Novel Alleles of the Chemokine-Receptor Gene CCR5
American Journal of Human Genetics
The CCR5 gene encodes a cell-surface chemokine-receptor molecule that serves as a coreceptor for macrophage-tropic strains of HIV-1. Mutations in this gene may alter expression or function of the protein product, thereby altering chemokine binding/signaling or HIV-1 infection of cells that normally express CCR5 protein. Indeed, homozygotes for a 32-bp deletion allele of CCR5 (CCR5-Δ32), which causes a frameshift at amino acid 185, are relatively resistant to HIV-1 infection. Here we report the identification of 16 additional mutations in the coding region of the CCR5 gene, all but 3 of which are codon altering or "nonsynonymous." Most mutations were rare (found only once or twice in the sample); five were detected exclusively among African Americans, whereas eight were observed only in Caucasians. The mutations included 11 codon-altering nonsynonymous variants, one trinucleotide deletion, one chain-termination mutant, and three synonymous mutations. The high predominance of codon-altering alleles among CCR5 mutants (14/17 [81%], including CCR5-Δ32) is consistent with an adaptive accumulation of function-altering alleles for this gene, perhaps as a consequence of historic selective pressures.
Carrington, Mary; Teri Kissner; Bernard Gerrard; Sergey Ivanov; Stephen J. O'Brien; and Michael Dean. 1997. "Novel Alleles of the Chemokine-Receptor Gene CCR5." American Journal of Human Genetics 61, (6): 1261-1267. http://nsuworks.nova.edu/cnso_bio_facarticles/675