SEQ ID NO: 106) atgactgggggaggaaatattacagaaatcacctatttcatcctgctgggattctcagattttcccaggatcataa aagtgctcttcactatattcctggtgatctacattacatctctggcctggaacctctccctcattgttttaataaggatggattcc cacctccatacacccatgtatttcttcctcagtaacctgtccttcatagatgtctgctatatcagctccacagtccccaagatg ctctccaacctcttacaggaacagcaaactatcacttttgttggttgtattattcagtactttatcttttcaacgatgggactgag tgagtcttgtctcatgacagccatggcttatgatcgttatgctgccatttgtaaccccctgctctattcatccatcatgtcaccc accctctgtgtttggatggtactgggagcctacatgactggcctcactgcttctttattccaaattggtgctttgcttcaactcc acttctgtgggtctaatgtcatcagacatttcttctgtgacatgccccaactgttaatcttgtcctgtactgacactttctttgtac aggtcatgactgctatattaaccatgttctttgggatagcaagtgccctagttatcatgatatcctatggctatattggcatctc catcatgaagatcacttcagctaaaggcaggtccaaggcattcaacacctgtgcttctcatctaacagctgtttccctcttct atacatcaggaatctttgtctatttgagttccagctctggaggttcttcaagctttgacagatttgcatctgttttctacactgtgg tcattcccatgttaaatcccttgatttacagtttgaggaacaaagaaattaaagatgccttaaagaggttgcaaaagagaaa ctggggaagctcaaactgg (SEQ ID NO: 105) MOOSE06888 ctg30162 162624..163103, 175517..175972,

MK EQDSNVTEFVLLGLSSSWELQLFLFLLFLFFYIAJVLGNLLIVVT VQAIXAHLLQSPMYYFLGHLSFTDLCLSCVTVPKMLGDFLQQGKSISFSGCLA QΓYFLIΪFLGASEMFLLTVMAYDRYVAICNPLRYLTVMNPQLCLWLVLACW CGGFFFLSMQTLLTFQLPFCNAQV3D3JYFCDV33PVLI^ACADTTLINMLVVA NSGLISLGCFLILLASYKVILLSLQKQSAESRRKALSTCGSHLTVVTFFFVPCI FIYLRPSTTFPLDKA.VSVFYTTITPMLNPLIYTLRNEDVKNAMRQLWSSKISL KEK (SEQ ID NO: 108) atgaaaaaagaacaagattctaatgtgacagaatttgttcttctgggcctatcatcttcttgggagctgcagctatt tctcttcttactatttttgtttttttacattgctattgtcctgggaaacctcttgatagtggtaacagtgcaagcccatgctcacctg ctccaatctcctatgtattattttttaggtcatctctctttcattgacctatgcctgagctgtgttactgtgccaaagatgttaggg gatttcctacagcagggcaagagcatctctttttcaggatgcctggcccagatctacttcctccactttctaggagccagtg agatgtttttgctgacagtcatggcctatgacaggtatgttgccatctgtaaccctttgcgctaccttacagtcatgaaccccc agctatgcctttggttggttcttgcctgctggtgtgggggttttatccactctatcatgcagaccctcctgaccttccagctgc ccttctgtaatgctcaggttatagaccattacttttgtgatgtccacccagtcctaaaacttgcctgtgctgatacaactctgat aaatatgttggtagttgccaacagtggtctcatctccctgggttgtttcctcattcttttggcctcctacaaagtcattctgctta gtcttcaaaaacagtctgcagagagccgacgcaaagctctctctacctgtggatctcatctgactgtagtaactttcttctttg ttccgtgtatctttatttatctccgtccatccactactttcccattggataaagctgtgtctgtgttctataccaccatcaccccaa tgttgaacccactcatctatactctgaggaatgaggatgtaaagaatgccatgaggcagctatggagtagcaagatctcct tgaaggaaaaa (SEQ ID NO: 107)

MOOSE06889 ctg30162 1516718..1516750, 1570040..1570948,

MKGANLSQGMEFELLGLTTDPQLQP LFWFLGMYTATLLGNLVMF LLIHVSATLHTPMYSLLKSLSFLDFCYSSTWPQTLVNFLAKRKVISYFGCMT QIVIFFYAGFATSECYLIAAMAYDRYAAICNPLLYSTIMSPEVCASLIVGS YSA

GFLNSLKTGClFSLIffCGAJJWTHFFCDGPPILSLSCVDTSLCEILLFIFAGFN LLSCTLT3LISYFLILNTIUKMSSAQGRFKAFSTCASHLTAICLFFGTTLFMYLR PRSSYSLTQDRTVAVIYTVVIPVLNPLMYSLRNKDVKKALIKLLTCMFSPTR W (SEQ ID NO: 110) atgaaaggggcaaacctgagccaagggatggagtttgagctcttgggcctcaccactgacccccagctcca gaggctgctcttcgtggtgttcctgggcatgtacacagccactctgctggggaacctggtcatgttcctcctgatccatgtg agtgccaccctgcacacacccatgtactccctcctgaagagcctctccttcttggatttctgctactcctccacggttgtgcc ccagaccctggtgaacttcttggccaagaggaaagtgatctcttattttggctgcatgactcagatgttcttctatgcgggttt tgccaccagtgagtgctatctcatcgctgccatggcctatgaccgctatgccgctatttgtaaccccctgctctactcaacc atcatgtctcctgaggtctgtgcctcgctgattgtgggctcctacagtgcaggattcctcaattctcttatccacactggctgt atctttagtctgaaattctgcggtgctcatgtcgtcactcacttcttctgtgatgggccacccatcctgtccttgtcttgtgtaga cacctcactgtgtgagatcctgctcttcatttttgctggtttcaaccttttgagctgcaccctcaccatcttgatctcctacttctt aattctcaacaccatcctgaaaatgagctcggcccagggcaggtttaaggcattttccacctgtgcatcccacctcactgc catctgcctcttctttggcacaacactttttatgtacctgcgccccaggtccagctactccttgacccaggaccgcacagttg ctgtcatctacacagtggtgatcccagtgctgaaccccctcatgtactctttgagaaacaaggatgtgaagaaagctttaat aaagttacttacctgtatgttttcccccacaagatgg (SEQ ID NO: 109)

MOOSE06891 ctgl4877 3511302..3511312, 3527441..3528371,

MGQTNVTSWRDFVFLGFSSSGELQLLLFALFLSLYLVTLTSNVFTJIAI RLDSHLHTPMYLFLSFLSFSETCYTLGUPRMLSGLAGGDQAISYVGCAAQM FFSASWACTNCFLLAAMGFDRYVAICAPLHYASFfMNPTLCAQLVITSFLTG YLFGLGMTLVIFHLSFCSSHEIQHFFCDTPPVLSLACGDTGPSELRIFILSLLVL LVSFFFITISYAYILAAILT ^,SAEGQ35KAFSTCASHLTVVJJHYGCASFVYLRP K^SYSLE3 DQL3AMTYTVVTPLLNPIVYSLRTRAIQTALRNAFRGRLLGSQW (SEQ ID NO: 112) atggggcagaccaacgtaacctcctggagggattttgtcttcctgggcttctccagttctggggagttgcagct ccttctctttgccttgttcctctctctgtatctagtcactctgaccagcaatgtcttcattatcatagccatcaggctggatagcc atctgcacacccccatgtacctcttcctttccttcctatccttctctgagacctgctacactttgggcatcatccctagaatgct ctctggcctggctgggggggaccaggctatctcctatgtgggctgtgctgcccagatgttcttttctgcctcatgggcctgt actaactgcttccttctggctgccatgggctttgacagatatgtggccatctgtgctccactccactatgccagccacatgaa tcctaccctctgtgcccagctggtcattacttccttcctgactggatacctctttggactgggaatgacactagttattttccac ctctcattctgcagctcccatgaaatccagcactttttttgtgacacgccacctgtgctgagcctagcctgtggagatacag gcccgagtgagctgaggatctttatcctcagtcttttggtcctcttggtctccttcttcttcatcaccatctcctacgcctacatc ttggcagcaatactgaggatcccctctgctgaggggcagaagaaggccttctccacttgtgcctcgcaccttacagtggt cattattcattatggctgtgcttccttcgtgtacctgaggcccaaagccagctactctcttgagagagatcagcttattgccat gacctatactgtagtgacccccctccttaatcccattgtttatagtctaaggactagggctatacagacagctctgaggaatg ctttcagagggagattgctggggagccagtgg (SEQ ID NO: 111)

MOOSE06899 ctgl5944 2268933.-2269865, KNQTAGVTFILLGFSEFPDLQIPLFLVFLT3ΥTITVMGNLGM31vrvπi3NP

TO.HTPMYFFLSHLSFVDFCYSTTITPKLLENLVVΕDPJISFTGCIMQFFFACIFV VTETFMLAAMAYDRFVAVCNPLLYTVAMSQRLCSLLVAASYSWSLVCSLT YTYFLLTLSFCRTNFINNFVCEHAA3VAVSCSDPYMSQKVILVSATFNEISSV V3ILTSYAFIFITVM PSTGGI^KKAFSTCASHLTAITIFHGTILFLYCVPNSKS SWLMVKVASVFYTVVIPMLNPLIYSLRNKDVKETVRKLVITiα,LCIJKM

(SEQ ID NO: 114) aaaaatcagactgctggagtcaccttcatcctcttgggcttctcagaatttccagaccttcagatacccctgttcc tggtcttcctgaccatctacacaatcactgtgatggggaatctgggcatgatcatggtcatcaggatcaaccccaaactcc acacccctatgtactttttcctcagccacttgtcctttgttgatttctgttattccaccacaattacaccaaaactgctggagaac ttggttgtggaagacagaatcatctccttcacaggatgcatcatgcaattcttctttgcctgtatatttgtggtgacagaaacat tcatgctggcagcgatggcttatgacagatttgtggcagtgtgtaaccctctgctttacacagttgcaatgtcccagaggctt tgctccttgttagtggctgcatcatactcttggagtttagtttgttccttaacatacacatactttctgttgactttatcttttt^ gactaacttcattaataactttgtctgtgagcacgctgccattgttgctgtgtcctgctctgacccctacatgagccagaaggt calutagtttctgcaacattcaatgaaataagcagcgtggtgatcattctcacttcctatgctttcatttttatcactgtcatgaa gatgccttccactggggggcgcaagaaagcgttctccacgtgtgcctcccacctgaccgccattaccattttccatggga ctatcctttttctctactgtgttcctaactccaaaagttcatggctcatggtcaaggtggcctctgtcttttacacagtggtcattc ccatgctgaaccccttgatctatagcctcaggaacaaagatgtaaaagagacagtcaggaagttagtcattaccaaattatt atgtcataaaatg (SEQ ID NO: 113) MOOSE06901 ctgl59444763657.-4764577, 4783485..4783520,

MQPYTKNWTQVTEFVMMGFAGIHEAHLLFFILFLTMYLFTLVENLAI ILVVGLDHRLRRPMYFFLTHLSCLEIWYTSVTVPI MLAGFIGVDGGKNISYA GCLSQLF3FTFLGATECFLLAAMAYDRYVAICMPLHYGAFVSWGTCIRLAA ACWLVGFLTPILPIYLLSQLTFCGPNVIDHFSCDASPLLALSCSDVTWKETVD FLVSLAVLLASSMVIAVSYGNIVWTLLHIRSAAERWKAFSTCAAHLTVVSLF

YGTLFFMYVQTKVTSS3NFNKVVS YSVVTPMLNPL3YSL3iNI EVKGALG RTLLI RRHLCSQK (SEQ ID NO: 116) atgcaaccatataccaaaaactggacccaggtaactgaatttgtcatgatgggctttgctggcatccatgaagc acacctcctcttcttcatactcttcctcaccatgtacctgttcaccttggtggagaatttggccatcattttagtggtgggtttgg accaccgactacggagacccatgtatttcttcctgacacacttgtcctgccttgaaatctggtacacttctgttacagtgccc aagatgctggctggttttattggggtggatggtggcaagaatatctcttatgctggttgcctatcccagctcttcatcttcacct ttcttggggcaactgagtgtttcctactggctgccatggcctatgatcgttatgtggccatttgtatgcctctccactatgggg cttttgtgtcctggggcacctgcatccgtctggcagctgcctgttggctggtaggtttcctcacacccatcttgccaatctac ctcttgtctcagctaacattttgtggcccaaatgtcattgaccatttctcctgtgatgcctcacccttgctagccttgtcgtgctc agatgtcacttggaaggagactgtggatttcctggtgtctctggctgtgctactggcctcctctatggtcattgctgtgtccta tggcaacatcgtctggacactgctgcacatccgctcagctgctgagcgctggaaggccttctctacctgtgcagctcacct gactgtggtgagcctcttctatggcactcttttctttatgtatgtccagaccaaggtgacctcctccatcaacttcaacaaggt ggtatctgtcttctactctgttgtcacgcccatgctcaatcctctcatctacagtcttaggaacaaggaagtgaagggagctc tgggtcgaacacttctcaaaagaagacatttatgcagccaaaaa (SEQ ID NO: 115)

MOOSE06904 ctgl5285 7136188..7136217, 7137011..7137334,

7223003..7223590,

MI NRTMFGEFILLGLTNQPELQVMTFIFLFLTYMLSILGNLTΠTLTLLD P3ILQTPMYFFLILNFSFLEISFTSFFPILFLTSMTTGNKVISFAGCLTQYFFAIFL GATEFYLLASMSYDRYVALCIO^>LHYLT3MSSRVCIQLVFCSWLGGFLAILPPΠ LMTQVDFCVSNTLNHYYCDYGPLVELACSDTSLLELMISVMTATΓVFTMIPFS LIVTSY3I LGA3UAMASTQS3^RKVFSTCSSHLLVVSLFFGTASITY3RPQAGSS VTTDRVLSLFYTVITPMLNPΠYTLRNEDVRRALRHLVEGI HSIIPSV (SEQ

I NO: 118) atgaaaaacagaaccatgtttggtgagtttattctactgggccttacaaatcaacctgaactccaagtgatgatat tcatctttctgttcctcacctacatgctaagtatcctaggaaatctgactattatcaccctcaccttactagacccccacctcca gacccccatgtatttcttcctccggaatttctccttcttagaaatttccttcacatccatttttattcccagatttctgaccagcatg acaacaggaaataaagttatcagctttgctggctgcttgactcagtatttttttgctatatttcttggagctaccgagttttacct cctggcctccatgtcttatgatcgttatgtggccatctgcaaacccttgcattacctgactattatgagcagcagagtctgcat acaactagtgttctgctcctggttggggggattcctagcaatcttaccaccaatcatcctgatgacccaggtagatttctgtg tctccaacattctgaatcactattactgtgactatgggcctctcgtggagcttgcctgctcagacacaagcctcttagaactg atgatctccgtgatgacagccaccatagtcttcattatgatccccttctctctgattgtcacctcttacatccgcatcctgggtg ccatcctagcaatggcctccacccagagccgccgcaaggtcttctccacctgctcctcccatctgctcgtggtctctctctt ctttggaacagccagcatcacctacatccggccgcaggcaggctcctctgttaccacagaccgcgtcctcagtctcttcta cacagtcatcacacccatgctcaaccccatcatctacacccttcggaacaaggacgtgaggagggccctgcgacacttg gtggaaggaaaacactcccatccctctgtg (SEQ ID NO: 117)

MOOSE06908 ctgl59443578921..3579826, 3636467..3636502,

MTLGNSTEVTEFYLLGFGAQHEFWCILFIVFLLIYVTSIMGNSGΠLLIN TDSRFQTLTYFFLQHLAFVDICYTS AITPKMLQSFTEEKNLILFQGCVIQFLVY ATFATSDCYLLAMMAVDPYVAICKPLHYTVIMSRTVCIRLVAGSYIMGSINA SVQTGFTCSLSFCKSNSINHFFCDWPILALSCSNVDINIMLLVVFVGSNLTFT

GLVVπ?SYIY3] LAT3LiαvJSSSAG3 KKSFSTCASHLTAVT3FYGTLSY]vlYLQSH SNNSQENMKVAFIFYGTVIPMLNPLIYSLIϋSu^VJ EALKTLLKI j LCSQQ (SEQ ID NO: 120) atgacactaggaaacagcactgaagtcactgaattctatcttctgggatttggtgcccagcatgagttttggtgta tcctcttcattgtattccttctcatctatgtgacctccataatgggtaatagtggaataatcttactcatcaacacagattccaga tttcaaacactcacgtactt tttctacaacatttggcttttgttgatatctgttacacttctgctatcactcccaagatgctccaaa gcttcacagaagaaaagaatttgatattatttcagggctgtgtgatacaattcttagtttatgcaacatttgcaaccagtgact gttatctcctggctatgatggcagtggatccttatgttgccatctgtaagccccttcactatactgtaatcatgtcccgaacag tctgcatccgtttggtagctggttcatacatcatgggctcaataaatgcctctgtacaaacaggttttacatgttcactgtcctt ctgcaagtccaatagcatcaatcactttttctgtgatgttccccctattcttgctctttcatgctccaatgttgacatcaacatcat gctacttgttgtctttgtgggatctaacttgatattcactgggttggtcgtcatcttttcctacatctacatcatggccaccatcct gaaaatgtcttctagtgcaggaaggaaaaaatccttctcaacatgtgcttcccacctgaccgcagtcaccattttctatggg acactctcttacatgtatttgcagtctcattctaataattcccaggaaaatatgaaagtggcctttatattttatggcacagttatt cccatgttaaatcctttaatctatagcttgagaaataaggaagtaaaagaagctttaaaaacacttctcaaaagaagacattt atgcagccaacaa (SEQ ID NO: 119)

MOOSE06909 ctgl5285 7251039..7251953, 7304530..7304565, MAGENHTTLPEFLLLGFSDLKALQGPLFWWLLVYLVTLLGNSLIILL TQVSPALHSPMYFFLRQLSVVELFYTTDΓVPRTLANLGSPHPQAISFQGCAAQ IVΓYΎFIVLGISECCLLTAMAYDRYVAICQPLRYSTLLSPRACMAMVGTSWLT GΠTATTHASLIFSLPFRS3JP]IPIJFLCDILPVLI^ASAGΪOIRSEISVMTATIVFI MIPFSLΓN/TSYIPJLGAILAMASTQSRRKVFSTCSSHLLVVSLFFGTASITYIRP QAGSSVTTDRVLSLFYTVITPMLNPIIYTLJ^NKDVRRALRHLRLIRIOΑ KSSQ I (SEQ ID NO: 122) atggctggggaaaaccatactacactgcctgaattcctccttctgggattctctgacctcaaggccctgcaggg ccccctgttctgggtggtgcttctggtctacctggtcaccttgctgggtaactccctgatcatcctcctcacacaggtcagcc ctgccctgcactcccccatgtacttcttcctgcgccaactctcagtggtggagctcttctacaccactgacatcgtgcccag gaccctggccaatctgggctccccgcatccccaggccatctctttccagggctgtgcagcccagatgtacgtcttcattgt cctgggcatctcggagtgctgcctgctcacggccatggcctatgaccgatatgttgccatctgccagcccctacgctattc caccctcttgagcccacgggcctgcatggccatggtgggtacctcctggctcacaggcatcatcacggccaccacccat gcctccctcatcttctctctaccttttcgcagccacccgatcatcccgcactttctctgtgacatcctgccagtactgaggctg gcaagtgctgggaagcacaggagcgagatctccgtgatgacagccaccatagtcttcattatgatccccttctctctgatt gtcacctcttacatccgcatcctgggtgccatcctagcaatggcctccacccagagccgccgcaaggtcttctccacctg ctcctcccatctgctcgtggtctctctcttctttggaacagccagcatcacctacatccggccgcaggcaggctcctctgtta ccacagaccgcgtcctcagtctcttctacacagtcatcacacccatgctcaaccccatcatctacacccttcggaacaagg acgtgaggagggccctgcgacacttgaggttaataagaaaaaaaaaaaaatcctcacaaatt (SEQ ID NO: 121)

MOOSE06910 ctg301622022696..2022718, 2049308..2050235,

MGKTKNTSLDAVVTDF3LLGLSITPPNLRSLLFLVFFIIYILTQLGNLLIL LTMWADPIO,CA3^IvIY3LLGVLSFLDMWLSSVTWRLTXDFTPSJJ AJPFGGC VAQLYFFIJFLGSTQCFLYTLMAYDRYLAICQPLFfYPVLMNGRLCTVLVAG AWVAGSIVfflGSIQATLTFRLPYCGPNQVDYFICDIRAVLRLACADTTVNELV

