Grant: Foundation Grant

Around 7000 rare genetic diseases (RDs) affect more than 1 million Canadians, most of them children. When considered together, RDs are a common cause of disability, early mortality, and healthcare costs. Over the past several years my research program has efficiently examined the protein-coding portion of the genome (~1%) to understand the cause of many RDs; however, as many as 60% of patients remain undiagnosed after this analysis. These patients often undergo a diagnostic journey involving multiple specialist consultations, imaging studies, invasive investigations, and other laboratory and genetic tests; a slow (5 to 30 years for 25%) process referred to as the diagnostic odyssey. These families are faced with significant uncertainty surrounding treatment, prognosis and the chances of future children or other family members also being affected. The goal of my research is to understand the genetic cause of unsolved RDs to end the diagnostic journey for as many Canadians with RD as possible. Given the rarity of all of the diseases we study, my program will help design and employ international RD patient data-sharing so that we, and indeed all RD scientists, can readily identify families with the same disease and changes in the same gene to prove causality. To look more broadly, my program will use the latest and most comprehensive technologies to examine a person's entire genome to identify the genetic cause of unsolved RDs. Finally, my program will develop new tests to determine whether a given genetic change has an impact on protein function. The outputs of my RD research program will lead to new insights into human biology in health and disease, develop novel diagnostic tools and tailor management to improve the care for Canadians with RDs, while enhancing global synergy, thereby ensuring continuing Canadian leadership in this realm.