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; 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

doi:10.1126/science.aal1641

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 SestanMaxwell 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

Research output: Contribution to journal › Article › peer-review

191 Citations (Scopus)

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 language	English
Article number	395
Number of pages	10
Journal	Science
Volume	356
Issue number	6336
DOIs	https://doi.org/10.1126/science.aal1641
Publication status	Published - 28 Apr 2017
Externally published	Yes

Bibliographical note

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© Copyright 2016 by the American Association for the Advancement of Science.

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McConnell, M. J., Moran, J. V., Abyzov, A., Akbarian, S., Bae, T., Cortes-Ciriano, I., Erwin, J. A., Fasching, L., Flasch, D. A., Freed, D., Ganz, J., Jaffe, A. E., Kwan, K. Y., Kwon, M., Lodato, M. A., Mills, R. E., Paquola, A. C. M., Rodin, R. E., Rosenbluh, C., ... Brain Somatic Mosaicism Network (2017). Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network. Science, 356(6336), Article 395. https://doi.org/10.1126/science.aal1641

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title = "Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network",

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.",

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

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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. https://doi.org/10.1126/science.aal1641

TY - JOUR

T1 - Intersection of diverse neuronal genomes and neuropsychiatric disease

T2 - The Brain Somatic Mosaicism Network

AU - McConnell, Michael J.

AU - Moran, John V.

AU - Abyzov, Alexej

AU - Akbarian, Schahram

AU - Bae, Taejeong

AU - Cortes-Ciriano, Isidro

AU - Erwin, Jennifer A.

AU - Fasching, Liana

AU - Flasch, Diane A.

AU - Freed, Donald

AU - Ganz, Javier

AU - Jaffe, Andrew E.

AU - Kwan, Kenneth Y.

AU - Kwon, Minseok

AU - Lodato, Michael A.

AU - Mills, Ryan E.

AU - Paquola, Apua C.M.

AU - Rodin, Rachel E.

AU - Rosenbluh, Chaggai

AU - Sestan, Nenad

AU - Sherman, Maxwell A.

AU - Shin, Joo Heon

AU - Song, Saera

AU - Straub, Richard E.

AU - Thorpe, Jeremy

AU - Weinberger, Daniel R.

AU - Urban, Alexander E.

AU - Zhou, Bo

AU - Gage, Fred H.

AU - Lehner, Thomas

AU - Senthil, Geetha

AU - Walsh, Christopher A.

AU - Chess, Andrew

AU - Courchesne, Eric

AU - Gleeson, Joseph G.

AU - Kidd, Jeffrey M.

AU - Park, Peter J.

AU - Pevsner, Jonathan

AU - Vaccarino, Flora M.

AU - Brain Somatic Mosaicism Network

PY - 2017/4/28

Y1 - 2017/4/28

N2 - 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.

AB - 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.

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DO - 10.1126/science.aal1641

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SN - 0036-8075

VL - 356

JO - Science

JF - Science

IS - 6336

M1 - 395

ER -

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

Abstract

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