Human Molecular Genetics, Vol 7, 399-406, Copyright © 1998 by Oxford University Press
F Libert, P Cochaux, G Beckman, M Samson, M Aksenova, A Cao, A Czeizel, M Claustres, C de la Rua, M Ferrari, C Ferrec, G Glover, B Grinde, S Guran, V Kucinskas, J Lavinha, B Mercier, G Ogur, L Peltonen, C Rosatelli, M Schwartz, V Spitsyn, L Timar, L Beckman and G Vassart
The chemokine receptor CCR5 is encoded by the CMKBR5 gene located on the
p21.3 region of human chromosome 3, and constitutes the major co- receptor
for the macrophage-tropic strains of HIV-1. A mutant allele of the CCR5
gene, Delta ccr5 , was shown to provide to homozygotes with a strong
resistance against infection by HIV. The frequency of the Delta ccr5 allele
was investigated in 18 European populations. A North to South gradient was
found, with the highest allele frequencies in Finnish and Mordvinian
populations (16%), and the lowest in Sardinia (4%). Highly polymorphic
microsatellites (IRI3.1, D3S4579 and IRI3.2, D3S4580 ) located respectively
11 kb upstream and 68 kb downstream of the CCR5 gene deletion were used to
determine the haplotype of the chromosomes carrying the Delta ccr5 variant.
A strong linkage disequilibrium was found between Delta ccr5 and specific
alleles of the IRI3.1 and IRI3.2 microsatellites: >95% of the Delta ccr5
chromosomes carried the IRI3.1-0 allele, while 88% carried the IRI3.2-0
allele. These alleles were found respectively in only 2 or 1.5% of the
chromosomes carrying a wild-type CCR5 gene. From these data, it was
inferred that most, if not all Delta ccr5 alleles originate from a single
mutation event, and that this mutation event probably took place a few
thousand years ago in Northeastern Europe. The high frequency of the Delta
ccr5 allele in Caucasian populations cannot be explained easily by random
genetic drift, suggesting that a selection advantage is or has been
associated with homo- or heterozygous carriers of the Delta ccr5 allele.
ARTICLES
The deltaccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe
IRIBHN and Service de Genetique Medicale, Universite Libre de Bruxelles, Campus Erasme, B-1070 Brussels, Belgium.
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