Congenital Ichthyosis
Congenital ichthyosis is a skin disease that is common among dogs of theGolden Retriever breed. The disorder is characterized by the excessive scaling ofskin, often visible at a few weeks of age. The scales may persist throughout theanimal’s life and progressively blacken. Infectious complications are occasionallyassociated with the condition. The age of onset and clinical symptoms of thecondition may vary in large scale.
Congenital ichthyosis in Golden Retrievers is caused by a mutation in PNPLA1
gene [1]. The mutation leads to the presence of a premature stop codon, resulting
in the synthesis of a truncated protein which is assumed to be biologically inactive
or has an altered biological activity. The disease is inherited in an autosomal
recessive pattern [1].
References:
1. Grall A, et al. PNPLA1 mutations cause autosomal recessive congenital ichtyosis in golden retriever dogs andhumans. Nature Genetics. 2012:44(2); 140-147.

Indications for genetic testing:
1. Carrier testing prior to breeding
2. Testing for affected dogs

Dry Eye and Curly Coat Syndrome
Dry eye and curly coat syndrome (Congenital keratoconjuctivitis sicca andichthyosiform dermatosis) is found in Cavalier King Charles Spaniels. The
disease affects the eyes and skin. Eye conditions are characterized by failure oftear production resulting in conjunctivitis, corneal ulceration and blindness. Skin
disorder includes curly or rough coat, hyperkeratinization of glabrous skin andfootpads.
The disease is associated with a single base deletion in the gene FAM83H. The
disease has autosomal recessive inheritance.
Indications for genetic testing:
1. Carrier testing prior to breeding
2. Testing for affected dogsEpisodic Falling Syndrome
Episodic falling syndrome (EFS) (also known as “sudden collapse”) is canine
paroxysmal hypertonicity disorder found in Cavalier King Charles Spaniels.
Episodes are induced by exercise, stress or excitement and characterized byprogressive hypertonicity throughout the thoracic and pelvic limbs. Typical sign ofthe disorder is temporary inability to relax the affected limb and trunk muscles. The
age of onset is between three and seven month of age, and affects both male andfemale dogs.
EFS is caused by 15.7 kb deletion in the BCAN gene encoding the brain-specificextracellular matrix proteoglycan brevican. The disease is inherited in an autosomal
recessive manner.

Indications for genetic testing:
1. Carrier testing prior to breeding
2. Testing for affected dogs

Exercise-Induced Collapse
Exercise-induced collapse (EIC) is a life-threatening condition most commonly
affecting Labrador retrievers. The disorder in dogs is characterized by muscle
weakness, loss of control of the limbs and lack of coordination after intense
exercise. If the exercise is continued, the dogs usually collapse. The symptoms ofthe disease commonly appear as dogs enter in strenuous training, however dogs
may not develop any symptoms depending on their lifestyle.
EIC has been associated with a mutation in DNM1 gene. A single nucleotide
substitution results in the conversion of arginine to leucine (p.Arg256Leu) [1]. The
carrier frequency of this mutation has been estimated as high as 37% in someLabrador retriever populations. Also, this mutation has been detected in other EIC
affected dogs including Curly-Coated and Chesapeake Bay Retrievers, BoykinSpaniels, Bouvier des Flanders, German Wirehaired Pointers, Old English
Sheepdogs, Cocker Spaniels and Pembroke Welsh Corgis. The pattern ofinheritance is autosomal recessive.
References:
1. Patterson EE, Minor KM, Tchernatynskaia AV, et al. A canine DNM1 mutation is highly associated with the syndrome of
exercise-induced collapse. Nat Genet. 2008 Oct;40(10):1235-9.