TFVDVRVVAASCFMLILLSYAl IJAILKJRTADGRJ AFSTCGSJJLIVVTVY YWCIFIYLRAGS3Π PLDGAAAVFYTVVTPLLNPLIYTL3^QEVKSALKRITA AIHICSKW (SEQ DD NO: 124) atgggaaagaccaaaaacacatcgctggatgccgtggtgacagatttcattcttctgggtttgtctcacccccc aaatctaagaagcctcctcttcctggtcttcttcatcatttacatcctcactcagctggggaacctgctcattctgctcaccatg tgggctgacccgaagctctgtgctcgccccatgtacattcttctgggagtgctctcattcctggacatgtggctctcctcagt caccgttcctcggcttattttggattttactccttccatcaaggctatcccgtttggtggctgtgtggctcaactgtatttctttca cttcctgggcagcacccagtgcttcctctacaccttgatggcctatgacaggtacctagcaatatgtcagcccctgcactac ccagtgctcatgaatgggaggttatgcacagtccttgtggctggagcttgggtcgccggctccatgcatgggtctatccag gccaccttgaccttccgcctgccctactgtgggcccaatcaggtggattactttatctgtgacatccgcgcagtattgagac tggcctgtgctgacacaactgtcaatgagcttgtgacctttgtggacgtcagggtagtggccgccagttgcttcatgttaatt ctgctctcctatgccaacatagtccatgccatcctgaagatacgcaccgctgatgggaggcgccgggccttctccacctg tggctcccacctaatcgtggtcacagtctactatgtcccctgtattttcatctaccttagggctggctccaaagaccccctgg atggggcagcggctgtgttttacactgttgtcactccattactgaaccccctcatctatacactgaggaaccaggaagtgaa gtctgccctgaagaggataacagcagcgattcacatctgctctaaatgg (SEQ ID NO: 123)

MOOSE06911 ctg4256 15849243..15849993, 15905554..15905744,

MPNSTTVMEFLLMRFSDVWTLQILHSASFFMLYLVTLMGNILΓVTVT

TCDSSLHMPMYFFLRNLHLSLroMMYISTIVPiaviLVNYLLDQRTISFVGCTA QHFLYLTLVGAEFFLLGLMAYDRYVAICNPLRYPVLMSRRVCWMLTAGSWF GGSLDGFLLTPITMSFPFCNSRELNHFFCEAPAVLIΑ_^ACADTALYETVMYVC CVLMLL3PFSWLASYAPJLTTVQCMSSVEGRKKAFATCSS3JMTWSLFYGA AMYTYMLPHSYHIΠ^>AQDKVLS YT]LTPMLNPLΓ^SL3^NKDVTGALKEIAL GRFKGPQRV (SEQ ID NO: 126) atgcccaattcaaccaccgtgatggaatttctcctcatgaggttttctgatgtgtggacactacagattttacattct gcatccttctttatgttgtatttggtaactctaatgggaaacatcctcattgtgaccgtcaccacctgtgacagcagccttcac atgcccatgtacttcttcctcaggaatctccacctttccttaattgacatgatgtatatttccactattgtgcctaagatgctggtt aattacctgctggatcaaaggaccatttcctttgtggggtgcacagctcaacacttcctctaccttacccttgtgggagctga attcttcctgctgggcctcatggcctatgaccgctatgtggccatttgcaaccctctgagataccctgtcctcatgagccgc cgggtctgttggatgattatagcaggttcctggtttgggggctctttggatggcttcctcctaacccccatcaccatgagcttt cccttctgcaattcccgggagattaaccacttcttctgtgaggcaccagcagtcctgaagttggcatgtgcagacacagcc ctctacgagacagtgatgtatgtgtgctgtgttttgatgctgctgattcctttctctgtagtccttgcttcctatgcccgaatcct gactacagttcagtgcatgagctcagtggagggcaggaagaaggcatttgccacttgctcatcccacatgactgtggtgt ccttgttctacggggctgccatgtacacctacatgctgccacattcttaccacaagccagcccaggacaaagtcctctctgt gttttacaccattctcacacccatgctgaaccccctcatctacagccttagaaacaaggatgtgactggagctctgaagag ggccttggggaggttcaagggtcctcaaagggtg (SEQ ID NO: i25)

MOOSE06916 ctg4256 14869648..14870589,

MAWENQTFNSDFILLGIFNHSPPHTFLFFLVLGIFLVAFMGNSVMVLL 3YLDTQLHTPMYFLLSQLSLMDLMLICTTVPKMAFNYLSGSKSISMAGCVTQ IFFYISLSGSECFLLAVMAYDRYIAICHPLRYTNLMNPKICGLMATFSWTLGS TDGITOAVATFSFSFCGS1^IAHFFCEFPSLLILSCNDTS3FEEVIFICCIVMLVFP VAIIlASYAGVILAV3IJMGSGEG3^KTFTTCSSHLMVVGMYYGAALFMYIPvP TSDHSPTQD3avT\^SWYTILTPMLNPLIYSLRNKEVTRAFMKXLGKGKSESEL (SEQ ID NO: 128) atggcatgggagaatcagaccttcaactccgacttcatcctccttggaatcttcaatcacagcccaccacacac gttcctcttctttctggtcctgggcatctttttagtggccttcatgggaaactctgtcatggttctcctcatctacctggacaccc agctccacacccccatgtacttcctcctcagccaactgtccctcatggacctcatgctcatctgcaccaccgtacccaagat ggccttcaactacttgtctggcagcaagtccatttctatggctggttgtgtcacacaaattttcttctatatatcactgtctggct ctgaatgttttcttttggctgttatggcttatgaccgctatattgctatttgccaccctctaagatataccaatctcatgaatccta aaatttgtggacttatggctaccttctcctggatcctgggctctacagatggaatcattgatgctgtagccacattttccttctc cttttgtgggtctcgggaaatagcccacttcttctgtgaattcccttccctactaatcctctcatgcaatgacacatcaatatttg aagaggttattttcatctgctgtatagtaatgcttgttttccctgttgcaatcatcattgcttcctatgctggagttattctggctgt cattcacatgggatctggagagggtcgtcgcaaaactttcacgacctgttcctctcacctcatggtggtgggaatgtactat ggagcagctttgttcatgtacatacggcccacatctgatcactccccaacgcaggacaagatggtgtctgtattctacacc atcctcactcccatgctgaatcccctcatctacagcctccgcaacaaggaggtgactagagcattcatgaagatcttagga aagggcaagtctgagagtgagtta (SEQ ID NO: 127)

MOOSE06924 ctg4256 14789445..14789460, 14803021..14803946,

MAJ^NSTFNSDFILLGJFNHSPTHTFLFFLVLAJFSVAFMGNSVMVLLI YLDTQLHTPMYLLLSQLSLMDLMLICTTWI MAFNYLSGSKSISMAGCATQI FFYTSLLGSECFLLAVMAYDRYTAICHPLRYTNLMSPKICGLMTAFSWJLGS TDGΠDVVATFSFSYCGSREIAHFFCDFPSLLILSCSDTSIFEI LFICCIVMIVFP VAIIIASYARVILAVIIJMGSGEGRRKAFTTCSSJJLLVVGMYYGAALFMYIRP TSDRSPTQDIOIVSWYTILTPMLNPLIYSLRNKJ5VTRAFMKILGKGNISSSI

(SEQ ID NO: 130) atggcaagggagaattcgaccttcaactccgacttcatcctcctgggaatcttcaatcacagccccacccaca ccttcctcttctttctggtcctggccatcttttcagtggccttcatgggaaactctgtcatggttctcctcatctacctggacacc cagctccacacccccatgtacctcctcctcagccaactgtccctcatggacctcatgctcatctgcaccaccgtacccaag atggccttcaactacctgtctggcagcaagtccatttctatggctggttgtgccacacaaattttcttctatacatcactgcttg gctctgagtgctttcttttggctgttatggcttatgaccgctacactgccatttgccaccctctaagatacaccaatctcatgag ccctaaaatttgtggacttatgactgccttttcctggatcctgggctctacggatggaattattgatgttgtagcaacattttcct tctcctactgtgggtctcgggaaatagcccacttcttctgtgacttcccctccctactaatcctctcatgcagtgacacatcaa tatfrgaaaagattcttttcatctgctgtatagtaatgattgttttccctgttgcaatcatcattgcttcctatgctcgagttatcctg gctgtcattcacatgggatctggagagggtcgtcgcaaagcttttactacttgttcctctcacctcttggtggtgggaatgta ctatggagcagctttgttcatgtacatacggcccacatctgatcgctccccaacacaggacaagatggtgtctgtattctac accatcctcactcccatgttgaatcccctcatctacagcctccgcaacaaggaggtgaccagagcattcatgaagatctta ggaaagggcaacataagttcatcaata (SEQ ID NO: 129)

MOOSE06927 ctgl39104182589..4183512, 4253928..4253945,

MEQDNTTLLTEFVLTGLTYQPEWK.MPLFLVFLVIYLIT1VWNLGLIAL IWNDPQLHIPMYFFLGSLAFVDAWISSTVTP3 JLVNFLAKNRMISLSECMIQ FFSFAFGGTTECFLLATMAYDRYVAICKPLLYPV3MNNSLCIRLLAFSFLGGF LIJALmEVLIFRLTFCNSNTJIJ3JFYCDirPLFMISCTDPSJNFLMVFILSGSIQVFT IVTVLNSYTFALFTILI a SVRGVRKAFSTCGAHLLSVSLYYGPLffMYLRPA SPQADDQDM3DSVFYTIJ3PLLNPI3YSL3^N QVIDSFT3<α IVKRNQKHSSN (SEQ ID NO: 132) atggaacaggataatacaacattgctgacagagtttgttctcacaggacttacatatcagccagagtggaaaat gcccctgttcttggtgttcttggtgatctatctcatcactattgtgtggaaccttggtctgattgctcttatctggaatgacccac aacttcacatccccatgtacttttttcttgggagtttagcctttgttgatgcttggatatcttccacagtaactcccaaaatgttgg ttaatttcttggccaaaaacaggatgatatctctgtctgaatgcatgattcaatttttttcctttgcatttggtggaactacagaat gttttctcttggcaacaatggcatatgatcgctatgtagccatatgcaaacctttactatatccagtgattatgaacaattcact atgcatacggctgttagccttctcatttttaggtggcttcctccatgccttaattcatgaagtccttatattcagattaaccttctg caattctaacataatacatcatttttactgtgatattataccactgtttatgatttcctgtactgacccttctattaattttctaatggt ttttattttgtctggctcaattcaggtattcaccattgtgacagttcttaattcttacacatttgctcttttcacaatcctaaaaaaga agtctgttagaggcgtaaggaaagccttttccacctgtggagcccatctcttatctgtctctttatattatggcccacttatcttc^' atgtatttgcgccctgcatctccacaagcagatgaccaagatatgatagactctgtcttttatacaatcataattcctttgctaa atcccattatctacagtctgagaaataaacaagtaatagattcattcacaaaaatggtaaaaagaaatcaaaagcattcttca aat (SEQ ID NO: 131)

MOOSE06929 ctgl3361 38992807..38993472, 39003872..39004156,

MEPLNRTEVSEFFLKGFSGYPALEHLLFPLCSAMYLVTLLGNTAIMA VSVLDHJLHTPVYFFLGNLSTLDICYTPTFVPLMLVHLLSSRKTISFARTISFP GCALQMYLTLALGSTECLLLAVMAYDRYVAICQPLRYPELMSGQTCMQM

AALSWGTGFANSLLQSILVWHLPFCGHVINYFYEILAVLKLACGDISLNALA LMVATAVLTLA LLLICLSYLFILSAJLRWSAAGRC3IAFSTCSAi TVVVVF YGTISFMYF KAKDPNVDKTVALFYGVVTPSLNP3IYSL3 NAEVKAAVLTL LRGGLLSRKA. (SEQ ID NO: 134) atggagccgctcaacagaacagaggtgtccgagttctttctgaaaggattttctggctacccagccctggagc atctgctcttccctctgtgctcagccatgtacctggtgaccctcctggggaacacagccatcatggcggtgagcgtgctag atatccacctgcacacgcccgtgtacttcttcctgggcaacctctctaccctggacatctgctacacgcccacctttgtgcct ctgatgctggtccacctcctgtcatcccggaagaccatctcctttgctaggaccatttccttccctggctgtgccctgcagat gtacctgaccctggcgctgggatcaacggagtgcctgctgctggctgtgatggcatatgaccgttatgtggctatctgcca gccgcttaggtacccagagctcatgagtgggcagacctgcatgcagatggcagcgctgagctgggggacaggctttgc caactcactgctacagtccatccttgtctggcacctccccttctgtggccacgtcatcaactacttctatgagatcttggcagt gctaaaactggcctgtggggacatctccctcaatgcgctggcattaatggtggccacagccgtcctgacactggccccc ctcttgctcatctgcctgtcttaccttttcatcctgtctgccatccttagggtaccctctgctgcaggccggtgcaaagccttct ccacctgctcagcccaccgcacagtggtggtggttttttatgggacaatctccttcatgtacttcaaacccaaggccaagg atcccaacgtggataagactgtcgcattgttctacggggttgtgacgccctcgctgaaccccatcatttacagcctgagga atgcagaggtgaaagctgccgtcctaactctgctgagaggaggtttgctctccaggaaagca (SEQ ID NO: 133)

MOOSE06931 ctg4256 14682446..14682793, 14711763..14712371, MAWENQTFNSDFLLLGIFNHSPTHTFLFFLVLAJFSVAFMGNS3MVLL 3YLDTQLHTPI^TYFLLSQLSLIvTOLMLICTTW3a_vIAFNYLSGSKSISMAGCATQ IFFYISLLGSECFLLACFLLAAMAYDRYAAVCHPLRYPTLMSWQLCLRMTM SSWLLGAADGLLQAVATLSFPYCGAHEIDHFFCEAPVLVRLACADTSVFEN AMYICCVLMLLWFSLILSSYGLILAAVLLMRSTEAJ^EXAFATCSSHVAVVG LFYGAGTFTYMI^KSIJRSTINUHDKVVSAFYTIVIFTPLLNPLIYSVRNSEVKEAL KRWLGTCVNLKHQ (SEQ ID NO: 136) atggcatgggagaatcagaccttcaactctgacttcctcctcctgggaatcttcaatcatagccccacccacac cttcctcttctttctggtcctggccatcttttcagtggccttcatgggaaactccatcatggttctcctcatctacctggataccc agctccacacccccatgtacttcctcctcagccaactgtccctcatggacctcatgctcatctgcaccactgtacccaagat ggccttcaactacttgtctggcagcaagtccatttctatggctggctgtgccacacaaattttcttctatatatcattgcttggct ccgaatgctttctgttggcttgcttcctcttagcagccatggcctatgaccgctatgcggctgtctgccacccactccgatat cccactctcatgagctggcagctgtgcctgaggatgaccatgtcgtcctggctcctgggtgcagctgacggcctcctgca ggctgttgctaccctgagcttcccatattgcggtgcacacgagatcgatcacttcttctgcgaggcccccgtgttggtgcgt ttggcttgtgctgacacttcagtcttcgaaaacgccatgtacatctgctgtgtgttaatgctcctggtccccttttccctcatcct gtcctcctatggtctcatcctcgctgctgttctgctcatgcgctctacagaagcccgcaagaaggcctttgccacctgctctt cacatgtggctgtggtgggactcttttatggagctggcatttttacctatatgagacccaaatcccacaggtccactaacca cgataaggttgtgtcagccttctatactatgttcacccctttactaaatcccctcatctacagtgtgaggaacagtgaggtca aggaagccctgaaacggtggctggggacgtgtgtaaacctaaaacaccag (SEQ ID NO: 135) MOOSE06932 ctgl59444535454.4536368, 4542570..4542593,

ASGNHTPVTKFILQGFSNYPDLQELLFGATLLIYAITWGNLGMMALI FTDSHLQSPMYFFLNVLSFLDICYSSVVTPKLLVNFLVSDKSISFEGCWQLA FFVVHVTAESFLLASMAYDRFLAICQPLHYGS3MTRGTCLQLVAVSYAFGG ANSAIQTGNWAXPFCGPNQLTHYYCDIPPLLHLACANTATARVVLYVFSAL VTLLPAAVILTSYCLVLVAIGRMRSVAGREIΦLSTCASIJFLAIAIFYGTVVFT

YVQPHGSTNNTNGQVVS YTIIffMLNPFIYSL3 NKΕVKGALQRKLQKFVC HSKK (SEQ ID NO: 138) gccagtggcaaccacaccccagtcaccaagttcatcttgcagggattctccaattatccagacctccaggagc ttctcttcggagccatcctgctcatctatgccataacagtggtgggcaacttgggaatgatggcactcatcttcacagactc ccatctccaaagcccaatgtatttcttcctcaatgtcctctcgtttcttgatatttgttactcttctgtggtcacacctaagctcttg gtcaacttcctggtctctgacaagtccatctcttttgagggctgtgtggtccagctcgccttctttgtagtgcatgtgacagct gagagcttcctgctggcctccatggcctatgaccgcttcctagccatctgtcaacccctccattatggttctatcatgaccag ggggacctgtctccagctggtagctgtgtcctatgcatttggtggagccaactccgctatccagactggaaatgtctttgcc ctgcctttctgtgggcccaaccagctaacacactactactgtgacataccaccccttctccacctggcttgtgccaacacag ccacagcaagagtggtcctctatgtcttttctgctctggtcacccttctgcctgctgcagtcattctcacctcctactgcttggt cttggtggccattgggaggatgcgctcagtagcagggagggagaaggacctctccacttgtgcctcccactttctggcca ttgccattttctatggcactgtggttttcacctatgttcagccccatggatctactaacaataccaatggccaagtagtgtccgt cttctacaccatcataattcccatgctcaatcccttcatctatagcctccgcaacaaggaggtgaagggcgctctgcagag gaagcttcagaaatttgtttgtcatagcaaaaaa (SEQ ID NO:137)

MOOSE06935 ctg4256 15779735..15780627, 15792256..15792301,

MEQSNYSVYADFILLGLITHPAFPGLLFAWFS3FVVAITANLVMILLI 3JMDS3^HTPMYFLLSQLS3 DTIYICITVPKMLQDLLSiπ KTISFLGCAVQIF YLTLIGGEFFLLGLMAYDRYVAVCNPLRYPLLMNRRVCLFMVVGSWVGGS LDGFMLTPVTMSFPFCRSRE3N33FFCE3PAVLKLSCTDTSLYETLMYACCVL

MLL3PLSVISVSYTHILLTV3J3^MNSAEG3 RE-AFATCSSHJJVrVVSVFYGAAFY TNVLPHSYHTPEIODKVVSAFYTILTPMLNPLIYSLRNKDVAAALRKVLGRC GSSQSI (SEQ ID NO: 140) atggagcagagcaattattccgtgtatgccgactttatccttctgggcctcatcacccatcctgccttccccggg cttctctttgcagtagtcttctccatctttgtggtggctataacagccaacttggtcatgattctgctcatccacatggactccc gcctccacacacccatgtacttcttgctcagccagctctccatcatggataccatctacatctgtatcactgtccccaagatg ctccaggacctcctgtccaaggacaagaccatttccttcctgggctgtgcagttcaaatcttctacctgaccctgattggag gggaattcttcctgctgggtctcatggcctatgaccgctatgtggctgtgtgcaaccctctacggtaccctctcctcatgaac cgcagggtttgcttattcatggtggtcggctcctgggttggtggttccttggatgggttcatgctgactcctgtcactatgagt ttccccttctgtagatcccgagagatcaatcactttttctgtgagatcccagccgtgctgaagttgtcttgcacagacacgtc actctatgagaccctgatgtatgcctgctgcgtgctgatgctgcttatccctctatctgtcatctctgtgtcctacacgcacatc ctcctgactgtccacaggatgaactctgctgagggccggcgcaaagcctttgctacgtgttcctcccacattatggtggtg agcgttttctacggggcagccttctacaccaacgtgctgccccactcctaccacactccagagaaagataaagtggtgtct gccttctacaccatcctcacccccatgctcaacccactcatctacagcttgaggaataaagatgtggctgcagctctgagg aaagtactagggagatgtggttcctcccagagcatc (SEQ ID NO: 139)

