Mapping Diabetes to a Compound, Gene

Source: Dumas, M-E., Wilder, S.P., Bihoruea, M-T., Barton, R.H., Fearnside, J.F., Argoud, K., D’Amato, L., Wallis, R.H., Blancher, C., Keun, H.C., Baunsgaard, D., Scott, J., Sidelmann, U.G., Nicholson, J.K., and Gauguier, D. Direct quantitative trait locus mapping of mammalian metabolic phenotypes in diabetic and normoglycemic rat models. 2007. Nature Genetics, 39 (5): 666-72

The authors took three mouse lines and did an unbiased NMR metabonomics approach, two of these lines were diabetic. They then used both R/qtl and QTL Reaper to map NMR compounds among offspring of crosses within these strains. After identifying a number of candidate loci that matched both mapping methods, the authors used NMR to identify a molecule that had mapped (benzoate). They then used cognate mouse lines (essentially allele-replaced mice) to test phenotypic response for a region that had shown up from both forms of QTL mapping and also had substantial transcript abundance differences between the lines. The authors found that the cognate strains explained a large amount of the difference for benzoate, but also for a number of other metabolites that were related to the pathway. This was an excellent study in using QTL to identify controlling loci in metabolism, discover the compound, and observe the allelic affect.

Other notes:
-only 110 consistent linkages
-Bonferroni corrected reduced to 22 significant peaks
-mQTLs were less abundant than eQTLs
-Noticed multiple loci linked to same metabolite, suggests polygenic control
=found epigenetic effects