UC Davis School of Veterinary Medicine Veterinary Genetics Laboratory

Labrador Retriever Genetic Health Panel

Tests Offered:
CNM | CMS | Cystinuria Type 1-A | DM | EIC | HNPK | HUU | Narcolepsy | PKDef | PRCD | SD2 | XLMTM | Dilute (Panel 2 only)

Centronuclear Myopathy (CNM)

Centronuclear myopathy (CNM) is a naturally occurring, hereditary myopathy of Labrador Retrievers resulting from a mutation in the protein tyrosine phosphatase-like member A gene (PTPLA).  This condition is also known as: type II muscle fiber deficiency, autosomal recessive muscular dystrophy and hereditary myopathy. The disease is inherited in an autosomal recessive fashion with both sexes being equally affected.  CNM typically manifests in puppies at 2-5 months.  Signs of CNM include: generalized loss of muscle tone and control, exercise intolerance and an awkward gait. Dogs with one normal copy and one mutant copy of the gene do not display signs.  Breeding two carriers is predicted to produce 25% affected offspring and 50% carriers of the disease.

The VGL offers a DNA test for CNM to assist owners and breeders in identifying affected and carrier dogs. The test uses DNA collected from buccal (cheek) swabs, thus avoiding blood sample collection. Breeders can use results from the test as a tool for selection of mating pairs to avoid producing affected dogs.

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Allow 3-6 business days for results.

Results reported as:

N/N

No copies of the CNM mutation detected. Dog is normal.

N/CNM

1 copy of the CNM mutation. Dog is a carrier and unaffected. If bred to another carrier, 25% of offpsring are predicted to be affected.

CNM/CNM

2 copies of the CNM mutation. Dog is affected.

This test is specific for the CNM mutation described in Labrador Retrievers.

References:

Pelé M, L. Tiret, JL Kessler, S Blot, JJ Panthier. 2005. SINE exonic insertion in the PTPLA gene leads to multiple splicing defects and segregates with the autosomal recessive centronuclear myopathy in dogs. Human Molecular Genetics 14(11):1417-1427. [PubMed: 15829503].

Maurer M, J Mary, L Guillaud et al. 2012. Centronuclear myopathy in Labrador Retrievers: A recent founder mutation in the PTPLA gene has rapidly disseminated worldwide. Plos One 7(10): e46408. [PubMed: 23071563].

 

Congenital Myasthenic Syndrome (CMS)

Congenital myasthenic syndrome (CMS) is an inherited neuromuscular disorder characterized by severe generalized skeletal muscle weakness and fatigue, usually induced by exercise. Puppies with this syndrome generally collapse after a few minutes of rigorous exercise, but typically recover after some rest. Signs usually appear between 6 to 12 weeks of age.

CMS is caused by a single nucleotide mutation (c.1010T>C) in exon 14 of the Collagen-like Tail Subunit of Asymmetric Acetylcholinesterase (COLQ) gene. This variant is predicted to cause improper anchoring of ColQ protein to the basal lamina of muscle cells and impair the termination of signal transmission within the neuromuscular junction, where motor neurons and muscle fibers connect. Malfunction of signal transmission affects muscle contraction. The mode of inheritance is autosomal recessive, which means that males and females are equally affected and that two copies of the mutation are needed to cause CMS.

According to the referenced paper below, only 2 Labrador Retrievers were reported to be affected and homozygous for this mutation but 16 out of 58 (28%) of their relatives were carriers. No carriers were found among 288 unrelated Labrador Retrievers, which suggests that the mutation is not widespread within the breed. Coincidentally, 2 human CMS patients were reported to be homozygous for an identical mutation (c.1010T>C), thus supporting the causality of the dog mutation. Screening of a random set of Labradors Retrievers at the VGL resulted in a frequency of 1.1% for the CMS disease allele.

The VGL offers a DNA test for CMS. Test results assist veterinarians with differential diagnosis of CMS and help breeders identify carriers among breeding stock and select appropriate mates to reduce the risk of producing CMS-affected offspring.


