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PMID: 14504236 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

A method for detecting recent selection in the human genome from allele age estimates.

Genetics ·Vol. 165 ·No. 1 ·2003-09-00 ·Pages 287-97

Toomajian C, Ajioka RS, Jorde LB, Kushner JP, Kreitman M

Abstract

Mutations that have recently increased in frequency by positive natural selection are an important component of naturally occurring variation that affects fitness. To identify such variants, we developed a method to test for recent selection by estimating the age of an allele from the extent of haplotype sharing at linked sites. Neutral coalescent simulations are then used to determine the likelihood of this age given the allele's observed frequency. We applied this method to a common disease allele, the hemochromatosis-associated HFE C282Y mutation. Our results allow us to reject neutral models incorporating plausible human demographic histories for HFE C282Y and one other young but common allele, indicating positive selection at HFE or a linked locus. This method will be useful for scanning the human genome for alleles under selection using the haplotype map now being constructed.

MeSH Terms
Alleles Evolution, Molecular Genetic Markers Genome, Human Hemochromatosis Protein Heterozygote Histocompatibility Antigens Class I/genetics Humans Membrane Proteins/genetics Selection, Genetic
Chemicals
Genetic Markers HFE protein, human Hemochromatosis Protein Histocompatibility Antigens Class I Membrane Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Toomajian Christopher
Committee on Genetics, University of Chicago, Chicago, Illinois 60637, USA. [email protected]
Ajioka Richard S
Jorde Lynn B
Kushner James P
Kreitman Martin
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
DOI
10.1093/genetics/165.1.287
Email
[email protected]
Published
2003-09-00
Pages
287-97
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1462736
Subset
IM
Grants
NIDDK NIH HHS · R01 DK20630-21 · United States
NIGMS NIH HHS · T32 GM07197 · United States
NCRR NIH HHS · M01 RR 00064 · United States
NIGMS NIH HHS · GM-59290 · United States
NIGMS NIH HHS · GM39355 · United States
External Links
PubMed source DOI: 10.1093/genetics/165.1.287 PMC Full Text View journal details
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