MOOSE06944 ctgl59444923328..4923807, 4934939..4935415,

MAEMNLTLVTEFLLIAFTEYPEWALPLFLLFLFMYLITVLGNLEMΠLI LMDHQLHAPMYFLLSHLAFMDVCYSSΓΓVPQMLAVLLEHGAALSYTRCAA QFFLFTFFGSIDC YLLALMAYDRYLAVCQPLLYVTILTQQARLSLV AGAYVA GLISALVRTCLCSTVTAFTLSFCGNNEINFIFCDLPPLLI SCGDSYTQEWIJV FALFVMPACILVILVSYLFIIVAILQIHSAGGRAKTFSTCASHLTAVALFFGTLI FMYL3 DNTGQSSEGDRVVSVLYTVVTPMLNPL3YSLRNI^VXEATILKALSK SKPARRP (SEQ ID NO: 142) atggcagagatgaacctcaccttggtgaccgagttcctccttattgcattcactgaatatcctgaatgggcactc cctctcttcctcttgtttttatttatgtatctcatcaccgtattggggaacttagagatgattattctgatcctcatggatcaccag ctccacgctccaatgtatttccttctgagtcacctcgctttcatggacgtctgctactcatctatcactgtcccccagatgctg gcagtgctgctggagcatggggcagctttatcttacacacgctgtgctgctcagttctttctgttcaccttctttggttccatcg actgctacctcttggccctcatggcctatgaccgctacttggctgtgtgccagcccctgctttatgtcaccatcctgacacag caggcccgcttgagtcttgtggctggggcttacgttgctggtctcatcagtgccttggtgcggacatgcctttgttcgacgg tcacagccttcactctctccttttgtggaaacaatgagatcaacttcattttctgtgacctccctcctctattaaaactctcctgt ggggacagctacactcaggaagtggtgattattgtgtttgctcttttcgtcatgcctgcctgtatcttggtgatcttggtatcct acctgtttatcattgtggccatcctgcagatccactctgctggaggccgggccaagaccttctccacctgcgcctcccacc tcactgccgtcgctcttttctttggcaccctcatcttcatgtacctgcgagacaacacaggccagtcctccgagggagacc gagtggtgtctgtgctctacacggtggtgaccccaatgctgaatccccttatctatagcctgagaaacaaggaggtaaaa gaggccactaggaaagccctgagcaaatcaaagcctgctagaagaccc (SEQ ID NO: 141)

MOOSE06949 ctg4256 15008940..15009881,

MKTGNQSFGTDFLLVGLFQYGW3NSLLFVV3ATLFTVALTGNIMLIHL IRLNTRLHTPMYFLLSQLSIVDLMYISTTVPKMAVSFLSQSKT3RFLGCEIQTY

VTLALGGTEALLLGFMSYDRYVAIC3JPL33YPMLMSKKICCLMVACAWASG S3NAFmTLYWQLPFCRS3 LIN33FFCEWALLSLVCQDTSQYEYTVLLSGLIIL LLPFLAILASYARVLIVVFQMSSGKGQAKAVSTCSSHLIVASLFYATTLFTYT I^HSLRSPSPJDKAVAWYTIVTPLLNPFIYSLRNKEVTGAVIIIILLGYWICCR KY (SEQ ID NO: 144) atgaaaacaggaaatcaaagttttgggacagattttctacttgttggtcttttccaatatggctggataaactctctt ctctttgtcgtcattgccaccctctttacagttgctctgacaggaaatatcatgctgatccacctcattcgactgaacaccaga ctccacactccaatgtactttctgctcagtcagctctccatcgttgacctcatgtacatctccaccacagtgcccaagatggc agtcagcttcctctcacagagtaagaccattagatttttgggctgtgagattcaaacgtatgtgttcttggcccttggtggaac tgaagcccttctccttggttttatgtcttatgatcgctatgtagctatctgtcaccctttacattatcctatgcttatgagcaagaa gatctgctgcctcatggttgcatgtgcatgggccagtggttctatcaatgctttcatacatacattgtatgtgtttcagcttccat tctgtaggtctcggctcattaaccactttttctgtgaagttccagctctactatcattggtgtgtcaggacacctcccagtatga gtatacagtcctcctgagtggacttattatcttgctactaccattcctagccattctggcttcctatgctcgtgtgcttattgtggt attccagatgagctcaggaaaaggacaggcaaaagctgtttccacttgttcctcccacctgattgtggcaagcctgttctat gcaaccactctctttacctacacaaggccacactccttgcgttccccttcacgggataaggcggtggcagtattttacacca ttgtcacacctctactgaacccatttatctacagcctgagaaataaggaagtgacgggggcagtgaggagactgttggga tattggatatgctgtagaaaatat (SEQ ID NO: 143)

MOOSE06952 ctg22fin2 127652..127674, 157267..158171, 190073..190089, ME3 KNRFAFVNEFILQGFSCEWTIQIFLFSLFTTTYALTITGNGAIAFV

LWCDRRLHTPMYMFLGNFSFLE3WYVSSTVP30vdLVI^LSEKKNISFAGCFL QFYFFFSLGTSECLLLTVMAFDQYLAICRPLLYPNIMTGHLYAKLVILCWVC GFLWFLIPJVLISQMPFCGPNIJDHVVCDPGPRFALDCVSAPRIQLFCYTLSSL V GNFLFπGSYTLVLE-AMLGIVffSSTGi KAFSTCGSHLAVVSLCYSSLMV MYVSPGLGHSTGMQKffiTLFYAMVTPLFNPLIYSLQNKEIKAALRKVLGKK QFCSKM (SEQ ID NO: 146) atggaaaggaaaaaccgctttgcttttgtaaatgaatttatactccaaggtttctcttgtgagtggacaattcagat cttcctcttctcactctttactacaacatatgcactgactataacagggaatggagccattgcttttgtcctgtggtgtgaccg gcgacttcacactcccatgtacatgttcctgggaaatttctcctttttagagatatggtatgtctcttctacagttcccaagatgt tggtcaacttcctttcagagaaaaaaaacatctcctttgctggatgttttctccagrtttatttcttctt atgcttgcttttgactgtgatggcctttgatcagtaccttgctatctgccgtcccttgctctatcctaatatcatgactgggcatc tctatgccaaactggtcatactgtgctgggtttgtggatttctgtggttcctgatccccattgttctcatctctcagatgcccttct gtggcccaaacattattgaccatgttgtgtgtgacccagggccacgatttgcattggattgtgtttctgccccaagaatccaa ctgttttgctacactctaagctcattagttatttttggtaacttcctctttattattggatcctatactcttgtcctgaaagctatgttg ggtatgccttcaagcactgggagacataaggccttctctacctgtgggtctcatttggctgtggtatcactgtgctatagctc tcttatggtcatgtatgtgagcccaggactcggacattctacagggatgcagaaaattgaaactttgttctatgctatggtga ccccactcttcaatccccttatctatagcctccagaataaggagataaaggcagccctgaggaaagttctggggaagaaa cagttttgcagcaaaatg (SEQ ID NO: 145) MOOSE06953 ctg30162417211..418141,

MDKNQTEVMREFFLSGFSQTPSffiAGLFVLFLFFYMS3WVGNVLIMV TVASDKYLNSSPMYFLLGNLSFLDLCYSTVTTPKLLADFFNHEKLISYDQCI VQLFFLHFVGAAEMFLLTVMAYDRYVAICRPLHYTTVMSRGLCCVLVAAS WMGGFVHSTVQTILTVHLPFCGPNQVENTFFCDVPPVKLACADTFVIELLM VSNSGLISTISFVVLISSYTTILVKI SI^GRRKALSTCASHLMVVTLFFGPCIFI YAI^FSTFSVDKMVSVLYNVITPMLl\rPLIYTL3^NEΕVKSAMQKLWVIlNGLT WKK (SEQ ID NO: 148) atggataaaaaccaaacagaagtgatgagagaatttttcttgtcagggttctcacagacaccatctattgaagca gggctatttgtactatttcttttcttctatatgtccatttgggttggcaatgtcctcatcatggtcacagtagcatctgataaatac ctgaattcatcacccatgtatttccttcttggcaacctctcatttctggacctatgttattcaacagtaacgacccctaagcttct ggctgacttctttaatcatgaaaaactcatttcctatgaccaatgcattgtgcaactcttcttcctgcattttgtaggggcagct gagatgttcctgctcacagtgatggcgtacgatcgctatgttgcaatctgtcgcccgctgcactacaccactgtcatgagtc gggggttatgctgtgtgttggttgctgcctcctggatgggaggatttgtgcactccactgtccagaccattctcactgtccat ctacccttttgtgggccaaatcaggtggaaaacacttttttttgtgatgttccccctgtcatcaaacttgcttgtgctgacacttt tgtcattgaattgctcatggtatctaacagtgggttgatctccaccatctcctttgtggtgctgatttcctcctacaccactatcc tagtcaagattcgctccaaggaaggaaggcgaaaggcactctccacgtgtgcctctcacctcatggtggtaacactgtttt ttggaccctgtattttcatctacgctcgtcctttctctacattttctgtggacaagatggtgtctgtactctacaatgttattaccc caatgctaaaccccctcatctacacacttcggaacaaagaggtaaagtcagccatgcagaagctctgggtcagaaatgg gcttacttggaaaaag (SEQ ID NO: 147)

MOOSE06954 ctgl 5944 3276061..3276997,

MQRSNHTVTEFILLGFTTDPGMQLGLFWFLGVYSLTVVGNSTLΓVLI

CNDSCLHTPMYFFTGNLSFLDLWYSSVYTPKILVTCISEDKSISFAGCLCQFF

FSAGLAYSECYLLAAVAYDRYVAISKPLLYAQAMSTKXCALLVAVSYCGGF INSSΠTIO TFSFNFCMNIIDDFFCDLLPLVELACGEKGGYKIMMYFLLASNV ICPAVLJXASYLFIITSVLMSSSKGYLKAFSTCSSHLTSVTLYYGSILYTYALPR SSYSFDMD3πVSTFYTVVFPMLNLMT^SL3^NKDVKEALKKLLSHKSIlLSPP (SEQ ID NO: 150) atgcagaggagcaatcatacagtgactgagtttatactgctgggcttcaccacagacccaggaatgcagctg ggcctcttcgtggtgttcctgggcgtgtactctctcactgtggtaggaaatagcaccctcatcgtgttgatctgtaatgactc ctgcctccacacacccatgtattttttcactggaaatctgtcgtttctggatctctggtattcttctgtctacaccccaaagatcc tagtgacctgcatctctgaagacaaaagcatctcctttgctggctgcctgtgtcagttcttcttctctgcagggctggcctata gtgagtgctacctgctggctgccgtggcttatgaccgctacgtggccatctccaagcccctgctttatgcccaggccatgt ccataaagctgtgtgcattgctggtagcagtctcatattgtggtggctttattaactcttcaatcatcaccaagaaaacgt ttc ctttaacttctgccgtgaaaacatcattgatgactttttctgtgatttgcttcccttggtggagctggcctgtggcgagaaggg cggctataaaattatgatgtacttcctgctggcctccaatgtcatctgccccgcagtgctcatcctggcctcctacctctttat catcaccagtgtcttgaggatctcctcctccaagggctacctcaaagccttctccacatgctcctcccacctgacctctgtc actttatactatggctccattctctacatctacgctctccccagatctagctattcttttgatatggacaaaatagtttctacatttt acactgtggtattccccatgttgaatctcatgatctacagcctaaggaataaggatgtgaaagaggctctgaaaaaacttct ctcccataaatcaagattatctccacca (SEQ ID NO: 149)

MOOSE06957 ctgl3910 4016560..4017448, 4027068..4027121,

MAEENKILVTHFVLTGLTDHPGLQAPLFLVFLVIYLITLVGNLGLMAL IWKDPHLHTPIYLFLGSLAFADACTSSSVTSKMLINFFLSK-NHMLSMAKCAT QFYFFGSNATTECFLLWMAYDRYVAICNPLLYPWMSNSLCTQFIGISYFIG

FLHSAIHVGLLFRLTFCRSNII3TYFYCEILQLF3πSCTNPTVNILL3FIFSAFIQVF TFMTLIVSYSYILSAILKKJ^EKGRSKAFSTCSAHLLSVSLFYGTLFFMYVSS RSGSAADQAKMYSLFYTI3IPLLNPFlYSL3iNKEVIΞRCIRNLLICRFIFFIS (SEQ ID NO: 152) atggcagaagaaaataagattctggtgactcactttgtcctcacaggactcacagatcatccagggctgcagg cgcccctgttcctggtgttcttggtcatctacctcatcaccctggtgggcaaccttggcctgatggctctcatctggaagga cccccaccttcacacccccatatacttatttcttggcagtttagcctttgcagatgcatgcacttcatcctctgtaacttctaag atgcttatcaatttttttttatcaaagaatcatatgctatccatggctaagtgtgccacccagttttacttttttggttccaatgcaa ccacagaatgcttcctgctggtagtgatggcctatgaccgctatgtagccatatgcaatcccttgctttatccagtggtgatg tccaatagcctctgtactcagtttataggtatttcatatlttattggttttctgcattcagcgattcatgtgggtttgttatttagatta actttctgcaggtccaatattatacattatttctactgtgaaattttacagctgttcaaaatttcttgcaccaatcctacagttaata tacttctgattfrcatcttttcagcatttatacaagtcttcacttttatgactcttatcgtctcttactcctatattctctctgccatcct gaaaaagaagtctgagaagggtagaagcaaagccttctctacttgcagtgcccatctgctctctgtctctttgttctacggc accctcttcttcatgtatgtgagttctaggtctggatcagctgcagatcaggccaaaatgtattctttattttacacaataataat tcctttactaaatccttttatttacagcctaaggaacaaagaggtgcataggtgcataagaaacttactgatatgtagattcat attttttatttct (SEQ ID NO: 151)

MOOSE06959 ctgl3464 3864087..3864422, 3883462..3884061,

MVGANHSVVSEF LGLTNSWE3RLLLLVFSSMFYMASMMGNSLIL LTVTSDP33LHSPMYFLLAl^SF3bLGVSSVTSP3ζM3YDLFiyKHEVISFGGCJA

QIFFIJJVIGGVEMMVLLJAMAFDRYVAVC^LIJYLTIMIIPItMCILI VASWA iGL SLVQLSFVVNLPFCGPNVLDSFYCDIPQLIKXACTNTYKLQFMVTANS GFISLSAFFLL3LSY3FILATLQI HSSGGSSKAVSTLSAHITVVVLFFGPLIFFYV WPSPPTHL1^3π^?LA3FDAJFTPFLNPVIYTFRNREI^αAIRRVFGQFMGFRKT (SEQ ID NO: 154) atggttggggcaaatcactccgtggtgtcagagtttgtgttcctgggactcaccaattcctgggagatccgactt ctcctccttgtgttctcctccatgttttacatggccagtatgatgggaaactctctcattttgctcactgtgacttctgaccctca cttgcactcccccatgtattttctgttagccaacctctccttcattgacctgggtgtttcctctgtcacttctcccaaaatgattta tgacctgttcagaaagcacgaagtcatctcctttggaggctgcatcgctcaaatcttcttcatccacgtcattggcggtgtgg agatgatggtgctgctcatagccatggcctttgacagatatgttgccgtatgtaagccccttcactacctgaccatcatgcat ccaagaatgtgcattttgattctagtggcttcctgggccattggtctcattcactcattggtccaattgtcttttgtagtaaacttg cccttctgtggccctaatgtgttggacagcttttactgtgacatacctcagctcatcaaacttgcttgcacaaatacctataaa ctgcagttcatggttactgctaatagtgggttcatttccttgagtgctttcttcttgctcatcctctcttacatcttcattctggcca ctcttcagaaacactcctcaggaggctcatccaaggctgtctctactctgtcagctcatattactgttgtggttttattctttggt ccactgatttttttctatgtatggccctctcctccaacacatctgaataaatttctagccatatttgatgccattttcactccttttct gaatccagtcatctacacattcaggaacagggaaatgaagattgcaataaggagagtgttcggtcaatttatgggttttaga aaaact (SEQ ID NO: 153)

MOOSE06965 _. ctgl3464 3819604..3820057, 3832510..3833006, MDEANHSWSEFVFLGLSDSRKIQLLLFLFFSVFYVSSLMGNLL3VLT

VTSDPI^QSPMYFLLANLSI3NLVFCSSTAPKMIYDLFRKHKTISFGGCVVQIF FIHAVGGTEMVLLIAMAFDRYVAICKPLHYLTIMNPQRCILFLVISWIIATSSπ GLIHSLVQLVFWDLPFCGPNJFDSFYCDLPRLLRLACTNTQELEFMVTVNS GLISVGSFVLLVISYJFILFTVWIOISSGGLAKALSTLSAITVTVVILFFGPLMFF YTWPSPTSHLDKYLA3FDAFITPFLNP V3YTFRNKDMKVAMIi3iLCSIlLAHFT KI (SEQ ID NO: 156) atggatgaagccaatcactctgtggtctctgagtttgtgttcctgggactctctgactcgcggaagatccagctc ctcctcttcctctttttctcagtgttctatgtatcaagcctgatgggaaatctcctcattgtgctaactgtgacctctgaccctcgt ttacagtcccccatgtacttcctgctggccaacctttccatcatcaatttggtattttgttcctccacagctcccaagatgattta tgaccttttcaggaagcacaagaccatctcttttgggggctgtgtagttcagatcttctttatccatgcagttgggggaactg agatggtgctgctcatagccatggcttttgaccgatatgtggccatatgtaagcctctccactacctgaccatcatgaaccc acaaaggtgcaltttgtttttagtcatttcctggattatagccacttcctctatcattggccttatccactcattggtccaattagtt tttgtggtagatttacctttttgtggtcctaatatctttgacagtttttactgtgatctccctcggctcctcagacttgcctgtacca acacccaagaactggagttcatggtcactgtcaatagtggactcatttctgtgggctcctttgtcttgctggtaatttcctacat cttcattctgttcactgtttggaaacattcttctggtggtctagccaaggccctctctaccctgtcagctcatgtcactgtggtc atcttgttctttgggccactgatgtttttctacacatggccttctcccacatcacacctggataaatatcttgctatttttgatgcat ttattactccttttctgaatccagttatctacacattcaggaacaaagacatgaaagtggcaatgaggagactgtgcagtcgt cttgcgcattttacaaagatt (SEQ TD NO: 155) MOOSE06970 ctg30162 1054913..1054933, 1055717..1056623,

1081348..1081364,

MEIRNFSDPTEFVLAGLPNLNSARVELFSVFLLVYLLNLTGNVLIVGV VRADTRLQTPMYFFLGNLSCLEILLTSVITPKMLSNFLSRQHTISFAACITQFY FYFFLGASEFLLLAVMSADRYLAICHPLRYPLLMSGAVCFRVALACWVGGL VPVLGPTVAVALLPFCKQGAWQHFFCDSGPLLRLACTNT3< 3ζLEETDFVLA

SLVIVSSLLITAVSYGL3VLAVLS3PSASGRQI AFSTCTSHLIWTLFYGSAIFL YVl^SQSGSVDTNWAVTVITTFVTPLLNPFJYALRNEQVl^ALKDMFl KJαi DCSFN (SEQ ID NO: 158) atggagataaggaactttagtgatccaacagagttcgtcctggcagggctcccaaatctcaacagcgcaaga gtggaattattttctgtgtttcttcttgtctatctcctgaatctgacaggcaatgtgttgattgtgggggtggtaagggctgatac tcgactacagacccctatgtacttctttctgggtaacctgtcctgcctagagatactgctcacttctgtcatcattccaaagat gctgagcaatttcctctcaaggcaacacactatttcctttgctgcatgtatcacccaattctatttctacttctttctcggggcct ccgagttcttactgttggctgtcatgtctgcggatcgctacctggccatctgtcatcctctgcgctaccccttgctcatgagtg gggctgtgtgctttcgtgtggccttggcctgctgggtggggggactcgtccctgtgcttggtcccacagtggctgtggcct tgcttcctttctgtaagcagggtgctgtggtacagcacttcttctgcgacagtggcccactgctccgcctggcttgcaccaa caccaagaagctggaggagactgactttgtcctggcctccctcgtcattgtatcttccttgctgatcactgctgtgtcctacg gcctcattgtgctggcagtcctgagcatcccctctgcttcaggccgtcagaaggccttctctacctgtacctcccacttgata gtggtgaccctcttctatggaagtgccatttttctctatgtgcggccatcgcagagtggttctgtggacactaactgggcagt gacagtaataacgacatttgtgacaccactgttgaatccattcatctatgccttacgtaatgagcaagtcaaggaagctttga aggacatgtttaggaagaagagggactgtagctttaat (SEQ TD NO: 157) MOOSE06974 ctgl3517 1291127..1292063,

