2021 has been an exciting year for Paw Print Genetics (PPG) and canine genetic health. With the addition of 15 new genetic disease and trait tests in July 2021, PPG has now added more than 50 new canine test offerings this year alone! However, when it comes to specific genetic diseases, variability in the population size of affected breeds and the frequency of the associated mutations, means that some diseases are much more likely to be seen in veterinary hospitals than others.
Here we will highlight four new genetic disease tests offered at PPG for canine diseases common enough to be seen in general veterinary practice. In addition, we will briefly discuss PPG’s new web-based disease and coat color probability calculators which assist breeders and veterinarians in selecting ideal parents for producing healthy puppies in the coat colors and patterns desired.
Progressive retinal atrophy (Giant Schauzer Type), also known as generalized PRA or PRA5, is an autosomal recessive form of PRA affecting the giant schnauzer and several other breeds. Dogs inheriting two copies of the associated NECAP1 gene mutation experience adult-onset rod and cone photoreceptor degeneration resulting in progressive vision loss and classic PRA eye exam abnormalities including attenuated retinal blood vessels, retinal thinning, and increased tapetal reflectivity. Most affected dogs will progress to complete blindness.
6% out of 322 giant schnauzers tested carried one copy of the associated NECAP1 mutation.1 However, the frequency of this mutation in the overall giant schnauzer population or other breed populations is unknown.
Cerebellar Ataxia 2 (Belgian Shepherd Type) is an early-onset autosomal recessive disease marked by profound cerebellar dysfunction secondary to degeneration of neurons in the cerebellum, brainstem, and cervical spinal cord. Dysfunction in neuronal potassium regulation is a suspected factor in disease. Also known as spongy degeneration with cerebellar ataxia, subtype 2 (SDCA2), puppies inheriting two copies of the associated ATP1B2 mutation present around four weeks of age with rapidly progressing neurological signs including ataxia and an inability to walk within two to three weeks of initial presentation. Some affected puppies may also develop seizures, pacing, circling, and central blindness. Affected dogs generally die or are humanely euthanized within the first two months of life due to quality-of-life concerns.
15% out of 251 Belgian Malinois tested carried one copy of the associated ATP1B2 mutation.2 Since it is common practice in some areas of the world to interbreed the four Belgian shepherd varieties, it is indicated to test any variety of Belgian shepherd for Cerebellar Ataxia 2 prior to breeding. The frequency of this mutation in the overall Belgian shepherd population is unknown for all varieties.
Leukoencephalomyelopathy (LEMP) is another autosomal recessive neurodegenerative disease test now available at Paw Print Genetics. Known to affect the Great Dane and Rottweiler, dogs from these breeds inheriting two copies of the associated NAPEPLD mutation present as early as one year of age with slowly progressive neurological disease secondary to neurodegeneration in the cervical spinal cord, brain stem, and brain. Clinical signs include progressive ataxia, tetraparesis, hypermetria, wide-based stance, and limb crossing. Affected dogs may have evidence of toenail wear or foot trauma secondary to dragging feet. Although not a painful disease, most affected dogs are humanely euthanized by 5 years of age due to increasingly severe neurological dysfunction and a lack of treatment options.
7% out of 233 Rottweilers and 9% out of 262 Great Danes tested carried one copy of the NAPEPLD mutation.3 However, the frequency of the mutation in the overall Rottweiler and Great Dane populations is unknown.
Multiple mutations in the amino acid transporter genes SLC3A1 and SLC7A9 have been associated with an androgen-dependent cystinuria in the bulldog, French bulldog, and mastiff. Variant 2 (SLC3A1) is a linked marker, strongly associated with cystinuria. Intact male dogs inheriting two copies of this mutation (one from each parent) are expected to develop cystinuria within the first 2 years of life, placing them at increased risk of urolithiasis and urinary obstruction. Since this disease is androgen-dependent, female dogs inheriting two copies of this mutation do not develop clinical signs. In addition, castration of affected males dramatically reduces urine cystine levels and risk of stone formation.
