This week, over 8,300 researchers, exhibitors, and journalists arrived in Houston to attend the 2019 American Society of Human Genetics’ (ASHG) Annual Meeting to learn more about cutting edge research in the field of human genetics and genomics. Interestingly, one issue kept popping up throughout the ASHG meeting: the lack of diversity in human genomics research.
This isn’t a new issue.
The human reference genome — the sequence to which all DNA is mapped in reference to — is largely based on individuals of European descent, making it difficult for individuals from under-represented groups to benefit from current progress in genomics. In fact, 70% of the human reference sequence actually originates from a single individual. While this reference genome has helped pushed the field forward, it doesn’t accurately represent our global genomic landscape.
Researchers are aware of this issue — and here’s how they’re tackling diversity in genomics research.
One remarkable effort is being carried out by the Human Hereditary and Health in Africa (H3Africa) consortium, which was launched in 2013 to address the under-representation of African individuals in genomics. H3Africa, with support from the National Institutes of Health, sequenced the entire genome of 426 individuals from 13 different countries, providing a more complete picture of Africa’s genomic diversity.
In the opening ASHG plenary session, Neil Hanchard, assistant professor at the Baylor College of Medicine, shared that this large-scale sequencing effort identified over three million novel single nucleotide variants — which have not yet been observed in current (largely European) genomic databases. For example, surveyed populations from Mali and Botswana had at least 6,000 novel common variants. This concept of "rare" and "common" variants is particularly important since how frequent a variant is in a population is often used to infer pathogenicity (i.e. how damaging it is). The H3Africa consortia’s initial findings show that some previously classified pathogenic variants are in fact not rare and are found in variable frequencies across African genomes.
“This is a starting point,” said Hanchard at the plenary meeting. “African genomes have the potential to inform the [genomics] field more globally.”
In a similar vein, a group of US researchers sequenced over 300 genomes from around the world, including both male and female individuals from different sub populations. By looking at breakpoints and sequence content, the researchers were able to use a technique called de novo assembly to align unique sequences (which previously could not be mapped) to the reference genome, thus constructing a more representative, and detailed, reference genome.
In addition to ongoing efforts like the ambitious All of Us program, these efforts can together help us move towards a future where people everywhere — regardless of their geographic location or ethnicity - will all be able to reap the benefits of human genomics research.