Claude Bhérer was a student in biological anthropology in 2002 when the untimely death of a nephew inspired her to pursue a career in population genetics. “My nephew died of acute fulminant lactic acidosis just two days after he was born,” says the assistant professor in the School of Biomedical Sciences in McGill’s Faculty of Medicine and Health Sciences. “As luck would have it, the gene responsible for the condition was identified only a few months later, and that led to the discovery that his four-year-old sister also had it.”
Bhérer has since devoted much of her career to studying the “founder effect.” The concept refers to the genetic consequences that can occur when a subgroup of founders leaves a source population to form a new population – for example, pioneers from Charlevoix leave to colonize the Saguenay-Lac-Saint-Jean region. The hereditary disease affecting her sister’s two children – called Leigh Syndrome French Canadian type, also known as lactic acidosis – is surprisingly common in populations from the Charlevoix, Saguenay-Lac-Saint-Jean, and Haute-Côte-Nord regions. Quebec’s public health agency has identified three other genetic diseases that also affect these populations, for which there are now free screening tests.
But the story of the founder effect in Quebec does not stop there. After carrying out a systematic analysis of rare genetic diseases, Bhérer and her team have found that more than 100 already-known genetic variants are more common in Quebec than elsewhere. “We were surprised. This represents as many potential ‘founder’ genetic variants, most of which have not yet been described in the context of Quebec,” says Bhérer, who is also looking at the founder effect in New Brunswick and Newfoundland.
The search for new therapies
In 2022, Bhérer founded her own research group specializing in human population genetics within the McGill Canada Excellence Research Chair in Genomic Medicine. The mission of the chair is to use genetics and genomics to support the discovery and development of new therapies. “In the case of congenital lactic acidosis, we still have a lot of work to do to find a therapy,” she explains. As with most rare diseases, science still hasn’t been able to identify all the factors that explain the disease, nor explain why some people develop fulminant cases while others are less affected – such as her niece, who is now an adult.
In addition to her research into genetic variation and rare diseases in founder populations, Bhérer is working on a “digital health platform” project that will use connected watches, smartphones, and blood glucose monitors to collect real-time data on what is happening to people with the Leigh Syndrome French Canadian type. “What triggers the attacks? What factors are at play? Or, on the contrary, why do patients get better? We are hoping to be able to analyze the data using artificial intelligence tools.”
The challenge of EDI in genetics
Bhérer’s other major research theme relates to Equity, Diversity and Inclusion (EDI).
EDI is a now a major issue in genetics and genomics. “Most of the available data comes from cohorts with a large majority of participants of European origin. We know much less about the genetic factors of non-European populations, such as those of African origin. Quebec put in place an action plan on rare diseases in 2023. Yet population screening for certain genetic diseases could be improved,” Bhérer says.
In 2022, Bhérer organized a two-day symposium on EDI that attracted over 300 participants, including several leading international equity specialists. She is also working with other researchers at McGill and elsewhere to develop the pan-Canadian genomic library. “We need to move EDI forward to better understand the genomic diversity of people living in Canada,” she says.
The benefits of genetic studies
Even though therapies for rare diseases are still quite scarce at the moment, genetic studies such as those being carried out by Bhérer and her team are already bringing significant benefits.
“As soon as the genetic basis of a disease has been identified, the scientific results can quickly be applied in clinical practice for diagnoses, screening, prevention and care,” she explains. “This also makes it possible to study patient cohorts and establish patient registries to understand the course of the disease. The identification of genes also means families can be linked to support groups and aid networks, which play a very important role in the case of rare diseases.”
And if there is a treatment is on the horizon?
“We would put resources in place to be able set up a clinical trial here quickly.”
Translated by Julie Barlow