title: Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes.
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.
authors.affiliation: Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD 21702-1201, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Stephens
authors.forename: D E
authors.initials: DE
authors.lastname: Reich
authors.forename: D B
authors.initials: DB
authors.lastname: Goldstein
authors.forename: H D
authors.initials: HD
authors.lastname: Shin
authors.forename: M W
authors.initials: MW
authors.lastname: Smith
authors.forename: M
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authors.lastname: Carrington
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authors.lastname: Winkler
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authors.lastname: Huttley
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authors.lastname: Allikmets
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authors.lastname: Schriml
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authors.lastname: Malasky
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authors.initials: MD
authors.lastname: Ramos
authors.forename: S
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authors.lastname: Morlot
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authors.lastname: Tzetis
authors.forename: C
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authors.lastname: Oddoux
authors.forename: F S
authors.initials: FS
authors.lastname: di Giovine
authors.forename: G
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authors.lastname: Nasioulas
authors.forename: D
authors.initials: D
authors.lastname: Chandler
authors.forename: M
authors.initials: M
authors.lastname: Aseev
authors.forename: M
authors.initials: M
authors.lastname: Hanson
authors.forename: L
authors.initials: L
authors.lastname: Kalaydjieva
authors.forename: D
authors.initials: D
authors.lastname: Glavac
authors.forename: P
authors.initials: P
authors.lastname: Gasparini
authors.forename: E
authors.initials: E
authors.lastname: Kanavakis
authors.forename: M
authors.initials: M
authors.lastname: Claustres
authors.forename: M
authors.initials: M
authors.lastname: Kambouris
authors.forename: H
authors.initials: H
authors.lastname: Ostrer
authors.forename: G
authors.initials: G
authors.lastname: Duff
authors.forename: V
authors.initials: V
authors.lastname: Baranov
authors.forename: H
authors.initials: H
authors.lastname: Sibul
authors.forename: A
authors.initials: A
authors.lastname: Metspalu
authors.forename: D
authors.initials: D
authors.lastname: Goldman
authors.forename: N
authors.initials: N
authors.lastname: Martin
authors.forename: D
authors.initials: D
authors.lastname: Duffy
authors.forename: J
authors.initials: J
authors.lastname: Schmidtke
authors.forename: X
authors.initials: X
authors.lastname: Estivill
authors.forename: S J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: M
authors.initials: M
authors.lastname: Dean
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology; D000483:Alleles; D019143:Evolution, Molecular; D017353:Gene Deletion; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D006822:Hybrid Cells; D007113:Immunity, Innate / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*
chemical_list: D019713:Receptors, CCR5