A frameshift-deletion mutation in Reelin causes cerebellar hypoplasia in White Swiss Shepherd dogs.
RELN
Reelin
canine
cerebellar hypoplasia
dogs
mutation
neurological development
whole genome sequencing
Journal
Animal genetics
ISSN: 1365-2052
Titre abrégé: Anim Genet
Pays: England
ID NLM: 8605704
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
revised:
31
05
2023
received:
31
05
2023
accepted:
05
06
2023
medline:
14
9
2023
pubmed:
19
6
2023
entrez:
19
6
2023
Statut:
ppublish
Résumé
Cerebellar hypoplasia is a heterogeneous neurological condition in which the cerebellum is smaller than usual or not completely developed. The condition can have genetic origins, with Mendelian-effect mutations described in several mammalian species. Here, we describe a genetic investigation of cerebellar hypoplasia in White Swiss Shepherd dogs, where two affected puppies were identified from a litter with a recent common ancestor on both sides of their pedigree. Whole genome sequencing was conducted for 10 dogs in this family, and filtering of these data based on a recessive transmission hypothesis highlighted five protein-altering candidate variants - including a frameshift-deletion of the Reelin (RELN) gene (p.Val947*). Given the status of RELN as a gene responsible for cerebellar hypoplasia in humans, sheep and mice, these data strongly suggest the loss-of-function variant as underlying these effects. This variant has not been found in other dog breeds nor in a cohort of European White Swiss Shepherds, suggesting a recent mutation event. This finding will support the genotyping of a more diverse sample of dogs, and should aid future management of the harmful allele through optimised mating schemes.
Substances chimiques
Reelin Protein
0
Banques de données
RefSeq
['XM_038562771.1', 'XP_038418699.1', 'XM_038562736.1', 'XM_038566048.1', 'XM_038565308.1', 'XM_038567212.1']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
632-636Informations de copyright
© 2023 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.
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