The relative importance of principal and modifying genes in determining some human diseases

Summary

Bell’s data on the age of onset of some human hereditary diseases are discussed. In glaucoma, peroneal atrophy, Friedreich’s ataxia, spastic ataxia, and spastic paraplegia, the age of onset in all affected members of a pedigree is nearly the same, while different pedigress differ widely. Thus a number of different main genes must be responsible for the clinically indistinguishable diseases in different families. In optic atrophy and Huntington’s chorea the differences of age of onset within a pedigree are nearly as large as those between different pedigrees. So the same main gene may be responsible for all cases, while modifying genes account for much of the difference in age of onset. The bearing of these facts on evolutionary theories is discussed.