MIHK-NHTPVTEVPLMGIPHTKGMENVLFVLFLAFYLFTLLGNLLILLA VLTFSNLHTPMYFFLGNLSVFD3FFPSVSSPKMMLCLVGQSCTISFQGCASQL FFIJIiFLGCTECFLYTVI^AYDRFAAICIJPLPYTVIM RRVCALLTLGTWTGS CLHASVLTLLTFia.SYCGPNEVDNIFFCDIPWLPLACADTSLARTVSFINVG VVALMCFLLILTSYACrVIS3LIUSSSEGI^RRAFSTCSAIJLTSILLFYGPIVLIYL IH⁾ASSPWLDSVVQVLNMVffSLNPLIYTL3^NKGVI LALIlKVLIQGV3JNCGR (SEQ ID NO: 160) atgaagataaagaatcacactccagtaactgaggtccccctgatgggaatccctcatacaaaggggatggaa aatgtgctttttgtcttatttctggccttctacctcttcaccttgctggggaacctactcattcttctggccgtcctcactttctcca acctccacacccccatgtatttcttcctgggaaacctgtctgtgtttgacatatttttcccttcagtgagttcccccaaaatgat gctctgcttagtgggacaaagctgcaccatctctttccagggttgtgcctcccagctcttctttcaccatttcctgggttgcac cgagtgtttcctgtacactgtgatggcctatgaccgatttgcagccatctgccaccctttgccatacacggtcatcatgaaac gcagggtgtgtgccctcctgacgctaggcacctggacggggagctgtctgcatgcatctgtcctcacactcctcatcttta agttatcctactgtggccccaatgaagtggacaatatttttttctgtgatattccggtggtgctgcccctggcctgcgcagac acctctctagcacggacagtgagtttcatcaacgtaggtgttgttgcgctcatgtgttttcttcttatcctcacctcttatgcttg cattgttatctctatactgaaaatcagttcctcagaaggtaggcgcagagccttctcaacctgcagtgcccatctgacgtcc atcctgctcttctatggaccaatagtcctcatttatctccgacctgcctccagcccttggctggactctgtggttcaggtgttg aataatattgttatcccttccctgaatcctttgatatatactttgagaaacaaaggtgtaaagctggcactgagaaaggtgctc attcaaggagtacataattgtggaagg (SEQ ID NO: 159)

MOOSE06975 ctgl80 11555451..11556386,

MALGNHSTITEFLLLGLSADPN ALLFVLFLGIYLLTIMENLMLLLMI RADSCLHKPMYFFLSHLSFVDLCFSSVIVPKMLENLLSQRKTIS VEGCLAQV

FFVFVTAGTEACLLSGMAYDRHAAICRPLLYGQIMGKQLYMHLVWGSWGL GFLDALI^JVLLAVNMVFCEAKIIHHYSYEMPSLLPLSCSDISRSLIALLCSTLL HGLGNFLLVFLSYTRΠSTILSISSTSGRSKAFSTCSAHLTAVTLYYGSGLLRH LMPNSGSPTEL3FSVQYTVVTPIYΠ NSLLYSLIQNKEVKVALKRTLEKYLQYTR R (SEQ ID NO: 162) atggccttggggaatcacagcaccatcaccgagttcctcctccttgggctgtctgccgaccccaacatccggg ctctgctctttgtgctgttcctggggatttacctcctgaccataatggaaaacctgatgctgctgctcatgatcagggctgatt cttgtctccataagcccatgtatttcttcctgagtcacctctcttttgttgatctctgcttctcttcagtcattgtgcccaagatgct ggagaacctcctgtcacagaggaaaaccatttcagtagagggctgcctggctcaggtcttctttgtgtttgtcactgcagg gactgaagcctgccttctctcagggatggcctatgaccgccatgctgccatctgccgcccactactttatggacagatcat gggtaaacagctgtatatgcaccttgtgtggggctcatggggactgggctttctggacgcactcatcaatgtcctcctagct gtaaacatggtcttttgtgaagccaaaatcattcaccactacagctatgagatgccatccctcctccctctgtcctgctctgat atctccagaagcctcatcgccttgctctgctccactctcctacatgggctgggaaacttccttttggtcttcttatcctacaccc gtataatctctaccatcctaagcatcagctctacctcgggcagaagcaaggccttctccacctgctctgcccacctcactgc agtgacactttactatggctcaggtttgctccgccatctcatgccaaactcaggttcccccatagagttgatcttctctgtgca gtatactgtagtcactcccatgctgaattccctcatctatagcctgaaaaataaggaagtgaaggtagctctgaaaagaact ttggaaaaatatttgcaatataccagacgt (SEQ ID NO: 161)

MOOSE06977 ctg4256 15681676..15682181, 15705271-15705688, 15721124..15721138,

TSQNQTASTDFTLTGLFAESKIJAALLYTVTFLLFLMALTGNALLILLI HSEPPLHTPMYFFISQLALMDLMYLCVTVPKMLVGQVTGDDTISPSGCGIQ MFFHLTLAGAEVFLLAAMAYDRYAAVCRPLHYPLLMNQRVCQLLVSACW VLGMVDGLLLTPITMSFPFCQSWETHHFFCEVPAVTILSCSDTSLYETLMYLC CVLMLLIPVTπSSSYLLILLTV3ΪRMNSAEGRiα AFATCSSHLTVVILFYGAA VYTYMLPSSYHTPEIΠ)MMVS YTIUTPVLNPLΓYSLRNIΠDVMGALKKMLT VRFTHSEW (SEQ D3 NO: 164) acttctcagaatcaaacagcaagcactgatttcaccctcacgggactctttgctgagagcaagcatgctgccct cctctacaccgtgaccttccttcttttcttgatggccctcactgggaatgccctcctcatcctcctcatccactcagagccccg

. 5 cctccacacccccatgtacttcttcatcagccagctcgcgctcatggatctcatgtacctatgcgtgactgtgcccaagatg cttgtgggccaggtcactggagatgataccatttccccgtcaggctgtgggatccagatgttcttccacctgaccctggct ggagctgaggttttcctcctggctgccatggcctatgaccgatatgctgctgtttgcagacctctccattacccactgctgat gaaccagagggtgtgccagctcctggtgtcagcctgctgggttttgggaatggttgatggtttgttgctcacccccattacc atgagcttccccttttgccaatcctgggagattcatcatttcttctgtgaagtccctgctgtaacgatcctgtcctgctcagaca

10 cctcactctatgagaccctcatgtacctatgctgtgtcctcatgctcctcatccctgtgacgatcatttcaagctcctatttactc atcctcctcaccgtccacaggatgaactcagcagagggccggaaaaaggcctttgccacctgctcctcccacctgactgt ggtcatcctcttctatggggctgccgtctacacctacatgctccccagctcctaccacacccctgagaaggacatgatggt atctgtcttctataccatcctcactccggtgctgaaccctttaatctatagtcttaggaataaggatgtcatgggggctctgaa gaaaatgttaactgtgagattcactcactcagagtgg (SEQ ID NO: 163)

15

MOOSE06978 ctg4256 14815855-14816791,

MEMRNTTPDF3LLGLFNHTRAHQVLFMMVLS3VLTSLFGNSLMILLIH 3^TG3^HTPMYFLLSQLSLMDVMLVSTTW JAADYLTGNKAISRAGCGV Q3FFLPTLGGGECFLLAAMAYDRYAAVCHPLRYPTLMSWQLCLRMTMSSW

' 20 LLGAADGLLQAVATLSFPYCGAHE3DHFFCEAPVLVPvLACADTS VFENAMY ICCVLMLLWFSLILSSYGLILAAVLHMRSTEARKXAFATCSSHVAVVGLFY GAA1FTYMRPKSIJRSTNIJDKVVSAFYSMFTPLLNPLIYSVRNSEVKEALKR WLGTCVNLKHQ (SEQ ID NO: 166) atggagatgagaaatactaccccagactttattctcctgggactctttaaccacaccagagcccaccaagtcct

25 cttcatgatggttctgagtatcgttttgacctccctgtttggcaattccctcatgattctcctgattcaccgggacaccggccg gctccacacgcccatgtacttcctcctgagccaactctccctcatggacgtgatgctggtttccaccactgtgcccaaaatg gcggctgactacttgaccggaaataaggccatctcccgcgctggctgtggtgtgcagatcttcttcctccccacactgggt ggtggagagtgcttcctcttagcagccatggcctatgaccgctatgcggctgtctgccacccactccgatatcccactctc atgagctggcagctgtgcctgaggatgaccatgtcgtcctggctcctgggtgcagctgacgggctcctgcaggctgttgc

30 taccctgagcttcccatattgcggtgcacacgagatcgatcacttcttctgcgaggcccccgtgctggtgcgtttggcttgt gctgacacttcagtcttcgaaaacgccatgtacatctgctgtgtgttaatgctcctggtccccttttccctcatcctgtcctcct atggtctcatcctcgctgctgttctgcacatgcgctctacagaagcccgcaagaaggccttcgccacctgctcttcacatgt ggctgtggtgggactcttttatggagctgccatttttacctatatgagacccaaatcccacaggtccactaaccacgacaag gttgtgtcagccttctatagtatgttcacccctttactaaaccccctcatctacagtgtgaggaacagtgaggtcaaggaag

35 ccctgaaacggtggctggggacatgtgtaaacctgaaacaccag (SEQ D3 NO: 165)

MOOSE06983 ctgl5296 2052460..2053387,

MENRNNVTEFVLLGLTENPKMQKITFVVFFFVIYΠTVVGNALIVVTIT 40 ASPSLGSPMYLFLAYLSF3DACYSSVNTPK ITDSLYGKNTILFNGCMTQVFG

E3TFFGGAEG3XLTVMAYDRYVAIC30^>L33YMTIMNQCVYALLMGVVWMGG FLHATIQILF3FQLPFCGPNVroHFMCDLNPLLNLACTDTF£MLGLFIAANSGFI CLLl^VLLLVSYVV3LRSLRTHSLEARFfKALSTCVSfflTVVILFFVPCIFVYM I^AATLPIDKAVAIFYTMITPMLNPLIYTLIWAQMKNAIRKXCSRKDISGNK

45 (SEQ ID NO: 168) atggagaataggaataacgtgacagagtttgttttactagggcttacagagaatccaaagatgcagaaaatcat atttgttgtgtttttttttgtcatctatatcatcactgtggtgggaaatgcgctcattgtggtcaccatcactgccagcccatcact ggggtcccccatgtaccttttcctggcctatctctcctttatagatgcctgctattcttctgtcaatacccctaagctgatcaca gattcactctatggaaagaacaccatcctattcaatggatgcatgactcaagtctttggagaacatttcttcggaggtgcag

5₀ agggtatcctacttactgtgatggcctatgaccgctatgtggccatctgcaagcccttgcactatatgactatcatgaacca gtgtgtgtatgccctgctaatgggagtggtgtggatgggaggctttcttcatgcaaccatacagatcctcttcatcttccaatt acctttctgtggtcctaatgtcatagatcactttatgtgtgatctgaaccctttgctcaacctcgcctgcactgacacccatatg ctgggactcttcattgctgccaacagtggattcatctgcttgttaaactttgtcctcctgctggtctcctatgtggtcatcttgcg ctccctaaggactcacagcttggaggcaaggcacaaagccctctccacctgtgtctcccacatcacagttgtcatcttattc

5 tttgtgccctgcatatttgtgtacatgagacctgcagctactttacctattgataaagcagttgctatattctacactatgataac tcctatgttaaaccccttaatctataccttgaggaatgcccagatgaaaaatgccatcaggaaattgtgtagtagaaaggac atttcaggtaacaaa (SEQ DD NO: 167)

MOOSE06987 ctgl4877 4245409..4246339, l o MKRANΉTELREFVFQGFSNFPEHQLTFFWFLALYTFLTLAGNFΠLAI

ΓYVDHHLHTPMYFFLSVLSTSETFYSLVΠPRMLSSLVGLSQSISLEGCGTQ3FF

FLGFAITNCLLLAVMEYDFIYVAVCNPLRYSVIIVINWRVCAILASSVCATGFS LSLVQTVAJFRLLFCTPLIEHFFCDVQPVLDLAWATPM3NDILTL3MSLLAITA PAIFLFISYVLπST3LiπTSAEGGKKTFATYASHLTVV3IHYGCASIAYFiα^>NLE 15 NTiπ)QDQLISVTYTVITPLLNPVVYGLRNKEVQDALQRVLGRKFFS (SEQ ID NO: 170) atgaagagagccaatcacacagagttaagagagtttgttttccaaggtttctccaattttccagaacatcagctc acattttttgtggtctttctcgccctctacacattcctaactctggctggcaatttcatcattctggccataatctatgttgaccat cacctccatactcctatgtacttctttttaagtgtgctatccacttcagagactttctattccctggtcattatcccacgcatgcttt 0 ccagccttgtaggcctgagccaatccatttccctggagggctgtgggactcagatctttttttttcttggctttgccatcacca actgcctcctgctagcagtaatggaatatgatcactacgtggccgtctgcaacccacttcgatactcagtcatcatgaattg gagggtgtgtgctatactggcatcatcagtctgtgccacagggttctcactctcactggttcagactgtggccattttcaggt tgctcttttgcaccccactgattgagcatttcttctgtgatgttcagcctgtgttggacctggcctgggctaccccaatgatca atgatattctgaccttaattatgagcctccttgccatcacagccccagccatcttcctcttcatctcttatgtccttattatttcca 5 ccattctcaagatcacctcagctgaaggcgggaagaagacctttgccacctatgcatcccacctcactgtggtcattatcc actatggctgtgcctccattgcctacttcaagcccaatttggagaataccaaagatcaggatcagttaatctcagtgaccta cactgtcataacacctttactaaaccctgttgtgtatggtctgagaaataaagaagtccaggatgctctgcagagagtgctg ggtaggaaattcttctcc (SEQ ID NO: 169) 0

MOOSE06997 ctgl5944 2146092..2147018,

MQQNNSVTEFILLGLTQDPLRQIΑVFVIFLIFYMGTWGNMLIIVTIKS SRTLGSPIVΓYFFLFYLSFADSCFSTSTAPRLWDALSEKKΠTYNECMTQVFAL

JJLFGClNffilFVLILMAVDRYVAICiαPLRYPTIMSQQVCIJLIVLAWIGSLIHSTA 5 QHLALRLPFCGPYLIDHYCCDLQPLLKXACMDTYMINLLLVSNSGAICSSSF

MILπSY ILHSLRl^SAKG J KALSACTSHIIVVILFFGPCTFr TRPPTTFPM DKMVAVFYTIGPPFL1^LIYTL3^AEV30 [AM3^KLWHGKIISENK (SEQ ID NO: 172) atgcagcaaaataacagtgtgactgaattcatactgttaggattaacacaggatcccttgaggcagaaaatagt 0 gtttgtaatcttcttaattttctatatgggaactgtggtggggaatatgctcattattgtgaccatcaagtccagccggacacta ggaagccccatgtacttctttctattfratttgtcctttgcagattcttgcttttcaacttccaca ctctctctgaaaagaaaattataacctacaatgagtgcatgacacaagtctttgcactacatttatttggctgcatggagatct ttgtcctcattctcatggctgttgatcgctatgtggccatctgtaagcccttgcgttacccaaccatcatgagccagcaggtct gcatcatcctgattgttcttgcctggatagggtctttaatacactctacagctcagattatcctggccttaagattgcctttctgt 5 ggaccctatttgattgatcattattgctgtgatttgcagcccttgttgaaacttgcctgcatggacacttacatgatcaacctgc tgttggtgtctaacagtggggcaatttgctcaagtagtttcatgattttgataatttcatatattgtcatcttgcattcactgagaa accacagtgccaaagggaagaaaaaggctctctccgcttgcacgtctcacataattgtagtcatcttattctttggcccatgt atattcatatatacacgccccccgaccactttccccatggacaagatggtggcagtattttatactattggaccaccctttctc aatccactcatctacacactgaggaatgcagaagtgaaaaatgccatgagaaagttatggcatggcaaaattatttcagaa 0 aacaaa (SEQ ID NO: 171) MOOSE07000 ctgl5408 7625248..7626159,

EFLLLGISEDPELQPVLAGLTLSMYLVTVLRNLLIILAVSSDSHLHTSM

YFVLSNLRWVDIGFTSATWEMΓVDMQSHSRVISYAGCLTQMSFLVFFACIE DMLLTVMSYDQFLAJCHPLHYPVIVNPHFCVFLVLVSFFLSLLDSQLHRWIV LQFTFFK-NVΈISNFVCEPSQLLNLACSDSVJNTJFIYLDSTMFGFLPISGILLSYY KJVPSILRMSLSDVKYKAFSTCGSHLAVFCLFYGAGIGVYLTSAVSPPSGNG VVASVMYTVVTPMLNPFIYSLRNRDIQSAPWRLRSTTVESHDL (SEQ DD

NO: 174) gaattcctcctcctgggaatctcagaggatccagaactgcagcccgtcctcgctgggctgaccctgtccatgt acctggtcacggtgctgaggaacctgctcatcatcctggctgtcagctctgactcccacctccacacctccatgtacttcgt cctctccaacctgcgctgggttgacatcggtttcacctcggccacggttcccaagatgattgtggacatgcagtcgcatag cagagtcatctcttatgcgggctgcctgacacagatgtctttcttggtcttttttgcatgtatagaagacatgctcctgactgtg atgtcctatgaccaatttttggccatctgtcaccccctgcactacccagtcatcgtgaatcctcacttctgtgtcttcttagtttt ggtgtcctttttccttagcctgttggattcccagctgcatagatggattgtgttacaattcaccttcttcaagaatgtggaaatct ctaattttgtctgtgagccatctcaacttctcaaccttgcctgttctgacagcgtcatcaatatcatattcatatatttagatagta ctatgtttggttttcttcccatttcagggatccttttgtcttactataaaattgtcccctccattctaaggatgtcattgtcagatgt gaagtataaagccttctccacctgtggctctcacctggcagttttttgcttattttacggagcaggcattggcgtgtacctgac ttcagctgtgtcaccaccttccggcaatggtgtggtggcttcagtgatgtacactgtggtcacccccatgctgaaccctttca tctacagcctgagaaacagggacattcaaagtgccccgtggaggctgcgcagcacaacagttgaatctcatgatctc

(SEQ ID NO: 173)

MOOSE07007 ctgl5944 53957-54635, 59582-59592, 62271-62501,

MEPRKNVTDFVLLGFTQNPKEQKVLFVMFLLFYILTMVGNLLIVVTV TVSETLGSPMSFFLAGLTFIDΠYSSSISPRLISDLFFGNNSISFQSFMAQLFIEHL FGGSEVFLLLVMAYDRWAIC30^>L1JYLV3MRQWCVLLLVVSWVGGFLQS QLSITΪ^'GLPFCGPLWROIJFFCDMYPLLKXACTDTHVIGLLVVANGGLSCTI AFLLLLISYGVILHSLKKXRSSSEGRHKALSTCGSHITVVILFFWCIFIVΓYVT^ PLTLPIDKSLTVFYTVITPMLNPLIYTLRNAEMK.NAMKKLWTRKRK (SEQ ID NO: 176) atggagccaaggaaaaatgtgactgactttgtcctcttgggcttcacacagaatccaaaggagcagaaagtac tt ttgttatgttcttgctcttctacattttgaccatggtgggcaacctgctcattgtagtgaccgtaactgtcagtgagaccctg ggctcaccaatgtccttctttcttgctggcttaacatttatagatatcatttattcttcatccatttcccccagattgatttcagactt gttctttgggaataattccatatccttccaatctttcatggcccagctctttatcgagcacctttttggtgggtcagaggtctttct cctgttggtgatggcctatgaccgctatgtggccatctgtaagcccttgcattatttggttatcatgagacaatgggtgtgtgt tttgctgctggtagtgtcctgggttggaggatttctgcaatcagtatttcaacttagcattatttatgggctcccattctgtggcc ccaatgtcattgatcattttttctgtgacatgtatcccttattgaaactggcctgcactgacacccatgttattggcctcttagtg gtggccaatggaggactgtcttgcactattgcgtttctgctcttactcatctcttatggtgtcatcctgcactctctaaagaaac ttagatcaagcagtgaagggaggcacaaagccttatccacctgtggctcccatatcactgtggtgatcctcttctttgtccct tgtattttcatgtatgtgagacctcctttgaccttacccattgataaatccttgactgtgttttacactgttatcacacctatgttga accctctaatctatactttaagaaatgcagagatgaaaaatgctatgaagaagctctggactagaaaaagaaaa (SEQ ID NO: 175)

