Date of Award
Doctor of Philosophy
Max F. Rothschild
Michael G. Conzemius
Rupture of the cranial cruciate ligament (CCLR) in the dog is the most common cause of hind limb lameness. When CCLR occurs it results in instability in the knee leading to progressive, debilitating arthritis and lameness. Particular breeds of dogs (e.g. Newfoundland) are predisposed to CCLR while other breeds (e.g. Greyhound) have dramatically reduced frequency of this disorder supporting a heritable basis for the CCLR trait. For this study, we first estimated the economic impact to veterinary clients for the medical and surgical management for CCLR at 1.3 billion in the U.S. in 2003. Next, we examined medical records for a diagnosis of CCLR for all Newfoundlands that were presented to the Iowa State University Veterinary Teaching Hospital. One hundred sixty three Newfoundlands were evaluated from January 1, 1996, through December 31, 2002, and 22% were diagnosed with CCLR. In addition, a large-scale recruitment study was undertaken from the National Newfoundland Registry and local breeders and included 411 Newfoundlands, of which 92 (22%; 53 females and 39 males) were affected with CCLR and 319 (182 females and 137 males) were unaffected. The average inbreeding coefficient for those animals that were inbred was 0.05 (range 0.004--0.17), heritability was 0.27, and the segregation analysis predicted a recessive pattern of inheritance. The frequency of the recessive allele was 0.60 with 51% penetrance. Biological candidate gene analysis yielded single nucleotide polymorphisms (SNPs) in COL9A1, COL9A2, COMP, and FBN. Association analyses using restriction fragment length polymorphisms designed from the SNPs were performed on 90 dogs selected from a population of Newfoundlands; 45 unaffected and 45 affected with CCLR. There was no statistically significant association with the SNPs and CCLR status. Two cumulative genome scans were performed, first with 97 microsatellites (MSATs) and then, in a collaborative effort with UC-Davis, an additional 320 MSATs were used (MSAT interval approximately every 6.7 cM). Initial results indicate CCLR status association to seven chromosomes that had 4 or more markers with statistical significance; chromosomes 3, 5, 10, 14, 18, 23, and 27. Fine mapping these chromosomal regions should further narrow the list of potential CCLR candidate genes.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu
Vicki Lea Wilke
Wilke, Vicki Lea, "Analysis of genomic region(s) and gene(s) associated with cranial cruciate ligament rupture in the dog " (2006). Retrospective Theses and Dissertations. 1316.