Please note: Disease penetrance and incidence in breeds can vary according to populations and geographical regions. Some diseases for that breed may not be relevant to the population in that country. For relevance of a particular disease we recommend you consult your breed club or canine health committee. It is recommended that if the disease is considered not relevant to your population then you screen for all potential diseases if importing a dog or semen for breeding purposes.

                                                           
For a list of disease by breed please click here
1red Scale 1 a very low degree of severity, It is a trait and so is tested based on preference, not for usually health concerns.
2red Scale 2 has a low degree of severity, as it generally poses no health concerns.
3red Scale 3 has a moderate degree of severity, as it is not a fatal disease, thought it can decrease the quality of life.
4red Scale 4 has a high degree of severity due to the affects on affected dogs, often results in a decreased quality of life and life span.
5red Scale 5 has an extreme degree of severity. It can cause significant decrease of quality of life and immediate death.

Canine Disease
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Arrythmogenic Right Ventricular Cardiomyopathy
Picture 6

Category:
Cardiac

Mode of Inheritance:
Autosomal Recessive (Incomplete penetrance)

Severity:
4red

Breeds Affected:
Boxer

Description:
Boxer ARVC is an adult onset heart muscle disease that can lead to sudden death or the development of congestive heart failure where the dog starts to cough or becomes short of breath. This is a disease that primarily affects the electrical system of the heart so the best way to test for it is a 24 hour Holter monitor. This is an inherited disease, but it is adult onset. The average age where the clinical signs may be observed or a Holter monitor becomes abnormal is 6 years of age. However, this is widely variant. Some dogs will show it younger and some, not until they are much older! Also some develop a severe disease and other develop a mild form.

We are testing for a genetic deletion for a gene that functions by holding cardiac cells together. This is very similar to what is known about the disease in human beings and much of what we know about the disease in humans may be applicable to the dog.

Reference:
1. Meurs, K.M et al;Genome-wide association identifies a deletion in the 30 untranslated region of Striatin in a canine model of arrhythmogenic right ventricular cardiomyopathy. Hum Genet (2010) 128:315–324
2. Scansen BA, Meurs KM, Spier AW, Koplitz S, Baumwart RD. Temporal variability of ventricular arrhythmias in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy. Journal of Veterinary Internal Medicine, 2009; 23:1020-4. 3. Baumwart RD, Meurs KM, Raman SV. Magnetic resonance imaging of right ventricular morphology and function in boxer dogs with arrhythmogenic right ventricular cardiomyopathy. Journal of Veterinary Internal Medicine, 2009; 23:271-4. 4. Basso C, Fox PR, Meurs KM, Towbin JA, Spier AW, Calabrese F, Maron BJ, Thiene G. Arrhythmogenic right ventricular cardiomyopathy causing sudden cardiac death in boxer dogs: a new animal model of human disease. Circulation, 2004; 109:1180-5. 5. Spier AW, Meurs KM. Assessment of heart rate variability in Boxers with arrhythmogenic right ventricular cardiomyopathy. Journal of the American Veterinary Medical Association, 2004; 224:534-7.
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Autosomal Hereditary Recessive Nephropathy

kidney

Category: Metabolic

Mode of Inheritance:
Autosomal Recessive

Severity:
5red

Breeds Affected: Cocker Spaniel

Description:
An inherited kidney disease that causes juvenile-onset renal failure has been recognized in Cocker Spaniels worldwide. The disease is caused by abnormalities of the collagen content of the walls of the glomerular capillaries through which blood filtration occurs in the kidneys. This renal disease is analogous to a condition called Alport syndrome that occurs in people.
Dogs with the disease develop chronic renal failure, usually while they are between 6 months and 2 years of age. Clinical signs that are often observed include excessive water consumption (polydipsia), excessive urine volume (polyuria), reduced growth rate or weight loss, poor quality hair coat, reduced appetite, and vomiting. Such signs can develop insidiously and escape recognition until the degree of renal failure is so severe that overt uremia supervenes. At this late stage of the disease, physical examination findings may include thin body condition, dehydration, pallor of mucous membranes, uremic breath odor, and oral ulcerations. Alternatively, especially at earlier stages of the disease, physical exam findings may be normal.

Reference:
  • Ashley G. Davidson, Rebecca J. Bell, George E. Lees, Clifford E. Kashtan, George S. Davidson, Keith E. Murphy "Genetic Cause of Autosomal Recessive Hereditary Nephropathy in the English Cocker Spaniel" Journal of Veterinary Internal Medicine Volume 21, Issue 3,pages 394–401, May 2007
  • Robinson WF; Huxtable CR; Gooding, JP. (1985) Familial nephropathy in cocker spaniels. Australian Veterinary Journal. 62: 109-112.   online abstract
  • Lees GE, Wilson PD, Helman RG, Homco LD, Frey MS. (1997) Glomerular ultrastructural findings similar to hereditary nephritis in 4 English cocker spaniels. Journal of Veterinary Internal Medicine. 11(2):80-5.   online abstract
  • Lees GE, Helman RG, Kashtan CE, Michael AF, Homco LD, Millichamp NJ, Ninomiya Y, Sado Y, Naito I, Kim Y. (1998) A model of autosomal recessive Alport syndrome in English cocker spaniel dogs. Kidney Int. 54(3):706-19.   online abstract
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Canine Hyperuricosuria

Picture 6

Category:
Metabolic

Mode of Inheritance:
Autosomal Recessive

Severity:
2red

Breeds Affected:
American Staffordshire Terrier, Australian Shepherd, Dalmatian, Bulldog, Black Russian Terrier, German Shepherd, Giant Schnauzer, Jack Russell Terrier, Weimeraner, South African Boerboel.

Description:
Hyperuricosuria means elevated levels of uric acid in the urine. This trait predisposes dogs to form stones in their bladders or sometimes kidneys. These stones often must be removed surgically and can be difficult to treat. Hyperuricosuria is inherited as a simple autosomal recessive trait. The trait can occur in any breed but is most commonly found in the Dalmatian, Bulldog and Black Russian Terrier. Dalmatians are considered to be homozygous for hyperuricosuria. A mutation in exon 5 of the gene Solute carrier family 2, member 9 (SLC2A9) has been found to be associated with hyperuricosuria in dogs. A DNA test for this specific mutation can determine if dogs are normal or if they carry one or two copies of the mutation. Dogs that carry two copies of the mutation will be affected and susceptible to develop bladder/kidney stones.

Reference:
1. Karmi N, Safra N, Young A, Bannasch DL. Validation of a urine test and characterization of the putative genetic mutation for hyperuricosuria in Bulldogs and
Black Russian Terriers. Am J Vet Res. 2010;71(8):909-14.   
online abstract
2. Bannasch et al:PLoS Genetics 2008. Mutations in the SLC2A9 gene cause hyperuricosuria and hyperuricemia in the dog. DanikaBannasch, NoaSafra, Amy Young, NiliKarmi,
R. S. Schaible, G. V. Ling.



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Canine Leukocyte Adhesion Deficiency

Picture 7

Category: Haematologic / Immunologic

Mode of Inheritance:
Autosomal Recessive

Severity:
5red

Breeds Affected:
Irish Setter, Red and White Setter

Description:
This condition is an inherited fatal immunodeficiency disease that affect functionality of white blood cells (leucocytes). Pups that inherit two recessive genes for CLAD usually die early in life from multiple severe infections, even when treated with massive doses of antibiotics.
CLAD is related to the same disease in humans (LAD) and cattle (BLAD). So far, CLAD has been found only in Irish Setters. Research on the disease was carried out in England and Scandinavia, where the carrier rate is close to 12%. However, CLAD was first identified clinically in the United States.

Reference:
1. Debenham, Millington, Kijas, Andersson and Binns, Journal of Small Animal Practice. Vol 43, February 2002
  • 2.Kijas, JM, Bauer TR, Gafvert S, Marklund S, Trowald-Wigh G, Johannisson A, Hedhammar A, Binns M, Juneja RK, Hickstein, DD, Andersson L (1999) A missense mutation in the beta-2 integrin gene (ITGB2) causes canine leukocyte adhesion deficiency. Genomics 61: 101-107. ;  online abstract
  • 3.Foureman P, Whiteley M, Giger U.(2002) Canine leukocyte adhesion deficiency: presence of the Cys36Ser beta-2 integrin mutation in an affected US Irish Setter cross-breed dog and in US Irish Red and White Setters. J Vet Intern Med. 16(5):518-23. ;  online abstract
  • 4. Bauer TR Jr, Gu YC, Creevy KE, Tuschong LM, Embree L, Holland SM, Sokolic RA, Hickstein DD. (2004) Leukocyte adhesion deficiency in children and Irish setter dogs. Pediatr Res. 55(3):363-7. ;  online abstractweb reference
  • 5. Gu YC, Bauer TR Jr, Ackermann MR, Smith CW, Kehrli ME Jr, Starost MF, Hickstein DD. (2004) The genetic immunodeficiency disease, leukocyte adhesion deficiency, in humans, dogs, cattle, and mice. Comp Med. 54(4):363-72. ;  online abstract

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Canine Multifocal Retinopathy

Category:
Ophthalmic

Mode of Inheritance:
Autosomal Recessive

Severity:
2red

Breeds Affected:
Great Pyrenees, Coton de Tulear, Dogue de Bordeaux, Mastiffs or Lapponian Herders

Description:
This is a recessively inherited eye disease causing retinal deformation. Manifested by numerous distinct (i.e. multi-focal), roughly circular patches of elevated retina with accumulation of material that produces gray-tan-pink colored lesions. These lesions, looking somewhat like blisters, vary in location and size, although typically they are present in both eyes of the affected dog.Discrete areas of tapetal hyper-reflectivity might also be seen. The disease generally develops in young dogs before 4 months and might progress slowly, might appear to heal, or might even appear and then go away again. Some dogs affected with CMR do not show clinical symptoms of disease until later in life. Some lesions disappear with no remaining sign, while some lesions leave a wrinkled area – a fold. Some leave the lasting lesion of a blister formation. Most dogs exhibit no noticeable problem with vision despite their abnormal appearing retinas. And in almost all cases, CMR does not progress significantly over time.

Reference:
  • 1. Grahn BH, Philibert H, Cullen CL, Houston DM, Semple HA, Schmutz SM. (1998) Multifocal retinopathy of Great Pyrenees dogs. Veterinary Ophthalmology. 1(4):211-221. ;  online abstract
  • 2. Guziewicz KE, Zangerl B, Lindauer SJ, Mullins RF, Sandmeyer LS, Grahn BH, Stone EM, Acland GM, Aguirre GD. (2007) Bestrophin gene mutations cause canine multifocal retinopathy: a novel animal model for best disease. : Invest Ophthalmol Vis Sci. 48(5):1959-67.;  online abstract

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Centronuclear Myopathy

C myopathy Download Video Warning footage may be distressing for some viewers

Category:
Neurological

Mode of Inheritance:
Autosomal Recessive

Severity:
5red

Breeds Affected:
Labrador Retriever, Labradoodle

Description:
Centronuclear myopathy is a recessively inherited muscular disease. At birth, affected puppies are indistinguishable from their control littermates but as from two weeks of age, a progressive significant weight loss is observed. At one month of age, the absence of tendon reflexes is noticed and used as an early and reliable diagnosis. The age of onset of the disabling phenotype varies between 2 to 5 months, with an awkward gait and a decreased exercise tolerance and difficulty eating associated with a generalized muscle weakness. The pup will never recover from this disabling disease.

