PRIMATE COMPARATIVE NEUROGENETICS AND MOLECULAR EVOLUTION

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该提案的目标是系统地探索哺乳动物的分子和基因组进化，重点是人类和非人类灵长类动物，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，重点是显示阳性选择证据的区域或与疾病相关的基因。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式物种（特别是恒河猴和普通绒猴）。它还将包括物种之间（分歧）和物种内部（多态性）的差异。然后，我们将在体外功能上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水平和通过与生理措施的相关性来评估非人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，如果特定的精神疾病或症状是人类特有的，由人类特有的遗传变化，以及在何种程度和方式，这些精神疾病及其治疗可以在其他生物体，特别是非人类灵长类动物建模。这将使研究人员能够利用分子进化和比较遗传学的力量，在未来的人类疾病研究中发挥更大的作用，并完善候选基因分析，更好地将神经精神疾病的动物模型置于背景中。人类灵长类动物，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，重点是显示阳性选择证据的区域或与疾病相关的基因。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式物种（特别是恒河猴和普通绒猴）。它还将包括物种之间（分歧）和物种内部（多态性）的差异。然后，我们将在体外功能上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水平以及与生理指标的相关性来评估非人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，如果特定的精神疾病或症状是人类特有的，由人类特有的遗传变化，以及在何种程度和方式，这些精神疾病及其治疗可以在其他生物体，特别是非人类灵长类动物建模。这将使研究人员能够利用分子进化和比较遗传学的力量，在未来的人类疾病研究中发挥更大的作用，并改进候选基因分析，更好地将其置于神经精神疾病的动物模型中。

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.