Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans

Ananyo Choudhury; Michèle Ramsay; Scott Hazelhurst; Shaun Aron; Soraya Bardien; Gerrit Botha; Emile R Chimusa; Alan Christoffels; Junaid Gamieldien; Mahjoubeh J Sefid-Dashti; Fourie Joubert; Ayton Meintjes; Nicola Mulder; Raj Ramesar; Jasper Rees; Kathrine Scholtz; Dhriti Sengupta; Himla Soodyall; Philip Venter; Louise Warnich; Michael S Pepper

doi:10.1038/s41467-017-00663-9

Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans

Nat Commun. 2017 Dec 12;8(1):2062. doi: 10.1038/s41467-017-00663-9.

Authors

Ananyo Choudhury¹, Michèle Ramsay^{2

3}, Scott Hazelhurst^{1

4}, Shaun Aron¹, Soraya Bardien⁵, Gerrit Botha⁶, Emile R Chimusa⁷, Alan Christoffels⁸, Junaid Gamieldien⁸, Mahjoubeh J Sefid-Dashti⁸, Fourie Joubert⁹, Ayton Meintjes⁶, Nicola Mulder⁶, Raj Ramesar⁷, Jasper Rees¹⁰, Kathrine Scholtz¹¹, Dhriti Sengupta¹, Himla Soodyall^{12

13}, Philip Venter¹⁴, Louise Warnich¹⁵, Michael S Pepper¹⁶

Affiliations

¹ Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.
² Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa. Michele.ramsay@wits.ac.za.
³ Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2000, South Africa. Michele.ramsay@wits.ac.za.
⁴ School of Electrical and Information Engineering, University of the Witwatersrand, Johannesburg, 2050, South Africa.
⁵ Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa.
⁶ Computational Biology Division, Department of Integrative Biomedical Sciences, IDM, University of Cape Town, Cape Town, 7925, South Africa.
⁷ Division of Human Genetics, Department of Pathology, IDM, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa.
⁸ South African MRC Bioinformatics Unit, South African National Bioinformatics Institute, University of the Western Cape, Bellville, 7925, South Africa.
⁹ Department of Biochemistry and Genomics Research Institute, Centre for Bioinformatics and Computational Biology, University of Pretoria, Pretoria, 0083, South Africa.
¹⁰ Agricultural Research Council, Pretoria, 0184, South Africa.
¹¹ Department of Preclinical Sciences, School of Health Care Sciences, Faculty of Health Sciences, University of Limpopo, Mankweng, 0727, South Africa.
¹² Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2000, South Africa.
¹³ National Health Laboratory Service, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2000, South Africa.
¹⁴ Department of Medical Sciences, School of Health Sciences, Faculty of Health Sciences, University of Limpopo, Mankweng, 0727, South Africa.
¹⁵ Department of Genetics, Stellenbosch University, Stellenbosch, 7600, South Africa.
¹⁶ Institute for Cellular and Molecular Medicine, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, 0084, South Africa. michael.pepper@up.ac.za.

Abstract

The Southern African Human Genome Programme is a national initiative that aspires to unlock the unique genetic character of southern African populations for a better understanding of human genetic diversity. In this pilot study the Southern African Human Genome Programme characterizes the genomes of 24 individuals (8 Coloured and 16 black southeastern Bantu-speakers) using deep whole-genome sequencing. A total of ~16 million unique variants are identified. Despite the shallow time depth since divergence between the two main southeastern Bantu-speaking groups (Nguni and Sotho-Tswana), principal component analysis and structure analysis reveal significant (p < 10^-6) differentiation, and F_ST analysis identifies regions with high divergence. The Coloured individuals show evidence of varying proportions of admixture with Khoesan, Bantu-speakers, Europeans, and populations from the Indian sub-continent. Whole-genome sequencing data reveal extensive genomic diversity, increasing our understanding of the complex and region-specific history of African populations and highlighting its potential impact on biomedical research and genetic susceptibility to disease.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Black People / genetics*
DNA Mutational Analysis / methods
Genetic Predisposition to Disease / genetics*
Genetic Variation / genetics*
Genome, Human*
Healthy Volunteers
Humans
Male
Mutation / genetics
Pilot Projects
Principal Component Analysis
South Africa

Abstract

Publication types

MeSH terms

Grants and funding