Clinical signs are progressively accentuated and generally stabilized at one year of age. In adults, the most striking macroscopic feature of the disease progression is the atrophy of temporal, cervical and leg muscles. Dogs may require medical care, essentially because they suffer from respiratory complications due to megaœsophagus.A hallmark of muscles from Labradors affected by muscular myopathy is a centralization of nuclei in muscular cells (Figures 2 and 3). This can be observed on an histological section of a biopsied muscle.

Reference:

1. Pelé, M., Tiret, L., Kessler, J.L., Blot, S. and Panthier, J.J. SINE exonic insertion in the PTPLA gene leads to multiple splicing defects and segregates with the autosomal recessive centronuclear myopathy in dogs, Hum Molecular Genetics, 2005, Vol 14, No 11, pp. 1417-1427.
2. Kramer JW, Hegreberg GA, Hamilton MJ. (1981) Inheritance of a neuromuscular disorder of Labrador retriever dogs. J Am Vet Med Assoc. 1179(4):380-1. ;  online abstract
3. McKerrell RE, Braund KG (1987) Hereditary myopathy in Labrador Retrievers: clinical variations. Journal of Small Animal Practice 28: 479-489.;  
online abstract
4. Amman, JF, Laughlin MH, Korthuis RJ (1988) Muscle hemodynamics in hereditary myopathy of Labrador Retrievers. American Journal of Veterinary Research 49: 1127-1130.


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Cerebellar Ataxia



Category:
Neurological

Mode of Inheritance:
Autosomal Recessive

Severity:
4red

Breeds Affected: American Staffordhsire Terrier, American Pit Bull Terrier

Description:
Cerebellar ataxia is cause by problem in the part of the brain called the cerebellum. Any disease that damages the cerebellum can produce the signs of ataxia. Cerebellar Ataxia is an autosomal recessive a genetic defect that leads to degeneration of the cerebellum. The first signs of the disease usually appear between 3 and 5 years of age in affected dogs. They are: loss of balance, difficulty cornering, and falling when shaking their head. As the signs progress, most dogs seem to have difficulty initiating movements. When they became unable to walk without falling repeatedly, owners usually make the difficult choice to euthanize.

The incidence of Cerebellar Ataxia has increased greatly in the last few years due to affected dogs being bred before they exhibited the first symptoms. Pilot studies revealed a high frequency of carrier dogs in the frenchand American populations of AmStaff (up to 30%).

Reference:

1. Hanzlicek D, Kathmann I, Bley T, Srenk P, Botteron C, Gaillard C, Jaggy A. (2003) [Cerebellar cortical abiotrophy in American Staffordshire
terriers: clinical and pathological description of 3 cases] Schweiz Arch Tierheilkd.145(8):369-75. (German.)   
online abstract
  • 2. Speciale J, de Lahunta A. (2003) Cerebellar degeneration in a mature Staffordshire terrier. J Am Anim Hosp Assoc. 39(5):459-62.   online abstract
  • 3. Siso S, Navarro C, Hanzlicek D, Vandevelde M. (2004) Adult onset thalamocerebellar degeneration in dogs associated to neuronal storage of ceroid lipopigment. Acta Neuropathol (Berl). [Epub ahead of print]   online abstract
  • 4. Olby N, Blot S, Thibaud JL, Phillips J, O'Brien DP, Burr J, Berg J, Brown T, Breen M. (2004) Cerebellar cortical degeneration in adult American Staffordshire Terriers. J Vet Intern Med. 18(2):201-8.  online abstract
  • 5. Abitbol M, Thibaud JL, Olby NJ, Hitte C, Puech JP, Maurer M, Pilot-Storck F, Hédan B, Dréano S, Brahimi S, Delattre D, André C, Gray F, Delisle F, Caillaud C, Bernex F, Panthier JJ, Aubin-Houzelstein G, Blot S, Tiret L. A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14775-80.   online abstract

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Collie Eye Anomaly Choroidal Hyperplasia

Picture 2

Category:
Ophthalmic

Mode of Inheritance:
Autosomal Recessive

Severity:
3red

Breeds Affected:
Australian Shepherd, Border Collie, Lancashire Heeler, Rough Collie, Shetland Sheepdog, Smooth Collie

Description:
Collie eye anomaly (CEA) is a congenital, inherited, bilateral eye disease of dogs involving the retina, choroid, and sclera. It can be a mild disease or cause blindness. CEA is caused by a simple autosomalrecessive gene defect. There is no treatment. CEA is caused by improper development of the eye. Failure of the cells of the posterior portion of the optic vesicles to express growth hormone affects the differentiation of other cells of the eye. The choroid, especially lateral to the optic disc, is hypoplastic (underdeveloped). A coloboma, or hole, may form in or near the optic disc due to a failed closure of embryonic tissue. The degree of these abnormalities varies between individual dogs, and even between the same dog's eyes. CEA is inherited as an autosomal recessive trait that has a penetrance reaching 100 percent, and has been located to canine chromosome 37. The most common sign of CEA is the presence of an area of undeveloped choroid (appearing as a pale spot) lateral to the optic disc. The choroid is a collection of blood vessels supplying the retina. CEA can also cause retinal or scleral coloboma, coloboma of the optic disc, retinal detachment, or intraocular hemorrhage. It can be diagnosed by fundoscopy by the age of six or seven weeks. Severe cases may be blind.

Reference:
  • 1. Rubin LF, Nelson EJ and Sharp CA. (1991) Collie eye anomaly in Australian Shepherd dogs. Prog in Veterinary and Comparative Ophthalmology 1:105.
  • 2. Lowe JK, Kukekova AV, Kirkness EF, Langlois MC, Aguirre GD, Acland GM, Ostrander EA. (2003) Linkage mapping of the primary disease locus for collie eye anomaly. Genomics. 82(1):86-95.   online abstract
  • 3. Munyard KA, Sherry CR, Sherry L. (2007) A retrospective evaluation of congenital ocular defects in Australian Shepherd dogs in Australia.Vet Ophthalmol. 10(1):19-22.   online abstract
  • 4. Parker HG, Kukekova AV, Akey DT, Goldstein O, Kirkness EF, Baysac KC, Mosher DS, Aguirre GD, Acland GM, Ostrander EA. (2007) Breed relationships facilitate fine-mapping studies: a 7.8-kb deletion cosegregates with Collie eye anomaly across multiple dog breeds. Genome Res. 17(11):1562-71.   online abstract
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Cone Degeneration

Category:
Ophthalmic

Mode of Inheritance:
Autosomal Recessive

Severity:
4red

Breeds Affected:
Alaskan Malamute, German Shorthaired Pointer, Pointer

Description:
CD disease causes day blindness due to degeneration of the retinal “cones” – cone-shaped cells in the retina that respond primarily to bright daylight. CD can be diagnosed in the early weeks of the affected dog’s life. Between 8 and 12 weeks of age, when retinal development is normally completed in dogs, signs of vision problems are noticeable. The pups become day-blind and are photophobic – meaning that exposure to bright light is irritating or even painful. The pup will shun brightly-lit areas. Vision in dim light remains normal. The retina of the affected dog initially appears normal when examined by an ophthalmologist and initially the ERG (electroretinogram) recording is normal. However, the ERG response from the degenerating cones declines with age and is non-recordable in the mature CD-affected dog.
In contrast to PRA (Progressive Retinal Atrophy), which is the more common type of retinal disease in many dog breeds, CD does not affect night vision. A second type of cell in the retina, the “rods” – rod-shaped cells that respond primarily to dim light and detect movement – are not involved in this disease. The CD-affected dog keeps the ability to see at night or in dimly-lit areas.
CD is the canine version of the human genetic disease achromatopsia – total color blindness and day-blindness. Another name for day blindness is “hemerolopia.”

Reference:
1. Sidjanin DJ, Lowe JK, McElwee JL, Milne BS, Phippen TM, Sargan DR, Aguirre GD, Acland GM, Ostrander EA. (2002) Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3. Hum Mol Genet. 11(16):1823-33. ;  online abstract
2. Aguirre GD, Rubin LF. (1975) The electroretinogram in dogs with inherited cone degeneration. Invest Ophthalmol. 14 (11): 840-7. ;  
online abstract
3. Sidjanin DJ, Lowe J, Mellersh C, E.A. Ostrander EA, Milne B, Sargan D, Aguirre GD, Acland GM (2002) Identification of a Mutation Responsible for Hereditary Cone Degeneration in Dog. Investigative Ophthalmology and Visual Science 43(4): Abs 3671.;  
online abstract
4. Sidjanin DJ, Lowe JK, McElwee JL, Milne BS, Phippen TM, Sargan DR, Aguirre GD, Acland GM, Ostrander EA. (2002) Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3. Hum Mol Genet. 11(16):1823-33. ;  
online abstract

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Congenital Hypothyroidism

hypothyroidism

Category: Metabolic

Mode of Inheritance:
Autosomal Recessive

Severity:
3red

Breeds Affected: Toy Fox Terrier

Description:
This is a simple autosomal recessive trait in Toy Fox Terriers (TFTs). Neonatal affected pups exhibited inactivity, abnormal hair coat, stenotic (narrow) ear canals, and delayed eye opening. Palpable ventrolateral cervical (neck) swellings were evident by 1 week of age. Serum thyroid hormone and thyroid-stimulating hormone concentrations were low and high, respectively.

Oral thyroid hormone replacement therapy restored near-normal growth and development. At 8 weeks of age, further testing usually indicate an iodine organification defect. Biochemical analysis of thyroid tissue from affected dogs suggesting thyroid peroxidase deficiency. A nonsense mutation in the thyroid peroxidase gene of affected dogs was discovered and demonstrated to segregate with the disease.

Reference:
  • Fyfe JC, Kampschmidt K, Dang V, Poteet BA, He Q, Lowrie C, Graham PA, Fetro VM. (2003) Congenital hypothyroidism with goiter in toy fox terriers. J Vet Intern Med 17(1):50-7;  online abstract


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Congenital Stationary Night Blindness *

Category:
Ophthalmic

Mode of Inheritance:
Autosomal Recessive

Severity:
3red

Breeds Affected: Briard

Description:
Congenital Stationary Night Blindness (CSNB), also known as hereditary retinal dystrophy, congenital night blindness with varying degrees of visual impairment in affected dogs ranging from normal day vision to profound day blindness. Profound visual impairment may be present at a very young age (5-6 weeks). An abnormal ERG (electroretinogram) recording can also be observed with severely depressed rod and cone mediated responses. The genetic mutation that causes CSNB was confirmed by researchers at Cornell University. The mutation is in the retinal pigment epithelium-specific protein 65kD (RPE65) gene which is located on canine chromosome 6. This mutation causes retinal dysfunction and accumulation of lipid vacuoles in the retinal pigment epithelium. Mutations in the RPE65 gene are also responsible for childhood-onset severe retinal dystrophy in humans, thus the dog is a model of this human disease. To determine the efficacy of gene therapy to treat this type of genetic disorder in a non-rodent model, a retrovirus containing the wild-type RPE65 gene was used to restore vision in a dog with CSNB.

