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Hum Immunol. 2018 Dec;79(12):839-847. doi: 10.1016/j.humimm.2018.09.004. Epub 2018 Sep 18.

Allelic resolution NGS HLA typing of Class I and Class II loci and haplotypes in Cape Town, South Africa.

Author information

1
Immucor, Sirona Genomics, Mountain View, CA, USA. Electronic address: yrthor@gmail.com.
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
Immucor, Sirona Genomics, Mountain View, CA, USA.
6
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 A∗23:17, A∗43:01, A∗29:11, A∗68:27:01, A∗01:23, B∗14:01:01, B∗15:10:01, B∗39:10:01, B∗45:07, B∗82:02:01 and C∗08:04:01 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:

Allele frequency; Genetic distance; HLA; Haplotype frequency; Linkage disequilibrium; NGS; Population

PMID:
30240896
DOI:
10.1016/j.humimm.2018.09.004
[Indexed for MEDLINE]

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