Skeletal muscle mitochondrial bioenergetics and associations with myostatin genotypes in the Thoroughbred horse

Rooney, Mary F.; Porter, Richard K.; Katz, Lisa; Hill, Emmeline W.

doi:10.1371/journal.pone.0186247

Cited by 26 publications

(48 citation statements)

References 89 publications

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“…Thus, very the low polymorphic feature of the horse PRNP gene is worth noting. Furthermore, since previous studies indicated that Thoroughbred, which considered very inbred status, has several SNPs in the other gene, thus we presumed that very low polymorphic PRNP gene is not caused by inbred status of Thoroughbred [34,35]. However, study just in inbred species may skew data and limit interpretation.…”

Section: Discussionmentioning

confidence: 93%

The first report of polymorphisms and genetic characteristics of the prion protein gene (PRNP) in horses

Kim

Jeong

2018

Prion

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Prion diseases have a wide host range, but prion-infected cases have never been reported in horses. Genetic polymorphisms that can directly impact the structural stability of horse prion protein have not been investigated thus far. In addition, we noticed that previous studies focusing on horse-specific amino acids and secondary structure predictions of prion protein were performed for limited parts of the protein. In this study, we found genetic polymorphisms in the horse prion protein gene (PRNP) in 201 Thoroughbred horses. The identified polymorphism was assessed to determine whether this polymorphism impedes stability of protein using PolyPhen-2, PROVEAN and PANTHER. In addition, we evaluated horse-specific amino acids in horse and mouse prion proteins using same methods. We found only one single nucleotide polymorphism (SNP) in the horse prion protein, and three annotation tools predicted that the SNP is benign. In addition, horse-specific amino acids showed different effects on horse and mouse prion proteins, respectively. Abbreviations: PRNP: prion protein gene; SNP: single nucleotide polymorphism; CJD: Creutzfeldt-Jakob disease; CWD: chronic wasting disease; TME: transmissible mink encephalopathy; FSE: feline spongiform encephalopathy; MD: molecular dynamics; ER: endoplasmic reticulum; GPI: glycosylphosphatidylinositol; NMR: nuclear magnetic resonance; ORF: open reading frame; GWAS: genome-wide association study; NAPA: non-adaptive prion amplification; HMM: hidden Markov model; NCBI: National Center for Biotechnology Information.

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Section: Discussionmentioning

confidence: 93%

The first report of polymorphisms and genetic characteristics of the prion protein gene (PRNP) in horses

Kim

Jeong

2018

Prion

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“…The observation of high LD in this region, and the extremely long haplotypes, indicates that multiple genetic markers may be indicative of the presence of the SINE. [28,31] resulting in muscle fibre type variation [29,32], precocity [4] and rates of differential growth [5,33] in Thoroughbreds, which consequently influences measured speed variables [8] and distance aptitude at various stages of racing. We have shown here, in agreement with previous work discussed above, that although genomic variation at the MSTN locus is the main determinant of best race distance, there are other genetic markers that also contribute to the trait.…”

Section: Discussionmentioning

confidence: 99%

The contribution of myostatin (MSTN) and additional modifying genetic loci to race distance aptitude in Thoroughbred horses racing in different geographic regions

Hill

McGivney

Rooney

et al. 2019

Equine Veterinary Journal

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Summary Background Race distance aptitude in Thoroughbred horses is highly heritable and is influenced largely by variation at the myostatin gene (MSTN). Objectives In addition to MSTN, we hypothesised that other modifying loci contribute to best race distance. Study design Using 3006 Thoroughbreds, including 835 ‘elite’ horses, which were >3 years old, had race records and were sampled from Europe/Middle‐East, Australia/New Zealand, North America and South Africa, we performed genome‐wide association (GWA) tests and separately developed a genomic prediction algorithm to comprehensively catalogue additive genetic variation contributing to best race distance. Methods 48,896 single‐nucleotide polymorphism (SNP) genotypes were generated from high‐density SNP genotyping arrays. Heritability estimates, tests of GWA and genomic prediction models were derived for the phenotypes: average race distance, best race distance for elite, nonelite and all winning horses. Results Heritability estimates were high (hm2 = 0.51, best race distance – elite; hm2 = 0.42, best race distance – nonelite; hm2 = 0.40, best race distance – all) and most of the variation was attributed to the MSTN gene. MSTN locus SNPs were the most strongly associated with the trait and included BIEC2‐438999 (ECA18:66913090; P = 4.51 × 10−110, average race distance; P = 2.33 × 10−42, best race distance – elite). The genomic prediction algorithm enabled the inclusion of variation from all SNPs in a model that partitioned horses into short and long cohorts following assignment of MSTN genotype. Additional genes with minor contributions to best race distance were identified. Main limitations The nongenetic influence of owner/trainer decisions on placement of horses in suitable races could not be controlled. Conclusions MSTN is the single most important genetic contributor to best race distance in the Thoroughbred. Employment of genetic prediction models will lead to more accurate placing of horses in races that are best suited to their inherited genetic potential for distance aptitude.

