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Direct quantitative trait locus mapping of mammalian metabolic phenotypes in diabetic and normoglycemic rat models.

Authors: Dumas, ME  Wilder, SP  Bihoreau, MT  Barton, RH  Fearnside, JF  Argoud, K  D'Amato, L  Wallis, RH  Blancher, C  Keun, HC  Baunsgaard, D  Scott, J  Sidelmann, UG  Nicholson, JK  Gauguier, D 
Citation: Dumas ME, etal., Nat Genet. 2007 Apr 15;.
Pubmed: (View Article at PubMed) PMID:17435758
DOI: Full-text: DOI:10.1038/ng2026

Characterizing the relationships between genomic and phenotypic variation is essential to understanding disease etiology. Information-dense data sets derived from pathophysiological, proteomic and transcriptomic profiling have been applied to map quantitative trait loci (QTLs). Metabolic traits, already used in QTL studies in plants, are essential phenotypes in mammalian genetics to define disease biomarkers. Using a complex mammalian system, here we show chromosomal mapping of untargeted plasma metabolic fingerprints derived from NMR spectroscopic analysis in a cross between diabetic and control rats. We propose candidate metabolites for the most significant QTLs. Metabolite profiling in congenic strains provided evidence of QTL replication. Linkage to a gut microbial metabolite (benzoate) can be explained by deletion of a uridine diphosphate glucuronosyltransferase. Mapping metabotypic QTLs provides a practical approach to understanding genome-phenotype relationships in mammals and may uncover deeper biological complexity, as extended genome (microbiome) perturbations that affect disease processes through transgenomic effects may influence QTL detection.


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CRRD Object Information
CRRD ID: 1601533
Created: 2007-04-24
Species: All species
Last Modified: 2007-04-24
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.