DISC1 in Schizophrenia: Genetic Mouse Models and Human Genomic Imaging (original) (raw)

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1Department of Psychiatry, The Royal Edinburgh Hospital, Morningside Terrace, Edinburgh EH10 5HF, UK

2Medical Genetics Section, Institute of Genetics and Molecular Medicine, University of Edinburgh Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK

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2Medical Genetics Section, Institute of Genetics and Molecular Medicine, University of Edinburgh Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK

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1Department of Psychiatry, The Royal Edinburgh Hospital, Morningside Terrace, Edinburgh EH10 5HF, UK

2Medical Genetics Section, Institute of Genetics and Molecular Medicine, University of Edinburgh Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK

Search for other works by this author on:

,

1Department of Psychiatry, The Royal Edinburgh Hospital, Morningside Terrace, Edinburgh EH10 5HF, UK

2Medical Genetics Section, Institute of Genetics and Molecular Medicine, University of Edinburgh Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK

Search for other works by this author on:

,

1Department of Psychiatry, The Royal Edinburgh Hospital, Morningside Terrace, Edinburgh EH10 5HF, UK

Search for other works by this author on:

2Medical Genetics Section, Institute of Genetics and Molecular Medicine, University of Edinburgh Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK

Search for other works by this author on:

Published:

13 December 2010

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Mandy Johnstone, Pippa A. Thomson, Jeremy Hall, Andrew M. McIntosh, Stephen M. Lawrie, David J. Porteous, DISC1 in Schizophrenia: Genetic Mouse Models and Human Genomic Imaging, Schizophrenia Bulletin, Volume 37, Issue 1, January 2011, Pages 14–20, https://doi.org/10.1093/schbul/sbq135
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Abstract

Schizophrenia and related disorders have a major genetic component. Several large-scale studies have uncovered a number of possible candidate genes, but these have yet to be consistently replicated and their underlying biological function remains elusive. One exception is ‘Disrupted in schizophrenia 1’ (DISC1), a gene locus originally identified in a large Scottish family, showing a heavy burden of major mental illnesses associated with a balanced t(1;11)(q42.1;q14.3) chromosome translocation. Substantial genetic and biological research on DISC1 has been reported in the intervening 10 years: DISC1 is now recognized as a genetic risk factor for a spectrum of psychiatric disorders and DISC1 impacts on many aspects of central nervous system (CNS) function, including neurodevelopment, neurosignaling, and synaptic functioning. Evidence has emerged from genetic studies showing a relationship between DISC1 and quantitative traits, including working memory, cognitive aging, gray matter volume in the prefrontal cortex, and abnormalities in hippocampal structures and function. DISC1 interacts with numerous proteins also involved in neuronal migration, neurite outgrowth, cytoskeletal modulation, and signal transduction, some of which have been reported as independent genetic susceptibility factors for psychiatric morbidity. Here, we focus on the growing literature relating genetic variation in the DISC1 pathway to functional and structural studies of the brain in humans and in the mouse.

© The Author 2010. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Topic:

• signal transduction
• genes
• genome
• hippocampus
• mental disorders
• schizophrenia
• diagnostic imaging
• genetics
• mice
• genetic research
• nervous system development

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