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

被引：391

作者：

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 ^{[1
]}

Dean, M

机构：

[1] NCI, Lab Genom Divers, Frederick, MD 21702 USA

[2] NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick, MD 21702 USA

[3] Hosp Duran Reynals, IRO, Dept Mol Genet, Barcelona, Spain

[4] Med Hsch Hannover, Inst Humangenet, Hannover, Germany

[5] Univ Athens, St Sophias Childrens Hosp, Dept Pediat 1, GR-10679 Athens, Greece

[6] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Natl Retrovirus Reference Ctr, GR-10679 Athens, Greece

[7] NYU, Med Ctr, Human Genet Program, Dept Pediat, New York, NY 10016 USA

[8] Univ Sheffield, Dept Mol & Med Genet, Sheffield, S Yorkshire, England

[9] Edith Cowan Univ, Ctr Human Genet, Perth, WA, Australia

[10] Russian Acad Med Sci, Inst Obstet & Gynecol, St Petersburg, Russia

[11] Univ Ljubljana, Lab Mol Pathol, Ljubljana, Slovenia

[12] IRCCS, CSS Hosp, Natl Med Genet Serv, San Giovanni Rotondo, Italy

[13] CNRS, UPR 9008, Biochim Genet Lab, F-9008 Montpellier, France

[14] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia

[15] Tartu State Univ, Estonian Bioctr, EE-202400 Tartu, Estonia

[16] Tartu State Univ, Childrens Hosp, EE-202400 Tartu, Estonia

[17] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA

[18] Univ Oxford, Dept Zool, Oxford OX1 3PS, England

[19] Royal Brisband Hosp, Queensland Inst Med Res, Herston, Qld, Australia

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 1998年 / 62卷 / 06期

关键词：

D O I：

10.1086/301867

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The CCR5-Delta 32 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 dine of CCR5-Delta 32 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-Delta 32-containing ancestral haplotype to be similar to 700 years ago, with an estimated range of 275-1,875 years. The geographic dine of CCR5-Delta 32 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.

引用

页码：1507 / 1515

页数：9

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