TAP1 polymorphisms in several human ethnic groups: Characteristics, evolution, and genotyping strategies

Genetic variations in the locus encoding the transporter associated with an tigen processing, subunit 1 (TAP1), were systematically studied using sampl es from Caucasians, Africans, Brazilians, and compared with data from:chimp anzees. PCR-amplified genomic se quences corresponding to the 11 exons were analyzed by single-strand conformation polymorphism (SSCP) and sequencing. Six nonsynonymous and 2 synonymous single nucleotide polymorphisms (SNPs) were found to be common in-one ethnic group or another, and they involved c odons 254 (Gly-GGC/Gly-GGT) in exon 3, 333 (Ile-ATC/Val-GTC) in exon 4, 370 (Ala-GCT/Val-GTT) in exon 5,- 458 (Val-GTG/Leu-TTG) in exon 6,518 (Val-GTC /Ile-ATC) in exon 7, 637 (Asp-GAC/Gly-GGC), 648 (Arg-CGA/Gln-CAA) and 661 ( Pro-CCG/Pro-CCA) in exon 10. At each SNP site the sequence listed first was predominant.:in all ethnic groups. Several SNPs segregated on the same chr omosome regardless of populations and species. Together, the SNPs produced 5 major human TAP1 alleles, 4 of which matched the officially recognized al leles *0101, *02011, *0301, and *0401; the 5th allele differed from each of those by at least 4 SNPs. Overall, TAP1*0101 was the predominant allele in all ethnic groups, with frequencies ranging from 0.667 in Zambians to 0.80 8 in US Caucasians. The TAP1*0401 frequency showed the greatest difference between Africans (0.221-0.254) and Caucasians (0.033), with Brazilians (0.0 58) fitting in the middle. Consistent with earlier work based on Caucasians and gorillas, *0101 appeared to be the newest human TAP1 allele, suggestin g a dramatic spread of *0101 into all human populations examined. Character ization of TAP1 polymorphisms allowed the design of a PCR-based genotyping scheme that targeted 7 SNP sites and required 2 separate genotyping techniq ues. Human Immunology 62, 256-268 (2001). (C) American Society for Histocom patibility and Immunogenetics, 2001. Published by Elsevier Science Inc.