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

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Nicolas Toussaint, Yushi Redhead, Marta Vidal-garcía, Lucas Lo Vercio, Wei Liu, Elizabeth M. C. Fisher, Benedikt Hallgrímsson, Victor L. J. Tybulewicz, Julia A. Schnabel, Jeremy B. A. Green

Original languageEnglish
Article number188631
JournalDevelopment (Cambridge)
Volume148
Issue number18
DOIs
Accepted/In press1 Feb 2021
PublishedSep 2021

Bibliographical note

Funding Information: V.L.J.T. and E.M.C.F. were supported by the Wellcome Trust (grants 080174, 098327 and 098328) and V.L.J.T. by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001194), the UK Medical Research Council (FC001194) and the Wellcome Trust (FC001194). Y.R. was supported by the Francis Crick Institute and King's College London. J.B.A.G. was supported by King's College London. N.T. and J.A.S. acknowledge support from the Wellcome Trust/Engineering and Physical Sciences Research Council Centre for Medical Engineering (WT 203148/Z/16/Z) and theWellcome Trust IEH Award (102431). B.H. was supported by a Canadian Institutes of Health Research Foundation grant, the National Institutes of Health (R01 R01DE019638) and the Canada Foundation for Innovation. M.V.G. was supported by an ACHRI Postdoctoral Fellowship and L.L.V. by an Eyes High Postdoctoral Fellowship (University of Calgary). Open access funding provided by the Francis Crick Institute. Deposited in PMC for immediate release. Publisher Copyright: © 2021 Company of Biologists Ltd. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

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    Uploaded date:27 May 2021

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King's Authors

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.

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