Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Am J Hum Genet. 2022 Nov 3;109(11):1947-1959. doi: 10.1016/j.ajhg.2022.10.002.
The past decade has witnessed a rapid evolution in rare disease (RD) research, fueled by the availability of genome-wide (exome and genome) sequencing. In 2011, as this transformative technology was introduced to the research community, the Care4Rare Canada Consortium was launched: initially as FORGE, followed by Care4Rare, and Care4Rare SOLVE. Over what amounted to three eras of diagnosis and discovery, the Care4Rare Consortium used exome sequencing and, more recently, genome and other 'omic technologies to identify the molecular cause of unsolved RDs. We achieved a diagnostic yield of 34% (623/1,806 of participating families), including the discovery of deleterious variants in 121 genes not previously associated with disease, and we continue to study candidate variants in novel genes for 145 families. The Consortium has made significant contributions to RD research, including development of platforms for data collection and sharing and instigating a Canadian network to catalyze functional characterization research of novel genes. The Consortium was instrumental to implementing genome-wide sequencing as a publicly funded test for RD diagnosis in Canada. Despite the successes of the past decade, the challenge of solving all RDs remains enormous, and the work is far from over. We must leverage clinical and 'omic data for secondary use, develop tools and policies to support safe data sharing, continue to explore the utility of new and emerging technologies, and optimize research protocols to delineate complex disease mechanisms. Successful approaches in each of these realms is required to offer diagnostic clarity to all families with RDs.
过去十年见证了罕见病（RD）研究的快速发展，这得益于全基因组（外显子组和基因组）测序技术的可用性。2011 年，这项变革性技术被引入研究界，加拿大 Care4Rare 联盟成立：最初是 FORGE，随后是 Care4Rare，以及 Care4Rare SOLVE。在三个诊断和发现的时代中，Care4Rare 联盟使用外显子组测序，最近还使用基因组和其他“组学”技术来确定未解决的 RD 的分子原因。我们的诊断率达到了 34%（623/1806 个参与家庭），包括在 121 个以前与疾病无关的基因中发现有害变异，我们还在继续研究 145 个家庭中 121 个新基因的候选变异。该联盟为 RD 研究做出了重大贡献，包括开发数据收集和共享平台，并发起了一个加拿大网络，以促进对新基因的功能特征研究。该联盟为在加拿大实施全基因组测序作为 RD 诊断的公共资助测试做出了重要贡献。尽管过去十年取得了成功，但解决所有 RD 的挑战仍然巨大，工作远未完成。我们必须利用临床和“组学”数据进行二次利用，开发工具和政策以支持安全的数据共享，继续探索新出现技术的实用性，并优化研究方案以阐明复杂的疾病机制。需要在这些领域中的每一个领域中采用成功的方法，才能为所有 RD 家庭提供明确的诊断。
