Expanding the Use of Genomics to Unravel Rare Diseases: Care4Rare EXPAND

Care4Rare EXPAND is a four-year collaborative research project to build a rare disease (RD) dataset. We will generate a diverse genomic asset of 17,650 datasets from 7,150 families with RD, including: 13,000 short-read genomes, 2,000 long-read genomes, 650 transcriptomes, and 2,000 methylomes. Our datasets will reflect diverse genetic ancestries as participating institutions serve vast catchment areas (urban, rural, remote), new Canadians and communities unique to Canada (French Canadians, Indigenous and Anabaptist). EXPAND will use Care4Rare’s established workflows to capture comprehensive phenotypic data, metadata and other omics. We will deposit clinical data into our centralized repositories, Genomics4RD and Centre québécois de données génomiques (CQDG), which will be integrated into the Pan-Canadian Genome Library (PCGL). We will also use our All for One Connect REB-approved registry protocol to collect re-contact data, which will also be incorporated into the PCGL. EXPAND builds on Care4Rare’s 15 years of success applying genomics for RD diagnosis and discovery. We expect a diagnostic yield of 30-35 per cent, ending a costly and burdensome diagnostic odyssey for 2,200 families. Families living with RD are marginalized, facing substantial barriers to accessing appropriate care and social services. C4R-EXPAND will reduce these disparities by enabling accurate diagnoses and increasing visibility. Comprehensive data generated from C4R-EXPAND will ultimately improve interpretation and access to testing, and advance genomic health for all.