Reference:
  • 1. Narfstrom K, Wrigstad A, Nilsson SE (1989) The Briard dog: a new animal model of congenital stationary night blindness. British Journal of Ophthalmolology 73: 750-6. ;  online abstract
  • 2. Anderson RE, Maude MB, Narfstrom K, Nilsson SEG (1997). Lipids of plasma, retina, and retinal pigment epithelium in Swedish Briard dogs with a slowly progressive retinal dystrophy. Experimental Eye Research 64: 181-187. ;  online abstract
  • 3.Veske A, Nilsson SE, Narfstrom K, Gal A (1999) Retinal dystrophy of Swedish briard/briard-beagle dogs is due to a 4-bp deletion in RPE65. Genomics 57: 57-61. ;  online abstract
  • 4. Narfstrom K. (1999) Retinal dystrophy or 'congenital stationary night blindness' in the Briard dog. Veterinary Ophthalmology 2(1):75-76. ;  online abstract
  • 5. Acland GM, Aguirre GD, Ray J, Zhang Q, Aleman TS, Cideciyan AV, Pearce-Kelling SE, Anand V, Zeng Y, Maguire AM, Jacobson SG, Hauswirth WW, Bennett J. (2001) Gene therapy restores vision in a canine model of childhood blindness. Nat Genet. 2001 May;28(1):92-5. PMID: 11326284;  online abstract
  • 6. Wrigstad A, Narfstrom K, Nilsson SE. (1994) Slowly progressive changes of the retina and retinal pigment epithelium in Briard dogs with hereditary retinal dystrophy. A morphological study. Doc Ophthalmol. 87(4):337-54. ;  online abstract
  • 7. Lightfoot RM, Cabral L, Gooch L, Bedford PG, Boulton ME. (1996) Retinal pigment epithelial dystrophy in Briard dogs. Res Vet Sci.60(1):17-23. ;  online abstract


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Copper Toxicosis

copper toxicosis

Category: Ophthalmic

Mode of Inheritance:
Autosomal Recessive

Severity:
5red

Breeds Affected: Bedlington Terrier

Description:
Canine copper toxicosis ("CT") is an autosomal recessive disorder of copper accumulation which results in severe liver disease in several dog breeds. Unless specific anti-copper treatment is instituted, most affected dogs die at three to seven years of age. CT is, in particular, a severe problem in Bedlington Terriers. The frequency of CT in Bedlingtons is significant enough to be a major health concern. Affected dogs may be definitively diagnosed by invasive liver biopsy, but this technique cannot identify CT carriers. Therefore, CT carriers continue to be bred, creating extreme difficulties for responsible Bedlington breeders and owners who wish to halt the perpetuation of the disease.

Initially a linked marker test was developed as an aid to breeders, and more recently a direct test was developed that identifies a type of mutation known as a deletion. This particular deletion eliminates a major section of a copper metabolism gene, Commd1. This deletion test identifies the overwhelming majority of disease causing alleles and should be the focus of most testing.


Reference:
1. 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. Anim Genet. 36(6):497-501;  online abstract
2. Spee B, Arends B, van den Ingh TS, Penning LC, Rothuizen J. (2006) Copper metabolism and oxidative stress in chronic inflammatory and cholestatic liver diseases in dogs. J Vet Intern Med. 20(5):1085-92. ;  
online abstract
3. Spee B, Arends B, van Wees AM, Bode P, Penning LC, Rothuizen J. (2007) Functional consequences of RNA interference targeting COMMD1 in a canine hepatic cell line in relation to copper toxicosis. Anim Genet. 38(2):168-70;  
online abstract
4. Spee B, Arends B, van den Ingh TS, Penning LC, Rothuizen J. (2006) Copper metabolism and oxidative stress in chronic inflammatory and cholestatic liver diseases in dogs. J Vet Intern Med. 20(5):1085-92. ;  
online abstract

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Cystinuria

Cystinuria

Category:
Metabolic

Mode of Inheritance:
Autosomal Recessive

Severity:
3red

Breeds Affected: Landseer, Newfoundland, Labrador Retriever, Labradoodle

Description:
Cystinuria is a genetic kidney defect. In this disease, cystine is not re-absorbed by the kidney and therefore high concentrations can accumulate and precipitate in the urine. Since normal urine does not contain cystine, the presence of cystine in the urine tells you the dog has cystinuria. Many dogs who test positive for cystinuria do not go on to form stones, however they do have increased risk and some do go on to form stones that can obstruct (block) the urinary tract. This can be a fatal condition is not treated promptly.
Cystinuria is an autosomal recessive, inherited disease meaning that both parents of an affected dog were themselves affected or carriers of the disease. The disease affects many breeds but it is especially severe in Newfoundlands.

Reference:
  • 1. CRANE CW, TURNER AW. (1956) Amino acid patterns of urine and blood plasma in a cystinuric Labrador dog. Nature. 177(4501):237-8. No abstract available. ;  online abstract
  • 2. Lui J-L, Van Hoeven M, Seng AS, Giger U, Henthorn P (2004). Molecular and Biochemical Heterogeneity of Cystinuria in dogs. (Abstract). 2nd International Conference “Advances in Canine & Feline Genomics”. pp84.

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Degenerative Myelopathy

DM

Category:
Neurological

Mode of Inheritance:
Autosomal Recessive

Severity:
4red

Breeds Affected: American Eskimo Dog, Bernese Mountain Dog, Boxer, Cardigan Welsh Corgi, Chesapeake Bay Retriever, German Shepherd Dog, Golden Retriever, Great Pyrenees, Kerry Blue Terrier, Pembroke Welsh Corgi, Poodle, Pug, Rhodesian Ridgeback, Shetland Sheepdog, Soft Coated Wheaten Terrier, Wire Fox Terrier.

Description:
This disease, a result of gradual loss of both myelin (the insulation around nerve fibers) and spinal cord nerve fibers which begins in the thoracic spine, causes progressive loss of coordination and weakness in the back legs which eventually leads to the dog being unable to walk. Loss of bowel and bladder control result as well. Unlike spinal cord injuries, this form of spinal paralysis is generally not painful as the nerves which would transmit the pain degenerate.

The disease results in hind limb paralysis over time and there is no recognized effective treatment for affected dogs. But DNA tests will help dog breeders in their efforts to reduce the incidence of canine degenerative myelopathy and may eventually lead to a better understanding of the disease.

Reference:
  • 1. Miller AD, Barber R, Porter BF, Peters RM, Kent M, Platt SR, Schatzberg SJ. (2009) Degenerative myelopathy in two Boxer dogs. Vet Pathol. 46(4):684-7. ;  online abstract
  • 2. Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF, Perloski M, Biagi T, Baranowska I, Long S, March PA, Olby NJ, Shelton GD, Khan S, O'Brien DP, Lindblad-Toh K, Coates JR. (2009) Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2794-9;  online abstract
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Dermoid Sinus

dermoid sinus

Category:
Cutaneous +- Neurological

Mode of Inheritance:
Autosomal Recessive

Severity:
3red

Breeds Affected: Rhodesian Ridgeback

Description:
Dog Dermoid Sinus, also known as pilonidal cyst sinus is a cyst-like structure that lies below the skin along the back and is sometimes connected to the spine. A genetically autosomal skin condition in dogs that shares similar condition in humans, the appearance of dermoid sinus is often single or multiple dimples or lumps on the dorsal midline. The can often be felt as “strings” connecting the skin to underlying tissues.

The sinus is caused in the embryonic stage of development. In normal development, the neural tube from which the spine develops separates from the skin. In the case of a dog dermoid sinus, this separation has not fully taken place. The result is that in some cases, the dermoid sinus remains connected to the dog’s spinal cord; in other cases, the sinus terminates in a "blind sac" that is less dangerous to remove. The dermoid sinus contains hair follicles, sebaceous glands, and sweat glands. If the sinus becomes infected, it can result in meningitis and myelitis, symptoms of which are spinal pain, rigidity, and fever. In serious cases, the condition can be life threatening. Surgery is also a popular remedy, with veterinary surgeons removing abnormal tissue and closing any connections to the spine, although in some cases, regrowth of the sinus occurs. A variety of tests, such as a myelogram or a fistulogram may be undertaken to determine how deep the sinus goes.


Reference:

1. Marks, S.L., Harari, J., Dernell, W.S. (1993). Dermoid Sinus in a Rhodesian Ridgeback. Journal of Small Animal Practice 34: 356- 358.
2. Tshamala, M., Moens, Y. (2000). True dermoid cyst in a Rhodesian ridgeback. Journal of Small Animal Practice 41: 352-353. ;  
online abstract
3. Hillbertz NH, Andersson G. (2006) Autosomal dominant mutation causing the dorsal ridge predisposes for dermoid sinus in Rhodesian ridgeback dogs. J Small Anim Pract. 47(4):184-8. ;  
online abstract
4. Karlsson EK, Baranowska I, Wade CM, Salmon Hillbertz NH, Zody MC, Anderson N, Biagi TM, Patterson N, Pielberg GR, Kulbokas EJ 3rd, Comstock KE, Keller ET, Mesirov JP, von Euler H, KÀmpe O, Hedhammar A, Lander ES, Andersson G, Andersson L, Lindblad-Toh K. (2007) Efficient mapping of mendelian traits in dogs through genome-wide association. Nat Genet. 39(11):1321-8. Epub 2007 Sep 30. ;  
online abstract

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Dilated Cardiomyopathy

DCM

Category:
Cardiac

Mode of Inheritance:
Autosomal Recessive

Severity:
5red

Breeds Affected: Doberman Pinscher

Description:
Doberman pinscher DCM is an adult onset heart muscle disease that can lead to sudden death or the development of congestive heart failure where the dog starts to cough or becomes short of breath. This is an inherited disease, but it is adult onset. The average age at which clinical signs may be observed or a Holter monitor becomes abnormal is 6 years of age. However, this is widely variant. Some dogs will show it younger and some, not until they are much older!
This disease can affect the electrical system of the heart or the contractility of the heart muscle. Since the disease is adult onset and can start at varying ages, we recommend an annual echocardiogram and Holter monitoring after 3 years of age.
Reference:
1. Hammer TA, Venta PJ, Eyster GE (1996) The genetic basis of dilated cardiomyopathy in Doberman pinschers. Animal Genetics 27:109 (abstract)
2. Minors SL, O'Grady MR (1998) Resting and dobutamine stress echocardiographic factors associated with the development of occult dilated cardiomyopathy in healthy Doberman pinscher dogs. Journal of Veterinary Internal Medicine 12: 369-380. ;  
online abstract
3. Biesiadecki BJ, Elder BD, Yu ZB, Jin JP.(2002) Cardiac troponin T variants produced by aberrant splicing of multiple exons in animals with high instances of dilated cardiomyopathy. J Biol Chem. [epub ahead of print] -Doberman alternate splicing -exclusion of part of exon 7, inclusion of embryonic exon 5;  
online abstract
4. Calvert CA, Chapman WL Jr, Toal RL. (1982) Congestive cardiomyopathy in Doberman pinscher dogs. J Am Vet Med Assoc. 181(6):598-602. ;  
online abstract
5.Everett RM, McGann J, Wimberly HC, Althoff J. (1999) Dilated cardiomyopathy of Doberman pinschers: retrospective histomorphologic evaluation of heart from 32 cases. Vet Pathol. 36(3):221-7. ;  
online abstract
6.Meurs KM, Fox PR, Norgard M, Spier AW, Lamb A, Koplitz SL, Baumwart RD.(2007) A prospective genetic evaluation of familial dilated cardiomyopathy in the Doberman pinscher. J Vet Intern Med. 21(5):1016-20.;  
online abstract

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Dominant - PRA

Category:
Ophthalmic

Mode of Inheritance:
Autosomal Dominant

Severity:
4red

Breeds Affected: Bull Mastiff, English Mastiff

Description:
Progressive Retinal Atrophy (PRA) is an inherited progressive degenerative eye diseases affecting the retina which ultimately result in blindness and disorientation. Typically the first symptom of PRA is night blindness followed by increased reflectivity of the fundus or a "green sheen" to the eyes when viewed in dim light.
PRA is essentially the slow death of retinal tissue; the tissue thins considerably over time causing degeneration of the photosensitive rods and cones of the eye. Dominant PRA has various levels of severity of retinal thinning, with the most affected area being the central retina. This condition has been detected in mastiffs as young as 4 months.
Dominant PRA has a high degree of severity, due to the dominant mode of inheritance; there is a very high risk of affected pups.

