Intra-individual Change Over Time in DNA Methylation With Familial Clustering

Abstract

Epigenetic marks are modifications of DNA or associated proteins, other than the DNA sequence itself, that are heritable through cell division. These include DNA methylation, a covalent modification of cytosine; histone modifications affecting the nucleosomes around which the DNA is coiled; and alterations in nucleosomal packing or higher-order folding of chromatin. We and others have suggested that epigenetics might play a role in the etiology of common human diseases.^1-3 In a recent review in JAMA by 1 of us (A.P.F.), it was noted that epigenetics stands at the epicenter of modern medicine because it unites nuclear reprogramming during development, environmentally induced changes on the body, and the ability of cells to respond appropriately to external stimuli.⁴ That is because epigenetic changes, unlike the DNA sequence, distinguish one tissue type from another and dietary and other environmental exposures alter the epigenetic program; the ability of genes to alter their expression is controlled by epigenetic factors such as DNA methylation.^5,6 Diseases in which epigenetic change has been shown to play a major role include cancer and some disorders of the immune system, and epigenetic defects may also contribute to chronic diseases such as diabetes, bipolar disorder, and autism and loss of normal responsiveness to stress that accompanies aging.^7-9