Health Disease Mutation
Dogs with cystinuria are not able to re-absorb the amino acid cystine in their kidneys and therefore high concentrations can accumulate in the urinary tract. This causes formation of cystine crystals and stones that can obstruct the urinary tract. While cystinuria has been reported in a number of breeds, it is particularly severe in Newfoundlands. The genetic mutation that causes cystinuria in the Newfoundland was identified by researchers at University of Pennsylvania. The mutation is in the SLC3A1 gene located on canine chromosome 10.
Cystinuria is a recessively inherited disorder meaning that dogs must inherit two copies of the mutated SLC3A1 gene to be at risk of developing the clinical signs. To date, the SLC3A1 mutation has been identified in the Newfoundland.
Mixed-breed dogs that have inherited two copies of this mutation can also develop cystinuria. Educating clients with dogs who are susceptible to cystinuria is important so they can recognize the clinical signs and care for their dogs appropriately.
References:
Henthorn PS, Liu J, Gidalevich T, Fang J, Casal ML, Patterson DF, Giger U. Canine cystinuria: polymorphism in the canine SLC3A1 gene and identification of a nonsense mutation in cystinuric Newfoundland dogs. Human Genetics, 2000; 107:295-303.
Factor VII (FVII) deficiency is an inherited disorder in dogs that can cause mild to moderate bleeding tendencies. FVII is a vitamin K-dependent clotting factor that, when activated, plays a significant role in the initiation of coagulation. FVII deficiency is also noted in humans and over 130 causative mutations have been identified in the human FVII gene. A genetic mutation that causes FVII deficiency was found by researchers at the University of Pennsylvania. FVII deficiency is caused by a G to A missense mutation in exon 5 of the FVII gene. This mutation results in a substitution of glycine 96 for glutamic acid (G96E) which causes a reduction in FVII secretion into the blood stream and activity resulting in decreased clotting abilities.
FVII deficiency is a recessive disorder meaning that dogs must inherit two copies of the mutated FVII gene to be at risk of developing the clinical signs. To date, the FVII deficiency mutation in FVII has been identified the Beagle and Alaskan Klee Kai.
Mixed-breed dogs that have inherited two copies of this mutation can also develop FVII deficiency. Educating clients with dogs who are susceptible to FVII deficiency is important so they can recognize the clinical signs and care for their dogs appropriately.
References:
Callan MB, Aljamali MN, Margaritis P, Griot-Wenk ME, Pollak ES, Werner P, Giger U, High KA. A novel missense mutation responsible for factor VII deficiency in research Beagle colonies. Journal of Thrombosis and Haemostasis, 2006; 4:2616-22.
Kaae JA, Callan MB, Brooks MB. Hereditary factor VII deficiency in the Alaskan Klee Kai dog. Journal of Veterinary Internal Medicine, 2007; 21:976-81.
Hyperuricosuria (HUU) is an inherited disorder in dogs that can cause hyperuricemia and the development of urate stones in the kidneys and bladder. Most dogs convert uric acid to allantoin during purine metabolism; allantoin is very soluble and is excreted in the urine. Dogs with HUU are unable to convert uric acid to allantoin and thus develop high levels of uric acid in the blood and urine. HUU was first identified in the Dalmatian as a cause of frequent urate bladder stones in the breed and all Dalmatians are predisposed to HUU. Treatment consists of a diet that is low in purines, urine alkalization, allopurinol treatment to prevent uric acid production, and surgery to remove the stones if needed. A genetic mutation that causes HUU was found by researchers at the University of California, Davis. HUU is caused by a mutation in exon 5 of the Solute carrier family 2, member 9 (SLC2A9) gene. This mutation affects uric acid transport in both the liver and kidneys.
HUU is a recessive disorder meaning that dogs must inherit two copies of the mutated SLC2A9 gene to be at risk of developing the clinical signs. To date, the HUU mutation in SLC2A9 has been identified in several breeds but is most commonly found in the Dalmatian, Bulldog, and Black Russian Terrier.
