The parent-of-origin-dependent manner in which this subset of genes is expressed is tightly regulated through epigenetic processes, including DNA methylation at differentially methylated regions (DMRs), which directly affects the genes’ expression. The ways in which imprinted gene regulation might affect brain development could be either by disrupting regulation of nutrient acquisition, hormones, or fetal growth, or, more directly, by influenc­ing neuronal growth and pruning, or axonal sprouting and interconnections. IGF2, eg, plays a major role in balancing nutrients for growth across the placental membranes, and altered regulation may indirectly affect brain development by influencing the supply of nutrients during critical stages of development. Other imprinted genes, such as neuronatin (NNAT), may play a more direct role, as this imprinted gene has been implicated in regulation of ion channels during brain development.

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