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Direct quantitative trait locus mapping of mammalian metabolic phenotypes in diabetic and normoglycemic rat models
- Source :
- Nature Genetics. 39:666-672
- Publication Year :
- 2007
- Publisher :
- Springer Science and Business Media LLC, 2007.
-
Abstract
- 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.
- Subjects :
- Glucuronosyltransferase
Mammalian Genetics
Genetic Linkage
Molecular Sequence Data
Quantitative Trait Loci
Congenic
Disease
Biology
Quantitative trait locus
Benzoates
chemistry.chemical_compound
Diabetes Mellitus
Genetics
Animals
Microbiome
Nuclear Magnetic Resonance, Biomolecular
Genome
Base Sequence
Molecular Structure
food and beverages
Sequence Analysis, DNA
Phenotype
Rats
Uridine diphosphate
Metabolism
chemistry
biology.protein
Lod Score
Biomarkers
Subjects
Details
- ISSN :
- 15461718 and 10614036
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Nature Genetics
- Accession number :
- edsair.doi.dedup.....84eb80740df057a85e7f26e3fb16c399