Nusbaum C, Slonim D K, Harris K L, Birren B W, Steen R G, Stein L D, Miller J, Dietrich W F, Nahf R, Wang V, Merport O, Castle A B, Husain Z, Farino G, Gray D, Anderson M O, Devine R, Horton L T, Ye W, Wu X, Kouyoumjian V, Zemsteva I S, Wu Y, Collymore A J, Courtney D F, Tam J, Cadman M, Haynes A R, Heuston C, Marsland T, Southwell A, Trickett P, Strivens M A, Ross M T, Makalowski W, Xu Y, Boguski M S, Carter N P, Denny P, Brown S D, Hudson T J, Lander E S
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Nat Genet. 1999 Aug;22(4):388-93. doi: 10.1038/11967.
A physical map of the mouse genome is an essential tool for both positional cloning and genomic sequencing in this key model system for biomedical research. Indeed, the construction of a mouse physical map with markers spaced at an average interval of 300 kb is one of the stated goals of the Human Genome Project. Here we report the results of a project at the Whitehead Institute/MIT Center for Genome Research to construct such a physical map of the mouse. We built the map by screening sequenced-tagged sites (STSs) against a large-insert yeast artificial chromosome (YAC) library and then integrating the STS-content information with a dense genetic map. The integrated map shows the location of 9,787 loci, providing landmarks with an average spacing of approximately 300 kb and affording YAC coverage of approximately 92% of the mouse genome. We also report the results of a project at the MRC UK Mouse Genome Centre targeted at chromosome X. The project produced a YAC-based map containing 619 loci (with 121 loci in common with the Whitehead map and 498 additional loci), providing especially dense coverage of this sex chromosome. The YAC-based physical map directly facilitates positional cloning of mouse mutations by providing ready access to most of the genome. More generally, use of this map in addition to a newly constructed radiation hybrid (RH) map provides a comprehensive framework for mouse genomic studies.
在这个生物医学研究的关键模型系统中,小鼠基因组物理图谱对于定位克隆和基因组测序而言都是必不可少的工具。实际上,构建平均间隔为300 kb的标记小鼠物理图谱是人类基因组计划既定目标之一。在此,我们报告了怀特黑德研究所/麻省理工学院基因组研究中心构建此类小鼠物理图谱的项目结果。我们通过针对一个大插入酵母人工染色体(YAC)文库筛选序列标签位点(STS),然后将STS含量信息与密集遗传图谱整合来构建该图谱。整合后的图谱显示了9787个基因座的位置,提供了平均间距约为300 kb的地标,并使YAC覆盖了约92%的小鼠基因组。我们还报告了英国医学研究理事会小鼠基因组中心针对X染色体的一个项目结果。该项目产生了一个基于YAC的图谱,包含619个基因座(其中121个基因座与怀特黑德图谱相同,另有498个基因座),为这条性染色体提供了特别密集的覆盖。基于YAC的物理图谱通过提供对大部分基因组的便捷访问,直接促进了小鼠突变的定位克隆。更一般地说,除了新构建的辐射杂种(RH)图谱外,使用该图谱为小鼠基因组研究提供了一个全面的框架。