Test Detail

Multidisease panel for the Shetland Sheepdog (Sheltie) that groups the six tests of its components: Collie eye anomaly (CEA, NHEJ1), BBS2-related progressive retinal atrophy, CNGA1-related progressive retinal atrophy, von Willebrand disease type 3 (vWD3, VWF), degenerative myelopathy (DM, SOD1 exon 2) and MDR-1 defect (ABCB1, drug sensitivity). Each test reports the clear/carrier/affected status for the corresponding variant. The panel does not replace the ocular examination or haematological monitoring: vWD3 is a severe coagulopathy and DM has incomplete penetrance.

Applicable breed: Shetland Sheepdog. Carrier frequencies are not published systematically for the six variants (limited data). The MDR-1 defect is well documented in the breed and CEA has been described in the Shetland Sheepdog, although specific frequencies are not firmly established; BBS2-PRA is considered rare and breed-specific, CNGA1-PRA has no consolidated carrier frequency and Shetland vWD3 is based on a patent. Overall: limited data except for MDR-1 and CEA.

- Choroidal hypoplasia, retinal folds, optic disc coloboma and retinal detachment in severe cases (CEA)
- Initial night blindness and progressive retinal atrophy (BBS2-PRA, CNGA1-PRA)
- Spontaneous or prolonged bleeding after surgery or trauma, mucocutaneous bleeding and epistaxis (vWD3)
- Progressive pelvic limb paresis with proprioceptive ataxia in the adult (DM)
- Neurotoxicity after ivermectin and other drugs that are substrates of P-glycoprotein (MDR-1)

The tests in the panel were developed separately. CEA was mapped to canine chromosome 37 and Parker et al. (2007) showed that a 7.8 kb deletion in NHEJ1 cosegregates with the disease in several herding breeds; OMIA classifies it as a locus-linked marker. PRA in the Sheltie was linked to BBS2 (Hitti-Malin et al., 2021) and to CNGA1 (Wiik et al., 2015). vWD3 was associated with null mutations in VWF; for the Shetland the variant appears in a US patent, not in peer-reviewed literature. Canine DM was linked to the SOD1 exon 2 variant (Awano et al., 2009). The MDR-1 defect was associated with a deletion in ABCB1 initially described in collies (Mealey et al., 2001).

- Genotype breeding animals before mating; the panel covers the six conditions in a single sample
- For CEA, BBS2-PRA, CNGA1-PRA, vWD3 and DM (recessive): do not mate carrier x carrier (25% risk of affected homozygotes); carrier x clear produces no affected animals and gives 50% carriers
- For MDR-1: avoid mating two mutated homozygotes; heterozygotes may be mated with clear animals
- Given the severity of vWD3, assess bleeding time and vWF dosing before surgery in animals not genotyped
- After a confirmed clinical case, do not repeat the parental mating and inform the buyer of the status

Annual ocular examination (ECVO) is complementary for conditions not detected by DNA or of late onset. vWD3 is confirmed by vWF antigen and activity measurement; in affected animals, avoid antiplatelet drugs before surgery. MDR-1 sensitivity requires reviewing contraindicated drugs (ivermectin, loperamide, chemotherapeutic agents). DM is a diagnosis of exclusion: rule out spinal cord compression, disc herniation and neoplasia before attributing the condition to SOD1. Differentiate the two PRAs by age of onset and electroretinography.

Componente CEA (vcui):
1. Lowe JK et al. 2003. Linkage mapping of the primary disease locus for collie eye anomaly. Genomics. PMID: 12809679
2. Parker HG et al. 2007. A 7.8-kb deletion cosegregates with Collie eye anomaly across multiple dog breeds. Genome Res. PMID: 17916641
3. OMIA:000218-9615. Choroidal hypoplasia, NHEJ1-related.

Componente BBS2-PRA (qhqi):
4. Hitti-Malin RJ et al. 2021. A missense variant in BBS2 leads to a novel syndromic retinal degeneration in the Shetland sheepdog. Genes (Basel). PMID: 34828377
5. OMIA:002484-9615. Bardet-Biedl syndrome 2.

Componente CNGA1-PRA (qyzy):
6. Wiik AC et al. 2015. Progressive retinal atrophy in Shetland sheepdog is associated with a mutation in the CNGA1 gene. Anim Genet. PMID: 26202106
7. OMIA:001977-9615. Retinal atrophy, progressive, CNGA1-related.

Componente vWD3 (zpfm):
8. Rieger M et al. 1998. Identification of mutations in the canine von Willebrand factor gene associated with type III von Willebrand disease. Thromb Haemost. PMID: 9716162
9. Venta PJ et al. 2000. Mutation causing von Willebrand's disease in Scottish Terriers. J Vet Intern Med. PMID: 10668811
10. Armas-Jimenez AC et al. 2025. A VWF missense variant in Havanese dogs with type 3 von Willebrand disease. Anim Genet. PMID: 40504041
11. OMIA:001058-9615. Von Willebrand disease III. (La variante del Shetland deriva de la patente US6074832A, no revisada por pares.)

Componente DM (dnvf):
12. Awano T et al. 2009. Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy. Proc Natl Acad Sci U S A. PMID: 19188595
13. Coates JR et al. 2010. Canine degenerative myelopathy. Vet Clin North Am Small Anim Pract. PMID: 20732599
14. OMIA:000263-9615. Degenerative myelopathy.

Componente MDR-1 (samk):
15. Mealey KL et al. 2001. Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics. PMID: 11692082
16. Mealey KL. 2004. Therapeutic implications of the MDR-1 gene. J Vet Pharmacol Ther. PMID: 15500562