Novel alleles of the chemokine-receptor gene CCR5

Am J Hum Genet. 1997 Dec;61(6):1261-7. doi: 10.1086/301645.

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.

MeSH terms

  • Alleles*
  • Amino Acid Sequence
  • Cohort Studies
  • Continental Population Groups / genetics
  • DNA Mutational Analysis
  • Evolution, Molecular
  • Gene Frequency
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV-1
  • Humans
  • Immunity, Innate / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Receptors, CCR5 / chemistry
  • Receptors, CCR5 / genetics*
  • Selection, Genetic
  • Sequence Alignment
  • Sequence Homology, Amino Acid

Substances

  • Receptors, CCR5