Polymorphisms associated with hypertension

Abstract

The invention discloses a collection of polymorphic sites in genes know or suspected to have a role in hypertension. The invention provides nucleic acids including such polymorphic sites. The nucleic acids can be used as probes or primers or for expressing variant proteins. The invention also provide methods of analyzing the polymorphic forms occupying the polymorphic sites.

What is claimed is:  
     
         1 . A nucleic acid of between 10 and 100 bases comprising at least 10 contiguous nucleotides including a polymorphic site from a sequence shown in Table 1, column 8 or the complement thereof.  
     
     
         2 . The nucleic acid of  claim 1  that is DNA.  
     
     
         3 . The nucleic acid of  claim 1  that is RNA.  
     
     
         4 . The nucleic acid of  claim 1  that is less than 50 bases.  
     
     
         5 . The nucleic acid of  claim 1  that is less than 20 bases.  
     
     
         6 . The nucleic acid of  claim 1 , wherein the polymorphic form occupying the polymorphic site is a reference base shown in Table 1, column 3.  
     
     
         7 . The nucleic acid of  claim 1 , wherein the polymorphic form occupying the polymorphic site is an alternative base shown in Table 1, column 5.  
     
     
         8 . The nucleic acid of  claim 7 , wherein the alternative base correlates with hypertension or susceptibility thereto.  
     
     
         9 . The nucleic acid of  claim 1 , wherein the polymorphic site is one for which reference and alternative bases shown in columns 3 and 5 of Table 1 are respectively components of different codons encoding different amino acids.  
     
     
         10 . The nucleic acid of  claim 1 , which is from a gene encoding a human angiotensin I receptor.  
     
     
         11 . The nucleic acid of  claim 1 , which is from a gene encoding an angiotensin II receptor.  
     
     
         12 . The nucleic acid of  claim 1 , which is from a gene encoding an atrial natriuretic peptide.  
     
     
         13 . The nucleic acid of  claim 1 , which is from a gene encoding a β-3-adrenergic receptor.  
     
     
         14 . The nucleic acid of  claim 1 , which is from a gene encoding a bradykinin receptor B2.  
     
     
         15 . The nucleic acid of  claim 1 , which is from a gene encoding a mineralocorticoid receptor  
     
     
         16 . The nucleic acid of  claim 1 , which is from a gene encoding a renin protein.  
     
     
         17 . The nucleic acid of  claim 1 , which from a gene encoding an angiotensinogen protein.  
     
     
         18 . The nucleic acid of  claim 1 , which from a gene encoding a sodium calcium ion channel.  
     
     
         19 . The nucleic acid of  claim 1 , which is from a gene encoding an angiotensin converting protein.  
     
     
         20 . The nucleic acid of  claim 1 , which is from a gene encoding an angiotensin converting protein.  
     
     
         21 . Allele-specific oligonucleotide that hybridizes to a sequence including a polymorphic site shown in Table 1 or the complement thereof.  
     
     
         22 . The allele-specific oligonucleotide of  claim 21  that is a probe.  
     
     
         23 . An isolated nucleic acid comprising a sequence of Table 1, column 8 or the complement thereof, wherein the polymorphic site within the sequence or its complement is occupied by a base other than the reference base show in Table 1, column 3.  
     
     
         24 . A method of analyzing a nucleic acid, comprising: 
 obtaining the nucleic acid from an individual; and    determining a base occupying any one of the polymorphic sites shown in Table 1 or other polymorphic sites in equilibrium dislinkage therewith.    
     
     
         25 . The method of  claim 24 , wherein the determining comprises determining a set of bases occupying a set of the polymorphic sites shown in Table 1.  
     
     
         26 . The method of  claim 25 , wherein the nucleic acid is obtained from a plurality of individuals, and a base occupying one of the polymorphic positions is determined in each of the individuals, and the method further comprising testing each individual for the presence of a disease phenotype, and correlating the presence of the disease phenotype with the base.  
     
     
         27 . The method of  claim 24 , wherein the determined base is correlated with susceptibility to hypertension.  
     
     
         28 . A method of diagnosing a phenotype comprising: 
 determining which polymorphic form(s) are present in a sample from a subject at one or more polymorphic sites shown in Table 1;    diagnosing the presence of a phenotype correlated with the form(s) in the subject.    
     
     
         29 . The method of  claim 28 , wherein the phenotype is hypertension.  
     
     
         30 . A method of screening for a polymorphic site suitable for diagnosing a phenotype, comprising: 
 identifying a polymorphic site linked to a polymorphic site shown in Table 1, wherein a polymorphic form of the polymorphic site shown in Table 1 has been correlated with a phenotype; and    determining haplotypes in a population of individuals to indicate whether the linked polymorphic site has a polymorphic form in equlibrium dislinkage with the polymorphic form correlated with the phenotype.    
     
     
         31 . The method of  claim 30 , wherein the polymorphic form of the polymorphic site shown in Table I has been correlated with hypertension.  
     
     
         32 . The method of  claim 30 , wherein the linked polymorphic site and the polymorphic site shown in Table 1 are from the same gene.  
     
     
         33 . A computer-readable storage medium for storing data for access by an application program being executed on a data processing system, comprising: 
 a data structure stored in the computer-readable storage medium, the data structure including information resident in a database used by the application program and including: 
 a plurality of records, each record of the plurality comprising information identifying a polymorphisms shown in Table 1.  
   
     
     
         34 . The computer-readable storage medium of  claim 33 , wherein each record has a field identifying a base occupying a polymorphic site and a location of the polymorphic site.  
     
     
         35 . The computer-readable storage medium of  claim 33 , wherein each record identifies a nucleic acid segment of between 10 and 100 bases from a fragment shown in Table 1 including a polymorphic site, or the complement of the segment.  
     
     
         36 . The computer-readable storage medium of  claim 33 , comprising at least 10 records, each record comprising information identifying a different polymorphism shown in Table 1.  
     
     
         37 . The computer-readable storage medium of  claim 33 , comprising at least 10 records, each record comprising information identifying a different polymorphism shown in Table 1.  
     
     
         38 . A signal carrying data for access by an application program being executed on a data processing system, comprising: 
 a data structure encoded in the signal, said data structure including information resident in a database used by the application program and including: 
 a plurality of records, each record of the plurality comprising information identifying a polymorphism shown in Table 1