Genetic factors that contribute to interindividual variations in plasma low density lipoprotein-cholesterol levels.
The interplay of multiple genes and environmental factors generates interindividual variation in plasma low density lipoprotein-cholesterol (LDL-C) concentrations. As a result, it has been difficult to identify individual genes that contribute to variation in plasma LDL-C levels using classical linkage analysis. We have exploited a genetic defect in the gene encoding the LDL receptor that is associated with a dramatically elevated plasma LDL-C level to unmask an allele at another locus that lowers plasma LDL-C levels. The existence of such an allele was implied by the analysis of a human pedigree with familial hypercholesterolaemia in which a third of the familial hypercholesterolaemia heterozygotes had normal levels of LDL-C. To develop an animal model of this LDL-C lowering effect and to identify genes that modify the plasma LDL-C level, we crossed LDL receptor-deficient mice with other strains of mice.
Cohen
J
J
Center for Human Nutrition, University of Texas, Southwestern Medical Center, Dallas 75235, USA.
Gaw
A
A
Barnes
R I
RI
Landschulz
K T
KT
Hobbs
H H
HH
D000483:Alleles; D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000235:genetics*; D005799:Genes, Dominant; D008040:Genetic Linkage; D014644:Genetic Variation; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008957:Models, Genetic; D005810:Multigene Family; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011647:Puerto Rico
D008077:Lipoproteins, LDL; D002784:Cholesterol