Reference:
Petersen-Jones, Simon M. (2003). "Progressive Retinal Atrophy: An Overview". Proceedings of the 28th World Congress of the World Small Animal Veterinary Association. http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2003&PID=6687&O=Generic. Retrieved 2007-03-10.

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Dwarfism

Pasted Graphic

Category:
Metabolic

Mode of Inheritance:
Autosomal Recessive

Severity:
5red

Breeds Affected: German Shepherd

Description:
This inherited disorder is encountered most often in German shepherd dogs, but it has also been reported in a dutch breed the Saarloos wolfhounds. In this condition the pituitary gland in the brain fails to produce adequate amounts of several hormones. These hormones (such as growth hormone) are essential for numerous body functions, such as growth, reproduction, hair and skin growth, lactation, metabolism and handling stress. Pituitary dwarfs are significantly smaller than their healthy littermates, they retain their puppy hair coat. In time, the hair coat will be largely lost and the animal will become bald and the skin hyperpigmented. The growth retardation and the abnormal hair coat are mostly noticed by 2 to 3 months of age. The deficiency also leads to underdevelopment of the kidneys, causing chronic renal failure. The deficiency will also result in an underactive thyroid gland, causing the animals to be slow and dull. Furthermore, the insufficiency of the gonadotropins will result in failure of one or both testis to move, or "descend" into the scrotum (cryptorchidism) in male dwarfs. Female dwarfs do go into heat, but they do not ovulate.
Without proper treatment, the prognosis is poor. Many dwarfs will not live more than 4 to 5 years.

Reference:
  • 1. Andresen E, Willeberg P (1976) Pituitary dwarfism in German shepherd dogs: additional evidence of simple, autosomal recessive inheritance. Nordisk Veterinaermedicin 28: 481-6. ;  online abstract
  • 2. Lantinga-van Leeuwen IS, Kooistra HS, Mol JA, Renier C, Breen M, van Oost BA. (2000b) Cloning, characterization, and physical mapping of the canine Prop-1 gene (PROP1): exclusion as a candidate for combined pituitary hormone deficiency in German shepherd dogs. Cytogenetics Cell Genetics 88(1-2):140-4. ;  online abstract
  • 3. van Oost BA, Versteeg SA, Imholz S, Kooistra HS. (2002) Exclusion of the lim homeodomain gene LHX4 as a candidate gene for pituitary dwarfism in German shepherd dogs. Mol Cell Endocrinol. 197(1-2):57-62.;  online abstract

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Exercise Induced Collapse



Category:
Metabolic

Mode of Inheritance:
Autosomal Recessive

Severity:
2red

Breeds Affected: Labrador Retriever, Labradoodle

Description:
This inherited disease is common in Labrador Retrievers, but is also found in other breeds. Signs first become apparent in young dogs, usually between 5 months and 3 years of age (averaging 14 months). In dogs used for field trials, this usually coincides with the age at which they enter heavy training. Littermates and other related dogs are commonly affected, but depending on their temperament and lifestyle, they may or may notmanifest signs. Affected dogs exhibiting signs of collapse are usually described as being extremely fit, muscular, prime athletic specimens of their breed with an excitable temperament and lots of drive.

Note: A few affected dogs have died during exerciseor while resting immediately after an episode of EIC, so an affected dog's exercise should alwaysbe stopped at the first hint of incoordination or wobbliness.

Reference:
  • 1. Patterson EE, Minor KM, Tchernatynskaia AV, Taylor SM, Shelton GD, Ekenstedt KJ, Mickelson JR.A canine DNM1 mutation is highly associated with the syndrome of exercise-induced collapse. NatGenet. 2008 Oct;40(10):1235-9.;  online abstract
  • 2. Taylor SM, Shmon CL, Shelton GD, Patterson EN, Minor K, Mickelson JR. (2008). Exercise-induced collapse of Labrador retrievers: survey results and preliminary investigation of heritability. J Am Anim Hosp Assoc. 44(6):295-301. PMID: ;  online abstract
  • 3. Taylor, S.M. in Blackwell's Five Minute Veterinary Consult: Canine and Feline 4th edn. Exercise induced weakness/collapse in Labrador Retrievers, 458–459 (Blackwell Publishing Professional, Ames, Iowa, 2007). (No abstract available).

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Factor VII Deficiency

nose bleed

Category:
Haematologic

Mode of Inheritance:
Autosomal Recessive

Severity:
2red

Breeds Affected: Airedale Terrier, Alaskan Klee Kei, Beagle, Giant Schnauzer, Scottish Deerhound

Description:
Factor VII (FVII) is a blood clotting compound essential for normal clotting. A documented autosomal recessive genetic mutation leads to lower levels of this factor, which in turn leads to mild to moderate clotting problems. Affected animals may bleed excessively after surgery or trauma. Affected dogs bruise easily and nose bleeds maybe seen. The condition may go unnoticed for long time and discovered only when a surgery is performed or if the dog had an accident, in both cases increased bleeding will be noticed which can be difficult to control. Your vet will suspect a bleeding disorder.

Reference:
1. Spurling NW, Burton LK, Peacock R,, Pilling T (1972) Hereditary factor VII deficiency in the beagle. British Journal of Haematology 23: 59-67. ;  online abstract
  • 2. Spurling NW. (1986) Hereditary blood coagulation factor-VII deficiency in the beagle: immunological characterisation of the defect. Comparative Biochemistry Physiology A. 83(4):755-60. ;  online abstract
  • 3. Mills JN, Labuc RH, Lawley MJ (1997) Factor VII deficiency in an Alaskan malamute. Australian Veterinary Journal 75: 320-322. ;  online abstract
  • 4. Noguchi M, Fujii T, Michizono A. (1987) [Congenital deficiency of factor VII in a canine family] Jikken Dobutsu. 36(4):423-30. Japanese.;  online abstract

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Fucosidosis

Category:
Metabolic

Mode of Inheritance:
Autosomal Recessive

Severity:
4red

Breeds Affected: English Springer Spaniel

Description:
This is a severe, progressive and ultimately fatal autosomal recessive trait.The disease affects young adults, usually between 18 months and 4 years of age, and ischaracterised by nervous signs that progress over a period of several months. These signs include incoordination and ataxia (loss of control of movement), change in temperament, loss of learnedbehaviour, loss of balance, apparent deafness, visual impairment and varying degrees of depression.In addition,affected dogs lose weight and may suffer from swallowing difficulties and sometimes regurgitationof food.

The disease is caused by the absence of an enzyme called alpha-L-fucosidase. This enzyme is one of many required to break down complex compounds into simple molecules that the body can use. When
the enzyme is absent, the pathway is blocked and the more complex compounds build up in the cells of the affected animal. These substances accumulate in many tissues but it is the accumulation in the brain and peripheral nerves that is mostimportant since it interferes with normal function, giving rise to the clinical signs described above,eventually resulting in death.

Reference:
  • 1. Hartley WJ, Canfield PJ, Donnelly TM (1982). A suspected new canine storage disease. Acta Neuropathologia 56: 225-232. ;  online abstract
  • 2. Kelly WR, Clague AE, Barns RJ, Bate MJ, MacKay BM (1983). Canine alpha-L-fucosidosis: a storage disease of Springer Spaniels. Acta Neuropathologica 60: 9-13. ;  online abstract
  • 3. Skelly BJ, Sargan DR, Herrtage ME, Winchester BG (1996). The molecular defect underlying canine fucosidosis. Journal of Medical Genetics 33: 284-288. ;  online abstract

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Globoid Cell Leukodystrophy / Krabbe’s Disease

Globoid cell

Category: Neurological

Mode of Inheritance:
Autosomal Recessive

Severity:
5red

Breeds Affected: Basset Hound, Beagle, Cairn Terrier, Coonhound, Dalmatian, Labradoodle, Miniature Poodle,Pomeranian, West Highland White Terrier,

Description:
A severe, autosomal recessive disorder resulting from a deficiency of the nervous system enzyme galactocerebrosidase (GALC) activity whereby the white matter is degenerated. Clinically, the symptoms appear between the 1st and 3rd months of age. Weakness of the limbs and tremors appear first, followed by muscular atrophy and neurological degeneration. The affected dogs may live until 8 or 9 months of age, when the symptoms become so severe that the dog is usually euthanized. Pathological studies of the white matter from affected dogs show characteristic globoid cells and loss of myelin.

Reference:
  • 1. Johnson GR, Oliver JE, Selcer R (1975). Globoid cell leukodystrophy in a Beagle. Journal of the American Veterinary Medical Association 167: 380-384. ;  online abstract
  • 2. Bjerkas I (1977) Hereditary 'cavitating' leucodystrophy in Dalmatian dogs: light and electron microscopic studies. Acta Neuropathologia 40: 163-169. ;  online abstract
  • 3. Zaki FA, Kay WL (1973). Globoid cell leukodystrophy in a Poodle (miniature). Journal of the American Veterinary Medical Association 163: 248-250. ;  online abstract
  • 4. Zaki FA, Kay WL (1973). Globoid cell leukodystrophy in a Poodle (miniature). Journal of the American Veterinary Medical Association 163: 248-250.
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GM1 – Gangliosidosis

Category:
Neurological

Mode of Inheritance:
Autosomal Recessive

Severity:
5red

Breeds Affected: Portuguese Water Dog

Description:
A lysosomal storage disease that leads to neurological disorders as a result in accumulation of gangliosides (major constituents and substrates of plasma membranes in a variety of cells), especially affecting cells of the nervous system, including brain, spinal cord, and autonomic ganglia.

In affected dogs, clinical signs are typically observed at around 4 to 5 months of age. In most cases, the disease is clinically manifested as a progressing disorder. Common signs of disease include vision problems, lethargy, difficulty walking, paralysis of the extremities, spasticity of the muscles and death in a period of approximately 8 months to 1 year of age.

Reference:
  • 1. Saunders GK, Wood PA Myers RK Shell LG Carithers R (1988) GM1 gangliosidosis in Portuguese water dogs: pathologic and biochemical findings. Veterinary Pathology 25: 265-9. ;  online abstract
  • 2. Shell LG, Potthoff AI, Carithers R, Katherman A, Saunders GK, Wood PA, Giger U. (1989) Neuronal-visceral GM1 gangliosidosis in Portuguese water dogs. Journal of Veterinary Internal Medicine. 3(1):1-7. ;  online abstract
  • 3. Muller G, Baumgartner W, Moritz A, Sewell A, Kustermannkuhn B (1998). Biochemical findings in a breeding colony of Alaskan huskies suffering from GM(1)-gangliosidosis. Journal of Inherited Metabolic Disease 21: 430-431. ;  online abstract
  • 4. Wang ZH, Zeng B, Shibuya H, Johnson GS, Alroy J, Pastores GM, Raghavan S, Kolodny EH. (2000) Isolation and characterization of the normal canine beta-galactosidase gene and its mutation in a dog model of GM1-gangliosidosis. Journal of Inherited Metabolic Diseases. 23(6):593-606. ;  online abstract

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gray collie>
Gray Collie Syndrome (canine cyclic neutropenia)

gray collie

Category:
Hematological

Mode of Inheritance:
Autosomal Recessive

Severity:
5red

Breeds Affected: Collie (rough), Collie (smooth)

Description:
Canine Cyclic Neutropenia is a genetic disorder that affects the bone marrow stem cells, which are responsible for developing all blood cells in the body. This disorder leads to cyclic fluctuation in the number of blood cells, the number of the neutrophil (white blood cells) blood cells falls down sharply every 10 to 12 days, and then it returns to normal. Affected puppies look weaker and smaller than their litter siblings and have a noticeable pale gray, pinkish gray or beige coat colour. Due to the changing number of blood cells, the puppies become susceptible to infections and by the age of 10 to 12 weeks they start exhibiting various clinical signs such as fever, diarrhoea, eye and/or respiratory infections. Puppies rarely live beyond the age of 3 years and usually die within few weeks after birth.