Indications for genetic testing:
1. Carrier testing prior to breeding
2. Testing for affected dogs

Multi-Drug ResistanceSeveral drugs such as ivermectin, doramectin, loperamide, vincristine,
vinblastine anddoxorubicin that are used in the treatment of dogs may induce
serious side-effects. It has been described that several dog breeds are more prone
to side-effects from these drugs. In dogs with genetic predisposition, the underlining
cause of this drug sensitivity is a mutation in MDR1 gene [1,2].
MDR1 protein is a drug transporter. The 4-bp deletion in MDR1 gene results in aframeshift in protein translation leading to a premature stop codon [1]. The
defective protein has reduced drug elimination ability and the accumulation oftoxins occurs. Exposure to certain drugs in dogs with MDR1 mutation may result inserious neurological symptoms including seizures, ataxia, blindness and death.
MDR1 mutation has been found in Australian Shepherd, Collie, Long-haired
Whippet, McNab, Silken Windhound and several other breeds [3].
References:
1. Mealey, K.L., et al. (2001) Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene.
Pharmacogenetics, 11, 727–733.
2. Mealey, K.L., et al. (2003) Increased toxicity of P-glycoprotein-substrate chemotherapeutic agents in a dog with theMDR1 deletion mutation associated with ivermectin sensitivity. Journal of the American Veterinary Medical Association,
223, 1453–1455
3. Gramer, I. et al. (2011). Breed distribution of the nt230(del4) MDR1 mutation in dogs. Vet J. 2011 Jul;189(1):67-71.

Indications for genetic testing:
1. Carrier testing prior to breeding
2. Testing for affected dogs

Primary Lens Luxation
Primary lens luxation (PLL) is a potentially blinding genetic ocular disorder indogs, particularly in terrier and terrier-type breeds. The disease is characterizedby the rapid displacement of lens from its normal location in the eye. Although thefirst symptoms of the condition can be detected at around 20 months of age, thelens luxation occurs between 3 to 8 years depending on the breed [1].
To date, only one mutation in ADAMTS17 genehas been associated with PLL indogs. This single nucleotide substitution (c.1473+1G>A) in intron 10 causes theskipping of exon and frameshift resulting in a premature termination codon that ispredicted to lead to a truncated protein [2]. The disease is inherited in an autosomal
recessive pattern.
The most commonly affected breeds are terriers, however, the mutation has also
been found in other PLL- affected dogs including Australian Cattle dog, Chinese
Crested, Jagdterrier, Parson Russell terrier, Patterdale terrier, Rat terrier,
Sealyham terrier, Tenterfield terrier, Tibetan terrier, Toy Fox terrier, Volpino
Italiano, Welsh terrier, Wire-haired Fox terrier, Yorkshire terrier[3].
References:
1. Curtis R, Barnett KC, Lewis SJ. Clinical and pathological observations concerning the aetiology of primary lens
luxation in the dog. Veterinary Record 1983; 112: 238–246.
2. Farias FH, Johnson GS, Taylor JF et al. An ADAMTS17 splice donor site mutation in dogs with primary lens luxation.
Investigative Ophthalmology and Visual Science 2010; 51: 4716–4721.
3. Gould D, Pettitt L, McLaughlin B, et al. ADAMTS17 mutation associated with primary lens luxation is widespreadamong breeds. Vet Ophthalmol. 2011 Nov;14(6):378-84.

Indications for genetic testing:
1. Carrier testing prior to breeding
2. Testing for affected dogs

