School of Biological Sciences, Highfield Campus, University of Southampton, Southampton, United Kingdom.
PLoS One. 2021 May 27;16(5):e0243121. doi: 10.1371/journal.pone.0243121. eCollection 2021.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by a triad of behavioural impairments and includes disruption in social behaviour. ASD has a clear genetic underpinning and hundreds of genes are implicated in its aetiology. However, how single penetrant genes disrupt activity of neural circuits which lead to affected behaviours is only beginning to be understood and less is known about how low penetrant genes interact to disrupt emergent behaviours. Investigations are well served by experimental approaches that allow tractable investigation of the underpinning genetic basis of circuits that control behaviours that operate in the biological domains that are neuro-atypical in autism. The model organism C. elegans provides an experimental platform to investigate the effect of genetic mutations on behavioural outputs including those that impact social biology. Here we use progeny-derived social cues that modulate C. elegans food leaving to assay genetic determinants of social behaviour. We used the SAFRI Gene database to identify C. elegans orthologues of human ASD associated genes. We identified a number of mutants that displayed selective deficits in response to progeny. The genetic determinants of this complex social behaviour highlight the important contribution of synaptopathy and implicates genes within cell signalling, epigenetics and phospholipid metabolism functional domains. The approach overlaps with a growing number of studies that investigate potential molecular determinants of autism in C. elegans. However, our use of a complex, sensory integrative, emergent behaviour provides routes to enrich new or underexplored biology with the identification of novel candidate genes with a definable role in social behaviour.
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征是行为损伤的三联征，包括社交行为中断。ASD 有明确的遗传基础，有数百个基因与发病机制有关。然而，单一穿透性基因如何破坏导致异常行为的神经回路的活动，这才刚刚开始被理解，而关于低穿透性基因如何相互作用破坏新兴行为则知之甚少。实验方法非常适合研究能够控制在自闭症中神经异常的生物学领域的行为的潜在遗传基础的回路。模式生物秀丽隐杆线虫为研究遗传突变对行为输出的影响提供了一个实验平台，包括那些影响社交生物学的行为。在这里，我们使用后代衍生的社交线索来调节秀丽隐杆线虫的食物离开，以检测社交行为的遗传决定因素。我们使用 SAFRI 基因数据库来鉴定秀丽隐杆线虫与人自闭症相关基因的同源物。我们鉴定了一些在响应后代时表现出选择性缺陷的突变体。这种复杂社交行为的遗传决定因素突出了突触病的重要贡献，并暗示了细胞信号转导、表观遗传学和磷脂代谢功能域内的基因。该方法与越来越多的研究重叠，这些研究调查了秀丽隐杆线虫中自闭症的潜在分子决定因素。然而，我们使用复杂的、感觉综合的、新兴的行为，为识别在社交行为中具有明确作用的新的或研究不足的生物学提供了途径，从而确定新的候选基因。
