The Case for Selection at CCR5-Δ32

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The Case for Selection at CCR5-Δ32

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Title: The Case for Selection at CCR5-Δ32
Author: Walsh, Emily; Schaffner, Steve F; Varilly, Patrick; Fry, Ben; Hutcheson, Holli B; Cullen, Mike; Mikkelsen, Tarjei S; Roy, Jessica; Patterson, Nick; Sabeti, Pardis Christine; Cooper, Richard; Reich, David Emil; Altshuler, David Matthew; O'Brien, Stephen James; Lander, Eric Steven

Note: Order does not necessarily reflect citation order of authors.

Citation: Sabeti, Pardis C., Emily Walsh, Steve F. Schaffner, Patrik Varilly, Ben Fry, Holli B. Hutcheson, Mike Cullen, et al. 2005. The Case for Selection at Δ. PLoS Biology 3(11): e378.
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Abstract: The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Δ32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Δ32 arose within the past 1,000 y and rose to its present high frequency (5%–14%) in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Δ32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Δ32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5), they imply that the pattern of genetic variation seen atCCR5-Δ32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome.
Published Version: doi:10.1371/journal.pbio.0030378
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1275522/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4460864

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  • FAS Scholarly Articles [7078]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University
 
 

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