Gene interactions identified as personalised medicine’s missing link

By Lucy Ingham

The ability to affordably sequence genomes has prompted numerous predictions about the rise of personalised medicine, however so far this has failed to come to pass. But in research published today, scientists have identified gene interactions as the key barrier to this medical revolution taking off.

Personalised medicine, where individuals are prescribed pharmaceuticals based on their own genetic makeup, has been raised as a possibility since the Human Genome Project was completed in 2003. It was thought that as more people had their genomes sequenced scientists would unearth genes responsible for predispositions to specific diseases, which would enable medication to be tailored to individuals.

However, while tens of thousands of people around the world have now had their genomes sequenced, it has not produced the clear genetic interactions initially predicted. And the reason for this is gene interactions: how different genes impact each other in the results and responses they produce.

“The simple idea of a single gene leading to a single disease is more likely to be an exception than a rule,” explained study co-author Brenda Andrews, director of the University of Toronto’s Donnelly Centre for Cellular and Biomolecular Research.

“All the genome sequencing data is highlighting the complexity of inheritance for the human genetics community.”

Gene interactions likely to have a bigger impact on personalised medicine than single genes

While a number of high-profile genes have been found to cause specific diseases, such as cystic fibrosis, these are increasingly looking like the exception, not the rule, when it comes to how genetics impacts the way we develop diseases.

“It would be a simpler problem if one particular mutation resulted in Disease X all of the time, but that’s often not the case,” said study co-author Michael Costanzo, senior research associate at the University of Toronto.

“To understand the effect of combinations of variants is really difficult. We suspect it’s particular sets of mutations that really impact what the disease outcome is going to be in a personal genome.”

However, while gene interactions are emerging as key to personalised medicine, their understanding of them remains relatively limited, impacting how much information can currently be translated into real-world treatments.

“How genes interact with each other is important and, given our current understanding of gene-gene interactions, it’s not a problem that’s easily solved by reading individual genome sequences,” said Costanzo.

Towards understanding gene interactions

For scientists in this field, the key challenge is now to begin to understand these gene interactions – but given the complexity involved, vast amounts of data is required.

“If most genetic diseases involve gene combinations, collecting enough patient data to find these interactions is a huge challenge,” said Costanzo.

“We can’t think about genes in isolation anymore,” added study co-author Charles Boone, University of Toronto Donnelly Centre professor and co-director of the Canadian Institute for Advanced Research’s Genetic Networks programme.

“We have to start looking at variants of multiple genes as a major component of genetic disease, because those combinations are going to be different for different people and these specific combinations may not only profoundly affect disease susceptibility, but they will likely dictate new personalised therapies.”

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