Kepler Lexis D, McDiarmid Troy A, Rankin Catharine H
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2211 Wesbrook Mall, Vancouver, British Columbia V6T 2B5, Canada.
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2211 Wesbrook Mall, Vancouver, British Columbia V6T 2B5, Canada; Department of Psychology, University of British Columbia, 2136 West Mall, Vancouver, British Columbia V6T 1Z4, Canada.
Neurobiol Learn Mem. 2020 May;171:107208. doi: 10.1016/j.nlm.2020.107208. Epub 2020 Mar 5.
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.
习惯化是一种高度保守的非联想学习形式，其改变被怀疑与多种神经发育障碍中存在的一系列复杂行为表型有关。虽然通过应用下一代测序及相关技术在理解这些疾病的遗传学方面取得了进展，但仅从测序数据很难确定基因变异的致病性以及学习和记忆障碍的原因。高通量遗传模式生物，如线虫秀丽隐杆线虫、果蝇黑腹果蝇和斑马鱼斑马丹尼奥，提供了低成本且高效的方法来研究已确定的神经发育障碍风险基因的功能以及特定疾病相关变异的功能后果。在这里，我们回顾了在基因型优先方法中评估习惯化的方式，该方法最初用于验证神经发育障碍候选基因，现在则用于系统地表征大型候选基因列表。然后，我们讨论了习惯化与其他技术相结合的令人兴奋的方式，它可以用作评估推定基因和遗传变异的致病性、发现并确认分子网络以及确定潜在治疗途径的工具。