Reference:
  • 1. Lund JE, Padgett GA, Ott RL. (1967) Cyclic neutropenia in grey collie dogs. Blood. 29(4):452-61. ;  online abstract
  • 2. Yang TJ. (1987) Pathobiology of canine cyclic hematopoiesis. In Vivo 15: 297-302. ;  online abstract
  • 3. Avalos BR, Broudy, VC, Ceselski, SK, Druker, BJ, Griffin, JD, Hammond, WP (1994) Abnormal response to granulocyte colony-stimulating factor (G-CSF) in canine cyclic hematopoiesis is not caused by altered G-CSF receptor expression. Blood 84: 789-794. ;  online abstract
  • 4. Benson KF, Li FQ, Person RE, Albani D, Duan Z, Wechsler J, Meade-White K, Williams K, Acland GM, Niemeyer G, Lothrop CD, Horwitz M. (2003) Mutations associated with neutropenia in dogs and humans disrupt intracellular transport of neutrophil elastase. Nat Genet. 35(1):90-6. ;  online abstract

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Hereditary Cataract ( includes Juvenile and Dominant)

Pasted Graphic 2

Category:
Ophthalmic

Mode of Inheritance:
Autosomal Recessive expect in Australian Shepherd where it is Autosomal Dominant.

Severity:
3red

Breeds Affected: Australian Shepherd (Dominant), Boston Terrier (Juvenile), French Bulldog, Staffordshire Bull Terrier,

Description:
Cataracts are a clouding of lens of the eye caused by a breakdown of tissue in the eye. This generally results in an inability to see clearly, and can cause total blindness. Not all cataracts in dogs are hereditary, but some are often familial, this type is known as Hereditary Cataracts.
A mutation causes this type of cataracts in several dog breeds. There are several mutation involved in HC in the different breeds. We test for all types. Dogs are typically affected bilaterally (in both eyes) with onset typically occurring between 12 months and 3 years of age. Cataracts usually begin small and grow progressively, though the speed of growth is highly variable. Some cataracts will grow so slowly that the dog's vision remains relatively clear, while others will grow such that the dog will quickly go blind. Corrective surgery is possible, though it is costly and is not always effective.


Reference:
  • 1. 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. Vet Ophthalmol. 2006 Sep-Oct;9(5):369-78.
  •   online abstract
  • 2. Bras ID, Colitz CM, Kusewitt DF, Chandler H, Lu P, Gemensky-Metzler AJ, Wilkie DA. (2007) Evaluation of advanced glycation end-products in diabetic and inherited canine cataracts. Graefes Arch Clin
  • Exp Ophthalmol. 245(2):249-57.   online abstract
  • 3. Mellersh CS, McLaughlin B, Ahonen S, Pettitt L, Lohi H, Barnett KC. (2009) Mutation in HSF4 is associated with hereditary cataract in the Australian Shepherd. Vet Ophthalmol. 12(6):372-8.  online abstract

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Ivermectin and Multi Drug Sensitivity MDR1

Category:
Metabolic

Mode of Inheritance:
Autosomal Recessive

Severity:
3red

Breeds Affected: Border Collie, Collie Rough and Smooth, Various Breeds

Description:
Some dog breeds are more sensitive to certain drugs than other breeds. Collies and related breeds, for instance, can have adverse reactions to drugs such as ivermectin. Drug sensitivities result from a mutation in the multi-drug resistance gene (MDR1). This gene encodes a protein, P-glycoprotein that is responsible for pumping many drugs and other toxins out of the brain. Dogs with the mutant gene cannot pump some drugs out of the brain as a normal dog would, which may result in abnormal neurologic signs. The result may be an illness requiring an extended hospital stay - or even death. This test is most commonly used for Ivermectin sensitivity but many other drugs are included. Notably chemotherapy agents and Acepromazine and Butorphanol which tend to cause deeper and more prolonged sedation - see complete list below. Veterinarians are recommended to reduce the dosage by 25% in MDR1 carriers [+/-] and by 30 -50% in MDR1 affected dogs.;

Anti-Parasitic Drugs -
Ivermectin substances: Diapec®, Ecomectin®, Equimax®,Eqvalan®, Ivomec®, Noromectin®, Paramectin®, Qualimec®, Sumex® &Virbamec®
Doramectine substances:Dectomax®, Moxidectine substances: Cydectin® &Equest®
Loperamide substances - Immodium® [anti-diarrhoeal]
Metronidazole substances -
Flagyl
Chemotherapy Agents -
Vinblastine, Doxorubicine, Paclitaxel, Docetaxel, Methotrexat& Vincristine Glucocorticoids (Steroids commonly used to treat auto-immune diseases): Dexamethason
Immuno-suppressives:
Cyclosporine A
Heart glycosides:
Digoxine & Methyldigoxine
Antiarrhythmics:
Verapamil, Diltiazem & Chinidine
Analgesics -
Morphine & Butorphenol
Anti-emetics:
Metoclopramide, Ondansetron & Domperidon
Antibiotics - Sparfloxacin, Grepafloxacin; Erythromycin
Antihistamines - Ebastin
Tranquillisers - Acepromazine
Other drugs; Etoposide; Mitoxantrone; Ondansetron; Paclitaxel; Rifampicin.

Reference:
  • 1. Nelson OL, Carsten E, Bentjen SA, Mealey KL. (2003) Ivermectin toxicity in an Australian Shepherd dog with the MDR1 mutation associated with ivermectin sensitivity in Collies. J Vet Intern Med. 17(3):354-6.  
  •  online abstract
  • 2. Mealey KL, Bentjen SA, Waiting DK. (2002)Frequency of the mutant MDR1 allele associated with ivermectin sensitivity in a sample population of collies from the northwestern United States. American Journal of Veterinary Research. 63(4):479-81.   online abstract
  • 3. Neff MW, Robertson KR, Wong AK, Safra N, Broman KW, Slatkin M, Mealey KL, Pedersen NC. (2004) Breed distribution and history of canine mdr1-1Delta, a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage. Proc Natl Acad Sci U S A. 101(32):11725-30.   online abstract
  • 4. Geyer, J., Doring, B., Godoy, J. R., Moritz, A., Petzinger, E. (2005). Development of a PCR-based diagnostic test detecting a nt230(del4) MDR1 mutation in dogs: verification in a moxidectin-sensitive Australian Shepherd. J. vet. Pharmacol. Therap.28, 95-99  online abstract
  • 5. Geyer J, Doring B, Godoy JR, Leidolf R, Moritz A, Petzinger E. (2005) Frequency of the nt230 (del4) MDR1 mutation in Collies and related dog breeds in Germany. J Vet Pharmacol Ther.28(6):545-51.   online abstract
  • 6. Mealey KL, Meurs KM, (2008) Breed distribution of the ABCB1-1Delta (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping. J Am Vet Med Assoc. 233(6):921-4.  online abstract
  • 7. Klintzsch S, Meerkamp K, Döring B, Geyer J. (2009) Detection of the nt230[del4] MDR1 mutation in dogs by a fluorogenic 5' nuclease TaqMan allelic discrimination method. Vet J. 2009 Sep 2.   online abstract
  • 8. Barbet JL, Snook T, Gay JM, Mealey KL. (2009) ABCB1-1 Delta (MDR1-1 Delta) genotype is associated with adverse reactions in dogs treated with milbemycin oxime for generalized demodicosis. Vet Dermatol. 2009 Apr;20(2):111-4.  online abstract
  • 9. Gramer I, Leidolf R, Döring B, Klintzsch S, Krämer EM, Yalcin E, Petzinger E, Geyer J. Breed distribution of the nt230(del4) MDR1 mutation in dogs. Vet J. 2010 Jul 21. [Epub ahead of print]   online abstract

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L-2-hydroxyglutaric Aciduria

Category:
Metabolic

Mode of Inheritance:
Autosomal Recessive

Severity:
4red

Breeds Affected: Staffordshire Bull Terrier

Description:
L-2-HGA (L-2-hydroxyglutaric aciduria) is a neurometabolic disorder characterised by elevated levels of L-2-hydroxyglutaric acid in urine, plasma and cerebrospinal fluid.
L-2-HGA affects the central nervous system, with clinical signs usually apparent between 6 months and one year (although they can appear later). Symptoms include epileptic seizures, "wobbly" gait, tremors, muscle stiffness as a result of exercise or excitement and altered behavior such as personality disorders, poor learning abilities, and seizures. Unfortunately there is no cure and most affected dogs will need to be euthanized at an early age. The disorder shows an autosomal recessive mode of inheritance: two copies of the defective gene (one inherited from each parent) have to be present for a dog to be affected by the disease.

Reference:
  • 1. Shires PK, Nafe LA, Hulse DA. (1983) Myotonia in a Staffordshire terrier. Journal of the American Veterinary Medical Association 183: 229.;  online abstract
  • 2. Abramson CJ, Platt SR, Jakobs C, Verhoeven NM, Dennis R, L. Garosi L and Shelton GD, (2003b) l-2-Hydroxyglutaric aciduria in Staffordshire Bull Terriers, J Vet Internal Med 17:551–556.;  online abstract
  • 3. 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. J Med Genet. 44(5):334-40.;  online abstract
  • 4. Scurrell E, Davies E, Baines E, Cherubini GB, Platt S, Blakemore W, Williams A, Schöniger S. (2008) Neuropathological findings in a Staffordshire bull terrier with l-2-hydroxyglutaric aciduria. J Comp Pathol. 138(2-3):160-4. ;  online abstract

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Merle

Merle

Category:
Ophthalmic and Auditory

Mode of Inheritance:
Autosomal Recessive

Severity:
3red

Breeds Affected: Shetland Sheepdog, Collie, Great Dane, Cardigan Welsh Corgi, Australian Shepherd, Border Collie, Chihuahua, Cocker Spaniel, Dachshund, Catahoula Leopard Dog, Norwegian Hound, Pyrenean Shepherd, Pomeranian, Various other Breeds

Description:
The merle coat colour is a mutation in the dog SILV gene characterized by patches of dilute pigment in combination with areas of full pigmentation. If the basic colour of the dog is black, the effect of the merle gene is a soft gray, often referred to as “blue”. If the basic colour of the dog is red, the effect of the merle gene is a pale red. The merle coat pattern is characteristic of a number of breeds.

Unfortunately there are some health problems ssociated with the Merle gene. Both heterozygous merle (Mm) and homozygous double merle (MM) dogs may exhibit auditory and ophthalmic abnormalities including mild to severe deafness, increased intraocular pressure, ametropia, microphthalmia and colobomas. The double merle genotype may also be associated with abnormalities of skeletal, cardiac and reproductive systems.

Reference:
Clark, Leigh Anne; Jacquelyn M. Wahl, Christine A. Rees, and Keith E. Murphy (2005-11-26). "Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog" (PDF). PNAS Early Edition. Louisiana State University. http://www.lsu.edu/deafness/ClarkPNASMerle.pdf. Retrieved 2007-05-15.

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Mucopolysaccharidosis

Category:
Metabolic / Neurological

Mode of Inheritance:
Autosomal Recessive

Severity:
4red

Breeds Affected: Schipperke

Description:
This is an inherited disease classified as a lysosomal storage disease (LSD). Lysosomes are "bags" within cells of the body, filled with special enzymes which disassemble molecules in an orderly manner. If one of the enzymes is missing, due to mutations in the gene for that enzyme, the disassembly stops, and undegraded molecules accumulate in lysosomes (hence the term LSD), and the cells become sick or die, which leads to disease.

