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Canine Brachycephaly Is Associated with a Retrotransposon-Mediated Missplicing of SMOC2

Marchant, T W; Johnson, E J; McTeir, L; Johnson, C I; Gow, A; Liuti, T; Kuehn, D; Svenson, K; Bermingham, M L; Drögemüller, M; Nussbaumer, M; Davey, M G; Argyle, D J; Powell, R M; Guilherme, S; Lang, J; Ter Haar, G; Leeb, T; Schwarz, T; Mellanby, R J; Clements, D N; Schoenebeck, J J


T W Marchant

E J Johnson

L McTeir

C I Johnson

A Gow

T Liuti

D Kuehn

K Svenson

M L Bermingham

M Drögemüller

M Nussbaumer

M G Davey

D J Argyle

R M Powell

S Guilherme

J Lang

G Ter Haar

T Leeb

T Schwarz

R J Mellanby

D N Clements

J J Schoenebeck


In morphological terms, “form” is used to describe an object’s shape and size. In dogs, facial form is stunningly diverse. Facial retrusion, the proximodistal shortening of the snout and widening of the hard palate is common to brachycephalic dogs and is a welfare concern, as the incidence of respiratory distress and ocular trauma observed in this class of dogs is highly correlated with their skull form. Progress to identify the molecular underpinnings of facial retrusion is limited to association of a missense mutation in BMP3 among small brachycephalic dogs. Here, we used morphometrics of skull isosurfaces derived from 374 pedigree and mixed-breed dogs to dissect the genetics of skull form. Through deconvolution of facial forms, we identified quantitative trait loci that are responsible for canine facial shapes and sizes. Our novel insights include recognition that the FGF4 retrogene insertion, previously associated with appendicular chondrodysplasia, also reduces neurocranium size. Focusing on facial shape, we resolved a quantitative trait locus on canine chromosome 1 to a 188-kb critical interval that encompasses SMOC2. An intronic, transposable element within SMOC2 promotes the utilization of cryptic splice sites, causing its incorporation into transcripts, and drastically reduces SMOC2 gene expression in brachycephalic dogs. SMOC2 disruption affects the facial skeleton in a dose-dependent manner. The size effects of the associated SMOC2 haplotype are profound, accounting for 36% of facial length variation in the dogs we tested. Our data bring new focus to SMOC2 by highlighting its clinical implications in both human and veterinary medicine.


Marchant, T. W., Johnson, E. J., McTeir, L., Johnson, C. I., Gow, A., Liuti, T., …Schoenebeck, J. J. (2017). Canine Brachycephaly Is Associated with a Retrotransposon-Mediated Missplicing of SMOC2. Current Biology, 27(11), 1573-1584.

Journal Article Type Other
Acceptance Date Apr 27, 2017
Publication Date May 25, 2017
Deposit Date May 31, 2017
Publicly Available Date May 31, 2017
Print ISSN 0960-9822
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 27
Issue 11
Pages 1573-1584
Public URL


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