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Genetic Variation in Long-Range Enhancers

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Behavioral Neurogenomics

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 42))

Abstract

Cis-regulatory elements (CREs), including insulators, promoters, and enhancers, play critical roles in the establishment and maintenance of normal cellular function. Within each cell, the 3D structure of chromatin is arranged in specific patterns to expose the CREs required for optimal spatiotemporal regulation of gene expression. CREs can act over large distances along the linear genome, facilitated by looping of the intervening chromatin to allow direct interaction between distal regulatory elements and their target genes. A number of pathologies are associated with dysregulation of CRE function, including developmental disorders, cancers, and neuropsychiatric disease. A majority of known neuropsychiatric disease risk loci are noncoding, and increasing evidence suggests that they contribute to disease through disruption of CREs. As such, rather than directly altering the amino acid content of proteins, these variants are instead thought to affect where, when, and to what extent a given gene is expressed. The distances over which CREs can operate often render their target genes difficult to identify. Furthermore, as many risk loci contain multiple variants in high linkage disequilibrium, identification of the causative single nucleotide polymorphism(s) therein is not straightforward. Thus, deciphering the genetic etiology of complex neuropsychiatric disorders presents a significant challenge.

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Authors and Affiliations

  1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    John F. Fullard & Panos Roussos

  2. Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    John F. Fullard, Samir Rahman & Panos Roussos

  3. Department of Genetics and Genomic Science and Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    John F. Fullard, Samir Rahman & Panos Roussos

  4. Mental Illness Research, Education, and Clinical Center (VISN 2 South), James J. Peters VA Medical Center, Bronx, NY, USA

    Panos Roussos

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  1. John F. Fullard
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  2. Samir Rahman
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  3. Panos Roussos
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Correspondence to Panos Roussos .

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Editors and Affiliations

  1. Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany

    Elisabeth B. Binder

  2. McLean Hospital, Harvard Medical School, Belmont, MA, USA

    Torsten Klengel

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Fullard, J.F., Rahman, S., Roussos, P. (2019). Genetic Variation in Long-Range Enhancers. In: Binder, E., Klengel, T. (eds) Behavioral Neurogenomics. Current Topics in Behavioral Neurosciences, vol 42. Springer, Cham. https://doi.org/10.1007/7854_2019_110

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