Abstract
An F2 pedigree based on the mouse lines DU6i and DBA/2 with extremely different growth and obesity characteristics was generated to search for QTLs affecting serum concentrations of triglycerides (TG), total cholesterol (CHOL), HDL cholesterol (HDL-C), and LDL cholesterol (LDL-C). Compared with many other studies, we searched for spontaneous genetic variants contributing to high lipid levels under a standard breeding diet. Significant QTLs for CHOL were identified on chromosomes 4 and 6, and a female-specific locus on chromosome 3. QTLs for HDL-C were detected on chromosome 11 for both sexes, and on chromosome 1 for females. These QTLs are located in syntenic human regions that have QTLs that have not been previously confirmed in animal studies. LDL-C QTLs have been mapped for both sexes to chromosome 8 and in males on chromosome 13. Epistatic interactions that significantly accounted for the phenotypic variance of HDL-C, CHOL, and LDL-C serum concentrations were also detected with one interaction between chromosomes 8 and 15, accounting for 22% of the observed variance in LDL-C levels. The identified loci coincide in part with regions controlling growth and obesity. Thus, multiple genes or pleiotropic effects may be assumed. The identified QTLs for cholesterol and its transport proteins as subcomponents of risk for coronary heart disease will further improve our understanding of the genetic net controlling plasma lipid concentrations.
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Acknowledgments
Excellent technical assistance was provided by Hannelore Tychsen for DNA preparation and genotyping. We thank Jürgen Kratzsch from the Department of Clinical Chemistry and Pathobiochemistry at the University of Leipzig, and Beate Gomolka for their help in the evaluation of lipid measurements in mice. This work was supported by grants from the German Research Foundation (BR 1285/5), the German National Genome Research Network (NGFN2, registration no. 01GS0486), and the H. Wilhelm Schaumann Stiftung to GAB. CSH acknowledges support from the BBSRC and MAFF.
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Brockmann, G.A., Karatayli, E., Neuschl, C. et al. Genetic control of lipids in the mouse cross DU6i × DBA/2. Mamm Genome 18, 757–766 (2007). https://doi.org/10.1007/s00335-007-9068-7
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DOI: https://doi.org/10.1007/s00335-007-9068-7