Alterations in habituation, a highly conserved form of non-associative learning, are suspected to contribute to a range of the complex behavioural phenotypes present in multiple neurodevelopmental disorders. While progress has been made in understanding the genetics of these disorders through the application of next-generation sequencing and related technologies, the pathogenicity of genetic variants and causes of learning and memory impairments can be difficult to determine from sequencing data alone. High-throughput genetic model organisms such as the roundworm Caenorhabditis elegans, fruit fly Drosophila melanogaster, and zebrafish Danio rerio offer low-cost and efficient methods to investigate the functions of identified neurodevelopmental disorder risk genes and the functional consequences of specific disorder-associated variants. Here, we review ways assessing habituation has been used in the genotype-first approach to first validate neurodevelopmental disorder candidate genes and now to systematically characterize large candidate gene lists. We then discuss exciting ways habituation, in combination with other techniques, can be used as a tool to assess the pathogenicity of putative genes and genetic variants, uncover and confirm molecular networks, and identify potential therapeutic avenues.

中文翻译：

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在高通量遗传模型生物中的习性作为研究神经发育障碍机制的工具。

习惯性改变（一种高度保守的非联想学习形式）被怀疑会导致多种神经发育障碍中一系列复杂的行为表型。尽管已经通过下一代测序和相关技术的应用在了解这些疾病的遗传学方面取得了进展，但是仅通过测序数据就难以确定遗传变异的致病性以及学习和记忆障碍的原因。高通量遗传模型生物，例如the虫秀丽隐杆线虫，果蝇果蝇和斑马鱼Danio rerio，提供了低成本，有效的方法来研究已鉴定的神经发育障碍风险基因的功能以及与特定疾病相关的变异体的功能后果。这里，我们回顾了评估习惯性的方法已在基因型优先方法中用于首先验证神经发育障碍候选基因，现在来系统地表征大型候选基因列表。然后，我们讨论与其他技术结合使用的令人兴奋的方式，习惯化可以用作评估推定基因和遗传变异的致病性，发现和确认分子网络以及确定潜在治疗途径的工具。