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Phenotypic plasticity and the epigenetics of human disease

Abstract

It is becoming clear that epigenetic changes are involved in human disease as well as during normal development. A unifying theme of disease epigenetics is defects in phenotypic plasticity — cells' ability to change their behaviour in response to internal or external environmental cues. This model proposes that hereditary disorders of the epigenetic apparatus lead to developmental defects, that cancer epigenetics involves disruption of the stem-cell programme, and that common diseases with late-onset phenotypes involve interactions between the epigenome, the genome and the environment. Increased understanding of epigenetic-disease mechanisms could lead to disease-risk stratification for targeted intervention and to targeted therapies.

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Figure 1: The nature of epigenetic lesions.
Figure 2: Beckwith–Wiedemann syndrome as an example of a monogenic disease that reveals mechanisms of normal epigenetic regulation.
Figure 3: Phenotypic plasticity and the epigenetics of human disease and ageing.
Figure 4: The epigenome at the intersection between environment and genetic variation.

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Acknowledgements

I thank H. Bjornsson, R. Ohlsson, T. Ekstrom, D. Gius and C. Ladd-Acosta for their many thoughtful insights, and J. Fairman for her artistry. This work was supported by a grant from the NIH.

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Feinberg, A. Phenotypic plasticity and the epigenetics of human disease. Nature 447, 433–440 (2007). https://doi.org/10.1038/nature05919

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