Evolutionary Roles of Homozygosity & Copy Number Variation in Mental Disorders

纯合性的进化作用

• 批准号: 7785629
• 负责人: Matthew Charles Keller
• 金额: $ 15.56万
• 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/7785629
• 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; Future; Gene Dosage; Genes; Genetic; Genetic Risk; 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; 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. PUBLIC HEALTH RELEVANCE: The proposed project should increase the molecular genetic and evolutionary understanding of schizophrenia and major depression, clarifying the degree to which rare versus common variants account for their risk, leading to follow-up (e.g., resequencing) investigations of important genomic regions, and potentially informing translational research aimed at developing diagnostic tests and treatments related to gene dosage.

描述（由申请人提供）：这一指导研究科学家发展奖的目的是建立Matthew Keller博士为精神遗传学的独立研究者。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步，以建立一个跨学科研究计划，以理解精神障碍的遗传变异。具体而言，培训和研究集中于拷贝数变异（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，因此有潜力为这一探究领域做出重要贡献。进化遗传学有助于将发现置于丰富的概念框架中，将它们与深层文学联系起来，并提出了一些关键的假设。 培训目标是发展开展独立资助的跨学科研究职业所需的技能。培训包括：（1）来自三名导师和四名顾问的直接合作和培训，这些导师是本申请核心方面的领导者； （2）生物信息学，统计遗传学，精神病学和进化遗传学的课程； （3）参加研讨会和会议，涵盖了基因组数据，精神遗传学和进化遗传学的分析； （4）教学课程和指导研究生； （5）编写R01应用程序的指导。行为遗传学研究所提供了丰富的智力环境，以实现这一培训。 该研究项目将使用来自多个来源的整个基因组SNP数据来研究CNV和EH与精神分裂症和重大抑郁症的关系。研究CNV和EH允许评估常见和罕见的遗传变异。这本身就是重要的，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的线索。这项研究有可能进一步了解精神障碍的进化理解，从而导致有关有助于其风险的分子机制的具体数据，并提出未来研究的特定途径。 公共卫生相关性：拟议项目应增加对精神分裂症和重度抑郁症的分子遗传和进化理解，阐明稀有与普通变体的程度，从而导致对重要基因组区域的随访（例如，重新配置）的后续研究（例如，重新配置）研究，并有潜在地将诊断诊断与治疗相关的转化研究旨在为Gene dosegens与Gene dosage开发临床。