Estimating fine scale changes in recombination rates across species

估计物种间重组率的精细变化

• 批准号: 8936876
• 负责人: JEFFREY D WALL
• 金额: $ 31.3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8936876
• 关键词: Address; Animal Model; Binding; Binding Sites; Biological; Biological Process; Cells; Chromosome Segregation; Computing Methodologies; Data; Data Set; Epigenetic Process; Eukaryota; Event; Evolution; Genealogy; Genes; Genetic Polymorphism; Genetic Recombination; Genetic Variation; Genome; Human; Knowledge; Linkage Disequilibrium; Location; Mammals; Meiosis; Methods; Monkeys; Motivation; Mus; Natural Selections; Pan Genus; Pattern; Pongidae; Process; Sampling; Scanning; Signal Transduction; Structure; Testing; Theoretical model; Variant; Work; base; genome sequencing; homologous recombination; improved; novel; public health relevance

 DESCRIPTION (provided by applicant): Homologous recombination is a fundamental process crucial for proper alignment and segregation of chromosomes during meiosis and the efficacy of natural selection. Across many species, recombination events tend to cluster into narrow 'hotspots', short regions (< 2 Kb) where the crossover rate is much higher than in the surrounding sequence. The reliable identification of these recombination hotspots is a crucial step in understanding the biological basis of recombination rate variation, and in interpreting patterns of genetic variation. Current computational methods for identifying hotspots make biologically unrealistic assumptions and have extremely low power. This proposal focuses on developing improved methods for estimating fine-scale recombination rates and identifying hotspots, and these will be more accurate, more powerful and more general than previous approaches. The new methods will then be applied to whole genome sequence data sets from a wide range of mammals to address several open questions regarding the biological mechanisms governing recombination rate variation, hotspot formation and loss.

 描述（由申请人提供）：同源重组是减数分裂期间染色体正确排列和分离以及自然选择效力的关键基本过程。在许多物种中，重组事件倾向于聚集成狭窄的“热点”，短区域（< 2 Kb），其中交叉率远高于周围序列。这些重组热点的可靠鉴定是理解重组率变异的生物学基础和解释遗传变异模式的关键一步。当前用于识别热点的计算方法做出了生物学上不切实际的假设，并且功效极低。该提案的重点是开发改进的方法来估计精细尺度重组率和识别热点，这些方法将比以前的方法更准确，更强大，更通用。然后，新方法将应用于来自各种哺乳动物的全基因组序列数据集，以解决有关重组率变化，热点形成和丢失的生物学机制的几个悬而未决的问题。