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

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 FST 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.

Importance of human demographic history knowledge in genetic studies involving multi-ethnic cohorts

“…Previous studies on intricate languages in China, and Australia suggest consistency of genetic and linguistic evolution, with striking evidence of compatible phylogenetic signal and phonological evolution 29, 30 . In SSA such studies are hindered by paucity of data with only a limited number of reasonably close populations available, impeding more detailed analysis 18, 31 . A recent study highlights population differentiation between two South Eastern Bantu groups in South Africa, which were assumed to be genetically homogenous, further emphasising the importance of having a clear perspective of population structure in disease-association studies 18 .…”

“…In SSA such studies are hindered by paucity of data with only a limited number of reasonably close populations available, impeding more detailed analysis 18, 31 . A recent study highlights population differentiation between two South Eastern Bantu groups in South Africa, which were assumed to be genetically homogenous, further emphasising the importance of having a clear perspective of population structure in disease-association studies 18 . This result was arrived at by understanding ethnolinguistic divisions within the present-day population, and purposely recruiting from rural areas or regions with little ethnolinguistic diversity 18 .…”

“…We then used ADMIXTURE (v1.3) to estimate ancestry for K values from 2 through 20 17 . Distruct plots of the output ancestry fractions were generated using Genesis (v 0.2.6b) 18 .…”

“…An understanding of their demographic history could provide some clues as to what one may expect. Perhaps refer to the recent paper on South African genomes by Choudhury et al 1 .…”

Unraveling African diversity from a cross‐disciplinary perspective

“…31 34 This consortium also encourages the formation of intracontinental collaborations and development of training programs and facilities necessary to lead high-quality genomics and biomedical research in Africa. 35 One of the H3Africa projects, the AWI-Gen study, was designed to determine genetic and environmental contributions to cardiometabolic diseases and related traits in African groups. In this large-scale GWAS study, association and fine-mapping analyses have been conducted to discover novel genetic associations of lipid traits with genes that have only been observed to be polymorphic in African populations.…”