Systems Genetics Resource Consortium

自从格雷戈尔·孟德尔首先阐明了遗传学和遗传的原理以来， 了解遗传特征，如对疾病的易感性，在很大程度上涉及到研究生物系统 一次一个组件。然而，当面对基因组时，一次一次的方法不能扩展。 由-30,000个基因组成，与人类和其他哺乳动物一样。这一限制进一步加剧了 基因和环境之间复杂的相互作用。析因试验，描述在 罗纳德·费舍尔爵士于1930年提出的《S》一书，其中一个系统的许多或所有组件同时被改变 通过随机化，效率要高得多。同时对所有基因进行分析将是至关重要的，如果我们要 想象一下，当我们对人类(哺乳动物)生物学有足够深入的了解时，我们可以合成重组 生物学知识，能够准确预测并智能地改变具有复杂病因的特征，如 对常见病的易感性。 随着认识到需要一个新的模型人群来理解复杂的人类疾病 病因，我们设计了协作十字(CC)。CC提供了整合基因的翻译工具 对遗传网络和生物分子空间变异图的功能研究，包含所有 主要DNA序列和感兴趣的终末期疾病表型之间的生物分子，使用 真实的种群结构，这对于理解复杂的生物过程是必不可少的，比如 疾病易感性的改变。CC是一个由重组自交系(RL)组成的大型、高度创新的小组 小鼠结合了8个遗传多样性的创始菌株的基因组-A/J，C57BL/6J，12981/SvlmJ， NOD/LTJ、NZO/HILU、CAST/EIJ、PWK/PhJ和WSB/EIJ-捕获几乎90%的已知变化 存在于实验室小鼠体内。 为了实现生产CC的目标，我们成立了系统遗传学资源联盟， 将1)开发CC及其相关的畜牧业和表型数据库，2)在 开发以识别合成致命事件并进行质量控制，以及3)为CC开发一个门户网站 用于社区访问数据和分析程序。

Since Gregor Mendel first elucidated the principles of genetics and inheritance, the experimental basis for understanding heritable traits, like susceptibility to disease has largely involved studying biological systems one component at a time. However, the one-at-a-time approach does not scale when faced with a genome consisting of -30,000 genes as occurs in humans and other mammals. This limitation is further compounded by the complex interaction between genes and the environment. Factorial experimentation, described in the 1930's by Sir Ronald Fisher, in which many or all components of a system are altered simultaneously through randomization, is far more efficient. Analyses of all genes concurrently will be essential if we are to imagine a time when we understand human (mammalian) biology sufficiently well to synthetically reassemble biological knowledge to accurately predict and intelligently alter traits with complex etiologies, like susceptibility to common diseases. With the realization that a new model population was needed to understand human diseases with complex etiologies, we designed the Collaborative Cross (CC). The CC provides a translational tool to integrate gene functional studies into genetic networks and variation maps of the biomolecular space, containing all the biomolecules between the primary DMAsequence and the terminal disease phenotypes of interest, using a realistic population structure, which will be essential to understand the intricacies of biological processes like altered disease susceptibility. The CC is a large, highly innovative panel of recombinant inbred (Rl)lines of mice that combines the genomes of eight genetically diverse founder strains - A/J, C57BL/6J, 12981/SvlmJ, NOD/LtJ, NZO/HILU, CAST/EiJ, PWK/PhJ, and WSB/EiJ - to capture almost 90%of the known variation present in laboratory mice. To achieve the goal of producing the CC, we have formed the Systems Genetics Resource Consortium that will 1) develop the CC and assocaited husbandry and phenotype databases, 2) genotype the CC during development to identify synthetic lethal events and for quality control, and 3) develop a web portal for the CC for community access to data and analytic programs.