Sensory and developmental phenotyping of C. elegans parses autism associated genes into behavioural classifications

Differences in sensory processing and development are traits described by the diagnostic criteria for autism spectrum disorder (ASD). The inclusion of sensory processing has been accompanied by increased investigation of this criterion to better understand how autism risk genes bring about changes in sensory biology. The contribution of epigenetic modifiers to sensory and developmental phenotypes is of particular interest, given they represent genetically encoded signalling cascades that regulate the environments' ability to modulate gene expression. ~50% of the highest confidence genes ranked on the Simons Foundation Autism Research Institute (SFARI) can be classified as epigenetic modifiers, further highlighting the contribution of aberrant epigenetic function in shaping the landscape of ASD. Here, we utilise the model organism C. elegans to investigate epigenetic modifiers, their role in sensory and developmental biology and behavioural outcomes. C. elegans provides robust readouts for both developmental and sensory biology allowing phenotypic signatures of ASD to be systematically investigated. 52 epigenetic modifiers (65 strains) were selected for study in C. elegans based on gene function, presence of an orthologue in C. elegans and the availability of viable putative null strains. This identified significant changes to reproduction, gross development and sensory processing across the range of epigenetic modifiers. We identified subgroups of mutant strains with either impaired sensation or development, or both. This study provides a link between the ASD phenotypes of sensory impairment and developmental delay and suggests sensory testing in human cohorts can help to further refine sub-categorisation of heterogenous ASD cohorts.