Genome-wide detection and characterization of positive selection in human populations.
Sabeti, Pardis C. 1*; Varilly, Patrick 1*; Fry, Ben 1; Lohmueller, Jason 1; Hostetter, Elizabeth 1; Cotsapas, Chris 1,2; Xie, Xiaohui 1; Byrne, Elizabeth H. 1; McCarroll, Steven A. 1,2; Gaudet, Rachelle 3; Schaffner, Stephen F. 1; Lander, Eric S. 1,4,5,6; The International HapMap Consortium +
[Letter]
Nature.
449(7164):913-918, October 18, 2007.
(Format: HTML, PDF)
With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2) 1. We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection 2, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population: LARGE and DMD, both related to infection by the Lassa virus 3, in West Africa; SLC24A5 and SLC45A2, both involved in skin pigmentation 4,5, in Europe; and EDAR and EDA2R, both involved in development of hair follicles 6, in Asia.
(C) 2007 Nature Publishing Group