A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia
Author(s)
Skene, Nathan G
Roy, Marcia
Grant, Seth GN
Type
Journal Article
Abstract
The genetic mechanisms regulating the brain and behaviour across the lifespan are poorly understood. We found that lifespan transcriptome trajectories describe a calendar of gene regulatory events in the brain of humans and mice. Transcriptome trajectories defined a sequence of gene expression changes in neuronal, glial and endothelial cell-types, which enabled prediction of age from tissue samples. A major lifespan landmark was the peak change in trajectories occurring in humans at 26 years and in mice at 5 months of age. This species-conserved peak was delayed in females and marked a reorganization of expression of synaptic and schizophrenia-susceptibility genes. The lifespan calendar predicted the characteristic age of onset in young adults and sex differences in schizophrenia. We propose a genomic program generates a lifespan calendar of gene regulation that times age-dependent molecular organization of the brain and mutations that interrupt the program in young adults cause schizophrenia.
Date Issued
2017-09-12
Date Acceptance
2017-08-15
Citation
eLife, 2017, 6
ISSN
2050-084X
Publisher
eLife Sciences Publications Ltd
Journal / Book Title
eLife
Volume
6
Copyright Statement
© 2017 Skene et al. This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000410294200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biology
Life Sciences & Biomedicine - Other Topics
DE-NOVO MUTATIONS
DORSOLATERAL PREFRONTAL CORTEX
AGE-OF-ONSET
INTELLECTUAL DISABILITY
POSTSYNAPTIC DENSITY
CORTICAL DEVELOPMENT
SIGNALING COMPLEXES
BIPOLAR DISORDER
GENE-EXPRESSION
NMDA RECEPTORS
Publication Status
Published
Article Number
e17915
Date Publish Online
2017-09-12