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 Aseev & 19 others 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, Michael Dean

Research output: Contribution to journalArticle

381 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Haplotypes
HIV-1
Acquired Immunodeficiency Syndrome
North American Indians
Alleles
Genealogy and Heraldry
Linkage Disequilibrium
Virus Diseases
Chemokines
Ethnic Groups
Gene Frequency
African Americans
Microsatellite Repeats
Chromosomes
Genotype
Lymphocytes
Population
Surveys and Questionnaires

ASJC Scopus subject areas

  • Genetics

Cite this

Stephens, J. C., Reich, D. E., Goldstein, D. B., Shin, H. D., Smith, M. W., Carrington, M., ... 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

Dating the origin of the CCR5-Δ32 AIDS-resistance allele by the coalescence of haplotypes. / Stephens, J. Claiborne; Reich, David E.; Goldstein, David B.; Shin, Hyoung Doo; Smith, Michael W.; Carrington, Mary; Winkler, Cheryl; Huttley, Gavin A.; Allikmets, Rando; Schriml, Lynn; Gerrard, Bernard; Malasky, Michael; Ramos, Maria D.; Morlot, Susanne; Tzetis, Maria; Oddoux, Carole; Di Giovine, Francesco S.; Nasioulas, Georgios; Chandler, David; Aseev, Michael; Hanson, Matthew; Kalaydjieva, Luba; Glavac, Damjan; Gasparini, Paolo; Kanavakis, E.; Claustres, Mireille; Kambouris, Marios; Ostrer, Harry; Duff, Gordon; Baranov, Vladislav; Sibul, Hiljar; Metspalu, Andres; Goldman, David; Martin, Nick; Duffy, David; Schmidtke, Jorg; Estivill, Xavier; O'Brien, Stephen J.; Dean, Michael.

In: American Journal of Human Genetics, Vol. 62, No. 6, 06.1998, p. 1507-1515.

Research output: Contribution to journalArticle

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 1998, 'Dating the origin of the CCR5-Δ32 AIDS-resistance allele by the coalescence of haplotypes', American Journal of Human Genetics, vol. 62, no. 6, pp. 1507-1515. https://doi.org/10.1086/301867
Stephens JC, Reich DE, Goldstein DB, Shin HD, Smith MW, Carrington M et al. Dating the origin of the CCR5-Δ32 AIDS-resistance allele by the coalescence of haplotypes. American Journal of Human Genetics. 1998 Jun;62(6):1507-1515. https://doi.org/10.1086/301867
Stephens, J. Claiborne ; Reich, David E. ; Goldstein, David B. ; Shin, Hyoung Doo ; Smith, Michael W. ; Carrington, Mary ; Winkler, Cheryl ; Huttley, Gavin A. ; Allikmets, Rando ; Schriml, Lynn ; Gerrard, Bernard ; Malasky, Michael ; Ramos, Maria D. ; Morlot, Susanne ; Tzetis, Maria ; Oddoux, Carole ; Di Giovine, Francesco S. ; Nasioulas, Georgios ; Chandler, David ; Aseev, Michael ; Hanson, Matthew ; Kalaydjieva, Luba ; Glavac, Damjan ; Gasparini, Paolo ; Kanavakis, E. ; Claustres, Mireille ; Kambouris, Marios ; Ostrer, Harry ; Duff, Gordon ; Baranov, Vladislav ; Sibul, Hiljar ; Metspalu, Andres ; Goldman, David ; Martin, Nick ; Duffy, David ; Schmidtke, Jorg ; Estivill, Xavier ; O'Brien, Stephen J. ; Dean, Michael. / Dating the origin of the CCR5-Δ32 AIDS-resistance allele by the coalescence of haplotypes. In: American Journal of Human Genetics. 1998 ; Vol. 62, No. 6. pp. 1507-1515.
@article{b3583653f9ca45c5ac7c362b65df90d4,
title = "Dating the origin of the CCR5-Δ32 AIDS-resistance allele by the coalescence of haplotypes",
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.",
author = "Stephens, {J. Claiborne} and Reich, {David E.} and Goldstein, {David B.} and Shin, {Hyoung Doo} and Smith, {Michael W.} and Mary Carrington and Cheryl Winkler and Huttley, {Gavin A.} and Rando Allikmets and Lynn Schriml and Bernard Gerrard and Michael Malasky and Ramos, {Maria D.} and Susanne Morlot and Maria Tzetis and Carole Oddoux and {Di Giovine}, {Francesco S.} and Georgios Nasioulas and David Chandler and Michael Aseev and Matthew Hanson and Luba Kalaydjieva and Damjan Glavac and Paolo Gasparini and E. Kanavakis and Mireille Claustres and Marios Kambouris and Harry Ostrer and Gordon Duff and Vladislav Baranov and Hiljar Sibul and Andres Metspalu and David Goldman and Nick Martin and David Duffy and Jorg Schmidtke and Xavier Estivill and O'Brien, {Stephen J.} and Michael Dean",
year = "1998",
month = "6",
doi = "10.1086/301867",
language = "English (US)",
volume = "62",
pages = "1507--1515",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - Dating the origin of the CCR5-Δ32 AIDS-resistance allele by the coalescence of haplotypes

AU - Stephens, J. Claiborne

AU - Reich, David E.

AU - Goldstein, David B.

AU - Shin, Hyoung Doo

AU - Smith, Michael W.

AU - Carrington, Mary

AU - Winkler, Cheryl

AU - Huttley, Gavin A.

AU - Allikmets, Rando

AU - Schriml, Lynn

AU - Gerrard, Bernard

AU - Malasky, Michael

AU - Ramos, Maria D.

AU - Morlot, Susanne

AU - Tzetis, Maria

AU - Oddoux, Carole

AU - Di Giovine, Francesco S.

AU - Nasioulas, Georgios

AU - Chandler, David

AU - Aseev, Michael

AU - Hanson, Matthew

AU - Kalaydjieva, Luba

AU - Glavac, Damjan

AU - Gasparini, Paolo

AU - Kanavakis, E.

AU - Claustres, Mireille

AU - Kambouris, Marios

AU - Ostrer, Harry

AU - Duff, Gordon

AU - Baranov, Vladislav

AU - Sibul, Hiljar

AU - Metspalu, Andres

AU - Goldman, David

AU - Martin, Nick

AU - Duffy, David

AU - Schmidtke, Jorg

AU - Estivill, Xavier

AU - O'Brien, Stephen J.

AU - Dean, Michael

PY - 1998/6

Y1 - 1998/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=17344372255&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17344372255&partnerID=8YFLogxK

U2 - 10.1086/301867

DO - 10.1086/301867

M3 - Article

VL - 62

SP - 1507

EP - 1515

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 6

ER -