Novel G protein-coupled receptors
OwnerGabriel Vogeliinventor
Life of this patent
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Abstract
The present invention provides a gene encoding a G protein-coupled receptor termed nGPCR-x; constructs and recombinant host cells incorporating the genes; the nGPCR-x polypeptides encoded by the gene; antibodies to the nGPCR-x polypeptides; and methods of making and using all of the foregoing.
Claims81
An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a polypeptide comprising an amino acid sequence homologous to sequences selected from the group consisting of:
- SEQ ID NO:129 to SEQ ID NO:257;
- said nucleic acid molecule encoding at least a portion of nGPCR-x.
An isolated nucleic acid molecule comprising at least 10 nucleotides, said nucleic acid molecule comprising a nucleotide sequence complementary to at least a portion of a sequence selected from the group of sequences consisting of SEQ ID NO:1 to SEQ ID NO:128.
A method for identifying a compound which binds nGPCR-x comprising the steps of:
- a) contacting nGPCR-x with a compound;
- and
- b) determining whether said compound binds nGPCR-x.
A method for identifying a compound which binds a nucleic acid molecule encoding nGPCR-x comprising the steps of:
- a) contacting said nucleic acid molecule encoding nGPCR-x with a compound;
- and
- b) determining whether said compound binds said nucleic acid molecule.
A method for identifying a compound which modulates the activity of nGPCR-x comprising the steps of:
- a) contacting nGPCR-x with a compound;
- and
- b) determining whether nGPCR-x activity has been modulated.
A method of identifying an animal homolog of nGPCR-x comprising the steps:
- a) comparing the nucleic acid sequences of the animal with a sequence selected from the group of sequence consisting of SEQ ID NO:1 to SEQ ID NO:128, and portions thereof, said portions being at least 10 nucleotides;
- and
- b) identifying nucleic acid sequences of the animal that are homologous to said sequence selected from the group sequence consisting of SEQ ID NO:1 to SEQ ID NO:128, and portions thereof, said portions comprising at least 10 nucleotides.
A method of screening a human subject to diagnose a disorder affecting the brain or genetic predisposition therefor, comprising the steps of:
- (a) assaying nucleic acid of a human subject to determine a presence or an absence of a mutation altering an amino acid sequence, expression, or biological activity of at least one nGPCR-x that is expressed in the brain, wherein the nGPCR-x comprises an amino acid sequence selected from the group consisting of SEQ ID NO:129 to SEQ ID NO:257, and allelic variants thereof, and wherein the nucleic acid corresponds to a gene encoding the nGPCR-x;
- and
- (b) diagnosing the disorder or predisposition from the presence or absence of said mutation, wherein the presence of a mutation altering the amino acid sequence, expression, or biological activity of the nGPCR-x in the nucleic acid correlates with an increased risk of developing the disorder.
A method of screening for an nGPCR-x hereditary mental disorder genotype in a human patient, comprising the steps of:
- (a) providing a biological sample comprising nucleic acid from said patient, said nucleic acid including sequences corresponding to alleles of nGPCR-x;
- and
- (b) detecting the presence of one or more mutations in the nGPCR-x allele;
- wherein the presence of a mutation in a nGPCR-x allele is indicative of a hereditary mental disorder genotype.
A kit for screening a human subject to diagnose a mental disorder or a genetic predisposition therefor, comprising, in association:
- (a) an oligonucleotide useful as a probe for identifying polymorphisms in a human nGPCR-x gene, the oligonucleotide comprising 6-50 nucleotides in a sequence that is identical or complementary to a sequence of a wild type human nGPCR-x gene sequence or nGPCR-x coding sequence, except for one sequence difference selected from the group consisting of a nucleotide addition, a nucleotide deletion, or nucleotide substitution;
- and
- (b) a media packaged with the oligonucleotide, said media containing information for identifying polymorphisms that correlate with mental disorder or a genetic predisposition therefor, the polymorphisms being identifiable using the oligonucleotide as a probe.
A method of identifying a nGPCR-x allelic variant that correlates with a mental disorder, comprising the steps of:
- (a) providing a biological sample comprising nucleic acid from a human patient diagnosed with a mental disorder, or from the patient's genetic progenitors or progeny;
- (b) detecting in the nucleic acid the presence of one or more mutations in an nGPCR-x that is expressed in the brain, wherein the nGPCR-x comprises an amino acid sequence selected from the group consisting of SEQ ID NO:129 to SEQ ID NO:257, and allelic variants thereof, and wherein the nucleic acid includes sequence corresponding to the gene or genes encoding nGPCR-x;
- wherein the one or more mutations detected indicates an allelic variant that correlates with a mental disorder.
A purified polynucleotide comprising a nucleotide sequence encoding nGPCR-x of a human with a mental disorder;
- wherein said polynucleotide hybridizes to the complement of a sequence selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:128 under the following hybridization conditions:
- (a) hybridization for 16 hours at 42° C. in a hybridization solution comprising 50% formamide, 1% SDS, 1 M NaCl, 10% dextran sulfate and
- (b) washing 2 times for 30 minutes at 60° C. in a wash solution comprising 0.1× SSC and 1% SDS;
- and
- wherein the polynucleotide that encodes nGPCR-x amino acid sequence of the human differs from the sequence selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:128 by at least one residue.
A method to identify compounds useful for the treatment of a mental disorder, said method comprising the steps of:
- (a) contacting a composition comprising nGPCR-x with a compound suspected of binding nGPCR-x;
- (b) detecting binding between nGPCR-x and the compound suspected of binding nGPCR-x;
- wherein compounds identified as binding nGPCR-x are candidate compounds useful for the treatment of a mental disorder.
A method for identifying a compound useful as a modulator of binding between nGPCR-x and a binding partner of nGPCR-x comprising the steps of:
- (a) contacting the binding partner and a composition comprising nGPCR-x in the presence and in the absence of a putative modulator compound;
- (b) detecting binding between the binding partner and nGPCR-x;
- wherein decreased or increased binding between the binding partner and nGPCR-x in the presence of the putative modulator, as compared to binding in the absence of the putative modulator is indicative a modulator compound useful for the treatment of a mental disorder.
Dependencies are inferred from the claim text.