Abstract
Introduction Recombinant meiotic event(s) can occur within human families. Chromosomal crossover is the exchange of genetic material between homologous chromosomes that results in recombinant chromosomes. Even though crossover at HLA region is a rare event, the resulting haplotype would introduce linkage disequilibrium at HLA loci which could decrease the chance for hematopoietic stem cell transplant (HSCT) patient to find a suitable matched donor. The aim of the study was to investigate the frequency of recombination and the crossover location within the HLA class I and II regions. Methods HSCT patients and related family members as potential donors with clearly defined haplotypes within family were included in the study. All the patients and majority of family members were HLA typed at class I-A, B, C and class II-DR, DQ, DP using molecular methods (SSO and/or SBT) with some related donors serologically typed. Crossover haplotypes in patients ( N = 5219) or related donors ( N = 15,224) were analyzed and the crossover location between HLA loci was identified for each case. Results Crossover between HLA loci was identified in 202 individuals. The frequency of recombination was found to be 0.73% (38/5219) in HSCT patients and 1.08% (164/15224) in related potential donors. The overall crossover rate was 0.99% in the study population. There were two potential donors with recombination on both haplotypes. Five individuals in four families inherited the recombinant haplotype from a parent. Seven families had two members with recombination haplotype. The rate of recombination was 50.5% between HLA-B x DR, 36.63% between HLA-A x C, 9.41% between HLA-DQ x DP, and 3.47% between HLA-C x B loci. Conclusion Crossover events were observed between nearly all the neighboring HLA loci (A-C, C-B, B-DR, DQ-DP) except for between HLA-DR and DQ. We didn’t observe any recombination event between these loci in the study. The recombination rate is overall about 1% in the study population. The crossover hot spots appear to be between HLA-B and DR, HLA-A and HLA-C. It’s interesting to note that crossover event was lower in patients with different leukemia malignancies than in healthy family members. The finding suggests that leukemia patients were not disadvantaged from recombination in HLA regions.
Published Version
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