QTL/microarray approach using pathway information

We modified a gene set analysis to identify intersection sets with significantly affected expression for which the changes in the individual gene sets are less significant. The gene expression profiles in liver tissues of four strains of mice from publicly available microarray sources were analyzed to detect trait-associated pathways using information on the QTL regions of blood concentrations of high density lipoproteins (HDL) cholesterol and insulin-like growth factor 1 (IGF-1). Several metabolic pathways related to HDL levels, including lipid metabolism, ABC transporters and cytochrome P450 pathways were detected for HDL QTL regions. Most of the pathways identified for the IGF-1 phenotype were signal transduction pathways associated with biological processes for IGF-1's regulation.We have developed a method of identifying pathways associated with a quantitative trait using information on QTL. Our approach provides insights into genotype-phenotype relations at the level of biological pathways which may help to elucidate the genetic architecture underlying variation in phenotypic traits.In the last decade, a large number of quantitative trait loci (QTL) have been mapped in various organisms, and positional information on QTL is already included in resources such as Online Mendelian Inheritance in Man [1], Mouse Genome Database [2] and AnimalQTLdb [3]. Most previously reported QTL were detected by linkage analyses, but mapping resolutions were too low to identify underlying genes or causative mutations by direct experiments (i.e., the confidence intervals often span tens of map units that contain dozens to hundreds of genes). On the other hand, microarray-based gene expression profiling can be used to discover genes related to a quantitative trait of interest [4]. Combining information on QTL with microarray data enables genes underlying genetically complex traits to be linked to QTL regions. Wayne and McIntyre (2002) [5] proposed the QTL/microarray approach to disc