Genomic Organization of Recombination Hot Spots

描述（由申请人提供）：了解哺乳动物重组的基因组分布对于1)优化通过连锁不平衡定位人类疾病基因的关联研究策略，2)优化实验哺乳动物基因定位和克隆的实验策略，3)理解重组热点在进化过程中的作用，以及4)理解遗传重组作为一个生物学过程具有相当重要的意义。

DESCRIPTION (provided by applicant): Understanding the genomic distribution of mammalian recombination is a matter of considerable importance for 1) optimizing strategies for association studies mapping human disease genes by linkage disequilibrium, 2) optimizing experimental strategies for mapping and cloning genes in experimental mammals, 3) understanding the role of recombinational hotspots in evolutionary processes, and 4) understanding genetic recombination as a biological process. The purpose of the proposed research is to provide a molecular description of the locations and properties of hotspots in a sample of the mouse genome. We will map to a resolution of 1.5 Kb, the locations of 900-1000 crossovers occurring in five 5-megabase regions of the mouse genome, selected for specific characteristics. The crossovers, which we expect to describe nearly 80 recombinational hotspots, will be identified in DNAs from (C57BL/6J x CAST/EiJ) F2 progeny. Our hotspot characterizations will provide the locations and recombination frequencies of all hotspots down to a level of 0.02 cM/hotspot, and will include the haplotype and sex specificity of each hotspot. To our knowledge, this will be the first such large-scale effort for a mammal. Informatics studies will attempt to identify key hotspot sequences and chromosomal features that define hotspot locations. Additionally, for one of the chromosomal regions, we will carry out a genetic test for the existence of trans-acting genes required for hotspot activity.