Detecting recent positive selection in the human genome from haplotype structure

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 and Eric S. Lander ()
Additional contact information
Pardis C. Sabeti: Whitehead Institute/MIT Center for Genome Research, Nine Cambridge Center
David E. Reich: Whitehead Institute/MIT Center for Genome Research, Nine Cambridge Center
John M. Higgins: Whitehead Institute/MIT Center for Genome Research, Nine Cambridge Center
Haninah Z. P. Levine: Whitehead Institute/MIT Center for Genome Research, Nine Cambridge Center
Daniel J. Richter: Whitehead Institute/MIT Center for Genome Research, Nine Cambridge Center
Stephen F. Schaffner: Whitehead Institute/MIT Center for Genome Research, Nine Cambridge Center
Stacey B. Gabriel: Whitehead Institute/MIT Center for Genome Research, Nine Cambridge Center
Jill V. Platko: Whitehead Institute/MIT Center for Genome Research, Nine Cambridge Center
Nick J. Patterson: Whitehead Institute/MIT Center for Genome Research, Nine Cambridge Center
Gavin J. McDonald: Whitehead Institute/MIT Center for Genome Research, Nine Cambridge Center
Hans C. Ackerman: Wellcome Trust Centre for Human Genetics
Sarah J. Campbell: Wellcome Trust Centre for Human Genetics
David Altshuler: Whitehead Institute/MIT Center for Genome Research, Nine Cambridge Center
Richard Cooper: Loyola University Medical School
Dominic Kwiatkowski: Wellcome Trust Centre for Human Genetics
Ryk Ward: University of Oxford
Eric S. Lander: Whitehead Institute/MIT Center for Genome Research, Nine Cambridge Center

Nature, 2002, vol. 419, issue 6909, 832-837

Abstract: Abstract 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: G6PD1 and CD40 ligand2. 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.

Date: 2002
References: Add references at CitEc
Citations: View citations in EconPapers (7)

Downloads: (external link)
https://www.nature.com/articles/nature01140 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:419:y:2002:i:6909:d:10.1038_nature01140

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01140

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().