Woo Jung Hoon, Zheng Tian, Kim Ju Han
Seoul National University Biomedical Informatics (SNUBI), Seoul National University College of Medicine, Seoul 110-799, Korea.
Proc IEEE Int Symp Bioinformatics Bioeng. 2007 Oct;2007:433-439. doi: 10.1109/BIBE.2007.4375598.
The genetical genomics approach has been used to study the genetic basis of variation in gene expression, where putative transcriptional regulators of genes are identified via genetic quantitative trait mapping. The genetic regulators identified through such efforts can partially account for an individual gene's natural variation. However, genes in a molecular pathway often exhibit coordinated activities, the patterns and levels of which are also regulated. In an effort to understand these complicated mechanisms, we propose a method that searches for the genomic regulators of set-wise co-expression of related genes, based on current genetical genomics data. Using this method, we studied genomic regulators of 233 biological pathways for a BXD RI data set. For 15 pathways, we obtained significant regulatory loci after controlling for the false discovery rate. The results presented in this paper constitute important evidence of the heritability of mRNA co-expression between individuals. We have shown that, by defining new phenotypes using existing genetical genomics data, evidence on regulation of co-expression can be derived.
遗传基因组学方法已被用于研究基因表达变异的遗传基础，其中通过遗传数量性状定位来识别基因的假定转录调节因子。通过这些努力鉴定出的遗传调节因子可以部分解释单个基因的自然变异。然而，分子途径中的基因通常表现出协调的活性，其模式和水平也受到调节。为了理解这些复杂的机制，我们基于当前的遗传基因组学数据，提出了一种寻找相关基因集共表达的基因组调节因子的方法。使用这种方法，我们针对一个BXD RI数据集研究了233条生物学途径的基因组调节因子。对于15条途径，在控制了错误发现率后，我们获得了显著的调节位点。本文给出的结果构成了个体间mRNA共表达遗传性的重要证据。我们已经表明，通过使用现有的遗传基因组学数据定义新的表型，可以获得关于共表达调节的证据。