MOOSE07013 ctgl432629348918..29348945, 29359704..29360614, MLRSTWTQQFLLLGLSEDPELQTJLAGLSLSMYLVTVLRNLLSILAV

SSDSJJPHTPMYFFLSNLCWADIGFTLATVPKMIVDMGSHSKVISYGGCLTQ MSFLVLFAC DMFLTVMAYDCFVAICrøLITYPVIVNPHLCVFFVLVSFFLS LLDSQLHSW LQFTFFIQ^JVEISNFVCEPSQLLKLASYDSVINSIFIYFDNTMF GFLPISGILLSYYKIVPSILRISSSDGKYKAFSACGCHLAVVCLFYGTGIGVYL TSAVAPPLRNGMVAS VMYAVVTPMLNPFIYSLRNRDIQS ALWRVCNKTVES HDL (SEQ ID NO: 178) atgttgcggtccacggtggtcacacagcaattcctccttctgggactctcagaggatccagaactgcagacca tccttgctgggctgtccctgtccatgtatctggtcacggtgctgaggaacctgctcagcatcctggctgtcagctctgactc ccacccccacacacccatgtacttcttcctctccaacctgtgctgggctgacatcggtttcaccttggccacggttcccaaa atgattgtggacatggggtcgcatagcaaagtcatctcttatgggggctgcctgacacagatgtctttcttggtactttttgca tgtatagtagacatgttcctgactgtgatggcttatgactgctttgtagccatctgtcgccctctgcactacccagtcatcgtg aatcctcacctctgtgtcttcttcgttttggtgtcctttttccttagcctgttggattcccagctgcacagttggattgtgttacaat tcaccttcttcaagaatgtggaaatctctaattttgtctgtgagccatctcaacttctcaagcttgcctcttatgacagcgtcatc aatagcatattcatatal ttgataatactatgtttggttttcttcccatttcagggatccttttgtcttactataaaattgtcccctcc attctaaggatttcatcatcagatgggaagtacaaagccttctcagcctgtggctgtcacctggcagttgtttgcttattttatg gaacaggcattggcgtgtacctgacttcagctgtggcaccacccctcaggaatggtatggtggcgtcagtgatgtacgct gtggtcacccccatgctgaaccctttcatctacagcctgagaaacagggacattcaaagtgccctgtggagggtgtgcaa caaaacagtcgaatctcatgatctg (SEQ ID NO: 177) MOOSE07014 ctgl3910 4108517..4108789, 4139748..4140401,

4154576..4154593,

MEEENATLLTEFVLTGLLYQPQWKJPLFLTFLVIYLITIMGNLGLIAVI WKDPIJLQJPMYLLLGNLAFVDA SSTVTPKMLNNFLAKS -MMISLSECM VQFFSFVISVTTECFISASMAYDRYVAICKALLYPVTMTNGLCIQLLVLSFIGG LLIJALIJJEIFLFI^TFCNSNπQIJFYCDIJPLL3πSCTDSFJNFLIvrvF3FADSIQVF

TIGT3DISYTLVLLIIL3QvKSVKGIQKAVSTCGAHLLSVSLYYGPLVFMYVGSA SPQADDQDMMESLFYTVrWLLNSMT^SL3^KQVL SFT3Ω^3ζRNVASKSW (SEQ DD NO: 180) atggaagaggaaaatgcaacattgctgacagagtttgttctcacaggacttttatatcaaccacagtggaaaat acccctgttcctgacattcttggtaatatatctcatcaccatcatggggaatcttggtctgattgctgtcatctggaaagaccct caccttcagatcccaatgtacttactcctcgggaatttagcttttgtagatgcttggatatcatctacagtgactccaaagatg ctgaataacttcttagctaagagtaagatgatgatatctctctctgaatgcatggtacaatttttttcctttgtaatcagtgtaacc acagaatgttttatctcggcatcaatggcatatgatcgctatgtagccatttgcaaagctttactttatccagtcattatgacca acggactatgcatccagctattagtcttgtcatttataggtggccttcttcatgctttaatccatgaaatttttttattcagattaac cttctgtaattccaacataatacaacacttttactgtgacattatcccattgttaaagatttcctgtactgattcttttattaactttct aatggtttttal^cgcagattcaattcaagtttttaccattggaactattcttatatcttatacacttgtcctccttataatcttaaa aaataagtctgtcaaagggatacaaaaagctgtctccacctgtggagctcatctcttatctgtatctttatactatgggcccct tgtcttcatgtatgtgggctctgcatccccgcaagcagatgaccaagatatgatggagtctctattttacactgtcatcgttcc tttattaaattccatgatctacagcctgagaaacaagcaagtaatagcttcattcacaaaaatgttcaaaagaaatgttgcttc caaatcttgg (SEQ DD NO: 179)

MOOSE07017 ctgl5296 2084296-2085220,

MVNRNNVTEFILLGLIENPIOJQKI3FVVFFV3YITTMIGNVLIVVTVTA SPSLRSPMYFYLAYLSF3DACYSSVNAPKXITDSLYENKTILLNGCMTQVFGE HFFGGVEVILLTVlvL YDRYVVIC3α^>LITYTT3 KQHVCSLLVGVSWVGGFLH

ATVQILFIFQLPFCGPNVIDHFMWDLNPLLNLVCTNTHTLGLFVAANSGFICL LNFLLLLVSYMVILYSLRTHSLEARCKALSTCVSHITVVILFFIPCIFVYMRPP ATLProKAVAWYTMIAPMLNPLIYTLIWAQMKNAIRKLCSRKAISSVK (SEQ ID NO: 182) atggtgaatagaaacaatgtgacagagtttattctactggggcttatagagaatccaaaaatgcagaaaatcat atttgttgtgl ttttgtcatctacatcaccaccatgataggaaatgtgctcattgtggtcaccgtcactgccagcccatcattg aggtcccccatgtacttttacctggcctatctgtcctttattgatgcctgctattcctccgtcaatgcccctaagctgatcacag attcactctatgaaaacaagactatcttactcaatggatgtatgactcaagtctttggagaacattttttcggaggtgttgaggt catcctacttactgtaatggcctatgaccgctacgtggtcatctgcaagcccttgcactataccaccatcatgaagcagcat gtttgtagcctgctagtgggagtgtcatgggtaggaggctttcttcatgcaaccgtacagatcctcttcatcttccaattacct ttctgtggtcctaatgtcatagatcactttatgtgggatctcaaccctttgctcaatcttgtctgcactaatacccacactctagg actcttcgttgctgccaacagtgggttcatatgcctgttaaactttctcttgctcctggtctcctatatggtcatactgtactcctt aaggacccacagcttagaggcaaggtgcaaagccctctccacctgtgtctcccacatcacagttgtcatcttattctttatac cctgcatatttgtgtacatgagacctccagctactttacccattgataaagcagttgctgtattctacactatgatagctcctat gttaaaccccttaatctacaccttgaggaatgctcagatgaaaaatgccattaggaaattgtgtagtaggaaagctatttcaa gtgtcaaa (SEQ ID NO: 181)

MOOSE07018 ^' ctgl4667 1532711- 1533656,

MGRWVNQSYTDGFFLLGIFSHSQTDLVLFSAVMVVFTVALCGNVLL IFLLYLDAGLHTPMYFFLSQLSLIVROLMLVCNIV KMAANFLSGRKSISFVGC GIQIGFFVSLVGSEGLLLGLMAYDRYVAVSHPLHYPILMNQRVCLQITGSSW AFG3JDGVIQMVAAMGLPYCGSRSVDHFFCEVQALLKXACADTSLFDTLLFA CCWMLLLPFSΠMASYACISLGAVLRIRSAQAWKKALATCSSHLTAVTLFY

GLDRCRIGSQH (SEQ DD NO: 184) atgggaagatgggtgaaccagtcctacacagatggcttcttcctcttgggcatcttttcccacagccagactga ccttgtcctcttctctgcagttatggtggtcttcacagtggccctctgtgggaatgtcctcctcatcttcctcatctacctggac gctggacttcacacccccatgtacttcttcctcagccagctctccctcatggacctcatgttggtctgtaacattgtgccaaa gatggcagccaacttcctgtctggcaggaagtccatctcctttgtgggctgtggcatacaaattggcttttttgtctctcttgtg ggatctgaggggctcttgctgggactcatggcttatgaccgctacgtggccgttagccacccacttcactatcccatcctc atgaatcagagggtctgtctccagattactgggagctcctgggcctttgggataatagatggagtgattcagatggtggca gccatgggcttaccttactgtggctcaaggagcgtggatcactttttctgtgaggtacaagctttattgaagctggcctgtgc agacacttccctttttgacaccctcctctttgcttgctgtgtcttcatgcttctccttcccttctccatcatcatggcctcctatgct tgcatctctctaggggctgtgctccgaatacgctctgctcaggcctggaaaaaagccctggccacctgctcctcccaccta acagctgtcaccctcttctatggggcagccatgttcatgtacctgaggcctaggcgctaccgggcccctagccatgacaa ggtggcctctatcttctacacagtccttactcccatgctgaaccccctcatttacagcttgaggaatggggaggtgatgggg gcactgaggaaggggctggaccgctgcaggattggcagccagcac (SEQ DD NO: 183)

MOOSE07021 ctgl3495 316138..316149, 333772-334699, ETTNTTGFVNEFILLGFPCRWEIQILLFVVFSLIYLLTLLGNTSΠCAVW

SSQKXHTPMY3LLANFSFLEICCVSSDVPIMAANLISQTQSISCAGCLLRFYFF SMCAAECLFLSVMSFDRFPAICRPLIIYPTLMTHHVCAHIFVIFCWVGGCLW LLTPLTLISQVLFCGPNTIDHFFCDLAPLLALSCAPIPGITLTCGΠSALIIFLTFL

YILGTYFCVLSTVLQWSGLGRHKAFSTCGCHLA SLFYGSLMVINJYVSPG SGDYHGIKI FVTLFYTLSTPFFNPLIYSFI^NKDMKEALKKFL3^NRHTSSRW (SEQ ID NO: 186) gagactactaataccactggatttgtaaatgagttcatcctcttgggcttcccctgccgctgggagatccagatc ctcctttttgtggtcttctctctcatctaccttctgaccctcctaggtaacacatccatcatctgtgctgtgtggtcaagccagaa actccacacacctatgtacatcctactggccaatttctccttcctggagatctgctgtgtcagttctgacgtgcccataatggc agccaatctcatctcccagacacagagcatctcctgtgctggctgcctgctccggttctacttcttctccatgtgtgctgcag agtgcttatttctgtcagtgatgtcttfrgataggtttcctgccatttgtagacctttgcactatcccaccttaatgacccatcacg tttgtgctcatatttttgtgatcttctgctgggtgggtggctgtctctggttattgacccctttgacactaatatctcaggtcctctt ttgtggtccaaacactatcgaccattttttctgtgatctggcacctttgctggcactgtcttgtgctccaatacctggaattactc tgacttgtggtatcattagcgctctcatcatctttcttaccttcttgtatatccttgggacttatttctgtgttctaagcacagtgct acaggtgccttcaggcttaggaaggcataaggctttctcaacttgtggctgtcaccttgctgtagtgtctctcttctatggttct cttatggtgatgtatgttagcccaggttctggggactatcatgggataaagaaatttgtgaccttgttctatactttgtcaactc cattctttaatcctctgatctacagtttccggaacaaggatatgaaagaggcactaaagaaatttctgaggaatcgccacac tagctccaggtgg (SEQ ID NO: 185) MOOSE07022 ctgl3495 424915..424986, 442610-443537,

ETTNITGFVNEFJJ LGFPCRWEIQILLFWFSLTYLLTLLGNTSΠCAVWS SQIΑ_JHTPMYILLANFSFLEICCVSSDWIMAANLISQTQSISCAGCLL3 FYFFS MCAAECLFLSVMSFDRFPAICRPLHYPTLMTHHVCAHIFVIFCWVGGCLWL LTPLTLISQVLFCGPNTIDHFFCDLAPLLALSCAPIPGITLTCGΠSALIIFLTFLY ILGTYFCVLSTVLQWSGLG3 3IAFSTCGCHLAVVSLFYGSIJSIVMYVSPGS GDYHG3JDA^?ATLFYTLSTPFFNPLR^SF3^ DI^KEALKKFLRNRHTSSRW

(SEQ ID NO: 188) gagactactaatatcactggatttgtgaatgagttcatcctcttgggcttcccctgccgctgggagatccagatc ctcctttttgtggtcttctctctcatctaccttctgaccctcctaggtaacacatccatcatctgtgctgtgtggtcaagccagaa actccacacacctatgtacatcctactggccaatttctccttcctggagatctgctgtgtcagttctgacgtgcccataatggc agccaatctcatctcccagacacagagcatctcctgtgctggctgcctgctccggttctacttcttctccatgtgtgctgcag agtgcttatttctgtcagtgatgtcttttgataggtttcctgccatttgtagacctttgcactatcccaccttaatgacccatcacg tttgtgctcatatttttgtgatcttctgctgggtgggtggctgtctctggttattgacccctttgacactaatatctcaggtgctctt ttgtggtccaaacactatcgaccattttttctgtgatctggcacctttgctggcactgtcttgtgctccaatacctggaattactc tgacttgtggtatcattagcgctctcatcatctttcttaccttcttgtatatccttgggacttatttctgtgttctaagcacagtgct acaggtgccttcaggcttaggaaggcataaggctttctcaacttgtggctgtcaccttgctgtagtgtctctcttctatggttct cttatggtgatgtatgttagcccaggttctggggactatcatgggataaagaaatttgcgaccttgttctatactttgtcaactc cattctttaatcctctgatctacagtttccggaacaaggatatgaaagaggcactaaagaaatttctgaggaatcgccacac tagctccaggtgg (SEQ ID NO: 187)

MOOSE07056 ctgl2475 4195646..4196574, 4197205..4197226,

MESERTTMDGSPVFYLLG3PSLPETFFLPVFFIFLLFYLLILMGNALILV AVVAEPSL3T30^>MYFFLINLSTLDILFTTTTVPKMLSLFLLGDI FLSFSSCLLQ IVLYLFQSFTCSEAF3LVVMAYDRYNAICHPLHYPVLMNPQTNATLAASAWLT

ALLLP3RAWRTSQMAYNSIAYTYHCFCDHLAWQASCSDTTPQTLMGFCIA MVVSFLPLLLVLLSYVIJIXASVLMSSLEGRAI AFSTCSSHLLVVGTYYSSIAI AYVAY3^ADLPLDFHMGNVVYAJLTPJLNPLIYTL3 N3^VKAAITKIMSQDP GCDRS (SEQ ID NO: 190) atggagtcagaaagaaccactatggatggctcacccgtcttctatctattgggcatcccctctctgccagagac cttcttcctccctgtgttttttattttcctcctcttctaccttctcatcctgatgggtaatgccctgatcctggtggccgtggtggc agagcccagcctccacaagcccatgtacttctttctgatcaatctctccaccttggacatccttttcaccacaaccactgtcc ccaagatgctgtccttattcttgcttggggaccgcttcctcagcttttcttcctgcttactgcagatgtacctcttccaaagtttta catgttcagaagccttcatcctggtggtcatggcctatgaccgctatgtggctatctgccacccactgcactaccctgtcctc atgaacccacagaccaatgctaccttggcagccagtgcctggctaactgccctcctcctgcccatcccagcagtagtaag gacctcccagatggcatataacagcattgcctacafctaccactgcttctgtgatcatctggctgtggtccaggcctcctgct ctgacaccaccccccagaccctcatgggcttctgcatcgccatggtggtgtccttcctcccccttctcctggtgcttctctcc tatgtccacatcctggcctcagtgcttcgcatcagttccctagaaggacgggcaaaagccttctccacctgcagctcccac cttctggtcgtgggcacctactactcatctattgccatagcctacgtggcctacagggctgacctgccccttgacttccatat catgggcaatgtggtatatgccattctcacaccaattctcaaccccctcatttacacgctgagaaacagggatgtaaaggc agccatcaccaaaatcatgtctcaagacccaggctgtgacaggagc (SEQ ID NO: 189)

MOOSE07089 ctgl4145 504679..505560, 516893..516938, 566393-566433,

MPSINDTIJFYPPFFLLLGIPGLDTLIJIWISFPFCIvΥL3AIVGNMTILFVI KTEHSLHQPMFYFLAMLSM3DLGLSTST3PKMLGIFWFNLQEISFGGCLLQM

FF3IIMFTGMETVLLVVMAYD3^VAIClNffLQYTM TI^TISILASVVVG3iNL VLVTPFVFLILI^PFCG33NIWHTYCEHRGLAGLACAPI3πNIIYGLMVISYIIV DVILIASSYVLILT^ iπ.PSQDVRLKAI^fTCGSFfVCVMLCFYTPAFFSFMTH RFGQNffHY3IIJULANLYVVWPALNPVIYGRYEmCI^^ RIWKMGKN (SEQ ID NO: 192) atgccttctatcaatgacacccacttctatccccccttcttcctcctgctaggaataccaggactggacactttac atatctggatttctttcccattctgtattgtgtacctgattgccattgtggggaatatgaccattctctttgtgatcaaaactgaac atagtctacaccagcccatgttctacttcctggccatgttgtctatgattgatctgggtctgtccacatccactatccccaaaat gctaggaatcttctggttcaacctccaagagatcagctttgggggatgccttcttcagatgttctttattcacatgtttacaggc atggagactgttctgttggtggtcatggcttatgaccgctttgttgccatctgcaaccctctccagtacaccatgatcctcacc aataaaaccatcagtatcctagcttctgtggttgttggaagaaatttagttcttgtaaccccatttgtgtttctcattctgcgtctg ccattctgtgggcataacatcgtacctcacacatactgtgagcacaggggtctggccgggttggcctgtgcacccattaa gatcaacataatctatgggctcatggtgatttcttatattattgtggatgtgatcttaattgcctcttcctatgtgcttatccttaga gctgtτtttcgccttccctctcaagatgtccgactaaaggccttcaatacctgtggttctcatgtctgtgttatgctgtgcttttac acaccagcatttttttclfrtatgacacatcgttttggccaaaacattccccactatatccatattcttttggctaacctgtatgtg gttgtcccacctgcccttaaccctgtcatttatggaagatatgaaatacattgtatgagaaataaggatttaaaggcagcaaa aaagaagcttatccatcggatttggaaaatgggtaaaaac (SEQ ID NO: 191)

MOOSE07094 ctg832 2478916..2478965, 2485728-2486631, MLPSNITSTHPAVFLLVGIPGLEHLHAWISIPFCFAYTLALLGNCTLLFI

IILADAALHEPMYLFLAMLAT3DLVLSSTTLPKMLA3FWFIIDQEINFFACLVQ IVIFFLHSFSIMESAVLLAMAFDRYVAICKPLIIYTTVLTGSLITKIGMAAVAW AVTLMTPLPFLLRRFFfYCRGPVIAHCYCEHMAVV3π_JACGDTSFNNIYGIAV AMF VLDLLFVILSYVFILQAVLQLASQEARYKAFGTCVSHIGAILSTYTPV VISSVMIJRVARHAAPRVΗ3XLAIFYLLFPPMVNPIIYGVKTKQIRRSLIKAVST

LRATCTT (SEQ ID NO: 194) atgcttccctctaatatcacctcaacacatccagctgtctttttgttggtaggaattcctggtttggaacacctgcat gcctggatctccatccccttctgctttgcttatactctggccctgctaggcaactgtacccttctcttcattatccgggctgatg cagccctccatgaacccatgtacctctttctggccatgttggcaaccattgacttggttctttcttctacaacgctgcccaaaa tgcttgccatattctggttcagggatcaggagatcaacttctttgcctgtctggtccagatgttcttccttcactccttctccatc atggagtcagcagtgctgctggccatggcctttgaccgctatgtggccatctgcaagccattgcactacacgacggtcct gactgggtccctcatcaccaagattggcatggctgctgtggcctgggctgtgacactaatgactccactccccttcctgct cagacgcttccactactgccgaggcccagtgattgcccattgctactgtgaacacatggctgtggtaaggctggcgtgtg gggacactagcttcaacaatatctatggcattgctgtggccatgtttattgtggtgttggacctgctctttgttatcctgtcttat gtcttcatccttcaggcagttctccagcttgcctctcaggaggcccgctacaaggcatttgggacatgtgtgtctcacatag gtgccatcctgtccacctacactccagtagtcatctcttcagtcatgcaccgtgtagcccgccatgctgcccctcgtgtcca catactccttgctattttctatctccttttcccacccatggtcaatcctatcatatatggagtcaagaccaagcagattcgcaga agtttgattaaggcagtttcaacgttgcgagcaacatgtactaca (SEQ ID NO: 193) MOOSE07095 ctgl4145 821868-821911, 862956-863828, 891947..891977,

