Mapping of obesity QTLs in a cross between mouse lines divergently selected on fat content

A genome-wide quantitative trait locus (QTL) analysis was performed in a polygenic obesity mouse model resulting from a long-term selection experiment. The parental lines were outbred lines divergently selected for 53 generations for high-fat (fat, F line) or low-fat (lean, L line) percentage (fat%)...

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Bibliographic Details
Published in:Mammalian genome 2000, Vol.11 (1), p.2-7
Main Authors: Horvat, Simon, Bünger, Lutz, Falconer, Victoria M, Mackay, Pamela, Law, Andy, Bulfield, Grahame, Keightley, Peter D
Format: Article
Language:English
Subjects:
animal models
Animals
chromosome 12
chromosome 15
chromosome 2
Chromosome Mapping
Crosses, Genetic
Disease Models, Animal
DNA - chemistry
Electrophoresis, Agar Gel
Female
Fob1 gene
Fob2 gene
Fob3 gene
Fob4 gene
genes
Genetics
Genomes
Genomics
lipid content
loci
Male
Mice
Mice, Inbred ICR
mutation
Obesity
Obesity - genetics
outbred lines
phenotypic variation
Polymerase Chain Reaction
quantitative trait loci
Quantitative Trait, Heritable
Sequence Analysis, DNA
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Summary:A genome-wide quantitative trait locus (QTL) analysis was performed in a polygenic obesity mouse model resulting from a long-term selection experiment. The parental lines were outbred lines divergently selected for 53 generations for high-fat (fat, F line) or low-fat (lean, L line) percentage (fat%) that differed fivefold in fat% at 14 weeks of age. An F₂ population of 436 mice was used for the QTL analysis with 71 markers distributed across the genome. The analysis revealed significant QTLs Fob1 (for F-line obesity QTL 1), Fob2, Fob3, and Fob4, on Chromosomes (Chrs) 2, 12, 15, and X, respectively. None of these QTLs map to regions of known single gene obesity mutations (Lep ᵒᵇ , Lepr ᵈᵇ , Cpe ᶠᵃᵗ , A ʸ , tub), though they map to regions of previously described obesity QTLs and candidate genes. The effects of Fob1, Fob3, Fob4 were additive, and that of Fob2 was dominant. Fob2 also showed a significant female-specific effect. Fob1, Fob2, Fob3, and Fob4 explained 4.9%, 19.5%, 14.4%, and 7.3% of the F₂ phenotypic variance for fat%, respectively. This study identified four loci that contributed to the response to divergent selection and control a significant proportion of the difference in obesity between the F and L lines.
ISSN:0938-8990
1432-1777
DOI:10.1007/s003350010002