Genetic basis of cranial cruciate ligament rupture (CCLR) in dogs

Abstract

Cranial Cruciate Ligament rupture (CCLR) is one of the most common forms of lameness in dogs and is analogous to rupture of the anterior cruciate ligament in humans, for which it can serve as a model. As there is a strong breed-related predisposition to CCLR in dogs, a study was undertaken to consider putative genetic components in susceptible dog breeds. A candidate gene, single nucleotide polymorphism (SNP) genotyping approach using MALDI-TOF mass spectrometry (Sequenom Ltd) was designed to investigate several CCLR-susceptible dog breeds and identify CCLR-associated genes/gene regions that may confer susceptibility or resistance. A meta-analysis was performed using the breed case/control candidate gene data to identify SNP associations that were common to the whole cohort of susceptible dogs. We identified SNPs in key genes involved in ligament strength, stability and extracellular matrix formation (COL5A1, COL5A2, COL1A1, COL3A1, COL11A1, COL24A1, FBN1, LOX, LTBP2) which were significantly associated with CCLR susceptibility across the dog breeds used in this study. These SNPs could have an involvement in CCLR due to a detrimental effect on ligament structure and strength. This is the first published candidate gene study that has revealed significant genetic associations with canine CCLR.

• Candidate genes
• cranial cruciate ligament rupture
• dogs

Acknowledgments

We thank Professor William Ollier at Manchester University, and the Centre for Integrated Genomic & Medical Research (CIGMR) for infrastructure support and collaboration, and to Dr Dan Carr and Dr Ana Alfirevic at the Wolfson Centre for Pharmacology at University of Liverpool, for Sequenom genotyping training and assistance. The authors acknowledge support of dog owners in the UK and North America, as well as the assistance of veterinary surgeons in collecting and submitting DNA samples.