The clinical signs in the dogs are related to brain disease, appear between 2-4 years of age, and include tremor, and difficulty in balancing, walking, and negotiating obstacles such as stairs. The disease is progressive, and owners have chosen euthanasia, usually 1-2 years after recognizing clinical signs. There are several types of mucopolysaccharidosis in different types of dog breeds, associated with different genes that code for the specific enzymes involved

Reference:
  • 1. Knowles K, Alroy J, Castagnaro M, Raghavan SS, Jakowski RM, Freden GO. (1993) Adult-onset lysosomal storage disease in a Schipperke dog: clinical, morphological and biochemical studies. Acta Neuropathol. 86(3):306-12.;  online abstract
  • 2. Ellinwood NM, Wang P, Skeen T, Sharp NJ, Cesta M, Decker S, Edwards NJ, Bublot I, Thompson JN, Bush W, Hardam E, Haskins ME, Giger U. (2003) A model of mucopolysaccharidosis IIIB (Sanfilippo syndrome type IIIB): N-acetyl-alpha-D-glucosaminidase deficiency in Schipperke dogs. J Inherit Metab Dis. 26(5):489-504. ;  online abstract
  • 3. Ellinwood NM, Van Hoeven M, Seng A, Berman L., Sarvas LG, Haskins ME and Giger U (2004) Molecular basis of Mucopolysaccharidosis type IIIB in Schipperkes. (Abstract). 2nd International Conference “Advances in Canine & Feline Genomics”. pp68.;  online abstract
  • 4. Haskins ME. (2007) Animal models for mucopolysaccharidosis disorders and their clinical relevance. Acta Paediatr Suppl. 96(455):56-62.;  online abstract
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Muscular Dystrophy X-linked

m dystrophy

Category:
Muscular

Mode of Inheritance:
Autosomal Recessive - X linked

Severity:
5red

Breeds Affected: Golden Retriever

Description:
MD is a degenerative muscle disease associated with a deficiency of the protein dystrophin. While rare, this canine disease is severely disabling and eventually fatal.
MD is mostly found in males. It is carried on the X chromosome, so a male golden retriever dog only needs one parent to pass on the defective gene, unlike a female golden, who needs to inherit the gene from both parents. Since MD presents itself by about eight weeks of age, anyone planning to breed dogs, especially golden retriever dogs, or acquire a puppy will benefit from knowing more about MD. No cure exists, however researchers have found promising stem cell therapies for affected dogs that may become available in the future.

Reference:
1. Ambrósio CE, Fadel L, Gaiad TP, Martins DS, Araújo KP, Zucconi E, Brolio MP, Giglio RF, Morini AC, Jazedje T, Froes TR, Feitosa ML, Valadares MC, Beltrão-Braga PC, Meirelles FV, Miglino MA. (2009) Identification of three distinguishable phenotypes in golden retriever muscular dystrophy. Genet Mol Res. 8(2):389-96.
2. Fletcher S; Carville KS; Howell JM; Mann CJ; Wilton SD (2001)Evaluation of a short interspersed nucleotide element in the 3 ' untranslated region of the defective dystrophin gene of dogs with muscular dystrophy AMERICAN J. VETERINARY RES. 62: 1964-1968 ISSN/ISBN: 0002-9645
3. Sampaolesi M, Blot S, D'Antona G, Granger N, Tonlorenzi R, Innocenzi A, Mognol P, Thibaud JL, Galvez BG, Barthélémy I, Perani L, Mantero S, Guttinger M, Pansarasa O, Rinaldi C, Cusella De Angelis 4. MG, Torrente Y, Bordignon C, Bottinelli R, Cossu G. (2006) Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature. 2006 444(7119):574-9. ;  
online abstract
5. Bretag AH, (2007) Stem cell treatment of dystrophic dogs. Nature. 450(7173):E23; discussion E23-5. PMID: 18097347;  
online abstract

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Myotonia Congenita



Category: Muscular

Mode of Inheritance:
Autosomal Recessive

Severity:
4red

Breeds Affected: Miniature Schnauzer

Description:
This is a hereditary pathogenic condition affecting skeletal muscle and is characterized by a delay of relaxation of the muscles following a stimulus or after cessation of voluntary activity. Affected animals have significant excessive growth of the muscles (muscle hypertrophy). Myotonia congenita results from genetic defects in the skeletal muscle chloride ion channel causing reduced conductance. Signs include difficulty in rising after a period of rest, a stiff and stilted gait when walking, and a bunnyhop type movement when running. In addition, there are increased respiratory sounds, difficulty when swallowing, abnormal bark and dental abnormalities.

Reference:
  • 1. Vite CH, Melniczek J, Patterson D, Giger U. (1999) Congenital myotonic myopathy in the schnauzer (miniature): an autosomal recessive trait. Journal of Heredity. 90(5):578-80. ;  online abstract
  • 2. Rhodes TH, Vite CH, Giger U, Patterson DF, Fahlke C, George AL Jr. (1999)A missense mutation in canine C1C-1 causes recessive myotonia congenita in the dog. FEBS Lett.ers 456(1):54-8. ;  online abstract
  • 3. Bhalerao DP, Rajpurohit Y, Vite CH, Giger U. (2002) Detection of a genetic mutation for myotonia congenita among Miniature Schnauzers and identification of a common carrier ancestor. Am J Vet Res. 63(10):1443-7.;  online abstract
  • 4. Gracis M, Keith D, Vite CH. (2000) Dental and craniofacial findings in eight miniature schnauzer dogs affected by myotonia congenita: preliminary results. J Vet Dent. 17(3) :119-27.;  online abstract

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Myotubular Myopathy - X linked

Category:
Muscular

Mode of Inheritance:
Autosomal Recessive - X linked

Severity:
5red

Breeds Affected:
Labrador Retriever, Labradoodle

Description:
This disease is caused by mutations in the gene that codes for the myotubular protein, thought to be involved in cellular transport. Approximately 80% of males with a diagnosis of myotubular myopathy by muscle biopsy will have the mutation.

Patients with the disease generally present with muscle weakness, feeding difficulties, respiratory distress, and delayed motor milestones. Death in early age is common in males with the classic form of this condition. Milder forms of XLMTM have been identified and are characterized by fewer respiratory complications and longer life expectancy than observed in the severe cases.

Reference:
Bergman RL, Inzana KD, Monroe WE, Shell LG, Liu LA, Engvall E, Shelton GD. (2002) Dystrophin-deficient muscular dystrophy in a labrador retriever.Journal of the American Animal Hospital Association 38(3):255-61. ;  online abstract

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Narcolepsy

Category:
Neurological

Mode of Inheritance:
Autosomal Recessive

Severity:
2red

Breeds Affected: Dachsund, Doberman, Labrador Retriever, Labradoodle

Description:
A neurological disease that is frequently inherited in an autosomal recessive fashion. Affected dogs appear to fall asleep, suddenly losing control of their hind legs or collapsing in complete paralysis, while still being entirely aware of their surroundings. Attacks last from a few seconds to a few minutes and end with no residual effects. Some sporadic cases of narcolepsy are not inherited.

Reference:
1. Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E. (1999) The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98: 365-76. ;  online abstract
2. Foutz AS, Mitler MM, Cavalli-Sforza LL, Dement WC. (1979) Genetic factors in canine narcolepsy. Sleep. 1(4):413-21. ;  
online abstract
3. Riehl J, Nishino S, Cederberg R, Dement WC, Mignot E. (1998) Development of cataplexy in genetically narcoleptic Dobermans. Exp Neurol. 152(2):292-302. ;  
online abstract
4. Mitler MM, Soave O, Dement WC. (1976) Narcolepsy in seven dogs. J Am Vet Med Assoc. 168(11):1036-8. ;  
online abstract
5. John J, Wu MF, Maidment NT, Lam HA, Boehmer LN, Patton M, Siegel JM. (2004) Developmental changes in CSF hypocretin-1 (orexin-A) level in normal and genetically narcoleptic Doberman pinschers. J Physiol. [Epub ahead of print] ;  
online abstract

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Natural Bob Tail

nbt

Category:
Neurological

Mode of Inheritance:
Autosomal Dominant

Severity:
3red

Breeds Affected: Australian Shepherd, Rottweiller, Boxer, Pembroke Welsh Corgi, Various other Breeds

Description:
This dominant genetic mutation is responsible for a natural shortening of the tailbone. The mutation causes a shorted tail or absence of tail to occur. There are various levels of severity that occur, from almost no tail to a shortened tail. Although in itself it poses no health concerns, in the case of a homozygous dominant dog, the allele becomes lethal in the embryonic stage and the affected dog does not survive. Breeding NBT dogs can be high risk. Natural Bob Tail is a dominant trait, which means that it only requires a single copy of the NBT gene in order to express the trait. The problem arises when a dog received 2 copies of the gene (1 from the sire and one from the dam), its called homozygous. When it occurs, the gene becomes lethal and the affected pup dies (usually in the embryonic stage). Rarely other spinal cord abnormalities can form which are not usually compatible with life.

Reference:
1. Hytönen et al (2008), "Ancestral T-Box mutation is present in many, but not all, short-tailed dog breeds", Journal of Heredity, Advance Access published online on October 14, 2008, doi:10.1093/jhered/esn085
2. Haworth K, Putt W, Cattanach B, Breen M, Binns M, Lingaas F, Edwards YH. (2001) Canine homolog of the T-box transcription factor T; failure of the protein to bind to its DNA target leads to a short-tail phenotype. Mammalian Genome. 2001 Mar;12(3):212-8.   
online abstract
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Neonatal Encephalopathy



Category:
Neurological

Mode of Inheritance:
Autosomal Recessive

Severity:
5red

Breeds Affected: Standard Poodle

Description:
Fatal developmental brain disease which is inherited as an autosomal recessive trait. Most affected puppies die shortly after birth. With intensive nursing care, affected pups can be kept alive for a few weeks; however, unfortunately none have survived past their fifth week.

Reference:
Chen X, Johnson GS, Schnabel RD, Taylor JF, Johnson GC, Parker HG, Patterson EE, Katz ML, Awano T, Khan S, O'Brien DP. (2008) A neonatal encephalopathy with seizures in standard poodle dogs with a missense mutation in the canine ortholog of ATF2. Neurogenetics. 2008 Feb;9(1):41-9. Epub 2007 Dec 12. PMID: 18074159 ;  online abstract

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Neuronal Ceroid Lipofuscinosis



Category:
Neurological

Mode of Inheritance:
Autosomal Recessive

Severity:
5red

Breeds Affected: American Bulldog, Border Collie, Dachsund

Description:
NCL is a nervous system storage disease that results in degenerative changes primarily in the cerebellum, but also in other multiple areas of the brain and spinal cord. As the central nervous system degenerates the quality of life decreases as well as the affected dog’s lifespan.
Signs usually start at 2-3 years of age (later in some breeds) and include progressive mental and motor deterioration, over-expressed and unintentional muscle movements and loss of coordination. Affected dogs will usually adopt a wide stance, occasional muscle twitching, sadly most affected dogs die or are euthanized before 5 years of age.

