Estimating fine scale changes in recombination rates across species

 描述(由申请人提供)：同源重组是减数分裂过程中染色体正确排列和分离以及自然选择的有效性的关键。在许多物种中，重组事件往往聚集在狭窄的“热点”、短区域(&lt；2kb)中，其中交叉率比周围序列中的交叉率高得多。这些重组热点的可靠识别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。目前用于识别热点的计算方法做的是生物学上不切实际的假设，而且计算能力极低。这项提议的重点是开发改进的方法来估计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、更强大和更通用。然后，这些新方法将被应用于来自广泛哺乳动物的全基因组序列数据集，以解决关于重组率变异、热点形成和丢失的生物学机制的几个公开问题。

 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.