CUMULATIVE MULTILOCUS MAP OF MOUSE CHROMOSOME 5

确定基因顺序的明确的小鼠基因组遗传图谱 以一种明确的方式并准确地估计重组距离 基因间的相互作用是分析人类免疫缺陷的分子基础的重要工具。 突变损伤及其相关结构基因的确定 突变的表型。遗传图谱在遗传特征分析中的应用 老鼠的突变很容易延伸到人类遗传学中的类似问题，因为 密切的遗传联系在进化上有很高的可能性 保守的。小鼠基因图谱的历史构建 广泛依赖于2、3和4因子杂交以及 整合这些累积结果的复合地图 重组数据。这些方法通常受到使用的限制 一组生化指标的突变基因标记或有限的变异性 定义的基因。我们的实验室和其他实验室已经转向使用不同的 作为增加遗传变异性的来源的小鼠物种，并利用这些 资源，就有可能鉴定出与实验室不同的小鼠。 用Southern技术分析了100%的探针的菌株。我们有 用实验室菌株与小鼠品种进行回交， 对染色体上的大量基因进行分离，从而形成 多位点连锁检测资源。我们已经设计出了使用 这些回交资源使我们能够将新的基因定位到以前的 以高效和累积的方式表现出杂交的特点。这个 这些方法的结果是开发了多位点连锁图谱 明确地对基因进行了排序，并提供了对图谱高度可靠的估计 距离。这项建议特别描述了小鼠物种的使用 与携带5号染色体突变标记的小鼠回交。我们建议 一种跨越鼠标的联动测试资源的开发 5号染色体从着丝粒到最远端的标记。一次 构建的这一图谱可用于分析与W 小鼠中与c-kit癌基因相关的基因复合体。地图将会 也更好地定义了与人类染色体4q和7q的同源连锁。

A well-defined genetic map of the mouse genome that establishes gene order in an unambiguous manner and accurately estimates recombinational distances between genes is an important tool for analyzing the molecular basis of mutational lesions and determining the structural genes associated with mutant phenotypes. The application of the genetic map to characterize mouse mutations readily extends to similar concerns in human genetics since close genetic linkages have a high probability of being evolutionarily conserved. The historical construction of gene maps in the mouse has relied extensively upon 2, 3, and 4 factor crosses and the compilation of composite maps that integrate the results of these accumulated recombinational data. These approaches were generally limited by the use of mutant gene markers or limited variability for a set of biochemically defined genes. Our laboratory and others have turned to the use of diverse Mus species as a source of increased genetic variability and, using these resources, it is possible to identify mice that differ from laboratory strains for 100% of the probes analyzed using Southern techniques. We have produced backcrosses of Mus species with laboratory strains that co- segregate for a large number of genes on a chromosome and thus become multilocus linkage testing resources. We have devised methods of using these backcross resources that allow us to map new genes to a previously characterized cross in a highly efficient and cumulative manner. The result of these approaches is the development of multilocus linkage maps that order genes unambiguously and provide highly reliable estimates of map distance. This proposal specifically describes the use of Mus species backcrosses with mice carrying mutant markers for chromosome 5. We propose the development of a linkage testing resource that will span mouse chromosome 5 from the centromere to the most distal marker. Once constructed, this map can be used to analyze genes associated with the W gene complex in mouse associated with the c-kit oncogene. The map will also better define homologous linkages with human chromosome 4q and 7q.