The genetic analysis of familial traits - II. Double gene substitutions, with special reference to hereditary dwarfism
The limits between which the expected ratios of affected offspring of parents of all possible phenotypes will lie, when a trait is determined by two complementary dominant genes on different chromosomes, or two independent recessive genes, have been investigated in this communication. The proportions expected vary with the incidence of the trait in the population. In the case of a trait determined by two independent complementary dominant genes the limiting value for matings of two normal parents is the same as that for a single recessive trait. When the two gene frequencies are of the same order this limit is reached rapidly.
Recorded data of various pathological conditions have been examined from this standpoint, and it has been shown that the extant observations on ateleiosis, and the Japanese cases of hereditary optic atrophy are interpretable on the assumption that this condition is significantly determined by two dominant genes. It is unlikely that this explanation will be found to apply to achondroplasia. It is possible that it applies to cleft palate, harelip and glioma retinae.
The foregoing analysis emphasises four prerequisites for the application of factorial analysis to clinical data. These are: first, exact information concerning the frequency of familial traits in the general population; second, the elimination of any bias due to neglect of families with a low familial incidence; third, the collection of random samples of matings involving one affected parent unbiassed by the possibility that such matings may or may not yield affected offspring; and finally, searching enquiry into the tendency to assortative mating.
One significant outcome of the present enquiry is the fact that the expected proportions of affected individuals calculated in such a way as to make allowance for the small size of the human family diverge at the lower limit much less rapidly than is at all obvious at first sight, as the number of genes determining a given trait increases.
Volume 100, 2021
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