Oral Presentation Society for Molecular Biology and Evolution Conference 2016

A dominant TRPV4 variant underlies osteochondrodysplasia in Scottish fold cats (#72)

Barbara Gandolfi 1 , Sultan Alamri 2 , Bill G Darby 3 , Jim C Lattimer 1 , Richard Malik 4 , Claire M Wade 5 , Leslie A Lyons 1 , Jianlin Cheng 6 , John F Bateman 2 , Peter McIntyre 3 , Shireen R Lamande 2 , Bianca Haase 5
  1. Veterinary Medicine and Surgery, University of Missouri-Columbia, Columbia, USA
  2. Murdoch Childrens Research Institute, Melbourne, VIC, Australia
  3. School of Medical Sciences, RMIT University, Bundoora, VIC, Australia
  4. Centre for Veterinary Education, University of Sydney, Sydney, NSW, Australia
  5. Veterinary Science, University of Sydney, Sydney, NSW, Australia
  6. Computer Science Department, Informatics Institute, C. Bond Life Science Center, University of Missouri, Columbia, MO, USA

Inherited osteoarthropathy in human is characterized by a progressive arthropathy of fingers and toes and while affected individuals appear normal at birth, they develop severe arthropathy by adulthood. The distinctive and defining physical trait of the Scottish Fold cat breed is the characteristic ear phenotype. Scottish fold cats have ears which fold forward, this presumably reflecting lack of resilience of the pinna and auricular cartilages. There is convincing evidence that Scottish Fold cats have an underlying congenital defect which affects the structure and function of cartilage, resulting in progressive bone, joint and cartilage abnormalities that subsequently lead to progressive dysfunction. Cats develop a variable osteochondrodystrophy causing abnormal bone development likely through defective endochondral ossification, progressive osteoarthritis and lameness. Pedigree analyses and breeding experiments have shown that the trait is inherited as an autosomal monogenic dominant trait with variable expression. We applied a whole-genome SNP association mapping approach using a total of 78 cats (53 Scottish fold cats and 25 Scottish shorthairs). DNA samples were genotyped with the feline Illumina 63kSNP genotyping microarray. A genome-wide significant association on chromosome D3 has been identified and confirmed with fine structure mapping. A candidate gene analysis revealed a missense mutation in a calcium channel associated with skeletal dysplasia in humans.