|Keywords:||Diergeneeskunde; chondrodysplasia, short stature, endochondral ossification, fgf4 retrogene, FGF4, FGFR3, IHH, ILK, NPR2, DDR2, SPRED2, SHOX, linkage analysis, gene sequencing, downstream enhancer element, CpG-methylation, X-inactivation, CGG-repeat, SNPs, canine, human.|
|Full text PDF:||http://dspace.library.uu.nl:8080/handle/1874/179026|
Chondrodysplasia is characterized by a disturbed cartilage growth, endochondral ossification or both, leading to short stature. Besides disproportionately short front legs there is malformation of the elbow joint and carpus, which reduces the range of motion and ultimately leads to osteoarthrosis of the joints. It is a hereditary disease but the mode of inheritance is still unknown. In the Bouvier des Flandres a genetically interesting phenomenon exists in that several litters are completely affected, while both parents are healthy. The well-being of affected animals is often severely compromised, making it essential to diminish the prevalence of this disease through specific breeding advice. The aim of this study was to investigate the role of candidate genes as cause of chondrodysplasia in the Labrador Retriever and Bouvier des Flandres. In 2009 a fibroblast growth factor retrogene was demonstrated by Parker et al. to be strongly associated with chondrodysplasia in chondrodysplastic breeds, like the Basset Hound and Pembroke Welsh Corgi. However, here it was found that affected Labradors (n=13) and Bouviers (n=24) of the research population did not exhibit the specific retrogene. Linkage analysis using microsatellite markers was then conducted on a number of candidate genes. Based on LOD-scores, most of these candidate genes were excluded or were highly unlikely to play a role in this disease. Bouvier patients display an extraordinary phenotype that differs from that of Labrador patients. It resembles the phenotype of humans with Leri-Weill dyschondrosteosis and Langer Mesomelic dysplasia, two types of chondrodysplasia caused by mutations or deletions of the SHOX-gene. Therefore, the SHOX gene was denominated as an important candidate gene and was investigated, performing linkage analysis, gene sequencing and determination of the degree of CpG-methylation to check for epigenetic silencing. Further research of the SHOX-gene needs to be conducted in the future.