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The Neuroepigenome: Implications of Chemical and Physical Modifications of Genomic DNA in Schizophrenia

  • Kiran Girdhar
    Affiliations
    Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, New York

    Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York

    Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, New York
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  • Samir Rahman
    Affiliations
    Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, New York

    Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York

    Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, New York
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  • Pengfei Dong
    Affiliations
    Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, New York

    Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York

    Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, New York
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  • John F. Fullard
    Affiliations
    Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, New York

    Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York

    Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, New York
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  • Panos Roussos
    Correspondence
    Address correspondence to Panos Roussos, M.D., Ph.D.
    Affiliations
    Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, New York

    Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York

    Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, New York

    Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York

    Mental Illness Research Education and Clinical Center, James J. Peters VA Medical Center, Bronx, New York
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      Abstract

      Schizophrenia is a chronic mental illness with a substantial genetic component. To unfold the complex etiology of schizophrenia, it is important to understand the interplay between genetic and nongenetic factors. Genetic factors involve variation in the DNA sequences of protein-coding genes, which directly contribute to phenotypic traits, and variation in noncoding sequences, which comprise 98% of the genome and contain DNA elements known to play a role in regulating gene expression. The epigenome refers to the chemical modifications on both DNA and the structural proteins that package DNA into the nucleus, which together regulate gene expression in specific cell types, conditions, and developmental stages. The dynamic nature of the epigenome makes it an ideal tool to investigate the relationship between inherited genetic mutations associated with schizophrenia and altered gene regulation throughout the course of brain development. In this review, we focus on the current understanding of the role of epigenetic marks and their three-dimensional nuclear organization in the developmental trajectory of distinct brain cell types to decipher the complex gene regulatory mechanisms that are disrupted in schizophrenia.

      Keywords

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