Genomic Organization of Recombination Hot Spots

了解哺乳动物重组的基因组分布是一个相当重要的问题。 重要性：1）优化关联研究的策略，通过连锁定位人类疾病基因 不平衡，2）优化实验策略，定位和克隆实验中的基因 哺乳动物，3）理解重组热点在进化过程中的作用，以及4）根据- 遗传重组是一个生物学过程。 拟议研究的目的是提供一个位置的分子描述， 小鼠基因组样本中热点的性质。我们将映射到1.5 Kb的分辨率， 在小鼠基因组的5个5兆碱基区域中发生的900-1000个交换的位置，选择用于 具体特点。我们预计，这些交叉将描述近80个重组热点， 将在来自（C57 BL/6 J X CAST/EiJ）F2后代的DNA中鉴定。我们的热点特征将 提供所有热点的位置和重组频率，低至0.02 cM/热点的水平，以及 将包括每个热点的单倍型和性别特异性。据我们所知，这将是第一个这样的 对哺乳动物来说是大规模的努力。 信息学研究将试图确定关键的热点序列和染色体特征， 热点位置 此外，对于其中一个染色体区域，我们将进行基因测试，以确定是否存在 热点活动所需的反式作用基因。

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) understandingthe role of recombinational hotspots in evolutionary processes, and 4) under- standing 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 hotspotactivity.