Beyond the Genome: Transcriptome Based Diagnostics for Rare Diseases and Cancer


Human Health


Rare genetic diseases affect more than 500,000 children in Canada, often causing severe disability and early death, while cancer is the leading cause of non-accidental death in childhood. Early diagnosis at the molecular level is essential so that the right treatment for each individual can begin as early as possible. The most advanced genetic tests, however, are able to diagnose fewer than half of all children with rare disease and cannot detect important genetic changes in tumours that are critical for successful treatment.

In the first phase of this competition, Drs. Adam Shlien and James Dowling of the Hospital for Sick Children, with co-leaders Drs. Michael Wilson and Michael Brudno, demonstrated that RNA sequencing (RNA-seq), an emerging technology that examines the activity and structure of genes, can find disease-causing genetic variants (Dowling) and detect mutations and fusions in cancer genes (Shlien). Importantly, many of these mutations are not found by current genetic testing. In this second phase, they are combining their strengths to further develop and optimize the technological elements of RNA-seq and definitively determine how well it performs as a clinical test. Their goal is to create a clinically viable, comprehensive RNA-seq–based diagnostic platform for rare diseases and cancer. This platform will be fully automated, using advanced robotics and algorithms, and will improve in accuracy for every sample it is run on.

Their work will result in the first clinical RNA-seq diagnostic test in Canada. When fully implemented, the test will significantly increase the success rate of genetic testing in children with rare genetic diseases and cancer and improve access to clinical trials. The researchers will also create a dynamic digital library to integrate RNA-seq data with a range of health information, setting the stage for true precision medicine for all Canadians.