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Allelic resolution NGS HLA typing of Class I and Class II loci and haplotypes in Cape Town,South Africa
Authors:Yvonne R Thorstenson  Lisa E Creary  Huang Huang  Virginie Rozot  Tracy T Nguyen  Farbod Babrzadeh  Sandeep Kancharla  Marilyn Fukushima  Raquel Kuehn  Chunlin Wang  Ming Li  Sujatha Krishnakumar  Michael Mindrinos  Marcelo A Fernandez Viña  Thomas J Scriba  Mark M Davis
Institution:1. Immucor, Sirona Genomics, Mountain View, CA, USA;2. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA;3. Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA;4. South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa;5. Stanford University and Howard Hughes Medical Institute, Stanford, CA
Abstract:The development of next-generation sequencing (NGS) methods for HLA genotyping has already had an impact on the scope and precision of HLA research. In this study, allelic resolution HLA typing was obtained for 402 individuals from Cape Town, South Africa. The data were produced by high-throughput NGS sequencing as part of a study of T-cell responses to Mycobacterium tuberculosis in collaboration with the University of Cape Town and Stanford University. All samples were genotyped for 11 HLA loci, namely HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1, -DRB3, -DRB4, and -DRB5. NGS HLA typing of samples from Cape Town inhabitants revealed a unique cohort, including unusual haplotypes, and 22 novel alleles not previously reported in the IPD-IMGT/HLA Database. Eight novel alleles were in Class I loci and 14 were in Class II. There were 62 different alleles of HLA-A, 72 of HLA-B, and 47 of HLA-C. Alleles A123:17, A143:01, A129:11, A168:27:01, A101:23, B114:01:01, B115:10:01, B139:10:01, B145:07, B182:02:01 and C108:04:01 were notably more frequent in Cape Town compared to other populations reported in the literature. Class II loci had 21 different alleles of DPA1, 46 of DPB1, 27 of DQA1, 26 of DQB1, 41 of DRB1, 5 of DRB3, 4 of DRB4 and 6 of DRB5. The Cape Town cohort exhibited high degrees of HLA diversity and relatively high heterozygosity at most loci. Genetic distances between Cape Town and five other sub-Saharan African populations were also calculated and compared to European Americans.
Keywords:HLA  NGS  Allele frequency  Haplotype frequency  Population  Linkage disequilibrium  Genetic distance
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