Genetic panel of the bobtail (Old English Sheepdog) grouping five hereditary conditions: hereditary ataxia/juvenile cerebellar ataxia (HA, Purkinje cell degeneration), exercise-induced collapse (EIC, paralysis after intense exertion), primary ciliary dyskinesia (PCD, defect of respiratory cilia with recurrent bronchopneumonias and situs inversus), degenerative myelopathy (DM, SOD1 exon 2 variant) and sensitivity to ivermectin and other drugs (MDR1, defect of the P-glycoprotein of the blood-brain barrier).

Bobtail (Old English Sheepdog). PCD due to CCDC39 has an estimated carrier frequency of ~19% in European bobtails and ~7% in North American ones. MDR1 is present in the bobtail and other herding breeds. For HA and EIC the population frequencies are not reliably published (limited data). DM exon 2 has no published cases in the breed (included as a precaution). EIC/DNM1: validated in Bobtail by the discovering lab and testable via OFA; without a KC scheme or breed-specific publication.

- HA: cerebellar ataxia of juvenile-young adult onset (6 months-4 years), hypermetria, tremor, abnormal gait; slow progression\n- EIC: after intense exercise, stiffness of the pelvic limbs, ataxia, falling; with consciousness preserved\n- PCD: cough, rhinorrhoea, recurrent bronchopneumonias from the first weeks; possible situs inversus and sterility in males\n- DM: paresis/ataxia of the pelvic limbs in the adult, progression to paraplegia\n- MDR1: neurotoxicity from ivermectin, moxidectin, loperamide and other P-glycoprotein substrates

HA of the bobtail and the Gordon setter was associated with a variant in RAB24 (c.113A>C, p.Q38P) by Agler and colleagues (2014, PLoS Genetics), with a haplotype shared between the two breeds due to a founder effect. PCD of the bobtail was attributed to a nonsense mutation in CCDC39 by Merveille and colleagues (2011/2014, J Vet Intern Med), which allowed CCDC39 to be identified as a new human PCD gene. DM exon 2 of SOD1 is not documented with published cases in Bobtail (OMIA:000263 does not list the breed); it is included as a precaution (no cases published in the breed). MDR1 (ABCB1) is indeed present in the breed. Canine EIC is associated with the classic DNM1 variant (Patterson 2008); the mutation has also been identified in Bobtail/Old English Sheepdog among other breeds (validated by the laboratory that discovered the gene).

- Genotype breeding dogs for RAB24, CCDC39, SOD1 exon 2 and ABCB1 before mating\n- Do not cross two carriers for the same variant\n- A carrier may be crossed with a clear animal and the offspring intended for breeding must be tested\n- After a confirmed case, do not repeat the parental cross and communicate the status to the buyer\n- For homozygous MDR1: avoid ivermectin, moxidectin, loperamide and other P-gp substrate drugs; warn the veterinarian\n- For PCD: intensive respiratory monitoring in puppies and consider radiographic screening for situs in suspected animals

HA of the bobtail must be distinguished from other cerebellar ataxias (storage, degenerative, toxic). PCD can be confused with recurrent bacterial bronchitis or feline/canine asthma; the definitive diagnosis combines ciliary biopsy with electron microscopy and genetic test. MDR1 must be borne in mind when prescribing in bobtails, since standard doses of ivermectin can be neurotoxic in homozygotes.

1. Agler C et al. (2014) Canine hereditary ataxia in Old English Sheepdogs and Gordon Setters is associated with a defect in the autophagy gene encoding RAB24. PLoS Genet 10:e1003991. PMID: 24516392
2. Merveille AC et al. (2014) Clinical findings and prevalence of the mutation associated with primary ciliary dyskinesia in Old English Sheepdogs. J Vet Intern Med 28:771-8. PMID: 24773602
3. Patterson EE et al. 2008, mutación de DNM1 asociada al colapso inducido por el ejercicio (PMID 18806795)
4. Minor KM et al. 2011, DNM1 en Labrador y otras razas (PMID 21782486)
5. OFA: EIC/DNM1, Old English Sheepdog entre las razas con test registrado (criterio de inclusión: demanda de criadores del club USA; sin esquema UK KC)