Primary Open Angle Glaucoma

Primary open angle glaucoma (POAG) is a genetic disorder that is characterised
by increased intraocular pressure leading to optic nerve and retina damage andresulting in partial or complete blindness. Symptoms of POAG include painful eyes,
red and dilated pupils, cloudy cornea, as well as behavioural changes with loss ofappetite, eye scratching and apathy. In affected dogs, the first symptoms of thedisease begin at 8 to 16 months of age [1].
The prevalence of POAG in Beagle dogs is around 1% [2]. The disease in Beagles
is caused by a single nucleotide substitution in ADAMTS10 gene [1]. This mutation
results in the substitution of glycine to arginine (p.Gly661Arg) and has a deleterious
effect on protein function [1]. To date, ADAMTS10 mutation has not been observedin POAG-affected breeds other than Beagles [3]. The disease is inherited in
an autosomal recessive pattern.
POAG is treatable, however, the success of the treatment depends largely upon thetime of the diagnosis. Genetic testing of ADAMTS10 mutation in Beagles enables
the identification of dogs with high risk for developing POAG prior to themanifestation of clinical symptoms.
References:
1. Kuchtey J, Olson LM, Rinkoski T, et al. Mapping of the disease locus and identification of ADAMTS10 as a candidate
gene in a canine model of primary open angle glaucoma. PLoS Genet. 2011;7:e1001306.
2. Gelatt KN, MacKay EO. Prevalence of the breed-related glaucomas in pure-bred dogs in North America. Vet
Ophthalmol. 2004;7:97–111.
3. Kuchtey J, Kunkel J, Esson D, et al. Screening ADAMTS10 in Dog Populations Supports Gly661Arg as the GlaucomaCausing Variant in Beagles. Invest Ophthalmol Vis Sci. 2013 Mar 13;54(3):1881-6.

Indications for genetic testing:
1. Carrier testing prior to breeding
2. Testing for affected dogs

Progressive Retinal Atrophy – GR-PRA1
Progressive retinal atrophy (PRA) in dogs is characterized by the degeneration of
the retina, causing progressive vision loss leading to complete blindness. The firstclinical symptom of the disorder typically includes night blindness due to thedegeneration of rod cells that are essential for night vision. At later stage of thedisorder, the cone cells are damaged, gradually affecting the sight during thedaylight. The disease results in complete blindness in the affected animal [1].
Several forms of PRA have been described in more than 100 dog breeds. While theclinical symptoms of different forms of PRA are similar, the etiology, age of onset
and the rate of progression vary.
Several forms of PRA are described in the Golden Retrievers, including the prcdPRA, GR-PRA1 and GR-PRA2. GR-PRA1 is caused by a mutation in SLC4A3
gene [2]. The disease occurs due to a single nucleotide insertion causing aframeshift resulting in a premature termination codon. The frequency of the mutant
allele is approximately 2% to 6% among the Golden Retrievers in Europe. GRPRA1 has an average age of onset at approximately 7 years. The disease isinherited in an autosomal recessive pattern.
References:
1. Dostal J, et al. Progressive rod-cone degeneration (PRCD) in selected dog breeds and variability in its phenotypicexpression. Veterinarni Medicina, 2011:56(5); 243-247
2. Downs, et al. A frameshift mutation in golden retriever dogs with progressive retinal atrophy endorded SLC4A3 as acandidate gene for human retinal degenerations. PLoS ONE 2011:6(6); e21452

Indications for genetic testing:
1. Carrier testing prior to breeding
2. Testing for affected dogs

Progressive Retinal Atrophy – GR-PRA2
Progressive retinal atrophy (PRA) in dogs is characterized by the degeneration of
the retina, causing progressive vision loss leading to complete blindness. The firstclinical symptom of the disorder typically includes night blindness due to thedegeneration of rod cells that are essential for night vision. At later stage of thedisorder, the cone cells are damaged, gradually affecting the sight during thedaylight. The disease results in complete blindness in the affected animal [1].
Several forms of PRA have been described in more than 100 dog breeds. While theclinical symptoms of different forms of PRA are similar, the etiology, age of onset
and the rate of progression vary.
Several forms of PRA are described in the Golden Retrievers, including the prcdPRA, GR-PRA1 andGR-PRA-2. Geneticists at the Animal Health Trust andscientists at the Swedish University of Agricultural Sciences and Uppsala University
have identified a recessive mutation that causes a form of PRA in the GoldenRetriever, known as GR-PRA2.
According to Animal Health Trust (www.aht.org.uk), the GR-PRA2 accounts forapproximately 15% of known PRA cases in the breed. GR-PRA1 and GR-PRA2 in
combination with the prcd-PRA test, identifies nearly all causes of PRA in the breed.
Although, there are still a few cases of PRA in the golden retriever that are caused
by unidentified mutations.

