P072NGS characterization of extended HLA haplotypes in Jamaican families from the caribbean bone marrow registry: A study of the 17th international HLA & immunogenetics workshop

Aim Family studies are the gold standard for studying HLA haplotype segregation. This information is critical when studying haplotype associations among populations where few members of the population have been typed, rendering bioinformatics algorithms less reliable. Here, we characterize HLA haplotypes in 5 Jamaican families identified through the Caribbean Bone Marrow Registry. Methods Twenty Jamaican individuals of 5 families were tested by NGS HLA genotypes at loci A, B, C, DRB345, DRB1, DQA1, DQB1, DPA1 & DPB1. We initially attempted full gene sequencing but amplification failed repeatedly due to suboptimal DNA quality from buccal swabs. Typing was performed using Scisco Genomics kit on the MiSeq. Identified haplotypes were compared to haplotype frequency ranking among the 5 major US populations (Caucasians (CAU), African Americans (AFA), Hispanics (HIS), Asian Pacific Islanders (API), and Native Americans (NAM)) using the NMDP Haplostats. Haplostats provides data on 6-locus 2-field resolution, which could give a higher estimate than the 9-locus 3-field haplotypes described here. Results Typing was successful in all individuals and all loci except for failed DPB1 typing on 2 subjects due to low DNA quantity. Analysis of 20 members identified 17 unique haplotypes. The most common haplotype among CAU, HIS, and NAM and 2nd most common in AFA (Haplotype A in Table 1) was observed in 3 families. Another haplotype in 2 families (B) was uncommon among CAU, HIS & AFA (ranked 20466, 23219 & 8463, respectively) and not reported in other populations. Overall observed haplotypes were more common in AFA than other population and 2 haplotypes (C & D) were seen only in AFA. One haplotype (E) was seen only in API (ranked 5660). One haplotype (F) was not reported for any population. Conclusions Although the number of tested families is small, this data suggest that the Jamaican population is unique and diverse, and supports the proposition of establishing a local/regional BMT registry to maximize the chances of identifying matched donors.