A new genomic resource released by scientists this month promises to streamline the use of genomic testing and precision medicine for patients of all ancestries. It is a significant advance that comes two decades after the first human genome sequence was declared complete.
The original human genome sequence was based largely on the DNA of a single person, with bits and pieces of DNA from other individuals added over time as scientists learned more about our genomic blueprints. This genome sequence served as a reference for the entire genomics community; any DNA sequenced from another person was immediately compared to the reference to glean important insights about disease risk and other traits.
But all along, researchers knew that having a single reference genome would limit what they could learn about other people — especially people whose ancestry isn’t represented by that genome. The genome-based tests used to guide precision medicine, for example, often can’t find genetic variants that have not been previously identified in the reference genome. Genetic variants that are common in other populations might be clinically meaningful, but are likely to go undetected without a more representative reference.
Now, scientists have published what they call a “pangenome” reference. It’s a collection of high-quality genome sequences from 47 people of diverse ancestries from Africa, Asia, and North and South America. The work comes from the Human Pangenome Reference Consortium, a large collaboration of scientists funded to the tune of $40 million by the National Human Genome Research Institute (NHGRI). It’s the first phase of a larger project that aims to sequence 350 people by 2024 to capture a broad range of human genetic diversity.
One of the most important outcomes of this new resource should be to improve genome interpretation — the task of spotting clinically relevant genetic variants to diagnose or prevent disease or to match a patient to the right treatment. “Everyone has a unique genome, so using a single reference genome sequence for every person can lead to inequities in genomic analyses,” said Adam Phillippy, a consortium member and scientist at NHGRI, in a statement announcing the pangenome. Scientists and doctors will have a better chance of finding key genetic variants when they compare someone’s DNA data to this large reference set of genomes than they did when the reference was just one genome.
“This will help make the reference useful for all people, thereby helping to reduce the chances of propagating health disparities,” said Eric Green, NHGRI director, in the same statement.
The pangenome could also provide a much-needed foundation for new initiatives to automate the genome interpretation process or even to incorporate AI into interpretation. Until now, efforts to streamline the discovery of genetic variants and other key steps needed to interpret a genome have been constrained by the limited utility of a single reference genome. With nearly four dozen genomes — and by this time next year, potentially hundreds of genomes — it should be much easier to deploy advanced computational tools and improve what is now a largely manual process.