Register kit
HIGH QUALITY DNA
TESTING YOU CAN TRUST
OUR PANELS
The tests in our DNA health testing panels are selected based on the scientific evidence available for disorders in the breed. Our scientists stay up to date with the latest developments and discoveries in the field to ensure that our testing panels are as up-to-date as possible.
DID YOU KNOW?
Our ISO-accredited testing services are relied upon by UK police forces for assessing the suitability of canine recruits for police duties.
TESTIMONIALS
approx. 2 weeks
Typical turnaround
9
Conditions screened
Simple cheek swab
At-home sampling
UK laboratory
Tested in-house
Acral Mutilation SyndromeAMS
Acral Mutilation Syndrome (AMS) can result in an insensitivity to pain and self-mutilation of the limb extremities. This can present as extreme licking of the paws and biting of the digits and claws developing from a young age (3-12 months). It is possible for a genetically at-risk dog to exhibit none of the symptoms of this syndrome.
Acral Mutilation Syndrome is an autosomal recessive condition caused by a mutation in a lincRNA upstream of the GDNF gene.
How it's inherited
Recessive
What your result means
Clear (N/N): your dog has no copies of the AMS variant and will not develop the condition, nor pass it on.
Carrier (N/AMS): your dog has one copy. It will not develop AMS, but if bred to another carrier, on average 25% of puppies would be affected. Breeding a carrier to a clear dog produces no affected puppies.
Affected (AMS/AMS): your dog has two copies and is expected to develop the condition. Discuss management with your vet.
Centronuclear MyopathyCNM
Centronuclear Myopathy (CNM) is a reduction in muscle fibres causing muscle weakness, abnormal posture and gait, and exercise intolerance and collapse. Symptoms are variable but dogs are generally weak by five months of age and progression of the disorder ends around one year.
Centronuclear Myopathy is an autosomal recessive condition caused by a mutation in the HACD1 gene.
How it's inherited
Recessive
What your result means
Clear (N/N): no copies; not expected to develop CNM, nor pass it on.
Carrier (N/CNM): one copy. Healthy, but can pass it on. Breeding two carriers risks affected puppies.
Affected (CNM/CNM): two copies; expected to develop CNM. Discuss with your vet.
Degenerative MyelopathyDM
Degenerative Myelopathy (DM) is a progressive disease of the spinal cord that usually appears in older dogs. It gradually weakens the hind limbs, leading to loss of coordination and eventually difficulty walking. It is not painful, but it is progressive. Knowing a dog's status supports breeding decisions and early awareness.
An autosomal recessive condition with variable expression between breeds caused by a mutation in the SOD1 gene.
Signs to look for
Usually from around 8 years old: wobbliness or dragging of the hind paws, loss of coordination in the back legs, worn nails, and gradually progressing hind-limb weakness.
How it's inherited
Recessive with incomplete penetrance — a dog needs two copies to be at risk, but not every at-risk dog develops signs.
What your result means
Clear (N/N): no copies of the variant; not expected to develop this inherited form.
Carrier (N/DM): one copy. Very unlikely to develop DM, but can pass the variant on.
At risk (DM/DM): two copies. At risk of developing DM, though not all at-risk dogs do.
Exercise-Induced CollapseEIC
Exercise Induced Collapse (EIC) is a neuromuscular disorder. After strenuous activity affected dogs will display hindlimb weakness and incoordination with usually a return to normal after around 30 minutes.
An autosomal recessive condition caused by a mutation in the DNM1 gene.
How it's inherited
Recessive
What your result means
Clear (N/N): no copies; not expected to develop EIC, nor pass it on.
Carrier (N/EIC): one copy. Healthy, but can pass it on. Breeding two carriers risks affected puppies.
Affected (EIC/EIC): two copies; expected to develop EIC. Discuss with your vet.
Familial Nephropathy - Cocker TypeFN
Familial Nephropathy – Cocker Type, also known as Alport syndrome, is an inherited kidney disorder affecting English Cocker Spaniels, caused by a variant in the COL4A4 gene. The condition affects the structure of the kidneys and can lead to progressive loss of kidney function, and may also cause abnormalities affecting the eyes and ears. It is inherited as an autosomal recessive condition caused by a mutation on the COL4A4 gene.
A different COL4A4 variant causes Familial Nephropathy in English Springer Spaniels, so this test is specific to the Cocker Type.
How it's inherited
Recessive
What your result means
Clear (N/N): no copies; not expected to develop FN, nor pass it on.
Carrier (N/FN): one copy. Healthy, but can pass it on. Breeding two carriers risks affected puppies.
