PRIMATE COMPARATIVE NEUROGENETICS AND MOLECULAR EVOLUTION

灵长类动物比较神经遗传学和分子进化

• 批准号: 8357962
• 负责人: Eric J. Vallender
• 金额: $ 1.38万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357962
• 关键词: Animal Model; Callithrix jacchus jacchus; Candidate Disease Gene; Cataloging; Catalogs; Disease; Evolution; Funding; Genes; Genetic; Genetic Polymorphism; Genomics; Goals; Grant; Human; In Vitro; Macaca mulatta; Mammals; Measurement; Measures; Mental disorders; Messenger RNA; Modeling; Molecular; Molecular Evolution; Mutation; National Center for Research Resources; New England; Organism; Physiological; Primates; Principal Investigator; Research; Research Infrastructure; Research Personnel; Resources; Source; Symptoms; United States National Institutes of Health; Variant; Work; base; comparative; cost; human disease; in vivo; neurogenetics; neuropsychiatry; nonhuman primate

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of this proposal is to systematically explore the molecular and genomic evolution of mammals focused on humans and non-human primates in order to better understand the context of human disease. First we will catalog the differences between species with a focus on regions showing evidence for positive selection or genes demonstrated to be associated with disease. This effort will make use of all major primate lineages but will in particular focus on the more commonly used biomedical model species (notably rhesus macaques and common marmosets). It will also include both differences between (divergence) and within (polymorphism) species. We will then functionally investigate the consequences of these differences, as well as the functionality of ancestral sequences, in vitro. We will also assess the effects of polymorphic variation from non-human primates ex vivo and in vivo through measurement of mRNA levels and through correlation with physiological measures. This work will elucidate if specific psychiatric disorders or symptoms are unique to humans resulting from human-specific genetic changes and the extent to which and ways that these psychiatric disorders and their treatment can be modeled in other organisms, particularly non-human primates. This will allow researchers to leverage the power of molecular evolution and comparative genetics to greater effect in studies of human disease going forward and to refine candidate gene analyses and better place into context animal models of neuropsychiatric disease.The goal of this proposal is to systematically explore the molecular and genomic evolution of mammals focused on humans and non-human primates in order to better understand the context of human disease. First we will catalog the differences between species with a focus on regions showing evidence for positive selection or genes demonstrated to be associated with disease. This effort will make use of all major primate lineages but will in particular focus on the more commonly used biomedical model species (notably rhesus macaques and common marmosets). It will also include both differences between (divergence) and within (polymorphism) species. We will then functionally investigate the consequences of these differences, as well as the functionality of ancestral sequences, in vitro. We will also assess the effects of polymorphic variation from non-human primates ex vivo and in vivo through measurement of mRNA levels and through correlation with physiological measures. This work will elucidate if specific psychiatric disorders or symptoms are unique to humans resulting from human-specific genetic changes and the extent to which and ways that these psychiatric disorders and their treatment can be modeled in other organisms, particularly non-human primates. This will allow researchers to leverage the power of molecular evolution and comparative genetics to greater effect in studies of human disease going forward and to refine candidate gene analyses and better place into context animal models of neuropsychiatric disease.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 该提案的目的是系统地探索专注于人类和非人类灵长类动物的哺乳动物的分子和基因组进化，以便更好地了解人类疾病的背景。首先，我们将分类物种之间的差异，重点是显示阳性选择或证明与疾病相关的基因的证据。这种努力将利用所有主要的灵长类动物谱系，但特别是专注于更常用的生物医学模型物种（尤其是恒河猕猴和常见的摩尔马人）。它还将包括（差异）和（多态性）物种之间的差异。然后，我们将在体外研究这些差异的后果以及祖先序列的功能。我们还将通过测量mRNA水平以及与生理测量的相关性来评估非人类灵长类动物的多态性变异和体内的影响。这项工作将阐明特定的精神疾病或症状是由人类特异性遗传变化而引起的人类独有的，以及这些精神疾病及其治疗的程度和方式，可以在其他生物体（尤其是非人类灵长类动物）中建模。这将使研究人员能够利用分子进化和比较遗传学的力量在人类疾病的研究中更大的影响，并完善候选基因分析，并更好地将其置于神经精神病的上下文动物模型中。该提议的目的是系统地探索哺乳动物的分子和基因组进化的人类疾病，以对人类疾病的良好态度良好地探索人类疾病，从而更好地探索人类疾病，以更好地理解人类和非胡属氏症。首先，我们将分类物种之间的差异，重点是显示阳性选择或证明与疾病相关的基因的证据。这种努力将利用所有主要的灵长类动物谱系，但特别是专注于更常用的生物医学模型物种（尤其是恒河猕猴和常见的摩尔马人）。它还将包括（差异）和（多态性）物种之间的差异。然后，我们将在体外研究这些差异的后果以及祖先序列的功能。我们还将通过测量mRNA水平以及与生理测量的相关性来评估非人类灵长类动物的多态性变异和体内的影响。这项工作将阐明特定的精神疾病或症状是由人类特异性遗传变化而引起的人类独有的，以及这些精神疾病及其治疗的程度和方式，可以在其他生物体（尤其是非人类灵长类动物）中建模。这将使研究人员能够利用分子进化和比较遗传学的力量在未来的人类疾病的研究中更大的作用，并完善候选基因分析，并更好地成为神经精神病的动物模型。