Testing candidate genes for attention-deficit/hyperactivity disorder in fruit flies using a high throughput assay for complex behavior

Fruit flies are important model organisms for functional testing of candidate genes in multiple disciplines, including the study of human diseases. Here we use a high-throughput locomotor activity assay to test the response on activity behavior of gene disruption in Drosophila melanogaster. The aim was to investigate the impact of disruption of 14 candidate genes for human attention-deficit/hyperactivity disorder (ADHD) on fly behavior. By obtaining a range of correlated measures describing the space of variables for behavioral activity we show, that some mutants display similar phenotypic responses, and furthermore, that the genes disrupted in those mutants had common molecular functions; namely processes related to cGMP activity, cation channels and serotonin receptors. All but one of the candidate genes resulted in aberrant behavioral activity, suggesting involvement of these genes in behavioral activity in fruit flies. Results provide additional support for the investigated genes being risk candidate genes for ADHD in humans.果蝇是多学科领域中用于候选基因功能验证的重要模式生物，相关研究范畴涵盖人类疾病探究。本研究采用高通量运动活性检测实验，检测黑腹果蝇（Drosophila melanogaster）的基因敲除对其运动行为活性的影响，旨在探究人类注意缺陷与多动障碍（attention-deficit/hyperactivity disorder, ADHD）相关的14个候选基因的敲除对果蝇行为的调控效应。通过获取一系列可描述行为活性变量空间的相关测量指标，本研究证实部分突变体呈现出相似的表型响应；进一步分析发现，这些突变体中被敲除的基因具有共同的分子功能，即与环磷酸鸟苷（cGMP）活性、阳离子通道及5-羟色胺受体相关的生物学过程。除1个候选基因外，其余所有候选基因的敲除均导致果蝇行为活性异常，提示这些基因参与果蝇的行为活性调控。本研究结果为这些候选基因作为人类ADHD风险候选基因提供了进一步的学术佐证。