Reference:
  • 1. Studdert VP, Mitten RW (1991). Clinical Features of Ceroid Lipofuscinosis in Border Collie Dogs. Australian Veterinary Journal 68: 137-140.   online abstract
  • 2. Taylor RM, Farrow BR. (1992) Ceroid lipofuscinosis in the border collie dog: retinal lesions in an animal model of juvenile Batten disease. Am J Med Genet. 1992 Feb 15;42(4):622-7.   online abstract
  • 3. Taylor RM, Farrow BR. 91988)Ceroid-lipofuscinosis in border collie dogs. Acta Neuropathol (Berl). 75(6):627-31.  online abstract
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Phosphofructokinase Deficiency

Category:
Metabolic

Mode of Inheritance:
Autosomal Recessive

Severity:
2red

Breeds Affected: American Cocker Spaniel, Cocker Spaniel, English Springer Spaniel

Description:
This is an autosomal recessive genetic disease which prevents the metabolism of glucose into available energy resulting in exercise intolerance and muscle disease. PFK deficiency also destroys red blood cells in affected dogs, leading to anemia. Affected dogs will exhibit signs when stressed, during times of exercise, heat, or prolonged barking. These signs include pale gums, weakness, cramps and high fever. The most identifiable symptom is often dark coloured urine due to the premature breakdown of blood products. PFK can be detected early, and with careful monitoring and management stress and excitement levels, an affected dog may be able to have a relatively normal lifespan.

Reference:
1. Giger U, Reilly MP, Asakura T, Baldwin CJ, Harvey JW. (1986) Autosomal recessive inherited phosphofructokinase deficiency in English springer spaniel dogs. Animal Genetics. 17(1):15-23. ;  online abstract
2. Giger U, Smith BF, Woods CB, Patterson DF, Stedman H (1992) Inherited phosphofructo-kinase deficiency in an American cocker spaniel. Journal of the American Veterinary Medical Association 201: 1569-71. ;  
online abstract

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Polyneuropathy/Neuropathy (NDRG1)

greyhound neuropathy

Category: Neurological

Mode of Inheritance:
Autosomal Recessive

Severity:
5red

Breeds Affected: Greyhound

Description:
Greyhound Neuropathy is a neurological disease marked by muscle weakness, exercise intolerance and an odd “bunny-hopping” gait. Symptoms first appear clinically in young dogs at three to nine months of age and progress to the point where most affected dogs are euthanized within their first year. The disease is inherited as a autosomal recessive trait, meaning that Carriers show no symptoms.

Reference:
Drögemüller C et al. A Deletion in the N-Myc Downstream Regulated Gene 1 (NDRG1)Gene in Greyhounds with Polyneuropathy PLoS One. 2010 Jun 22;5(6):e11258.
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Primary Lens Luxation

Pasted Graphic 4

Category:
Ophthalmic

Mode of Inheritance:
Autosomal Recessive (incomplete penetrance)

Severity:
4red

Breeds Affected: Chinese Crested Dog, Jack Russell Terrier, Jagd Terrier, Lancashire Heeler, Miniature Bull Terrier, Parson Russell Terrier, Patterdale Terrier, Rat Terrier, Sealyham Terrier, Tenterfield Terrier, Tibetan Terrier, Volpino Italiano

Description:
Primary Lens Luxation (PLL) is a well-recognised, painful and blinding inherited eye condition that affects many breeds of dogs. In affected dogs the zonular fibres which support the lens breakdown or disintegrate, causing the lens to fall into the wrong position within the eye. If the lens falls into the anterior chamber of the eye glaucoma and loss of vision can quickly result.
The DNA test we are now offering examines the DNA from each dog being tested for the presence or absence of this precise mutation. It is thus a ‘mutation-based test’ and not a ‘linkage-based test’.

Reference:
  • 1. Curtis R, Barnett KC, Startup FG. (1983) Primary lens luxation in the miniature bull terrier. Vet Rec. 112(14):328-30.   online abstract
  • 2. Sargan DR, Withers D, Pettitt L, Squire M, Gould DJ, Mellersh CS. (2007)Mapping the mutation causing lens luxation in several terrier breeds. J Hered. 98(5):534-8. Epub 2007 Jun 15.   online abstract
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Progressive Retinal Atrophy of Golden Retriever

Category: Ophthalmic

Mode of Inheritance:
Autosomal Recessive

Severity:
4red

Breeds Affected: Golden Retriever

Description:
PRA is a well-recognised inherited condition characterised by bilateral degeneration of the retina which causes progressive vision loss that culminates in total blindness. There is no treatment for PRA, of which several genetically distinct forms are recognised, each caused by a different mutation in a specific gene. The various forms of PRA are typically breed-specific, with clinically
affected dogs of the same breed usually sharing an identical mutation. Clinically affected dogs of different breeds, however, usually have different mutations, although PRA-mutations can be
shared by several breeds. Geneticists at the AHT, in collaboration with scientists from at the Swedish University of Agricultural Sciences and Uppsala University, have identified a recessive mutation that is associated with the development of
PRA in the Golden Retriever. The DNA test we are offering examines the DNA from each dog being tested for the presence or absence of this precise mutation and is thus a ‘mutation-based test’ and not a ‘linkage-based test’.

Reference:
Cathryn Mellersh,Canine Genetics at the AHT "New DNA test for progressive retinal atrophy in golden retrievers" Veterinary Record 2010;167:471 doi:10.1136/vr.c5215
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Progressive Retinal Atrophy - rcd 3

Category: Ophthalmic

Mode of Inheritance:
Autosomal Recessive

Severity:
4red

Breeds Affected: Cardigan Welsh Corgi

Description:
A form of Progressive Retinal Atrophy, a progressive disease that causes the degeneration of photosensitive tissues in the eye, which leads to blindness. Normally the vision receptors in the eyes undergo a continual process of replacement and renewal, with this disease this process slows and eventually stops. The thinning of the retinal tissue leads to the degeneration of the photosensitive receptors sensitive to dim light (rods), causing night blindness, and then the receptors sensitive to bright light (cones), causing day blindness. Rcd3 has an early onset compared to other forms of PRA. Signs of rcd3 can be seen in pups as early as 6 weeks old and affected dogs are usually blind by 1-2 years of age.

Reference:
Petersen-Jones SM, Zhu FX. Development and use of a polymerase chain reaction-based diagnostic test for the causal mutation of progressive retinal atrophy in Cardigan Welsh Corgis. American Journal of Veterinary Research 617):844-846, 2000.

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Progressive Retinal Atrophy - Cord 1

Category: Ophthalmic

Mode of Inheritance:
Autosomal Recessive

Severity:
3red

Breeds Affected: English Springer Spaniel, Miniature Long-Haired Dachshund, Miniature Smooth-Haired Dachshund, Miniature Wire-Haired Dachshund

Description:
Cone-Rod Dystrophy 1 - Progressive Retinal Atrophy (cord1 - PRA) is an inherited disease of the eye that affects the cone and rod cells that make up the dog's retina and often leading to blindness.
This form of PRA has been documented in scientific literature and was believed to have an age of onset of around 2-10 years with the average age of diagnosis of the Miniature Long-haired Dachshunds in one study was 4.98 years. It is possible that the factors causing this variation could delay the onset of obvious clinical signs beyond the lifespan of the dog, so owners may never see behavioural changes and never recognise that their dog has a problem. However, the dog will still be genetically-affected by the disease and have two copies of the cord1 mutation.

Reference:
Mellersh,C.S., Boursnell,M.E.G., Pettitt,L., Ryder,E.J., Holmes,N.G., Grafham,D., Forman,O.P., Sampson,J., Barnett,K.C., Blanton,S., Binns,M.M., Vaudin,M. (2006) Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics 88 293-301
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Progressive Retinal Atrophy -Rcd1

Category:
Ophthalmic

Mode of Inheritance:
Autosomal Recessive

Severity:
4red

Breeds Affected: Irish Setter, Red and White setter

Description:
A progressive disorder of the retina, which is sensitive to light, that eventually leads to blindness in dogs. PRA is essentially the slow death of retinal tissue; the tissue thins considerably over time causing degeneration of the photosensitive rods and cones of the eye. The disease is an early onset form of Progressive Retinal Atrophy; pups begin showing signs of night blindness by 6 weeks of age, and are completely blind by 1-2 years of age.

Reference:
1. Clements PJ, Gregory CY, Peterson-Jones SM, Sargan DR, Bhattacharya SS. (1993) Confirmation of the rod cGMP phosphodiesterase beta subunit (PDE beta) nonsense mutation in affected rcd-1 Irish setters in the UK and development of a diagnostic test. Current Eye Research 12: 861-6. ;  online abstract
2. Ray K, Baldwin VJ, Acland GM, Aguirre GD. (1995) Molecular diagnostic tests for ascertainment of genotype at the rod cone dysplasia 1 (rcd1) locus in Irish setters. Curr Eye Res. 14(3):243-7. ;  
online abstract

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Progressive Retinal Atrophy -rcd1a

Category:
Ophthalmic

Mode of Inheritance:
Autosomal Recessive

Severity:
3red

Breeds Affected: Sloughi

Description:
A progressive disorder of the retina, which is sensitive to light, that eventually leads to blindness in dogs. PRA is essentially the slow death of retinal tissue; the tissue thins considerably over time causing degeneration of the photosensitive rods and cones of the eye. This type of PRA has been documented in Sloughis repeatedly. The Sloughi PRA disease has late onset with first noticeable signs of vision loss usually evident at 2 to 3 years of age. The inheritance pattern of this disease is autosomal recessive, meaning a dog is affected when it inherits one disease gene from each parent, where each parent is either a carrier or affected with PRA.

Reference:
Dekomien G, Runte M, Godde R, Epplen JT. (2000) Generalized progressive retinal atrophy of Sloughi dogs is due to an 8-bp insertion in exon 21 of the PDE6B gene. Cytogenetics Cell Genetics. 90(3-4):261-7. ;  online abstract

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Progressive Rod Cone Degeneration - PRA

Category:
Ophthalmic

Mode of Inheritance:
Autosomal Recessive

Severity:
3red

Breeds Affected: American Cocker Spaniel, American Eskimo Dog, Australian Cattle Dog, Australian Shepherd, Australian Stumpy Tail Cattle Dog, Chesapeake Bay Retriever, Chinese Crested, Cockapoo, Cocker Spaniel, Finnish Lapphund, Golden Retreiver, Goldendoodle, Labradoodle, Labrador Retriever, Poodle (Toy and Miniature), Nova Scotia Duck Tolling Retriever, Portuguese Water Dog, Swedish Lapphund, Yorkshire Terrier

Description:
PRCD is the progressive degeneration of photoreceptors (rods and cones) in the dog’s eye causing degenerative abrasions of the retina, resulting in blindness. PRCD is a late onset form of PRA, however there is variation of the age of onset between the many breeds it affects. Variation in the time of onset is due to a combination of genetic and environmental factors.
The initial symptom of PRCD is usually night blindness, as the degeneration of the retina affects the rods, reducing visual abilities in dim lights. Night blindness usually progresses to day blindness quickly, as the cones in the eye sensitive to bright lights deteriorate. Sadly, PRCD regularly leads to total blindness, for which there is no treatment or cure.

