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Hereditary Ataxia Bobtail & Gordon Setter Type (HA)
| Acronym: | HA |
| Gene: | RAB24 |
| Mutation: | c.113A>C |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Hereditary Ataxia Bobtail and Gordon Setter Type (HA) is a congenital neurodegenerative disorder occurring in Bobtail and Gordon Setter dog breed. Hereditary ataxia is a heterogeneous group of movement disorders. Within this group, forms of hereditary ataxia differ from each other in several ways, such as the age of onset or mode of inheritance. They can be inherited as autosomal dominant, recessive, or X-linked traits. HA inherited as a dominant disorder is also known as spinocerebellar ataxia or SCA. Until now, hereditary cerebellar degenerative disorders have been identified in over 20 breeds of dogs and are most commonly inherited as an autosomal recessive trait. Cerebellum, also known as the ”little brain”, is a part of the brain that has an important role in motor control, in a way that it contributes to coordination, precision, and accurate timing. One of the cells present in the cerebellum is the Purkinje cells or Purkinje neurons. Together, the Purkinje cells and the cerebellum have an essential role in the body’s motor function.
Hereditary ataxia is characterized by the slow degeneration of the cerebellar cortex, with dramatic Purkinje neuron loss which results in a progressive gaint dysfunction. Hereditary Ataxia Bobtail and Gordon Setter Type is an early onset disorder that is first noted in juvenile to young adult dogs, between the ages of six months to four years. Common clinical signs that affected dogs develop are hypermetria, a truncal sway, and intention tremor, and signs that progress to cause severe gaint disturbances. Histopathological examination reveals loss of Purkinje cell, granule cell, and molecular layer neurons, which causes atrophy of the cerebellar cortex. Hereditary Ataxia Bobtail and Gordon Setter Type (HA) is linked to a mutation in RAB24, the gene encoding for GTPase Rab24 protein. This enzyme has an important role in membranous transport within the cell and cell division. It is highly expressed in the brain, unlike the rest of the body where its expression is at low levels.
The disorder is inherited as an autosomal recessive disorder. Healthy parents of an affected puppy are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the Hereditary Ataxia Bobtail and Gordon Setter Type (HA). At conception, when mating two carrier dogs, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Agler C, Nielsen DM, Urkasemsin G, Singleton A, Tonomura N, 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(2): e1003991. doi:10.1371/journal.pgen.1003991.