Solving the “cold case” of Dalmatian chondrodysplasia

Presenter Suvi Mäkeläinen
Authors Mäkeläinen Suvi (1,*), Ekman Stina (2), Hedhammar Åke (3), Hansson Kerstin (3), Bergström F. Tomas (1)
Affiliations 1. Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Sweden. 2. Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Sweden. 3. Department of Clinical Sciences, Swedish University of Agricultural Sciences, Sweden. * Current address Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Sweden.
Presentation Type Talk


Skeletal dysplasias represent a heterogeneous group of inherited diseases causing abnormalities in cartilage and bone, and resulting in varying degrees of short stature and dwarfism. In humans, 771 different types of skeletal dysplasias, associated with 552 genes, have been identified to date. Several dog breeds have been reported to suffer from different types of these disorders, leading to disproportionate dwarfism as the main phenotypic feature. To our knowledge, the first cases of Dalmatian dogs with skeletal dysplasias were observed in the early 80’s in Sweden, and multiple affected litters were born during the 80’s and 90’s. By the time, the phenotype was carefully investigated using radiological and histopathological examinations. Now 30 years later, we sequenced the genomes of samples collected in 1992 and identified a strong candidate variant leading to a premature stop codon. The variant is predicted to trigger non-sense mediated decay, a cellular process removing too short gene products and preventing the production of truncated protein products. Mutations in the identified gene cause a corresponding human disease, acromesomelic dysplasia, affecting the growth of the lower arms and legs of young children. Revisiting the clinical investigation from the 90s and the recent genomic analyses of the same samples, suggests that this cold case of dwarfism in Dalmatian dogs has now been solved.