Letter abstract
Nature Genetics 39, 666 - 672 (2007)
Published online: 15 April 2007 | doi:10.1038/ng2026
Direct quantitative trait locus mapping of mammalian metabolic phenotypes in diabetic and normoglycemic rat models
Marc-Emmanuel Dumas1,5, Steven P Wilder2,5, Marie-Thérèse Bihoreau2, Richard H Barton1, Jane F Fearnside2, Karène Argoud2, Lisa D'Amato2, Robert H Wallis2, Christine Blancher2, Hector C Keun1, Dorrit Baunsgaard3, James Scott4, Ulla Grove Sidelmann3, Jeremy K Nicholson1 & Dominique Gauguier2
Characterizing the relationships between genomic and phenotypic variation is essential to understanding disease etiology. Information-dense data sets derived from pathophysiological1, proteomic2, 3 and transcriptomic4 profiling have been applied to map quantitative trait loci (QTLs). Metabolic traits, already used in QTL studies in plants5, 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 analysis6 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 genome7 (microbiome) perturbations that affect disease processes through transgenomic effects8 may influence QTL detection.
- Imperial College London, Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Sir Alexander Fleming Building, Exhibition Road, South Kensington, London SW7 2AZ, UK.
- The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.
- NovoNordisk A/S, Novo Nordisk Park DK-2760 Måløv, Denmark.
- Imperial College London, National Heart and Lung Institute, Faculty of Medicine, South Kensington, The Flowers Building, London SW7 2AZ, UK.
- These authors contributed equally to this work.
Correspondence to: Jeremy K Nicholson1 e-mail: j.nicholson@imperial.ac.uk
Correspondence to: Dominique Gauguier2 e-mail: gdomi@well.ox.ac.uk
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse modelMolecular Systems Biology Article (22 May 2007)
Chromosomal mapping of genetic loci associated with non-insulin dependent diabetes in the GK ratNature Genetics Article (01 Jan 1996)
SNP and haplotype mapping for genetic analysis in the ratNature Genetics Technical Report (01 May 2008)
See all 4 matches for Research