Evolutionary Roles of Homozygosity & Copy Number Variation in Mental Disorders

纯合性的进化作用

• 批准号: 8394943
• 负责人: Matthew Charles Keller
• 金额: $ 16.09万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-11 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8394943
• 关键词: Accounting; Affect; Area; Award; Behavioral Genetics; Bioinformatics; Collaborations; Copy Number Polymorphism; DNA Resequencing; Data; Diagnostic tests; Disease; Educational process of instructing; Educational workshop; Environment; Equilibrium; Framingham Heart Study; Funding; Gene Dosage; Genes; Genetic; Genetic Variation; Genome; Genomics; Goals; Human Genetics; Individual; Institutes; Interdisciplinary Study; Investigation; Knowledge; Lead; Link; Literature; Major Depressive Disorder; Mental Retardation; Mental disorders; Mentored Research Scientist Development Award; Mentors; Molecular; Molecular Genetics; Mutation; National Institute of Mental Health; Pilot Projects; Play; Positioning Attribute; Psychiatry; Recording of previous events; Research; Research Personnel; Research Project Grants; Research Training; Risk; Role; Running; Sampling; Schizophrenia; Source; Training; Translational Research; Variant; Writing; X Chromosome; career; career development; disorder risk; follow-up; genetic variant; genome sequencing; graduate student; programs; psychogenetics; public health relevance; research and development; skills; symposium

DESCRIPTION (provided by applicant): The objective of this Mentored Research Scientist Development Award is to establish Dr. Matthew Keller as an independent investigator in psychiatric genetics. The application brings together advances from evolutionary genetics, statistical genetics, and psychiatry to build an interdisciplinary research program for understanding the genetic variation underlying mental disorders. Specifically, training and research focus on how copy number variants (CNVs) and extended homozygosity (EH) influence mental disorder risk. Efforts to link such variation to mental disorders are just beginning, and so there is a potential for making important contributions to this area of inquiry. Evolutionary genetics helps situate findings within a rich conceptual framework, linking them to a deep literature and suggesting several critical hypotheses. The training goal is to develop the skills needed to launch an independently funded, interdisciplinary research career. The training includes: (1) direct collaboration and training from three mentors and four consultants who are leaders in core aspects of this application; (2) coursework in bioinformatics, statistical genetics, psychiatry, and evolutionary genetics; (3) attendance at workshops and conferences covering analysis of genomic data, psychiatric genetics, and evolutionary genetics; (4) teaching courses and mentoring graduate students; and (5) guidance in writing an R01 application. The Institute for Behavioral Genetics offers rich intellectual environments for achieving this training. The research project will use whole genome SNP data from several sources to examine how CNVs and EH are related to schizophrenia and major depression. Studying CNVs and EH allows assessment of common as well as rare genetic variants. This is important in its own right, but also can provide important clues to the evolutionary history of mental disorders and the genes affecting them. This research has the potential to further the evolutionary understanding of mental disorders, lead to concrete data on the molecular mechanisms that contribute to their risk, and suggest specific avenues of future research.

描述（由申请人提供）：该导师研究科学家发展奖的目的是使 Matthew Keller 博士成为精神科遗传学领域的独立研究者。该应用程序汇集了进化遗传学、统计遗传学和精神病学的进展，建立了一个跨学科研究计划，以了解精神障碍背后的遗传变异。具体来说，培训和研究重点关注拷贝数变异 (CNV) 和扩展纯合性 (EH) 如何影响精神障碍风险。将这种变异与精神障碍联系起来的努力才刚刚开始，因此有可能为这一研究领域做出重要贡献。进化遗传学有助于将研究结果置于丰富的概念框架内，将它们与深入的文献联系起来，并提出几个关键假设。 培训目标是培养开展独立资助的跨学科研究职业所需的技能。培训内容包括：（1）由三名导师和四名顾问直接协作和培训，他们是该应用程序核心方面的领导者； (2) 生物信息学、统计遗传学、精神病学和进化遗传学课程； (3) 参加涵盖基因组数据分析、精神遗传学和进化遗传学的研讨会和会议； （四）教授课程和指导研究生； (5) 撰写 R01 申请的指导。行为遗传学研究所为实现这一培训提供了丰富的智力环境。 该研究项目将使用多个来源的全基因组 SNP 数据来研究 CNV 和 EH 与精神分裂症和重度抑郁症的关系。研究 CNV 和 EH 可以评估常见和罕见的遗传变异。这本身很重要，但也可以为精神障碍的进化史和影响它们的基因提供重要线索。这项研究有可能进一步加深对精神障碍的进化理解，获得有关导致其风险的分子机制的具体数据，并为未来研究的具体途径提出建议。