GENETIC MAPPING OF MOUSE CHROMOSOMAL GENES

小鼠已被用作基因组分析的模式哺乳动物系统。我们一直致力于通过分析来自种间或亚种间交配的几个多位点杂交来开发小鼠的高密度遗传图谱。这些小鼠的DNA已经为1200多个基因座进行了分型，其中大约一半也被其他研究人员绘制了基因图谱。这使我们能够将新定义的基因映射到遗传图谱中的特定位置，并将我们的数据整合到每条染色体的合成图谱中。重点是绘制表达的基因图谱，以便能够与其他物种的图谱进行比较分析，并有助于确定与遗传性发育障碍有关的基因。最近，这些研究已经导致了编码趋化因子受体、热休克蛋白、在晶状体、胸腺基质或结缔组织中表达的基因、免疫系统基因和SH3结构域基因的基因图谱。首先，这些信息有助于比较分析人类和老鼠的同源基因。例如，我们研究了人类和小鼠的甲酰肽受体基因簇。我们发现，在这些物种中，fpr基因簇经历了差异扩张，以至于一个表达人类基因的基因在小鼠中没有对应的基因，而四个小鼠基因(其中只有两个是伪基因)没有人类的对应基因。其次，接近已知的发育突变可以确定这样的基因是异常表型的潜在候选基因。我们最近将编码晶状体蛋白伽马晶体蛋白的基因定位在小鼠16号染色体近端，靠近导致晶状体混浊(白内障)的发育突变。晶状体蛋白基因现在被认为是这种突变的潜在候选基因。我们最近开始使用物理图谱技术。我们正在使用脉冲场凝胶来确定重组不能分离的基因的顺序和距离。我们最近应用这种方法来确定Myc和新发现的乳腺肿瘤病毒的肿瘤特异性整合部位的接近程度。我们还使用辐射杂交DNA面板来开发Chr5的综合物理和遗传图谱。到目前为止，我们已经在该染色体的RH图谱上添加了近50个座位。-小鼠基因组、图谱、比较图谱

The mouse has been used as the model mammalian system for genome analysis. We have been engaged in the development of a high density genetic map of the mouse by analysis of several multilocus crosses derived from interspecies or intersubspecies matings. DNAs from these mice have been typed for over 1200 loci, about half of which have also been genetically mapped by other investigators. This permits us to map newly defined genes to specific positions in the genetic map, and to integrate our data into composite maps of each chromosome. Emphasis has been placed on mapping expressed genes to permit comparative analysis with the maps of other species and to contribute to efforts to identify genes involved in inherited developmental disorders. These studies have, most recently, resulted in the genetic mapping of genes encoding chemokine receptors, heat shock proteins, genes expressed in lens, thymic stroma, or connective tissue, immune system genes, and SH3 domain genes.Specific map locations can be useful for several reasons. First, such information contributes to the comparative analysis of homologous genes in man and mouse. For example, we examined the cluster of formylpeptide receptor genes in man and mouse. We found that the FPR gene cluster has undergone differential expansion in these species such that one expressed human gene has no counterpart in mouse, and 4 of the mouse genes (only two of which are pseudogenes) have no human counterparts. Second, proximity to a known developmental mutation can identify such a gene as a potential candidate for the abnormal phenotype. We recently mapped the gene encoding the lens protein gamma crystallin to proximal mouse chromosome 16 near a developmental mutation that results in lens opacity (cataracts). The lens protein gene is now being evaluated as a potential candidate for this mutation.We have recently begun using physical mapping techniques. We are using pulsed field gels to determine gene order and distance for genes not separable by recombination. We have most recently applied this approach to determine the proximity of Myc and a newly identified tumor specific integration site of mammary tumor virus. We are also using a radiation hybrid DNA panel to develop an integrated physical and genetic map of Chr 5. To date, we have added almost 50 loci to the RH map of this chromosome. - Mouse genome, mapping, comparative mapping