Test Detail

Multi-disease genetic panel for the Collie bringing together the six tests of its components: Collie eye anomaly (CEA, NHEJ1), rcd2 progressive retinal atrophy (RD3), inflammatory pulmonary disease (IPD, AKNA), degenerative myelopathy (DM, SOD1 exon 2), ivermectin sensitivity (MDR-1, ABCB1) and dermatomyositis (DMS, PAN2 + MAP3K7CL + DLA). Each condition has its own molecular basis and inheritance; DMS is polygenic and CEA has variable expression. The panel is complementary to ophthalmological, respiratory, neurological and pharmacological examination.

Applicable breed: Collie. The MDR-1 mutation and the CEA deletion are frequent in Collie lines; in DMS, most collies are homozygous for DLA-DRB1*002:01 and the frequency of PAN2/MAP3K7CL risk alleles is high, although the clinical incidence is lower than the prevalence of risk genotypes. IPD was described in a sample of 88 Rough Collies with ~20% carriers (a sample that included relatives of the cases). The frequencies of rcd2-PRA are not reliably published. Overall: limited data except for MDR-1, CEA and DMS.

- Genotype breeding animals before mating; the panel covers the six conditions in a single sample
- For CEA, rcd2-PRA, IPD and DM (recessive): do not mate two carriers (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 can be mated with clear animals; communicate the pharmacological sensitivity to the buyer
- For DMS: test the three loci (PAN2, MAP3K7CL, DLA) and prioritise low-risk combinations; the absence of risk alleles does not guarantee protection
- After a confirmed clinical case, do not repeat the parental mating and communicate the status to the buyer

CEA is confirmed by neonatal ophthalmology (ideally at 6-8 weeks, before pigmentation) and molecular testing; the go normal phenomenon does not indicate that the dog is healthy or that it does not transmit the allele. MDR-1 sensitivity requires avoiding ivermectin and other P-gp substrates (loperamide, several chemotherapeutic agents) in homozygotes and heterozygotes. DMS requires skin biopsy for definitive diagnosis and is distinguished from demodicosis, dermatophytosis, pemphigoid and cutaneous lupus; the risk haplotype does not confirm the disease. DM is a diagnosis of exclusion: rule out spinal cord compression. IPD is distinguished from infectious, allergic and aspiration respiratory processes.

Componente IPD (qmlo):
1. Hug P et al. 2019. AKNA frameshift variant in three dogs with recurrent inflammatory pulmonary disease. Genes (Basel). PMID: 31357536
2. OMIA:002205-9615. Recurrent inflammatory pulmonary disease.

Componente DMS (lmwb):
3. Evans JM et al. 2017. Beyond the MHC: a canine model of dermatomyositis shows a complex pattern of genetic risk. PLoS Genet. PMID: 28158183
4. OMIA:000270-9615. Dermatomyositis.

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

Componente DM (dnvf):
8. 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
9. Coates JR et al. 2010. Canine degenerative myelopathy. Vet Clin North Am Small Anim Pract. PMID: 20732599
10. OMIA:000263-9615. Degenerative myelopathy.

Componente rcd2-PRA (npte):
11. Kukekova AV et al. 2009. Canine RD3 mutation establishes rod-cone dysplasia type 2 (rcd2). Mamm Genome. PMID: 19130129
12. OMIA:001260-9615. Retinal atrophy - Rod-cone dysplasia 2, RD3-related.

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