title: Genotyping TAP2 variants in North American Caucasians, Brazilians, and Africans.
abstract: The protein forms of transporter associated with antigen processing, subunit 2 (TAP2), differ either by amino acid substitutions (Thr374Ala, Ile379Val, Ile467Val, Thr565Ala, Val577Met, Cys651Arg, and Ala665Thr) or by a truncation (Gln687Stop) of 17 amino acid residues at the C-terminus. Nonsynonymous single nucleotide polymorphisms (N-SNPs) causing these amino acid variations except 577Val were detected in genomic DNA samples from North American Caucasians (n = 76), Brazilians (n = 148), Rwandans (n = 285), and Zambians (n = 117). Exclusive (100%) and nearly exclusive (>95%) linkage disequilibrium was seen with a number of N-SNPs. The average heterozygosity at any given dimorphic site ranged from 7.3% to 44.6%, and at least four N-SNPs showed clear population specificity. N-SNP combinations alone led to the identification of 16 relatively common alleles, which appeared to form at least three lineages. Further analyses of 101 cDNA samples from Brazilians detected nine expressed TAP2 alleles, four of which matched the official assignments. Genetic complexity at the TAP2 locus was further enhanced by two out of five synonymous SNPs (S-SNPs), especially the GGT386GGG (Gly) that had similar heterozygosity rates in Caucasians (28.9%), Rwandans (33.3%), and Zambians (33.3%). Overall, distribution of both synonymous and nonsynonymous SNPs in the various ethnic groups examined here conformed well to the Hardy-Weinberg equilibrium, and between 57.9% and 77.0% of subjects in each ethnic group were heterozygous with two TAP2 alleles predicted to differ by at least one amino acid residue. Such complexity of TAP2 polymorphisms, in the form of SNPs as well as alleles, is likely to complicate the analyses of disease associations and haplotype structures in the HLA class II region.
authors: Program in Epidemiology of Infection and Immunity, School of Public Health, Department of Medicine, University of Alabama at Birmingham, 35294, USA. jtang@uab.edu
authors: J
authors: J
authors: Tang
authors: D O
authors: DO
authors: Freedman
authors: S
authors: S
authors: Allen
authors: E
authors: E
authors: Karita
authors: R
authors: R
authors: Musonda
authors: C
authors: C
authors: Braga
authors: B D
authors: BD
authors: Jamieson
authors: L
authors: L
authors: Louie
authors: R A
authors: RA
authors: Kaslow
mesh_terms: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D001938:Brazil; D004247:DNA; D019143:Evolution, Molecular; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D009656:North America; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
chemical_list: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; C071692:TAP2 protein, human; D004247:DNA