Functional testing of ASD-associated genes

There is a dire need for functional (causal) studies that move the field of neurodevelopmental disorders beyond statistical associations gleaned through genome-wide association studies (GWAS) and other “omic” approaches toward experimental manipulations of autism spectrum disorder (ASD)-associated genes and their genetic variants. ASDs are a genetically and phenotypically highly heterogeneous group of neurodevelopmental disorders with deficits in social interactions and communication, repetitive behaviors, and abnormalities in sensory processing (1). To date, >100 candidate genes and genetic variants are implicated in ASD through statistical associations, many of which are associated with other neurodevelopmental disorders. Functional tests of these ASD-associated genes can provide a means to uncover mechanisms involved in the underlying etiologies of ASD. One way forward is to test gene function in model systems. These include mammalian models such as nonhuman primates and mice and more simple high-throughput models such as zebrafish, Drosophila melanogaster, and Caenorhabditis elegans as well as human induced pluripotent stem cells and organoids along with postmortem brain samples. These models each have their advantages and disadvantages; however, the integration of findings from these models will provide insight into the mechanisms underlying ASD. In PNAS, McDiarmid et al. (2) report an elegant scalable, high-throughput pipeline to test functions of ASD-associated genes in the simple model organism, C. elegans.

↵¹Email: marla.sokolowski{at}utoronto.ca.