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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, Δ ccr5 , was shown to provide to homozygotes with a strong resistance against infection by HIV. The frequency of the Δ 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 Δ ccr5  variant. A strong linkage disequilibrium was found between Δ ccr5  and specific alleles of the IRI3.1 and IRI3.2 microsatellites: &gt;95% of the Δ 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 Δ 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 Δ 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 Δ ccr5  allele.

The Δ ccr5 Mutation Conferring Protection Against HIV-1 in Caucasian Populations Has a Single and Recent Origin in Northeastern Europe