Littlejohn MDSneddon NDittmer KKeehan MStephen MDrögemüller MGarrick D2024-05-292024-05-292023-10Littlejohn MD, Sneddon N, Dittmer K, Keehan M, Stephen M, Drögemüller M, Garrick D. (2023). A frameshift-deletion mutation in Reelin causes cerebellar hypoplasia in White Swiss Shepherd dogs.. Anim Genet. 54. 5. (pp. 632-636).0268-9146https://mro.massey.ac.nz/handle/10179/69700Cerebellar 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.(c) The author/shttps://creativecommons.org/licenses/by-nc/4.0/RELNReelincaninecerebellar hypoplasiadogsmutationneurological developmentwhole genome sequencingAnimalsDogsHumansCerebellumDog DiseasesFrameshift MutationMammalsMutationSequence DeletionSwitzerlandReelin ProteinJournal article10.1111/age.133361365-2052CC BY-NCjournal-article632-636https://www.ncbi.nlm.nih.gov/pubmed/37334487