Affected (FN/FN): two copies; expected to develop FN. Discuss with your vet.
Hereditary Nasal ParakeratosisHNPK
Hereditary Nasal Parakeratosis (HNPK) causes a dry, rough, and crusty nose which can sometimes crack painfully. Affected dogs are otherwise healthy but the must be continually treated to prevent excessive dryness.
An autosomal recessive condition caused by a mutation in the SUV39H2 gene.
Note: Whippets present a different variant so this test is not applicable to Whippets as it is the Retriever type.
How it's inherited
Recessive
What your result means
Clear (N/N): no copies; not expected to develop HPNK, nor pass it on.
Carrier (N/HPNK): one copy. Healthy, but can pass it on. Breeding two carriers risks affected puppies.
Affected (HPNK/HPNK): two copies; expected to develop HPNK. Discuss with your vet.
HyperuricosuriaHUU
Hyperuricosuria (HUU) is caused by a variant in the SLC2A9 gene, which affects how the body processes and removes uric acid. Affected dogs are at increased risk of developing urinary stones, which can cause signs such as blood in the urine, frequent or difficult urination, and in severe cases, urinary blockage. HUU is inherited as an autosomal recessive condition, meaning a dog must inherit two copies of the variant to be genetically affected.
How it's inherited
Recessive
What your result means
Clear (N/N): no copies; not expected to develop HUU, nor pass it on.
Carrier (N/HUU): one copy. Healthy, but can pass it on. Breeding two carriers risks affected puppies.
Affected (HUU/HUU): two copies; expected to develop HUU. Discuss with your vet.
Progressive Retinal Atrophy (cord1/rcd4)PRA-cord1/rcd4
Progressive Retinal Atrophy (PRA) is a group of eye disorders which cause progressive degeneration of the retina through thinning and decreased blood flow. Depending on the variant the rod (dim light) or cone (bright light) photoreceptor cells of the eye may also be affected and age of onset and speed of progression can vary. Affected dogs typically have initial vision loss in low light, then peripheral vision loss, and eventually total blindness.
How it's inherited
Recessive
What your result means
Clear (N/N): no copies; not expected to develop PRA-cord1/crd4, nor pass it on.
Carrier (N/PRA): one copy. Healthy, but can pass it on. Breeding two carriers risks affected puppies.
Affected (PRA/PRA): two copies; expected to develop PRA-cord1/crd4. Discuss with your vet.
Skeletal Dysplasia 2SD2
Skeletal Dysplasia (SD2) causes short legs with a normal body, often slightly shorter in the front than the back legs. Height becomes 6cm smaller on average, though this can be variable due to other factors. Affected dogs are not prone to other health problems and lead a normal life.
An autosomal recessive condition caused by a mutation in the COL11A2 gene.
How it's inherited
Recessive
What your result means
Clear (N/N): no copies; not expected to develop SD2, nor pass it on.
Carrier (N/SD2): one copy. Healthy, but can pass it on. Breeding two carriers risks affected puppies.
Affected (SD2/SD2): two copies; expected to develop SD2. Discuss with your vet.
Acral Mutilation SyndromeAMS
- Gene
- GDNF
- Variant
- chr4.g.70,875,561C>T
- Inheritance
- autosomal recessive
- OMIA
- OMIA001514 9615
Molecular mechanism
Acral Mutilation Syndrome (AMS) is a neurological condition that causes acral analgesia, typically presents at a young age. Proprioception, motor abilities, and spinal reflexes are unaffected, but intermittent prescence of intense licking, biting, and self-mutilation of the feet can occur (Plassais et al., 2016). The condition is inherited as an autosomal recessive condition however not every homozygous carrier of the mutation, an at risk dog, shows clinical signs of the disease. Plassais et al., (2016) first sequenced and identified the gene variant, chr4.g.70,875,561C\u0026gt;T, in 300 affected dogs and confirmed it was not present on the 900 unaffected dogs from 130 breeds.
Frequency has not yet been studied although in 250 clinically affected dogs across four sporting breeds they were distinctly genomically different from 900 unaffected dogs across 130 breeds (Correard et al., 2017).
References
Correard, S., Plassais, J., Lagoutte, L., Paradis, M., Guagère, E., Quignon, P., Derrien, T., André, C. : A spontaneous dog model for a human sensory neuropathy: identification of a mutation in the upstream region of a neurotrophic factor. Bull Acad Vét Fr 169:190-194, 2017. DOI: 10.4267/2042/61953.
