Chromosome-Wide Mapping of Recombinational Activity

重组活动的染色体范围图谱

• 批准号: 7771708
• 负责人: Petko M Petkov
• 金额: $ 44.05万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7771708
• 关键词: Animals; Backcrossings; Biological Assay; Biological Process; Breeding; Chromosome Mapping; Chromosome Structures; Chromosomes; Chromosomes, Human, Pair 1; Data; Development; Disease; Distal; Event; Experimental Designs; Feasibility Studies; Female; Frequencies; Genes; Genetic; Genetic Crosses; Genetic Polymorphism; Genetic Recombination; Genetic Variation; Genome; Goals; Human; Infertility; Knowledge; Laboratories; Laboratory Organism; Length; Linkage Disequilibrium; Malignant Neoplasms; Mammals; Maps; Meiosis; Mouse Strains; Mus; Parents; Performance; Positioning Attribute; Process; Public Health; Recombinants; Resolution; Resources; Role; Sampling; Scheme; Sex Distribution; Site; Specificity; System; Testing; Work; density; gene cloning; human disease; imprint; improved; male; sex; sperm cell

DESCRIPTION (provided by applicant): Hotspots, the chromosomal regions where meiotic crossovers tend to localize, limit mapping resolution in experimental organisms and confound the use of linkage disequilibrium to map disease genes in humans. The goal of the proposed project is to generate the first high-resolution, large-scale map of recombination hotspots for an entire chromosome. This information will provide a resource for identifying and characterizing hotspots anywhere in the genome, and for understanding the relationship between hotspots and the functional and structural organization of the genome. To generate the map, we will first map an estimated 500-1,000 hotspots on mouse Chr 1 at 50-kb resolution in each of two crosses involving genetically distinct mouse strains. Three thousand female meioses and three thousand male meioses will be used in each cross. Recombination activity in the two crosses will then be compared, allowing testing of hotspots for genetic variation, sex specificity, and imprinting effects. Hotspots found to be sex- or strain- specific will then be mapped to 3-kb resolution, followed by performance of sperm assays on a broad pool of F1 samples from 16 strains to identify, for each hotspot, the parental strains in which recombination is initiated. Relevance to Public Health: The proposed work will have significant, immediate applications in mapping genes underlying any disease with a significant genetic component, both in humans and experimental animals, and will help to improve our understanding of processes leading to development of genetically influenced human diseases, such as cancer and infertility.

描述（由申请人提供）：热点，即减数分裂交叉倾向于定位的染色体区域，限制了实验生物体中的图谱分辨率，并混淆了使用连锁不平衡来绘制人类疾病基因图谱。该项目的目标是生成第一个高分辨率、大规模的整个染色体重组热点图。这些信息将为识别和表征基因组中任何位置的热点以及了解热点与基因组的功能和结构组织之间的关系提供资源。为了生成图谱，我们将首先在涉及遗传不同的小鼠品系的两个杂交中以 50 kb 分辨率绘制小鼠 Chr 1 上估计的 500-1,000 个热点。每个杂交中将使用三千个雌性减数分裂和三千个雄性减数分裂。然后将比较两个杂交中的重组活性，从而可以测试遗传变异、性别特异性和印记效应的热点。然后将发现的性别或品系特异性热点映射到 3 kb 分辨率，然后对来自 16 个品系的大量 F1 样本进行精子分析，以针对每个热点识别启动重组的亲本品系。与公共卫生的相关性：拟议的工作将在绘制人类和实验动物中具有重要遗传成分的任何疾病的基因图谱方面具有重要的、直接的应用，并将有助于提高我们对导致遗传影响的人类疾病（例如癌症和不育症）发展过程的理解。