Structural variations, the regulatory landscape of the genome and their alteration in human disease

Authors

  • Malte Spielmann,

    1. Institute for Medical Genetics and Human Genetics, Charité – Universitätsmedizin Berlin, Berlin, Germany
    2. FG Development and Disease, Max-Planck-Institute for Molecular Genetics, Berlin, Germany
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  • Stefan Mundlos

    Corresponding author
    1. Institute for Medical Genetics and Human Genetics, Charité – Universitätsmedizin Berlin, Berlin, Germany
    2. FG Development and Disease, Max-Planck-Institute for Molecular Genetics, Berlin, Germany
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Abstract

High-throughput genomic technologies are revolutionizing human genetics. So far the focus has been on the 1.5% of the genome, which is coding, in spite of the fact that the great majority of genomic variants fall outside the coding regions. Recent efforts to annotate the non-coding sequence show that over 80% of the genome is biochemically active. The genome is divided into regulatory domains consisting of sequence regions that enhance and/or silence the expression of nearby genes and are, in some cases, separated by boundaries with insulator activity. In this paper, we review the recent advances in the identification of variations that influence gene regulation and their consequences for human disease. We hypothesize that structural variations outside of the coding genome can interfere with normal gene regulation by disrupting the regulatory landscape. Therefore, the regulatory landscape of the genome has also to be taken into consideration when investigating the pathology of human disease.

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