Testing is recommended for: Labrador Retrievers. This test does not detect the mutation that causes CMS in Jack Russell Terriers or Old Danish Pointing Dogs.

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Allow 5-10 business days for results.

Results reported as:

N/N

No copies of the CMS mutation detected. Dog is normal.

N/CMS

1 copy of the CMS mutation detected. Dog is a carrier and unaffected. If bred to another carrier, 25% of offspring are predicted to be affected.

CMS/CMS

2 copies of the CMS mutation detected. Dog is affected and will develop congenital myasthenic syndrome.

Reference:

Rinz CJ, Levine J, Minor KM, Humphries HD, Lara R, Starr-Moss AN, Guo LT, Williams DC, Shelton GD, Clark LA. 2014. A COLQ missense mutation in Labrador Retrievers having congenital myasthenic syndrome. PLoS One 9(8):e106425. [PubMed: 25166616].

 

Cystinuria Type I-A in Labrador Retrievers

Cystinuria Type I-A is an inherited metabolic disorder that affects kidney function. Affected dogs fail to reabsorb cystine in their kidneys, which leads to the formation of cystine crystals and uroliths in the urinary tract. Signs of this disease include urinary obstruction, stranguria (difficulty in passing urine) and hematuria (presence of blood in the urine). Obstruction of urine flow is more common and occurs earlier in males because of their urinary tract anatomy. Affected male dogs typically show signs between 6 and 14 months of age while female dogs tend to present these later. Dogs with cystinuria often have frequent episodes of urinary tract inflammation that can lead to kidney failure and death, if not treated.

Cystinuria Type I-A in Labrador Retrievers is caused by a single nucleotide deletion (c.350delG) in exon 1 of the solute carrier family 3, member 1 (SLC3A1) gene. The mode of inheritance for this disease is autosomal recessive, which means that males and females are equally affected and that two copies of the deletion are needed to cause cystinuria type I-A. Screening of a random set of Labradors Retrievers at the VGL determined that the cystinuria type I-A disease allele is rare in this breed, with a frequency less than 1%.

The VGL offers a DNA test for cystinuria type I-A. Test results assist veterinarians with diagnosis of this disease. Test results help breeders identify carriers and affected dogs among breeding stock and plan safe mating combinations to avoid producing affected offspring.

Testing recommended for: Labrador Retrievers. This test does not detect cystinuria in other breeds.

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Allow 5-10 business days for results.

Results reported as:

N/N

No copies of the cystinuria type I-A mutation detected. Dog is normal.

N/C

1 copy of the cystinuria type I-A mutation detected. Dog is a carrier. If bred to another carrier, 25% of offspring are predicted to be affected.

C/C

2 copies of the cystinuria type I-A mutation detected. Dog is affected and will develop cystinuria.

Reference:

Brons AK, Henthorn P, Raj K, Fitzgerald CA, Liu J, Sewell AC, Giger U. 2014. SLC3A1 and SLC7A9 mutations in autosomal recessive or dominant canine cystinuria: a new classification system. J Vet Inter Med 27(6): 1400-1408. [PMID: 24001348].

 

Degenerative Myelopathy (DM)

Degenerative myelopathy (DM) is an inherited neurologic disorder of dogs similar to Lou Gehrig’s disease in humans and results from a mutation (c.118G>A) in the SOD1 gene. Affected dogs usually present clinical signs of disease in adulthood (at least 8 years of age) with gradual muscle wasting and loss of coordination that typically begins in the hind limbs because of nerve degeneration. Disease progression continues until the dog is unable to walk. Small breed dogs tend to progress more slowly. In late stages of the disease, dogs may become incontinent and the forelimbs may be affected. Affected dogs may fully lose the ability to walk 6 months to 2 years after the onset of signs. The disease is inherited in an autosomal recessive fashion with incomplete penetrance. Thus, two copies of the SOD1 mutation (DM/DM) confer increased risk for DM but not all DM/DM dogs across breeds will develop the disease. The variable presentation between breeds suggests that other genetic and environmental factors play a role in disease expression. There is ongoing research to identify other genetic factors that modify risk for DM in different breeds. In addition, similar disease presentation is observed in some animals lacking the SOD1 mutation. Breeding two carriers of the SOD1 mutation together is predicted to produce 25% of pups that may develop DM.


