Stepwise oligogenic segregation and linkage analysis illustrated with dopamine‐β‐hydroxylase activity

Abstract

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 singlelocus and multifactorial components or to the combined effects of 2 loci.