Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network
Year: 2017
Type: article
Abstract: Neuropsychiatric disorders have a complex genetic architecture. Human genetic population-based studies have identified numerous heritable sequence and structural genomic variants associated with susceptibility to neuropsychiatric disease. However, these germline variants do not fully account for disease risk. During brain development, progenitor cells undergo billions of cell divisions to generate the ~80 billion neurons in the brain. The failure to accurately repair DNA damage arising during replication, transcription, and cellular metabolism amid this dramatic cellular expansion can lead to somatic mutations. Somatic mutations that alter subsets of neuronal transcriptomes and proteomes can, in turn, affect cell proliferation and survival and lead to neurodevelopmental disorders. The long life span of individual neurons and the direct relationship between neural circuits and behavior suggest that somatic mutations in small populations of neurons can significantly affect individual neurodevelopment. The Brain Somatic Mosaicism Network has been founded to study somatic mosaicism both in neurotypical human brains and in the context of complex neuropsychiatric disorders.
Source: Science
Authors: Michael J. McConnell, John V. Moran, Alexej Abyzov, Schahram Akbarian, Taejeong Bae, Isidro Cortes-Ciriano, Jennifer A. Erwin, Liana Fasching, Diane A. Flasch, Donald Freed, Javier Ganz, Andrew E. Jaffe, Kenneth Y. Kwan, Minseok Kwon, Michael A. Lodato, Ryan E. Mills, Apua C. M. Paquola, Rachel E. Rodin, Chaggai Rosenbluh, Nenad Sestan, Maxwell A. Sherman, Joo Heon Shin, Saera Song, Richard E. Straub, Jeremy Thorpe, Daniel R. Weinberger, Alexander E. Urban, Bo Zhou, Fred H. Gage, Thomas Lehner, Geetha Senthil, Christopher A. Walsh, Andrew Chess, Eric Courchesne, Joseph G. Gleeson, Jeffrey M. Kidd, Peter J. Park, Jonathan Pevsner, Flora M. Vaccarino, Brain Somatic Mosaicism Network, Alison R. Barton, Stefan Bekiranov, Craig L. Bohrson, Ian E. Burbulis, William Chronister, Gianfilippo Coppola, Kenneth Daily, Alissa M. D’Gama, Sarah B. Emery, Trenton J. Frisbie, Tianliuyun Gao, Attila Gulyás-Kovács, Mark Haakenson, Jason M. Keil, Huira C. Kopera, Mandy M. Lam, Eunjung Alice Lee, Tomas Marques-Bonet, Gary W. Mathern, John B. Moldovan, Matthew T. Oetjens, Larsson Omberg, Mette A. Peters, Sirisha Pochareddy, Tiziano Pramparo, Aakrosh Ratan, Tiziana Sanavia, Lei Shi, Mario Skarica, Jia Wang, Meiyan Wang, Yifan Wang, Margaret Wierman, Matthew Wolpert, Mollie Woodworth, Xuefang Zhao, Weichen Zhou
Institutions: University of Virginia Medical Center, University of Virginia, University of Michigan, Michigan Medicine, Mayo Clinic, Icahn School of Medicine at Mount Sinai, Harvard University, Salk Institute for Biological Studies, Yale University, Kennedy Krieger Institute, Johns Hopkins University, Johns Hopkins Medicine, Broad Institute, Boston Children's Hospital, Howard Hughes Medical Institute, Manton Center for Orphan Disease Research, Lieber Institute for Brain Development, University of California San Diego, Rockefeller University, Stanford Medicine, Stanford University, National Institutes of Health, National Institute of Mental Health
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: National Institutes of Health, National Institute on Aging, National Institute of Mental Health, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1027127931, G1044130170, G1077869373, G1965258318, G2851032130, G2901194989, G2922423489, G3105910846, G3179019324, G333256199, G362946481, G3703698255, G3881003010, G3891119071, 3/3-Schizophrenia Genetics and Brain Somatic Mosaicism, G458239709, G469079489, G5015292506, G5375661091, G5739803538, G5827989630, G5857194480, G6165620158, University of California San Diego Neuroscience Microscopy Imaging Core, Mosaicism in focal cortical dysplasias spectrum seen in neuropsychiatric disease, Developmental Functional Genomics in ASD Toddlers, G680976502, G6944132047, G707340384, G7111798235, G8010825012, University of Michigan Training Program in Genomic Science, Cancer Center Support Grant (CCSG), Yale Clinical and Translational Science Award, Fellowship in Geriatric Mental Health
OpenAlex ID: W2609808058