title: Genome-wide survey indicates involvement of loci on canine chromosomes 7 and 31 in patellar luxation in Flat-Coated Retrievers.
abstract: BACKGROUND
  Patellar luxation is an orthopedic disorder in which the patella moves out of its normal location within the femoral trochlea of the knee and it can lead to osteoarthritis, lameness, and pain. In dogs it is a heritable trait, with both environmental and genetic factors contributing to the phenotype. The prevalence of patellar luxation in the Dutch Flat-Coated Retriever population is 24%. In this study, we investigated the molecular genetics of the disorder in this population.
  
  
  RESULTS
  Genome-wide association analysis of 15,823 single nucleotide polymorphisms (SNPs) in 45 cases and 40 controls revealed that patellar luxation was significantly associated with a region on chromosome CFA07, and possibly with regions on CFA03, CFA31, and CFA36. The exons of the genes in these regions, 0.5 Mb combined, were analyzed further. These exons from 15 cases and a pooled sample from 15 controls were enriched using custom genomic hybridization arrays and analyzed by massive parallel DNA sequencing. In total 7257 variations were detected. Subsequently, a selection of 144 of these SNPs were genotyped in 95 Flat-Coated Retrievers. Nine SNPs, in eight genes on CFA07 and CFA31, were associated with patellar luxation (P <10-4). Genotyping of these SNPs in samples from a variety of breeds revealed that the disease-associated allele of one synonymous SNP in a pseudogene of FMO6 was unique to Flat-Coated Retrievers.
  
  
  CONCLUSIONS
  Genome-wide association analysis followed by targeted DNA sequencing identified loci on chromosomes 7 and 31 as being involved in patellar luxation in the Flat-Coated Retriever breed.
authors.forename: Ineke C M
authors.initials: IC
authors.lastname: Lavrijsen
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. P.A.J.Leegwater@uu.nl.
authors.forename: Peter A J
authors.initials: PA
authors.lastname: Leegwater
authors.forename: Chalika
authors.initials: C
authors.lastname: Wangdee
authors.forename: Frank G
authors.initials: FG
authors.lastname: van Steenbeek
authors.forename: Monique
authors.initials: M
authors.lastname: Schwencke
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Breur
authors.forename: Freek J
authors.initials: FJ
authors.lastname: Meutstege
authors.forename: Isaac J
authors.initials: IJ
authors.lastname: Nijman
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.forename: Henri C M
authors.initials: HC
authors.lastname: Heuven
authors.forename: Herman A W
authors.initials: HA
authors.lastname: Hazewinkel
mesh_terms: D000818:Animals; D001947:Breeding; D016022:Case-Control Studies; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs / Q000235:genetics*; D005091:Exons; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D008297:Male; D009426:Netherlands; D010329:Patella / Q000002:abnormalities*; D031222:Patellar Dislocation / Q000235:genetics / Q000662:veterinary*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA