A pathway model of lipid metabolism to predict the effect of genetic variability on lipid levels.
Complex phenotypes such as serum lipid concentrations involve numerous genes and require the analysis of the combined effects of these gene products. We modeled the interactions of six key lipid metabolism genes by means of differential equations. We tested the model by inserting the effects of known mutations in the low-density lipoprotein receptor gene and the lipoprotein lipase gene, as well as the effects of a high-fat diet, and observed that the predictions corresponded very well to published measurements. Models such as the one that we present here will become indispensable for analyzing and understanding the effects of variation in multiple genes.
Knoblauch
H
H
Franz Volhard Clinic, and Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University, Berlin, Germany.
Schuster
H
H
Luft
F C
FC
Reich
J
J
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D004041:Dietary Fats / Q000378:metabolism; D014644:Genetic Variation; D006023:Glycoproteins; D006801:Humans; D007700:Kinetics; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D053419:Lipoproteins, IDL; D008954:Models, Biological; D010641:Phenotype; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D011973:Receptors, LDL / Q000378:metabolism
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D004041:Dietary Fats; D006023:Glycoproteins; D008055:Lipids; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D011973:Receptors, LDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D008049:Lipase; D008071:Lipoprotein Lipase