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. 2008 Apr 25;320(5875):539-43.
doi: 10.1126/science.1155174. Epub 2008 Mar 27.

Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia

Tom Walsh  1 , Jon M McClellan, Shane E McCarthy, Anjené M Addington, Sarah B Pierce, Greg M Cooper, Alex S Nord, Mary Kusenda, Dheeraj Malhotra, Abhishek Bhandari, Sunday M Stray, Caitlin F Rippey, Patricia Roccanova, Vlad Makarov, B Lakshmi, Robert L Findling, Linmarie Sikich, Thomas Stromberg, Barry Merriman, Nitin Gogtay, Philip Butler, Kristen Eckstrand, Laila Noory, Peter Gochman, Robert Long, Zugen Chen, Sean Davis, Carl Baker, Evan E Eichler, Paul S Meltzer, Stanley F Nelson, Andrew B Singleton, Ming K Lee, Judith L Rapoport, Mary-Claire King, Jonathan Sebat
Affiliations

Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia

Tom Walsh et al. Science. .

Abstract

Schizophrenia is a devastating neurodevelopmental disorder whose genetic influences remain elusive. We hypothesize that individually rare structural variants contribute to the illness. Microdeletions and microduplications >100 kilobases were identified by microarray comparative genomic hybridization of genomic DNA from 150 individuals with schizophrenia and 268 ancestry-matched controls. All variants were validated by high-resolution platforms. Novel deletions and duplications of genes were present in 5% of controls versus 15% of cases and 20% of young-onset cases, both highly significant differences. The association was independently replicated in patients with childhood-onset schizophrenia as compared with their parents. Mutations in cases disrupted genes disproportionately from signaling networks controlling neurodevelopment, including neuregulin and glutamate pathways. These results suggest that multiple, individually rare mutations altering genes in neurodevelopmental pathways contribute to schizophrenia.

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  • Gene mutations and cognitive delay.
    Leonard CM, Kuldau JM. Leonard CM, et al. Science. 2008 Aug 1;321(5889):640. doi: 10.1126/science.321.5889.640a. Science. 2008. PMID: 18669843 No abstract available.

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