School of Biodiversity, One Health & Veterinary Medicine

SBOHVM scientists have identified a new genetic variation in dogs which causes Leigh Syndrome in humans

In a new study published in Nature, SBOHVM scientists have used a new way to research genetic variations linked to Leigh syndrome in domestic dogs.

Subacute necrotizing encephalopathy, or Leigh syndrome, was first identified in human patients in 1951. This neurological disease affects the function of mitochondrial DNA, which affects cell and neurological functions, along with brain function. 113 genes have been linked to the Leigh syndrome spectrum in humans, 16 of which are linked to mitochondrial DNA, which is the powerhouse of cells that converts chemical energy from food. The first clinical signs are most frequently observed in children after a metabolic challenge, such as an acute infection. Patients show developmental regression, problems with movement and balance and difficulty swallowing. Clinical progression is then often rapid, and death may occur early in infancy. One of the main criteria for early diagnosis of the disease are changes identified in the brain by magnetic resonance imaging (MRI).

Until now, only 2 genetic variations linked to Leigh syndrome have been identified in Alaskan huskies along with a genetic variation that causes brain lesions in Yorkshire terriers.

In this study, two Jack-Russell Terrier × Chihuahua (Jack-Chi) littermates presented with clinical and magnetic resonance imaging (MRI) signs strongly resembling human disease of the Leigh syndrome spectrum.

Our SBOHVM scientists used a variety of methods to confirm the disease's presence, including the novel use of fruit flies to carry out genetic analysis and confirm the cellular factors that lead to it.

The study, which used a fruit fly model confirmed for the first time that a naturally occurring genetic variation affects mitochondrial and cell function.  This can be used to support future diagnosis and as a result, the unintentional breeding of carriers of the disease in dogs.  The research will also support future study of the disease in humans in future.

Full details of the research can be found in the Nature publication.

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First published: 22 February 2024