P098 HLA haplotype diversity in Cape Town, South Africa

Aim Africans represent the most genetically diverse population in the world, but have not been as well studied with respect to their HLA types compared to the inhabitants of western countries. Thus it was of interest to apply our high-throughput HLA sequencing technology to a cohort of 403 healthy adolescents from Cape Town, South Africa, as part of a study of T-cell responses to Mycobacterium tuberculosis in collaboration with Stanford University. Methods Cryopreserved PBMC samples from 403 adolescents were collected and shipped to Stanford University from Cape Town. High resolution HLA typing was performed using MIA FORA NGS kit and analysis software. The whole gene coverage included HLA-A, -B, -C, -DPA1, -DQA1, and -DQB1; all exons and introns for -DRB1 and -DRB3/4/5 except partial coverage for exon 6 and intron 1; and all exons and introns between exons 2 and 4 for HLA-DPB1. NGS sequencing libraries were prepared using a semi-automated protocol and sequenced in high-throughput format on the Illumina NextSeq platform. HLA allele candidates were computed and final HLA typing was confirmed using MIA FORA NGS analysis software. Results HLA typing revealed a unique population, including unusual haplotypes, and novel alleles not previously reported in the IMGT/HLA database. The frequency of HLA-A, -B, -DRB1 haplotypes in Cape Town were compared to those represented in the US National Marrow Donor Program. As might be expected, 14 of the top 16 haplotypes in the Cape Town cohort were observed in the African American cohort. However there were important exceptions, including a frequent haplotype found in African American but not observed in Cape Town and two frequent Cape Town haplotypes not observed in African American samples. Conclusion High resolution HLA typing is a powerful method to characterize HLA allele and haplotype diversity in population studies. C. Wang: Consultant; Company/Organization; Immucor. M. Li: Employee; Company/Organization; Immucor. M. Fukushima: Employee; Company/Organization; Immucor. R. Kuehn: Employee; Company/Organization; Immucor. S. Krishnakumar: Employee; Company/Organization; Immucor. M. Mindrinos: Employee; Company/Organization; Immucor.