Plassais , J., Lagoutte, L., Correard, S., Paradis, M., Guaguère, E., Hédan, B., Pommier, A., Botherel, N., Cadiergues, M.-C., Pilorge, P., Silversides, D., Bizot, M., Samuels, M., Arnan, C., Johnson, R., Hitte, C., Salbert, G., Méreau, A., Quignon, P., Derrien, T., André, C. : A point mutation in a lincRNA upstream of GDNF is associated to a canine insensitivity to pain: A spontaneous model for human sensory neuropathies. PLoS Genetics 12:e1006482, 2016. Pubmed reference: 28033318. DOI: 10.1371/journal.pgen.1006482.
Centronuclear MyopathyCNM
- Gene
- HACD1
- Variant
- PTPLA*g9459-9460ins236
- Inheritance
- autosomal recessive
- OMIA
- OMIA001374 9615
Molecular mechanism
Centronuclear Myopathy (CNM) is an inherited neuromuscular disorder characterised by progressive skeletal muscle weakness, hypotonia and muscle atrophy, with clinical signs typically developing from approximately one month of age, although onset may occasionally be delayed until six months of age (Walmsley et al., 2017). Disease severity is variable, ranging from reduced exercise tolerance and gait abnormalities to marked muscle atrophy and collapse (McKerrel \u0026amp; Braund, 1987; Blot et al., 2002). Some affected dogs develop oesophageal muscle weakness, resulting in difficulty swallowing and an increased risk of sudden death, while clinical signs may also be exacerbated by exposure to cold temperatures (McKerrel \u0026amp; Braund, 1987).
Centronuclear Myopathy is inherited as an autosomal recessive condition. Pelé et al., (2005) identified a SINE insertion (PTPLA.9459_9460ins236) in exon 2 of the PTPLA (HACD1) gene on canine chromosome 2 (CFA2) as the causative variant. A worldwide survey of 7,426 Labrador Retrievers identified all 80 clinically affected dogs as homozygous for the variant, while none of the 1,172 heterozygous dogs developed disease, supporting its role as the causative mutation (Maurer et al., 2012). The carrier frequency was reported to be particularly high in the UK (19%), highlighting the importance of genetic testing to identify carriers and inform breeding decisions (Maurer et al., 2012).
References
Blot, S., Tiret, L., Devillaire, A.C., Fardeau, M., Dreyfus, P.A. : Phenotypic description of a canine centronuclear myopathy. Journal of Neurological Science 199:S9, 2002.
Maurer, M., Mary, J., Guillaud, L., Fender, M., Pelé, M., Bilzer, T., Olby, N., Penderis, J., Shelton, G.D., Panthier, J.J., Thibaud, J.L., Barthélémy, I., Aubin-Houzelstein, G., Blot, S., Hitte, C., Tiret, L. : Centronuclear myopathy in Labrador retrievers: a recent founder mutation in the PTPLA gene has rapidly disseminated worldwide. PLoS One 7:e46408, 2012. Pubmed reference: 23071563. DOI: 10.1371/journal.pone.0046408.
McKerrell, R.E., Braund, K.G. : Hereditary myopathy in Labrador Retrievers: clinical variations. Journal of Small Animal Practice 28:479–489, 1987.
Walmsley, G.L., Blot, S., Venner, K., Sewry, C., Laporte, J., Blondelle, J., Barthelemy, I., Maurer, M., Blanchard-Gutton, N., Pilot-Storck, F., et al. (2017). Progressive structural defects in canine centronuclear myopathy indicate a role for HACD1 in maintaining skeletal muscle membrane systems. Am. J. Pathol. 187, 441-456. https://doi.org/10.1016/j.ajpath.2016.10.002
Degenerative MyelopathyDM
- Gene
- SOD1
- Variant
- c.118G>A (p.Glu40Lys)
- Inheritance
- autosomal recessive
- OMIA
- OMIA 000263 9615
- Reported frequency
- One of the most widespread canine disease variants, reported across very many breeds with varying penetrance.
Molecular mechanism
Degenerative Myelopathy (DM) is a progressive neurodegenerative disease of the spinal cord that typically affects dogs older than 8 years of age. The condition is characterised by progressive muscle atrophy and weakness of the limbs, advancing to tetraparesis (Awano et al., 2009) and eventually respiratory muscle failure (Nardone et al., 2016). DM is inherited as an autosomal recessive condition with variable expression between breeds. Missense mutation (c.118G\u0026gt;A; p.E40K) in exon 2 of the SOD1 gene on canine chromosome 31 (CFA31) was identified as the primary genetic risk factor by Awano et al., (2009). However, some dogs homozygous for the variant remain clinically unaffected, demonstrating incomplete penetrance. The SOD1.118G\u0026gt;A risk allele has been identified in 222 dog breeds. Burnese Mountain Dogs are also susceptible to this version of DM in addition to their breed-specific variant of DM, see DM- BMD variant for further information.
