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Osteochondrosis (OC) is an orthopedic syndrome of the joints that occurs in children and adolescents and domestic animals, particularly pigs, horses, and dogs. OC is the most frequent cause of leg weakness in rapidly growing pigs causing animal welfare issues and economic losses. In this study, a genome-wide association study (GWAS) was performed using the Porcine 60k SNPChip in animals of the breed Large White ( n  = 298) to identify chromosome regions and candidate genes associated with OC lesion scores. A total of 19 SNPs on chromosomes (SSC) 3, 5, 8, 10, 14, and 18 were significantly associated with OC lesion scores ( p -values ≤ 10 −5 ). The SNPs  MARC0098684 ,  MARC00840086 ,  MARC0093124 , and  ASGA0062794  at SSC14 36.1–38.2 Mb encompass a region of six linkage disequilibrium (LD) blocks. The most significant SNP  ASGA0062794  is located in a LD block spanning 465 kb and covering the gene encoding T-box transcription factor 5 ( TBX5 ). A SNP (c.54T > C) identified in  TBX5  was significantly associated with OC lesion scores in a single-marker analysis.  TBX5  c.54T > C showed highest LD with  ASGA00627974  ( r  2  = 0.96) and superior association with OC lesion scores over other SNPs when included in the genome scan, whereas its treatment as an additional fixed effect in the GWAS statistical model led to a drop of significance of nearby markers. Moreover, real-time PCR showed different transcript abundance of  TBX5  in healthy and defect cartilage. The results imply that the association signal obtained on SCC14 is largely attributable to  TBX5  c.54T > C likely to be in LD with a regulatory polymorphism of  TBX5 . The transcription factor  TBX5  interacts with  GJA5  and  MEF2C  both being involved in vascularization. This study provides evidence for epistatic interaction of  TBX5  and  MEF2C , thus supporting deficiency of blood supply to growth cartilage as being fundamental for the initiation of OC.

Genome-Wide Association Identifies TBX5 as Candidate Gene for Osteochondrosis Providing a Functional Link to Cartilage Perfusion as Initial Factor