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PMID: 9585595 Published · ppublish English Journal Article

Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes.

American journal of human genetics ·Vol. 62 ·No. 6 ·1998-06-00 ·Pages 1507-15

Stephens JC, Reich DE, Goldstein DB, Shin HD, Smith MW, Carrington M, Winkler C, Huttley GA, Allikmets R, Schriml L, Gerrard B, Malasky M, Ramos MD, Morlot S, Tzetis M, Oddoux C, di Giovine FS, Nasioulas G, Chandler D, Aseev M, Hanson M, Kalaydjieva L, Glavac D, Gasparini P, Kanavakis E, Claustres M, Kambouris M, Ostrer H, Duff G, Baranov V, Sibul H, Metspalu A, Goldman D, Martin N, Duffy D, Schmidtke J, Estivill X, O'Brien SJ, Dean M

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.

MeSH Terms
Acquired Immunodeficiency Syndrome/genetics,immunology Alleles Evolution, Molecular Gene Deletion Gene Frequency Haplotypes Humans Hybrid Cells Immunity, Innate/genetics Receptors, CCR5/genetics
Chemicals
Receptors, CCR5
Authors & Affiliations
39 authors, click to expand affiliations / ORCID
Stephens J C
Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD 21702-1201, USA.
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
Aseev M
Hanson M
Kalaydjieva L
Glavac D
Gasparini P
Kanavakis E
Claustres M
Kambouris M
Ostrer H
Duff G
Baranov V
Sibul H
Metspalu A
Goldman D
Martin N
Duffy D
Schmidtke J
Estivill X
O'Brien S J
Dean M
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/301867
Published
1998-06-00
Pages
1507-15
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1377146
Subset
IM
External Links
PubMed source DOI: 10.1086/301867 PMC Full Text View journal details
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