A frameshift-deletion mutation in Reelin causes cerebellar hypoplasia in White Swiss Shepherd dogs

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dc.citation.issue5
dc.citation.volume54
dc.contributor.authorLittlejohn MD
dc.contributor.authorSneddon N
dc.contributor.authorDittmer K
dc.contributor.authorKeehan M
dc.contributor.authorStephen M
dc.contributor.authorDrögemüller M
dc.contributor.authorGarrick D
dc.coverage.spatialEngland
dc.date.accessioned2024-05-29T23:26:20Z
dc.date.available2024-05-29T23:26:20Z
dc.date.issued2023-10
dc.description.abstractCerebellar 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.
dc.description.confidentialfalse
dc.edition.editionOctober 2023
dc.format.pagination632-636
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/37334487
dc.identifier.citationLittlejohn 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).
dc.identifier.doi10.1111/age.13336
dc.identifier.eissn1365-2052
dc.identifier.elements-typejournal-article
dc.identifier.issn0268-9146
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/69700
dc.languageeng
dc.publisherJohn Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics
dc.publisher.urihttps://onlinelibrary.wiley.com/doi/10.1111/age.13336
dc.relation.isPartOfAnim Genet
dc.rights(c) The author/sen
dc.rights.licenseCC BY-NCen
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/en
dc.subjectRELN
dc.subjectReelin
dc.subjectcanine
dc.subjectcerebellar hypoplasia
dc.subjectdogs
dc.subjectmutation
dc.subjectneurological development
dc.subjectwhole genome sequencing
dc.subjectAnimals
dc.subjectDogs
dc.subjectHumans
dc.subjectCerebellum
dc.subjectDog Diseases
dc.subjectFrameshift Mutation
dc.subjectMammals
dc.subjectMutation
dc.subjectSequence Deletion
dc.subjectSwitzerland
dc.subjectReelin Protein
dc.titleA frameshift-deletion mutation in Reelin causes cerebellar hypoplasia in White Swiss Shepherd dogs
dc.typeJournal article
pubs.elements-id462361
pubs.organisational-groupOther
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