Harbison Susan T, Carbone Mary Anna, Ayroles Julien F, Stone Eric A, Lyman Richard F, Mackay Trudy F C
Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA.
Nat Genet. 2009 Mar;41(3):371-5. doi: 10.1038/ng.330. Epub 2009 Feb 22.
Sleep disorders are common in humans, and sleep loss increases the risk of obesity and diabetes. Studies in Drosophila have revealed molecular pathways and neural tissues regulating sleep; however, genes that maintain genetic variation for sleep in natural populations are unknown. Here, we characterized sleep in 40 wild-derived Drosophila lines and observed abundant genetic variation in sleep architecture. We associated sleep with genome-wide variation in gene expression to identify candidate genes. We independently confirmed that molecular polymorphisms in Catsup (Catecholamines up) are associated with variation in sleep and that P-element mutations in four candidate genes affect sleep and gene expression. Transcripts associated with sleep grouped into biologically plausible genetically correlated transcriptional modules. We confirmed co-regulated gene expression using P-element mutants. Quantitative genetic analysis of natural phenotypic variation is an efficient method for revealing candidate genes and pathways.
睡眠障碍在人类中很常见，睡眠不足会增加肥胖和糖尿病的风险。对果蝇的研究揭示了调节睡眠的分子途径和神经组织；然而，在自然种群中维持睡眠遗传变异的基因尚不清楚。在这里，我们对40个野生果蝇品系的睡眠进行了表征，并观察到睡眠结构中存在丰富的遗传变异。我们将睡眠与全基因组基因表达变异相关联，以确定候选基因。我们独立证实，Catsup（儿茶酚胺上调）中的分子多态性与睡眠变异相关，并且四个候选基因中的P元素突变会影响睡眠和基因表达。与睡眠相关的转录本聚集在生物学上合理的基因相关转录模块中。我们使用P元素突变体证实了共调控的基因表达。对自然表型变异进行数量遗传学分析是揭示候选基因和途径的有效方法。
