Using sticklebacks as a model for identifying genes related to risk- taking behav

使用刺鱼作为模型来识别与冒险行为相关的基因

• 批准号: 7351735
• 负责人: Alison Marie Bell
• 金额: $ 26.21万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7351735
• 关键词: Address; Affect; Aggressive behavior; Alcohol or Other Drugs use; Animal Model; Animals; Antisocial Personality Disorder; Arts; Behavior; Behavior Disorders; Behavioral; Bioinformatics; Biological Models; Candidate Disease Gene; Caring; Clinical; Clinical Psychology; Collaborations; Complement; Complex; Condition; Core Facility; Dangerous Behavior; Data; Development; Diagnosis; Disease; Disinhibition; Dissection; Environment; Environmental Risk Factor; Esthesia; Ethology; Etiology; Evolution; Exposure to; Face; Failure; Fishes; Food; Gasterosteidae; Gene Expression; Genes; Genetic; Genetic Variation; Genome; Genomics; Goals; Head; Health; Heredity; Human; Illinois; Individual; Inherited; Letters; Life; Life Stress; Link; Mission; Modeling; Molecular; Molecular Profiling; NIH Program Announcements; Neuroendocrinology; Neurosecretory Systems; Oral cavity; Organism; Outcome; Pathway interactions; Phenotype; Polymerase Chain Reaction; Population; Predatory Behavior; Primates; Psychologist; Psychopathology; Public Health; Purpose; Qualifying; RNA Interference; Recording of previous events; Research; Research Personnel; Risk; Risk-Taking; Rodent; Science; Scientist; Self-Injurious Behavior; Societies; Source; Staging; Swimming; System; Testing; Time; Transgenic Organisms; United States National Institutes of Health; Universities; Variant; Violence; Work; addiction; base; behavior influence; behavior observation; behavioral genomics; cost; design; experience; externalizing behavior; fascinate; genetic risk factor; improved; innovation; novel; psychopharmacologic; response; stressor; success; tool; trait

DESCRIPTION (provided by applicant): Despite the obvious costs to individuals and society and importance for health, we know relatively little about the etiology of risk-taking behaviors. Progress toward understanding the genetic and environmental factors influencing the propensity to engage in self-harm, violence and sensation seeking behaviors will be hastened by the availability of a genomically tractable animal model. Our long term goal is to develop stickleback fish (Gasterosteus aculeatus) as a model system to understand how genes interact with the environment to influence behaviors. The overall objective of this application is to identify and test candidate genes and pathways underlying natural variation in risk-taking behaviors. Our central hypothesis is that there are inherited and environmentally-responsive genes that affect risk-taking behaviors in sticklebacks, and those genes are shared with other animals, including humans. The rationale that underlies the proposed research is that an unbiased approach to studying natural variation in the propensity to engage in risk-taking behaviors which are both genetically based and environmentally-sensitive is likely to identify candidate genes that are relevant to human health. Identification of the genes pathways underlying risk-taking behaviors will contribute to the NIH mission to improve the health of the nation by aiding psychopharmacological efforts for the treatment and diagnosis of externalizing disorders in humans. Guided by strong preliminary data, this hypothesis will be tested by pursuing three specific aims: 1) Identify genes associated with differences in risk- taking behaviors between individuals and populations; 2) Identify genes underlying risk-taking behaviors that are responsive to adverse environmental conditions; 3) Test candidate genes related to risk-taking behaviors in replicated populations. Under Aim 1, the gene expression profiles of risk-prone versus risk-averse individuals will be compared using whole-genome expression microarrays. Under the second Aim, the behavior and gene expression of individuals that are exposed to stressful environments will be compared against unstressed conspecifics. The two stressors are absence of parental care, which has an important effect on risk-taking behaviors in this species, and exposure to predators during development. Under Aim 3, the genes that are good candidates from Aims 1 and 2 will be tested in independent, replicate populations. This timely project capitalizes on the availability of new genomic information for an organism with a well-described and fascinating behavioral repertoire that until recently has been exempt from molecular dissection. The key innovation of this work is that it takes advantage of genetic and environmental sources of variation to identify candidate genes and uses the unique evolutionary history of sticklebacks to test a biomedically-relevant hypothesis in a replicated manner. The proposed studies use a new animal model to address fundamental questions about the origin of behaviors that have adverse consequences for health. The studies have potential application to understanding the etiology of human psychopathology. The proposed research has relevance to public health, because it will suggest candidate genes and pathways for the diagnosis and treatment of behavioral disorders in humans.

描述（由申请人提供）：尽管对个人和社会造成明显的成本以及对健康的重要性，但我们对冒险行为的病因知之甚少。基因组上易于处理的动物模型的出现将加速了解影响自残、暴力和寻求感觉行为倾向的遗传和环境因素的进展。我们的长期目标是开发刺鱼（Gasterosteus aculeatus）作为模型系统，以了解基因如何与环境相互作用以影响行为。该应用程序的总体目标是识别和测试冒险行为自然变异背后的候选基因和途径。我们的中心假设是，存在影响刺鱼冒险行为的遗传性和环境响应基因，并且这些基因与包括人类在内的其他动物共享。拟议研究的基本原理是，采用公正的方法来研究基于遗传和环境敏感的冒险行为倾向的自然变化，可能会识别出与人类健康相关的候选基因。确定冒险行为背后的基因途径将有助于美国国立卫生研究院的使命，即通过帮助精神药理学努力治疗和诊断人类外在疾病来改善国民的健康。在强有力的初步数据的指导下，这一假设将通过追求三个具体目标进行检验：1）识别与个体和群体之间冒险行为差异相关的基因； 2）识别对不利环境条件做出反应的冒险行为背后的基因； 3）在复制群体中测试与冒险行为相关的候选基因。在目标 1 下，将使用全基因组表达微阵列比较倾向于风险和规避风险个体的基因表达谱。在第二个目标下，暴露于压力环境中的个体的行为和基因表达将与未受压力的同种人进行比较。这两个压力源是缺乏父母的照顾，这对该物种的冒险行为有重要影响，以及在发育过程中暴露于捕食者。在目标 3 下，来自目标 1 和 2 的良好候选基因将在独立的重复群体中进行测试。这个及时的项目利用了一种生物体的新基因组信息，该生物体具有详细描述且令人着迷的行为库，直到最近才免于进行分子解剖。这项工作的关键创新在于，它利用遗传和环境变异来源来识别候选基因，并利用刺鱼独特的进化历史以重复的方式检验生物医学相关的假设。 拟议的研究使用一种新的动物模型来解决有关对健康产生不利影响的行为起源的基本问题。这些研究对于理解人类精神病理学的病因学具有潜在的应用价值。拟议的研究与公共卫生相关，因为它将提出用于诊断和治疗人类行为障碍的候选基因和途径。