An integrated clinical program and crowdsourcing strategy for genomic sequencing and Mendelian disease gene discovery
Year: 2018
Type: review
Abstract: Despite major progress in defining the genetic basis of Mendelian disorders, the molecular etiology of many cases remains unknown. Patients with these undiagnosed disorders often have complex presentations and require treatment by multiple health care specialists. Here, we describe an integrated clinical diagnostic and research program using whole-exome and whole-genome sequencing (WES/WGS) for Mendelian disease gene discovery. This program employs specific case ascertainment parameters, a WES/WGS computational analysis pipeline that is optimized for Mendelian disease gene discovery with variant callers tuned to specific inheritance modes, an interdisciplinary crowdsourcing strategy for genomic sequence analysis, matchmaking for additional cases, and integration of the findings regarding gene causality with the clinical management plan. The interdisciplinary gene discovery team includes clinical, computational, and experimental biomedical specialists who interact to identify the genetic etiology of the disease, and when so warranted, to devise improved or novel treatments for affected patients. This program effectively integrates the clinical and research missions of an academic medical center and affords both diagnostic and therapeutic options for patients suffering from genetic disease. It may therefore be germane to other academic medical institutions engaged in implementing genomic medicine programs.
Source: npj Genomic Medicine
Authors: Alireza Haghighi, Joel B. Krier, Agnes Toth-Petroczy, Christopher A. Cassa, Natasha Y. Frank, Nikkola Carmichael, Elizabeth Fieg, Andrew Bjonnes, Anwoy Mohanty, Lauren C. Briere, Sharyn Lincoln, Stephanie Lucia, Vandana A. Gupta, Onuralp Söylemez, Sheila Sutti, Kameron Kooshesh, Haiyan Qiu, Christopher J. Fay, Victoria Perroni, Jamie Valerius, Meredith Hanna, Alexander Frank, Jodie Ouahed, Scott B. Snapper, Angeliki Pantazi, Sameer S. Chopra, Ignaty Leshchiner, Nathan O. Stitziel, Anna Feldweg, Michael Mannstadt, Joseph Loscalzo, David A. Sweetser, Eric Liao, Joan M. Stoler, Catherine B. Nowak, Pedro A. Sanchez-Lara, Ophir D. Klein, Hazel Perry, Nikolaos A. Patsopoulos, Soumya Raychaudhuri, Wolfram Goessling, Robert C. Green, Christine E. Seidman, Calum A. MacRae, Shamil R. Sunyaev, Richard L. Maas, Dana Vuzman
Institutions: Broad Institute, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard University, Massachusetts Institute of Technology, Massachusetts General Hospital, Boston Children's Hospital, Dana-Farber Cancer Institute, Washington University in St. Louis, Boston Children's at Waltham, Cedars-Sinai Medical Center, University of California, Los Angeles, University of California, San Francisco, University of Manchester
Language: English
Topic: Genomics and Rare Diseases
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: U.S. Department of Health and Human Services, Leona M. and Harry B. Helmsley Charitable Trust, Crohn's and Colitis Foundation, National Institutes of Health, Brigham Research Institute, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Dental and Craniofacial Research
Awards: G1219793785, New methods and enhanced software for predicting functional SNPs, G3681705081, G3894996385, Center for Integrated Approached to Undiagnosed Diseases, G6696414317, Rapid Identification and Validation of Human Craniofacial Development Genes, G8283695447, G9000252305, Integrated Epithelial and Muscosal Biology, G932305573
OpenAlex ID: W2887339643