Abstract: 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 ( = 92) and four hours after high-intensity exercise ( = 77); = 60 were sampled at both time points. Genotypes were generated from the Illumina Equine SNP70 BeadChip. Applying a False Discovery Rate (FDR) corrected -value threshold ( < 0.05), association tests identified 3,583 -eQTL associated with expression of 1,456 genes at rest; 4,992 -eQTL associated with the expression of 1,922 genes post-exercise; 1,703 -eQTL associated with 563 genes at rest; and 1,219 -eQTL associated with 425 genes post-exercise. The gene with the highest -eQTL association at both time-points was the endosome-associated-trafficking regulator 1 gene (; Rest: = 3.81 × 10, Post-exercise: = 1.66 × 10), 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. The incorporation of the eQTL identified with genome and transcriptome-wide association may reveal useful biological links between genetic variants and their impact on traits of interest, such as elite racing performance and adaptation to training.
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This study delves into the genetic determinants of traits and inherited diseases in Thoroughbred horses. By examining gene expression in skeletal muscle before and after high-intensity exercise, the research identified certain genetic loci that influence gene expression and may have an impact on metabolic function and athletic performance.
Understanding the Research Objective
The goal of this research was to better understand the genetic basis behind phenotypic traits and inherited diseases. Phenotypic traits are discernible characteristics that are the outcome of interactions between genes and environment.
Considering how gene expression influences these traits can reveal biologically significant genetic loci linked to the traits’ manifestation.
The study centered on Thoroughbred horses, specifically looking at skeletal muscle gene expression at rest and after intense exercise. The researchers hoped that these examinations could unveil functional links between genomic variants, gene expression, and phenotypes, like elite racing performance and training adaptation.
The Methodology Employed
The researchers measured gene expression in the gluteus medius (a muscle) of 111 Thoroughbreds through RNA sequencing. These horses were all in race training, and samples were taken both at rest and four hours after high-intensity exercise.
Traits of interest were identified using False Discovery Rate (FDR) corrected p-value threshold, locating eQTL (expression quantitative trait loci) which influence gene expression and may reveal biologically relevant variants.
Research Findings
The study identified thousands of eQTL associated with gene expression at rest and post-exercise. These eQTL corresponded with a significant number of genes.
The gene with the most significant association was the endosome-associated-trafficking regulator 1 gene, which may play a role in regulating the glucose transporter protein SLC2A1.
Functional analysis revealed that genes with significant eQTL are enriched for cofactor metabolic processes, suggesting heritable variation in elements like gene regulatory sequences, microRNA, and transcription factor genes that could be associated with metabolic function.
Implications of the Findings
The findings suggest that heritable variations in certain genomic elements may influence muscle and athletic performance phenotypes in Thoroughbred horses.
Linking these identified eQTL with wider genomic and transcriptomic databases could reveal biologically significant correlations between genetic variations and their impact on notable traits such as racing performance and training adaptation.
Cite This Article
APA
Farries G, Bryan K, McGivney CL, McGettigan PA, Gough KF, Browne JA, MacHugh DE, Katz LM, Hill EW.
(2019).
Expression Quantitative Trait Loci in Equine Skeletal Muscle Reveals Heritable Variation in Metabolism and the Training Responsive Transcriptome.
Front Genet, 10, 1215.
https://doi.org/10.3389/fgene.2019.01215
UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
Bryan, Kenneth
UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
McGivney, Charlotte L
UCD School of Veterinary Medicine, University College Dublin, Dublin, Ireland.
McGettigan, Paul A
UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
Gough, Katie F
UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
Browne, John A
UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
MacHugh, David E
UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
Katz, Lisa Michelle
UCD School of Veterinary Medicine, University College Dublin, Dublin, Ireland.
Hill, Emmeline W
UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
Research and Development, Plusvital Ltd., Dublin, Ireland.
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