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Moyses-Oliveira, Mariana; Yadav, Rachita; Erdin, Serkan; Talkowski, Michael E
Current opinion in genetics & development, December 2020, 2020-12-00, 20201201, Volume: 65Journal Article
•Exome sequencing on unprecedented scale has identified 400 genes associated with ASD and NDD.•Functional networks disrupted in NDD converge on distinct spatiotemporal expression patterns during early neurodevelopment.•There is growing evidence that genes involved in broad regulatory processes can alter synaptic function.•Signaling pathways and cytoskeleton dynamics may underlie convergent pathogenic mechanisms in ASD and NDD. Over the last two years, remarkable gene discovery efforts have implicated disruption of pathways involving gene regulatory functions and neuronal processes in autism spectrum disorder (ASD), and more broadly defined neurodevelopmental disorders (NDDs). Functional studies in the developing brain and across cell types demonstrate that the spatiotemporal expression patterns of many of these genes coalesce on subnetworks with distinct developmental trajectories. Here, we review the convergent biological processes derived from gene discovery and functional genomics in ASD and NDD from 2018−2020. We further probe the mechanistic insights that suggest these frequently perturbed pathways are interconnected and, ultimately, converge on specific functional deficits in human neurodevelopment.
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