The VGL offers a genetic test for the SOD1 c.118G>A mutation, reported here as DM. Genetic screening helps breeders establish the genetic status of breeding stock and select mating pairs appropriately to reduce the risk of producing DM-affected offspring.

Testing is appropriate for: many breeds

The Degenerative Myelopathy (DM) test is a patented test. The Veterinary Genetics Laboratory is authorized to offer the DM test to residents of the United States, Canada and Australia.

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Allow 5-10 business days for results.

Results reported as:

N/N

No copies of the DM mutation.

N/DM

1 copy of the DM mutation.

DM/DM

2 copies of the DM mutation; dog may develop DM disease.

References:

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. 106(8):2794-2799. [PubMed: 19188595].

Coates JR, March PA, Oglesbee M, Ruaux CG, Olby NJ, Berghaus RD, O'Brien DP, Keating JH, Johnson GS, Williams DA. 2007. Clinical characterization of a familial degenerative myelopathy in Pembroke Welsh Corgi dogs. J Vet Intern Med. 21(6):1323-1331. [PubMed: 18196743].

Shelton GD, Johnson GC, O’Brien DP, Katz ML, Pesayco JP, Chang BJ, Mizisin AP, Coates JR. 2012. Degenerative myelopathy associated with a missense mutation in the superoxide dismutase 1 (SOD1) gene progresses to peripheral neuropathy in Pembroke Welsh Corgis and Boxers. J Neurol Sci 318(1-2):55-64. [PubMed: 22542607].

Zeng R, Coates JR, Johnson GC, Hansen L, Awano T, Kolicheski A, Ivansson E, Perloski M, Lindblad-Toh K, O'Brien DP, Guo J, Katz ML, Johnson GS. 2014. Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy. J Vet Intern Med 28(2):515-521. [PubMed: 24524809].

 

Exercise-Induced Collapse (EIC)

Exercise-Induced Collapse (EIC) is a genetic neuromuscular disorder characterized by muscle weakness, lack of coordination and life-threatening collapse after intense exercise in otherwise apparent healthy dogs. Affected dogs tolerate mild to moderate activity but will display signs of EIC after 5-20 minutes of strenuous exercise. The severity of EIC varies, some affected dogs continue to run while dragging their hind legs while others have progression of weakness from rear to forelimbs resulting in a total inability to move. EIC events are often accompanied by a dramatic elevation of body temperature, although unaffected dogs also exhibit elevated temperatures under the same exercise conditions. EIC episodes last from 5-25 minutes with a gradual return to normal with no apparent residual weakness or stiffness. Affected dogs show signs of the disorder as early as 5 months of age, which is typically when more strenuous training and activity begins. Dogs with EIC can lead full, productive lives with proper management.  Owners of affected dogs should familiarize themselves with the types of activities that are appropriate for their dogs as well as specific triggers of EIC episodes.

EIC is caused by a mutation in dynamin 1 gene (DNM1 c.767G>T). It is inherited as an autosomal recessive disorder, which means that both males and females are affected equally, and that two copies of the mutation are needed to cause the disease. Dogs with one copy of the normal gene and one copy of the mutation (carriers) do not exhibit any signs of EIC.

The Veterinary Genetics Laboratory offers a genetic test for EIC. Test results assist veterinarians with diagnosis of EIC and help breeders identify carriers among breeding stock to avoid producing affected dogs. Matings between carriers are expected to produce 25% of affected puppies.

Testing recommendation:  Australian Cobberdog, Australian Labradoodle, Bouvier des Flandres, Boykin Spaniel, Cardigan Welsh Corgi, Chesapeake Bay Retriever, Cockapoo, Cocker Spaniel, Clumber Spaniels, Curly Coated Retriever, Deutsch-Drahthaar, English Cocker Spaniel, German Wirehaired Pointer, Labrador crosses, Labradoodle, Labrador Retriever, Old English Sheepdog, Pembroke Welsh Corgi, Vizsla

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Allow 5-10 business days for results.

