The deltaccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe

The chemokine receptor CCR5 is encoded by the CMKBR5 gene located on thep21.3 region of human chromosome 3, and constitutes the major co- receptorfor the macrophage-tropic strains of HIV-1. A mutant allele of the CCR5gene, Delta ccr5 , was shown to provide to homozygotes with a strongresistance against infection by HIV. The frequency of the Delta ccr5 allelewas investigated in 18 European populations. A North to South gradient wasfound, with the highest allele frequencies in Finnish and Mordvinianpopulations (16%), and the lowest in Sardinia (4%). Highly polymorphicmicrosatellites (IRI3.1, D3S4579 and IRI3.2, D3S4580 ) located respectively11 kb upstream and 68 kb downstream of the CCR5 gene deletion were used todetermine the haplotype of the chromosomes carrying the Delta ccr5 variant.A strong linkage disequilibrium was found between Delta ccr5 and specificalleles of the IRI3.1 and IRI3.2 microsatellites: >95% of the Delta ccr5chromosomes carried the IRI3.1-0 allele, while 88% carried the IRI3.2-0allele. These alleles were found respectively in only 2 or 1.5% of thechromosomes carrying a wild-type CCR5 gene. From these data, it wasinferred that most, if not all Delta ccr5 alleles originate from a singlemutation event, and that this mutation event probably took place a fewthousand years ago in Northeastern Europe. The high frequency of the Deltaccr5 allele in Caucasian populations cannot be explained easily by randomgenetic drift, suggesting that a selection advantage is or has beenassociated with homo- or heterozygous carriers of the Delta ccr5 allele.