Genetic analysis of total cholesterol and triglycerides in a pedigree of St. Thomas rabbits.

Abstract

A pedigree consisting of 103 New Zealand White hyperlipidemic and normal rabbits was used in a genetic analysis of total cholesterol and triglyceride levels to test for Mendelian control of hyperlipidemia. The founder male of this pedigree was identified through hypercholesterolemia and evidence suggested vertical transmission of a hypercholesterolemic phenotype in this pedigree, although a combined hyperlipidemia phenotype (elevated cholesterol and triglycerides) also occurred in many descendents of the original founders. Segregation analysis of quantitative measures of total cholesterol and triglycerides in this pedigree was employed to test hypotheses about Mendelian control in the presence of substantial inbreeding. A simple Mendelian model was the best explanation for triglycerides in these animals. This best fitting model was essentially co-dominant with genotypic specific variances, where the heterozygote was hypertriglyceridemic and the mutant homozygote showed even more extreme values. The observed distribution of total cholesterol was also compatible with a mixture of distinct genotypic distributions, but there was evidence of non-Mendelian transmission in this pedigree. The observed hypertriglyceridemia in these animals may reflect an abnormality of very low density lipoprotein metabolism described previously. Further studies will be required to elucidate the genetic control of hypercholesterolemia and the associated combined hyperlipidemia in these rabbits.