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

项目概要/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。为了满足高需求， 耶基斯国家灵长类动物研究中心（Yerkes National Primate Research Center）对艾滋病相关研究的动物进行了仔细的研究。 在我们的无特定病原体（SPF）菌落的主持下，我们的育种计划受到监控。遗传 在SPF群体中对恒河猴的特征进行鉴定对于：（1）确保足够的遗传多样性 和长期健康的殖民地和（2）提供合适的实验动物的艾滋病研究，不 含有已知影响SIV感染的等位基因。耶基斯SPF MHC基因分型核心的主要作用是 （1）确定动物的亲子关系，设计遗传策略，以避免近亲繁殖，最大限度地提高遗传 殖民地的多样性和（2）确定已知影响SIV感染的基因座的基因型（主要是MHC I类和II类基因），并将这些信息提供给艾滋病研究人员。自2010年以来，这些服务 由Yerkes SPF基因分型核心执行，由U24支持。在上一个供资周期， 核心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 Yerkes SPF殖民地的分析，这一工具将在整个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建一个 高分辨率参考基因组和获取数百种动物的全基因组数据。这些 这些发展极大地拓宽了使用高分辨率基因分型作为殖民地的一部分的机会。 恒河猴SPF群体的管理。在本核心的次要目标目标3中，我们提出了一个 一种新的策略，将耶基斯SPF菌落的现有谱系信息与全基因组相结合， 测序和遗传插补，以建立动物深谱系的全基因组序列数据， 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 在未来的几年中，并建立恒河猴作为一个新兴的和有前途的模型，遗传研究。 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：应用最先进的MHC分型技术，为菌落管理提供信息， 为艾滋病相关研究鉴定动物。 目的3：建立一个具有全基因组范围内定义的基因型的纯种动物队列， 等位基因发现的平台。 总之，这些拟议的目标将确保耶基斯SPF的遗传多样性和可持续性 在未来的几年里，NHP为艾滋病研究人员提供了前所未有的基因数据， 动物，从而推进临床前研究，以预防，治疗和治愈艾滋病毒感染。 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.