Cleft palate: more genetic lessons from mice

Cleft palate occurred in high frequency (14%) in the F2 generation of the cross between two stocks of mice, LGG and SELH, neither of which produces more than 2% cleft palate. The cleft palate trait results from a new combination of alleles that is not present in either parental stock. The lack of cleft palate in the F2 generation after outcrosses of both parental stocks to other strains shows that this new combination of alleles has specific contributions from both parental strains, and also that there must be at least two loci involved. A deficiency of Mod-1 homozygotes in the SELH/LGG F2 adults suggests that one of the loci involved may be linked to Mod-1 and that the number of loci involved is few. Significantly more F2 males (19%) than females (9%) were affected with cleft palate. The data can be explained by a two-locus epistatic model with a dominant mutation (P) at one locus that causes cleft palate when not suppressed by or compensated for by a dominant allele (S) at a second locus. The parental stocks would be PPSS and ppss. In the F2 generation, the new combinations PPss and Ppss would express cleft palate, a total expected of 19%. Similar new combinations of alleles at two loci may explain some instances of high occurrence of cleft palate or other developmental threshold traits in previously unaffected human families.