Genomic Organization of Recombination Hot Spots

重组热点的基因组组织

• 批准号: 6985923
• 负责人: KENNETH PAIGEN
• 金额: $ 31.92万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6985923
• 关键词: animal genetic material tag; biochemical evolution; bioinformatics; genetic mapping; genetic recombination; laboratory mouse; molecular cloning; mutagens; regulatory gene

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.

描述（由申请人提供）：了解哺乳动物重组的基因组分布对于通过连锁不平衡来映射人类疾病基因的策略非常重要。 3）理解重组热点在进化过程中的作用，以及4）将遗传重组理解为生物学过程。 拟议研究的目的是提供小鼠基因组样品中热点的位置和特性的分子描述。我们将映射到1.5 kb的分辨率，这是在小鼠基因组的五个5-megabase区域中发生的900-1000个跨界的位置，这些位置选择用于特定特征。我们期望将近80个重组热点描述的跨界车将在DNA中从（C57BL/6J X cast/eij）F2后代中鉴定出来。我们的热点表征将为所有热点的位置和重组频率提供至0.02 cm/热点的水平，并包括每个热点的单倍型和性别特异性。据我们所知，这将是首次进行哺乳动物的大规模努力。 信息学研究将尝试确定定义热点位置的关键热点序列和染色体特征。 此外，对于其中一个染色体区域，我们将对热点活性所需的跨作用基因的存在进行基因检测。