MAVRNGTFLLLFVLPGFFGLEAYHIWLSIPLCLIYITAVLGNSILIVVTV ME3^NLIJVPIVRΠ⁷FLSMLAVMDILLSTTTWKALAIFWLQA HNIAFDACVTQG FFVHMMFVGESAILLAMAFDILFVAICAPLRYTTVLTWPVVGRIALAVITRSF CΠFPVJFLLIΠILPFCLTΪNITVTHSYCEHIGVAJ^AC^ LDVIUIAVSYSLIL31AW31LPSQDAPJΪI ALSTCGSHLCVILMFYVPSFFTLLTH HFGJMOTPQHVHIII ^YVAWPMIM'IV^ R (SEQ ID NO: 196) atggcagtacgaaacgggacttttcttctcctttttgtccttcctggcatccctgggttggaggcttatcacatttg gctgtcaatacctctttgcctcatttacatcactgcagtcctgggaaacagcatcctgatagtggttattgtcatggaacgtaa ccttcatgtgcccatgtatttcttcctctcaatgctggccgtcatggacatcctgctgtctaccaccactgtgcccaaggccct agccatcttttggcttcaagcacataacattgcttttgatgcctgtgtcacccaaggcttctttgtccatatgatgtttgtgggg gagtcagctatcctgttagccatggcctttgatcgctttgtggccatttgtgccccactgagatatacaacagtgctaacatg gcctgttgtggggaggattgctctggccgtcatcacccgaagcttctgcatcatcttcccagtcatattcttgctgaagcgg ctgcccttctgcctaaccaacattgttcctcactcctactgtgagcatattggagtggctcgtttagcctgtgctgacatcact gttaacatttggtatggcttctcagtgcccattgtcatggtcatcttggatgttatcctcatcgctgtgtcttactcactgatcctc cgagcagtgtttcgtttgccctcccaggatgctcggcacaaggccctcagcacttgtggctcccacctctgtgtcatcctta tgttttatgttccatccttctttaccttattgacccatcattttgggcgtaatattcctcaacatgtccatatcttgctggccaatctt tatgtggcagtgccaccaatgctgaaccccattgtctatggtgtgaagactaagcagatacgtgaggaattaaagagaaa attttctagctttattttcctgaaattccgg (SEQ ID NO: 195)

MOOSE07096 ctgl4145 135777-136689, 195682..195731,

MSDSNLSDNHLPDTFFLTG3PGLEAAHFWJAIPFCAMYLVALVGNAA LILVIAMDNALHAPMYLFLCLLSLTDLALSSTTVPKMLAILWLHAGEISFGG CLAQMFCVHSIYALESSILLAMAFDRYVAICNPLRYTT3LNHAVIGi GFVGL FRSVAJVSPFIFLLi LPYCG3JRVMTHTYCEHMGIAJ^ACAMTVNrVYGLTV A LAMGLDSπ.IAISYGFILIJAVFHLPSHDAQHJ^-ALSTCGS GIILVFYTPAFF SFLTIΪI^GHHEWi VHIFLANLYNLWPVLNPILYGARTl^I3^RRTLERLff CPF3FSDH (SEQ ID NO: 198) atgtcagattccaacctcagtgataaccatcttccagacaccttcttcttaacagggatcccagggctggaggct gcccacttctggattgccatccctttctgtgccatgtatcttgtagcactggttggaaatgctgccctcatcctggtcattgcc atggacaatgctcttcatgcacctatgtacctcttcctctgccttctctcactcacagacctggctctcagttctaccactgtgc ccaagatgctggccattttgtggctccatgctggtgagatttcctttggtggatgcctggcccagatgttttgtgtccatt ctatgctctggagtcctcgattctacttgccatggcctttgataggtatgtggctatctgtaacccattaaggtatacaaccatt ctcaaccatgctgtcataggcagaattggctttgttgggctattccgtagtgtggctattgtctcccccttcatcttcttgctga ggcgactcccctactgtggtcaccgtgtcatgacacacacatactgtgagcatatgggcatcgcccgactggcctgtgcc aacatcactgtcaatattgtctatgggctaactgtggctctgctggccatgggactggattccattctcattgccatttcctatg gctttatcctccatgcagtctttcaccriccatctcatgatgcccagcacaaagctctgagtacctgtggctcccacattggc atcatcctggttttctacatccctgccttcttctccttcctcacccaccgctttggtcaccacgaagtccccaagcatgtgcac atctttctggctaatctctatgtgctggtgcctcctgtactcaatcctattctctatggagctagaaccaaggagattcggaga aggacgttagagaggttgattccctgtccatttattttctctgatcac (SEQ ID NO: 197)

MOOSE07097 ctg832 2502047..2502070, 2543257..2544155,

2560940-2560964,

MPKGNSCFNPTSFLLMG3PGPEAS3IFWIAFPFCSMYALAVLGNMVVL LVVHSEPVLHQPMYLFLCMLST3DLVLCTSTVPKLLALFWA3aDAEINFGAC

AAQMFF3HGFSAVESGILLAMAFDRYLAICWPLHYGSLLSPESVGKLGAAA VLRGLGLMTPLTCLLAJπ_JSYCSRVVAJJSYCE3JMAVVEXACGGTQPNNIYGI TAATLWGTDSICIAVSYALILRAVLGLSSKEARAKTFGTCGSHLGV3LLFYT PGLFSFYTQRFGQHVPRHffllLLADLYLVWPIVIDNPIIYGMKTKQIWDGALR LLI KKKFSSKL (SEQ DD NO: 200) atgcccaaaggcaactcatgttttaacccaacctcctttctgctcatgggaattccaggcccggaggcatccca cttttggattgcttttcccttctgctccatgtatgccctggcagtgctgggaaacatggtggtgctgctagtggtacattcaga gcctgtattgcaccagcccatgtacctgttcctctgcatgctatccaccattgacctggtcctctgcacctccactgtgccca agctccttgcacttttttgggcaaaggatgctgagatcaactttggggcctgtgctgcccagatgttctttatccatggcttct cagctgtagaatctggtatactgctagcaatggcctttgaccgctacttagccatttgctggcctctgcactatgggtcattg ctctccccagagtctgtaggcaagctgggggctgcagccgtgcttcgtggtttgggactcatgaccccactcacctgctta ctggcaagactgagctactgcagtcgagtggtggcccactcctactgtgaacacatggctgtggtaaagctggcttgtgg aggaacacagccaaacaacatctatggcatcactgctgccacactggtggtgggcactgactccatctgtattgctgtctc ctatgcactcatcctccgagctgtgttaggtctttcctccaaggaggcaagggctaagacctttggcacttgtggctcccac ctgggtgtcatacttctcttctacacaccaggactcttctccttctacacacagcggtttggccagcacgtgccccggcaca tccacatccttctagctgacctctacctggttgtgccacccatgctcaaccccatcatctatggcatgaagaccaaacagat ctgggatggggccctccggcttctgaagaagaaaaaattctcctcaaagctg (SEQ ID NO: 199)

MOOSE07098 ctg832 3016603-3017389, 3027231..3027272, 3037428..3037502, 3041988..3042031, MNTTLFHPYSFLLLGIPGLESMHLWVGFPFFAVFLTAVLGNITILFVIQ TDSSL3I3JPIV[FYFLAILSSIDPGLSTSTIP1? LGTFWFTLREISFEGCLTQMFFIH LCTGMESAVLVAMAYDCYVAICDPLCYTLVLTNKWSVMALA3FLRPLVFV 3 FVLFIL3^PFCGHQIIPHTYGEHMGIAP SCASIRVNIIYGLCAISILVFDIIAI VISYVQILCAWLLSS3JDAiπ_JKAFSTCGSFr^CVMLTFYMPAFFSFMTHRFEN WSSTQFMKMITLSlSrLYVVWPMLWVIYG TK^ (SEQ DD NO: 202) atgaataccactctatttcatccttactctttccttcttctgggaattcctgggctggaaagtatgcatctctgggttg gttttcctttctttgctgtgttcctgacagctgtccttgggaatatcaccatcctttttgtgattcagactgacagtagtctccatc atcccatgttctacttcctggccattctgtcatctattgacccgggcctgtctacatccaccatccctaaaatgcttggcacctt ctggtttaccctgagagaaatctcctttgaaggatgccttacccagatgttcttcatccacctgtgcactggcatggaatcag ctgtgcttgtggccatggcctatgattgctatgtggccatctgtgaccctctttgctacacgttggtgctgacaaacaaggtg gtgtcagttatggcactggccatctttctgagacccttagtctttgtcataccctttgttctatttatcctaaggcttccattttgtg gacaccaaattattcctcatacttatggtgagcacatgggcattgcccgcctgtcttgtgccagcatcagggttaacatcatc tatggcttatgtgccatctctatcctggtctttgacatcatagcaattgtcatttcctatgtacagatcctttgtgctgtatttctact ctcttcacatgatgcacgactcaaggcattcagcacctgtggctctcatgtgtgtgtcatgttgactttctatatgcctgcatttt tctcattcatgacccataggtttgagaactggtcatctactcaatttatgaaaatgatcaccctgtccaatctctatgttgtggt gccaccaatgctcaatcctgtcatatatggagtcagaaccaagcagatctatgtctgcatgaataaggtgatcaggaagg aatgcataatcaagctttat (SEQ ID NO: 201)

MOOSE07099 ctgl4145 230662..231537, 238866-238872, 242726-242787,

MNNSDTRIAGCFLTG3PGLEQLHIWLS3PFCIMYIAALEGNGILICVILS QAIL1JEPMYIFLSMLASADVLLSTTTMPI ALANLWLGYSHISFDGCLTQMFF IIJFLF SAVLLAIvLAFDRYVAICSPLRYVTILTSKVIGKIVTATLSRSFITMFPSI FLLEHLHYCQIIVΠLTAHTFCEIJMGIAJJLSCSDISINVWYGLAAALLSTGLDIMLI

TVSYJJJILQAW3 LLSQDARSKALSTCGSHICVILLFYVPALFSVFAYRFGGRS IPCYVHIXLASLYVVIPPMLNPVIYGLRG3π)QI^ALII^MFDDQKHLKT (SEQ DD NO: 204) atgaacaactctgacactcgcatagcaggctgcttcctcactggcatccctgggctggagcaactacatatctg gctgtccatccccttctgcatcatgtacatcgctgccctggaaggcaatggcatcctaatttgtgtcatcctctcccaggcaa tcctgcatgagcccatgtacatattcttatctatgctggccagtgctgatgtcttgctctctaccaccaccatgcctaaggccc tggccaatttgtggctaggttatagccacatttcctttgatggctgcctcactcagatgttcttcattcacttcctcttcattcact ctgctgtcctgctggccatggcctttgaccgctatgtggccatctgctcccccctgcgatatgtcacaatcctcacaagcaa ggtcattgggaagatcgtcactgccaccctgagccgcagcttcatcattatgtttccatccatctttctccttgagcacctgc actattgccagatcaacatcattgcacacacattttgtgagcacatgggcattgcccatctgtcctgttctgatatctccatca atgtctggtatgggttggcagctgctcttctctccacaggcctggacatcatgcttattactgtttcctacatccacatcctcca agcagtcttccgcctcctttctcaagatgcccgctccaaggccctgagtacctgtggatcccatatctgtgtcatcctactctt ctatgtccctgcccttttttctgtctttgcctacaggtttggtgggagaagcatcccatgctatgtccatattctcctggccagc ctctacgttgtcattcctcctatgctcaatcccgttatttatggactgagaggaaaggaccaaaaaaatgcattaattaggtcc atgtttgatgatcagaagcatctgaaaaca (SEQ ID NO: 203)

MOOSE07101 ctgl4145 312446..312469, 327599-327638, 336013-336057,

366812-367600, 394801..394850,

MALEAQTSVSEFTLMGFPGTHTFLFFVFFLLLLLFVSTIVGNΓΠLVWA TEPVLHKPVYLFLCMLST3DLAASVSTVPKLLA3FWCGAGHIS ASACLAQMF

FIHAFCMMESTVLLAMAFDRYVAICHPLRYATILTDT3IAHIGVAAVVRGSLL

MLPCPFLIGRLNFCQSHVILHTYCEHMAVVKLACGDTIUPNRVYGLTAALLV

IGVDLFCIGLSYAJ.SAQAVLRLSSHEARSΪ ALGTCGSHVCVILISYTPALFSFF

THl^GIJHWVHffl3LLAlWYLLLPPALNPVVYGVKTKQIQGVWKELSWKAL HLTPS (SEQ ID NO: 206) atggctctggaagctcaaacctctgtctctgagtttatcctgatgggattccctggcattcacactttcttgttttttg ttttttttttgttgttgttgttgtttgtfrccacaattgtgggcaatataactattctggttgttgttg agcctgtgtacctttttctgtgcatgctctcaaccatcgacttggctgcctctgtctccacagttcccaagctactggctatctt ctggtgtggagccggacatatatctgcctctgcctgcctggcacagatgttcttcattcatgccttctgcatgatggagtcca ctgtgctactggccatggcctttgatcgctacgtggccatctgccacccactccgctatgccacaatcctcactgacaccat cattgcccacataggggtggcagctgtagtgcgaggctccctgctcatgctcccatgtcccttccttattgggcgtttgaac ttctgccaaagccatgtgatcctacacacgtactgtgagcacatggctgtggtgaagctggcctgtggagacaccaggcc taaccgtgtgtatgggctgacagctgcactgttggtcattggggttgacttgttttgcattggtctctcctatgccctaagtgc acaagctgtccttcgcctctcatcccatgaagctcggtccaaggccctagggacctgtggttcccatgtctgtgtcatcctc atctcttatacaccagccctcttctccttttttacacaccgctttggccatcacgttccagtccatattcacattcttttggccaat gtttatctgcttttgccacctgctcttaatcctgtggtatatggagttaagaccaaacagatccaaggagtatggaaggaact atcctggaaagcactacatttaactccttcc (SEQ ID NO: 205)

MOOSE07102 ctgl4145 712888..712906, 715624..715758, 718047..718075, 731046-731784, 779456-779472,

MDKENWLSQPSFLLVGTPGLEESQHWIALPLGILYLLALVGNVTILFΠ WMDPSLHQSMYLFLSMLAAIDLVLASSTAPKALAVLLVHAHEIGYIVCLIQ MFFTΉAFSSMESGVLVAMALDRYVAICHPLHHSTILHPGVIGRIGMWLVRG LLLLTPFPILLGTLTFCQATΠGJJAYCEHMAVVJΑ.ACSETTVNRAYGLTMALL VIGLDVLAIGVSYAHILQAVLKVPGSEARLKAFSTCGSHICVILVFYLTVQFI YISQK3^^>PDVPILLNTLHHL3PPALNP3VYGVRTKΕ3KQGIQNLLRRLHISKHW

(SEQ DD NO: 208) atggacaaagaaaactggctatcccagccttcttttctcctggtagggattccaggtttagaggaaagccagca ctggattgcactgcccctgggcatcctttacctccttgctttagtgggcaatgttaccattctcttcatcatctggatggaccc atccttgcaccaatctatgtacctcttcctgtccatgctagctgccatcgacctggttctggcctcctccactgcacccaaag cccttgcagtgctcctggttcatgcccacgagattgggtacatcgtctgcctgatccagatgttcttcatccatgcattctcct ccatggagtcaggggtacttgtggccatggctctggatcgctatgtagccatttgtcaccccttgcaccattccacaatcct gcatccaggggtcatagggcgcatcggaatggtggtgctggtgaggggattactactccttatccccttccccattttgttg ggaacacttatcttctgccaagccaccatcataggccatgcctattgtgaacatatggctgttgtgaaacttgcctgctcaga aaccacagtcaatcgagcttatgggctgactatggccttgcttgtgattgggctggatgttctggccattggtgtttcctatgc ccacatcctccaggcagtgctgaaggtaccagggagtgaggcccgacttaaggcgtttagcacatgtggctctcatattt gtgtcatcctggtcttctatcttacagtccagttcatatatatttctcagaagagaattcctccagatgtccccatcctgctcaa catcctgcaccaccttattcccccagctctgaaccccattgtttatggtgtgagaaccaaggagatcaagcagggaatcca gaacctgctgaggaggttacacataagtaagcattgg (SEQ DD NO: 207)

MOOSE07103 ctgl4145 410316..410336, 421168..421555, 422457-422479,

440449..440970,

ML^KQTEVSEFILLGFPG SWQHWLSLPLALLYLSALAANTLILIΠW QNPSLQQPIVΓ^IFLGILCMVDMGLATTIIPIΠLAIFWFDAKVISLPECFAQIYAI HFFVGMESGILLCMAFDRYVAICFIPLRYPSIVTSHACALLAVGTATFLRGVL LIIPFTFLTKRLPYCRGNILPHTYCDIIMSVAKLSCGNVKVNAJYGLLVIVALLI GGFDILCITISYTMTLRAWSLSSADARQΪ AFNTCTAHICAIVFSYTPAFFSFFS 3J3^GEH3IPPSCH ANIYLLLPPTMNPIVΥGVKTKQRØ Y (SEQ DD NO: 210) atgaatagaaaacagactgaggtctctgagttcatcctgctgggattcccgggcattcacagctggcaacact ggctatctctgcccctggcactactgtatctctcagcacttgctgcaaacaccctcatcctcatcatcatctggcagaaccct tctttacagcagcccatgtatattttccttggcatcctctgtatggtagacatgggtctggccactactatcatccctaagatcc tggccatcttctggtttgatgccaaggttattagcctccctgagtgctttgctcagatttatgccattcacttctttgtgggcatg gagtctggtatcctactctgcatggcttttgatagatatgtggctatttgtcaccctcttcgctatccatcaattgtcaccagtca tgcttgcgcattgttagctgttgggactgccaccttcctgagaggggtattactcattattccctttactttcctcaccaagcgc ctgccctactgcagaggcaatatacttccccatacctactgtgaccacatgtctgtagccaaattgtcctgtggtaatgtcaa ggtcaatgccatctatggtctgatggttgccctcctgattgggggctttgacatactgtgtatcaccatctcctataccatgatt ctccgggcagtggtcagcctctcctcagcagatgctcggcagaaggcctttaatacctgcactgcccacatttgtgccatt gttttctcctatactccagctttcttctccttcttttcccaccgctttggggaacacataatccccccttcttgccacatcattgta gccaatatttatctgctcctaccacccactatgaaccctattgtctatggggtgaaaaccaaacagatacgagactgtgtcat aaggatcctttcaggttctaaggataccaaatcctac (SEQ DD NO: 209)

MOOSE07106 ctgl4145 631211..631261, 677856-677876, 682019-682906,

MALSNSSWI LPQPSFFLVGffGLEESQ33WlALPLG3LYLLALVGNVTIL FJJWMDPSLHQSMYLFLSMLAAJDL ASSTAPT^ALAVLLVI^QEIGYTVCL IQMFFTHAFSSMESGVLVAMALDRYVAICHPLHHSTILHPGVIGHIGMVVLV RGLLLLIPFLTLLR3π,3FCQATπG3JAYCE3JIV[AVVKLACSETTVNIlAYGLTVA LLVYGLDVLAIGVSYAHILQAVLKWGl^ARLKAFSTCGSHVCVILVFYIPG MFSFLTFn^GHHWHHVHVLLAJLYl^WPALNPLVYRRVR^ LFNI AHLAPPL (SEQ ID NO: 212) atggcacttagcaattccagctggaggctaccccagccttcttttttcctggtaggaattccgggtttagaggaaagccagc actggatcgcactgcccctgggcatcctttacctccttgctctagtgggcaatgttaccattctcttcatcatctggatggacc catccttgcaccaatctatgtacctcttcctgtccatgctagctgccatcgacctggttgtggcctcctccactgcacccaaa gcccttgcagtgctcctggttcgtgcccaagagattggttacactgtctgcctgatccagatgttcttcacccatgcattctcc tccatggagtcaggggtacttgtggccatggctctggatcgctatgtagccatttgtcaccccttgcaccattccacaatcct gcatccaggggtcatagggcacatcggaatggtggtgctggtgcggggattactactcctcatccccttcctcattctgttg cgaaaacttatcttctgccaagccaccatcataggccatgcctattgtgaacatatggctgttgtgaaacttgcctgctcaga aaccacagtcaatcgagcttatgggctgactgtggccttgcttgtggttgggctggatgtcctggccattggtgtttcctatg cccacattctccaggcagtgctgaaggtaccaggaaatgaggcccgacttaaggcctttagcacatgtggctctcatgttt gtgtcatcctggtcttctatatcccgggaatgttctccttcctcactcaccgctttggtcatcatgtaccccatcacgtccatgtt cttctggccatactgtatcgccttgtgccacctgcactcaatcctcttgtctataggagggtgagaaataaggatattcatgct gccttcaagcatctgtttaacaaagcacatcttgcaccgccctta (SEQ ID NO: 211)

