睡眠与睡眠障碍的遗传学
Genetics of sleep and sleep disorders.
机构信息
Howard Hughes Medical institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
出版信息
Cell. 2011 Jul 22;146(2):194-207. doi: 10.1016/j.cell.2011.07.004.
Sleep remains one of the least understood phenomena in biology--even its role in synaptic plasticity remains debatable. Since sleep was recognized to be regulated genetically, intense research has launched on two fronts: the development of model organisms for deciphering the molecular mechanisms of sleep and attempts to identify genetic underpinnings of human sleep disorders. In this Review, we describe how unbiased, high-throughput screens in model organisms are uncovering sleep regulatory mechanisms and how pathways, such as the circadian clock network and specific neurotransmitter signals, have conserved effects on sleep from Drosophila to humans. At the same time, genome-wide association studies (GWAS) have uncovered ∼14 loci increasing susceptibility to sleep disorders, such as narcolepsy and restless leg syndrome. To conclude, we discuss how these different strategies will be critical to unambiguously defining the function of sleep.
睡眠仍然是生物学中最不为人理解的现象之一——即使它在突触可塑性中的作用仍存在争议。由于睡眠被认为是受基因调控的，因此在两个方面展开了激烈的研究：开发用于破译睡眠分子机制的模式生物，以及试图确定人类睡眠障碍的遗传基础。在这篇综述中，我们描述了如何在模式生物中进行无偏、高通量的筛选，以揭示睡眠调节机制，以及生物钟网络和特定神经递质信号等途径如何从果蝇到人类对睡眠产生保守影响。与此同时，全基因组关联研究（GWAS）已经发现了约 14 个增加睡眠障碍易感性的基因座，如嗜睡症和不宁腿综合征。最后，我们讨论了这些不同的策略将如何对明确定义睡眠的功能起到关键作用。
Zotero 插件