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\u0026#39;Brien, DP., Lindblad-Toh, K., Coates, JR. : Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 106:2794-9, 2009. Pubmed reference: 19188595. DOI: 10.1073/pnas.0812297106.
Nardone, R., Höller, Y., Taylor, A.C., Lochner, P., Tezzon, F., Golaszewski, S., Brigo, F., Trinka, E. : Canine degenerative myelopathy: a model of human amyotrophic lateral sclerosis. Zoology (Jena) 119:64-73, 2016. Pubmed reference: 26432396. DOI: 10.1016/j.zool.2015.09.003.
Zeng, R., Coates, J.R., Johnson, G.C., Hansen, L., Awano, T., Kolicheski, A., Ivansson, E., Perloski, M., Lindblad-Toh, K., O\u0026#39;Brien, D.P., Guo, J., Katz, M.L., Johnson, G.S. : Breed distribution of SOD1 alleles previously associated with canine degenerative myelopathy. J Vet Intern Med 28:515-21, 2014. Pubmed reference: 24524809. DOI: 10.1111/jvim.12317.
Exercise-Induced CollapseEIC
- Gene
- DNM1
- Variant
- c.767G>T; p.Arg256Leu
- Inheritance
- autosomal recessive
- OMIA
- OMIA001466 9615
Molecular mechanism
Exercise-Induced Collapse (EIC) is characterised by transient episodes of muscle weakness and collapse triggered by strenuous exercise in otherwise healthy young dogs. Clinical signs typically develop within 2 minutes of completing 5–15 minutes of intense exercise and include hindlimb weakness, incoordination and an unsteady gait, which may progress to collapse, extensor rigidity, loss of consciousness and, in rare cases, death. Most dogs recover completely within approximately 30 minutes (Taylor et al., 2008; Patterson et al., 2008).
In retriever breeds, EIC is inherited as an autosomal recessive condition. Patterson et al., (2008) identified a missense mutation (c.767G\u0026gt;T; p.Arg256Leu) in exon 6 of the DNM1 gene on canine chromosome 9 (CFA9) as the causative variant. The variant has been reported in Labrador Retrievers, Chesapeake Bay Retrievers and Curly Coated Retrievers, allowing genetic testing to identify affected and carrier dogs. In a Midwestern US population of Labrador Retrievers, the variant was reported at a relatively high frequency, with 37% of dogs identified as carriers and 3% as homozygous affected, highlighting the importance of genetic testing to inform breeding decisions (Patterson et al., 2008). Although Border Collies can exhibit similar clinical signs, no causative variant has yet been identified for this breed; therefore, this genetic test is not applicable to Border Collies (Norton et al., 2021).
References
Norton, E.M., Minor, K.M., Taylor, S.M., McCue, M.E., Mickelson, J.R. : Heritability and genomic architecture of episodic exercise-induced collapse in Border Collies. Genes (Basel) 12:1927, 2021. Pubmed reference: 34946876. DOI: 10.3390/genes12121927.
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. Nat Genet 40:1235-9, 2008. Pubmed reference: 18806795. DOI: 10.1038/ng.224.
Taylor, SM., Shmon, CL., Shelton, GD., Patterson, EN., Minor, K., Mickelson, JR. : Exercise-induced collapse of Labrador retrievers: survey results and preliminary investigation of heritability. J Am Anim Hosp Assoc 44:295-301, 2008. Pubmed reference: 18981194.
Familial Nephropathy - Cocker TypeFN
- Gene
- COL4A4
- Variant
- COL4A4_c.115A>T
- Inheritance
- autosomal recessive
- OMIA
- OMIA002618 9615
Molecular mechanism
Familial Nephropathy - Cocker Type, also known as Alport syndrome, is an inherited renal disorder affecting English Cocker Spaniels and also English Springer Spaniels with both having a different causative variant. The condition is inherited as an autosomal recessive trait and is associated with disease-causing variants in the COL4A4 gene. Type IV collagen is a major structural component of the glomerular basement membrane (GBM), where it contributes to the integrity of the glomerular filtration barrier. Mutations affecting type IV collagen can cause structural abnormalities of the GBM and progressive loss of renal function, with Alport syndrome also associated with abnormalities affecting the eye and ear (Savige et al., 2013; Miner 2012).
