Segregation and linkage analyses of a large pedigree with hypertriglyceridemia.

Abstract

AbstractBlood, urine, and saliva samples were obtained from 100 members (42 males and 58 females) of a large family with an increased incidence of cardiac illness to study the mode of genetic transmission of hyperlipidemia, and the linkage relations of this trait with polymorphic markers. Total cholesterol, triglycerides, and lipoprotein Svedberg fractions were determined, the atherogenic index was computed, and 30 markers, including 27 polymorphic ones, were determined.The fit of one distribution and mixtures of two and three distributions, on both the original and the logarithmic scale, were examined for each quantitative trait. Triglyceride levels showed a significantly better fit to a mixture of two lognormal distributions than to a single lognormal distribution. Triglycerides showed the highest proportion of variance accountable by genetic transmission (74.9%), followed by cholesterol (52.1%); these two traits were chosen for major gene pedigree analyses. Hypertriglyceridemia gave a good fit to an autosomal dominant mode of transmission, the minimum probability of miclassification being 9.3%. From a bivariate analysis of these two variables the linear function that best separates the two groups was derived and the minimum percentage of misclassification for this function was found to be 6.8%.Linkage analysis between the possible major locus for elevated triglycerides and the 27 polymorphic markers indicated no significant lod scores; but a positive lod score of 0.73 was obtained with pepsinogen, at equal male and female recombination fractions of 0.1. More data are needed to confirm or deny this possible linkage.