Dating the origin of the CCR5-Δ32 AIDS-resistance allele by the coalescence of haplotypes

J. Claiborne Stephens, David E. Reich, David B. Goldstein, Hyoung Doo Shin, Michael W. Smith, Mary Carrington, Cheryl Winkler, Gavin A. Huttley, Rando Allikmets, Lynn Schriml, Bernard Gerrard, Michael Malasky, Maria D. Ramos, Susanne Morlot, Maria Tzetis, Carole Oddoux, Francesco S. Di Giovine, Georgios Nasioulas, David Chandler, Michael AseevMatthew Hanson, Luba Kalaydjieva, Damjan Glavac, Paolo Gasparini, E. Kanavakis, Mireille Claustres, Marios Kambouris, Harry Ostrer, Gordon Duff, Vladislav Baranov, Hiljar Sibul, Andres Metspalu, David Goldman, Nick Martin, David Duffy, Jorg Schmidtke, Xavier Estivill, Stephen J. O'Brien, Michael Dean

Research output: Contribution to journalArticle

388 Scopus citations

Abstract

The CCR5-Δ32 deletion obliterates the CCR5 chemokine and the human immunodeficiency virus (HIV)-1 coreceptor on lymphoid cells, leading to strong resistance against HIV-1 infection and AIDS. A genotype survey of 4,166 individuals revealed a cline of CCR5-Δ32 allele frequencies of 0%-14% across Eurasia, whereas the variant is absent among native African, American Indian, and East Asian ethnic groups. Haplotype analysis of 192 Caucasian chromosomes revealed strong linkage disequilibrium between CCR5 and two microsatellite loci. By use of coalescence theory to interpret modern haplotype genealogy, we estimate the origin of the CCR5-Δ32-containing ancestral haplotype to be ~700 years ago, with an estimated range of 275- 1,875 years. The geographic cline of CCR5-Δ32 frequencies and its recent emergence are consistent with a historic strong selective event (e.g., an epidemic of a pathogen that, like HIV-1, utilizes CCR5), driving its frequency upward in ancestral Caucasian populations.

Original languageEnglish (US)
Pages (from-to)1507-1515
Number of pages9
JournalAmerican Journal of Human Genetics
Volume62
Issue number6
DOIs
StatePublished - Jun 1998

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Stephens, J. C., Reich, D. E., Goldstein, D. B., Shin, H. D., Smith, M. W., Carrington, M., Winkler, C., Huttley, G. A., Allikmets, R., Schriml, L., Gerrard, B., Malasky, M., Ramos, M. D., Morlot, S., Tzetis, M., Oddoux, C., Di Giovine, F. S., Nasioulas, G., Chandler, D., ... Dean, M. (1998). Dating the origin of the CCR5-Δ32 AIDS-resistance allele by the coalescence of haplotypes. American Journal of Human Genetics, 62(6), 1507-1515. https://doi.org/10.1086/301867