HLA class I (A, B) and II (DR, DQ) Gene and Haplotype Frequencies in Blood Donors from Wales

Abstract

Accurate estimates of HLA-A, B, DR and DQ phenotype, gene and haplotype frequencies (HF) in the normal population are of importance in, for example, disease susceptibility studies, platelet transfusion support and transplantation. HLA population genetics studies have been performed on numerous groups, however, no major studies have been carried out on the population of Wales. As part of the validation process for our routine HLA-A and B typing by PCR using sequence-specific primers (PCR-SSP) we examined 1,798 normal, unrelated Caucasoid blood donors living in Wales and recruited onto the Welsh Bone Marrow Donor Registry (WBMDR). Typing was performed by serology (HLA-A, B) and PCR-SSP at low resolution (HLA-A, B, DR, DQ) resulting in a particularly rigorous level of HLA specificity assignment. Four discrepancies were found between the HLA-A and B serological and PCR-SSP specificity assignments: (1) two instances of HLA-A2 by serology were undetected by PCR-SSP and were a new HLA-A2 allele – A*0224; (2) one example of HLA-B*15 by PCR-SSP failed to react by serology, and remained undetectable by serology in subsequent samples, and (3) one example of HLA-B45 by serology was identified as HLA-B*5002 by PCR-SSP. Hardy-Weinberg and homozygosity analysis showed that the goodness-of-fit was excellent (p > 0.05), for both phenotype distribution and the number of homozygotes identified, for all four loci. The phenotype and gene frequencies for the 18 HLA-A, 34 -B, 15 -DR and 8 -DQ specificities identified and two- and three-locus HF, linkage disequilibrium and related values for HLA-A/B, B/DR, DR/DQ and HLA-A/B/DR and B/DR/DQ were essentially typical of a northern European population. HLA-A2, B44, DR4 and DQ2 were the highest frequency phenotypes and HLA-A2403, A34, A74, B42, B75, B2708, B48, B67 and B703 occurred once only. There were no examples of: A36, A43, A69, A80, B46, B54, B59, B73, B76, B77, B7801, B8101 or DR18 specificities. DR17, DQ2 and A1, B8, DR17 were the highest frequency two- and three-locus haplotypes identified. Diverse HLA-A, B, DR phenotypes were identified in 87.0% (1,564) of subjects. When HLA-DQ was also considered, different four locus phenotypes were identified in 89.1% (1,602) of subjects. This frequency information will be beneficial as a high-quality reference control for disease susceptibility studies and in calculating the chances of identifying a bone marrow donor in a patient’s extended family. This process was successful for the validation of our HLA-A and -B PCR-SSP typing procedure and the findings suggest an accurate level of specificity assignment of WBMDR panel donors who had previously been typed by serology alone.

HLA-A alleles and infectious mononucleosis suggest a critical role for cytotoxic T-cell response in EBV-related Hodgkin lymphoma

“…The main focus of this analysis was a comparison of EBV-related and EBV-unrelated HL cases. To confirm that the EBV-unrelated HL cases were an appropriate control group, we first compared the prevalence of HLA-A*01 and HLA-A*02 in this group of cases with the corresponding prevalence in the background populations of the countries studied in a series of tests (25)(26)(27). These showed similar distributions of the HLA alleles in the patients and the background populations, as tests for homogeneity of all genotypes combined (P = 0.22), allele frequencies (HLA-A*01, P = 0.32; HLA-A*02, P = 0.84) and HLA-A*02 genotypes (P = 0.88) were all unremarkable.…”

“…Estimates of population genotype frequencies were obtained from previous reports (25)(26)(27). We used χ 2 tests to assess homogeneity in the distribution of HLA-A genotypes.…”

Cord blood banks collect units with different HLA alleles and haplotypes to volunteer donor banks: a comparative report from Swiss Blood stem cells

“…Population-based HLA allele and haplotype frequency analyses are useful tools to assess the diversity of a donor population and to optimize search strategies. [10][11][12][13][14] The national organization Swiss Blood stem cells (SBsc) registers UCB from two Swiss cord blood banks in two hospitals with distinct recruitment areas and different sociocultural background and also VUD recruited by the country-wide blood banks. Presently there is little information 15,16 about whether cord blood banks recruit donors with HLA-alleles and haplotypes different from adult donor registries within the same geographical area.…”

HLA-A, -B and -DR antigen frequencies of the London Cord Blood Bank units differ from those found in established bone marrow donor registries

“…However HLA-A26 and B57 were found at a significantly higher frequency in the cord blood panel than in the adult BBMR panel and these differences may reflect population differences between these two groups. The three most common HLA-A-B haplotypes found in the LCBB cord blood units of European Caucasoid ethnicity (A1-B8, A2-B44 and A3-B7) are also the three most common haplotypes found in the local BBMR volunteers, in Welsh bone marrow volunteers 15 and in Dutch bone marrow volunteers. 16 However the HLA-A-B haplotypes A26-B8, A33-B44 and A33-B58 which were found in the non-European Caucasoid cord blood units were not found in the BBMR volunteers, in Welsh bone marrow volunteers 15 or in Dutch bone marrow volunteers.…”

“…The three most common HLA-A-B haplotypes found in the LCBB cord blood units of European Caucasoid ethnicity (A1-B8, A2-B44 and A3-B7) are also the three most common haplotypes found in the local BBMR volunteers, in Welsh bone marrow volunteers 15 and in Dutch bone marrow volunteers. 16 However the HLA-A-B haplotypes A26-B8, A33-B44 and A33-B58 which were found in the non-European Caucasoid cord blood units were not found in the BBMR volunteers, in Welsh bone marrow volunteers 15 or in Dutch bone marrow volunteers. 16 The possibility of matching for haplotypes which may be restricted to certain ethnic groups also increases the likelihood of matches at the allele level.…”