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Am J Hum Genet. 2011 Sep 9;89(3):368-81. doi: 10.1016/j.ajhg.2011.07.025.

Genome-wide comparison of African-ancestry populations from CARe and other cohorts reveals signals of natural selection.

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1
Harvard- Massachusetts Institute of Technology (MIT) Division of Health, Science and Technology, Cambridge, USA. gbhatia@mit.edu

Abstract

The study of recent natural selection in human populations has important applications to human history and medicine. Positive natural selection drives the increase in beneficial alleles and plays a role in explaining diversity across human populations. By discovering traits subject to positive selection, we can better understand the population level response to environmental pressures including infectious disease. Our study examines unusual population differentiation between three large data sets to detect natural selection. The populations examined, African Americans, Nigerians, and Gambians, are genetically close to one another (F(ST) < 0.01 for all pairs), allowing us to detect selection even with moderate changes in allele frequency. We also develop a tree-based method to pinpoint the population in which selection occurred, incorporating information across populations. Our genome-wide significant results corroborate loci previously reported to be under selection in Africans including HBB and CD36. At the HLA locus on chromosome 6, results suggest the existence of multiple, independent targets of population-specific selective pressure. In addition, we report a genome-wide significant (p = 1.36 × 10(-11)) signal of selection in the prostate stem cell antigen (PSCA) gene. The most significantly differentiated marker in our analysis, rs2920283, is highly differentiated in both Africa and East Asia and has prior genome-wide significant associations to bladder and gastric cancers.

PMID:
21907010
PMCID:
PMC3169818
DOI:
10.1016/j.ajhg.2011.07.025
[Indexed for MEDLINE]
Free PMC Article
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