Effects of natural selection on interpopulation divergence at polymorphic sites in human protein-coding loci

Austin L. Hughes, Bernice Packer, Robert Welch, Andrew W. Bergen, Stephen J. Chanock, Meredith Yeager

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1181-1187
Number of pages7
JournalGenetics
Volume170
Issue number3
DOIs
StatePublished - Jul 2005

ASJC Scopus subject areas

  • Genetics

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