Results reported as:

N/N

No copies of the EIC mutation detected. Dog is normal.

N/EIC

1 copy of the EIC mutation detected. Dog is a carrier and unaffected. If bred to another carrier, 25% of offpring are predicted to be affected.

EIC/EIC

2 copies of the EIC mutation detected. Dog is affected and may exhibit exercise-induced collapse under intense activity.

References:

Patterson EE, Minor KM, Tchernatynskaia AV, Taylor SM, Shelton GD, Ekenstedt KJ, Mickelson JR. 2008. A canine DNM1 mutation is highly associated with the syndrome of exercise-induced collapse. Nat Genet. 40(10):1235-1239. [PubMed: 18806795].

Minor KM, Patterson EE, Keating MK, Gross SD, Ekenstedt KJ, Taylor SM, Mickelson JR. 2011. Presence and impact of the exercise-induced collapse associated DNM1 mutation in Labrador retrievers and other breeds. Vet J. 189(2):214-219. [PubMed: 21782486].

 

Hereditary Nasal Parakeratosis (HNPK)

Hereditary Nasal Parakeratosis (HNPK) is a genetic defect caused by a mutation in a gene that regulates differentiation of nose skin cells. The mutation affects specialized cells of the nose resulting in the formation of a crust with cracks over the nasal area of young dogs. Affected dogs are otherwise healthy although leaked fluid tends to accumulate in the cracks.

HNPK is inherited in an autosomal recessive fashion with males and females being equally affected. Dogs with one normal and one affected gene (carriers) show no signs of the disease. Carrier dogs will pass on the affected gene to 50% of their offspring.

The VGL offers a test for HNPK. Genetic testing for the HNPK mutation is recommended for Labrador Retrievers. Labradoodles and other crosses with Labrador Retriever content may also be at risk. The test assists veterinarians with diagnosis of HNPK and helps breeders to identify carriers to avoid breeding these together. Mating of carriers is expected to produce 25% of affected puppies.

ORDER TEST KITS | PRICE LIST
Allow 3-6 business days for results.

Results reported as:

N/N

No copies of the HNPK mutation detected. Dog is normal.

N/H

1 copy of the HNPK mutation detected. Dog is a carrier and unaffected. If bred to another carrier, 25% of offspring are predicted to be affected.

H/H

2 copies of the HNPK mutation detected. Dog has or will develop nasal parakeratosis.

Reference:

Jagannathan V, J. Bannoehr, P. Plattet, R. Hauswirth, C. Drogemuller, M. Drogemuller, D. J. Wiener, M. Doherr, M. Owczarek-Lipska, A. Galichet, M. M. Welle, K. Tengvall, K. Bergvall, H. Lohi, S. Rufenacht, M. Linek, M. Paradis, E. J. Muller, P. Roosje, T. Leeb. 2013. A mutation in the SUV39H2 gene in Labrador Retrievers with Hereditary Nasal Parakeratosis (HNPK) provides insights into the epigenetics of keratinocyte differentiation. PLOS Genetics. Oct 9(10)e1003848. https://doi.org/10.1371/journal.pgen.1003848. [PubMed: 24098150].

 

Canine Hyperuricosuria (HUU)

Hyperuricosuria (HUU) 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.

ORDER TEST KITS | PRICE LIST
Allow 3-6 business days for results.

Detailed Hyperuricosuria Information

The VGL offers a DNA test for hyperuricosuria to assist owners and breeders in identifying affected and carrier dogs. The test uses DNA collected from buccal swabs thus avoiding invasive blood collection. Breeders can use results from the test as a tool for selection of mating pairs to avoid producing affected dogs. The test is offered to all breeds, including American Pitbull Terrier, American Staffordshire Terrier, Australian Shepherd, Black Russian Terrier, Bulldog, Dalmatian, German Shepherd, Giant Schnauzer, Jack Russel/Parsons Terrier, Labrador Retriever and crosses, Large Munsterlander, South African Boerboel, Vizsla and Weimaraner.

