The distribution of fetal death in control mice and its implications on statistical tests for dominant lethal effects.

In dominant lethal testing fetal death is generally assumed to follow either a Poisson or binomial distribution. However, both of these models were found to be inappropriate when three large sets of mouse control data and other data sets from the literature were examined. The validity of statistical test procedures based on these inappropriate models was then studied in detail. It was found that chi-square tests (which assume an underlying binomial distribution) may seriously exaggerate the level of significance and hence should not be used. In contrast, the inappropriateness of the underlying Poisson or binomial model appeared to have little effect on the validity of pairwise comparisons by analysis of variance procedures. Unlike chi-square, these procedures regard the pregnant female rather than the individual implant as the experimental unit. However, a statistical analysis of dominant lethal data generally involves more than a series of pairwise comparisons, and it is unclear how an invalid underlying model may affect statistical test procedures in this more complex situation. Moreover, it is difficult to justify the use of statistical models that are demonstrably invalid when a reasonable alternative exists. Thus, until a satisfactory parametric model can be found and appropriate test procedures derived, we prefer to analyze dominant lethal data by non-parametric (distribution-free) methods. Proportion of dead implants per female appears to be a more meaningful measure of fetal death than number of dead implants per female for several seasons which include (1) analyses based on proportions take the total number of implants per female into account and (2) analyses based on proportions make more reasonable assumptions concerning pre-implantation losses and are more powerful when such losses occur. Despite our concern with the appropriateness of the underlying model, in practice we have found few instances in which non-parametric and analysis of variance procedures have led to markedly different conclusions.