GENETICS SOCIETY OF CANADA AWARD OF EXCELLENCE LECTURE: THE GENETICS OF COMMON FAMILIAL DISORDERS — MAJOR GENES OR MULTIFACTORIAL?

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Abstract
The common familial disorders were, until recently, neglected by geneticists because their familial distributions did not neatly fit the Mendelian mold, and no specific genes could be identified. The multifactorial-threshold model made the familial characteristics of these disorders more intelligible. Although it originally postulated a polygenic genetic component the model can also accommodate one or more major genes with low penetrance. The resulting upsurge of interest has led to (1) the development of increasingly sophisticated mathematical models from which to calculate recurrence risks for specific family situations and (2) the identification of specific predisposing genes in a number of such disorders. One of the corollaries of the model is that any pharmacological agent at therapeutic doses is likely to be teratogenic to at least some embryos, so that regulation should be in terms of "acceptably low" levels of teratogenicity rather than "safety".