African genome research is trying to take off on the continent

“Welcome back home!” The theme of the 14^th International Congress of Human Genetics (ICHG), which is organized every five years, was not chosen at random: For the first time, the conferences of specialists in this young discipline held at the end of February took place in Africa, in Cape Town. It is a strong symbol and “a way to remind people that we are all African,” said Professor Ambroise Wonkam, a world-renowned specialist and president of the African Society of Human Genetics (SAfGH), who organized the event.

Yet, since the publication of the first complete sequencing of a human genome, 22 years ago, less than 2% of all genomes listed come from people of African origin. This is a paradox as “the vast majority of human genetic diversity has remained on the continent,” said the Cameroonian researcher, who also heads the Department of Genetic Medicine at Johns-Hopkins University in Baltimore, USA (Maryland). “It is estimated that each African genome has five times more variation than a Caucasian genome.” With the exit of Homo sapiens from Africa 50,000 to 60,000 years ago, only a small sample of genetic diversity spread across the globe.

The vast majority of the research carried out over the past two decades has been conducted by European and American teams. “Researchers have worked with the genomes that were most easily accessible, and therefore mainly from populations of European origin. But the genomes of African populations present a much greater diversity than that which exists among Caucasian genomes,” said Hugues Abriel, professor of molecular medicine at the University of Bern, in Switzerland.

Although in recent years, researchers’ interest has extended to Asian populations, Africans remain forgotten. This has very concrete consequences for the improvement of diagnosis and treatment of genetic diseases on the continent. “As a medical geneticist, when I sequence the genome of a sick child, if I find an anomaly, the available databases do not help me, because they only contain information from populations of European origin,” said Shahida Moosa, head of the genetics medicine department at Tygerberg Hospital and professor at Stellenbosch University in Cape Town. It is therefore urgent to sequence DNA on the continent in order to develop an African genomic library.

A scientific necessity, an equality issue

Because a genetic variant can change the symptoms of a disease, sometimes for the same disease, it is a gene different from the one known in Caucasian genomes that is involved. “A mutation very frequently found in Western babies who are born deaf is almost never present in Africa,” said Wonkam. “On the other hand, in Ghana, we have identified seven new genes involved in deafness.”

Identifying these variations and improving knowledge about the genomes and genetic diseases of African populations is therefore not only a scientific necessity but also an equality issue. “When I started my project on cystic fibrosisI discovered that in the Democratic Republic of Congo, out of 100 million inhabitants, not a single case is officially recorded!” said Professor Abriel, who collaborates on several projects on the continent. “Yet we know, via small cohorts, that this disease does exist in Africa as well.”

When she applies for funding, Moosa is still often told that rare diseases and human genetics projects are not a priority in Africa. Yes, HIV, TB and malaria are scourges here, but we need to stop working in silos and pitting the issues against each other,” she says. “A better understanding of the human genetics of African populations will have benefits far beyond rare diseases! Genetics has enabled progress on many diseases, infectious and chronic ones in particular.”

To support his colleague’s point, Wonkam reminds us that the latest drugs developed to treat high cholesterol, which are mainly used in high-income countries, are the result of studies carried out on a variant of the PCSK9 gene that is very present in certain African populations, but rare among populations of European origin.

Increase local research capacity

The experts interviewed insist on the universality of the benefits to be gained from a better knowledge of African genetics, but also on the need for research to be done locally. “We don’t want any more ‘helicopter research’ done by experts who come to the continent for a few months and leave,” said Moosa. “Researchers from here have been used by some foreign colleagues and they remain distrustful, which is now detrimental to collaboration between African teams. However, we must work in networks if we want to move forward.”

Tea Human Heredity & Health in Africa (H3Africa) project, which has just ended, has trained many young African scientists in genetic sciences over the course of 10 years. “We hope to be able to follow up on this beautiful project by establishing centers of excellence in genomics on the continent, but discussions are underway with potential donors, so I can’t say more,” said Professor Wonkam.

In recent years, African and European universities have been forging close ties to ensure increased local research capacity. Such is the collaboration between The Guild of Research and the African Research Universities Alliance (ARUA), which seeks to bring this work to fruition through “African clusters of excellence,” said Guild member Abriel. As Wonkam explained in a recent op-ed published in Naturein order to create a library with well-stocked shelves, some 3 million genomes will need to be sequenced over the next decade, requiring $450 million a year.