Dating the Origin of the CCR5-Delta32 AIDS-resistance Allele by the Coalescence of Haplotypes

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1998 Jun 19

PMID 9585595

Citations 163

Authors

J C Stephens

D E Reich

D B Goldstein

H D Shin

M W Smith

M Carrington

C Winkler

G A Huttley

R Allikmets

L Schriml

B Gerrard

M Malasky

M D Ramos

S Morlot

M Tzetis

C Oddoux

F S Di Giovine

G Nasioulas

D Chandler

M Aseev

M Hanson

L Kalaydjieva

D Glavac

P Gasparini

E Kanavakis

M Claustres

M Kambouris

H Ostrer

G Duff

V Baranov

H Sibul

A Metspalu

D Goldman

N Martin

D Duffy

J Schmidtke

X Estivill

S J OBrien

M Dean

Affiliations

Soon will be listed here.

Abstract

The CCR5-Delta32 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-Delta32 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-Delta32-containing ancestral haplotype to be approximately 700 years ago, with an estimated range of 275-1,875 years. The geographic cline of CCR5-Delta32 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.

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