Applied Research Project

项目摘要/摘要-应用研究项目 SMSR的总体目标是为小鼠的复杂特征分析提供工具和资源。这个 复杂性状分析的最终目标是确定特定的基因和途径，这需要证据 因果关系。最好的因果关系是通过替换原始的特定等位基因变异来证明的 背景，在近交系背景上的等位基因变异的概述，和/或生化分析 基因工程细胞系或干细胞。为了推进复杂特征的研究，新的老鼠种群，如 已经开发了分集异交(DO)，以允许超高分辨率的测绘。小QTL 可以通过应用DO来获得种群是有代价的，因为个体DO 基因组不能通过标准畜牧业或辅助生殖技术复制，并且 因此，个体DO基因组不能进行基因工程。建议应用的总体目标 研究项目是探索通过克隆来稳定极端DO基因组的方法。这些 方法包括从成人成纤维细胞获得iPS细胞和100%iPS细胞来源的生产 嵌合体。在SMSR内建立这些协议将为新服务提供基础 因此，用于DO基因组稳定、候选基因测试和因果关系证明的试剂可以是 可通过资源获得。

PROJECT SUMMARY/ABSTRACT – Applied Research Project The overall goal of the SMSR is to provide the tools and resources for complex trait analysis in mice. The ultimate goal of complex trait analysis is the identification of specific genes and pathways, which requires proof of causation. Causation is best demonstrated through replacement of specific allelic variants in their original context, recapitulation of allelic variants on an inbred strain background, and/or biochemical assays in engineered cell lines or stem cells. To advance the study of complex traits novel mouse populations, like the Diversity Outcross (DO), have been developed to allow for ultra high-resolution mapping. The small QTL that can be obtained through application of the DO population comes at an expense because individual DO genomes cannot be reproduced through standard husbandry or assisted reproductive technologies, and therefore individual DO genomes cannot be genetically engineered. The overall goal of the proposed applied research project is to explore methods for stabilization of extreme DO genomes through cloning. These methods include the derivation of iPS cells from adult fibroblasts and the production of 100% iPS cell derived chimeras. The establishment of these protocols within the SMSR will provide the foundation for a new service whereby the reagents for DO genome stabilization, candidate gene testing and proof of causation can be available through the resource.