Equine developmental orthopaedic diseases--a genome-wide association study of first phalanx plantar osteochondral fragments in Standardbred trotters.

Palmar/plantar osteochondral fragments (POF) in fetlock joints commonly affect and influence the athletic performance of horses. In this study, we used the Equine SNP50 BeadChip® to perform a genome-wide association study of metatarsophalangeal POF in 176 Norwegian Standardbred trotter yearlings. Putative quantitative trait loci (QTL) for medial and/or lateral POF, and medial POF only were identified on ECA1, 2, 7, 9 and 31, whereas for lateral POF, only on ECA7, 11, 27 and X. The moderate number of QTL evidences a complex inheritance and suggests various genes controlling POF development in medial and lateral locations.

Genome-wide association analysis of osteochondrosis of the tibiotarsal joint in Norwegian Standardbred trotters.

Osteochondrosis (OC), a disturbance in the process of endochondral ossification, is by far the most important equine developmental orthopaedic disease and is also common in other domestic animals and humans. The purpose of this study was to identify quantitative trait loci (QTL) associated with osteochondrosis dissecans (OCD) at the intermediate ridge of the distal tibia in Norwegian Standardbred (SB) using the Illumina Equine SNP50 BeadChip whole-genome single-nucleotide polymorphism (SNP) assay. Radiographic data and blood samples were obtained from 464 SB yearlings. Based on the radiographic examination, 162 horses were selected for genotyping; 80 of these were cases with an OCD at the intermediate ridge of the distal tibia, and 82 were controls without any developmental lesions in the joints examined. Genotyped horses descended from 22 sires, and the number of horses in each half-sib group ranged from 3 to 14. The population structure necessitated statistical correction for stratification. When conducting a case-control genome-wide association study (GWAS), mixed-model analyses displayed regions on chromosomes (Equus callabus chromosome - ECA) 5, 10, 27 and 28 that showed moderate evidence of association (P ≤ 5 × 10(-5); this P-value is uncorrected i.e. not adjusted for multiple comparisons) with OCD in the tibiotarsal joint. Two SNPs on ECA10 represent the most significant hits (uncorrected P=1.19 × 10(-5) in the mixed-model). In the basic association (chi-square) test, these SNPs achieved statistical significance with the Bonferroni correction (P=0.038) and were close in the permuted logistic regression test (P=0.054). Putative QTL on ECA 5, 10, 27 and 28 represent interesting areas for future research, validation studies and fine mapping of candidate regions. Results presented here represent the first GWAS of OC in horses using the recently released Illumina Equine SNP50 BeadChip.

Heritability estimates of tarsocrural osteochondrosis and palmar/plantar first phalanx osteochondral fragments in Standardbred trotters.

REASONS FOR PERFORMING STUDY: The pathogenesis of osteochondrosis (OC) and palmar/plantar first phalanx osteochondral fragments (POFs) is multifactorial, but specific knowledge of heritability is limited. OBJECTIVES: To improve the precision of heritability estimates and to estimate the genetic correlation between tarsocrural OC and POFs in Standardbred trotters. Further aims were to examine whether the prevalence of OC/POFs was different in the American and French lineages that have contributed to the Norwegian population, and if the prevalence was affected by heterozygosity. STUDY DESIGN: Retrospective cohort study. METHODS: Categorical data on tarsocrural OC and POFs from 2 radiographic studies performed in 1989 and 2007/2008 (n = 1217) were analysed with sire threshold models that included 230 sires. RESULTS: Heritability of OC at the distal intermediate ridge of the tibia and/or the lateral trochlear ridge of the talus was estimated at 0.29 ± 0.15. For OC at the distal intermediate ridge of the tibia only, the estimate was 0.40 ± 0.17. Heritability of POFs in all 4 limbs was estimated at 0.23 ± 0.13; for metatarsophalangeal POFs this was 0.26 ± 0.13 and for medial metatarsophalangeal POFs 0.32 ± 0.14. Estimates of genetic correlation between OC and POFs ranged from 0.68 ± 0.27 to 0.73 ± 0.28 but were not significantly different from a zero-genetic correlation. Effects of lineages or heterozygosity were not observed. CONCLUSIONS AND POTENTIAL RELEVANCE: This study confirmed a moderate to high heritability of tarsocrural OC and POF, providing further evidence of the heritable nature of these diseases. Examination of specific lesions yielded the highest heritability; therefore, breeding programmes and future genome-analysis studies should focus on predilection sites rather than the entire disease complex.

Osteochondrosis and osteochondral fragments in Standardbred trotters: prevalence and relationships.

REASONS FOR PERFORMING STUDY: Developmental orthopaedic diseases (DOD) such as osteochondrosis (OC)/osteochondrosis dissecans (OCD), palmar/plantar osteochondral fragments (POF), ununited palmar/plantar eminences (UPE) and dorsoproximal first phalanx fragments are well recognised in the horse. Aetiopathogeneses are controversial and molecular genetic screening of DNA has recently been employed for their elucidation. Precise phenotypic definition and knowledge of breed-specific prevalence and interrelations are essential for the interpretation of following genomic studies in Standardbred trotters. OBJECTIVES: To assess the prevalence, trend of development and interrelation of DOD in tarsocrural, metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints in Standardbred trotters. METHODS: The tarsocrural and MCP/MTP joints of 464 Norwegian Standardbred yearlings were radiographed and the prevalence and interrelation of osteochondral lesions calculated. RESULTS: Osteochondral lesions were diagnosed in 50.7% of the horses. The prevalence of tarsocrural OC/OCD at the distal intermediate ridge of the tibia (DIT) and the lateral trochlear ridge of the talus (LTT) was 19.3%. The prevalence of OC/OCD in MCP joints was 3.6%, whereas those of POF and UPE in MCP/MTP joints were 23.1 and 3.9%, respectively. Interrelation was evident for 1) most equivalent lesions in joint homologues, 2) OCD DIT and OCD LTT and 3) POF and UPE. Lesions in hock and fetlock joints were generally not significantly associated. CONCLUSIONS: The prevalence of tarsocrural OC/OCD in Norwegian Standardbreds is apparently increasing, whereas that of other articular DOD appears stable. Association analyses verify bilateralism for most equivalent lesions and suggest aetiological resemblance also between other lesions. The absence of a significant association between tarsocrural OCD and POF implies that the lesions must be considered statistically different disorders. POTENTIAL RELEVANCE: The prevalence results emphasise that DOD should be considered in Standardbred breeding regimens (e.g. by sire selection subsequent to progeny testing). Also, improved phenotypic definitions will help elucidate the true causal genes in following genomic studies.