In English Cocker Spaniels, Davidson et al., (2007) identified a single-nucleotide substitution at base 115 of COL4A4, resulting in a premature stop codon in exon 3. The variant segregated with clinical status in affected dogs and obligate carriers. A different COL4A4 mutation was subsequently identified in English Springer Spaniels by Nowend et al., (2012), involving a single-nucleotide substitution at base 2806 that also results in a premature stop codon.
The c.115T variant has been reported at a frequency of 0.9% in English Cocker Spaniels in Brazil (Andrade et al., 2020). Genetic testing can identify dogs carrying the known disease-associated variants, supporting informed breeding decisions to reduce the risk of producing affected offspring. This genetic test is for the Cocker Type and does not test for the variant associated with Familial Nephropathy in English Springer Spaniels.
References
Davidson A.G., Bell R.J., Lees G.E., Kashtan C.E., Davidson G.S., Murphy K.E. Genetic Cause of Autosomal Recessive Hereditary Nephropathy in the English Cocker Spaniel. Journal of Veterinary Internal Medicine. 2007;21:394–401. doi: 10.1892/0891-6640(2007)21[394:gcoarh]2.0.co;2. [DOI] [PubMed] [Google Scholar]
De Brot S., Adamany J., Baiker K., Dhumeaux M., Allegrucci C., Polledo I., Grau-Roma L. Pathology in practice. Hereditary nephropathy (familial nephropathy) in an english cocker spaniel. Journal of the American Veterinary Medical Association. 2017;251:661–664. doi: 10.2460/javma.251.6.661. [DOI] [PubMed] [Google Scholar]
Miner J. H., The Glomerular Basement Membrane, Experimental Cell Research. (2012) 318, no. 9, 973–978, **https://doi.org/10.1016/j.yexcr.2012.02.031**, 2-s2.0-84859814741, 22410250.
Lees G.E. Kidney diseases caused by glomerular basement membrane type IV collagen defects in dogs. Journal of Veterinary Emergency and Critical Care (San Antonio) 2013;23:184–193. doi: 10.1111/vec.12031. [DOI] [PubMed] [Google Scholar]
Savige J., Gregory M., Gross O., Kashtan C., Ding J., and Flinter F., Expert Guidelines for the Management of Alport Syndrome and Thin Basement Membrane Nephropathy, Journal of the American Society of Nephrology. (2013) 24, no. 3, 364–375, **https://doi.org/10.1681/ASN.2012020148**, 2-s2.0-84874616744, 23349312.
Hereditary Nasal ParakeratosisHNPK
- Gene
- SUV39H2
- Variant
- Labrador c.972T>G; p.Asn324Lys
- Inheritance
- autosomal recessive
- OMIA
- OMIA001373 9615
Molecular mechanism
Hereditary Nasal Parakeratosis (HNPK) is an inherited skin disorder characterised by the development of crusting and fissuring of the nasal planum from a young age. Affected dogs are otherwise healthy, with the condition primarily affecting the nasal epidermis. Histopathological examination reveals marked parakeratotic hyperkeratosis, characterised by retention of nuclei within the stratum corneum and accumulation of proteinaceous fluid within the superficial epidermal layers (Jagannathan et al., 2013).
HNPK is inherited as an autosomal recessive condition (Page et al., 2003). Jagannathan et al., (2013) identified a missense mutation (c.972T\u0026gt;G; p.Asn324Lys) in the SUV39H2 gene on canine chromosome 2 (CFA2) as the causative variant in Labrador Retrievers.
Note: Whippets present a different variant so this test is not applicable to Whippets as it is the Retriever type.
References
Jagannathan, V., Bannoehr, J., Plattet, P., Hauswirth, R., Drögemüller, C., Drögemüller, M., Wiener, D.J., Doherr, M., Owczarek-Lipska, M., Galichet, A., Welle, M.M., Tengvall, K., Bergvall, K., Lohi, H., Rüfenacht, S., Linek, M., Paradis, M., Müller, E.J., Roosje, P., Leeb, T. : A mutation in the SUV39H2 gene in Labrador Retrievers with hereditary nasal parakeratosis (HNPK) provides insights into the epigenetics of keratinocyte differentiation. PLoS Genet 9:e1003848, 2013. Pubmed reference: 24098150. DOI: 10.1371/journal.pgen.1003848.
Page, N., Paradis, M., Lapointe, J.M., Dunstan, R.W. : Hereditary nasal parakeratosis in Labrador Retrievers Veterinary Dermatology 14:103-10, 2003. Pubmed reference: 12662268.
