Multi-disease panel aimed at the Australian Shepherd and the Miniature American Shepherd that groups together eight molecular tests for hereditary conditions described in these breeds: collie eye anomaly (CEA), prcd-PRA progressive retinal atrophy, brachyuria (natural short tail), HSF4-linked hereditary cataract, hyperuricosuria (HUU), neuronal ceroid lipofuscinosis (NCL), degenerative myelopathy (DM exon 2) and the MDR-1 defect with ivermectin sensitivity. Each test reports the clear/carrier/affected status for the corresponding variant and allows matings to be planned while avoiding diseased animals or animals sensitive to drugs. The panel does not replace ocular examination or clinical follow-up: several conditions are late-onset or of variable penetrance, and the molecular test is only one piece of reproductive management.

Applicable breeds: Australian Shepherd and Miniature American Shepherd. Carrier frequencies in the breeding population are not systematically published for the eight variants (limited data); the MDR-1 defect and prcd-PRA are documented in both breeds with detectable carriers, whereas other conditions (e.g. NCL, HUU) have scarcer casuistry and must be verified in the specific literature.

- Ocular fundus abnormalities: choroidal hypoplasia, possible detachments (CEA)\n- Reduced night vision and progressive retinal atrophy (prcd-PRA)\n- Bilateral cataract, frequently posterior (HSF4)\n- Natural short tail or partial absence of the tail (brachyuria)\n- Urolithiasis due to urate/uric acid stones (HUU)\n- Progressive neurological signs: ataxia, myoclonus, behavioural deterioration (NCL)\n- Progressive paresis of the thoracic and pelvic limbs with proprioceptive ataxia (DM)\n- Neurological toxicity after ivermectin and other drugs that are P-glycoprotein substrates (MDR-1)

The tests in the panel were developed independently as canine genetics groups characterised specific variants for each disease. prcd-PRA was associated with the PRCD gene and its molecular test became widespread in multiple breeds. Canine DM was linked to the exon 2 variant of SOD1 following the work of Awano and colleagues in 2009. The MDR-1 defect was associated with a deletion in ABCB1 initially described in collies and later extended to herding breeds. Natural brachyuria was linked to the T gene (Brachyury). Hereditary cataract of the Australian Shepherd was associated with an HSF4 variant with autosomal dominant inheritance and incomplete penetrance (Mellersh and colleagues, 2009). The exact molecular assignment of some specific variants in the breed (specific form of NCL in the Australian Shepherd, exact HUU variant in the breed) is less robust in the accessible literature and must be verified in the primary source. NCL6 due to CLN6 c.829T>C was described in an Australian Shepherd (2011); there are only two confirmed cases and there is no support for the Miniature American Shepherd. HUU due to SLC2A9 is screened in Australian Shepherd cohorts (Majchrakova 2023), with scarce clinical casuistry in the breed.

- Genotype breeding animals before mating; the panel allows eight conditions to be managed from a single sample\n- For the recessive conditions (CEA, prcd-PRA, HUU, NCL, DM): do not mate carrier×carrier (25% risk of affected homozygotes); carrier×clear produces 0% affected and 50% carriers\n- For the HSF4 cataract (dominant with incomplete penetrance in the Australian Shepherd): heterozygotes are at risk of developing cataract and can transmit the variant to 50% of the offspring; prioritise clear animals for breeding and perform annual ophthalmological assessment. Carrier×clear can produce up to 50% carrier offspring at risk, NOT 0% affected\n- For brachyuria (T): do not mate two animals with a natural short tail (risk of non-viable homozygotes).nimals with a natural short tail that are heterozygous because of the risk of non-viable homozygotes; know the genotype before deciding on a short tail\n- For MDR-1: avoid mating two mutated homozygotes (the whole litter would be sensitive to ivermectin and other P-gp drugs); heterozygotes may be mated to clear animals\n- After a confirmed clinical case, do not repeat the parental mating and inform the buyer of the status

Check the exact panel offered by each laboratory, because not all of them include the eight variants for the Australian/Miniature American Shepherd. Complementary annual ocular examination (ECVO) for conditions not detected by DNA or of late onset, and especially for the HSF4 cataract, which is dominant with incomplete penetrance: a heterozygous animal may not have cataract at the initial examination and develop it later. MDR-1 sensitivity makes it necessary to review the list of prohibited drugs (ivermectin at antiparasitic doses, loperamide, several chemotherapeutic agents) before attributing the presentation to DM. NCL6 is only documented in the Australian Shepherd (two cases); in the Miniature American the test reports the genotype with no known prevalence. any treatment. DM is a diagnosis of exclusion: rule out spinal cord compression, disc herniation and neoplasia before attributing the presentation to DM. NCL6 is only documented in the Australian Shepherd (two cases); in the Miniature American the test reports the genotype with no known prevalence. attributing the presentation to SOD1. HUU causes urolithiasis due to urate/uric acid stones (not cystine); it is confirmed by urinalysis (uric acid) and dietary management. Differentiate natural brachyuria from tail amputation or trauma.

1. Awano T et al. 2009, SOD1 exón 2 y mielopatía degenerativa (PMID 19188595)
2. Mealey KL et al. 2001, deleción ABCB1/MDR1 y sensibilidad a ivermectina (PMID 11692082)
3. Mellersh CS et al. 2009, HSF4 y catarata dominante en Pastor australiano (PMID 19883468)
4. Zangerl B et al. 2006, PRCD y prcd-PRA (PMID 16938425)
5. Hytönen MK et al. 2009, braquiuria T-box (PMID 18854372)
6. Missense en CLN6 en un Pastor australiano con NCL (2011, PMID 21234413)
7. Majchrakova et al. 2023, alelos de enfermedad en Pastor australiano europeo incl. HUU (PMID 36848350)