Journal
TISSUE ANTIGENS
Volume 73, Issue 1, Pages 17-32Publisher
WILEY-BLACKWELL PUBLISHING, INC
DOI: 10.1111/j.1399-0039.2008.01151.x
Keywords
balancing selection; European American; Eastern European; HLA; linkage disequilibrium; population study
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Funding
- Office of Naval Research [N00014-04-1-0795]
- National Institutes of Health [GM35326]
- NATIONAL CANCER INSTITUTE [P30CA051008] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U01AI067068] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM035326] Funding Source: NIH RePORTER
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Sequence-based typing was used to identify human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 alleles from 558 consecutively recruited US volunteers with Eastern European ancestry for an unrelated hematopoietic stem cell registry. Four of 31 HLA-A alleles, 29 HLA-C alleles, 59 HLA-B alleles, and 42 HLA-DRB1 alleles identified (A*0325, B*440204, Cw*0332, and *0732N) are novel. The HLA-A*02010101g allele was observed at a frequency of 0.28. Two-, three-, and four-locus haplotypes were estimated using the expectation-maximization algorithm. The highest frequency extended haplotypes (A*010101g-Cw*070101g-B*0801g-DRB1*0301 and A*03010101g-Cw*0702-B*0702-DRB1*1501) were observed at frequencies of 0.04 and 0.03, respectively. Linkage disequilibrium values (D(ij)(')) of the constituent two-locus haplotypes were highly significant for both extended haplotypes (P values were less than 8 x 10(-10)) but were consistently higher for the more frequent haplotype. Balancing selection was inferred to be acting on all the four loci, with the strongest evidence of balancing selection observed for the HLA-C locus. Comparisons of the A-C-B haplotypes and DRB1 frequencies in this population with those for African, European, and western Asian populations showed high degrees of identity with Czech, Polish, and Slovenian populations and significant differences from the general European American population.
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