Abstract
ABSTRACTCharacterising phenotypes often requires quantification of anatomical shape. Quantitative shape comparison (morphometrics) traditionally uses manually located landmarks and is limited by landmark number and operator accuracy. Here, we apply a landmark-free method to characterise the craniofacial skeletal phenotype of the Dp1Tyb mouse model of Down syndrome and a population of the Diversity Outbred (DO) mouse model, comparing it with a landmark-based approach. We identified cranial dysmorphologies in Dp1Tyb mice, especially smaller size and brachycephaly (front-back shortening), homologous to the human phenotype. Shape variation in the DO mice was partly attributable to allometry (size-dependent shape variation) and sexual dimorphism. The landmark-free method performed as well as, or better than, the landmark-based method but was less labour-intensive, required less user training and, uniquely, enabled fine mapping of local differences as planar expansion or shrinkage. Its higher resolution pinpointed reductions in interior mid-snout structures and occipital bones in both the models that were not otherwise apparent. We propose that this landmark-free pipeline could make morphometrics widely accessible beyond its traditional niches in zoology and palaeontology, especially in characterising developmental mutant phenotypes.
Highlights
IntroductionMorphometrics is less used in other fields, such as genetics and developmental biology
For the landmark-free approach we developed a pipeline based on previous approaches in morphometrics and neuroimaging
The reader is directed to the relevant section of Materials and Methods and to the supplementary Materials and Methods but, in brief, following thresholding to extract the skull structures from the μCT images, cartilaginous structures were removed (Fig. S2) and the images segmented using bone density to separate the mandibles from the crania (Fig. 1, step 1)
Summary
Morphometrics is less used in other fields, such as genetics and developmental biology. This may be because current morphometric methodologies, powerful, have several limitations. The number of landmarks always reflects a compromise between precision, which needs many anatomical landmarks to be located, and ease-of-use, which limits those numbers. Having many landmarks is preferable because differences are mapped where, or close to where, they occur. This improves spatial resolution and the fidelity of shape-difference visualisation, and has the potential to avoid the need to separate size and shape change as all mapping can be highly local. Some tens of landmarks are located manually, which takes considerable anatomical knowledge and training and time
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