School of Agriculture and Biology, Shanghai Jiaotong University, China.
Brief Bioinform. 2012 Sep;13(5):555-68. doi: 10.1093/bib/bbr079. Epub 2012 Feb 8.
The identification of imprinted genes is becoming a standard procedure in searching for quantitative trait loci (QTL) underlying complex traits. When a developmental characteristic such as growth or drug response is observed at multiple time points, understanding the dynamics of gene function governing the underlying feature should provide more biological information regarding the genetic control of an organism. Recognizing that differential imprinting can be development-specific, mapping imprinted genes considering the dynamic imprinting effect can provide additional biological insights into the epigenetic control of a complex trait. In this study, we proposed a Bayesian imprinted QTL (iQTL) mapping framework considering the dynamics of imprinting effects and model multiple iQTLs with an efficient Bayesian model selection procedure. The method overcomes the limitation of likelihood-based mapping procedure, and can simultaneously identify multiple iQTLs with different gene action modes across the whole genome with high computational efficiency. An inference procedure using Bayes factors to distinguish different imprinting patterns of iQTL was proposed. Monte Carlo simulations were conducted to evaluate the performance of the method. The utility of the approach was illustrated through an analysis of a body weight growth data set in an F(2) family derived from LG/J and SM/J mouse stains. The proposed Bayesian mapping method provides an efficient and computationally feasible framework for genome-wide multiple iQTL inference with complex developmental traits.
在寻找复杂性状的数量性状基因座 (QTL) 时,鉴定印记基因正成为一种标准程序。当在多个时间点观察到生长或药物反应等发育特征时,了解控制基础特征的基因功能的动态应该为遗传控制生物体提供更多的生物学信息。认识到差异印记可以是特定于发育的,考虑动态印记效应的印记基因作图可以为复杂性状的表观遗传控制提供额外的生物学见解。在这项研究中,我们提出了一种贝叶斯印记 QTL(iQTL)映射框架,该框架考虑了印记效应的动态,并通过有效的贝叶斯模型选择过程来模拟多个 iQTL。该方法克服了基于似然的映射过程的局限性,并且可以以高计算效率在整个基因组中同时识别具有不同基因作用模式的多个 iQTL。提出了一种使用贝叶斯因子来区分 iQTL 不同印记模式的推断程序。进行了蒙特卡罗模拟来评估该方法的性能。通过对来自 LG/J 和 SM/J 小鼠品系的 F(2) 家族的体重增长数据集的分析,说明了该方法的实用性。所提出的贝叶斯映射方法为具有复杂发育特征的全基因组多个 iQTL 推断提供了一种有效且计算可行的框架。