COMBINED PEDIGREE AND TWIN FAMILY STUDY TO DETERMINE THE SOURCES OF VARIATION IN SERUM BIOTINIDASE ACTIVITY - THE USEFULNESS OF MULTIPLE STUDY DESIGNS

Biotinidase, the enzyme responsible for recycling the vitamin biotin, is deficient in most individuals with late-onset multiple carboxylase deficiency. Based on clinical criteria, biotinidase deficiency appears to be inherited as an autosomal recessive trait; however, the inherit ance of biotinidase serum activity as a quantitative trait has not bee n studied previously. In this study, both segregation analysis of prob and families and the analysis of twin family data were used to determi ne the relative contributions of a major gene, polygenes and environme nt to the variation in serum biotinidase activity. Segregation analysi s of 24 families of biotinidase-deficient individuals indicated that s erum biotinidase activity is determined by the segregation of a single codominant major gene with the variability about the mean of each maj or genotype attributable to environmental effects. Significant polygen ic effects could not be detected by this analysis. Variance component analysis of 128 twin families, which included the twins, their spouses , and their offspring, indicated that 70% of total variance in biotini dase activity is attributable to additive genetic effects, 22% to indi vidual environmental effects, and 8% to shared environmental effects. The model also included an age effect for females. A portion (27%) of the estimated additive variance may be attributed to the segregation o f the major gene. This study emphasizes the usefulness of studying mul tiple data sets representing different types of family relationships. (C) 1993 Wiley-Liss, Inc.