The theory and applications of measuring broad-range and chromosome-wide recombination rate from allele frequency decay around a selected locus

Abstract
Recombination is the exchange of genetic material between homologous chromosomes via physical crossovers. High throughput sequencing approaches detect crossovers genome-wide to produce recombination rate maps but are difficult to scale as they require large numbers of recombinants individually sequenced. We present a simple and scalable pooled-sequencing approach to experimentally infer near chromosome-wide recombination rates by taking advantage of non-Mendelian allele frequency generated from a fitness differential at a locus under selection. As more crossovers decouple the selected locus from distal loci, the distorted allele frequency attenuates distally towards Mendelian and can be used to estimate the genetic distance. Here, we use marker selection to generate distorted allele frequency and theoretically derive the mathematical relationships between allele frequency attenuation, genetic distance, and recombination rate in marker selected pools. We implement...

摘要
重组是指同源染色体通过物理交换事件（crossover）交换遗传物质的过程。高通量测序（High-throughput sequencing）方法可在全基因组范围内检测染色体交换事件以构建重组率图谱，但该方法难以规模化应用，因其需要对大量重组个体分别进行测序。本研究提出一种简单且可规模化的混池测序（pooled sequencing）方法，可借助受选择位点（locus under selection）处适合度差异（fitness differential）产生的非孟德尔等位基因频率（non-Mendelian allele frequency），实验推断近乎全染色体范围的重组率。随着更多交换事件将受选择位点与远端位点解偶联，畸变的等位基因频率会向孟德尔频率方向沿远端逐渐衰减，据此可估算遗传距离。本研究通过标记选择（marker selection）产生畸变等位基因频率，并从理论上推导了标记选择混池中等位基因频率衰减、遗传距离与重组率之间的数学关系。本研究实施了……