title: Evaluation of a fibrillin 2 gene haplotype associated with hip dysplasia and incipient osteoarthritis in dogs.
abstract: OBJECTIVE
  To determine whether a mutation in the fibrillin 2 gene (FBN2) is associated with canine hip dysplasia (CHD) and osteoarthritis in dogs.
  
  
  METHODS
  1,551 dogs. Procedures-Hip conformation was measured radiographically. The FBN2 was sequenced from genomic DNA of 21 Labrador Retrievers and 2 Greyhounds, and a haplotype in intron 30 of FBN2 was sequenced in 90 additional Labrador Retrievers and 143 dogs of 6 other breeds. Steady-state values of FBN2 mRNA and control genes were measured in hip joint tissues of fourteen 8-month-old Labrador Retriever-Greyhound crossbreeds.
  
  
  RESULTS
  The Labrador Retrievers homozygous for a 10-bp deletion haplotype in intron 30 of FBN2 had significantly worse CHD as measured via higher distraction index and extended-hip joint radiograph score and a lower Norberg angle and dorsolateral subluxation score. Among 143 dogs of 6 other breeds, those homozygous for the same deletion haplotype also had significantly worse radiographic CHD. Among the 14 crossbred dogs, as the dorsolateral subluxation score decreased, the capsular FBN2 mRNA increased significantly. Those dogs with incipient hip joint osteoarthritis had significantly increased capsular FBN2 mRNA, compared with those dogs without osteoarthritis. Dogs homozygous for the FBN2 deletion haplotype had significantly less FBN2 mRNA in their femoral head articular cartilage.
  
  
  CONCLUSIONS
  The FBN2 deletion haplotype was associated with CHD. Capsular gene expression of FBN2 was confounded by incipient secondary osteoarthritis in dysplastic hip joints. Genes influencing complex traits in dogs can be identified by genome-wide screening, fine mapping, and candidate gene screening.
authors: Department of Clinical Sciences, College of Arts and Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
authors: Steven G
authors: SG
authors: Friedenberg
authors: Lan
authors: L
authors: Zhu
authors: Zhiwu
authors: Z
authors: Zhang
authors: Wendy van den Berg
authors: Wv
authors: Foels
authors: Peter A
authors: PA
authors: Schweitzer
authors: Wei
authors: W
authors: Wang
authors: Patricia J
authors: PJ
authors: Fisher
authors: Nathan L
authors: NL
authors: Dykes
authors: Elizabeth
authors: E
authors: Corey
authors: Margaret
authors: M
authors: Vernier-Singer
authors: Seung-Woo
authors: SW
authors: Jung
authors: Xihui
authors: X
authors: Sheng
authors: Linda S
authors: LS
authors: Hunter
authors: Sean P
authors: SP
authors: McDonough
authors: George
authors: G
authors: Lust
authors: Stuart P
authors: SP
authors: Bliss
authors: Ursula
authors: U
authors: Krotscheck
authors: Teresa M
authors: TM
authors: Gunn
authors: Rory J
authors: RJ
authors: Todhunter
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000000981:diagnostic imaging / Q000235:genetics*; D004285:Dogs / Q000235:genetics / Q000502:physiology; D005260:Female; D000071837:Fibrillins; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006619:Hip Dysplasia, Canine / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics* / Q000502:physiology; D009154:Mutation; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000235:genetics / Q000662:veterinary*; D012333:RNA, Messenger / Q000235:genetics; D011859:Radiography
chemical_list: D000071837:Fibrillins; D008840:Microfilament Proteins; D012333:RNA, Messenger