title: Genome-wide detection and characterization of positive selection in human populations.
abstract: 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). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, 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, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA. pardis@broad.mit.edu
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mesh_terms: D017920:Antiporters / Q000235:genetics; D053339:Edar Receptor / Q000737:chemistry / Q000235:genetics; D005787:Gene Frequency; D005828:Genetics, Population; D015894:Genome, Human / Q000235:genetics*; D005843:Geography; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017434:Protein Structure, Tertiary; D012641:Selection, Genetic
chemical_list: D017920:Antiporters; C506008:EDAR protein, human; D053339:Edar Receptor; C506584:SLC24A5 protein, human