Canine genetics success stories
Hereditary Cataract
Cataracts are a leading cause of blindness in dogs. Using a candidate gene approach, scientists at the Animal Health Trust have successfully identified the mutation that causes both hereditary cataract (HC) in Staffordshire Bull terriers and French Bulldogs and early onset hereditary cataract (EHC) in Boston terriers. This is the first mutation to be associated with HC in dogs and is an important breakthrough from both genetics and breeding viewpoints. A diagnostic test, exclusive to the Animal Health Trust, is now being offered which will determine the genetic status of dogs, with respect to this mutation, and inform breeders which dogs can be mated together safely, without the risk of producing
affected puppies.
Mellersh CS, Pettitt L, Forman OP, Vaudin M, Barnett KC. (2006).
Identification of mutations in HSF4 in dogs of three different breeds with hereditary cataracts. Veterinary Ophthalmology. 9(5):369-78.
L-2-hydroxyglutaric aciduria
L-2-hydroxyglutaric aciduria (L-2-HGA) is a devastating disease that affects the nervous system. Clinical symptoms appear between the ages of 6 months and one year of age, and include seizures, in coordination (ataxia or wobbly gait), tremors and altered behaviour. Towards the end of 2004 two scientific papers were published announcing the identification of the gene involved with L-2-HGA in humans. We sequenced the same gene in affected and unaffected dogs and identified the mutation causing L-2-HGA in Staffordshire bull terriers. A diagnostic test for L-2-HGA is currently being offered at the AHT to diagnose L-2-HGA in Staffordshire Bull Terriers.
Penderis J, Calvin J, Abramson C, Jakobs C, Pettitt L, Binns MM, Verhoeven NM, O'Driscoll E, Platt SR, Mellersh CS. (2007). L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model. Journal Medical Genetics. 44(5):334-40.
Cone-Rod Dystrophy
Cone-Rod Dystrophy is an inherited degenerative disease of the retina, forms of which affect many breeds of dog. Genetic analysis of both a large inbred pedigree and outbred dogs from the worldwide pet population enabled the AHT to identify the mutation that causes cone-rod dystrophy in Miniature Longhaired and Miniature Smooth haired Dachshunds. A diagnostic test for this mutation is currently being offered at the AHT. We have also found the identical mutation present in English Springer spaniels and, in collaboration with Dr Gary Johnson at the University of Missouri-Columbia, we have confirmed that dogs that carry two copies of the mutation have a significantly increased risk of developing cone-rod dystrophy; a diagnostic test for cone-rod dystrophy in the English Springer spaniel was launched in April 2007.
Copper toxicosis
Copper toxicosis in Bedlington terriers is a genetic disorder causing elevated liver copper levels. Affected dogs suffer from hepatitis and progressive cirrhosis of the liver. The gene causing this disorder had been discovered previously*, and a large deletion was shown to be the causative mutation in the disease. Additional work at the AHT has enabled the mutation to be fully characterized+, allowing development of a robust diagnostic test.
* van De Sluis B, Rothuizen J, Pearson PL, van Oost BA, Wijmenga C. 2002. Identification of a new copper metabolism gene by positional cloning in a purebred dog population. Human Molecular Genetics. 11(2):165-73.
+ Forman OP, Boursnell ME, Dunmore BJ, Stendall N, van den Sluis B, Fretwell N, Jones C, Wijmenga C, Rothuizen J, van Oost BA, Holmes NG, Binns MM, Jones P. (2005). Characterization of the COMMD1 (MURR1) mutation causing copper toxicosis in Bedlington terriers. Animal Genetics. 36(6):497-501.
