Sequencing African genomes illuminates health and migration history

Historically, knowledge of baseline genetic data for African populations has been sparse. To remedy this, the Human Heredity and Health in Africa (H3Africa) Consortium, a collaborative effort supported by the National Institutes of Health, led a global research project to sequence genomes from regions and countries across Africa. The research, including work from Baylor College of Medicine, paves the way for more broadly representative and relevant studies ranging from basic through clinical genetics. The findings are published in the journal Nature.

The Human Genome Sequencing Center at Baylor College of Medicine worked with the H3Africa consortium and local African governments to acquire consented samples from 13 countries across the continent and generate high-coverage whole genome sequence data on 314 individuals representing 50 ethnolinguistic groups. This allowed the researchers to examine rare genetic variants in an accurate and quantifiable way, in addition to the common variants that have been the focus of most of the previous genetic studies in Africans.

“We found an impressive breadth of genomic diversity among these genomes, and each ethnolinguistic group had unique genetic variants,” said Dr. Neil Hanchard, assistant professor of molecular and human genetics at Baylor College of Medicine and senior author on the study. “There was a great deal of variation among people in the same region of Africa, and even among those from the same country. This reflects the deep history and rich genomic diversity across Africa, from which we can learn much about population history, environmental adaptation and susceptibility to diseases.”

The research showed more than 3 million novel variants in the genomes sequenced. Beyond the sheer amount of variation within and among the groups studied, the researchers were able to use the data to examine historic patterns and pinpoint migration events that were previously unknown.

“For the first time, our data showed evidence of movement that took place 50 to 70 generations ago from East Africa to a region in central Nigeria. This movement is reflected in the genomes of a Nigerian ethnolinguistic group and is distinct from previous reports of gene flow between East and West Africa,” said Dr. Adebowale Adeyemo, deputy director of the Center for Research on Genomics and Global Health at the National Human Genome Research Institute, and a senior author on the study. “This data gives us a more complete picture of the genetic history of Africa.”

The researchers found more than 100 areas of the genome with evidence of being under natural selection. A sizable proportion of these regions were associated with genes related to immunity.

“When you consider which forces have shaped African genetic diversity, you might think of malaria and sleeping sickness,” Hanchard said. “Our study suggests that viral infections could also have influenced genomic differences between people, via genes that affect individuals’ disease susceptibility.”

There were also noticeable variations in selection signals between different parts of the continent. “Our findings suggest that adaptation to local environments, diets or pathogens might have accompanied the migration of populations to new geographic regions,” said Dr. Dhriti Sengupta, one of the lead analysts from SBIMB, University of Witwatersrand.

The researchers hope their work will lead to wider recognition of the extent of undocumented genomic variation across the African continent, and of the need for continued studies of the many diverse populations in Africa.

“Adding genomic data from diverse populations is essential to ensure that all global populations can benefit from the advances in health that precision medicine offers,” said Dr. Zané Lombard, associate professor at the Division of Human Genetics of the University of the Witwatersrand, South Africa, and a senior author on the study.

Dr. Richard Gibbs, Donna Muzny and Ginger Metcalf from the Human Genome Sequencing Center at Baylor contributed to this work. Find the complete list of all the contributors and their affiliations, as well as the financial support for this study in the publication.