Equine SNP50 BeadChip Research Articles

The identification of SNPs with indeterminate positions using the Equine SNP50 BeadChip

We have used linkage disequilibrium (LD) to identify single nucleotide polymorphisms (SNPs) on the Illumina Equine SNP50 BeadChip, which may be incorrectly positioned on the genome map. A total of 1201 Thoroughbred horses were genotyped using the Illumina Equine SNP50 BeadChip. LD was evaluated in a pairwise fashion between all autosomal SNPs, both within and across chromosomes. Filters were then applied to the data, firstly to identify SNPs that may have been mapped to the wrong chromosome and secondly to identify SNPs that may have been incorrectly positioned within chromosomes. We identified a single SNP on ECA28, which showed low LD with neighbouring SNPs but considerable LD with a group of SNPs on ECA10. Furthermore, a cluster of SNPs on ECA5 showed unusually low LD with surrounding SNPs. A total of 39 SNPs met the criteria for unusual within-chromosome LD. The results of this study indicate that some SNPs may be misplaced. This finding is significant, as misplaced SNPs may lead to difficulties in the application of genomic methods, such as homozygosity mapping, for which SNP order is important.

Genome-wide association studies for osteochondrosis in French Trotter horses1

A genome-wide association study for osteochondrosis (OC) in French Trotter horses was carried out to detect QTL using genotype data from the Illumina EquineSNP50 BeadChip assay. Analysis data came from 161 sire families of French Trotter horses with 525 progeny and family sizes ranging from 1 to 20. Genotypes were available for progeny (n = 525) and sires with at least 2 progeny (n = 98). Radiographic data were obtained from progeny using at least 10 views to reveal OC. All radiographic findings were described by at least 2 veterinary experts in equine orthopedics, and severity indices (scores) were assigned based on the size and location of the lesion. Traits used were a global score, the sum of all severity scores lesions (GM, quantitative measurement), and the presence or absence of OC on the fetlock (FM), hock (HM), and other sites (other). Data were analyzed using 2 mixed models including fixed effects, polygenic effects, and SNP or haplotype cluster effects. By combining results with both methods at moderate evidence of association threshold P < 5 × 10(-5), this genome-wide association study displayed 1 region for GM on the Equus caballus chromosome (ECA) 13, 2 for HM on ECA 3 and 14, and 1 for other on ECA 15. One region on ECA 3 for HM represented the most significant hit (P = 3 × 10(-6)). By comparing QTL between traits at a decreased threshold (P < 5 × 10(-4)), the 4 QTL detected for GM were associated to a QTL detected for FM or HM but never both. Another interesting result was that no QTL were found in common between HM and FM.

Results of a haplotype-based GWAS for recurrent laryngeal neuropathy in the horse

Recurrent laryngeal neuropathy (RLN) is a major upper-airway disease of horses that causes abnormal respiratory noise during exercise and can impair performance. Etiopathogenesis remains unclear but genetic factors have been suspected for many decades. The objective of this study was to identify risk loci associated with RLN. To that end we genotyped 234 cases (196 Warmbloods, 20 Trotters, 14 Thoroughbreds, and 4 Draft horses), 228 breed-matched controls, and 69 parents with the Illumina Equine SNP50 BeadChip. Using these data, we quantified population structure and performed single-marker and haplotype-based association studies, as well as family-based linkage analyses. We accounted for population stratification by modeling a random polygenic background effect with covariance structure estimated from genome-wide SNP data. Using the haplotype-based approach, we identified two genome-wide suggestive loci in Warmbloods, respectively on chromosomes 21 (p = 1.62 × 10(-6)) and 31 (p = 1.69 × 10(-5)). The two signals were driven by the enrichment of a "protective" haplotype in controls compared to cases.

Identification of the myostatin locus (MSTN) as having a major effect on optimum racing distance in the Thoroughbred horse in the USA

One hundred and eighty-nine Thoroughbred horses that had won Graded Stakes races in North America were genotyped with the Illumina Equine SNP50 bead chip. Association tests using PLINK to determine whether any SNPs were associated with optimum racing distance (7 furlongs and under compared to 8-10 furlongs) identified a locus on ECA18 that was statistically significant (-log 10 EMP2=1.63) at the genome-wide level following permutation analysis (10,000 permutations). Bioinformatic analysis revealed that the two ECA18 SNPs with the highest statistical significance spanned the MSTN (myostatin) locus. Mutations in myostatin in several mammalian species have been associated with increased muscling, with a preferential increase in fast glycolytic type IIB fibres, which would increase power potential. Thoroughbred horses that race over sprint distances, which are 5-7 furlongs, are often characterized by impressive hind quarter musculature, strongly suggesting that the association observed between the ECA18 SNPs and optimum race distance is mediated through MSTN.

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.

A genome-wide SNP-association study confirms a sequence variant (g.66493737C&gt;T) in the equine myostatin (MSTN) gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses

BackgroundThoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important.ResultsA genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of n = 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f) and middle-long distance (> 8 f) races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin (MSTN) [Punadj. = 6.96 × 10-6]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806) comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 (Punadj. = 1.61 × 10-9; PBonf. = 6.58 × 10-5). In a candidate gene study we have previously reported a SNP (g.66493737C>T) in MSTN associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the MSTN gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 (r2 = 0.86).ConclusionsComparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, P = 1.02 × 10-10; BIEC2-417495, Punadj. = 1.61 × 10-9). Functional investigations will be required to determine whether this polymorphism affects putative transcription-factor binding and gives rise to variation in gene and protein expression. Nonetheless, this study demonstrates that the g.66493737C>T SNP provides the most powerful genetic marker for prediction of race distance aptitude in Thoroughbreds.

Illumina Equine SNP50 Bead Chip Investigation of Adolescent idiopathic lordosis among American Saddlebred Horses

Illumina Equine SNP50 Bead Chip Investigation of Adolescent idiopathic lordosis among American Saddlebred Horses