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: 8172877
• 负责人: Eric J. Vallender
• 金额: $ 1.81万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172877
• 关键词: Animal Model; Callithrix jacchus jacchus; Candidate Disease Gene; Cataloging; Catalogs; Computer Retrieval of Information on Scientific Projects Database; Disease; Evolution; Funding; Genes; Genetic; Genetic Polymorphism; Genomics; Goals; Grant; Human; In Vitro; Institution; Macaca mulatta; Mammals; Measurement; Measures; Mental disorders; Messenger RNA; Modeling; Molecular; Molecular Evolution; Mutation; Organism; Physiological; Primates; Research; Research Personnel; Resources; Source; Symptoms; United States National Institutes of Health; Variant; Work; comparative; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该提案的目标是系统地探索以人类和非人类灵长类动物为重点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，我们将对物种之间的差异进行分类，重点关注显示正选择证据的区域或被证明与疾病相关的基因。这项工作将利用所有主要的灵长类动物谱系，但将特别关注更常用的生物医学模型物种（特别是恒河猴和普通狨猴）。它还将包括物种之间（分歧）和物种内部（多态性）的差异。然后，我们将在体外对这些差异的后果以及祖先序列的功能进行功能研究。我们还将通过测量 mRNA 水平并通过与生理测量的相关性来评估非人类灵长类动物离体和体内多态性变异的影响。这项工作将阐明特定的精神疾病或症状是否是人类独有的，是由人类特异性基因变化引起的，以及这些精神疾病及其治疗在其他生物体，特别是非人类灵长类动物中的建模程度和方式。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发挥更大的作用，并完善候选基因分析，更好地融入神经精神疾病的动物模型中。