« Genetic and genomic analyses of neurological diseases in dogs as a model of rare human diseases ».

The identification of genetic mutations involved in rare diseases is a prerequisite for a better understanding, therapies and care to patients. To this aim, animal models declaring spontaneous diseases, homologous to human diseases are very promising. Dogs spontaneously develop genetic diseases, rare in humans, but frequent in some dog breeds, which simplifies the genetic analyzes. My thesis focused on two neurological diseases: epilepsy and neuropathy.

For epilepsy, the goal was to identify genetic variants from genotyping data and sequencing of whole genome of dogs from two predisposed breeds. A disease-related locus has been identified in one breed and candidate point mutations and structural variants were identified in the two breeds and are being validated by targeted sequencing.

For neuropathy, the team previously identified a mutation upstream of the GDNF gene, responsible for sensory neuropathy in hunting dogs. I participated to the functional validation of this mutation. In addition, GDNF being an excellent candidate gene for human neuropathies, I sequenced this gene in 111 patients and extracted GDNF variants from a database of exomes and genomes from more than 600 patients. I identified 21 rare or unknown variants and prioritized them according to their in silico predicted impacts.

These two projects, combining genetics, genomics and functional analyses, in humans and dogs, show the dog's potential for identifying candidate genes in rare and / or complex diseases in humans.

Jury members :

  •  Mme Valérie DELAGUE, Directeur de Recherche INSERM, Université d'Aix-Marseille, Rapporteur
  •  M. Gaëtan LESCA, Maitre de conférences, Praticien hospitalier, Groupement Hospitalier Est, BRON, Rapporteur
  •  Mme Anne-Sophie LIA, Maitre de conférences, Praticien hospitalier, Université de Limoges, Examinateur
  •  M. Eric LEGUERN, Professeur d'université, Praticien hospitalier, Hôpital Pitié-Salpêtrière, Examinateur
  •  Mme Catherine ANDRÉ, Directeur de Recherche au CNRS, IGDR, Directeur de thèse
  •  Mme Pascale QUIGNON, Maitre de conférences, IGDR, Co-directeur de thèse
  •  Mme Catherine ESCRIOU, Maitre de conférences, Vet-agro Sup, Lyon, Membre invité

French defense

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