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）： 睡眠是一种全局状态，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，到细胞群网络，再到有机体层面的表型。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，并最终导致死亡。睡眠不足会增加个体患癌症、代谢综合征、精神疾病和其他疾病的风险。了解人类睡眠的生物学基础是一项极其困难的挑战，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、学校以及咖啡因和咖啡因等外源化学物质。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：昼夜节律起搏器（时钟）以约 24 小时的周期滴答作响，以及在清醒时增加并在睡眠时消散的稳态驱动力。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，但我们对睡眠量的调节机制几乎一无所知。当我们发现睡眠生理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、小鼠和果蝇中产生了类似的短睡眠表型。因此，本研究中确定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、人类和模式生物研究的知识将有助于更好地了解睡眠及其与健康和疾病的关系。 公共卫生相关性： 项目叙述我们人类一生中近三分之一的时间都处于睡眠状态，但我们对其调节的理解仍然有限。最近，当我们确定了第一个人类睡眠“需要”变异的遗传形式，以及导致该家族自然短睡眠综合症的基因/突变时，一个非常独特的机会出现在我们面前。该提案概述了一项扩大我们现有资源并确定睡眠调节途径中其他基因的计划。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不足增加许多疾病风险的机制产生重要影响。