Investigating Genetics of Human Natural Short Sleepers

研究人类自然短睡眠者的遗传学

• 批准号: 8898245
• 负责人: YING-HUI FU
• 金额: $ 44.42万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8898245
• 关键词: Affect; Alcohols; American; Animal Model; Arousal; Behavior; Binding; Bioinformatics; Biological; Caffeine; Candidate Disease Gene; Cell physiology; Cells; Cessation of life; Chemicals; Chronic; Circadian Rhythms; Code; Cognition; Collection; Complex; Data Set; Disadvantaged; Discipline; Disease; Employment; Epidemiology; Exons; Family; Foundations; Gene Mutation; Gene Structure; Genes; Genome; Health; Homeostasis; Hour; Human; Human Genetics; Immunity; Individual; Investigation; Investments; Knowledge; Lead; Left; Life; Life Style; Maintenance; Massive Parallel Sequencing; Metabolic syndrome; Metabolism; Methods; Molecular Probes; Morbidity - disease rate; Mus; Mutation; Open Reading Frames; Organism; Patient Self-Report; Pattern; Periodicity; Phenotype; Population; Price; Process; Proteins; Publications; Publishing; Regulation; Reporting; Research; Resources; Risk; Sampling; Schools; Sleep; Sleep Deprivation; Sleep Disorders; Societies; Socioeconomic Status; Surveys; Technology; Temperature; Ticks; Time; United States National Institutes of Health; Untranslated RNA; Variant; Wakefulness; Work; base; cancer risk; circadian pacemaker; cost; cost effective; dietary control; exome; exome sequencing; fly; genome sequencing; immune function; improved; mortality; motor control; novel; proband; screening; tool; transmission process

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.

描述（由申请人提供）： 睡眠是一种全球性的状态，其控制机制表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，再到生物体水平的表型。它们包括（但不限于）唤醒、运动控制、自主功能、行为和认知。我们生活在一个睡眠不足的社会。长期睡眠不足会损害体温控制、饮食代谢、免疫功能，最终导致死亡。睡眠不足会增加个体患癌症、代谢综合征、精神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学决定因素受到行为和其他因素的影响，包括生活方式的选择，社会经济地位，健康，就业，学校和外源性化学物质，如咖啡因和酒精。睡眠和昼夜节律功能是生物体中相互作用的不同过程。睡眠至少由两个过程控制：一个昼夜节律起搏器（时钟）以约24小时的周期滴答作响，以及一个在清醒期间增加并在睡眠期间消散的稳态驱动。尽管我们一生中大约有三分之一的时间处于睡眠状态，但我们对睡眠量的调节机制几乎一无所知。当我们发现一个独立的家庭对睡眠的生物需求大大减少时，一个独特的机会出现了。确定新的研究对象并扩大我们对这些家族的收集将为我们开始探索睡眠稳态的分子调节机制奠定基础。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、小鼠和苍蝇中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将成为我们解开神秘的睡眠相关机制的切入点。最终，结合多个基因、人类和模式生物的研究知识，将有助于更好地了解睡眠及其与健康和疾病的关系。