MOOSE07107 ctg8322378205..2378239, 2387723-2388376, 2430076..2430315, 2439245-2439266,

MDEUKNQYLPSSFWLTGJPGLESLHVWLSIPFGSMYLVAVVGNVTILA VV3πERSLHQPMYFFLCMLAA3DLVLSTSTffKLLGTFWFGDSSISFSACFTQM FFVHLATAVETGLLLTI^AFDRYVAICiπ^>LHY3α LTPQVMLGMSMAITIRAπ AITPLSWMVSHLPFCGSNVVVHSYCEHIALARLACADPVPSSLYSLIGSSLM VGSDVAFIAASYILILKAVFGLSSKTAQLKALSTCGSIIVGVMALYYLPGMA SIYAAWLGQDWPLHTQVLLADLYVI3PATLNPIIYGMRTKQLRERIWTCLT RFAFHSHW (SEQ ID NO: 214) atggataggaagaatcaatatctacccagctccttctggctcactggcatcccagggctggagtccctacacgt ctggctctccatcccctttggctccatgtacctggtggctgtggtggggaatgtgaccatcctggctgtggtaaagatagaa cgcagcctgcaccagcccatgtactttttcttgtgcatgttggctgccattgacctggttctgtctacttccactatacccaaa cttctgggaatcttctggttcggagacagctcaatcagctttagtgcttgtttcactcagatgttttttgtccacttagccacag ctgtggagacggggctgctgctgaccatggcttttgaccgctatgtagccatctgcaagcctctacactacaagagaattc tcacgcctcaagtgatgctgggaatgagtatggccatcaccatcagagctatcatagccataactccactgagttggatgg tgagtcatctacctttctgtggctccaatgtggttgtccactcctactgtgagcacatagctttggccaggttagcatgtgctg accccgtgcccagcagtctctacagtctgattggttcctctcttatggtgggctctgatgtggccttcattgctgcctcctatat cttaattctcaaggcagtatttggtctctcctcaaagactgctcagttgaaagcattaagcacatgtggctcccatgtggggg ttatggctttgtactatctacctgggatggcatccatctatgcggcctggttggggcaggatgtagtgcccttgcacaccca agtcctgctagctgacctgtacgtgatcatcccagccaccttaaatcccatcatctatggcatgaggaccaaacaactgcg ggagagaatatggacttgccttaccaggtttgcgtttcattctcattgg (SEQ ID NO: 213) MOOSE07109 ctgl4145 14326-14351, 39672-40567, 75320..75345,

MAUENCEIJYPIFYLTSFPGLEGIi WIFIPFFFMYMVAlSGNCFILIIIKT NPJ^HTPMYYLLSLLALTDLGLCVSTLPTTMGTFWFNSQSIYFGACQIQMFCI HSFSFMESSVLLIVfMSFDRFVAlCHPLRYSVπTGQQVVRAGLIVIFRGPVATff IVLLLI^FPYCGSVVLSHSFCLHQEVIQLACTDTTFNNLYGLMVVVFTVML DLVLIALSYGLILHTVAGLASQEEQRRAFQTCTAHLCAVLVFFVPMMGLSL VTJRFG3 APPAmLLMANVYLFWPMLNPI3ΥS3KT IIΪI^AJIiα,LG3^ ES (SEQ DD NO: 216) atggctttggaaaattgtgaacattaccccatattctatctcaccagctttcctggattggaaggcatcaaacact ggalπ catcccctttttctttatgtacatggttgccatctcaggcaattgtttcattctgatcattattaagaccaaccctcgtct gcacacacccatgtactatctactatccttgctggccctcactgacctggggctgtgtgtgtccacgttgcccaccactatg gggatcttctggtttaactcccagagtatctactttggagcgtgtcaaatccagatgttctgcatccactctttttccttcatgga gtcctcagtgctcctcatgatgtcctttgaccgctttgtggccatctgccaccctctgaggtattc'ggtcattatcactggcca gcaagtggtcagagcaggcctaattgtcatcttccggggacctgtggccactatccctattgtcctcctcctgaaggcttttc cctactgtggatctgtggtcctctcccactcattttgcctgcaccaggaagtgatacagctggcctgcacagataccacctt caataatctgtatggactgatggtggtagttttcactgtgatgctggacctggtgctcatcgcactgtcctatggactcatcct gcacacagtagcaggcctggcctcccaagaggagcagcgccgtgcctttcagacatgcaccgctcatctctgtgctgtg ctagtattctttgtgcccatgatggggctgtccctggtgcaccgttttgggaagcatgccccacctgctattcatcttcttatg gccaatgtctacctttttgtgcctcccatgcttaacccaatcatatacagcattaagaccaaggagatccaccgtgccattat caaactcctaggcagaaagcaaataccaaaggaatct (SEQ DD NO: 215)

MOOSE07112 ctg832 2800705-2800746, 2848788-2849679,

2852911-2852924,

MDRKYSSVSATFLLSGffGLERMHIWIS LCFMYLVSIPGNCTILFIIK TERSLHEPMYLFLSMLAL3DLGLSLCTLPTVLG3FWVGAREISHDACFAQLFF CFSFLESSVLLSMAFDRFVAICHPLHYVSILTNTVIGRIGLVSLGRSVALIFP LPFIVILJ^I^PYCGSPVLSHSYCLHQEVMKLACADMKANSIYGMFVIVSTVGI DSLLILFSYALJLRTVLSIASRAERFE.ALNTCVSHICAVLLFYTPMIGLSVIHRF GKQAPHLVQVVMGFMYLLFPPVMl^IΛ^SVKTKQIRDRLWRLSCSHSGHR GW (SEQ DD NO: 218) atggataggaagtacagcagcgtttctgctaccttcctgctgagtggcatccctgggctggagcgcatgcaca tctggatctccatcccactgtgcttcatgtatctggtttccatcccgggcaactgcacaattctttttatcattaaaacagagcg ctcacttcatgaacctatgtatctcttcctgtccatgctggctctgattgacctgggtctctccctttgcactctccctacagtcc tgggcatcttttgggttggagcacgagaaattagccatgatgcctgctttgctcagctctttttcattcactgcttctccttcctc gagtcctctgtgctactgtctatggcctttgaccgctttgtggctatctgccaccccttgcactatgtttccattctcaccaaca cagtcattggcaggattggcctggtctctctgggtcgtagtgtagcactcatttttccattaccttttatgctcaaaagattccc ctattgtggctccccagttctctcacattcttattgtctccaccaagaagtgatgaaattggcctgtgccgacatgaaggcca acagcatctacggcatgtttgtcatcgtctctacagtgggtatagactcactgctcatcctcttctcttatgctctgatcctgcg caccgtgctgtccatcgcctccagggctgagagattcaaggcccttaacacctgtgtttcccacatctgtgctgtgctgctc ttctacactcccatgattggcctctctgtcatccatcgctttggaaagcaggcaccccacctggtccaggtggtcatgggttt catgtatcttctctttcctcctgtgatgaatcccattgtctacagtgtgaagaccaaacagatccgggatcgactatggaggc ttagctgttctcattctggtcaccggggttgg (SEQ ID NO: 217)

MOOSE07115 ctg832 2583967-2584016, 2596315-2597225, MTTHNSTGSSHSLFILLSIPGLEDQHTWMSLPFFISYLVAFLGNSLIIFΠ

ITECSLITEPMYLFLCMLAVADLILSTTTVPKALAIFWFYAGAISLGGCVTQTF FJJJATFIEESGILLAMALDRYVAJCDPLFIYTTVLSRAKITKIGLAVVLRSFCVI IVIPDVFLVKRLPFCHSI^LPHTYCEHMAVAKFACADIHVNVWYGLSVLLYT VVLDALLILVSYSFILYTGFHLPSPQGARQKALGTCGSPLRVISMFYLPGTFTΠ TQRFGIJHVPLHTHILLANVCVLAPPMLNPIIYGINTRQIQELQSLQRTVWRFF KILKI (SEQ ID NO: 220) atgacaacccacaactccactggtagcagccactcactcttcattctgctgagcattcctggcttagaagacca gcacacatggatgtctctccccttctttatttcctaccttg tgctttccttgggaacagcctcatcatcttcatcatcatcactga atgcagcctccacgaacccatgtaccttttcctctgcatgctggctgtggctgaccttatcctgtctactaccactgtgccca aggccctagccatattttggttctatgctggagcaatatcccttggtggctgtgttacccaaatcttctttatccatgctaccttc atcgaggaatcaggaattctgttggcgatggcacttgaccgctatgtggccatctgtgatccactgcactataccacagtg ctcagtcgtgcaaaaatcacaaagattggcttggctgtggtcctgagaagcttctgtgtgatcatgccagatgtgtttctggt aaagcggctgcctttctgccatagcaatctgctgccacatacctactgtgagcacatggctgttgccaagtttgcttgtgctg atattcatgtcaatgtttggtatggcttgtctgtccttctctatactgtagtgctagatgccttgcttatcttagtgtcctatagcttc atcctgtatacaggcttccacctcccctccccccaaggagctcggcaaaaggctctgggcacatgtggctcccccctcag agtcatttccatgttctacttgcctggtatttttaccataattacccagcggtttgggcaccatgttcctctccatacacacatttt gctggctaatgtctgcgtgttggctcctcccatgctgaaccccatcatttatgggatcaacaccaggcagattcaagagtta caatcactacagagaacagtttggaggttcttcaaaatactgaagata (SEQ ID NO: 219) MOOSE07119 ctg832 2933027-2933930, 2961725-2961774,

MGDWNNSDAVEPIFILRGFPGLEYVHSWLSILFCLAYLVAFMGNVTI LSVIWIESSLHQPMYYFISILAVNDLGMSLSTLPTMLAVLWLDAPEIQASACY AQLFFmTFTFLESSVLLAMAFDRFVAICHPLHYPTILTNSVIGKIGLACLLRS LGWLPTPLLLRHYHYCHGNALSHAFCLHQDVLRLSCTDARTNSIYGLCWI ATLGVDSJFILLSYVLILNTVLDIASREEQLI ALNTCVSHICVVLJFFVPVIGVS

MVHRFGΩπ^IVΕαLMADIYLI^ MSKNL (SEQ ID NO: 222) atgggagactggaataacagtgatgctgtggagcccatatttatcctgaggggttttcctggactggagtatgtt cattcttggctctccatcctcttctgtcttgcatatttggtagcatttatgggtaatgttaccatcctgtctgtcatttggatagaat cctctctccatcagcccatgtattactttatttccatcttagcagtgaatgacctggggatgtccctgtctacacttcccaccat gcttgctgtgttatggttggatgctccagagatccaggcaagtgcttgctatgctcagctgttcttcatccacacattcacatt cctggagtcctcagtgttgctggccatggcctttgaccgttttgttgctatctgccatccactgcactaccccaccatcctca ccaacagtgtaattggcaaaattggtttggcctgtttgctacgaagcttgggagttgtacttcccacacctttgctactgaga cactatcactactgccatggcaatgccctctctcacgccttctgtttgcaccaggatgttctaagattatcctgtacagatgcc aggaccaacagtatttatgggctttgtgtagtcattgccacactaggtgtggattcaatcttcatacttctttcttatgttctgatt cttaatactgtgctggatattgcatctcgtgaagagcagctaaaggcactcaacacatgtgtatcccatatctgtgtggtgct tatcttctttgtgccagttattggggtgtcaatggtccatcgctttgggaagcatctgtctcccatagtccacatcctcatggca gacatctaccttcttcttcccccagtccttaaccctattgtctatagtgtcagaacaaagcagattcctgcagctgtgaggaa acataggagagccacacagatgagcaagaatcta (SEQ ID NO: 221)

MOOSE07120 ctg832 2607212..2608123, 2617445..2617486,

MPTVNHSGTSHTVFHLLGTPGLQDQHMWISIPFFISYVTALLGNSLLIF IILTKRSLHEPMYLFLCMLAGADIVLSTCTffQALAIFWFRAGDISLDRCITQL FFfflSTFISESG3LLVlV[AFDHYIAlCYPLRYTT3XTNALIKKICVTVSLRSYGTIF P3IFLLK3 _JTFCQNNIIPHTFCEHIGLAKYAC1^3R3NιT ΥGFSILMSTVVLDVV

L3FISYMLIL1JAWI3MPSPDACH3 VLNTFGS3JVCIJJLFYGSGIFTILTQRFGRH IPPCIHTPLANVCILAPPMLNPTJNGIKTKQIQEQLRRAMKQAIGRLrV (SEQ ID NO: 224) atgcctactgtaaaccacagtggcactagccacacagtcttccacttgctgggcatccctggcctacaggacc agcacatgtggatttctatcccattcttcatttcctatgtcaccgcccttcttgggaacagcctgctcatcttcattatcctcaca aagcgcagcctccatgaacccatgtacctcttcctctgcatgctggctggagcagacattgtcctctccacgtgcaccattc ctcaggccttagctatcttctggttccgtgctggggacatctccctggatcgttgcatcactcagctcttcttcatccattccac cttcatctctgagtcagggatcttgctggtgatggcctttgaccactatattgccatatgctacccactgaggtacaccacca ttcttacaaatgctctgatcaagaaaatttgtgtgactgtctctctgagaagttatggtacaattttccctatcatatttcttttaaa aagattgactttctgccagaataatattattccacacaccttttgtgaacacattggcctagccaaatatgcatgtaatgacatt cgaataaacatttggtatgggrtttccattctaatgtcgacggtggtcttagatgttgtactaatttttatttcctatatgctgattct ccatgctgtcttccacatgccttctccagatgcttgccacaaagctctcaacacatttggctcccatgtctgcatcatcatcct cttttatgggtctggcatcttcacaatccttacccagaggtttggacgccacattccaccttgtatccacatcccgttggctaa tgtctgcattctggctccacctatgctgaatcccattatttatgggatcaaaaccaagcaaatccaggaacagttgcgtagg gcaatgaaacaagccattggaagactgatagtc (SEQ ID NO: 223)

MOOSE07122 ctg832 2874415..2874462, 2880242-2880647,

2888479-2888518, 2894733-2894766, 2907503-2907904,

MEISTFYLVGIPGLEHANIWISIPICLMYTVAILGNCTILFFTKTEPSLHEP MYYFLSMLALSDLGLSLSSLPTMLRIFLFNAPGISPDACIAQEFFIHGFSAMES SVLL SFDRFIAICrøLRYTSTLTSARKCIFCILAFWYFGFLVIYIQSLYTIANL RYCI J NQLSHSYCLHQDVIV[KLACSDNRIDVIYGFFGALCLMVDFILIAVSY TLTLKTVLGJASKKEQLKALNTCVSHICAVJJFYLPII1\[LAVVIJRFARHVSPLIN VLIvLASTVLLLWPLTNPIVYCVKTKQI3^GLNV3αLTRKIRCRGD (SEQ ID NO: 226) atggaaatctctattttctacttggttgggatcccaggtttggagcatgccaatatttggatctctatccccatatgt ctcatgtacactgttgctatcctagggaattgtaccattctgtttttcataaaaacagagccttctttgcatgagcccatgtacta ttttctctccatgttggctctctctgacctgggactatccctctcctctctccctaccatgttaaggattttcctgttcaatgctcc aggaatttcccctgatgcctgtattgctcaagagtttttcatccatggattctcagctatggagtcatctgtacttcttataatgt cctttgatcgctttattgccatctgcaaccccctgagatacacttccatcctcaccagtgccagaaaatgtal ttctgtattttg gccttttggtactttggattcctcgttatctacattcagtctctctataccagaaacttgagatattgcaagaaaaaccaattatc ccattcctactgtctccaccaggatgtcatgaagttggcctgttctgacaacagaattgatgttatctatggcttttttggagca ctctgccttatggtagactttattctcattgctgtgtcttacaccctgatcctcaagactgtactgggaattgcatccaaaaagg agcagcttaaggctctcaatacttgtgtttcacacatctgtgcagtgatcatcttctacctgcccatcatcaacctggccgttg tccaccgctttgcccggcatgtctctcccctcattaatgttctcatggcaaatgttctcctacttgtacctccactgacgaacc caattgtttattgtgtaaaaactaaacagattagagatggactaaatgttaaattaacaagaaaaataagatgtcgtggagat (SEQ DD O: 225)

MOOSE07127 ctgl 8433 325800-326273, MEPENGTRTLGFLLLGLSEEPELQPVMFGLFLSMYLTTVFGNLLIJLAI

CSGSHLHTPMYFFLSNLSFVDICVTSTTVPKTLSNTRTQSKVITYAGCITQMY FFVLFIVLDSLLLTVMAYDQFVAIC3JPL3JYTV3VΗPIILCGLLVLASWIMSAL NSLI (SEQ DD NO: 228) atggaaccagagaatggtacgaggattttaggatttcttcttctgggactttcagaggaaccagaattgcagcc cgttatgtttggactcttcctctccatgtatctgacaactgtgtttggaaacctgctcatcatcctggccatctgctctggttccc acctccacacccccatgtacttcttcctctctaacctgtcctttgtagacatctgtgttacctccaccacagtcccaaagacac tgtcaaacatccggacacagagtaaagtcatcacctatgcaggttgcatcacccagatgtacttttttgtactctttatagtgtt ggacagcttactcttgaccgtgatggcctatgaccagtttgtggccatctgtcaccccctgcactacacggtcatcgtgaac cctcggctctgtggactgctggttctggcgtcctggatcatgagtgccctgaattccttgata (SEQ ID NO: 227)

MOOSE07139 ctgl9175 1685218-1685247, 1691111-1691175,

1691739-1691822, 1697143..1697152, 1702096..1702136, 1716968-1716987, 1719128-1719141, 1727477-1727523, 1733801..1733869, 1734090-1734156, 1745995-1746013, 1746077..1746099, 1747870..1747892, 1750716-1750733, 1753277-1753598, 1779680-1779700,

SPF3FSGLLFQLGLLPLFFFFFFFFLRWSLALNYLIMGCICWFLHNFSN VG3RLDCVTLMPRLLFSLVGPTCHISFLEGCARQWFYFFF3MGQLDSFLLLLY FNFLISSHLFILMWICNCMSJACMSLQiaLTISPLLLSFCLEr^II3RHFLCESVP LLLFLSCSVTRLEELMLSLTASGCVIMICFALTVLSYIRILATWQ3RSAASRR 3^_AFSTCSSHLGMVLLFYGTGSSTYM3 PTTRYSPLEGRLAAVFYSIL3PTLNPLI YSL3^QDIvIJ RALWKLYLQSHSHSGW (SEQ ID NO: 230) tctccatttatattttcaggtctcttatttcaacttgggttgcttccacttttttLttttttU LltLttlUttgagatggagtc tcgctcttaattacttaataatgggatgtatttgttggttcctgcacaacttctcaaatgtaggaatcagactagactgtgtcac cctgatgccaaggctgctctttagtctagtagggcccacttgtcacatttcctttttggagggttgtgctaggcagtggttttat ttcttttttattatgggtcaacttgattcttttttattattattatactttaatttcttaataagttctcatttgtttattctgatggtcttcatt tgtaattgtatgtccattgcctgtatgagtttgcaaaaacttctaacaatatcacctttattactaagtttttgtttggaaaatataa ttattaggcattttctttgtgaaagtgtgccacttctcctgttcctttcttgctctgtcaccaggctggaagagctaatgttgagt ctgacagccagtggctgtgtcatcatgatctgctttgccctcactgtcctctcttacatccgcatcttggccacagtggttcag atccgttcagcagccagccgccggaaggccttctccacctgttcttcccacctgggcatggtgctcctgttctatggcacc ggcagctccacctacatgcgacccaccacccgctactccccgctggaagggcgcttggctgctgtcttctactccatcct catacccaccctgaatccgctcatctacagcctgaggaaccaggacatgaagagagccctgtggaagctctatctccagt ctcactctcactcaggctgg (SEQ ID NO: 229)

Table IH

OLFACTORY GPCRs mmmmm m mmmmm '^■HttiHH 1H1 1M 111H TTHlT!l!T! Parkinson's Disease

