Genetic analysis of the mandible morphology in DDD.Cg-$A^{y}$/Sgn and C57BL/6J inbred mice

Abstract

Quantitative trait loci (QTL) mapping analysis was performed for the mandible morphology in DDD.Cg-$A^{y}/\hbox {Sgn}$ and C57BL/6J inbred mice. The size and shape of the mandible was analysed by landmark-based geometric morphometrics as the centroid size and principal components (PCs), respectively. The $A^{y}$ allele at the agouti locus significantly reduced the mandible size in DDD/Sgn background, and substantially altered the mandible shape in both strain backgrounds. Single-QTL scans, by including the agouti locus genotype ($A^{y}$ or non-$A^{y}$) as an additive covariate, identified three significant QTL for the centroid size on chromosomes 5, 6 and 17, along with four suggestive QTL on chromosomes 2, 12, 18 and 19. These QTLs explained 46.85% of the centroid size variation in $\hbox {F}_{2}$ mice. When the $\hbox {F}_{2} A^{y}$ and $\hbox {F}_{2}$ non-$A^{y}$ mice were analysed separately, additional significant QTL were identified on chromosomes 12 and 15 in $\hbox {F}_{2}$ non-$A^{y}$ mice. Single-QTL scans also identified 15 significant QTL for the PC1, PC2 and PC3. When the agouti locus genotype was included as an interactive covariate, nine significant QTLs were identified. Unexpectedly, these agouti-interacting QTLs were identified for relatively minor PCs, for which no significant single-QTL were identified. Therefore, it was suggested that the alteration of the mandible shape in $A^{y}$ mice was the consequence of interactions between the $A^{y}$ allele and genes that themselves have relatively small phenotypic effect. Although further in vivo studies are required, we postulated Pkd1 as a possible candidate gene underlying QTL for the centroid size on chromosome 17.