TAP1 Polymorphisms: Allelic Relationships and Frequencies in African and Caucasian Populations.
J Tang, S Allen, E Karita, R Musonda, PN Fultz, RA Kaslow, University of Alabama at Birmingham, Birmingham, AL; National AIDS Control Program, Rwanda; and Tropical Disease Research Center, Zambia.

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Genetic variations in the locus for the transporter associated with antigen processing, subunit 1 (TAP1) were studied in 2 Caucasian (N = 540), 2 African (N = 596) populations, as well as small numbers of chimpanzees and sooty mangabeys. PCR-amplified genomic sequences corresponding to the 11 exons were analyzed by single-strand conformation polymorphism (SSCP) and sequencing. All variants previously recognized in more than one individual or cell line were detected. Consistent with earlier work based on Caucasians and gorillas, the TAP1*0201 appeared to be the ancestral allele, suggesting a dramatic spread of the predominant human allele *0101 into all of the human populations examined. The 4 officially assigned human TAP1 alleles are largely defined by 3 exclusively linked amino acid substitutions at codon 333 (Ile/Val) in exon 4, and codons 637 (Asp/Gay) and 648 (Arg/Gln) in exon 10. Another amino acid substitution at codon position 370 (Ala/Val) in exon 5, in conjunction with the nonsynonymous nucleotide changes at codons 254 and 661, further divides the *0201 lineage into at least 3 alleles. Together, these human TAP1 alleles were found to be common, with frequencies ranging from 0.02 to 0.88. Additional novel alleles were only seen occasionally. A PCR-based genotyping scheme incorporating these allelic features was devised to facilitate reliable assignment of all frequent TAP1 alleles.