Academic Journal
Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network.
| Title: | Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network. |
|---|---|
| Authors: | Gulsuner S; Department of Medicine and Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA., Walsh T, Watts AC, Lee MK, Thornton AM, Casadei S, Rippey C, Shahin H, Nimgaonkar VL, Go RC, Savage RM, Swerdlow NR, Gur RE, Braff DL, King MC, McClellan JM |
| Source: | Cell [Cell] 2013 Aug 01; Vol. 154 (3), pp. 518-29. |
| Abstract: | Genes 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. (Copyright © 2013 Elsevier Inc. All rights reserved.) |
| Corporate Authors: | Consortium on the Genetics of Schizophrenia (COGS), PAARTNERS Study Group |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE |
| Imprint Name(s): | Publication: Cambridge, Ma : Cell Press Original Publication: Cambridge, MIT Press. |
| MeSH Terms: | Gene Regulatory Networks* , Mutation* , Protein Interaction Maps*, Prefrontal Cortex/*embryology , Schizophrenia/*genetics , Schizophrenia/*metabolism, Brain/embryology ; Brain/growth & development ; Brain/metabolism ; DNA Mutational Analysis ; Databases, Genetic ; Female ; Humans ; Male ; Neurogenesis ; Prefrontal Cortex/growth & development ; Prefrontal Cortex/metabolism ; Schizophrenia/physiopathology ; Transcription, Genetic ; Transcriptome |
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| Grant Information: | R03TW008696 United States TW FIC NIH HHS; R01MH083989 United States MH NIMH NIH HHS; R01 MH083849 United States MH NIMH NIH HHS; R01 MH083989 United States MH NIMH NIH HHS; R01MH083849 United States MH NIMH NIH HHS; R01MH084071 United States MH NIMH NIH HHS; R03 TW008696 United States TW FIC NIH HHS; R01MH083756 United States MH NIMH NIH HHS; R01 MH083756 United States MH NIMH NIH HHS; R01 MH086135 United States MH NIMH NIH HHS; R01 MH084071 United States MH NIMH NIH HHS; U01 MH096844 United States MH NIMH NIH HHS; R01 MH093533 United States MH NIMH NIH HHS; R01 CA157744 United States CA NCI NIH HHS; T32 GM007266 United States GM NIGMS NIH HHS |
| Contributed Indexing: | Investigator: D Braff; KS Cadenhead; ME Calkins; DJ Dobie; R Freedman; M Green; T Greenwood; RE Gur; RC Gur; L Lazzeroni; G Light; K Nuechterlein; A Olincy; A Radant; A Ray; N Schork; LJ Seidman; L Siever; J Silverman; WS Stone; C Sugar; N Swerdlow; D Tsuang; M Tsuang; B Turetsky; T Aduroja; T Allen; LD Bradford; ME Calkins; B Devlin; NB Edwards; R Ganguli; RC Go; RE Gur; RC Gur; J Kwentus; AC Lahti; P Lyons; K Mathos; R May; S McLeod-Bryant; JP McEvoy; L Montgomery-Barefield; VL Nimgaonkar; J O'Jile; A Santos; RM Savage; CL Swanson; W Wilson |
| Entry Date(s): | Date Created: 20130806 Date Completed: 20131028 Latest Revision: 20220316 |
| Update Code: | 20240513 |
| PubMed Central ID: | PMC3894107 |
| DOI: | 10.1016/j.cell.2013.06.049 |
| PMID: | 23911319 |
| ISSN: | 1097-4172 |
| DOI: | 10.1016/j.cell.2013.06.049 |
| Database: | MEDLINE |