title: Novel alleles of the chemokine-receptor gene CCR5.
abstract: 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-delta 32), 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-delta 32) is consistent with an adaptive accumulation of function-altering alleles for this gene, perhaps as a consequence of historic selective pressures.
authors.affiliation: Intramural Research Support Program, Scientific Applications International Corporation-Frederick, MD 21702, USA. carringt@ncifcrf.gov
authors.forename: M
authors.initials: M
authors.lastname: Carrington
authors.forename: T
authors.initials: T
authors.lastname: Kissner
authors.forename: B
authors.initials: B
authors.lastname: Gerrard
authors.forename: S
authors.initials: S
authors.lastname: Ivanov
authors.forename: S J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: M
authors.initials: M
authors.lastname: Dean
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D019143:Evolution, Molecular; D005787:Gene Frequency; D015658:HIV Infections / Q000235:genetics / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D044469:Racial Groups / Q000235:genetics; D019713:Receptors, CCR5 / Q000737:chemistry / Q000235:genetics*; D012641:Selection, Genetic; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D019713:Receptors, CCR5