Genomic imprinting: a paradigm for epigenetics of human diseases

Genomic imprinting is a remarkable phenomenon through which certain genes show monoallelic expression depending on their parent of origin. While imprinting may have evolved for viviparity and potentially as a mechanism to balance resource allocation in mammals, functional haploidy presents a clear risk to human health. Both epigenetic and genetic and aberrations at imprinted loci contribute to genomic imprinting disorders, such as Beckwith–Wiedemann, Silver–Russell, Prader–Willi and Angelman syndromes. Beyond these well-documented disorders, changes in the tissue-specific expression levels of imprinted genes may contribute far more widely to human disease. The expression of imprinted genes can be disrupted at the level of a single gene, at the level of an imprinted domain or through changes in imprinted gene networks. Importantly, imprinted genes can respond to prenatal adversity leading to persistent changes in gene expression. Consequently, in addition to identifying the functions of individual imprinted genes, it is important to understand the mechanisms through which imprints are established, maintained and erased, with erasure critical to ensure comprehensive erasure of epimutations in the germline. We review the critical aspects of genomic imprinting and imprinted human diseases as a paradigm for future studies on epigenetics of human development and disease