Biology Faculty Articles

Title

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

Document Type

Article

Publication Date

6-1998

Publication Title

American Journal of Human Genetics

ISSN

0002-9297

Volume

62

Issue/No.

6

First Page

1507

Last Page

1515

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.

Comments

©1998 by The American Society of Human Genetics.

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

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