The following chart details the expected outcomes of matings for all possible combinations of hyperuricosuria genotypes.

Female

Male

N/N

N/HU

HU/HU

N/N

100% N/N

50% N/N, 50% N/HU

100% N/HU

N/HU

50% N/N, 50% N/HU

25% N/N, 50% N/HU, 25% HU/HU

50% N/HU, 50% HU/HU

HU/HU

100% N/HU

50% N/HU, 50% HU/HU

100% HU/HU

Results reported as:

N/N

No copies of the hyperuricosuria mutation detected. Dog is normal.

N/HU

1 copy of the hyperuricosuria mutation detected. Dog is a carrier and unaffected. If bred to another carrier, 25% of offspring are predicted to be affected.

HU/HU

2 copies of the hyperuricosuria mutation detected. Dog is affected with HUU and susceptible to develop bladder/kidney stones.

We recommend testing of any dog that has formed kidney or bladder stones composed of urate or uric acid. If the dog has the mutation then treatment modalities for Dalmatians can be used to treat the dog.

References:

Bannasch D, N Safra, A Young, N Karmi, RS Schaible and GV Ling. 2008. Mutations in the SLC2A9 Gene Cause Hyperuricosuria and Hyperuricemia in the Dog. PLoS Genetics 4(11): e1000246. doi:10.1371/journal.pgen.1000246. [PubMed: 18989453].

Karmi N, EA Brown, SS Hughes, B McLaughlin, CS Mellersh, V Biourge, and DL Bannasch. 2010. Estimated Frequency of the Canine Hyperuricosuria Mutation in Different Dog Breeds. J Vet Intern Med 24:1337–1342. [PubMed: 21054540].

 

Narcolepsy in Labrador Retrievers

Narcolepsy is a disabling neurological disorder that has been identified in several dog breeds, including the Labrador Retriever. This disease affects the brain’s ability to control sleep-wake cycles. It is characterized by daytime sleepiness, erratic sleep patterns, fast transition to rapid eye movement (REM) sleep, and sleep paralysis, but the most striking symptom is cataplexy – sudden loss of muscle tone and collapse without loss of consciousness – which can be triggered by strong positive emotional stimulus such as play or food. Usually, signs appear between 4 weeks and 6 months of age and severity increases until animals are approximately 1 year old, when progression stops. 

Narcolepsy in Labrador Retrievers is caused by a single nucleotide change (or SNP) in the Hypocretin Receptor 2 (HCRTR2) gene that causes exon-skipping and produces an abnormal protein. The G to A substitution in the 5’ splice site causes the deletion of exon 6 which, in turn, produces a truncated HCRTR2 protein (330 amino acids instead of the normal 444) that cannot properly regulate sleep-wake cycles in affected dogs. The mode of inheritance for this disease is autosomal recessive, which means that males and females are equally affected and that two copies of the mutation are needed to cause narcolepsy. Screening of a random set of Labrador Retrievers at the VGL determined that the HCRTR2 disease allele is rare in this breed, with frequency less than 1%.

The VGL offers a DNA test for narcolepsy in Labrador Retrievers. Test results assist veterinarians with diagnosis of narcolepsy and help breeders identify carriers among breeding stock and select appropriate mates to reduce the risk of producing affected offspring. In order to avoid the possibility of producing affected puppies, matings between known carriers are not recommended. 

Testing recommended for: Labrador Retrievers and Labradoodles. This test does not detect the mutation that causes narcolepsy in Dobermans or Dachshunds.

ORDER TEST KITS | PRICE LIST
Allow 5-10 business days for results.

Results reported as:

N/N

No copies of the narcolepsy mutation detected. Dog is normal.

N/NAL

1 copy of the narcolepsy mutation detected. Dog is a carrier. If bred to another carrier, 25% of offspring are predicted to be affected.

NAL/NAL

2 copies of the narcolepsy mutation detected. Dog is affected and will develop narcolepsy.

References:

Hungs M., Fan J., Lin L., Lin X., Grigoriadis D., Maki R.A., Mignot E. 2001. Identification and Functional Analysis of Mutations in the Hypocretin (Orexin) genes of narcoleptic canines. Genome Res. 11:531-539. [PubMed: 11282968].


