Genetic Basis of Hereditary Ataxias in Canine Breeds

Hereditary ataxias in dogs encompass a spectrum of neurodegenerative conditions characterised by impaired coordination, balance deficits and cerebellar dysfunction. These disorders may arise from cerebellar cortical degeneration, spinocerebellar degeneration or multifocal degeneration with predominant spinocerebellar involvement. Advances in genomic technologies have revealed marked genetic heterogeneity, with both single‐gene and complex modes of inheritance implicated across breeds. Whole-genome and exome sequencing, together with linkage and homozygosity mapping, have identified pathogenic variants in genes encoding ion channels, cytoskeletal proteins and synaptic regulators. Examples include missense mutations in potassium and sodium channel subunits, repeat expansions in intronic regions and splice‐site mutations in genes essential for Purkinje cell integrity. The elucidation of these variants has informed genetic testing programmes, enabled targeted breeding strategies to reduce disease prevalence and provided naturally occurring models for human ataxias. Ongoing research seeks to refine genotype–phenotype correlations, explore modifier loci and develop potential therapeutic interventions.

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Genetic Basis of Hereditary Ataxias in Canine Breeds publication trend

The graph below shows the total number of articles in genetic basis of hereditary ataxias in canine breeds across all publications each year (not limited to Nature Index journals).

Technical terms

Autosomal recessive inheritance: A mode of inheritance in which two copies of a mutant allele (one from each parent) are required for disease manifestation.

Missense mutation: A single nucleotide change that results in the substitution of one amino acid for another in a protein sequence.

Homozygosity mapping: A genetic approach that identifies regions of the genome where affected individuals share identical segments inherited from a common ancestor.

Genome-wide association study (GWAS): An analysis that scans the genome for common genetic variants associated with a particular trait or disease.

Purkinje cell: A large, GABA-ergic neuron in the cerebellar cortex essential for motor coordination and balance.

Haplotype: A set of DNA variations or polymorphisms that tend to be inherited together on the same chromosome segment.

References

1. A Missense Variant in KCNJ10 in Belgian Shepherd Dogs Affected by Spongy Degeneration with Cerebellar Ataxia (SDCA1). G3: Genes, Genomes, Genetics (2017).
2. A Missense Variant in SCN8A in Alpine Dachsbracke Dogs Affected by Spinocerebellar Ataxia. Genes (2019).
3. Spinocerebellar ataxia in the Italian Spinone dog is associated with an intronic GAA repeat expansion in ITPR1. Mammalian Genome (2014).
4. Genome sequencing reveals a splice donor site mutation in the SNX14 gene associated with a novel cerebellar cortical degeneration in the Hungarian Vizsla dog breed. BMC Genomic Data (2016).
5. Phenotypic and genetic aspects of hereditary ataxia in dogs. Journal of Veterinary Internal Medicine (2023).
6. Cerebellar Abiotrophy in Australian Working Kelpies Is Associated with Two Major Risk Loci. Genes (2022).
7. Characterisation of canine KCNIP4: A novel gene for cerebellar ataxia identified by whole-genome sequencing two affected Norwegian Buhund dogs. PLOS Genetics (2020).