Glaucoma-causing ADAMTS17 mutations are also reproducibly associated with height in two domestic dog breeds: selection for short stature may have contributed to increased prevalence of glaucoma

Emily C Jeanes; James A C Oliver; Sally L Ricketts; David J Gould; Cathryn S Mellersh

doi:10.1186/s40575-019-0071-6

Glaucoma-causing ADAMTS17 mutations are also reproducibly associated with height in two domestic dog breeds: selection for short stature may have contributed to increased prevalence of glaucoma

Canine Genet Epidemiol. 2019 May 17:6:5. doi: 10.1186/s40575-019-0071-6. eCollection 2019.

Authors

Emily C Jeanes¹, James A C Oliver², Sally L Ricketts², David J Gould³, Cathryn S Mellersh²

Affiliations

¹ 1Centre for Small Animal Studies, Animal Health Trust, Lanwades Park, Kentford, Newmarket, CB8 7UU UK.
² 2Canine 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.

Abstract

Background: In humans, ADAMTS17 mutations are known to cause Weill-Marchesani-like syndrome, which is characterised by lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature. Breed-specific homozygous mutations in ADAMTS17 are associated with primary open angle glaucoma (POAG) in several dog breeds, including the Petit Basset Griffon Vendeen (PBGV) and Shar Pei (SP). We hypothesised that these mutations are associated with short stature in these breeds.

Methods: Two hundred thirty-three PBGV and 66 SP 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 likelihood ratio tests to assess the shape of the association by comparing a general model with a linear (per allele) model.

Results: The adjusted mean heights of affected, carrier, and clear PBGV were 33.49 cm (n = 21, 95% CI 32.78-34.19 cm), 34.88 cm (n = 85, 95% CI 34.53-35.25 cm), and 34.92 cm (n = 121, 95% CI 34.62-35.21 cm), respectively. The mean heights of affected, carrier, and clear SP were 43.96 cm (n = 9, 95% CI 41.88-46.03 cm), 47.56 cm (n = 28, 95% CI 45.50-48.63 cm), and 48.95 cm (n = 23, 95% CI 47.80-50.11 cm), respectively. There was a significant difference between the height of affected and clear animals in the PBGV (P = 0.001) and the SP (P = < 0.0001).

Conclusions: ADAMTS17 POAG mutations are significantly associated with height in these breeds.

Keywords: ADAMTS17; Height; Primary Lens luxation; Primary open angle Glaucoma; Weill-Marchesani-like syndrome.