New transporter associated with antigen processing (TAP-2) polymorphisms in the Shona people of Zimbabwe.
Most studies, to date, on transporter associated with antigen processing (TAP2) polymorphism have been conducted in Caucasians or Asians from industrialized countries. Because of the essential role of this molecule in antigen processing, the implication that polymorphism could be a major factor in human disease and the possible genetic variation at this locus among ethnically diverse populations, we undertook a study to analyze the full extent of TAP2 polymorphism in an indigenous Zimbabwean population (Shona ethnic group). Using single-stranded conformation polymorphism and DNA direct sequencing procedures, we detected the presence of 17 nucleotide sequence variations in the entire coding region of TAP2. Of these variants, 11 are nonconservative substitutions with respect to amino acid composition and are located in a region of the protein that could modulate its function. Six new polymorphic sites were identified in exon 1 (codons 15 Val-->Ala, 53 Leu-->Val), exon 3 (codon 220 Arg-->Arg), exon 4 (codons 257 Thr-->Ile, 313 Arg-->His), and exon10 (codon 609 Ala-->Val). Significant differences were seen in the distribution of the known 374Thr, 565Thr and 651Cys variants between African and non-African populations. These differences may reflect evolutionary pressures generated by environmental factors, such as prevalent pathogens in these geographically distinct regions. Further studies are needed to elucidate the net impact of TAP2 polymorphism on the protein's function and it's role in disease pathogenesis.
Lajoie
Julie
J
Laboratoire d'Immunogénétique, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada.
Zijenah
Lynn S
LS
Faucher
Marie-Claude
MC
Ward
Brian J
BJ
Roger
Michel
M
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D005006:Ethnicity; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D015030:Zimbabwe
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D005819:Genetic Markers; C071692:TAP2 protein, human