CUMULATIVE MULTILOCUS MAP OF MOUSE CHROMOSOME 5

小鼠 5 号染色体的累积多位点图谱

• 批准号: 3333210
• 负责人: VERNE M CHAPMAN
• 金额: $ 27.9万
• 依托单位: ROSWELL PARK CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3333210
• 关键词: biochemical evolution; chromosome translocation; chromosomes; complementary DNA; cytogenetics; gene mutation; genetic mapping; genetic markers; genetic models; genetic recombination; genetic regulatory element; genetic strain; genome; genotype; human population genetics; laboratory mouse; linkage mapping; model design /development; molecular cloning; molecular genetics; mutant; restriction fragment length polymorphism; southern blotting

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.

一个定义明确的小鼠基因组遗传图谱，建立基因顺序 并准确估计重组距离 基因之间的相互作用是分析基因突变的分子基础的重要工具。 突变病变和确定与 突变表型 应用遗传图谱表征 小鼠突变很容易扩展到人类遗传学中的类似问题， 紧密的遗传连锁在进化上很有可能 保守的 小鼠基因图谱的历史构建 广泛依赖于2，3，和4因子交叉和汇编 综合这些累积结果的合成地图 重组数据 这些方法通常受到使用的限制， 突变基因标记或有限的变异性，为一套生化 定义基因 我们的实验室和其他实验室已经转向使用各种 小鼠物种作为增加遗传变异性的来源，并利用这些 资源，有可能识别出与实验室不同的小鼠， 使用Southern技术分析100%的探针的菌株。 我们有 产生了小鼠物种与实验室菌株的回交， 在染色体上分离出大量的基因， 多位点连锁检测资源。 我们设计了一些方法 这些回交资源使我们能够将新的基因映射到以前的基因上， 以高效和累积的方式进行杂交。 的 这些方法的结果是多位点连锁图的发展 明确地对基因进行排序，并提供高度可靠的图谱估计， 距离 该提案具体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。 我们提出 开发一个连接测试资源，将跨越鼠标 5号染色体从着丝粒到最远端标记。 一旦 构建的，该图谱可用于分析与W 与c-kit癌基因相关的基因复合物。 地图会 也更好地定义了与人类染色体4 q和7 q的同源连锁。