Epigenomic Mechanisms of Human Developmental Disorders

Abstract Human development, which begins with gametogenesis and continues through post-zygotic, embryonic, fetal, and postnatal stages, is a complicated biological process orchestrated by a cascade of gene expression networks and regulatory signals that temporally and spatially control cellular differentiation and morphogenesis. Epigenetic regulatory processes are key elements of this system. Disruption of epigenetic regulatory networks, if compatible with life, can result in dysmorphology as well as neurological and intellectual abnormalities, commonly referred to as developmental delays and intellectual disabilities (DD/ID). This chapter describes epigenomic mechanisms of DD/ID, including imprinting defects, trinucleotide repeat expansions, and dysfunctions in genes encoding epigenomic machinery proteins. Epigenomic involvement in complex and multifactorial developmental conditions, as well as the interactions between the genome and epigenome in the establishment of such disorders, are discussed. The chapter concludes with a review of technological advances in epigenome-based molecular screening and diagnostics of developmental conditions.