References:
1. Dostal J, et al. Progressive rod-cone degeneration (PRCD) in selected dog breeds and variability in its phenotypicexpression. Veterinarni Medicina, 2011:56(5); 243-247

Indications for genetic testing:
1. Carrier testing prior to breeding
2. Testing for affected dogs

Progressive Rod-Cone Degeneration – prcdPRA
Progressive rod–cone degeneration (prcd-PRA), a form of progressive retinal
atrophy (PRA), is a canine genetic disease that is characterized by degeneration ofthe retina, causing progressive vision loss leading to blindness. PRA in dogs isconsidered as an equivalent to human retinitis pigmentosa (RP) and displays
phenotypic as well as genetic similarity to this disease [1]. The first clinical symptomof the disorder typically includes night blindness due to the degeneration of rod
cells that are essential for night vision. At later stage of the disorder, the cone cells
are damaged, gradually affecting sight during the daylight. The disease results incomplete blindness in the affected animal [2]. The disorder has been described inmany dog breeds including Labrador Retrievers. In the Golden Retrievers, prcdPRA, only accounts for a very small proportion of PRA cases. The age of onset ofthe disease and disease progression varies between the dog breeds; however, theclinical symptoms are first described usually in early adolescence or earlyadulthood.
Progressive rod-cone degeneration is caused by a mutation in the PRCD gene[1], where the substitution of nucleotide G to A in PRCD gene causes an amino acidchange from cysteine to tyrosine in the translated protein. The disease is inherited
in an autosomal recessive pattern.
References:
1. Zangerl B, et al. Identical mutation in a novel retinal gene causes progressive rod-cone degeneration in dogs andretinitis pigmentosa in humans. Genomics, 2006:88; 551-563
2. Dostal J, et al. Progressive rod-cone degeneration (PRCD) in selected dog breeds and variability in its phenotypic
expression. Veterinarni Medicina, 2011:56(5); 243-247

Indications for genetic testing:
1. Carrier testing prior to breeding
2. Testing for affected dogs

X-Linked Progressive Retinal Atrophy

Progressive retinal atrophy (PRA) in dogs is characterised by the degeneration of
the retina, causing progressive vision loss leading to complete blindness. The firstclinical symptom of the disorder typically includes night blindness due to thedegeneration of rod cells that are essential for night vision. At later stage of thedisorder, the cone cells are damaged, gradually affecting the sight during thedaylight. The disease results in complete blindness in the affected animal [1].
Several forms of PRA have been described in more than 100 dog breeds. While theclinical symptoms of different forms of PRA are similar, the aetiology, age of onset
and the rate of progression vary.
The first clinical symptoms of X-linked progressive retinal atrophy (XLPRA) indogs start to manifest around three to five years of age. Several types of XLPRA
have been described:XLPRA1 in Siberian Huskies and Samoyeds and XLPRA2in mongrel dogs [2] and XLPRA3 in Border Collies [3].
XLPRA1 is caused by a five nucleotide deletion in RPGR geneleading to apremature stop codon resulting in a truncated protein [2]. XLPRA2 is caused by aGA deletion in the same RPGR gene. The causative mutation of XLPRA3 has notbeen determined [3].The disease has an X-linked inheritance pattern [2].
References:
1. Dostal J, et al. Progressive rod-cone degeneration (PRCD) in selected dog breeds and variability in its phenotypicexpression. Veterinarni Medicina, 2011:56(5); 243-247.
2. Zhang Q, et al. Different RPGR exon ORF15 mutations in Canids provide insights into photoreceptor celldegeneration. Hum Mol Genet. 2002 May 1;11(9):993-1003.
3. Vilboux T, et al. Progressive retinal atrophy in the Border Collie: a new XLPRA. BMC Vet Res. 2008 Mar 3;4:10.

Indications for genetic testing:
1. Carrier testing prior to breeding
2. Testing for affected dogs