Mixed-breed dogs that have inherited two copies of this mutation can also develop HUU. Educating clients with dogs who are susceptible to HUU is important so they can recognize the clinical signs and care for their dogs appropriately.
References:
Bannasch D, Safra N, Young A, Karmi N, Schaible RS, Ling GV. Mutations in the SLC2A9 Gene Cause Hyperuricosuria and Hyperuricemia in the Dog. PLoS Genetics, 2008; 4: e1000246.
Karmi N, Brown EA, Hughes SS, McLaughlin B, Mellersh CS, Biourge V, Bannasch DL. Estimated Frequency of the Canine Hyperuricosuria Mutation in Different Dog Breeds. Journal of Veterinary and Internal Medicine, 2010; 24:1337–1342.
Myotonia congenita is an inherited condition in dogs that can cause hyperexcitable muscles that contract easily. Clinical signs can be first observed at a few weeks of age and include prominent shoulder and thigh muscles, difficulty getting up, stiff gait, and may bunny hop when running. Their tongue is enlarged and stiffens when touched and their lower jaws appear to be peak-shaped. They have difficulty swallowing and increased respiratory sounds. Treatment with procainamide daily may improve some of the clinical signs, however, affected dogs will never eat or exercise normally. A genetic mutation that causes myotonia congenita was found by researchers at the University of Pennsylvania and Vanderbilt University. Myotonia congenita is caused by a mutation in the chloride channel 1 (CLCN1) gene.
Myotonia congenita is a recessive disorder meaning that dogs must inherit two copies of the mutated CLCN1 gene to be at risk of developing the clinical signs. To date, the myotonia congenita mutation in CLCN1 has been identified exclusively in Miniature Schnauzers.
Mixed-breed dogs that have inherited two copies of this mutation can also develop myotonia congentia. Educating clients with dogs who are susceptible to myotonia congenita is important so they can recognize the clinical signs and care for their dogs appropriately.
References:
Rhodes TH, Vite CH, Giger U, Patterson DF, Fahlke C, George AL Jr. A missense mutation in canine C1C-1 causes recessive myotonia congenita in the dog. FEBS Letters, 1999; 456:54-8.
Bhalerao DP, Rajpurohit Y, Vite CH, Giger U. Detection of a genetic mutation for myotonia congenita among Miniature Schnauzers and identification of a common carrier ancestor. American Journal of Veterinary Research, 2002; 63:1443-7.
Primary lens luxation (PLL) is an inherited condition in dogs that can cause displacement of the ocular lenses. Initial luxation of the lens in one eye generally occurs between 3 and 8 years of age with displacement of the lens in the second eye occurring within weeks or months of the first. The ocular lens is held in position behind the pupil by zonular fibers. Abnormalities in these zonular fibers can be identified in dogs with PLL at less than two years of age. A genetic mutation that causes PLL was found by researchers at the University of Missouri and the Animal Health Trust. PLL is caused by a splice-donor-site mutation at the 5’ end of intron 10 in the ADAMTS17 gene which results in a RNA that skips exon 10 causing a frame-shift and truncated protein. There are likely several forms of PLL as some affected dogs cannot be explained by this mutation.
This form of PLL is likely a recessive disorder however heterozygous dogs may also have a low risk of developing PLL meaning that in general a dog must inherit two copies of the mutated ADAMTS17 gene to be at risk of developing the clinical signs, however some dogs with only one copy of the mutation may also be at risk. To date, this PLL mutation in the ADAMTS17 gene has been identified in a number of breeds including the Russell Terrier, Parson Russell Terrier, Miniature Bull Terrier, Lancashire Heeler, and Tibetan Terrier.
Mixed-breed dogs that have inherited one or two copies of this mutation may also develop PLL. Educating clients with dogs who are susceptible to PLL is important so they can recognize the clinical signs and care for their dogs appropriately.
