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Title: Effects of natural selection on interpopulation divergence at polymorphic sites in human protein-coding Loci.
Authors: Hughes AL,  Packer B,  Welch R,  Bergen AW,  Chanock SJ,  Yeager M
Journal: Genetics
Date: 2005 Jul
Branches: CGR, ITEB
PubMed ID: 15911586
PMC ID: PMC1242184
Abstract: To develop new strategies for searching for genetic associations with complex human diseases, we analyzed 2784 single-nucleotide polymorphisms (SNPs) in 396 protein-coding genes involved in biological processes relevant to cancer and other complex diseases, with respect to gene diversity within samples of individuals representing the three major historic human populations (African, European, and Asian) and with respect to interpopulation genetic distance. Reduced levels of both intrapopulation gene diversity and interpopulation genetic distance were seen in the case of SNPs located within the 5'-UTR and at nonsynonymous SNPs, causing radical changes to protein structure. Reduction of gene diversity at SNP loci in these categories was evidence of purifying selection acting at these sites, which in turn causes a reduction in interpopulation divergence. By contrast, a small number of SNP sites in these categories revealed unusually high genetic distances between the two most diverged populations (African and Asian); these loci may have historically been subject to divergent selection pressures.