Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis
- PMID:10391210
- DOI: 10.1038/10297
Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis
Abstract
Sequence variation in human genes is largely confined to single-nucleotide polymorphisms (SNPs) and is valuable in tests of association with common diseases and pharmacogenetic traits. We performed a systematic and comprehensive survey of molecular variation to assess the nature, pattern and frequency of SNPs in 75 candidate human genes for blood-pressure homeostasis and hypertension. We assayed 28 Mb (190 kb in 148 alleles) of genomic sequence, comprising the 5' and 3' untranslated regions (UTRs), introns and coding sequence of these genes, for sequence differences in individuals of African and Northern European descent using high-density variant detection arrays (VDAs). We identified 874 candidate human SNPs, of which 22% were confirmed by DNA sequencing to reveal a discordancy rate of 21% for VDA detection. The SNPs detected have an average minor allele frequency of 11%, and 387 are within the coding sequence (cSNPs). Of all cSNPs, 54% lead to a predicted change in the protein sequence, implying a high level of human protein diversity. These protein-altering SNPs are 38% of the total number of such SNPs expected, are more likely to be population-specific and are rarer in the human population, directly demonstrating the effects of natural selection on human genes. Overall, the degree of nucleotide polymorphism across these human genes, and orthologous great ape sequences, is highly variable and is correlated with the effects of functional conservation on gene sequences.
Similar articles
- Characterization of single-nucleotide polymorphisms in coding regions of human genes.Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES.Cargill M, et al.Nat Genet. 1999 Jul;22(3):231-8. doi: 10.1038/10290.Nat Genet. 1999.PMID:10391209
- Verification of 525 coding SNPs in 179 hypertension candidate genes in the Japanese population: identification of 159 SNPs in 93 genes.Okuda T, Fujioka Y, Kamide K, Kawano Y, Goto Y, Yoshimasa Y, Tomoike H, Iwai N, Hanai S, Miyata T.Okuda T, et al.J Hum Genet. 2002;47(8):387-94. doi: 10.1007/s100380200056.J Hum Genet. 2002.PMID:12181638
- Human-chimpanzee DNA sequence variation in the four major genes of the renin angiotensin system.Dufour C, Casane D, Denton D, Wickings J, Corvol P, Jeunemaitre X.Dufour C, et al.Genomics. 2000 Oct 1;69(1):14-26. doi: 10.1006/geno.2000.6313.Genomics. 2000.PMID:11013071
- The patterns of natural variation in human genes.Crawford DC, Akey DT, Nickerson DA.Crawford DC, et al.Annu Rev Genomics Hum Genet. 2005;6:287-312. doi: 10.1146/annurev.genom.6.080604.162309.Annu Rev Genomics Hum Genet. 2005.PMID:16124863Review.
- A single nucleotide polymorphism based approach for the identification and characterization of gene expression modulation using MassARRAY.Jurinke C, Denissenko MF, Oeth P, Ehrich M, van den Boom D, Cantor CR.Jurinke C, et al.Mutat Res. 2005 Jun 3;573(1-2):83-95. doi: 10.1016/j.mrfmmm.2005.01.007.Mutat Res. 2005.PMID:15829239Review.
Cited by
- The solute carrier 6 family of transporters.Bröer S, Gether U.Bröer S, et al.Br J Pharmacol. 2012 Sep;167(2):256-78. doi: 10.1111/j.1476-5381.2012.01975.x.Br J Pharmacol. 2012.PMID:22519513Free PMC article.Review.
- Effect of the rs168924 single-nucleotide polymorphism in the SLC6A2 catecholamine transporter gene on blood pressure in Caucasians.Zolk O, Ott C, Fromm MF, Schmieder RE.Zolk O, et al.J Clin Hypertens (Greenwich). 2012 May;14(5):293-8. doi: 10.1111/j.1751-7176.2012.00618.x. Epub 2012 Apr 9.J Clin Hypertens (Greenwich). 2012.PMID:22533655Free PMC article.
- When did the human population size start increasing?Wall JD, Przeworski M.Wall JD, et al.Genetics. 2000 Aug;155(4):1865-74. doi: 10.1093/genetics/155.4.1865.Genetics. 2000.PMID:10924481Free PMC article.
- Categorization of humans in biomedical research: genes, race and disease.Risch N, Burchard E, Ziv E, Tang H.Risch N, et al.Genome Biol. 2002 Jul 1;3(7):comment2007. doi: 10.1186/gb-2002-3-7-comment2007. Epub 2002 Jul 1.Genome Biol. 2002.PMID:12184798Free PMC article.
- The genetics of rheumatoid arthritis: influences on susceptibility, severity, and treatment response.Bridges SL Jr.Bridges SL Jr.Curr Rheumatol Rep. 1999 Dec;1(2):164-71. doi: 10.1007/s11926-999-0014-4.Curr Rheumatol Rep. 1999.PMID:11123031Review.
Publication types
MeSH terms
Substances
Related information
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous