STEPWISE OLIGOGENIC SEGREGATION AND LINKAGE ANALYSIS ILLUSTRATED WITH DOPAMINE-BETA-HYDROXYLASE ACTIVITY

A stepwise oligogenic method is developed that can be used to adjust the phenotype of a quantitative trait for the effects of a previously identified single-locus component. This method assumes that a single-locus component can be adequately identified through the use of segregation and/or linkage analysis under a 1-locus model and that the variation due to that locus can be removed from the phenotype leaving a residual that can be parameterized in terms of an additional single-locus component. Segregation and/or linkage analysis can then be used in an attempt to identify an additional single-locus component in the residual phenotype. This stepwise process can be repeated until no further single-locus effects are identified. The method is illustrated using family data on the specific activity of dopamine-β-hydroxylase (DBH), which a number of studies have suggested may be due either to the combined effects of single-locus and multifactorial components or to the combined effects of 2 loci.