Locus3 Marker:DlS2842 Lod:1.26 CM_RANGE of one LOD drop: 51

MOOSE06931 Olfactory DISTANCE 5.020 Mb MOOSE06924 Olfactory DISTANCE 5.127 Mb MOOSE06978 Olfactory DISTANCE 5.153 Mb MOOSE06916 Olfactory DISTANCE 5.207 Mb MOOSE06949 Olfactory DISTANCE 5.347 Mb MOOSE06839 Olfactory DISTANCE 5.386 Mb MOOSE06809 Olfactory DISTANCE 5.694 Mb MOOSE06882 Olfactory DISTANCE 5.812 Mb MOOSE06977 Olfactory DISTANCE 6.019 Mb MOOSE06935 Olfactory DISTANCE 6.117 Mb MOOSE06911 Olfactory DISTANCE 6.187 Mb n n n n n tr n 'i r n il u n t ri it n tr t ¥########################################

Hypertension

Locus 4 Marker:DllS4102 Lod:1.5 CM_RANGE of one LOD drop: 17

MOOSE06983 Olfactory DISTANCE: 11.68 Mb MOOSE07017 Olfactory DISTANCE: 11.71 Mb

TffTII ti ll It Itlt ti ll'ti 'tfumummMWffl mmmtfflffl

Anxiety

Locusl Marker:D9S1690 Lod:4.38 CM_RANGE of one LOD drop: 14 MOOSE06874 Olfactory DISTANCE: 3.324 Mb

RA (Rheumatoid Arthritis)

Locusl Marker:D3S3551 Lod:3.5 CM_RANGE of one LOD drop: 10

MOOSE07000 Olfactory DISTANCE: -3.42 Mb

Locus2 Marker:D6S265 Lod:3 CM_RANGE of one LOD drop: 6

MOOSE06803 Olfactory DISTANCE: -2.09 Mb

MOOSE06792 Olfactory DISTANCE: -1.00 Mb MOOSE06844 Olfactory DISTANCE: -0.75 Mb

MOOSE06791 Olfactory DISTANCE: -0.63 Mb

# J.Ut.tt.tt..ll II I I I¹ It II II II I I I I II II tl II II II II II II ti II ll.tl ll.ll ll ll.ir il.tl tl 1I.1.I ll.ll ll lUl ll !l It II II It II II tt tutu !l 11 II II !l tt tt tt If II

COPD (Chronic Obstructive Pulmonary Disease)

Locusl Marker:DlS2790 Lod:3.2 CMJ ANGE of one LOD drop: 12

MOOSE06987 Olfactory DISTANCE: -14.6 Mb

MOOSE06828 Olfactory DISTANCE: -14.5 Mb

Locus4 Marker:D19S884 Lod:2.9 CM_RANGE of one LOD drop: 20

MOOSE06786 Olfactory DISTANCE: 8.377 Mb

MOOSE07127 Olfactory DISTANCE: 8.483 Mb

OP (Osteoporosis)

Locus2 Marker:DllS4102 Lod:2.95 CM_RANGE of one LOD drop: 11

MOOSE06964 Olfactory DISTANCE: 11.43 Mb

MOOSE06983 Olfactory DISTANCE: 11.68 Mb

MOOSE07017 Olfactory DISTANCE: 11.71 Mb ######################################################

NIDDM (Non-insulin dep. Diabetes)

Locus2 Marker:D5S625 Lod:3.4 CM_RANGE of one LOD drop: 15 MOOSE06878 Olfactory DISTANCE: 8.980 Mb

MOOSE07018 Olfactory DISTANCE: 9.333 Mb Obesity

Locus4 Marker:D14S283 Lod:3.2 CM_RANGE of one LOD drop: 12

MOOSE06888 Olfactory DISTANCE: -2.47 Mb MOOSE06953 Olfactory DISTANCE: -2.21 Mb MOOSE06970 Olfactory DISTANCE: -1.57 Mb MOOSE06889 Olfactory DISTANCE: -1.11 Mb MOOSE06910 Olfactory DISTANCE: -0.61 Mb

Locus5 Marker:SHGC-1089Lod:4.6 CM_RANGE of one LOD drop: 20

MOOSE07021 Olfactory DISTANCE: -9.88 Mb MOOSE07022 Olfactory DISTANCE: -9.77 Mb

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Bipolar (Genome wide scan only)

Locusl Marker:DlS434 Lod:3.3 CM RANGE of one LOD drop: 25

AMD (Age-related Macular Degeneration)

Locus2 Marker:D3S3631 Lod:2.91 CM_RANGE of one LOD drop: 20

MOOSE07000 Olfactory DISTANCE: 14.51 Mb

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Asthma Locusl Marker:D3S3698 Lod:3.8 CM_RANGE of one LOD drop: 15

MOOSE07000 Olfactory DISTANCE: 12.19 Mb

Locus2 Marker:D3S1546 Lod:3.4 CM J ANGE of one OD drop: 17

MOOSE06957 Olfactory DISTANCE: -6.63 Mb MOOSE07014 Olfactory DISTANCE: -6.54 Mb MOOSE06927 Olfactory DISTANCE: -6.46 Mb Locus3 Marker:D3S1292 Lod:3.8 CM_RANGE of one LOD drop: 10

MOOSE07013 Olfactory DISTANCE: -7.52 Mb Locus4 Marker:DllS1887 Lod:4 CM_RANGE of one LOD drop: 9

MOOSE07056 Olfactory DISTANCE: -12.5 Mb

MI (Myocardial Infarction)

Locus2 Marker:D7S2513 Lod:1.75 CM_RANGE of one LOD drop: 22 MOOSE06850 Olfactory DISTANCE: 2.355 Mb

# 41.1.1.11. HMM 111111.11.1 11 I U 1 11 11 1 111111M4M1114W-4444U4444-44MM444l 114l44~U444l-11.il H If 44M..1 Ml 44M,lt,l Ml 4M.1.11.U.U.1UI.I1

Schizophrenia Locus3 Marker:D5S2050 Lod:1.52 CM_RANGE of one LOD drop: 50

MOOSE06878 Olfactory DISTANCE: 12.85 Mb

MOOSE07018 Olfactory DISTANCE: 13.20 Mb ttt I li ft It tt II it II It il trτrτrtt1til It i it 11 lt τtτr7Tτr τti ti II 11 It ITIt TrTTttlt ttll 11 It titrlt ll ll ti ll 1111 tτTT1ττtttτrtr 1111 TrTrT trJ

Osteoarthritis

Locusl Marker:D3S3653 Lod:2.6 CM_RANGE of one LOD drop: 12 MOOSE07000 Olfactory DISTANCE: 1.291 Mb

Longevity Locusl Marker:D9S1826 Lod:2.30 CM_RANGE of one LOD drop: 15

MOOSE06790 Olfactory DISTANCE: -14.5 Mb

MOOSE06800 Olfactory DISTANCE: -14.4 Mb

MOOSE06799 Olfactory DISTANCE: -14.4 Mb MOOSE06813 Olfactory DISTANCE: -14.3 Mb

MOOSE06827 Olfactory DISTANCE: -14.2 Mb

Locus2 Marker:DllS987 Lod:2.07 CM_RANGE of one LOD drop: 12 MOOSE06932 Olfactory DISTANCE: -14.6 Mb

MOOSE06901 Olfactory DISTANCE: -14.4 Mb

MOOSE06944 Olfactory DISTANCE: -14.2 Mb

MOOSE06837 Olfactory DISTANCE: -14.1 Mb

MOOSE06887 Olfactory DISTANCE: -12.6 Mb MOOSE06838 Olfactory DISTANCE: -12.5 Mb

MOOSE07056 Olfactory DISTANCE: 7.774 Mb Psoriasis

Locusl Marker:GDB:182383 Lod:10.61 CM RANGE of one LOD drop: 2

MOOSE06803 Olfactory DISTANCE: -3.61 Mb MOOSE06792 Olfactory DISTANCE: -2.52 Mb MOOSE06844 Olfactory DISTANCE: -2.27 Mb MOOSE06791 Olfactory DISTANCE: -2.15 Mb

Claims

CLAIMSWhat is claimed is:

1. An isolated nucleic acid molecule comprising an olfactory G protein-coupled receptor (GPCR) gene, wherein the GPCR gene has a nucleotide sequence selected from the group of nucleic acid sequences as shown in Tables I and II, or the complements of the group of nucleic acid sequences as shown in Tables I and II.

2. A nucleic acid encoding a polypeptide, wherein the polypeptide has an amino acid sequence selected from the group consisting of the group of amino acid sequences as shown in Tables I and II.

3. An isolated nucleic acid molecule which hybridizes under high stringency conditions to a nucleotide sequence selected from the group of nucleic acid sequences as shown in Tables I and π, or the complements of the group of nucleic acid sequences as shown in Tables I and II.

4. An isolated nucleic molecule that hybridizes under high stringency conditions to a nucleotide sequence encoding an amino acid sequence selected from the group consisting of the group of a ino acid sequences as shown in Tables I and II.

5. A method for assaying for the presence of a first nucleic acid molecule in a sample, comprising contacting said sample with a second nucleic acid molecule, where the second nucleic acid molecule comprises a nucleotide sequence selected from the group of nucleic acid sequences as shown in Tables I and II, and hybridizes to the first nucleic acid under high stringency conditions.

6. A vector comprising an isolated nucleic acid molecule selected from the group consisting of: (a) the nucleic acid sequences as shown in Tables I and II; (b) the complement of one of the nucleic acid sequences are shown in Tables I and JJ; or

(c) a nucleic acid encoding an amino acid molecule as shown in Tables I and II; wherein the nucleic acid molecule is operably linked to a regulatory sequence.

7. A recombinant host cell comprising the vector of Claim 6.

8. A method for producing a polypeptide encoded by an isolated nucleic acid molecule, comprising culturing the recombinant host cell of Claim 7 under conditions suitable for expression of the nucleic acid molecule.

9. An isolated polypeptide encoded by the nucleotide sequence of the group of nucleic acid sequences as shown in Tables I and U, or the complements thereof.

10. The isolated polypeptide of Claim 9, wherein the polypeptide has an amino acid sequence selected from the group consisting of the group of amino acid sequences as shown in Tables I and IJ.

11. An isolated polypeptide comprising an amino acid sequence, wherein the amino acid sequence is greater than about 95% identical to an arnino acid sequence selected from the group consisting of the group of arnino acid sequences as shown in Tables I and II.

12. A fusion protein comprising an isolated polypeptide of Claim 2.

13. A fusion protein comprising an isolated polypeptide of Claim 11.

14. An antibody, or an antigen-binding fragment thereof, which selectively binds to a polypeptide of Claim 2, or to a fragment or variant of said amino acid sequence.

15. An antibody, or an antigen-binding fragment thereof, which selectively binds to a polypeptide of Claim 11, or to a fragment or variant of said amino acid sequence.

16. A method of assaying for the presence of a polypeptide encoded by an isolated nucleic acid molecule according to Claim 1 in a sample, the method comprising contacting the sample with an antibody which specifically binds to the encoded polypeptide.

17. A method of identifying an agent which alters the activity of a GPCR, the method comprising:

(a) contacting a polypeptide of Claim 9, or a derivative or fragment thereof, with an agent to be tested;

(b) assessing the level of activity of the polypeptide or derivative or fragment thereof; and

(c) comparing the level of activity with a level of activity of the polypeptide or active derivative or fragment thereof in the absence of the agent; wherein if the level of activity of the polypeptide or derivative or fragment thereof in the presence of the agent differs, by an amount that is statistically significant, from the level in the absence of the agent, then the agent is an agent that alters activity of a GPCR.

18. An agent that alters the activity of a GPCR, identifiable according to the method of Claim 17.

19. The agent of Claim 18, where the agent is selected from the group consisting of: a GPCR gene binding agent; a G-protein; a peptidomimetic; a fusion protein; a prodrug; an antibody; and a ribozyme.

20. A method of altering activity of a polypeptide encoded by a GPCR gene, comprising contacting the polypeptide with an agent of Claim 19.

21. A method of identifying an agent which alters interaction of the polypeptide of Claim 9 with a GPCR gene binding agent, comprising: a) contacting the polypeptide or a derivative or fragment thereof, and the binding agent, with an agent to be. tested; b) assessing the interaction of the polypeptide or derivative or fragment thereof with the binding agent; and c) comparing the level of interaction with a level of interaction of the polypeptide or derivative or fragment thereof with the binding agent in the absence of the agent, wherein if the level of interaction of the polypeptide or derivative or fragment thereof in the presence of the agent differs by an amount that is statistically significant, from the level of interaction in the absence of the agent, then the agent is an agent that alters interaction of the polypeptide with the binding agent.

22. An agent that alters interaction of a GPCR gene polypeptide with a GPCR gene binding agent, identifiable according to the method of Claim 21.

23. An agent that alters interaction of a GPCR gene polypeptide with a GPCR gene binding agent, selected from the group consisting of: a second GPCR gene binding agent; a G-protein; a peptidomimetic; a fusion protein; a prodrug; an antibody; and a ribozyme.

24. A method of altering interaction of a GPCR gene polypeptide with a GPCR gene binding agent, comprising contacting the GPCR gene polypeptide and/or the GPCR gene binding agent with an agent of Claim 23.

25. A method of identifying an agent that alters expression of a GPCR gene, comprising the steps of: a) contacting a solution containing a nucleic acid comprising the promoter region of the GPCR gene operably linked to a reporter gene with an agent to be tested; b) assessing the level of expression of the reporter gene; and c) comparing the level of expression with a level of expression of the reporter gene in the absence of the agent, wherein if the level of expression of the reporter gene in the presence of the agent differs, by an amount that is statistically significant, from the level of expression in the absence of the agent, then the agent is an agent that alters expression of the GPCR gene.

26. An agent that alters expression of the GPCR gene, identifiable according to the method of Claim 25.

27. A method of identifying an agent that alters expression of a GPCR gene, comprising the steps of: a) contacting a solution containing a nucleic acid of Claim 1 or a derivative or fragment thereof with an agent to be tested; b) assessing expression of the nucleic acid, derivative or fragment; and c) comparing expression with expression of the nucleic acid, derivative or fragment in the absence of the agent, wherein if expression of the nucleotide, derivative or fragment in the presence of the agent differs, by an amount that is statistically significant, from the expression in the absence of the agent, then the agent is an agent that alters expression of the GPCR gene.

28. The method of Claim 27, wherein the expression of the nucleotide, derivative or fragment in the presence of the agent comprises expression of one or more splicing variant(s) that differ in kind or in quantity from the expression of one or more splicing variant(s) the absence of the agent.

29. An agent that alters expression of a GPCR gene, identifiable according to the method of Claim 27.

30. An agent that alters expression of a GPCR gene, selected from the group consisting of: antisense nucleic acid to a GPCR gene; a GPCR gene polypeptide; a GPCR gene receptor; a GPCR gene binding agent; a peptidomimetic; a fusion protein; a prodrug thereof; an antibody; and a ribozyme.

31. A method of altering expression of a GPCR gene, comprising contacting a cell containing a GPCR gene with an agent of Claim 30.

32. A method of identifying a polypeptide which interacts with a GPCR gene polypeptide, comprising employing a yeast two-hybrid system using a first vector which comprises a nucleic acid encoding a DNA binding domain and a GPCR gene polypeptide, splicing variant, or a fragment or derivative thereof, and a second vector which comprises a nucleic acid encoding a transcription activation domain and a nucleic acid encoding a test polypeptide, wherein if transcriptional activation occurs in the yeast two- hybrid system, the test polypeptide is a polypeptide which interacts with a

GPCR polypeptide.

33. A GPCR gene therapeutic agent selected from the group consisting of: a GPCR gene or fragment or derivative thereof; a polypeptide encoded by a GPCR gene; a G-protein; a GPCR gene binding agent; a peptidomimetic; a fusion protein; a prodrug; an antibody; an agent that alters GPCR gene expression; an agent that alters activity of a polypeptide encoded by a GPCR gene; an agent that alters posttranscriptional processing of a polypeptide encoded by a GPCR gene; an agent that alters interaction of a GPCR gene with a GPCR gene binding agent; an agent that alters transcription of splicing variants encoded by a GPCR gene; and a ribozyme.

34. A pharmaceutical composition comprising a GPCR gene therapeutic agent of Claim 33.

35. The pharmaceutical composition of Claim 34, wherein the GPCR gene therapeutic agent is an isolated nucleic acid molecule comprising a GPCR gene or fragment or derivative thereof.

36. The pharmaceutical composition of Claim 34, wherein the GPCR gene therapeutic agent is a polypeptide encoded by the GPCR gene.

37. A method of treating a disease or condition associated with a GPCR in an individual, comprising administering a GPCR gene therapeutic agent to the individual, in a therapeutically effective amount.

38. The method of Claim 37, wherein the GPCR gene therapeutic agent is a GPCR gene agonist.

39. The method of Claim 38 wherein the GPCR gene therapeutic agent is a GPCR gene antagonist.

40. A transgenic animal comprising a nucleic acid selected from the group consisting of: an exogenous GPCR gene and a nucleic acid encoding a

GPCR gene polypeptide.

41. A method for assaying a sample for the presence of a GPCR gene nucleic acid, comprising: a) contacting said sample with a nucleic acid comprising- a contiguous nucleotide sequence which is at least partially complementary to a part of the sequence of said GPCR gene nucleic acid under conditions appropriate for hybridization; and b) assessing whether hybridization has occurred between a GPCR gene nucleic acid and said nucleic acid comprising a contiguous nucleotide sequence which is at least partially complementary to a part of the sequence of said GPCR gene nucleic acid; wherein if hybridization has occurred, a GPCR gene is present in the nucleic acid.

42. The method of Claim 41, wherein said nucleic acid comprising a contiguous nucleotide sequence is completely complementary to a part of the sequence of said GPCR gene nucleic acid.

43. The method of Claim 41 , comprising amphfication of at least part of said

GPCR gene nucleic acid.

44. The method of Claim 41 , wherein said contiguous nucleotide sequence is

100 or fewer nucleotides in length and is either: a) at least 80% identical to a contiguous sequence of nucleotides in one of the nucleic acid sequences as shown in Tables I and U; b) at least 80% identical to the complement of a contiguous sequence of nucleotides in one of the nucleic acid sequences as shown in Tables I and IJ; or c) capable of selectively hybridizing to said GPCR gene nucleic acid.

45. A reagent for assaying a sample for the presence of a GPCR gene nucleic acid, said reagent comprising a nucleic acid comprising a contiguous nucleotide sequence which is at least partially complementary to a part of the ^■ . nucleotide sequence of said GPCR gene nucleic acid.

46. The reagent of Claim 45, wherein the nucleic acid comprises a contiguous nucleotide sequence that is completely complementary to a part of the nucleotide sequence of said GPCR gene nucleic acid.

47. A reagent kit for assaying a sample for the presence of a GPCR gene nucleic acid, comprising in separate containers: a) one or more labeled nucleic acids comprising a contiguous nucleotide sequence which is at least partially complementary to a part of the nucleotide sequence of said GPCR gene nucleic acid; and b) reagents for detection of said label.

48. The reagent kit of Claim 47, wherein the labeled nucleic acid comprises a contiguous nucleotide sequences which is completely complementary to a part of the nucleotide sequence of said GPCR gene nucleic acid.

49. A reagent kit for assaying a sample for the presence of a GPCR gene nucleic acid, comprising one or more nucleic acids comprising a contiguous nucleotide sequence which is at least partially complementary to a part of the nucleotide sequence of said GPCR gene nucleic acid, and which is capable of acting as a primer for said GPCR gene nucleic acid when maintained under conditions for primer extension.

50. The use of a nucleic acid which is 100 or fewer nucleotides in length and which is either: a) at least 80% identical to a contiguous sequence of nucleotides in one of the nucleic acid sequences as shown in Tables I and 31; b) at least 80% identical to the complement of a contiguous sequence of nucleotides in one of the nucleic acid sequences as shown in Tables I and LI; or c) capable of selectively hybridizing to said GPCR gene nucleic acid, for assaying a sample for the presence of a GPCR gene nucleic acid.

51. The use of a first nucleic acid which is 100 or fewer nucleotides in length and which is either: a) at least 80% identical to a contiguous sequence of nucleotides in one of the nucleic acid sequences as shown in Tables I and TJ; b) at least 80% identical to the complement of a contiguous sequence of nucleotides in one of the nucleic acid sequences as shown in Tables I and U; or c) capable of selectively hybridizing to said GPCR gene nucleic acid; for assaying a sample for the presence of a GPCR gene nucleic acid that has at least one nucleotide difference from the first nucleic acid.

52. The use of a nucleic acid which is 100 or fewer nucleotides in length and which is either: a) at least 80% identical to a contiguous sequence of nucleotides in one of the nucleic acid sequences as shown in Tables I and II; b) at least 80% identical to the complement of a contiguous sequence of nucleotides in one of the nucleic acid sequences as shown in Tables I and II; or c) capable of selectively hybridizing to said GPCR gene nucleic acid; for diagnosing a susceptibihty to a disease or condition associated with a GPCR.