Samantha M Baxter1, Jennifer E Posey2, Nicole J Lake3, Nara Sobreira4, Jessica X Chong5, Steven Buyske6, Elizabeth E Blue7, Lisa H Chadwick8, Zeynep H Coban-Akdemir9, Kimberly F Doheny4, Colleen P Davis10, Monkol Lek11, Christopher Wellington8, Shalini N Jhangiani12, Mark Gerstein13, Richard A Gibbs14, Richard P Lifton15, Daniel G MacArthur16, Tara C Matise17, James R Lupski18, David Valle4, Michael J Bamshad19, Ada Hamosh4, Shrikant Mane20, Deborah A Nickerson21, Heidi L Rehm22, Anne O'Donnell-Luria23. 1. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA. Electronic address: samantha@broadinstitute.org. 2. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX. 3. Department of Genetics, Yale School of Medicine, New Haven, CT; Murdoch Children's Research Institute, Melbourne, Victoria, Australia. 4. McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. 5. Department of Pediatrics, Division of Genetic Medicine, University of Washington and Seattle Children's Hospital, Seattle, WA; Brotman Baty Institute for Precision Medicine, Seattle, WA. 6. Department of Statistics, Rutgers University, Piscataway, NJ; Department of Genetics, Rutgers University, Piscataway, NJ. 7. Brotman Baty Institute for Precision Medicine, Seattle, WA; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA. 8. Division of Genome Sciences, National Human Genome Research Institute, Bethesda, MD. 9. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX. 10. Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA. 11. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA; Department of Genetics, Yale School of Medicine, New Haven, CT. 12. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX. 13. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT. 14. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX. 15. Department of Genetics, Yale School of Medicine, New Haven, CT; Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY. 16. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA; Centre for Population Genomics, Garvan Institute of Medical Research and UNSW Sydney, Sydney, New South Wales, Australia; Centre for Population Genomics, Murdoch Children's Research Institute, Melbourne, Victoria, Australia. 17. Department of Genetics, Rutgers University, Piscataway, NJ. 18. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX; Department of Pediatrics, Baylor College of Medicine, Houston, TX. 19. Department of Pediatrics, Division of Genetic Medicine, University of Washington and Seattle Children's Hospital, Seattle, WA; Brotman Baty Institute for Precision Medicine, Seattle, WA; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA. 20. Department of Genetics, Yale School of Medicine, New Haven, CT. 21. Brotman Baty Institute for Precision Medicine, Seattle, WA; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA. 22. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA. Electronic address: hrehm@broadinstitute.org. 23. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA; Department of Pediatrics, Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA. Electronic address: odonnell@broadinstitute.org.
Abstract
PURPOSE: Mendelian disease genomic research has undergone a massive transformation over the past decade. With increasing availability of exome and genome sequencing, the role of Mendelian research has expanded beyond data collection, sequencing, and analysis to worldwide data sharing and collaboration. METHODS: Over the past 10 years, the National Institutes of Health-supported Centers for Mendelian Genomics (CMGs) have played a major role in this research and clinical evolution. RESULTS: We highlight the cumulative gene discoveries facilitated by the program, biomedical research leveraged by the approach, and the larger impact on the research community. Beyond generating a list of gene-phenotype relationships and participating in widespread data sharing, the CMGs have created resources, tools, and training for the larger community to foster understanding of genes and genome variation. The CMGs have participated in a wide range of data sharing activities, including deposition of all eligible CMG data into the Analysis, Visualization, and Informatics Lab-space (AnVIL), sharing candidate genes through the Matchmaker Exchange and the CMG website, and sharing variants in Genotypes to Mendelian Phenotypes (Geno2MP) and VariantMatcher. CONCLUSION: The work is far from complete; strengthening communication between research and clinical realms, continued development and sharing of knowledge and tools, and improving access to richly characterized data sets are all required to diagnose the remaining molecularly undiagnosed patients.
PURPOSE: Mendelian disease genomic research has undergone a massive transformation over the past decade. With increasing availability of exome and genome sequencing, the role of Mendelian research has expanded beyond data collection, sequencing, and analysis to worldwide data sharing and collaboration. METHODS: Over the past 10 years, the National Institutes of Health-supported Centers for Mendelian Genomics (CMGs) have played a major role in this research and clinical evolution. RESULTS: We highlight the cumulative gene discoveries facilitated by the program, biomedical research leveraged by the approach, and the larger impact on the research community. Beyond generating a list of gene-phenotype relationships and participating in widespread data sharing, the CMGs have created resources, tools, and training for the larger community to foster understanding of genes and genome variation. The CMGs have participated in a wide range of data sharing activities, including deposition of all eligible CMG data into the Analysis, Visualization, and Informatics Lab-space (AnVIL), sharing candidate genes through the Matchmaker Exchange and the CMG website, and sharing variants in Genotypes to Mendelian Phenotypes (Geno2MP) and VariantMatcher. CONCLUSION: The work is far from complete; strengthening communication between research and clinical realms, continued development and sharing of knowledge and tools, and improving access to richly characterized data sets are all required to diagnose the remaining molecularly undiagnosed patients.
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Authors: Natasha T Strande; Erin Rooney Riggs; Adam H Buchanan; Ozge Ceyhan-Birsoy; Marina DiStefano; Selina S Dwight; Jenny Goldstein; Rajarshi Ghosh; Bryce A Seifert; Tam P Sneddon; Matt W Wright; Laura V Milko; J Michael Cherry; Monica A Giovanni; Michael F Murray; Julianne M O'Daniel; Erin M Ramos; Avni B Santani; Alan F Scott; Sharon E Plon; Heidi L Rehm; Christa L Martin; Jonathan S Berg Journal: Am J Hum Genet Date: 2017-05-25 Impact factor: 11.025
Authors: Minxian Wang; Justin Chun; Giulio Genovese; Andrea U Knob; Ava Benjamin; Maris S Wilkins; David J Friedman; Gerald B Appel; Richard P Lifton; Shrikant Mane; Martin R Pollak Journal: J Am Soc Nephrol Date: 2019-07-15 Impact factor: 10.121
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