title: Evidence for positive selection and population structure at the human MAO-A gene.
abstract: We report the analysis of human nucleotide diversity at a genetic locus known to be involved in a behavioral phenotype, the monoamine oxidase A gene. Sequencing of five regions totaling 18.8 kb and spanning 90 kb of the monoamine oxidase A gene was carried out in 56 male individuals from seven different ethnogeographic groups. We uncovered 41 segregating sites, which formed 46 distinct haplotypes. A permutation test detected substantial population structure in these samples. Consistent with differentiation between populations, linkage disequilibrium is higher than expected under panmixia, with no evidence of a decay with distance. The extent of linkage disequilibrium is not typical of nuclear loci and suggests that the underlying population structure may have been accentuated by a selective sweep that fixed different haplotypes in different populations, or by local adaptation. In support of this suggestion, we find both a reduction in levels of diversity (as measured by a Hudson-Kreitman-Aguade test with the DMD44 locus) and an excess of high frequency-derived variants, as expected after a recent episode of positive selection.
authors.affiliation: Department of Molecular Genetics and the Crown Human Genome Center, The Weizmann Institute of Science, Rehovot 76100, Israel. yoav.gilad@weizmann.ac.il
authors.forename: Yoav
authors.initials: Y
authors.lastname: Gilad
authors.forename: Shai
authors.initials: S
authors.lastname: Rosenberg
authors.forename: Molly
authors.initials: M
authors.lastname: Przeworski
authors.forename: Doron
authors.initials: D
authors.lastname: Lancet
authors.forename: Karl
authors.initials: K
authors.lastname: Skorecki
mesh_terms: D000818:Animals; D014644:Genetic Variation; D005824:Genetics, Behavioral; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D002679:Pan troglodytes; D011995:Recombination, Genetic; D012641:Selection, Genetic
chemical_list: D008995:Monoamine Oxidase