title: Identification of 2 loci associated with development of myxomatous mitral valve disease in Cavalier King Charles Spaniels.
abstract: Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs. It is characterized by chronic progressive degenerative lesions of the mitral valve. The valve leaflets become thickened and prolapse into the left atrium resulting in mitral regurgitation (MR). MMVD is most prevalent in small to medium sized dog breeds, Cavalier King Charles Spaniels (CKCS) in particular. The onset of MMVD is highly age dependent, and at the age of 10 years, nearly all CKCS are affected. The incidence of a similar disease in humans-mitral valve prolapse-is 1-5%. By defining CKCSs with an early onset of MMVD as cases and old dogs with no or mild signs of MMVD as controls, we conducted a genome-wide association study (GWAS) to identify loci associated with development of MMVD. We have identified a 1.58 Mb region on CFA13 (P(genome) = 4.0 × 10(-5)) and a 1.68 Mb region on CFA14 (P(genome) = 7.9 × 10(-4)) associated with development of MMVD. This confirms the power of using the dog as a model to uncover potential candidate regions involved in the molecular mechanisms behind complex traits.
authors.affiliation: Department of Animal and Veterinary Basic Sciences, Faculty of Life Sciences, University of Copenhagen, Groennegaardsvej 3, 1870 Frederiksberg C, Denmark.
authors.forename: Majbritt Busk
authors.initials: MB
authors.lastname: Madsen
authors.forename: Lisbeth Høier
authors.initials: LH
authors.lastname: Olsen
authors.forename: Jens
authors.initials: J
authors.lastname: Häggström
authors.forename: Katja
authors.initials: K
authors.lastname: Höglund
authors.forename: Ingrid
authors.initials: I
authors.lastname: Ljungvall
authors.forename: Torkel
authors.initials: T
authors.lastname: Falk
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wess
authors.forename: Hannah
authors.initials: H
authors.lastname: Stephenson
authors.forename: Joanna
authors.initials: J
authors.lastname: Dukes-McEwan
authors.forename: Valérie
authors.initials: V
authors.lastname: Chetboul
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Gouni
authors.forename: Helle Friis
authors.initials: HF
authors.lastname: Proschowsky
authors.forename: Susanna
authors.initials: S
authors.lastname: Cirera
authors.forename: Peter
authors.initials: P
authors.lastname: Karlskov-Mortensen
authors.forename: Merete
authors.initials: M
authors.lastname: Fredholm
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005060:Europe; D055106:Genome-Wide Association Study; D005838:Genotype; D008945:Mitral Valve Prolapse / Q000235:genetics / Q000662:veterinary*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013045:Species Specificity