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Interspecies comparisons of functional genetic variations and their implications in neuropsychiatry

Authors

  • Martien J.H. Kas,

    Corresponding author
    1. Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands
    • Department of Neuroscience and Pharmacology, University Medical Centre Utrecht, Utrecht, The Netherlands.
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  • Cigdem Gelegen,

    1. Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands
    2. Institute of Psychiatry, Social, Genetic and Developmental Psychiatry Research Centre, King's College London, London, UK
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  • Leonard C. Schalkwyk,

    1. Institute of Psychiatry, Social, Genetic and Developmental Psychiatry Research Centre, King's College London, London, UK
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  • David A. Collier

    1. Institute of Psychiatry, Social, Genetic and Developmental Psychiatry Research Centre, King's College London, London, UK
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  • Please cite this article as follows: Kas MJH, Gelegen C, Schalkwyk LC, Collier DA. 2009. Interspecies Comparisons of Functional Genetic Variations and Their Implications in Neuropsychiatry. Am J Med Genet Part B 150B:309–317.

Abstract

Animal studies are important for the identification and functional characterization of the biological substrates underlying complex psychiatric disorders. However, novel insights into the relationship between the genome and behavior are needed for the development of fully valid translational models. Based on the notion that in different species, the same genes may independently give rise to alleles with similar functional and phenotypic effects, either under similar selection or through similar genomic mechanisms, we propose the use of genetic validity as a tool for identifying analogous pathology between animals and human neuropsychiatric disorders. Furthermore, the identification of copy number variants which disrupt entire genes, reinforces the notion that transgenic animals, such as knockouts or knock-ins, may provide unexpectedly valid disease models for psychiatric traits. To illustrate interspecies comparison of genetic variations in relation to neurobehavioral traits, examples are provided for the BDNF, COMT, and DISC1 genes in mouse and man. We propose that alignment of individual genetic variations with endophenotypes obtained from mice and across categories of neuropsychiatric disorders will provide an important step in translational research. © 2008 Wiley-Liss, Inc.

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