Replication and narrowing of gene expression quantitative trait loci using inbred mice
- 225 Downloads
Gene expression quantitative trait locus (eQTL) mapping has become a powerful tool in systems biology. While many authors have made important discoveries using this approach, one persistent challenge in eQTL studies is the selection of loci and genes that should receive further biological investigation. In this study we compared eQTL generated from gene expression profiling in the livers of two panels of mouse strains: 41 BXD recombinant inbred and 36 Mouse Diversity Panel (MDP) strains. Cis-eQTL, loci in which the transcript and its maximum QTL are colocated, have been shown to be more reproducible than trans-eQTL, which are not colocated with the transcript. We observed that between 9.9 and 12.1% of cis-eQTL and between 2.0 and 12.6% of trans-eQTL replicated between the two panels depending on the degree of statistical stringency. Notably, a significant eQTL hotspot on distal chromosome 12 observed in the BXD panel was reproduced in the MDP. Furthermore, the shorter linkage disequilibrium in the MDP strains allowed us to considerably narrow the locus and limit the number of candidate genes to a cluster of Serpin genes, which code for extracellular proteases. We conclude that this strategy has some utility in increasing confidence and resolution in eQTL mapping studies; however, due to the high false-positive rate in the MDP, eQTL mapping in inbred strains is best carried out in combination with an eQTL linkage study.
KeywordsInbred Strain Recombinant Inbred Single Nucleotide Polymorphism Data Serpina1 Gene eQTL Mapping
We thank several anonymous reviewers for excellent suggestions and criticism which strengthened the final manuscript. Financial support for these studies was provided in part by the United States Environmental Protection Agency grants RD833825 and F08D20579. However, the research described in this article was not subjected to the Agency’s peer review and policy review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred. DMG was also supported by the UNC Environmental Sciences & Engineering Interdisciplinary Fellowship.
- Farrall M (2004) Quantitative genetic variation: a post-modern view. Hum Mol Genet 13 Spec No 1:R1-R7Google Scholar
- Shi C, Uzarowska A, Ouzunova M, Landbeck M, Wenzel G et al (2007) Identification of candidate genes associated with cell wall digestibility and eQTL (expression quantitative trait loci) analysis in a Flint × Flint maize recombinant inbred line population. BMC Genomics 8:22PubMedCrossRefGoogle Scholar
- Zhang Q, McMillan L, Pardo-Manuel de Villena F, Threadgill DW, Wang W (2009) Inferring genome-wide mosaic structure. Proceedings of the 14th Pacific Symposium on Biocomputing (PSB). Singapore: World Scientific Publishing, vol 14, pp 150–161Google Scholar