Variant 3 (SLC7A9) is an independent linked marker speculatively associated with cystinuria type 3. Variant 3 was discovered in a bulldog affected with cystinuria which had also inherited two copies of Variant 2.1 Given that mutations in SLC7A9 are commonly implicated in incompletely dominant cystinuria in humans, Variant 3 may also play a role in canine cystinuria type 3. However, at this time, it is unknown if dogs inheriting one or two copies of Variant 3 in the absence of Variant 2 will develop cystinuria. Therefore, urinary cystine testing may be indicated for dogs which have inherited Variant 3, especially prior to breeding.
Although the frequencies of Variants 2 and 3 in the overall affected breed populations are unknown, PPG test data has shown that both Variants appear to be relatively common among the affected breeds.
New for August 2021, PPG is proud to announce the release of two exciting new tools to assist breeders (and their veterinarians) in comparing test results from potential parents to ensure healthy puppies in the coat colors and traits desired. First, the PPG Coat Color and Trait calculator allows breeders to input dam and sire coat color and trait results for up to 6 different tests to determine the potential appearance outcome for a litter. In addition, PPG clients now have access to the PPG Disease calculator which allows for comparison of PPG test results from potential parents in order to determine if there are obvious disease risks prior to breeding. The disease calculator is reserved for dogs with PPG test results and is available for use after PPG clients have signed into their account. Veterinarians ordering testing for clients through a veterinary clinic account will also have access to these tools. Additional information about these calculators can be found in this blog by Dr. Blake Ballif, PPG’s Director of Development.
Paw Print Genetics has a friendly staff of knowledgeable veterinarians and geneticists ready to answer your questions or assist in choosing the most appropriate tests for diagnosis in clinical inherited disease cases. Please feel free to call the laboratory during normal business hours at 509-483-5950 (8 am to 5 pm Pacific time, Monday through Friday) or email us a question at AskUs@pawprintgenetics.com.
- Hitti RJ, Oliver JAC, Schofield EC, Bauer A, Kaukonen M, Forman OP, Leeb T, Lohi H, Burmeister LM, Sargan D, Melleresh CS. Whole Genome Sequencing of Giant Schnauzer Dogs with Progressive Retinal Atrophy Establishes NECAP1 as a Novel Candidate Gene for Retinal Degeneration. Genes (Basel). 2019 May 21;10(5). pii: E385. doi: 10.3390/genes10050385. [PubMed: 31117272]
- Mauri N, Kleiter M, Dietschi E et al: A SINE Insertion in ATP1B2 in Belgian Shepherd Dogs Affected by Spongy Degeneration with Cerebellar Ataxia (SDCA2). G3 (Bethesda) 2017 Vol 7 (8) pp. 2729-2737. [PubMed: 28620085]
- Minor KM, Letko A, Becker D, Drogemuller M, Mandigers PJJ, Bellekom SR, Leegwater PAJ, Stassen QEM, Purschbach K, Fischer A, Flegel T, Matiasek K, Ekenstedt KJ, Furrow E, Patterson EE, Platt SR, Kelly PA, Cassidy JP, Shelton GD, Lucot K, Bannasch DL, Martineau H, Muir CF, Priestnall SL, Henke D, Oevermann A, Jagannathan V, Mickelson JR, and Drogemuller C. Canine NAPEPLD-associated models of human myelin disorders. Sci Rep. 2018 Apr 11;8(1):5818. doi: 10.1038/s41598-018-23938-7. [PubMed: 29643404]
- Hirschvogel K, Matiasek K, Flatz K, Drogemuller M, Drogemuller C, Reiner B, Fischer A. Magnetic resonance imaging and genetic investigation of a case of rottweiler leukoencephalomyelopathy. BMC Vet Res. 2013 Mar 26;9:57. doi: 10.1186/1746-6148-9-57. [PubMed: 23531239]
- Harnevik L, Hoppe A, Soderkvist P. SLC7A9 cDNA cloning and mutational analysis of SLC3A1 and SLC7A9 in canine cystinuria. Mamm Genome. 2006 Jul;17(7):769-76. [PubMed: 16845473]