Investigating Genetics of Human Natural Short Sleepers

描述(由申请人提供)： 睡眠是一种全球状态，其控制机制体现在生物组织的各个层面--从基因和细胞内机制，到细胞群体网络，再到生物水平的表型。它们包括(但不限于)唤醒、运动控制、自主神经功能、行为和认知。我们生活在一个睡眠不足的社会。长期失眠会损害体温控制、饮食代谢和免疫功能，最终导致死亡。睡眠不足会增加个人患癌症、代谢综合征、精神疾病和其他疾病的风险。了解人类睡眠的生物学基础是一个极其困难的挑战，因为我们睡眠的生物决定因素受到行为和其他因素的影响，包括生活方式选择、社会经济地位、健康、就业、学校以及咖啡因和酒精等外源化学物质。睡眠和昼夜节律功能是生命有机体中相互作用的不同过程。睡眠至少由两个过程控制：一个昼夜节律的起搏器(时钟)以大约24小时的周期滴答作响，以及一个在清醒时增加、在睡眠中消散的动态平衡驱动。尽管我们一生中约有三分之一的时间是在睡眠状态中度过的，但我们对睡眠质量的调节机制几乎一无所知。当我们发现生理上睡眠需求大幅减少的独立家庭时，一个独特的机会出现了。识别新的受试者并扩大这些家族的集合将为我们开始探索睡眠稳态的分子调控机制奠定基础。最近，我们报道了导致这种短睡眠表型的第一个突变。有趣的是，这种突变在人类、小鼠和苍蝇身上产生了类似的短睡眠表型。因此，这项研究中发现的所有基因都将成为我们解开与睡眠相关的谜团机制的切入点。归根结底，将多个基因、人类和模型生物研究的知识结合起来，将有助于更好地理解睡眠及其与健康和疾病的关系。

DESCRIPTION (provided by applicant): Sleep is a global state and its control mechanisms are manifested at every level of biological organization- from genes and intracellular mechanisms, to networks of cell populations, to phenotypes at the organismal level. They include (but are not limited to) arousal, motor control, autonomic function, behavior, and cognition. We live in a sleep deprived society. Prolonged sleep loss impairs temperature control, dietary metabolism, immune function, and eventually leads to death. Sleep deprivation increases an individual's risk of cancer, metabolic syndrome, psychiatric, and other disorders. Understanding the biological basis of sleep in humans is an extremely difficult challenge since the biological determinants of our sleep are affected by behavior and other factors including life-style choices, socio-economic status, health, employment, school, and exogenous chemicals like caffeine and alcohol. Sleep and circadian function are distinct processes that interact in living organisms. Sleep is controlled by at least two processes: a circadian pacemaker (the clock) ticking with periodicity of ~24 hours, and a homeostatic drive that increases during wakefulness and dissipates during sleep. Despite of the fact that we spend around one third of our life in the state of sleep, we understand almost nothing about regulatory mechanisms governing sleep quantity. A unique opportunity presented itself when we identified independent families with a dramatically reduced biological need for sleep. Identification of new subjects and expanding our collection of these families will establish a foundation for us to begin probing the molecular regulatory mechanisms of sleep homeostasis. Recently, we reported the first mutation that causes this short-sleep phenotype. Interestingly, this mutation gave a similar short sleep phenotype in human, mouse, and fly. All the genes identified in this study will therefore become entry points for us to unravel the enigmatic sleep related mechanisms. Ultimately, combining the knowledge from studies in multiple genes and in humans and model organisms will lead to a better understanding of sleep and its relationship to health and disease.