Centers for Mendelian Genomics: A decade of facilitating gene discovery

• Published in: Genetics in medicine Vol. 24; no. 4; pp. 784 - 797
• Main Authors: Lake, Nicole J., Sobreira, Nara, Chong, Jessica X., Chadwick, Lisa H., Coban-Akdemir, Zeynep H., Doheny, Kimberly F., Lek, Monkol, Jhangiani, Shalini N., Lifton, Richard P., Matise, Tara C., Lupski, James R., Valle, David, Nickerson, Deborah A., Akay, Gulsen, Antonescu, Corina, Austin-Tse, Christina A., Bacus, Tamara J., Bahrambeigi, Vahid, Belmont, John W., Below, Jennifer E., Bilguvar, Kaya, Boehm, Corinne D., Boone, Philip M., Calame, Daniel, Cao, Xiaolong, Carvalho, Claudia, Chander, Varuna, Clarke, Declan, Delano, Kayla, Doddapaneni, Harshavardhan, Du, Renqian, Fatih, Jawid, Francioli, Laurent C., Fu, Jack, Gambin, Tomasz, Gandhi, Mira, Ganesh, Vijay S., Garimella, Kiran V., Gauthier, Laura D., Gonzaga-Jauregui, Claudia, Grochowski, Christopher M., Gu, Shen, Hansen, Adam, Harmanci, Arif O., Huang, Yongqing, Johanson, Eric, Karaca, Ender, Kumar, Sushant, Laricchia, Kristen M., Ling, Hua, Lipson, Rachel B., MacMillan, Melissa P., Marshall, Jamie L., Martin, Renan, McGee, Sean, Mekonnen, Betselote, Mullen, Thomas E., Murugan, Mullai, Muzny, Donna M., Myers, Ben, Neira, Juanita, Nielsen, Patrick M., Nudelman, Natalie, O’Leary, Melanie C., Pais, Lynn S., Patterson, Karynne, Pehlivan, Davut, Penney, Samantha, Pierce-Hoffman, Emma, Radhakrishnan, Aparna, Richardson, Matthew A., Roote, Gwendolin T., Sabo, Aniko, Scott, Daryl A., Shaw, Chad A., Shelford, Tameka, Shively, Kathryn M., Snow, Hana, Solomonson, Matthew, Song, Xiaofei, Stephan, Taylorlyn, Sutton, V. Reid, Sveden, Abigail, Valivullah, Zaheer, Wang, Lu, Wangler, Michael F., Watts, Nicholas A., Wilson, Michael W., Wiszniewski, Wojciech, Witmer, Dane, Witzgall, Lauren, Wohler, Elizabeth, Wu, Nan, Yi, Qian, Zeiger, Jordan E., Zhang, Chaofan, Zhang, Yeting, Zoghbi, Huda, van den Veyver, Igna, O’Donnell-Luria, Anne
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2022
• Subjects: Centers for Mendelian Genomics (CMG); Data sharing; Exome; Exome Sequencing; Genetic Association Studies; Genomics; Humans; Mendelian conditions; Novel gene-disease discovery; Phenotype; Rare disease tools; Centers for Mendelian Genomics (CMG); Novel gene-disease discovery; Data sharing; Mendelian conditions; Rare disease tools
• ISSN: 1098-3600; 1530-0366
• DOI: 10.1016/j.gim.2021.12.005

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. 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. 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. 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.