Investigating Genetics of Human Natural Short Sleepers

研究人类自然短睡眠者的遗传学

• 批准号: 8238185
• 负责人: YING-HUI FU
• 金额: $ 46.02万
• 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/8238185
• 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; Functional RNA; Gene Mutation; Gene Structure; Genes; Genome; Health; Homeostasis; Hour; Human; Human Genetics; Immunity; Individual; Investigation; Investments; Knowledge; Lead; Left; Life; Life Style; Maintenance; 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; Screening procedure; Sleep; Sleep Deprivation; Sleep Disorders; Societies; Socioeconomic Status; Surveys; Technology; Temperature; Ticks; Time; United States National Institutes of Health; Variant; Wakefulness; Work; base; cancer risk; circadian pacemaker; cost; cost effective; dietary control; exome; fly; genome sequencing; immune function; improved; mortality; motor control; novel; proband; 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. PUBLIC HEALTH RELEVANCE: Project Narrative We humans spend close to one third of our life in the state of sleep but our understanding of its regulation remains limited. A very unique opportunity presented itself to us recently when we identified the first human genetic form of sleep "need" variation, and the gene/mutation that leads to natural short sleep syndrome in this family. This proposal outlines a plan to expand our current resource and to identify additional genes that are in sleep regulation pathways. These resources and information will tremendously enhance our understanding of the mechanisms that regulate our sleep. This will have important implications for the mechanism through which sleep alterations and sleep deprivation increase risk of many diseases.

描述（由申请人提供）： 睡眠是一种全球状态，其控制机制在每个级别的生物组织中都表现出来 - 从基因和细胞内机制到细胞群体的网络，再到有机体的表型。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中。长时间的睡眠丧失会损害温度控制，饮食代谢，免疫功能，并最终导致死亡。睡眠剥夺会增加个人患癌症，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，就业，学校以及咖啡因和酒精（例如咖啡因和酒精）。睡眠和昼夜节律功能是在生物体中相互作用的不同过程。睡眠由至少两个过程控制：一个昼夜节律起搏器（时钟），周期性约为24小时，而稳态驱动器在清醒期间增加并在睡眠期间消失。尽管我们在睡眠状态下花费了大约三分之一的生命，但我们几乎对管理睡眠数量的监管机制一无所知。当我们确定具有大幅减少的睡眠需求的独立家庭时，就会出现独特的机会。确定新受试者并扩大我们对这些家庭的收集将为我们建立基础，以开始探测睡眠稳态的分子调节机制。最近，我们报道了引起这种短暂性表型的第一个突变。有趣的是，这种突变在人，小鼠和苍蝇中产生了类似的短睡眠表型。因此，本研究中鉴定出的所有基因将成为我们揭开神秘睡眠机制的入口点。最终，结合多个基因以及人类和模型生物的研究的知识将使对睡眠及其与健康和疾病的关系有更好的了解。 公共卫生相关性： 项目叙事我们人类在睡眠状态下花费了接近三分之一的生命，但是我们对其法规的理解仍然有限。最近，当我们确定了第一种人类睡眠“需求”变异的第一种人类遗传形式以及导致该家族自然短睡综合症的基因/突变时，一个非常独特的机会。该提案概述了扩大我们当前资源并确定睡眠调节途径的其他基因的计划。这些资源和信息将极大地增强我们对调节睡眠机制的理解。这将对睡眠改变和睡眠剥夺增加许多疾病风险的机制具有重要意义。