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.

中文翻译：

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调查秀丽隐杆线虫的自闭症相关基因揭示了候选人在社交行为中的作用

自闭症谱系障碍（ASD）是一种神经发育障碍，其特征是三项行为受损，包括社交行为中断。ASD具有明确的遗传基础，其病因涉及数百个基因。然而，单个渗透基因如何破坏导致受影响行为的神经回路活动只是开始被人们所了解，而关于低渗透基因如何相互作用以破坏新出现的行为的了解还很少。通过实验方法可以很好地完成调查工作，这些方法可以对控制自闭症神经非典型生物学区域内行为的电路的基础遗传学基础进行深入研究。模型生物线虫提供了一个实验平台，以研究遗传突变对行为输出（包括那些影响社会生物学的行为）的影响。在这里，我们使用子代来源的社会线索来调节秀丽隐杆线虫的食物离开，以分析社会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人类ASD相关基因的直向同源物。我们确定了许多突变体，显示出对子代的选择性缺陷。这种复杂的社会行为的遗传决定因素突出了突触病的重要贡献，并将基因牵连到细胞信号传导，表观遗传学和磷脂代谢功能域中。该方法与越来越多的研究秀丽隐线虫自闭症潜在分子决定因素的研究重叠。然而，我们对复杂的，感觉统合的，新出现的行为的使用为鉴定新的候选基因提供了途径，以丰富新的或未开发的生物学，这些候选基因在社会行为中具有明确的作用。