Translational Genetic Study of Fear and Anxiety

恐惧和焦虑的转化遗传学研究

• 批准号: 7033012
• 负责人: ABRAHAM A PALMER
• 金额: $ 15.71万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7033012
• 关键词: animal population genetics; anxiety disorders; behavior test; behavioral /social science research tag; behavioral genetics; bioinformatics; conditioning; ethology; fear; gene expression; genetic strain; genetic susceptibility; human genetic material tag; human population genetics; laboratory mouse; learning; linkage mapping; microarray technology; quantitative trait loci

DESCRIPTION (provided by applicant): The proposed 4-year training award is intended to provide the applicant with additional training in three areas: microarray study design and analysis, bioinformatic techniques, and translational genetics. Experts in all of these fields have agreed to participate in the training program. Additionally, structured course work is proposed that addresses the trainee's deficiencies. The proposed training environment is an interdisciplinary center established by Columbia University to promote interaction among biologists, geneticists, statisticians, computational biologists, bioinformaticians, and engineers for the purpose of forging interdisciplinary "genomic" solutions to biomedical problems. Experts in all relevant fields are already working on closely related projects under the umbrella of a program project grant that has been awarded to the sponsor of this training program. Thus, the environment is ideally suited to the training goals. The applicant is already expert in the tools of classical behavioral genetics, such as quantitative trait locus (QTL), analysis and the creation of selected lines. The research plan is designed to identify genes that influence naturally occurring variability in a genetically tractable form of fear learning in mice. Short term selected mouse lines will be created and used to identify QTL, and gene expression differences. Specific polymorphisms related to genes and gene expression will be identified by the synergistic application of traditional (QTL mapping) and modern (microarray and bioinformatics) techniques. By using the latter techniques, which are the training component of this application, specific genes will be rapidly identified. This proposal addresses the major weakness of traditional mouse QTL studies, which is that they are seldom powerful enough to identify specific genes. We predict that some of the identified genes will also control fear learning and anxiety disorders in human subjects. To test these hypotheses, the strongest candidate genes, gene classes, and pathways will be examined for polymorphisms in a large population (approximately 1000) of unrelated normal human subjects scored for fear learning, and other anxiety dimensions, as well as in a population of anxiety disorder patients. Our collaborators are ascertaining these human subjects as one component of the sponsor's program project grant. This training program will prepare the candidate for an academic career focused on the use of endophenotypes, animal models and bioinformatics to elucidate the genetic basis of psychiatric disease.

描述（由申请人提供）： 拟议的 4 年培训奖旨在为申请人提供三个领域的额外培训：微阵列研究设计和分析、生物信息学技术和转化遗传学。所有这些领域的专家都同意参加该培训计划。此外，还提出了结构化课程作业来解决学员的不足。拟议的培训环境是哥伦比亚大学建立的跨学科中心，旨在促进生物学家、遗传学家、统计学家、计算生物学家、生物信息学家和工程师之间的互动，以打造生物医学问题的跨学科“基因组”解决方案。所有相关领域的专家已经在授予该培训计划赞助商的计划项目拨款的保护下开展密切相关的项目。因此，环境非常适合培训目标。申请人已经是经典行为遗传学工具的专家，例如数量性状基因座（QTL）、分析和选定品系的创建。该研究计划旨在识别影响小鼠恐惧学习的遗传易处理形式自然发生变异的基因。将创建短期选定的小鼠品系并用于鉴定 QTL 和基因表达差异。与基因和基因表达相关的特定多态性将通过传统（QTL作图）和现代（微阵列和生物信息学）技术的协同应用来鉴定。通过使用后一种技术（该应用程序的训练组成部分），将快速识别特定基因。该提案解决了传统小鼠 QTL 研究的主要弱点，即它们很少强大到足以识别特定基因。我们预测，一些已识别的基因也将控制人类受试者的恐惧学习和焦虑症。为了检验这些假设，将在大量（大约 1000）不相关的正常人类受试者中检查最强的候选基因、基因类别和通路的多态性，这些受试者在恐惧学习和其他焦虑方面进行评分，以及在焦虑症患者。我们的合作者正在确定这些人类受试者作为赞助商计划项目拨款的组成部分。该培训计划将为候选人的学术生涯做好准备，重点是使用内表型、动物模型和生物信息学来阐明精神疾病的遗传基础。