Alleles at four HLA class II loci determined by oligonucleotide hybridization and their associations in five ethnic groups

Abstract

The use of polymerase chain reaction (PCR) and oligonucleotide hybridization offers a new approach for the definition of HLA class II alleles. It has been possible to determine 43 alleles of DRB1, four of DRB3, two of DRB4, four of DRB5, eight of DQA1, and 14 of DQB1. These alleles are inherited together in members of families and form closely associated groups which are found repeatedly and in characteristic patterns in different populations. We have determined the HLA class II alleles and analyzed their association in 431 healthy unrelated subjects including 161 North American Caucasians, 53 Latin Americans, 61 Blacks, 88 Chinese, and 68 Israeli Jews. For-locus haplotypes (DRB1; DRB3/4/5; DQA1; DQB1) were derived from 79 B cell lines and the analysis of segregation in 34 nuclear families. The B-cell lines yielded 37 and the families showed the same, and 20 other, haplotypic combinations. In addition to these 57 haplotypes, associated alleles were assigned in the unrelated panels following certain rules. The resulting haplotypes were assigned to groups known to share associated alleles. The groups were: 1) DR1, DR2, and DRw10 (13 haplotypes); 2) DR3 and DRw6 (26 haplotypes); 3) DR5 and DRw8 (24 haplotypes); 4) DR4, DR7, and DR9 (24 haplotypes). Their distribution in populations with different ethnic backgrounds was analyzed. The expressed DRB4 allele and its null mutant were determined by PCR and oligonucleotide hybridization. The different DR7 haplotypes resulting from these determinations were analyzed in a panel of 130 North American Caucasoids. This comprehensive analysis of class II HLA haplotypes in human populations should be useful in understanding the role of these genes and in various applications including anthropology, disease susceptibility, and transplantation of allogeneic organs and tissues.

Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations

“…In major outbred populations living in the USA (European Americans, African Americans, Hispanic or Latino Americans, Native Americans and Asian Pacific Islanders), we observed more than 25 HLA-A, 40 HLA-B, 15 HLA-C, 25 DRB1, 17 DQB1 and 15 DPB1 alleles with gene frequencies higher than 0.05 [21][22][23][24]. The allele distributions are fairly evenly distributed in most HLA loci analysed (A, B, C, DRB1, DQA1 and DQB1) with the exception of DPB1, in which only four alleles account for the majority of the genes of this locus.…”

“…We also studied subjects selfidentified as Native Americans from the USA [21,23]. In all populations, the number of allelic lineages was significantly reduced when compared with other populations.…”

“…Alleles at DQA1 and DQB1 that associate tightly with alleles of the DRB1*08 group are shown. These haplotype fragments were classified according to their frequencies in different populations [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] in these populations were from this locus, and it has been postulated that HLA-B has diversified more rapidly in the South American tribes. Interestingly, in many tribes the novel alleles are present at the highest gene frequencies, suggesting that the novel alleles generated in America were positively selected in these populations probably because they provided selective advantages.…”

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

“…HLA-DR and HLA-DQ demonstrate strong linkage disequilibrium (53)(54)(55)(56)(57). Allele mismatches in HLA-DR are likely to represent an extra eplet load related to both HLA-DR and HLA-DQ and vice versa.…”

cPRA Increases With DQA, DPA, and DPB Unacceptable Antigens in the Canadian cPRA Calculator

“…Race frequencies are not utilized. Typings were verified against known haplotype associations 8, 9, 10, 11; however, no robust DPA and DPB haplotype associations are reported and typing at these loci was entered as provided by the source laboratory. The calculator further permits stratification of cPRA by ABO blood group and region within Canada (Figure S1), although these were not utilized in the present analysis.…”