Grant: CIHR Fellowship

A rare disease is a disorder that affects less than 1 in 2000 people. Although individually rare, together, rare diseases affect approximately 1 in 12 people in Canada. Rare diseases are most often genetic, caused by mutations to our DNA that affect genes that are necessary for our cells and tissues to develop or function correctly. Despite great successes using current standard technologies to sequence and understand the genome, the genetic cause of thousands of rare diseases remains unsolved. A recently developed genome sequencing method, called long-read genome sequencing, has been shown to accurately detect certain types of mutations that are not well detected by the current sequencing technologies. My project will use this new long-read sequencing method to identify genetic causes of rare diseases that might have been missed by our standard sequencing technologies. I will apply long-read genome sequencing to a group of 100 individuals and their families with rare genetic diseases where causal mutations have yet to be found and will analyze the data to identify genetic mutations that underlie their rare disease. This study has important implications for the families involved, as receiving a genetic diagnosis is important for informing disease management and treatments, family planning, and offering relief from the burden of having an "unsolved" rare disease. It will also expand our understanding of the types of mutations that contribute to rare diseases and show the usefulness of this method as a diagnostic tool, which could in the future be used in clinical care settings to help more individuals with rare diseases. In the longer term, gaining a better understanding of the underlying causes of rare diseases can help direct research to lead to the development of targeted therapies to treat rare diseases.