HyperuricosuriaHUU
- Gene
- SLC2A9
- Variant
- c.616G>T; p.Cys188Phe
- Inheritance
- autosomal recessive
- OMIA
- OMIA000256 9615
Molecular mechanism
Hyperuricosuria (HUU)or Urolithiasis is an inherited metabolic disorder characterised by impaired uric acid transport, resulting in increased urinary excretion and blood concentrations of uric acid. Affected dogs are predisposed to the formation of ammonium urate uroliths within the urinary tract, although not all dogs carrying the causative variant will develop the disease (Bannasch et al., 2008). Clinical signs are associated with stone formation and may include haematuria, pollakiuria, dysuria and urethral obstruction, while severe obstruction can result in systemic illness including anorexia, vomiting, collapse and metabolic disturbances (Bartges et al., 1999; Bartges and Callens, 2015).
Hyperuricosuria is inherited as an autosomal recessive condition; however, the SLC2A9 variant represents a genetic risk factor for urate urolithiasis rather than a definitive predictor of clinical disease. Bannasch et al., (2008) identified a missense mutation (c.616G\u0026gt;T; p.Cys188Phe) in the SLC2A9 gene on canine chromosome 3 (CFA3) as the causative variant. The variant is fixed in Dalmatians, with all dogs reported to be homozygous, but has also been identified at lower frequencies in several other breeds, including Labrador Retrievers, Bulldogs, German Shepherd Dogs and Pomeranians (Bannasch et al., 2008; Karmi et al., 2010; Cosgrove et al., 2015).
References
Bannasch, D., Henthorn, PS. : Changing paradigms in diagnosis of inherited defects associated with urolithiasis. Vet Clin North Am Small Anim Pract 39:111-25, 2009. Pubmed reference: 19038654. DOI: 10.1016/j.cvsm.2008.09.006.
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 Genet 4:e1000246, 2008. Pubmed reference: 18989453. DOI: 10.1371/journal.pgen.1000246.
Bartges, J.W., Callens, A.J. : Urolithiasis. Vet Clin North Am Small Anim Pract 45:747-68, 2015. Pubmed reference: 26002797. DOI: 10.1016/j.cvsm.2015.03.001.
Bartges, J.W., Osborne, C.A., Lulich, J.P., Kruger, J.M., Sanderson, S.L., Koehler, L.A., Ulrich, L.K. : Canine urate urolithiasis. Etiopathogenesis, diagnosis, and management. Vet Clin North Am Small Anim Pract 29:161-91, xii-xiii, 1999. Pubmed reference: 10028157. DOI: 10.1016/s0195-5616(99)50010-7.
Cosgrove, L., Hammond, G., Mclauchlan, G. : Primary portal vein hypoplasia and SLC2A9 mutation associated with urate urolithiasis in a Spanish water dog. Can Vet J 56:1153-7, 2015. Pubmed reference: 26538670.
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 71:909-14, 2010. Pubmed reference: 20673090. DOI: 10.2460/ajvr.71.8.909.
Progressive Retinal Atrophy (cord1/rcd4)PRA-cord1/rcd4
- Gene
- RPGRIP1
- Variant
- p.(I49Kfs*26)
- Inheritance
- autosomal recessive
- OMIA
- OMIA001432 9615
Molecular mechanism
Progressive retinal atrophy (PRA) encompasses a genetically heterogeneous group of inherited retinal degenerative disorders characterised by the progressive loss of photoreceptor function, ultimately resulting in irreversible blindness. Although the clinical presentation is broadly similar across affected breeds, with initial degeneration of rod photoreceptors causing night blindness followed by cone degeneration and progressive loss of daylight vision, numerous genetically distinct forms of PRA have been identified (Miyadera et al., 2012; Mowat et al., 2024). Advances in canine molecular genetics have demonstrated that variants in multiple genes involved in photoreceptor development, maintenance and function can produce clinically similar retinal phenotypes. Consequently, breed-specific genetic testing is required, as different forms of PRA are associated with different causative variants.
PRA-RPGRIP1 (CORD1/RCD4): Progressive retinal atrophy associated with RPGRIP1 is inherited as an autosomal recessive condition. In Miniature Long-Haired Dachshunds, Mellersh et al., (2006) identified a 44-bp insertion in the RPGRIP1 gene that results in a frameshift and premature protein truncation. Although additional genetic factors may influence disease severity, this variant remains the primary genetic marker used for testing (Miyadera et al., 2012).
The expanding number of recognised PRA-associated variants highlights the marked genetic heterogeneity underlying inherited retinal degeneration in dogs. While many of these variants are breed-specific, others are shared across multiple breeds through historical founder events. Genetic testing enables accurate identification of affected and carrier dogs, supporting informed breeding decisions aimed at reducing disease prevalence while preserving genetic diversity. As additional causative variants continue to be identified, molecular testing will remain an important tool for improving the diagnosis, management and long-term control of progressive retinal atrophy in canine populations (Lewis \u0026amp; Mellersh, 2019; Mowat et al., 2024).
