Much has been achieved since the sequencing of the human genome project, but we are still only at the beginning of implementing truly personalized medicine. Could the proposed Three Million African Genomes project take us closer to the goal of inclusive, accurate genetic risk prediction that includes everyone regardless of their genetic ancestry?
This month is the 20th anniversary of the first publication of the draft human genome sequence. In the last two decades, genetics has advanced dramatically as a result, but it has become clear that human biobanks and genomic sequence databases have a diversity problem.
Earlier this month, Nature published an article by Ambroise Wonkam, M.D., Ph.D., a professor at the University of Cape Town and head of the African Society of Human Genetics. In the article, he outlines a proposal to set up a new sequencing project that aims to sequence 3 million genomes across Africa.
“Less than 2% of human genomes analyzed so far have been those of African people, despite the fact that Africa, where humans originated, contains more genetic diversity than any other continent,” he writes.
“The current lack of diversity in the global genomic resource really underscores the need for a project like this,” says Zané Lombard, Ph.D., an associate professor of human genetics at the University of the Witwatersrand.
Lombard and colleagues recently showed that high-depth sequencing of African genomes even on a small scale (they sequenced 426 individuals) can reveal a huge amount of previously unknown genetic variation – in their study alone they discovered 3 million new variants.
“We also show that we are not yet reaching a plateau in new discoveries, and therefore can learn much more by increasing the number of African genomes available in the global resource,” she adds.
Three million genomes is an ambitious goal, most genome projects to date have focused on sequencing thousands of people – such as the UK’s 100,000 genomes project. However, advances in next generation sequencing that have increased speed while also decreasing costs make it more achievable than it was 20 years ago.
“As I understand, Professor Wonkam has done some calculations, based on the number of ethnolinguistic groups in Africa versus the number represented in current public genomic datasets, to arrive at the number of 3 million genomes,” says Lombard.
In order for such a project to work, a large degree of collaboration between different African countries will be needed. The Human Heredity and Health in Africa (H3Africa) consortium was set up in 2010 to study the genomics and medical genetics of the African people. It has already started the groundwork of building such a network and indeed Lombard’s recent work sequencing African genomes on a small scale was a direct result of her work as a principal investigator for H3Africa.
Ananyo Choudhury, Ph.D., is a senior researcher at the Sydney Brenner Institute for Molecular Bioscience, also based at the University of the Witwatersrand. He was first author on the recent Nature paper that was co-authored by Lombard.
“This is definitely a very ambitious project and securing funding worth hundreds of millions of dollars would be first and perhaps the most difficult challenge,” he suggests.
“Although we are gradually developing the capacity to do cutting-edge genomic research in the continent, the scale of the proposed study is unprecedented. Therefore, setting up of computational infrastructure for efficient storage and processing of a genomic dataset of this size as well as finding a critical mass of people with the necessary computational and analytic skills would also be major challenge.”