Functional Neurogenomics to Dissect Disease Mechanisms Across Models.

Tremendous progress has been made in identifying genetic variants associated with neurodevelopmental disorders (NDDs), particularly autism spectrum disorder (ASD). However, the extensive (and growing) lists of associated genetic variants have led to a bottleneck in understanding the function of these genetic changes. To overcome this, functional genomics approaches-including high-throughput and high-content screens, in vivo Perturb-seq, and multiomics profiling-are being deployed across cellular and animal models at scale. Here, we first discuss recent findings on NDDs gleaned from human genetics studies. We then review recent technological advances and findings from functional neurogenomics in the context of ASD and other NDDs. Finally, we discuss how these methods might be applied in the future to refine efforts to identify convergent mechanisms impacted by multiple disease-associated genetic variants, as well as how they can advance the development of new therapeutic strategies.