High-depth African genomes inform human migration and health

TrypanoGEN Research Group.
H3Africa Consortium.
The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health.
We thank the members of the wider H3Africa Consortium (www.h3africa.org). WGS in H3Africa cohorts was supported by a grant from the National Human Genome Research Institute, National Institutes of Health (NIH/NHGRI) U54HG003273. The African Collaborative Center for Microbiome and Genomics Research (ACCME) is funded by NIH/NHGRI grant U54HG006947. The AWI-Gen Collaborative Centre is funded by NIH grant U54HG006938. The Exploring Perspectives on Genomics and Sickle Cell Public Health Interventions was funded by NHGRI/NIH grant U01HG007459. The Clinical and Genetic Studies of Hereditary Neurological Disorders in Mali study was funded by the NHGRI/NIH grant U01HG007044. The Collaborative African Genomics Network (CAfGEN) is funded by the National Institute of Allergy and Infectious Diseases (NIAID) of NIH and the NHGRI of the NIH (U54AI110398). ‘TrypanoGEN: an integrated approach to the identification of genetic determinants of susceptibility to trypanosomiasis’, was funded by the Wellcome Trust (099310/Z/12/Z). L.R.B. was supported by the CERCA Programme/Generalitat de Catalunya and by the Spanish Ministry of Economy and Competitiveness, through the ‘Severo Ochoa Programme for Centres of Excellence in R&D’ 2016–2019 (SEV-2015-0533). N.M. (principal investigator), S.A., G.B., G.W., J.K., Y.J.F., T.O., O.F., E.A., S.H., G. Mazandu, M. Mbiyvanga, A.B., S.K.K., E.R.C. and A. Moussa are funded by the NIH H3ABioNet grant under award number U24HG006941.