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

基本信息

批准号：
7808027
负责人：
Alison Marie Bell
金额：
$ 32.93万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
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/7808027
关键词：
Address Affect Aggressive behavior Alcohol or Other Drugs use Animal Model Animals Arts Behavior Behavior Disorders Behavioral Bioinformatics Biological Models Candidate Disease Gene Caring Clinical Clinical Psychology Collaborations Complement Complex Conduct Disorder 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 Personality Phenotype Population Predatory Behavior Primates Psychologist Psychopathology Public Health 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 adverse outcome anti social 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

项目摘要

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）：尽管个人和社会的成本明显，并且对健康的重要性，但我们对冒险行为的病因相对较少了解。朝着理解影响自我伤害，暴力和寻求行为倾向的遗传和环境因素的进展将因基因组障碍动物模型的可用性而加速。我们的长期目标是开发粘性鱼（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的是识别和测试候选基因和冒险行为自然变化的基本途径。我们的中心假设是，有遗传和环境响应的基因会影响棍子背部的冒险行为，这些基因与包括人类在内的其他动物共享。拟议的研究基础的理由是，一种无偏见的方法来研究从事风险行为的自然变化，这些行为既基于遗传，又对环境敏感的行为可能识别与人类健康相关的候选基因。识别基因途径冒险行为的基因途径将通过协助心理药物学努力来治疗和诊断人类外在疾病的治疗和诊断，从而有助于改善国家健康的任务。在强大的初步数据的指导下，将通过追求三个具体目的来检验该假设：1）确定与个人与人群之间的风险差异相关的基因； 2）确定对不利环境条件有反应的冒险行为的基因； 3）测试候选基因与复制人群中的冒险行为有关。在AIM 1下，将使用全基因组表达微阵列比较易风险和规避风险个体的基因表达谱。在第二个目的下，将与无重强度的同种相比，将接触到压力环境的个体的行为和基因表达将进行比较。这两个压力源是缺乏父母护理，这对该物种的冒险行为具有重要影响，并在发育过程中暴露于捕食者。在AIM 3下，AIMS 1和2的良好候选者的基因将在独立的，重复的人群中进行测试。这个及时的项目利用了新的基因组信息的可用性，并具有描述良好且引人入胜的行为曲目，直到最近才免于分子解剖。这项工作的关键创新是，它利用遗传和环境变异来源来识别候选基因，并利用粘背的独特进化历史来以复制的方式检验与生物医学相关的假设。拟议的研究使用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。这些研究具有潜在的应用于理解人类心理病理学的病因。拟议的研究与公共卫生有关，因为它将建议候选基因和途径诊断和治疗人类行为障碍。