Occurrence of paternal HLA-A/B and maternal HLA-B/DRB1 recombinants in one family

Using high resolution HLA typing, crossing over (CO) between HLA-A/B, B/DRB1, or DRB1/DPB1 loci can be identified among siblings from families with both parents or with large sibship. Locating the breaking points along the C I and II genomic regions can be estimated via SNP genotyping of the MHC region. We report the rare occurrence of two recombinant children in a single family and the application of SNP genotyping to pinpoint the CO in each. Blood specimens of 6 siblings from a HSCT family (F) were HLA-A/B/C/DRB1/DQB1/DPB1 typed by LABType (OLI), SBT (SeCore, Life Tech) and NGS (NXType on the Ion Torrent platform, OLI) methods. SNP genotyping for the six siblings was performed using the OMNIExpress-24 v1.1 to query over 713 K markers throughout the genome. Within the MHC there were 3754 SNPs covering the region between HLA-A position 29913067 and DQB1 position 32628428 a distance of 2.7 Mb. 100% concordant results were obtained from all three methods (Table 1). The 4 parental haplotypes segregated appropriately among siblings #3–6. This fact helps to determine sibling #1 and sibling #2 are paternal HLA-A & B and maternal HLA-B & DRB1 recombinants, respectively. The derivation of SNP haplotypes for the 6 siblings revealed the approximate breaking points where CO most likely have occurred for siblings 1 and 2. The actual breaking points were identified to have occurred within 700 bp in two respective regions, one centromerically to HLA-A for sibling 1 and the other centromerically to HLA-B for sibling 2. Precise break points will be discussed when analysis has been completed. Conclusion Two HLA recombinant children in family F have been identified. The probability of having the first two older children born as recombinants is (0.01) 2 (0.99) 4 when the birth order is specified. If birth order is not specified, the probability that two out of six children would be recombinants becomes N(N - 1)/2 x  (0.01) 2 (0.99) 4 . N denotes number of children in any family. In our case, the probability is 15(0.01) 2 (0.99) 4 . Download full-size image