New pangenome reference could deepen our understanding of human biology and disease

Reviewed by Megan Craig, M.Sc.Jun 5 2023

The first human genome, which has served as the reference until now, was released approximately 20 years ago. It was a landmark accomplishment that had a huge impact on biomedical research and changed the way scientists study human biology. But it was based on just a few individuals and did not capture the full genetic diversity of the human population.

An important step forward for both biology and biomedical research

Since this reference has been at the core of most genomic analysis, it leads to a bias and we might miss important things happening in regions of the human genome that are not present in the reference."

Guillaume Bourque, Professor in the Department of Human Genetics at McGill University and Director of Bioinformatics at the McGill Genome Center

He is among a large group of scientists who have recently published an article in Nature about the first generation of a new type of reference genome, called a pangenome, that represents 47 individuals that are as genetically diverse as possible, from Africa, Asia, and the Caribbean, to name just a few regions.

The researchers revealed that every time they sequenced a human genome, they found pieces of human DNA that were unique to each individual. The pangenome allows the integration of this new information into the reference. This may eventually have significant impacts in terms of developing targeted medical treatments associated with these unique or population-specific DNA sequences.

Pangenome should lead to deeper understanding of disease responses

Bourque adds, "This is very exciting because we can now look into regions of the genome that are present in some individuals but missing from the reference. The work of my PhD student Cristian Groza showed that we can detect 2-3% more active regions in the human genome that were missed before. While 2-3% may seem insignificant, those are regions that differ from one individual to the next and so they might be important in explaining differences in disease responses for instance. In fact, in a related study, published in Cell Genomics, we detected new regions that differ between individuals and are potentially important in the response to influenza infection. This is just the tip of the iceberg in terms of confirming that there are things actually happening in these new regions of the genome."

Full consequences of the pangenome reference remain unclear

Some of the benefits of this new pangenome reference have already been demonstrated. But the full implications of this new genetic reference tool remain to be determined since scientists can now study regions of the human genome that they couldn't explore before. Understanding their potential function and consequence will be the work of hundreds of groups for years to come. A major challenge is that a lot of genomic methods currently rely on a linear reference genome, they will need to be adapted to use a pangenome instead.

The use of the pangenome will also be important in the context of McGill University's new D2R program whose goal is to mobilize the university's research expertise to advance, in an inclusive way, the development of the next generation of RNA medicines for viral infections, cancer, and rare diseases.