Maintenance of the SPF Breeding Colonies at Yerkes National Primate Research Center: MHC Genetic Typing Core

项目摘要/摘要--MHC基因分型核心 恒河猴是艾滋病研究的重要动物模型。跟上…的高需求 对于与艾滋病相关的动物研究，耶克斯国家灵长类动物研究中心保持着谨慎的 在我们的无特定病原体(SPF)菌落的支持下进行的监测育种计划。遗传 SPF群体中恒河猴的特征对于：(1)确保足够的遗传多样性是必不可少的 以及(2)为艾滋病研究提供合适的实验动物，而不是 含有已知的影响SIV感染的等位基因。Yerkes SPF MHC基因分型核心的主要作用是 (1)确定动物的亲缘关系并设计遗传策略，以避免近亲交配和最大化遗传 菌落的多样性和(2)确定已知的影响SIV感染的基因座的基因型(主要是MHC 第一类和第二类基因)，并将这一信息提供给艾滋病研究人员。自2010年以来，这些服务一直是 由Yerkes SPF基因分型核心执行，支持U24。在上一个资金周期中， CORE开发了一种新的高通量亲子鉴定方法，我们用它来完成亲子鉴定 对Yerkes SPF群体的分析，这一工具将在即将到来的资助期内实施。 应用于恒河猴的下一代测序技术现在已经能够创造出一种 高分辨率参考基因组和数百种动物全基因组数据的获取。这些 发展已经深刻地扩大了将高分辨率基因分型作为菌落的一部分的机会 猕猴SPF群体的管理。在目标3，这个核心的次要目标，我们提出了一个 一种结合Yerkes SPF菌落现有系谱信息和全基因组的新策略 测序和遗传补充以建立深层次动物系谱的全基因组序列数据，地址为 低成本。这种方法将为获得整个群体的全基因组信息提供基础 在未来几年，并建立恒河猴作为一个新兴的和有希望的遗传学研究模型。 目的1：将先进的亲子鉴定和遗传育种策略应用于SPF恒河猴群体。 目的2：应用最新的MHC分型技术为菌群管理提供信息，并提供良好的 为与艾滋病相关的调查确定动物的特征。 目标3：建立一个在全基因组范围内定义为基因类型的家系动物队列 等位基因发现的平台。 综合起来，这些拟议的目标将确保耶克斯SPF的遗传多样性和可持续性 并为NHP艾滋病研究人员提供他们研究中前所未有的基因数据 从而推进预防、治疗和治愈艾滋病毒感染的临床前研究。 这一模式将有助于确定预防战略和治疗方法，以减轻艾滋病毒的负担。

Project Summary/Abstract--MHC Genetic Typing Core Rhesus macaques are a critical animal model for AIDS research. To keep pace with the high demand of animals for AIDS-related studies, the Yerkes National Primate Research Center maintains a carefully monitored breeding program under the auspices of our Specific Pathogen Free (SPF) colony. Genetic characterization of rhesus macaques in the SPF colony is essential to: (1) ensure adequate genetic diversity and long-term health of the colony and (2) provide suitable experimental animals to AIDS studies that do not contain alleles known to affect SIV infection. The primary role of the Yerkes SPF MHC Genetic Typing Core is to (1) establish parentage of animals and design genetic strategies to avoid inbreeding and maximize genetic diversity of the colony and (2) determine the genotype of loci known to affect SIV infection (primarily the MHC class I and II genes) and provide this information to AIDS researchers. Since 2010, these services have been performed by the Yerkes SPF Genetic Typing Core, enabled by U24 support. In the last funding cycle, the Core has developed a novel high-throughput assay for parentage, which we used to complete parentage analysis of the Yerkes SPF colony, and this tool will be implemented throughout the upcoming funding period. Next-generation sequencing technology applied to the rhesus macaque has now enabled the creation of a high-resolution reference genome and acquistion of whole-genome data on hundreds of animals. These developments have profoundly broadened the opportunities to use high-resolution genotyping as part of colony management for rhesus macaque SPF colonies. In Aim 3, the secondary objective of this Core, we propose a novel strategy that combines the existing pedigree information of the Yerkes SPF colony with whole-genome sequencing and genetic imputation to establish genome-wide sequence data for a deep pedigree of animals at low cost. This approach will provide the groundwork for obtaining genome-wide information of the entire colony in future years and establish the rhesus macaque as an emerging and promising model for genetic studies. Aim 1: To apply advanced parentage testing and genetic breeding strategies to the SPF rhesus colony. Aim 2: To apply state-of-the-art MHC typing to inform colony management and provide well- characterized animals for AIDS-related investigations. Aim 3: To develop a cohort of pedigreed animals with genotypes defined at a genome-wide scale as a platform for allele discovery. Taken together, these proposed aims will ensure the genetic diversity and sustainability of the Yerkes SPF colony for years to come and provide NHP AIDS researchers with unprecedented genetic data on their study animals, thereby advancing preclinical research to prevent, treat and cure HIV infection. This model will contribute to identifying preventive strategies and treatments to reduce the burden of HIV.