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Spatial and Temporal Mapping of De Novo Mutations in Schizophrenia to a Fetal Prefrontal Cortical Network
- Source :
- Cell. 154:518-529
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- SummaryGenes disrupted in schizophrenia may be revealed by de novo mutations in affected persons from otherwise healthy families. Furthermore, during normal brain development, genes are expressed in patterns specific to developmental stage and neuroanatomical structure. We identified de novo mutations in persons with schizophrenia and then mapped the responsible genes onto transcriptome profiles of normal human brain tissues from age 13 weeks gestation to adulthood. In the dorsolateral and ventrolateral prefrontal cortex during fetal development, genes harboring damaging de novo mutations in schizophrenia formed a network significantly enriched for transcriptional coexpression and protein interaction. The 50 genes in the network function in neuronal migration, synaptic transmission, signaling, transcriptional regulation, and transport. These results suggest that disruptions of fetal prefrontal cortical neurogenesis are critical to the pathophysiology of schizophrenia. These results also support the feasibility of integrating genomic and transcriptome analyses to map critical neurodevelopmental processes in time and space in the brain.
- Subjects :
- Male
Ventrolateral prefrontal cortex
Transcription, Genetic
Neurogenesis
DNA Mutational Analysis
Gene regulatory network
Prefrontal Cortex
Biology
Article
General Biochemistry, Genetics and Molecular Biology
Transcriptome
03 medical and health sciences
0302 clinical medicine
Databases, Genetic
Transcriptional regulation
medicine
Humans
Gene Regulatory Networks
Protein Interaction Maps
Prefrontal cortex
Gene
030304 developmental biology
Genetics
0303 health sciences
Biochemistry, Genetics and Molecular Biology(all)
Brain
Human brain
medicine.anatomical_structure
Mutation
Schizophrenia
Female
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 00928674
- Volume :
- 154
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....0b6b6e7138d7338531a9411bfa3e6f10