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“…Human patients with COQ8A mutations suffered seizures and other neurological symptoms and showed reduced coenzyme Q within skeletal muscle (Jacobsen et al; Mollet et al, 2008). An eQTL for COQ8A in skeletal muscle has already been identified in horses, with a 227 bp SINE insertion in the promotor region of MSTN (g.66495326_66495327ins227) on ECA18 associated with increased expression of COQ8A (previously known as ADCK3 ) in Thoroughbreds (Rooney et al, 2017). However it should be noted that this increase in COQ8A expression did not appear to accompany an COQ8A protein abundance, with no difference in COQ8A protein abundance across genotypes (Rooney et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Identification of expression quantitative trait loci in the skeletal muscle of Thoroughbreds reveals heritable variation in expression of genes relevant to cofactor metabolism

Farries

Bryan

McGivney

et al. 2019

Preprint

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Summary While over ten thousand genetic loci have been associated with phenotypic traits and inherited diseases in genome-wide association studies, in most cases only a relatively small proportion of the trait heritability is explained and biological mechanisms underpinning these traits have not been clearly identified. Expression quantitative trait loci (eQTL) are subsets of genomic loci shown experimentally to influence gene expression. Since gene expression is one of the primary determinants of phenotype, the identification of eQTL may reveal biologically relevant loci and provide functional links between genomic variants, gene expression and ultimately phenotype. Skeletal muscle (gluteus medius) gene expression was quantified by RNA-seq for 111 Thoroughbreds (47 male, 64 female) in race training at a single training establishment sampled at two time-points: at rest (n = 92) and four hours after high-intensity exercise (n = 77); n = 60 were sampled at both time points. Genotypes were generated from the Illumina Equine SNP70 BeadChip. Applying a Benjamini-Hochberg corrected P-value threshold (PFDR < 0.05), association tests identified 3,583 cis-eQTL associated with expression of 1,456 genes at rest; 4,992 cis-eQTL associated with the expression of 1,922 genes post-exercise; 1,703 trans-eQTL associated with 563 genes at rest; and 1,219 trans-eQTL associated with 425 genes post-exercise. The gene with the highest cis-eQTL association at both time-points was the endosome-associated-trafficking regulator 1 gene (ENTR1; Rest: PFDR = 3.81 × 10−27, Post-exercise: PFDR = 1.66 × 10−24), which has a potential role in the transcriptional regulation of the solute carrier family 2 member 1 glucose transporter protein (SLC2A1). Functional analysis of genes with significant eQTL revealed significant enrichment for cofactor metabolic processes. These results suggest heritable variation in genomic elements such as regulatory sequences (e.g. gene promoters, enhancers, silencers), microRNA and transcription factor genes, which are associated with metabolic function and may have roles in determining end-point muscle and athletic performance phenotypes in Thoroughbred horses.

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Skeletal muscle mitochondrial bioenergetics and associations with myostatin genotypes in the Thoroughbred horse

Cited by 26 publications

References 89 publications

The first report of polymorphisms and genetic characteristics of the prion protein gene (PRNP) in horses

The first report of polymorphisms and genetic characteristics of the prion protein gene (PRNP) in horses

The contribution of myostatin (MSTN) and additional modifying genetic loci to race distance aptitude in Thoroughbred horses racing in different geographic regions

Identification of expression quantitative trait loci in the skeletal muscle of Thoroughbreds reveals heritable variation in expression of genes relevant to cofactor metabolism

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