References
Aguirre, G.D., Lohi, H., Kaukonen, M., Murgiano, L. : Formal commentary. PLoS Genet 16:e1009059, 2020. Pubmed reference: 33151924. DOI: 10.1371/journal.pgen.1009059.
Clark, J.A., Anderson, H., Donner, J., Pearce-Kelling, S., Ekenstedt, K.J. : Global frequency analyses of canine progressive rod-cone degeneration-progressive retinal atrophy and Collie eye anomaly using commercial genetic testing data. Genes (Basel) 14:2093, 2023. Pubmed reference: 38003037. DOI: 10.3390/genes14112093.
Downs, L.M., Wallin-Håkansson, B., Boursnell, M., Marklund, S., Hedhammar, Å., Truvé, K., Hübinette, L., Lindblad-Toh, K., Bergström, T., Mellersh, C.S. : A frameshift mutation in golden retriever dogs with progressive retinal atrophy endorses SLC4A3 as a candidate gene for human retinal degenerations. PLoS One 6:e21452, 2011. Pubmed reference: 21738669. DOI: 10.1371/journal.pone.0021452.
Downs, L.M., Bell, J.S., Freeman, J., Hartley, C., Hayward, L.J., Mellersh, C.S. : Late-onset progressive retinal atrophy in the Gordon and Irish Setter breeds is associated with a frameshift mutation in C2orf71. Anim Genet 44:169-77, 2013. Pubmed reference: 22686255. DOI: 10.1111/j.1365-2052.2012.02379.x.
Downs, L.M., Mellersh, C.S. : An intronic SINE insertion in FAM161A that causes exon-skipping is associated with progressive retinal atrophy in Tibetan Spaniels and Tibetan Terriers. PLoS One 9:e93990, 2014. Pubmed reference: 24705771. DOI: 10.1371/journal.pone.0093990.
Downs, L.M., Wallin-Håkansson, B., Bergström, T., Mellersh, C.S. : A novel mutation in TTC8 is associated with progressive retinal atrophy in the golden retriever. Canine Genet Epidemiol 1:4, 2014. Pubmed reference: 26401321. DOI: 10.1186/2052-6687-1-4.
Goldstein, O., Mezey, JG., Boyko, AR., Gao, C., Wang, W., Bustamante, CD., Anguish, LJ., Jordan, JA., Pearce-Kelling, SE., Aguirre, GD., Acland, GM. : An ADAM9 mutation in canine cone-rod dystrophy 3 establishes homology with human cone-rod dystrophy 9. Mol Vis 16:1549-69, 2010. Pubmed reference: 20806078.
Karlskov-Mortensen, P., Proschowsky, H.F., Gao, F., Fredholm, M. : Identification of the mutation causing progressive retinal atrophy in Old Danish Pointing Dog. Anim Genet 49:237-241, 2018. Pubmed reference: 29624701. DOI: 10.1111/age.12659.
Kaukonen, M., Quintero, I.B., Mukarram, A.K., Hytönen, M.K., Holopainen, S., Wickström, K., Kyöstilä, K., Arumilli, M., Jalomäki, S., Daub, C.O., Kere, J., Lohi, H. : A putative silencer variant in a spontaneous canine model of retinitis pigmentosa. PLoS Genet 16:e1008659, 2020. Pubmed reference: 32150541. DOI: 10.1371/journal.pgen.1008659.
Kropatsch, R., Petrasch-Parwez, E., Seelow, D., Schlichting, A., Gerding, WM., Akkad, DA., Epplen, JT., Dekomien, G. : Generalized progressive retinal atrophy in the Irish Glen of Imaal Terrier is associated with a deletion in the ADAM9 gene. Mol Cell Probes 24:357-63, 2010. Pubmed reference: 20691256. DOI: 10.1016/j.mcp.2010.07.007.
Lewis, T.W., Mellersh, C.S. : Changes in mutation frequency of eight Mendelian inherited disorders in eight pedigree dog populations following introduction of a commercial DNA test. PLoS One 14:e0209864, 2019. Pubmed reference: 30650096. DOI: 10.1371/journal.pone.0209864.
Mellersh, CS., Boursnell, ME., Pettitt, L., Ryder, EJ., Holmes, NG., Grafham, D., Forman, OP., Sampson, J., Barnett, KC., Blanton, S., Binns, MM., Vaudin, M. : Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics 88:293-301, 2006. Pubmed reference: 16806805. DOI: 10.1016/j.ygeno.2006.05.004.
