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

Brain Somatic Mosaicism Network

Research output: Contribution to journalArticle

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

Fingerprint

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

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

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

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

Research output: Contribution to journalArticle

@article{619990b7c30a4cccb316da5d56ef2e40,
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 = "{Brain Somatic Mosaicism Network} and 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.}",
year = "2017",
month = "4",
day = "28",
doi = "10.1126/science.aal1641",
language = "English (US)",
volume = "356",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6336",

}

TY - JOUR

T1 - Intersection of diverse neuronal genomes and neuropsychiatric disease

T2 - The Brain Somatic Mosaicism Network

AU - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85018280420&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018280420&partnerID=8YFLogxK

U2 - 10.1126/science.aal1641

DO - 10.1126/science.aal1641

M3 - Article

C2 - 28450582

AN - SCOPUS:85018280420

VL - 356

JO - Science

JF - Science

SN - 0036-8075

IS - 6336

M1 - 395

ER -