A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia.
Elife
; 62017 09 12.
Article
en En
| MEDLINE
| ID: mdl-28893375
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Esquizofrenia
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Encéfalo
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Regulación de la Expresión Génica
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Perfilación de la Expresión Génica
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Genómica
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Transcriptoma
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Adult
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Aged
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Animals
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Elife
Año:
2017
Tipo del documento:
Article
País de afiliación:
Reino Unido