Lin L., Faraco J., Li R., Kadotani H., Rogers W., Lin X., Qiu X., de Jong P.J., Nishino S., Mignot E. 1999. The sleep disorder canine narcolepsy is caused by a mutation in the Hypocretin (Orexin) Receptor 2 gene. Cell 3:365-376. [PubMed: 10458611].

 

Pyruvate Kinase Deficiency (PKDef)

Pyruvate kinase deficiency (PKDef) is a chronic, severe hemolytic anemia caused by defective production of the enzyme pyruvate kinase. Low levels of this enzyme result in premature death of red blood cells and insufficient supply of oxygen to the body’s cells. Observable signs in affected dogs may include lethargy, low exercise tolerance and fatigue. Clinically, affected dogs present with severe anemia, increased bone density, enlarged spleen and liver as well as fibrous connective tissue replacement of bone marrow cells. Signs usually appear between 4 months and 2 years of age, and prognosis is generally poor for affected individuals, with complete liver failure typically occurring by 5 years of age.

PKDef in Labrador Retrievers is caused by a single nucleotide mutation (c.799C>T) in exon 7 of the Pyruvate Kinase L/R (PKLR) gene. The mode of inheritance for this disease is autosomal recessive, which means that males and females are equally affected and that two copies of the mutation are needed to cause PKDef. Screening of a random set of Labradors Retrievers at the VGL determined that the PKLR disease allele is rare in this breed, with frequency less than 1%.

The VGL offers a DNA test for PKDef. Test results assist veterinarians with diagnosis of PKDef and help breeders identify carriers among the breeding population. Carrier dogs, those with one defective and one normal copy, show no signs of disease but have half the normal level of pyruvate kinase activity. Breeding between two carriers is not recommended because 25% of the offspring are expected to be affected and 50% are expected to be carriers of the disease.

Testing recommended for: Labrador Retrievers and Labradoodles.

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Allow 5-10 business days for results.

Results reported as:

N/N

No copies of the PKDef mutation. Dog is normal.

N/K

1 copy of the PKDef mutation. Dog is a carrier and unaffected but has half the normal pyruvate kinase activity of N/N dogs. If bred to another carrier, 25% of offspring are predicted to be affected.

K/K

2 copies of the PKDef mutation. Dog is affected.

References:

Gultekin GI, Raj K, Foureman P, Lehman S, Manhart K, Giger U. 2012. Erythrocytic pyruvate kinase mutations causing hemolytic anemia, osteosclerosis, and secondary hemochromatosis in dogs. J Vet Intern Med 26(4):935-44. [PubMed: 22805166].

 

Progressive Rod-Cone Degeneration (PRA-prcd)

Progressive rod-cone degeneration (PRCD) is an inherited form of late-onset progressive retinal atrophy (PRA) that has been identified in many dog breeds. PRCD affects the photoreceptor cells in the eye involved in both night and day vision. The cells of the retina involved in low light vision, known as rods, are affected first resulting in night blindness. Subsequently, the bright light photoreceptors known as cones, which are also important for color vision, are also affected resulting in daytime visual deficit. The age of onset and rate of progression vary among breeds but retinal changes can be identified by screening performed by a veterinary ophthalmologist from adolescence to early adulthood. Most PRCD-affected dogs have noticeable visual impairment by 4 years of age typically progressing to complete blindness.

PRCD is caused by a single nucleotide change (G>A) at position 5 in the Progressive rod-cone degeneration (PRCD) gene that changes the second amino acid from cysteine to tyrosine (C2Y). This amino acid change occurs in a highly conserved region of the protein. The mode of inheritance for this disease is autosomal recessive, which means that males and females are equally affected and that two copies of the mutation are needed to cause PRCD. Exceptionally, a few dogs between 10-13 years of age have been identified that were clinically normal but had two copies of the PRCD mutation. The breeds involved in these cases were American Eskimo, American Cocker Spaniel, English Cocker Spaniel and Toy Poodle. It has been postulated that genetic modifier(s) that have not yet been identified may play a role in the progression of the disease.

