Document Detail

Detecting recent positive selection in the human genome from haplotype structure.
MedLine Citation:
PMID:  12397357     Owner:  NLM     Status:  MEDLINE    
The ability to detect recent natural selection in the human population would have profound implications for the study of human history and for medicine. Here, we introduce a framework for detecting the genetic imprint of recent positive selection by analysing long-range haplotypes in human populations. We first identify haplotypes at a locus of interest (core haplotypes). We then assess the age of each core haplotype by the decay of its association to alleles at various distances from the locus, as measured by extended haplotype homozygosity (EHH). Core haplotypes that have unusually high EHH and a high population frequency indicate the presence of a mutation that rose to prominence in the human gene pool faster than expected under neutral evolution. We applied this approach to investigate selection at two genes carrying common variants implicated in resistance to malaria: G6PD and CD40 ligand. At both loci, the core haplotypes carrying the proposed protective mutation stand out and show significant evidence of selection. More generally, the method could be used to scan the entire genome for evidence of recent positive selection.
Pardis C Sabeti; David E Reich; John M Higgins; Haninah Z P Levine; Daniel J Richter; Stephen F Schaffner; Stacey B Gabriel; Jill V Platko; Nick J Patterson; Gavin J McDonald; Hans C Ackerman; Sarah J Campbell; David Altshuler; Richard Cooper; Dominic Kwiatkowski; Ryk Ward; Eric S Lander
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2002-10-09
Journal Detail:
Title:  Nature     Volume:  419     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-10-24     Completed Date:  2002-11-22     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  832-7     Citation Subset:  IM    
Whitehead Institute/MIT Center for Genome Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.
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MeSH Terms
CD40 Ligand / genetics
Computer Simulation
Evolution, Molecular
Gene Pool
Genetic Predisposition to Disease / genetics*
Genetic Variation / genetics
Genome, Human*
Glucosephosphate Dehydrogenase / genetics
Haplotypes / genetics*
Malaria / enzymology,  genetics*,  parasitology
Mutation / genetics
Plasmodium falciparum / physiology
Polymorphism, Single Nucleotide / genetics
Selection, Genetic*
Time Factors
Reg. No./Substance:
147205-72-9/CD40 Ligand; EC Dehydrogenase
Comment In:
Curr Biol. 2003 Feb 4;13(3):R86-7   [PMID:  12573232 ]

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