A frameshift-deletion mutation in Reelin causes cerebellar hypoplasia in White Swiss Shepherd dogs.
Publisher DOI
PubMed ID
37334487
Abstract
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.
Date Issued
2023-10
Publication Type
Article
Subject(s)
Subjects
RELN Reelin canine cerebellar hypoplasia dogs mutation neurological development whole genome sequencing
Language(s)
en
Author(s)
Littlejohn, Mathew D | |
Sneddon, Nick | |
Dittmer, Keren | |
Keehan, Mike | |
Stephen, Melissa | |
Garrick, Dorian |
Additional Credits
Journal
Animal genetics
Publisher
Wiley
ISSN
1365-2052
Access(Rights)
open.access