Centers for Mendelian Genomics: A decade of facilitating gene discovery.

TitleCenters for Mendelian Genomics: A decade of facilitating gene discovery.
Publication TypeJournal Article
Year of Publication2022
AuthorsBaxter, SM, Posey, JE, Lake, NJ, Sobreira, N, Chong, JX, Buyske, S, Blue, EE, Chadwick, LH, Coban-Akdemir, ZH, Doheny, KF, Davis, CP, Lek, M, Wellington, C, Jhangiani, SN, Gerstein, M, Gibbs, RA, Lifton, RP, MacArthur, DG, Matise, TC, Lupski, JR, Valle, D, Bamshad, MJ, Hamosh, A, Mane, S, Nickerson, DA, Rehm, HL, O'Donnell-Luria, A
Corporate AuthorsCenters for Mendelian Genomics Consortium
JournalGenet Med
Date Published2022 Apr
KeywordsExome, Exome Sequencing, Genetic Association Studies, Genomics, Humans, Phenotype

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.

Alternate JournalGenet Med
PubMed ID35148959
PubMed Central IDPMC9119004
Grant ListUM1 HG008900 / HG / NHGRI NIH HHS / United States
UM1 HG006504 / HG / NHGRI NIH HHS / United States
UM1 HG006542 / HG / NHGRI NIH HHS / United States
R35 NS105078 / NS / NINDS NIH HHS / United States
K08 HG008986 / HG / NHGRI NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States
U24 HG008956 / HG / NHGRI NIH HHS / United States
P50 HD103538 / HD / NICHD NIH HHS / United States
R01 HG009141 / HG / NHGRI NIH HHS / United States