Testing for PRCD assists veterinarians with diagnosis of PRA and helps breeders identify carriers among breeding stock to select appropriate mates that will reduce the risk of producing affected offspring. To avoid the possibility of producing affected puppies, matings between known carriers are not recommended. 

Progressive retinal atrophy (PRA) is a medical classification that represents several inherited forms of retinal degeneration that are caused by mutations in different genes. PRCD is one form of PRA. Thus, a normal test result for PRCD (N/N or N/PRCD) does not exclude the possibility that a dog may carry or be affected by another PRA mutation.

Testing recommended for: Many breeds including, but not limited to: American Eskimo Dog, American Hairless Terrier, Australian Cattle Dog, Australian Cobberdog, Australian Shepherd, Black Russian Terrier, Barbet, Chesapeake Bay Retriever, Chinese Crested, Chihuahua, Cockapoo, American Cocker Spaniel, Coton de Tulear, English Cocker Spaniel, English Shepherd, Entlebucher Mountain Dog, Field Spaniel, Finnish Lapphund, German Spitz, Giant Schnauzer, Golden Retriever, Golden Doodle, Jack Russell Terrier, Japanese Chin, Lab/Golden Cross, Labradoodle, Australian Labradoodle, Labradoodle/Goldendoodle Cross, Labrador Retriever, Miniature American Shepherd, Norwegian Elkhound, Nova Scotia Duck Tolling Retriever, Pomeranian, Poodle (Standard, Medium, Miniature and Toy), Portuguese Water Dog, Puli, Silky Terrier, Schipperke, Spanish Water Dog, Standard Poodle, Swedish Jamthund, Swedish Lapphund, Tibetan Terrier, Xoloitzcuintle, Yorkshire Terrier.

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Allow 5-10 business days for results.

Results reported as:

N/N

No copies of the PRCD mutation detected. Dog is clear of this mutation.

N/PRCD

1 copy of the PRCD mutation detected. Dog is a carrier. If bred to another carrier, 25% of offspring are predicted to be affected.

PRCD/PRCD

2 copies of the PRCD mutation detected. Dog is likely to be affected and develop progressive retinal atrophy.

References:

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 88 (5):551-63. [PubMed: 16938425].


Dostal J, A Hrdlicova, Horak P. 2011. Progressive rod-cone degeneration (PRCD) in selected dog breeds and variability in its phenotypic expression. Veterinarni Medicina 56 (5):243–247.

 

Skeletal Dysplasia 2 in Labrador Retrievers (SD2)

Skeletal dysplasia 2 (SD2) is an inherited musculoskeletal disorder that causes a form of mild disproportionate dwarfism in affected dogs – their body length and width are normal, but their legs are shorter than normal. Radiological findings typically include shortened and sometimes slightly curved long bones with relatively wide epiphyses (rounded ends of long bones). The front legs are affected more frequently than hind legs. The disorder shows a subtle phenotype in which the height of affected dogs may overlap with that of small normal dogs; no ocular, auditory or secondary joint symptoms are associated with SD2. This disorder has been reported to occur more frequently in the “working” line of Labrador Retrievers, and less frequently in the “show” line.

SD2 in Labrador Retrievers is caused by a single nucleotide mutation (c.143G>C) on the collagen alpha-2(XI) chain (COL11A2) gene. The mode of inheritance for this disease is autosomal recessive, which means that males and females are equally affected and that two copies of the mutation are needed to cause the defect. Moreover, this mutation shows incomplete penetrance, and therefore not all affected dogs will show obvious physical characteristics of SD2. Screening of a random set of Labradors Retrievers at the VGL determined that the SD2 disease allele is rare in this breed, with frequency less than 1%.

The VGL offers a DNA test for SD2. Test results assist veterinarians with diagnosis of SD2 and help breeders identify carriers among the breeding stock. Of special note is that, because of the incomplete penetrance, not all affected dogs will show obvious signs of SD2, thus making genetic testing for this disorder important to detect dogs carrying the mutation.

Testing recommended for: Labrador Retrievers and Labradoodles.

