Systems Genetics Resource Consortium

自从孟德尔第一次阐明了遗传学和遗传学的原理以来， 理解遗传特征，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，当面对一个基因组时， 由约30，000个基因组成，如在人类和其他哺乳动物中所发生的。这种限制进一步加剧了 基因和环境之间复杂的相互作用。析因实验，描述于 1930年代由罗纳德费舍尔爵士提出，其中系统的许多或所有组件同时改变 通过随机化，是更有效的。如果我们要同时分析所有基因， 想象有一天，我们对人类（哺乳动物）生物学有了足够的了解， 生物学知识，以准确地预测和智能地改变具有复杂病因的特征，如 易患常见疾病。 随着认识到需要一种新的模型人群来了解具有复杂 病原学，我们设计了协作交叉（CC）。CC提供了一种翻译工具， 生物分子空间的遗传网络和变异图的功能研究，包含所有的 在一级DMA序列和感兴趣的终末疾病表型之间的生物分子， 现实的人口结构，这将是必不可少的了解生物过程的复杂性，如 改变疾病易感性。CC是一个大的、高度创新的重组近交（RI）系组， 将八种遗传多样性创始品系- A/J，C57 BL/6 J，12981/SvlmJ， NOD/LtJ、NZO/HILU、CAST/EiJ、PWK/PhJ和WSB/EiJ -捕获几乎90%的已知变化 存在于实验室小鼠中。 为了实现生产CC的目标，我们成立了系统遗传资源联盟， 将1）开发CC和相关的畜牧业和表型数据库，2）基因型CC期间， 开发以识别合成致死事件和进行质量控制，以及3）为CC开发门户网站 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.