학술논문
Outcome of over 1500 matches through the Matchmaker Exchange for rare disease gene discovery: The 2-year experience of Care4Rare Canada.
Document Type
Academic Journal
Author
Osmond M; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.; Hartley T; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.; Dyment DA; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada; Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.; Kernohan KD; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada; Newborn Screening Ontario, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.; Brudno M; Department of Computer Science, University of Toronto, Ontario, Canada; Techna Institute, University Health Network, Toronto, Ontario, Canada.; Buske OJ; PhenoTips, Toronto, Ontario, Canada.; Innes AM; Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Boycott KM; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada; Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada. Electronic address: kboycott@cheo.on.ca.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 9815831 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-0366 (Electronic) Linking ISSN: 10983600 NLM ISO Abbreviation: Genet Med Subsets: MEDLINE
Subject
Language
English
Abstract
Purpose: Matchmaking has emerged as a useful strategy for building evidence toward causality of novel disease genes in patients with undiagnosed rare diseases. The Matchmaker Exchange (MME) is a collaborative initiative that facilitates international data sharing for matchmaking purposes; however, data on user experience is limited.
Methods: Patients enrolled as part of the Finding of Rare Disease Genes in Canada (FORGE) and Care4Rare Canada research programs had their exome sequencing data reanalyzed by a multidisciplinary research team over a 2-year period. Compelling variants in genes not previously associated with a human phenotype were submitted through the MME node PhenomeCentral, and outcomes were collected.
Results: In this study, 194 novel candidate genes were submitted to the MME, resulting in 1514 matches, and 15% of the genes submitted resulted in collaborations. Most submissions resulted in at least 1 match, and most matches were with GeneMatcher (82%), where additional email exchange was required to evaluate the match because of the lack of phenotypic or inheritance information.
Conclusion: Matchmaking through the MME is an effective way to investigate novel candidate genes; however, it is a labor-intensive process. Engagement from the community to contribute phenotypic, genotypic, and inheritance data will ensure that matchmaking continues to be a useful approach in the future.
Competing Interests: Conflict of Interest Michael Brudno and Orion J. Buske have an equity interest in, and Orion J. Buske is an employee of PhenoTips, which licenses software used in the PhenomeCentral and Genomics4RD databases.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Methods: Patients enrolled as part of the Finding of Rare Disease Genes in Canada (FORGE) and Care4Rare Canada research programs had their exome sequencing data reanalyzed by a multidisciplinary research team over a 2-year period. Compelling variants in genes not previously associated with a human phenotype were submitted through the MME node PhenomeCentral, and outcomes were collected.
Results: In this study, 194 novel candidate genes were submitted to the MME, resulting in 1514 matches, and 15% of the genes submitted resulted in collaborations. Most submissions resulted in at least 1 match, and most matches were with GeneMatcher (82%), where additional email exchange was required to evaluate the match because of the lack of phenotypic or inheritance information.
Conclusion: Matchmaking through the MME is an effective way to investigate novel candidate genes; however, it is a labor-intensive process. Engagement from the community to contribute phenotypic, genotypic, and inheritance data will ensure that matchmaking continues to be a useful approach in the future.
Competing Interests: Conflict of Interest Michael Brudno and Orion J. Buske have an equity interest in, and Orion J. Buske is an employee of PhenoTips, which licenses software used in the PhenomeCentral and Genomics4RD databases.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)