Analysis of allele specific expression in mouse liver by RNA-Seq : Marked differences compared to cis-eQTL identified using genetic linkage

We report an analysis of allele specific expression [ASE] and parent-of origin expression in adult mouse liver using next generation sequencing (RNA-Seq) of reciprocal crosses of heterozygous F1 mice from the parental strains C57BL/6J and DBA/2J. The genes exhibiting ASE differed markedly from the putative cis-acting expression quantitative trait loci (cis-eQTL) identified in an intercross between the same strains. While about 60% of the ASE, mapped by RNA-Seq, were found in the eQTL gene set, only a small fraction of the eQTL, mapped by linkage analysis, were found in the ASE gene set.We discuss the various biological and technical factors that contribute to these differences, in particular strengths of the two approaches in making a distinction between local and cis eQTL. We also identify genes exhibiting parental imprinting and complex expression patterns. Our study demonstrates the importance of biological replicates, which is not currently the norm, to limit the number of false positives with such RNA-Seq data.