References:
Farias FH, Johnson GS, Taylor JF, Giuliano E, Katz ML, Sanders DN, Schnabel RD, McKay SD, Khan S, Gharahkhani P, O'Leary CA, Pettitt L, Forman OP, Boursnell M, McLaughlin B, Ahonen S, Lohi H, Hernandez-Merino E, Gould DJ, Sargan DR, Mellersh C. An ADAMTS17 splice donor site mutation in dogs with primary lens luxation. Investigative Ophthalmology and Visual Science, 2010; 51:4716-21.
Gould D, Pettitt L, McLaughlin B, Holmes N, Forman O, Thomas A, Ahonen S, Lohi H, O'Leary C, Sargan D, Mellersh C. ADAMTS17 mutation associated with primary lens luxation is widespread among breeds. Veterinary Ophthalmology, 2011; 14:378-384.
Phosphofructokinase (PFK) is an enzyme that is crucial for production of energy from sugar sources in all cells of the body, especially red blood cells and muscle cells. Lack of this enzyme causes exertional myopathy and hemolysis resulting in a range of effects including weakness and muscle cramps, discolored urine, anemia, and jaundice. The genetic mutation that causes PFK deficiency was identified by researchers at the University of Pennsylvania. The mutation is in the muscle type phosphofructokinase (M-PFK) gene located on canine chromosome 27. This mutation results in a shortened M-PFK protein that is rapidly degraded and therefore unstable. Additional mutations in this gene have also been identified in humans suffering from PFK deficiency.
PFK deficiency is a recessively inherited disorder meaning that dogs must inherit two copies of the mutated M-PFK gene to be at risk of developing the clinical signs. To date, the M-PFK mutation has been identified in the English Springer Spaniel and American Cocker Spaniel.
Mixed-breed dogs that have inherited two copies of this mutation can also develop PFK deficiency. Educating clients with dogs who are susceptible to PFK deficiency is important so they can recognize the clinical signs and care for their dogs appropriately.
References:
Giger U, Reilly MP, Asakura T, Baldwin CJ, Harvey JW. Autosomal recessive inherited phosphofructokinase deficiency in English springer spaniel dogs. Animal Genetics, 1986; 17:15-23.
Smith BF, Stedman H, Rajpurohit Y, Henthorn PS, Wolfe JH, Patterson DF, Giger U. Molecular basis of canine muscle type phosphofructokinase deficiency. Journal of Biological Chemistry, 1996; 271:20070-4.
Pyruvate kinase (PK) is an enzyme needed for normal energy production by the red blood cells. Its deficiency causes anemia and weakness, liver failure, abnormal bone density, heart murmur, and shortened life expectancy. The genetic mutation that causes PK deficiency was identified by researchers at Auburn University. The mutation is in the red blood cell-type pyruvate kinase (PKR) gene located on canine chromosome 7. This mutation results in a shortened R-type PK protein that is missing the catalytic site of the wild-type enzyme. Many mutations in this gene have also been identified in humans with PK deficiency.
PK deficiency is a recessively inherited disorder meaning that dogs must inherit two copies of the mutated M-PFK gene to be at risk of developing the clinical signs. To date, the PKR mutation has been identified in the Basenji.
Mixed-breed dogs that have inherited two copies of this mutation can also develop PK deficiency. Educating clients with dogs who are susceptible to PK deficiency is important so they can recognize the clinical signs and care for their dogs appropriately.
References:
Whitney KM, Goodman SA, Bailey EM, Lothrop CD Jr. The molecular basis of canine pyruvate kinase deficiency. Experimental Hematology, 1994; 22:866-74.
Whitney KM, Lothrop CD Jr. Genetic test for pyruvate kinase deficiency of Basenjis. Journal of the American Veterinary Medical Association, 1995; 207:918-21.
