Inheritance of many quantitative traits (e.g., blood pressure) in different pedigrees in a population can occur with more than a single pattern of genetic transmission. This genetic heterogeneity presents major problems for modelling inheritance, and currently available statistical techniques usually ignore the reality of heterogeneity by assuming the universal operation of common genetic and environmental influences throughout the population. The estimates of transmission parameters derived from such models than relate to overall population characteristics; they are in appropriate for individual pedigrees to the extent that transmission within each pedigree differs from the model describing the entire population. For the identification of simple genetic and environmental factors controlling quantitative phenotypes, the most biologically interesting families are likely to be those in which major genes contribute importantly to the inheritance of a trait of interest. Because current techniques simply will not efficiently identify such pedigrees and in many cases will fail to fit major gene transmission models, it is the purpose of this proposal to develop novel techniques for the identification of modes of transmission of genetically heterogeneous quantitative traits. We will use the techniques developed to explore the Tecumseh Health Study data base to identify families will evidence of major gene transmission patterns for blood pressure. Furthermore, we believe that the methods developed will be of general utility for the identification of specific modes of transmission of any quantitative trait, and the families identified will be useful to molecular geneticists interested in defining the specific genes mediating the transmission of hypertension in families.
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