ORDER TEST KITS | PRICE LIST
Allow 5-10 business days for results.

Results reported as:

N/N

No copies of the SD2 mutation detected. Dog is normal.

N/SD2

1 copy of the SD2 mutation detected. Dog is a carrier. If bred to another carrier, 25% of offspring are predicted to be affected.

SD2/SD2

2 copies of the SD2 mutation detected. Dog is affected and may show physical characteristics of SD2.

References:

Frischknecht M, Niehof-Oellers H, Jagannathan V, Owczarek-Lipska M, Drögemüller C, Dietschi E, Dolf G, Tellhelm B, Lang J, Tiira K, Lohi H, Leeb T. 2013. A COL11A2 mutation in Labrador Retrievers with mild disproportionate dwarfism PLoS One 8(3):e60149. [PubMed:23527306].

 

X-Linked Myotubular Myopathy in Labrador Retrievers

X-linked myotubular myopathy (XLMTM) is a subtype of centronuclear myopathies, rare genetic muscle disorders named after the central location of the muscle fiber nuclei. This disorder is characterized by early onset (as early as 7 weeks of age) of signs that include generalized muscle weakness, progressive muscle atrophy, a hoarse bark, episodic collapse, droopy jaw, and difficulty eating. Without the option of intensive supportive care, and because this disease is progressive, affected puppies invariably require euthanasia between 3 and 6 months of age.  

XLMTM in Labrador Retrievers is caused by a single nucleotide change (c.465C>A) in exon 7 of the Myotubular Myopathy 1 (MTM1) gene located on the X chromosome. This mutation causes altered localization and reduced quantities of the myotubularin protein in affected dogs, leading to an excessive variability in muscle fiber size and the presence of central nuclei (as opposed to peripheral nuclei in normal dogs). According to published information (see reference below), the mutation is thought to have appeared recently and to have a restricted geographic localization in some pedigrees in Canada. Screening of a random set of Labradors Retrievers at the VGL determined that the MTM1 disease allele is rare in this breed, with frequency less than 1%.

The mode of inheritance for this disease is X-linked recessive. Females have two X chromosomes, therefore for a female to be affected she must have two copies of the defective MTM1 gene to develop XLMTM. Clinical signs are predominantly absent in females with one normal and one affected copy of the gene (carriers). Males, on the other hand, only have one X chromosome and therefore if they inherit the defective copy of the MTM1 gene they will develop XLMTM. If the inherited copy is normal, males will not have the disease.

The VGL offers a DNA test for XLMTM. Test results assist veterinarians with diagnosis of MTM1 and help breeders identify carrier females to avoid matings that can produce affected dogs. When a carrier female is bred to a normal male, all female puppies will be normal but 50% of them will be carriers. Among male puppies from this type of cross, 50% will be normal and 50% will be affected.

Testing recommended for: Labrador Retrievers. This test does not detect the mutation that causes X-Linked Myotubular Myopathy in Rottweilers.  

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Allow 5-10 business days for results.

Results reported as:

N/N

No copies of the MTM1 mutation detected. Female is normal.

N/ MTML

1 copy of the MTM1 mutation detected. Female is a carrier and unaffected. If bred to an N male, 50% of female offspring are expected to be carriers and 50% of male offspring are expected to be affected.

MTML / MTML

2 copies of the MTM1 mutation detected. Female is affected. She has or will develop XLMTM.

N

No copy of the MTM1 mutation detected. Male is unaffected.

MTML

Affected male. Dog has or will develop XLMTM.

References:

Beggs AH, Böhm J, Snead E, Kozlowski M, Maurer M, Minor K, Childers MK, Taylor SM, Hitte C, Mickelson JR, Guo LT, Mizisin AP, Buj-Bello A, Tiret L, Laporte J, Shelton GD. 2010. MTM1 mutation associated with X-linked myotubular myopathy in Labrador Retrievers. Proc Natl Acad Sci USA 107(33):14697-14702. [PubMed: 20682747].

 

 

 
Veterinary Genetics Laboratory, Tel 530-752-2211, Email VGL