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Dysfunctional gene splicing as a potential contributor to neuropsychiatric disorders

Authors

  • Stephen J. Glatt,

    Corresponding author
    1. Psychiatric Genetic Epidemiology & Neurobiology Laboratory (PsychGENe Lab), Departments of Psychiatry and Behavioral Sciences & Neuroscience and Physiology, Medical Genetics Research Center, SUNY Upstate Medical University, Syracuse, New York
    • SUNY Upstate Medical University, 750 East Adams Street, Weiskotten Hall, Room 3283, Syracuse, NY 13210.
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  • Ori S. Cohen,

    1. Psychiatric Genetic Epidemiology & Neurobiology Laboratory (PsychGENe Lab), Departments of Psychiatry and Behavioral Sciences & Neuroscience and Physiology, Medical Genetics Research Center, SUNY Upstate Medical University, Syracuse, New York
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  • Stephen V. Faraone,

    1. Psychiatric Genetic Epidemiology & Neurobiology Laboratory (PsychGENe Lab), Departments of Psychiatry and Behavioral Sciences & Neuroscience and Physiology, Medical Genetics Research Center, SUNY Upstate Medical University, Syracuse, New York
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  • Ming T. Tsuang

    1. Center for Behavioral Genomics, Department of Psychiatry, Institute of Genomic Medicine, University of California, San Diego, California
    2. Veterans Affairs San Diego Healthcare System, San Diego, California
    3. Harvard Institute of Psychiatric Epidemiology and Genetics, Harvard Departments of Epidemiology and Psychiatry, Boston, Massachusetts
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  • Stephen V. Faraone and Ming T. Tsuang contributed equally to the work.

  • How to cite this article: Glatt SJ, Cohen OS, Faraone SV, Tsuang MT. 2011. Dysfunctional Gene Splicing as a Potential Contributor to Neuropsychiatric Disorders. Am J Med Genet Part B 156:382–392.

Abstract

Alternative pre-mRNA splicing is a major mechanism by which the proteomic diversity of eukaryotic genomes is amplified. Much akin to neuropsychiatric disorders themselves, alternative splicing events can be influenced by genetic, developmental, and environmental factors. Here, we review the evidence that abnormalities of splicing may contribute to the liability toward these disorders. First, we introduce the phenomenon of alternative splicing and describe the processes involved in its regulation. We then review the evidence for specific splicing abnormalities in a wide range of neuropsychiatric disorders, including psychotic disorders (schizophrenia), affective disorders (bipolar disorder and major depressive disorder), suicide, substance abuse disorders (cocaine abuse and alcoholism), and neurodevelopmental disorders (autism). Next, we provide a theoretical reworking of the concept of “gene-focused” epidemiologic and neurobiologic investigations. Lastly, we suggest potentially fruitful lines for future research that should illuminate the nature, extent, causes, and consequences of alternative splicing abnormalities in neuropsychiatric disorders. © 2011 Wiley-Liss, Inc.

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