Reference:
1. Sidjanin DJ, Miller B, Kijas J, McElwee J, Pillardy J, Malek J, Pai G, Feldblyum T, Fraser C, Acland G, Aguirre G. (2003) Radiation hybrid map, physical map, and low-pass genomic sequence of the canine prcd region on CFA9 and comparative mapping with the syntenic region on human chromosome 17 . Genomics. 81(2):138-48.   online abstract
2. Acland GM, Ray K, Mellersh CS, Gu W, Langston AA, Rine J, Ostrander EA, Aguirre GD (1998) Linkage analysis and comparative mapping of canine progressive rod-cone degeneration (prcd) establishes potential locus homology with retinitis pigmentosa (RP17) in humans. Proceedings of the National Academy of Sciences USA. 95:3048-53.   
online abstract
3. Zangerl B, Goldstein O, Philp AR, Lindauer SJ, Pearce-Kelling SE, Mullins RF, Graphodatsky AS, Ripoll D, Felix JS, Stone EM, Acland GM, Aguirre GD.. (2006) Identical mutation in a novel retinal gene causes progressive rod-cone degeneration in dogs and retinitis pigmentosa in humans. Genomics. 2006 Nov;88(5):551-63.   online abstract _________________________________________________________________________________________________________________________________________________________________________________________________
Pug Encephalitis



Category: Neurological

Mode of Inheritance:
Autosomal Recessive

Severity:
5red

Breeds Affected: Pug

Description:
Severe depression, ataxia, and generalized seizures affecting adolescent and young adult animals. Median onset age 19mo, and median survival 23 days. Tend to be young adult females. May be visual loss. Progressive necrotizing meningo-encephalitis with autoantibodies against Glial Fibrillary Acidic Protein +ve astrocytes. It has been suggested that normal pugs may leak large amounts of GFAP into CSF. No viruses isolated.

Reference:
  • 1. Cordy DR, Holliday TA. (1989) A necrotizing meningoencephalitis of pug dogs. Veterinary Pathology. 26(3):191-4. ;  online abstract
  • 2. Uchida K, Hasegawa T, Ikeda M, Yamaguchi R, Tateyama S. (1999) Detection of an autoantibody from Pug dogs with necrotizing encephalitis (Pug dog encephalitis). Vet Pathol. 36(4):301-7. ;  online abstract
  • 3. Levine JM, Fosgate GT, Porter B, Schatzberg SJ, Greer K. (2008) Epidemiology of necrotizing meningoencephalitis in Pug dogs. J Vet Intern Med. 22(4):961-8.;  online abstract
  • 4. Greer KA, Schatzberg SJ, Porter BF, Jones KA, Famula TR, Murphy KE. (2009) Heritability and transmission analysis of necrotizing meningoencephalitis in the Pug. Res Vet Sci. 86(3):438-42.;  online abstract
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Pyruvate Dehydrogenase Phosphatase 1 Deficiency

Category:
Metabolic

Mode of Inheritance:
Autosomal Recessive

Severity:
3red

Breeds Affected: Clumber Spaniel, Sussex Spaniel

Description:
Pyruvate Dehydrogenase Phosphatase 1 is an enzyme that is present in every cell of the body. It is involved in the conversion of food into energy and therefore it is not only vital for the function of the cells but for survival. Deficiency of the PDHP1 enzyme is a genetic disease that affects several breeds of dogs. The disease is characterised by dramatic exercise intolerance and post exercise collapse. Affected dogs may have a shortened life span due to heart and lung complications, there is also some indication that this mutation maybe involved with early foetal death or death in the neonatal period. Neurological symptom may also be seen.

Reference:
Cameron JM, Maj MC, Levandovskiy V, MacKay N, Shelton GD, Robinson BH. (2007) Identification of a canine model of pyruvate dehydrogenase phosphatase 1 deficiency. Mol Genet Metab. 90(1):15-23. ;  online abstract

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Pyruvate Kinase Deficiency

Category:
Metabolic

Mode of Inheritance:
Autosomal Recessive

Severity:
4red

Breeds Affected: Basenji, Beagle, West Highland White Terrier

Description:
Pyruvate Dehydrogenase Phosphatase 1 is an enzyme that is present in every cell of the body. It is involved in the conversion of food into energy and therefore it is not only vital for the function of the cells but for survival. Deficiency of the PDHP1 enzyme is a genetic disease that affects several breeds of dogs. The disease is characterised by dramatic exercise intolerance and post exercise collapse. Affected dogs may have a shortened life span due to heart and lung complications, there is also some indication that this mutation maybe involved with early foetal death or death in the neonatal period. Neurological symptom may also be seen.

Reference:
1. Prasse KW, Crouser D, Beutler E, Walker M, Schall WD. (1975) Pyruvate kinase deficiency anemia with terminal myelofibrosis and osteosclerosis in a beagle. Journal of the American Veterinary Medical Association. 166(12):1170-5.   online abstract
2. Muller-Soyano A, Platt O, Glader BE. (1986)Pyruvate kinase deficiency in dog and human erythrocytes: effects of energy depletion on cation composition and cellular hydration. Am J Hematol. 23(3):217-21.   online abstract
3. Giger U, Mason GD, Wang P. (1991)Abstract Inherited erythrocyte pyruvate kinase deficiency in a beagle dog. Vet Clin Pathol. 20(3):83-86.   
online abstract
4. Giger U (2000) Regenerative anemias caused by blood loss or hemolysis. In: Ettinger, SJ and Feldman EC. (eds.) Textbook of Veterinary Internal Medicine W. B. Saunders, Philadelphia, pp.1784-1804.  
online abstract

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Thrombopathia

Category: Haematologic

Mode of Inheritance:
Autosomal Recessive

Severity:
3red

Breeds Affected: Basset Hound

Description:
An inherited defect in platelets. Platelets are small, circulating cells that are the first line of defense in stopping the flow of blood from injured blood vessels and contribute to blood clotting and tissue repair. Therefore, individuals with the disease are at increased risk for spontaneous bleeding and they are also at high risk for excessive hemorrhage as a result of injury orsurgery. This is often seen as gingival bleeding, particularly during permanent tooth eruption, gastrointestinal bleeding, urinary tract bleeding, nose bleeds, hemorrhages of the skin (bruisingthat can range from small, pinpoint lesions to lesions as large as a half-dollar or larger).Gastrointestinal bleeds canalso be slow and insidious (microscopic and not visibly apparent) resulting in iron deficiencyanemia with time.

Reference:
1. Johnstone IB, Lotz F. (1979) An inherited platelet function defect in basset hounds, Can Vet J 20: 211–215. ;  online abstract
2. Patterson WR, Padgett GA, Bell TG. (1985) Abnormal release of storage pool adenine nucleotides from platelets of dogs affected with basset hound hereditary thrombopathy. Thromb Res. 37(1):61-71. ;  
online abstract

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Type A - PRA

Category:
Ophthalmic

Mode of Inheritance:
Autosomal Recessive

Severity:
3red

Breeds Affected: Miniature Schnauzer

Description:
A progressive disorder of the retina (the innermost layer of the eye) that leads to blindness in dogs. Type A PRA is the progressive degeneration of the retinal tissue. Normally the vision receptors in the eyes undergo a continual process of replacement and renewal, with PRA this process slows and eventually stops.

The thinning of the retinal tissue leads to the degeneration of the photosensitive receptors sensitive to dim light (rods), causing night blindness, and then the receptors sensitive to bright light (cones), causing day blindness. Type A PRA it is usually not seen until 2-5 years of age. Type A PRA is a difficult form of retinal atrophy as it can be partially dominant; some carrier animals appear partially affected when examined clinically. Disorientation is a common initial symptom of PRA, particularly at night due to the degeneration of the light sensitive rods specializing in dim light perception. Initial night blindness in most cases will progress slowly to day blindness also as the cones in the eye that respond to bright light are progressively damaged. Sadly, like humans, there is no treatment or cure for blindness in dogs.

Reference:
1. Parshall CJ, Wyman M, Nitroy S, Acland G, Aguirre G (1991) Photoreceptor dysplasia: An inherited progressive retinal atrophy of schnauzer (miniature) dogs. Progress in Veterinary and Comparative Ophthalmology 1:187-203.
2. Zhang Q, Baldwin VJ, Acland GM, Parshall CJ, Haskel J, Aguirre GD, Ray K (1999) Photoreceptor dysplasia (pd) in schnauzer (miniature) dogs: evaluation of candidate genes by molecular genetic analysis. Journal of Heredity 90: 57-61. ;  
online abstract
3. Lippmann T, Pasternack SM, Kraczyk B, Dudek SE, Dekomien G. (2006) Indirect exclusion of four candidate genes for generalized progressive retinal atrophy in several breeds of dogs. J Negat Results Biomed.5:19. ;  
online abstract

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von Willebrand’s Disease *

Category:
Haematologic

Mode of Inheritance:
Autosomal Dominant

Severity:
3red

Breeds Affected: Type I - Bernese Mountain Dog, Doberman, German Pinscher, Labradoodle, Manchester Terrier, Miniature Poodle, Papillion, Pembroke Welsh Corgi, Poodle ,Toy Poodle Type II - German Shorthaired Pointer, German Wirehaired Pointer, Pointer, Type III - Scottish Terrier, Shetland Sheepdog

Description:
von Willebrand's disease (vWD) is probably the most common inherited bleeding disorder in dogs. It is caused by lack of von Willebrand factor which is a protein that plays a key role in the blood clotting process resulting in prolonged bleeding. The disorder occurs in varying degrees of severity ranging from trivial bleeding to excessive life threatening haemorrhages.

Symptoms include spontaneous bleeding from the nose, gum and other mucous membranes. Excessive bleeding occurs after an injury, trauma or a surgery. Often dogs don’t show clinical signs until something starts the bleeding, such as nail trimming, teething, spaying, sterilizing, tail docking, cropping or other causes. Bleeding also occurs internally in the stomach, intestines, urinary tracts, the genitals and / or into the joints.
Type I von Willebrand's disease is considered relatively mild when compared to Type II in Scotch Terriers and Shetland Sheep Dogs and Type III in the German Wirehaired pointer, Type II and Type III are much more severe than type I.

Reference:
1. Brewer GJ, Venta PJ, Schall WD, Yuzbaziyan-Gurkan V, Li J (1998) DNA tests for von Willebrands disease in dobermans, scotties, shelties, and Manchester terriers. Canine Practice 23: 45.;  online abstract
2. Riehl J, Okura M, Mignot E, Nishino S. (2000) Inheritance of von Willebrand's disease in a colony of Doberman Pinschers. Am J Vet Res. 61(2):115-20.;  
online abstract
3. Sabino EP, Erb HN, Catalfamo JL. (2006) Development of a collagen-binding activity assay as a screening test for type II von Willebrand disease in dogs. J Am Vet Med Assoc. 228(4):567.;  
online abstract

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X Linked PRA

Category: Ophthalmic

Mode of Inheritance:
Autosomal Recessive - X linked

Severity:
2red

Breeds Affected: Samoyed, Siberian Husky

Description:
Normally, the vision receptors in the eyes undergo a continual process of replacement and renewal. But with PRA this process slows and, one day, stops. The night vision receptors are the first to fail, and then, a while later, day vision starts to degenerate. XL-PRA is a "late-onset" form of PRA. It usually isn't until dogs are three to five years old that the first clinical signs of disease start to manifest. Indeed, deterioration can happen as early as five months of age--but often goes unnoticed. Eventually, though, dog owners see that their pet's eyes have taken on a characteristic "shine." The pupils become increasingly dilated in the attempt to let in yet more light. Dogs develop "tunnel vision." It's like trying to look at the world through a narrow tube.
The disease is mostly found in males. It is carried on the X chromosome (the female Chromosome), so a male dog only needs one parent to pass on the defective gene, unlike a female, who needs to inherit the gene from both parents.

Reference:
1. Acland GM, Blanton SH, Hershfield B, Aguirre GD. (1994) XLPRA: a canine retinal degeneration inherited as an X-linked trait. American Journal of Medical Genetics 52: 27-33. ;  online abstract
2. Zeiss CJ, Ray K, Acland GM, Aguirre GD (2000) Mapping of X-linked progressive retinal atrophy (XLPRA), the canine homolog of retinitis pigmentosa 3 (RP3). Human Molecular Genetics 9: 531-7. ;  
online abstract

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