Sun Wei, Yuan Shinsheng, Li Ker-Chau
Department of Biostatistics, University of North Carolina, Chapel Hill, NC, 27599, USA.
BMC Genomics. 2008 May 23;9:242. doi: 10.1186/1471-2164-9-242.
Many studies have shown that the abundance level of gene expression is heritable. Analogous to the traditional genetic study, most researchers treat the expression of one gene as a quantitative trait and map it to expression quantitative trait loci (eQTL). This is 1D-trait mapping. 1D-trait mapping ignores the trait-trait interaction completely, which is a major shortcoming.
To overcome this limitation, we study the expression of a pair of genes and treat the variation in their co-expression pattern as a two dimensional quantitative trait. We develop a method to find gene pairs, whose co-expression patterns, including both signs and strengths, are mediated by genetic variations and map these 2D-traits to the corresponding genetic loci. We report several applications by combining 1D-trait mapping with 2D-trait mapping, including the contribution of genetic variations to the perturbations in the regulatory mechanisms of yeast metabolic pathways.
Our approach of 2D-trait mapping provides a novel and effective way to connect the genetic variation with higher order biological modules via gene expression profiles.
许多研究表明基因表达的丰度水平是可遗传的。与传统遗传学研究类似,大多数研究人员将单个基因的表达视为一个数量性状,并将其定位到表达数量性状基因座(eQTL)。这就是一维性状定位。一维性状定位完全忽略了性状与性状之间的相互作用,这是一个主要缺点。
为了克服这一局限性,我们研究一对基因的表达,并将它们共表达模式的变化视为二维数量性状。我们开发了一种方法来寻找共表达模式(包括正负和强度)由遗传变异介导的基因对,并将这些二维性状定位到相应的基因座。我们报告了将一维性状定位与二维性状定位相结合的几个应用,包括遗传变异对酵母代谢途径调控机制中扰动的贡献。
我们的二维性状定位方法提供了一种新颖有效的方式,通过基因表达谱将遗传变异与高阶生物模块联系起来。