Discover millions of new variants in African genomes

An estimated three million new genetic variants in more than 300 genomes have been discovered through a new large-scale African collaboration between researchers from the Human Genetics and Health in Africa (H3Africa) consortium, which includes academics from the University of Cape Town (UCT) . .

A paper on the study, entitled ‘High-depth African genomes inform human migration and health’, was published in the prestigious journal Nature on 28 October.

The summary begins with the following statement: ‘The African continent is considered the cradle of modern humans, and African genomes contain more genetic variation than that of any other continent, but only a fraction of the genetic diversity among individuals in Africa was investigated. “

“We need a better understanding of Africans to enable research into the genetic basis of diseases in these populations.”

The breadth of this study offers the opportunity to fill in some previously overlooked gaps by sequencing genomes from samples from populations not yet represented.

“We need a better understanding of Africans to enable research into the genetic basis of diseases in these populations,” said Professor Nicola Mulder, who leads H3ABioNet, a pan-African bioinformatics network for H3Africa.

African research, by Africans

The H3Africa consortium facilitates fundamental research on continental diseases and has more than 500 members across Africa, several of whom are part of groups within the Institute of Infectious Diseases and Molecular Medicine (IDM) at the UCT’s Faculty of Health Sciences.

The consortium develops infrastructure, resources, training and ethical guidelines to support a sustainable African research venture – led by African scientists – for Africans.

This new study provided H3Africa with the opportunity to engage in work consistent with its mandate, especially as the global version of African genomic data remains weak, and international projects often sample only a few African populations for sequencing.

“African genomes have many new variants and therefore contribute greatly to the global understanding of population genetics.”

This is an unfortunate oversight, as African genomes have many new variants and therefore contribute greatly to the global understanding of population genetics.

The study is repairing the lack of representation of populations that usually do not have much coverage. These factors are important as they allow for a more detailed study of the genetic landscape of African populations, which is very diverse.

Professor Mulder, who is a full member of the IDM and also Head of the Division of Computer Biology in the Department of Integrative Biomedical Sciences in the Faculty of Health Sciences of the UCT, is passionate about building capacity to enable African scientists to analyze data from research covering continent.

“This project was a great demonstration to put it into practice,” she said.

The complete genome sequence of 426 individuals from 13 African countries was performed, of which 314 were analyzed at high depth. This enabled the researchers to investigate rare genetic variants in an accurate and quantifiable way.

Together with collaborators, Mulder’s team applied expertise in the processing of large-scale data for human genomes and the analysis and interpretation of variants. Their findings point to extensive genomic diversity among these genomes, even within countries and regions, with unique variants identified in each ethnolinguistic group.

“It reflects the long history and rich genomic diversity in Africa, and it indicates an enormous space to identify new variants with additional sequence,” Mulder said.

Ancient migration events excavated

Apart from the amount of genetic variation discovered between the groups studied, while the regions are also underrepresented, the research revealed some historical migration patterns across the continent that the team was able to map.

The authors investigated common and rare genetic variants to examine human migration history and look at regions undergoing natural selection. Many of the regions selected were associated with genes associated with immunity and response to infectious diseases.

“These findings are extremely informative in understanding the frequency of many genetic traits and their association with infectious diseases.”

According to associate professor Emile Chimusa, from the Division of Human Genetics of the Faculty of Health Sciences, and a fellow member of the IDM, who worked on the selection section of the paper, the study shows that functionally important genetic variants related to physiological traits are very high. is. relevant to infectious diseases, and geographically limited to the local adaptation of a particular lifestyle or environment.

“These findings are extremely informative for understanding the frequency of many genetic traits and their association with infectious diseases, including those that cause susceptibility or resistance to diseases among African populations and populations of recent African descent,” he said.

These data helped them to examine historical patterns and to identify previously unknown migration events.

It also showed evidence of migration from East Africa to a region in Central Nigeria 50 to 70 generations ago, which differs from previous reports of gene flow between East and West Africa.

Clinical significance

“In addition, the study looked at medically relevant variants, and we found that some variants previously characterized as pathogenic are common in some populations. This shows how new African data can help to re-establish the clinical significance of variants. indicates, “said Mulder, who co-leads the data integration platform for the Wellcome Center for Infectious Disease Research in Africa (CIDRI-Africa).

The findings are broadly relevant, providing new insights into human history and migrations, and providing data for population genetics and health-related research.

The collaboration was between just under 20 institutions across the continent, including members of H3Africa. While previous African studies were mostly led by people outside the continent, this study was driven by African scientists.

“[This demonstrates] the recent growth in infrastructure and resources, as well as the skills needed in Africa to undertake generational analysis and interpretation of large-scale genomics, ”said Mulder.

Support for the consortium is provided by the United States National Institutes of Health (NIH)’s Office of Strategic Coordination, the Common Fund, in the director’s office, through the U54HG003273 and U24HG006941 grants.


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