EPIGENETICS IN DISEASE LEADER OR FOLLOWER PDF

Epub Jul 1. Epigenetics in disease: leader or follower? Epigenetic silencing is a pervasive mode of gene regulation in multicellular eukaryotes: stable differentiation of somatic cell types requires the maintenance of subsets of genes in an active or silent state. The variety of molecules involved, and the requirement for active maintenance of epigenetic states, creates the potential for errors on a large scale.

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Epub Jul 1. Epigenetics in disease: leader or follower? Epigenetic silencing is a pervasive mode of gene regulation in multicellular eukaryotes: stable differentiation of somatic cell types requires the maintenance of subsets of genes in an active or silent state. The variety of molecules involved, and the requirement for active maintenance of epigenetic states, creates the potential for errors on a large scale. When epigenetic errors - or epimutations - activate or inactivate a critical gene, they may cause disease.

An epimutation that occurs in the germline or early embryo can affect all, or most, of the soma and phenocopy genetic disease. But the stochastic and reversible nature of epigenetic phenomena predicts that epimutations are likely to be mosaic and inherited in a nonmendelian manner; epigenetic diseases will thus rarely behave in the comfortably predictable manner of genetic diseases but will display variable expressivity and complex patterns of inheritance.

Much phenotypic variation and common disease might be explained by epigenetic variation and aberration.

The known examples of true epigenetic disease are at present limited, but this may reflect only the difficulty in distinguishing causal epigenetic aberrations from those that are merely consequences of disease, a challenge further extended by the impact of environmental agents on epigenetic mechanisms. The rapidly developing molecular characterization of epigenomes, and the new ability to survey epigenetic marks on whole genomes, may answer many questions about the causal role of epigenetics in disease; these answers have the potential to transform our understanding of human disease.

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Epigenetics in disease: leader or follower?

David I. Martin,1 Jennifer E. Cropley2 and Catherine M. Epigenetic phe- or silent state. The variety of molecules nomena typically involve stable silencing involved, and the requirement for active of a gene or a gene regulatory element, or maintenance of epigenetic states, creates an equilibrium between silent and active the potential for errors on a large scale. When epigenetic errors—or epimuta- tions—activate or inactivate a critical gene, they may cause disease.

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EPIGENETICS IN DISEASE LEADER OR FOLLOWER PDF

Samuhn Citations Publications citing this paper. This hypothesis may be contrasted with ately large effect on phenotype if they foklower in a relevant organ in the case of LDL-R, the liver. In most cases the cause provides a clear example in which epi- environmental agents. Aberrations A Prototype for Epigenetic discuss how epigenetic aberrations may of imprinting are examples of epimuta- Disease Causality result in disease, how epigenetic mosa- tion and, in some cases they may be pure icism can modulate disease risk, and how epimutations i.

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