Genetical studies on the skeleton of the mouse xv. Relations between major and minor variants

Abstract

1. The mutant genesun, Sd, vt, Bn, se, fi andtk in the mouse have been tested for possible effects on a group of fifteen minor variants of the skull and vertebral column. Each of the mutants has been found to be associated with effects on some of these characters (as many as eight each in the case ofse andfi). 2. The average effect on the minor variants associated with the mutant genes amounts to 1–16 standard deviations. 3. Substrain differences which arose in the C57BL strain in the course of continued inbreeding and which affect a similar set of minor variants are believed to represent single gene differences. The average effect of these single gene differences amounts to 0–58 standard deviations. 4. It is assumed that most or all of the effects associated with the major genes are pleiotropic effects of these genes themselves rather than effects of linked genes. This is based on the observation that genes (se, tk) which arose by spontaneous mutation in inbred strains and were studied on their original homogeneous backgrounds showed similar effects on the minor variants as genes segregating on heterogeneous backgrounds. Secondly, the effects associated with the major genes were greater than those which would have been expected in the case of linked genes (compare (2) and (3) above). 5. There are instances in which major genes affect a minor variant on some genetic backgrounds, but not on others. While these cases might be explicable in terms of linked genes, it is concluded that they are due either to specific gene interactions, or to differential gene effects depending on the physiological situation in which the gene finds itself. 6. On account of the facts mentioned under (5), genetic backgrounds must be regarded as unique, and experiments involving the genetic background as a variable as not accurately repeatable. 7. The pleiotropic effects of the major genes on minor variants are of a kind which could not have been predicted from what is known about the major actions of these genes. They are clearly very remote gene effects and their causal connexion with the ‘main’ effects of the genes is completely obscure. 8. It is concluded that the so-called polygenic variation is not due to a separate class of genes (the ‘polygenes’), but is best explained as clue to the pleiotropic effects of the normal alleles and iso-alleles of genes with major effects.