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Imprinted Genes Implicated in the Puzzle of Autism

28 July 2015: FOXG1 is potentially involved in the development of autism spectrum disorder (ASD). In a recent study, Dr. Vaccarino and her colleagues at Yale University used a novel 3D organoid culture of human neural cells that were derived from induced pluripotent stem cells (iPSCs) obtained from the skin cells of people with and without severe idiopathic ASD. This study provides evidence that FOXG1 overexpression, rather than gene mutation, induces a GABAergic neuron fate that functions as a developmental precursor to ASD. DLGAP2, the other gene listed in the accompanying graphic, has also been implicated in the development of autism in a copy number variation (CNV) analysis of people with ASD. Interestingly, there is strong evidence that both of these genes are imprinted and expressed from the paternal allele (Luedi et al. 2007), as predicted by Christopher Badcock and Bernard Crespi in their imprinted brain theory.

Imprinted genes are monoallelically expressed in a parent-of-origin dependent manner. Since the nonfunctional copy is silenced epigenetically, environmental factors that alter the epigenome can result in what is called loss of imprinting (LOI). This results in imprinted genes being either hypo or hyper expressed because of alterations in the epigenome (e.g. DNA methylation) rather than mutations in the genome. To determine the overall role of imprinting in the puzzle of ASD requires the identification of the complete repertoire of human imprinted genes and their regulatory elements - The Imprintome. Although this information is presently not available, it is crucial to determine now if the expression of FOXG1 and/or DLGAP2 are epigenetically dysregulated in ASD.