P090 NGS characterization of HLA haplotypes in multi-generation families of Kuwaiti descent

Abstract

Objective Family studies remain the gold standard for studying HLA haplotype segregation. This information is particularly critical when studying haplotype associations among populations where not enough members of the population have been genotyped, rendering bioinformatics algorithms less reliable. In this study we characterize HLA haplotypes in 2 multi-generation families of Kuwaiti descent. Methods Two multi-generation families of Kuwaiti descent were tested for HLA genotypes by high resolution typing using NGS technology. We used a MiSeq-based platform (Illumina, Inc; San Diego, CA), Holotype HLA reagents, and HLA Twin analysis software (Omixon, Budapest, Hungary). All individuals were high-resolution typed at loci HLA-A, B, C, DRB1 & DQB1. The identified haplotypes were compared to haplotype frequencies and ranking among the 4 major US populations (Caucasians, African Americans, Hispanics and Asian Pacific Islanders) using the NMDP Haplostat software. Results The analysis of 14 members of a 4-generation family identified 8 haplotypes and of 6 members of a 3-generation family identified 5 haplotypes. The pedigree tree of both families is shown in the figure and the frequency and rank of each haplotype is shown in the table. No haplotypes were shared between the 2 families. Conclusion Many of the identified HLA haplotypes were not listed in Haplostat and none of them were among the most common 200 HLA haplotypes in any of the 4 major populations. Further characterization of Kuwaiti haplotypes through family studies is in progress however, these preliminary results suggest that the Kuwaiti population may have unique HLA haplotypes. Download : Download high-res image (123KB) Download : Download full-size image Download : Download high-res image (1MB) Download : Download full-size image