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.
Description:
M.R. and M.S.P. co-lead the SAHGP initiative, and the project was designed and
coordinated by the core working group including M.R., M.S.P., S.B., H.S., R.R., J.R., K.S.,
P.V., N.M., F.J., S.H., and L.V. M.R. and H.S. obtained ethics approval for the study. The
data analysis team was led by S.H. (PCA; STRUCTURE and Y chromosome analysis) and
included A.C. (novel SNV characterization, LOF variant, f2, FST, SFS, and ROH analysis),
N.M. (functional analysis), F.J. (variant calling), S.A. (variant calling), G.B. (functional
annotation and data curation), E.R.C. (admixture), J.G. (functional annotation), M.J.S.D.
(functional annotation), A.M. (functional annotation, SNV characterization, data curation,
and mtDNA analysis), and D.S. (regional FST analysis, data visualization). All
authors wrote the Methods section and notes on their analyses. M.R. and A.C. drafted the
manuscript, and A.C. was responsible for coordinating Tables and Figures (including the
Supplement).
