Dating the Origin of the CCR5-Δ32 AIDS-Resistance Allele by the Coalescence of Haplotypes

Authors

• J. Claiborne Stephens, National Cancer Institute at Frederick
• David E. Riech, University of Oxford
• David B. Goldstein, University of Oxford
• Hyoung Doo Shin, National Cancer Institute at Frederick
• Michael W. Smith, National Cancer Institute at Frederick
• Mary Carrington, National Cancer Institute at Frederick
• Cheryl Winkler, National Cancer Institute at Frederick
• Gavin A. Huttley, National Cancer Institute at Frederick
• Rando Allikmets, National Cancer Institute at Frederick
• Lynn Schriml, National Cancer Institute at Frederick
• Bernard Gerrard, National Cancer Institute at Frederick
• Michael Malasky, National Cancer Institute at Frederick
• Maria D. Ramos, Hospital Duran i Reynals - Barcelona, Spain
• Susanne Morlot, Medizinische Hochschule - Hannover, Germany
• Maria Tzetis, University of Athens School of Medicine
• Carole Oddoux, New York University Medical Center
• Francesco S. di Giovine, University of Sheffield - United Kingdom
• Georgios Nasioulas, University of Athens School of Medicine
• David Chandler, Edith Cowan University - Perth, Australia
• Michael Aseev, Russian Academy of Medical Sciences - St. Petersburg
• Matthew Hanson, National Cancer Institute at Frederick
• Luba Kalaydjieva, Edith Cowan University - Perth, Australia
• Damjan Glavac, University of Ljubljana - Slovenia
• Paolo Gasparini, IRCCS-CSS Hospital - San Giovanni Rotondo, Italy
• E. Kanavakis, University of Athens School of Medicine
• Mireille Claustres, Laboratoire de Biochimie Genetique - Montpellier, France
• Marios Kambouris, King Faisal Specialist Hospital and Research Center - Riyadh, Saudi Arabia
• Harry Ostrer, New York University Medical Center
• Gordon Duff, University of Sheffield - United Kingdom
• Vladislav Baranov, Russian Academy of Medical Sciences - St. Petersburg
• Hiljar Sibul, University of Tartu - Estonia
• Andres Metspalu, University of Tartu - Estonia
• David Goldman, National Institute on Alcohol Abuse and Alcoholism
• Nick Martin, Royal Brisband Hospital - Herston, Australia
• David Duffy, Royal Brisband Hospital - Herston, Australia
• Jorg Schmidtke, Medizinische Hochschule - Hannover, Germany
• Xavier Estivill, Hospital Duran i Reynals - Barcelona, Spain
• Stephen J. O'Brien, National Cancer Institute at FrederickFollow
• Michael Dean, National Cancer Institute at Frederick

ORCID

0000-0001-7353-8301

ResearcherID

N-1726-2015

Document Type

Article

Publication Title

American Journal of Human Genetics

ISSN

0002-9297

Publication Date

6-1998

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 approximately 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.

Volume

62

Issue

6

First Page

1507

Last Page

1515

Comments

©1998 by The American Society of Human Genetics.

NSUWorks Citation

Stephens, J. Claiborne; David E. Riech; 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 Aseev; Matthew 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; and Michael Dean. 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://nsuworks.nova.edu/cnso_bio_facarticles/676