OR24 HLA allele and haplotype frequencies characterized using next-generation sequencing methods in unrelated world-wide populations: Summary from the 17th international HLA and immunogenetics workshop

Abstract

Aim The primary goal of the 17th IHIWS was to advance the field of Histocompatibility and Immunogenetics research as well as clinical practices through the application of NGS technologies. Analyses of very-high resolution NGS HLA profiles sampled from different populations will be useful for reconstructing human history and may improve match predictions for unrelated donor selection algorithms. Methods In the unrelated population HLA diversity project, 15 laboratories from 10 different countries contributed HLA genotype data generated by various NGS methods. HLA population data included well-defined large datasets from the USA and East Asia and smaller samples from Europe, Australia, and Western Asia. Participants uploaded data in HML/XML format into the 17th IHIW database, data was systematically reviewed, and statistical analysis was performed using the genetic software PyPop v.0.7.0 to estimate; (i) allele frequencies, (ii) heterozygosity, (iii) conformity to HWE, (iv) selective neutrality, (v) 2-locus haplotypes and (vi) LD. The software BIGDAWG was used to estimate extended haplotype frequencies by an EM algorithm. Inter-population variance was determined using Nei’s genetic distances which were then used to construct phylogenetic dendrograms. Results Amongst each population, test of selective neutrality often revealed an excess of heterozygous compared with neutral expectations. A comparison of the HLA genetic diversity estimated at the 4 and 2 fields revealed that diversity at the majority of loci, particularly for populations of European descent, was lower at the 2-field resolution. African descent populations had a lower number of distinct HLA alleles at class I and II loci compared to other groups but exhibited higher levels of heterozygosity. Two-locus haplotype analyses revealed distinct HLA associations at the 4 − field. Analyses of extended haplotype frequencies, estimated both in the presence and absence of DP loci, showed unique haplotypes that were common to each ethnic group although some haplotypes were shared amongst different ethnic groups. Conclusions This workshop project provided a vast amount of new information about HLA genetic diversity at the intronic level and will be a useful resource for anthropological studies, disease association studies and transplantation.