The Case for Selection at CCR5-Delta32.

@article{citeulike:375037, abstract = {The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 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-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 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-Delta32 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.}, address = {Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.}, author = {Sabeti, Pardis C C. and Walsh, Emily and Schaffner, Steve F F. and Varilly, Patrick and Fry, Ben and Hutcheson, Holli B B. and Cullen, Mike and Mikkelsen, Tarjei S S. and Roy, Jessica and Patterson, Nick and Cooper, Richard and Reich, David and Altshuler, David and Oʼbrien, Stephen and Lander, Eric S S. }, citeulike-article-id = {375037}, doi = {10.1371/journal.pbio.0030378}, issn = {1545-7885}, journal = {PLoS Biol}, keywords = {hiv, selection}, month = {November}, number = {11}, posted-at = {2005-11-15 04:29:26}, priority = {4}, title = {The Case for Selection at CCR5-Delta32.}, url = {http://dx.doi.org/10.1371/journal.pbio.0030378}, volume = {3}, year = {2005} }

TY - JOUR ID - citeulike:375037 L3 - citeulike-article-id:375037 TI - The Case for Selection at CCR5-Delta32. JF - PLoS Biol VL - 3 IS - 11 AD - Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America. SN - 1545-7885 N2 - The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 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-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 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-Delta32 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. KW - hiv KW - selection AU - Sabeti, Pardis C AU - Walsh, Emily AU - Schaffner, Steve F AU - Varilly, Patrick AU - Fry, Ben AU - Hutcheson, Holli B AU - Cullen, Mike AU - Mikkelsen, Tarjei S AU - Roy, Jessica AU - Patterson, Nick AU - Cooper, Richard AU - Reich, David AU - Altshuler, David AU - Oʼbrien, Stephen AU - Lander, Eric S PY - 2005/11/01/ UR - http://dx.doi.org/10.1371/journal.pbio.0030378 ER -