In 2011, the Care4Rare Canada Consortium was created by Genome Canada and the Canadian Institutes for Health Research in order to explore the potential of genome-wide sequencing (GWS) for rare disease gene discovery. In a new article published in the American Journal of Human Genetics, members of the Consortium reflect on their progress so far, and the work that still remains to be done.

Since its inception the Consortium has undergone three phases, each building on the challenges encountered in the one before. First was FORGE (2011-2013), which focused on rapid discovery for recognisable syndromes. This was followed by Care4Rare (2013-2018), dedicated to solving N-of-1 rare diseases. Most recently, the program has operated under the name Care4Rare-SOLVE, and works to expand access to GWS for Canadians and provide diagnoses to families with suspected rare diseases following inconclusive exome sequencing. Overall, the program has seen a diagnostic yield of 34% to date, with 121 novel gene discoveries published, with additional genes and variants currently under investigation.

Overall, Care4Rare has had a significant impact in the building of new clinical genomic knowledge, and in facilitating access to clinical GWS for Canadians with rare diseases. More than a decade of finding solutions to various challenges has led to a number of lessons learned which can be applied both to the Consortium’s future activities, and to other gene discovery initiatives both within Canada and globally. There remains a need for improved leveraging of other types of omics data for secondary use, as well as policies which support safe data sharing in order to continue offering diagnostic clarity for families with rare diseases.