Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network

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 & 20 others 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,

Research output: Contribution to journalArticle

Abstract

Neuropsychiatric disorders have a complex genetic architecture. Human genetic populationbased 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 somaticmutations 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.

Original languageEnglish (US)
Article number395
JournalScience
Volume356
Issue number6336
DOIs
StatePublished - Apr 28 2017
Externally publishedYes

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Mosaicism
Brain Diseases
Genome
Brain
Neurons
Mutation
Genomic Structural Variation
Medical Genetics
Proteome
Transcriptome
Cell Division
DNA Damage
Cell Survival
Stem Cells
Cell Proliferation

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

McConnell, M. J., Moran, J. V., Abyzov, A., Akbarian, S., Bae, T., Cortes-Ciriano, I., ... Brain Somatic Mosaicism Network (2017). Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network. Science, 356(6336), [395]. DOI: 10.1126/science.aal1641

Intersection of diverse neuronal genomes and neuropsychiatric disease : The Brain Somatic Mosaicism Network. / McConnell, Michael J.; Moran, John V.; Abyzov, Alexej; Akbarian, Schahram; Bae, Taejeong; Cortes-Ciriano, Isidro; Erwin, Jennifer A.; Fasching, Liana; Flasch, Diane A.; Freed, Donald; Ganz, Javier; Jaffe, Andrew E.; Kwan, Kenneth Y.; Kwon, Minseok; Lodato, Michael A.; Mills, Ryan E.; Paquola, Apua C.M.; Rodin, Rachel E.; Rosenbluh, Chaggai; Sestan, Nenad; Sherman, Maxwell A.; Shin, Joo Heon; Song, Saera; Straub, Richard E.; Thorpe, Jeremy; Weinberger, Daniel R.; Urban, Alexander E.; Zhou, Bo; Gage, Fred H.; Lehner, Thomas; Senthil, Geetha; Walsh, Christopher A.; Chess, Andrew; Courchesne, Eric; Gleeson, Joseph G.; Kidd, Jeffrey M.; Park, Peter J.; Pevsner, Jonathan; Vaccarino, Flora M.; Brain Somatic Mosaicism Network.

In: Science, Vol. 356, No. 6336, 395, 28.04.2017.

Research output: Contribution to journalArticle

McConnell, MJ, Moran, JV, Abyzov, A, Akbarian, S, Bae, T, Cortes-Ciriano, I, Erwin, JA, Fasching, L, Flasch, DA, Freed, D, Ganz, J, Jaffe, AE, Kwan, KY, Kwon, M, Lodato, MA, Mills, RE, Paquola, ACM, Rodin, RE, Rosenbluh, C, Sestan, N, Sherman, MA, Shin, JH, Song, S, Straub, RE, Thorpe, J, Weinberger, DR, Urban, AE, Zhou, B, Gage, FH, Lehner, T, Senthil, G, Walsh, CA, Chess, A, Courchesne, E, Gleeson, JG, Kidd, JM, Park, PJ, Pevsner, J, Vaccarino, FM & Brain Somatic Mosaicism Network 2017, 'Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network' Science, vol 356, no. 6336, 395. DOI: 10.1126/science.aal1641
McConnell MJ, Moran JV, Abyzov A, Akbarian S, Bae T, Cortes-Ciriano I et al. Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network. Science. 2017 Apr 28;356(6336). 395. Available from, DOI: 10.1126/science.aal1641

McConnell, Michael J.; Moran, John V.; Abyzov, Alexej; Akbarian, Schahram; Bae, Taejeong; Cortes-Ciriano, Isidro; Erwin, Jennifer A.; Fasching, Liana; Flasch, Diane A.; Freed, Donald; Ganz, Javier; Jaffe, Andrew E.; Kwan, Kenneth Y.; Kwon, Minseok; Lodato, Michael A.; Mills, Ryan E.; Paquola, Apua C.M.; Rodin, Rachel E.; Rosenbluh, Chaggai; Sestan, Nenad; Sherman, Maxwell A.; Shin, Joo Heon; Song, Saera; Straub, Richard E.; Thorpe, Jeremy; Weinberger, Daniel R.; Urban, Alexander E.; Zhou, Bo; Gage, Fred H.; Lehner, Thomas; Senthil, Geetha; Walsh, Christopher A.; Chess, Andrew; Courchesne, Eric; Gleeson, Joseph G.; Kidd, Jeffrey M.; Park, Peter J.; Pevsner, Jonathan; Vaccarino, Flora M.; Brain Somatic Mosaicism Network / Intersection of diverse neuronal genomes and neuropsychiatric disease : The Brain Somatic Mosaicism Network.

In: Science, Vol. 356, No. 6336, 395, 28.04.2017.

Research output: Contribution to journalArticle

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