Genetics, biology and multifactorial diseases.

The schematic concept of "levels of causal interaction" is applied to the relation between genetics and biology. The strength of classical formal genetics lies in its power to proceed directly from observations on an external phenotype, to inferences concerning the nature and properties of the fundamental genetic factors. Its weakness comes from the fact that by short-circuiting the causal chain leading from genotype to phenotype, it creates a divorce between genetics and biology. It is argued that in order to reestablish an articulation of genetics and the biology of whole organisms, it will be necessary to study in detail the entire causal chain leading from a difference in a genetic factor to a difference in a corresponding phenotypic character. This proposal is illustrated by a consideration of multifactorial diseases, which appear to be due to strong interactions between a moderate number of distinct loci; the frequency of "abnormal" alleles at any given locus may be surprisingly high.