Baird Arabella Elizabeth Gardiner, Carter Stuart D, Innes John F, Ollier William E, Short Andrea D
Department of Infection Biology, Institute of Infection and Global Health, School of Veterinary Science, University of Liverpool , Liverpool , UK .
Connect Tissue Res. 2014 Aug;55(4):275-81. doi: 10.3109/03008207.2014.910199. Epub 2014 Apr 25.
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.
颅交叉韧带断裂（CCLR）是犬类跛行最常见的形式之一，类似于人类前交叉韧带断裂，犬类CCLR可作为人类前交叉韧带断裂的模型。由于犬类CCLR存在强烈的品种相关易感性，因此开展了一项研究，以探讨易感犬种中可能的遗传因素。设计了一种候选基因单核苷酸多态性（SNP）基因分型方法，使用基质辅助激光解吸电离飞行时间质谱（Sequenom有限公司）来研究几种CCLR易感犬种，并确定可能导致易感性或抗性的CCLR相关基因/基因区域。使用品种病例/对照候选基因数据进行荟萃分析，以确定整个易感犬队列共有的SNP关联。我们在参与韧带强度、稳定性和细胞外基质形成的关键基因（COL5A1、COL5A2、COL1A1、COL3A1、COL11A1、COL24A1、FBN1、LOX、LTBP2）中鉴定出SNP，这些SNP与本研究中使用的犬种的CCLR易感性显著相关。由于对韧带结构和强度有不利影响，这些SNP可能与CCLR有关。这是首次发表的揭示与犬类CCLR存在显著遗传关联的候选基因研究。
