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

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

doi:10.1016/j.humimm.2018.09.004

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

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

Authors

Yvonne R Thorstenson¹, Lisa E Creary², Huang Huang³, Virginie Rozot⁴, Tracy T Nguyen⁵, Farbod Babrzadeh⁵, Sandeep Kancharla⁵, Marilyn Fukushima⁵, Raquel Kuehn⁵, Chunlin Wang⁵, Ming Li⁵, Sujatha Krishnakumar⁵, Michael Mindrinos⁵, Marcelo A Fernandez Viña², Thomas J Scriba⁴, Mark M Davis⁶

Affiliations

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.

MeSH terms

Adolescent
Alleles
Female
Gene Frequency
Genotype
Genotyping Techniques / methods*
HLA Antigens / genetics*
Haplotypes
High-Throughput Nucleotide Sequencing / methods*
Histocompatibility Antigens Class I / genetics*
Histocompatibility Antigens Class II / genetics*
Humans
Linkage Disequilibrium
Male
South Africa

Substances

HLA Antigens
Histocompatibility Antigens Class I
Histocompatibility Antigens Class II

Grants and funding

U19 AI057229/AI/NIAID NIH HHS/United States