Association of primary open angle glaucoma ADAMTS17 mutations with height in two domestic dog breeds

Presenter Sally Ricketts
Authors EC Jeanes1, JAC Oliver2, SL Ricketts2, DJ Gould3 and CS Mellersh2
Affiliations 1. Centre for Small Animal Studies, Animal Health Trust, Lanwades Park, Kentford, Newmarket, CB8 7UU, UK; 2. Canine Genetics Research Group, Kennel Club Genetics Centre, Animal Health Trust, Lanwades Park, Kentford, Newmarket, CB8 7UU, UK. 3. Davies Veterinary Specialists, Manor Farm Business Park, Higham Gobion, Hitchin SG5 3HR, UK.
Presentation Type Talk


There are currently five known ADAMTS17 mutations in the dog that are associated with the development of either primary open angle glaucoma or primary lens luxation. Interestingly, these mutations have been identified in breeds of generally short stature including terriers and Basset breeds. In humans, mutations in the ADAMTS17 gene are associated with Weill-Marchesani syndrome – a disorder whose clinical characteristics include ocular manifestations such as microspherophakia, myopia, glaucoma, and cataract, in addition to brachydactyly and short stature. This led us to hypothesise that these mutations may also be associated with height in these breeds. To test this, we conducted an association analysis between breed-specific ADAMTS17 mutations and height in two of these breeds – the Petit Basset Griffon Vendeen and Shar Pei. Two hundred and twenty-seven Petit Basset Griffon Vendeen and 65 Shar Pei were genotyped for their breed-specific ADAMTS17 mutations. The height of each dog was measured at the withers. We used linear per allele regression to assess the association between ADAMTS17 mutations and height as a continuous variable, and linear regression and log-likelihood ratio tests to assess the shape of the association by comparing a general model with a linear per allele model. The mean heights of affected (n=21), carrier (n=84) and clear (n=122) Petit Basset Griffon Vendeen were 33.41 cm, 34.78 cm and 34.93 cm, respectively. The mean heights of affected (n=9), carrier (n=30) and clear (n=26) Shar Pei were 43.32 cm, 47.93 cm and 48.38 cm, respectively. Each breed-specific ADAMTS17 mutation showed a strong association with height in both breeds: Petit Basset Griffon Vendeen (P=7.9 x 10-3); Shar Pei (P=6.9 x 10-5). The shape of the associations appeared similar between the two breeds. In humans, ADAMTS17 affects skeletal development by modulating the extracellular matrix. A similar mechanism may be present in the dog. We speculate that selection for short stature might have inadvertently increased ADAMTS17 mutant allele frequencies and thus increased prevalence of primary open angle glaucoma in these breeds.