title: Mutations in C-C chemokine receptor type 5 (CCR5) in South African individuals.
abstract: BACKGROUND
  The importance of the C-C chemokine receptor type 5 (CCR5) in HIV infection and disease progression was recognized with the discovery of the Δ32 allele. Individuals homozygous for this mutation lack functional CCR5, and are almost completely resistant to HIV infection. Heterozygous individuals display decreased cell surface CCR5, which slows disease progression. Phenotypic expression of CCR5 is heterogeneous and its relation to genetic mutations in the CCR5 gene is not currently known for the South African population. This provided the rationale for investigating genetic variation in low CCR5 expressers in South Africa.
  
  
  METHODS
  Flow cytometry was used to measure the phenotypic distribution of CCR5 in 245 individuals by assessing both the percentage of CD4+CCR5+ T-cells and CCR5 density.
  
  
  RESULTS
  Genotypic data revealed 70 single nucleotide polymorphisms (SNPs), four insertions, and the Δ32 deletion within the 65 individuals selected for sequencing. The Δ32 mutation was detected only in the Caucasian group and included a single homozygous individual with an absence of CCR5 expression. A total of eight previously described open reading frame (ORF) mutations were found in this study, as well as 12 novel mutations with two in the ORF. Greater genetic diversity was present in the black South African group, with 39 mutations being exclusive to this group.
  
  
  CONCLUSIONS
  Using a unique approach to genotype in individuals with lower CCR5 expression we have identified novel SNPs which could affect HIV infection.
authors.affiliation: Department of Immunology, Faculty of Health Sciences, and Institute for Cellular and Molecular Medicine, University of Pretoria, PO Box 2034, Pretoria 0001, South Africa.
authors.forename: Fatima
authors.initials: F
authors.lastname: Barmania
authors.forename: Marnie
authors.initials: M
authors.lastname: Potgieter
authors.forename: Michael S
authors.initials: MS
authors.lastname: Pepper
mesh_terms: D024509:3' Flanking Region; D024506:5' Flanking Region; D000483:Alleles; D044383:Black People / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005091:Exons; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D007438:Introns; D009154:Mutation; D016366:Open Reading Frames; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism; D013019:South Africa; D044465:White People / Q000235:genetics*
chemical_list: D019713:Receptors, CCR5
keywords: CCR5; HIV; SNP; Δ32