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OwnerZenta Tsuchihashi, Lester Hui +5inventors
InventorsZenta Tsuchihashi, Lester Hui, Kim Zerba, Manling Ma-Edmonds, Mark Perrone, Brian Swanson, James Powell
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The invention provides polynucleotides and polypeptides corresponding to novel gene sequences associated with the incidence of cardiovascular disorders. The invention also provides polynucleotide fragments corresponding to the genomic and/or coding regions of these genes which comprise at least one polymorphic site per fragment. Allele-specific primers and probes which hybridize to these regions, and/or which comprise at least one polymorphic site are also provided. The polynucleotides, primers, and probes of the present invention are useful in phenotype correlations, paternity testing, medicine, and genetic analysis. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these novel polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders, particularly cardiovascular diseases related to these polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.
) An isolated nucleic acid derived from a human gene encoding a protein selected from a member of the group consisting of aminopeptidase P protein (XPNPEP2), bradykinin receptor B1 protein (BDKRB1), tachykinin receptor 1 protein (TACR1), C1 esterase inhibitor protein (CINH), kallikrein 1 protein (KLK1), bradykinin receptor B2 protein (BDKRB2), angiotension converting enzyme 2 protein (ACE2), and protease inhibitor 4 protein (PI4), wherein said nucleic acid comprises at least one polymorphic position.
) The isolated nucleic acid of claim 1 wherein said at least one polymorphic position for each said gene is a polymorphic position specified in Table V, or complement thereof.
) The isolated nucleic acid of claim 2 wherein the sequence at said at least one polymorphic position is depicted in a nucleic acid sequence selected from the group consisting of SEQ ID NO:
) The isolated nucleic acid of claim 3 wherein said at least one polymorphic position resides in a non-coding position within the genomic sequence of said gene.
) The isolated nucleic acid of claim 3 wherein said at least one polymorphic position resides in a coding position within the genomic sequence of said gene.
) The isolated nucleic acid of claim 5 wherein said at least one polymorphic position residing in a coding position results in a missense mutation of the translated product of said gene.
) The isolated nucleic acid of claim 5 wherein said at least one polymorphic position residing in a coding position results in a silent mutation of the translated product of said gene.
) The isolated nucleic acid of claim 4 wherein said at least one polymorphic position residing in a non-coding position resides within the untranslated region of said gene.
) The isolated nucleic acid of claim 4 wherein said at least one polymorphic position residing in a non-coding position resides within an intronic region of said gene.
) The isolated nucleic acid of claim 8 wherein said at least one polymorphic position is selected from the group consisting of:
) The isolated nucleic acid of claim 10 wherein said at least one polymorphic position is selected from the group consisting of:
) The isolated nucleic acid molecule according to claim 11, wherein asid nucleic acid sequence is at least 30 nucleotides in length.
) The isolated nucleic acid molecule according to claim 11, wherein said nucleic acid sequence is at least 40 nucleotides in length.
) A probe that hybridizes to a polymorphic position defined in claim 2.
) The probe of claim 14 wherein said probe is at least 15 nucleotides in length.
) The probe of claim 15 wherein a central position of the probe aligns with said polymorphic position.
) The probe of claim 15 wherein the 3′ end of the primer aligns with said polymorphic position.
) A method of analyzing at least one nucleic acid sample, comprising the steps of (1) obtaining said nucleic acid sample from one or more individuals;
) The method according to claim 18, further comprising the steps of (3) testing each individual for the presence of a disease phenotype;
) The method according to claim 19, wherein said one or more polymorphic position of said nucleic acid sequence is a polymorphic position specified in Table V for said gene.
) The method according to claim 20, wherein the nucleic acid sequence at said one or more polymorphic position is depicted in a nucleic acid sequence selected from the group consisting of SEQ ID NO:
) A method of constructing haplotypes using the isolated nucleic acids of claim 1, comprising the step of grouping at least two said nucleic acids.
) The method according to claim 22 further comprising the step of using said haplotypes to identify an individual for the presence of a disease phenotype, and correlating the presence of the disease phenotype with said haplotype.
) The method according to claim 19 further comprising the step of quantifying the nucleic acid sample comprising the polymorphic base.
25) The method according to claim 21 or 23 wherein the disease phenotype is angioedema or an angioedema-like disorder.
28) A method for identifying an individual at risk of developing a disorder upon administration of a pharmaceutically acceptable amount of an ACE inhibitor and/or vasopeptidase inhibitor comprising the steps of
32) A library of nucleic acids, each of which comprises one or more polymorphic positions within a gene encoding a human protein selected from the group consisting of aminopeptidase P protein (XPNPEP2), bradykinin receptor B1 protein (BDKRB1), tachykinin receptor 1 protein (TACR1), C1 esterase inhibitor protein (C1NH), kallikrein 1 protein (KLK1), bradykinin receptor B2 protein (BDKRB2), angiotension converting enzyme 2 protein (ACE2), and protease inhibitor 4 protein (PI4), wherein said polymorphic positions are selected from a group consisting of the polymorphic positions provided in Table V.
37) A kit for identifying an individual at risk of developing a disorder upon administration of a pharmaceutically acceptable amount of an ACE inhibitor and/or vasopeptidase inhibitor, said kit comprising
44) A method for identifying an individual at risk of developing a disorder upon administration of a pharmaceutically acceptable amount of an ACE inhibitor and/or vasopeptidase inhibitor comprising the steps of
48) A method for genotyping an individual comprising the steps of
Dependencies are inferred from the claim text.