SYNERGISTIC INTERACTIONS BETWEEN 2 SKELETAL MUTATIONS IN MICE - INDIVIDUAL AND COMBINED EFFECTS OF THE SEMIDOMINANTS CLEIDOCRANIAL DYSPLASIA (CCD) AND SHORT DIGITS (DSH)

Heterozygotes for cleidocranial dysplasia (Ccd) and short digits (Dsh) were crossed to test whether synergistic interactions occur between d ifferent dominant mutations whose individual pleiotropic phenotypic ef fects exhibit a common feature. These unlinked mutations are homozygou s lethal, and they are congenic on the C57BL/10 background. Each mutat ion caused more than 10 different anomalies and showed variable expres sivity. Each mutation produced several malformations that were present in every heterozygote. Seven different synergistic interactions were found, including one that yielded an entirely new abnormality not pred icted from any abnormalities found in either of the single heterozygot es. Although synergistic interactions between dominant mutations have not, to our knowledge, been described in humans, these findings in mic e increase the probability that they occur in humans. Under certain ci rcumstances in human populations, the segregation of mutations causing synergistic interactions of the type demonstrated might be confused w ith recessive inheritance. It will be important to learn whether syner gistic interactions can occur between other mutations. If they can, it will probably become important to take synergistic interactions into account when estimating the genetic hazards to humans from mutagens. T hree antagonistic interactions were also found.