COMPUTATION OF THE LIMITS TO TRAIT MAPPING IN EXISTING STRAINS OF LAB MICE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 无数品系的实验室小鼠被用作人类生物学的遗传和生理模型。研究人员使用在经典实验室品系中发现的多样性来揭示复杂表型的遗传基础，如疾病发病率和行为(例如，焦虑)。这一努力的一个主要限制是，经典小鼠品系的祖先是复杂的，被认为涉及来自全球的三到四个不同的小鼠亚种之间的杂交。这种杂交导致了来自单一亚种的大染色体块的马赛克，而不是重组。块状结构的存在已经在以前的研究中得到了证实，但目前对它的了解很少。清楚地描述实验室小鼠的祖先和染色体块大小，对于理解用目前的小鼠品系将表型映射到单个基因的限制至关重要。 作为了解导致重组实验室小鼠品系单倍型结构的祖先的第一步，我们正在检查几个野生来源小鼠品系的基因组结构。这个项目的核苷酸序列数据是公开的。关于经典实验室品系起源的一个中心假设是，它们是家鼠卡氏小鼠和肌肉小鼠(大约2000年前)杂交的结果，从而产生了小白鼠。在我们最初的工作中，我们将重点放在初级杂交的基因组证据上，这一杂交导致了M.molossinus的产生。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A myriad of lines of laboratory mice are used as genetic and physiological models of human biology. Researchers use the diversity found in the classical laboratory lines to uncover the genetic basis of complex phenotypes such as disease incidence and behavior (e.g., anxiety). A major limitation of this effort is that the ancestry of classical mouse lines is complex and is thought to involve hybridization between three or four different mouse subspecies from around the globe. This hybridization has resulted in a mosaic of large chromosomal blocks that are derived from single subspecies without recombination. The existence of the block structure has been established in previous research, but it is presently poorly understood. A clear description of the ancestry and chromosomal block sizes in laboratory mice is critical to understanding the limits to mapping phenotypes to individual genes with current mouse lines. As a first step to understanding the ancestry that gave rise to the haplotype structure in recombinant laboratory mouse strains, we are examining the genome structure of several wild-derived mouse strains. Nucleotide sequence data for this project is publicly available. A central hypothesis about the ancestry of classical laboratory lines is that they are the result of hybridization between the house mice Mus musculus castaneus and M. m. musculus (ca. 2000 years ago), which gave rise to M. m. molossinus. In our initial work we are focusing on genomic evidence for the primary hybridization that gave rise to M. m. molossinus.