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Dating the Origin of the Ccr5-Delta-32 Aids-Resistance Allele By the Coalescence of Haplotypes

  1. Author:
    Stephens, J. C.
    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.
    Digiovine, F. S.
    Nasioulas, G.
    Chandler, D.
    Aseev, M.
    Hanson, M.
    Kalaydjieva, L.
    Glavac, D.
    Gasparini, P.
    Kanavakis, E.
    Obrien, S. J.
    et al.
    1. Year: 1998
  2. Journal: American Journal of Human Genetics
    1. 62
    2. 6
    3. Pages: 1507-1515
  4. Type of Article: Article
  1. Abstract:

    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. [References: 64]

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