Predicting the genomic resolution of bulk segregant analysis.
Predicting the genomic resolution of bulk segregant analysis.
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DOI：
10.1093/g3journal/jkac012
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发表时间：
2022-03-04
期刊：
影响因子：
--
通讯作者：
Messer PW
中科院分区：
文献类型：
--
作者：
Shen R;Messer PW
批量分离分析是一种识别表型性状差异背后的遗传基因座的技术。基本的方法是比较来自表型分布相反尾部的两组个体，这些个体是从杂交群体中抽样的。对每个池进行测序和扫描，寻找显示池之间差异频率的等位基因，表明与观察到的特征差异的潜在关联。批量分离分析已经成功地应用于从酵母到玉米等生物的各种数量性状基因座的定位。然而，这些研究通常受到相当低的测绘分辨率的影响，我们仍然缺乏对实验参数如何影响这一分辨率的详细了解。在这里，我们使用聚合理论来计算简单单基因性状的整体分离分析的期望基因组分辨率。我们首先证明了在无限大的理想杂交种群中，如直观预期的那样，作图区域的预期长度与重组率、杂交世代数和样本基因组数成反比。在有限的群体中，样本系谱中的合并事件减少了杂交过程中潜在信息的重组事件的数量，从而增加了作图区域的长度。这是通过一个有效的种群大小参数结合到我们的模型中的，该参数指定了杂交种群的成对聚集率。我们的计算预测的作图分辨率与数值模拟密切匹配，并且对于中等水平的分离体池与替代等位基因的污染是令人惊讶的稳健的。此外，我们还证明了该方法可以很容易地扩展到对穿越方案的修改。我们的框架将允许研究人员预测他们的地图实验的预期功率，并评估如何调整他们的实验设计以优化地图分辨率。
Bulk segregant analysis is a technique for identifying the genetic loci that underlie phenotypic trait differences. The basic approach is to compare two pools of individuals from the opposing tails of the phenotypic distribution, sampled from an interbred population. Each pool is sequenced and scanned for alleles that show divergent frequencies between the pools, indicating potential association with the observed trait differences. Bulk segregant analysis has already been successfully applied to the mapping of various quantitative trait loci in organisms ranging from yeast to maize. However, these studies have typically suffered from rather low mapping resolution, and we still lack a detailed understanding of how this resolution is affected by experimental parameters. Here, we use coalescence theory to calculate the expected genomic resolution of bulk segregant analysis for a simple monogenic trait. We first show that in an idealized interbreeding population of infinite size, the expected length of the mapped region is inversely proportional to the recombination rate, the number of generations of interbreeding, and the number of genomes sampled, as intuitively expected. In a finite population, coalescence events in the genealogy of the sample reduce the number of potentially informative recombination events during interbreeding, thereby increasing the length of the mapped region. This is incorporated into our model by an effective population size parameter that specifies the pairwise coalescence rate of the interbreeding population. The mapping resolution predicted by our calculations closely matches numerical simulations and is surprisingly robust to moderate levels of contamination of the segregant pools with alternative alleles. Furthermore, we show that the approach can easily be extended to modifications of the crossing scheme. Our framework will allow researchers to predict the expected power of their mapping experiments, and to evaluate how their experimental design could be tuned to optimize mapping resolution.
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影响因子：
4.3
作者：
Kelleher J;Etheridge AM;McVean G
通讯作者：
McVean G
影响因子：
48
作者：
Lai, Chao-Qiang;Leips, Jeff;Mackay, Trudy F. C.
通讯作者：
Mackay, Trudy F. C.
DOI：
10.1073/pnas.1706865114
发表时间：
2017-07-18
影响因子：
11.1
作者：
Bryon, Astrid;Kurlovs, Andre H.;Van Leeuwen, Thomas
通讯作者：
Van Leeuwen, Thomas
影响因子：
2.6
作者：
Ranson, H;Paton, MG;Collins, FH
通讯作者：
Collins, FH
影响因子：
3.3
作者：
Pool JE
通讯作者：
Pool JE