Major new study unveils complexity and vast diversity of Africa’s genetic variation
February 2, 2021
Genomes arising
February 5, 2021

H3Africa Consortium Primes A Continent For Large-Scale Genomics Research

By Deborah Borfitz

February 2, 2021 | The Human Heredity and Health in Africa (H3Africa) Consortium is endeavoring to foster collaborative research on the world’s second-most populous continent, having spent the past decade bolstering the genomics research capacity here with 48 projects across 34 countries. Clinical geneticist and physician-scientist Neil Hanchard, M.D., Ph.D., through his academic position at Baylor College of Medicine, has, for example, been involved in a H3Africa-sponsored genomic study in children coinfected with HIV and tuberculosis whose principal investigator is based in Botswana.

Most recently, Hanchard was one of the senior authors on an H3Africa-sponsored study published in Nature (DOI: 10.1038/s41586-020-2859-7) showcasing the continent’s complex and vast diversity of genetic variation, which will be supporting research for decades to come. Only a fraction of the genetic diversity among African individuals had previously been surveyed, he says, even by large-scale efforts such as the 1000 Genomes Project.

The high level of genetic diversity vis-à-vis other continents makes anthropological sense given that people have lived in Africa, the birthplace of modern humans, longer than anywhere else on earth, says Hanchard. From that perspective, it could be considered unsurprising that the research team identified evidence for natural selection in and around 62 previously unreported genes.

The newly discovered variants were predominantly found in genes associated with viral immunity, DNA repair, and metabolism, Hanchard says. “We think most of those genetic signatures are relatively recent and likely to have some impact upon healthcare in persons of African ancestry.”

Researchers also observed complex patterns of ancestral mixing within and between populations, alongside evidence that Zambia was a likely intermediate site in the Bantu migration route to the south and east of the continent. The ancestry of people in one central Nigerian group was highly suggestive of historic in-migration from East Africa.

Whole-genome sequencing analyses was done on 426 individuals across 13 African countries. Participants represented 50 ethnolinguistic groups, including previously unsampled populations.

More than 100 areas of the genome had probably been under natural selection, the researchers concluded, a sizable proportion of which were associated with immunity-related genes. They believe viral infections, in addition to better-known insect-transmitted diseases like malaria and sleeping sickness, likely helped shape genomic differences across local geographies where people adopted certain dietary habits and were exposed to unique pathogens.

All told, researchers discovered over 3 million novel variants by comparing more than 1,000 African and 100,000 other genomes in public repositories (Exome Aggregation Consortium and Genome Aggregation Database) and most of them were found among the newly sampled ethnolinguistic groups. Even populations from the same country showed a great deal of variation among themselves, an observation wholly unsurprising—at least to the people living there, Hanchard says.

The implication is that many more novel genetic variants await discovery by sequencing African populations, Hanchard says. Notably, the research was conducted predominantly by local African researchers using local computational facilities, signaling that the continent now has the requisite infrastructure and analytic skills for large-scale genomics research.