Mowat, F.M., Iwabe, S., Aguirre, G.D., Petersen-Jones, S.M. : Consensus guidelines for nomenclature of companion animal inherited retinal disorders. Vet Ophthalmol 28:663-667, 2024. Pubmed reference: 38334230. DOI: 10.1111/vop.13185.
Miyadera, K., Acland, G.M., Aguirre, G.D. : Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies. Mamm Genome 23:40-61, 2012. Pubmed reference: 22065099. DOI: 10.1007/s00335-011-9361-3.
Murgiano, L., Becker, D., Torjman, D., Niggel, J.K., Milano, A., Cullen, C., Feng, R., Wang, F., Jagannathan, V., Pearce-Kelling, S., Katz, M.L., Leeb, T., Aguirre, G.D. : Complex structural PPT1 variant associated with non-syndromic canine retinal degeneration. G3 (Bethesda) 9:425-437, 2019. Pubmed reference: 30541930. DOI: 10.1534/g3.118.200859.
Petersen-Jones, S.M., Entz, D.D., Sargan, D.R. : CGMP phosphodiesterase-alpha mutation causes progressive retinal atrophy in the Cardigan Welsh corgi dog Investigative Ophthalmology \u0026amp; Visual Science 40:1637-1644, 1999. Pubmed reference: 10393029.
Suber, M.L., Pittler, S.J., Qin, N., Wright, G.C., Holcombe, V., Lee, R.H., Craft, C.M., Lolley, R.N., Baehr, W., Hurwitz, R.L. : Irish Setter Dogs Affected with Rod/Cone Dysplasia Contain a Nonsense Mutation in the Rod cGMP Phosphodiesterase beta- Subunit Gene Proceedings of the National Academy of Sciences of the United States of America 90:3968-3972, 1993. Pubmed reference: 8387203.
Svensson, M., Olsén, L., Winkler, P.A., Petersen-Jones, S.M., Bergström, T., Garncarz, Y., Narfström, K. : Progressive retinal atrophy in the Polski Owczarek Nizinny dog: a clinical and genetic study. Vet Ophthalmol 19:195-205, 2016. Pubmed reference: 26009980. DOI: 10.1111/vop.12284.
Wiik, A.C., Ropstad, E.O., Ekesten, B., Karlstam, L., Wade, C.M., Lingaas, F. : Progressive retinal atrophy in Shetland sheepdog is associated with a mutation in the CNGA1 gene. Anim Genet 46:515-21, 2015. Pubmed reference: 26202106. DOI: 10.1111/age.12323.
Winkler, P.A., Ekenstedt, K.J., Occelli, L.M., Frattaroli, A.V., Bartoe, J.T., Venta, P.J., Petersen-Jones, S.M. : A large animal model for CNGB1 autosomal recessive retinitis pigmentosa. PLoS One 8:e72229, 2013. Pubmed reference: 23977260. DOI: 10.1371/journal.pone.0072229.
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. : Identical mutation in a novel retinal gene causes progressive rod-cone degeneration in dogs and retinitis pigmentosa in humans. Genomics 88:551-563, 2006. Pubmed reference: 16938425. DOI: 10.1016/j.ygeno.2006.07.007.
Skeletal Dysplasia 2SD2
- Gene
- COL11A2
- Variant
- COL11A2:c.143G>C
- Inheritance
- autosomal recessive
- OMIA
- OMIA001772 9615
Molecular mechanism
Skeletal Dysplasia 2 (SD2) is an inherited mild form of disproportionate dwarfism in Labrador Retrievers, characterised by shortened limbs with a normal body length and width. Affected dogs have an average reduction in shoulder height of approximately 6 cm (Frischknecht et al., 2013). As shoulder height is influenced by both genetic and environmental factors, affected dogs cannot always be reliably identified by physical appearance alone (Frischknecht et al., 2013).
Skeletal Dysplasia 2 is inherited as a monogenic autosomal recessive condition. Frischknecht et al., (2013) identified a missense mutation (c.143G\u0026gt;C; p.Arg48Pro) in the COL11A2 gene on canine chromosome 12 (CFA12) as the most likely causative variant. The carrier frequency was estimated at approximately 12% in the European Labrador Retriever population at the time of variant discovery, highlighting the value of genetic testing to confirm the diagnosis and inform breeding decisions (Frischknecht et al., 2013).
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. : A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism. PLoS One 8:e60149, 2013. Pubmed reference: 23527306. DOI: 10.1371/journal.pone.0060149.
