Molecular mechanism

Acral Mutilation Syndrome (AMS) is a neurological condition that causes acral analgesia, typically presents at a young age. Proprioception, motor abilities, and spinal reflexes are unaffected, but intermittent prescence of intense licking, biting, and self-mutilation of the feet can occur (Plassais et al., 2016). The condition is inherited as an autosomal recessive condition however not every homozygous carrier of the mutation, an at risk dog, shows clinical signs of the disease. Plassais et al., (2016) first sequenced and identified the gene variant, chr4.g.70,875,561C\u0026gt;T, in 300 affected dogs and confirmed it was not present on the 900 unaffected dogs from 130 breeds.

Frequency has not yet been studied although in 250 clinically affected dogs across four sporting breeds they were distinctly genomically different from 900 unaffected dogs across 130 breeds (Correard et al., 2017).

Molecular mechanism

Degenerative Myelopathy (DM) is a progressive neurodegenerative disease of the spinal cord that typically affects dogs older than 8 years of age. The condition is characterised by progressive muscle atrophy and weakness of the limbs, advancing to tetraparesis (Awano et al., 2009) and eventually respiratory muscle failure (Nardone et al., 2016). DM is inherited as an autosomal recessive condition with variable expression between breeds. Missense mutation (c.118G\u0026gt;A; p.E40K) in exon 2 of the SOD1 gene on canine chromosome 31 (CFA31) was identified as the primary genetic risk factor by Awano et al., (2009). However, some dogs homozygous for the variant remain clinically unaffected, demonstrating incomplete penetrance. The SOD1.118G\u0026gt;A risk allele has been identified in 222 dog breeds. Burnese Mountain Dogs are also susceptible to this version of DM in addition to their breed-specific variant of DM, see DM- BMD variant for further information.

Molecular mechanism

Exercise-Induced Collapse (EIC) is characterised by transient episodes of muscle weakness and collapse triggered by strenuous exercise in otherwise healthy young dogs. Clinical signs typically develop within 2 minutes of completing 5–15 minutes of intense exercise and include hindlimb weakness, incoordination and an unsteady gait, which may progress to collapse, extensor rigidity, loss of consciousness and, in rare cases, death. Most dogs recover completely within approximately 30 minutes (Taylor et al., 2008; Patterson et al., 2008).
In retriever breeds, EIC is inherited as an autosomal recessive condition. Patterson et al., (2008) identified a missense mutation (c.767G\u0026gt;T; p.Arg256Leu) in exon 6 of the DNM1 gene on canine chromosome 9 (CFA9) as the causative variant. The variant has been reported in Labrador Retrievers, Chesapeake Bay Retrievers and Curly Coated Retrievers, allowing genetic testing to identify affected and carrier dogs. In a Midwestern US population of Labrador Retrievers, the variant was reported at a relatively high frequency, with 37% of dogs identified as carriers and 3% as homozygous affected, highlighting the importance of genetic testing to inform breeding decisions (Patterson et al., 2008). Although Border Collies can exhibit similar clinical signs, no causative variant has yet been identified for this breed; therefore, this genetic test is not applicable to Border Collies (Norton et al., 2021).

Molecular mechanism

Multidrug resistance (MDR1), or Ivermectin sensitivity, is an inherited drug sensitivity disorder caused by a mutation in the ABCB1 (MDR1) gene. The condition is inherited in an autosomal incomplete dominant manner, meaning dogs carrying one copy of the mutation may show increased sensitivity to certain medications, while dogs with two copies are at the greatest risk of severe adverse reactions (Mealey et al., 2003; Mealey \u0026amp; Meurs, 2008). The causative variant, first identified by Mealey et al., (2001), is a 4 bp deletion (c.296_299del4) that causes a frameshift and premature stop codon, resulting in loss of normal P-glycoprotein function.
P-glycoprotein is responsible for preventing certain drugs from accumulating within the brain. Dogs carrying the MDR1 mutation are unable to effectively transport these medications out of the central nervous system, making them susceptible to drug toxicity. Clinical signs can include tremors, excessive salivation, lethargy, disorientation, weakness, ataxia, blindness, seizures, coma, and in severe cases, death following exposure to affected medications (Mealey et al., 2001; Bissonnette et al., 2009; Gaens et al., 2019).
The MDR1 mutation is most commonly found in herding breeds, although its frequency varies considerably between breeds and populations (Mealey \u0026amp; Meurs, 2008; Gramer et al., 2011; Lerdkrai et al., 2021). Genetic testing helps identify dogs at increased risk, allowing appropriate medication choices to reduce the likelihood of adverse drug reactions.