A landmark-free morphometrics pipeline for high-resolution phenotyping: application to a mouse model of Down syndrome

Author:

Toussaint Nicolas1ORCID,Redhead Yushi23,Vidal-García Marta4ORCID,Lo Vercio Lucas4ORCID,Liu Wei4,Fisher Elizabeth M. C.5ORCID,Hallgrímsson Benedikt4ORCID,Tybulewicz Victor L. J.36ORCID,Schnabel Julia A.1ORCID,Green Jeremy B. A.2ORCID

Affiliation:

1. School of Biomedical Engineering and Imaging Sciences, King's College London, UK

2. Centre for Craniofacial Biology & Regeneration, King's College London, UK

3. The Francis Crick Institute, London NW1 1AT, UK

4. Department of Cell Biology & Anatomy, University of Calgary, Calgary AB T2N 4N1, Canada

5. Department of Neurodegenerative Disease, Institute of Neurology, University College London, London WC1N 3BG, UK

6. Department of Immunology & Inflammation, Imperial College London, London W12 0NN, UK

Abstract

ABSTRACT Characterising 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.

Funder

Wellcome Trust

Cancer Research UK

Medical Research Council

King's College London

Engineering and Physical Sciences Research Council

Canadian Institutes of Health Research Foundation

National Institutes of Health

Canada Foundation for Innovation

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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