Genetic mapping of recurrent exertional rhabdomyolysis in a population of North American Thoroughbreds.
Abstract: Recurrent exertional rhabdomyolysis is a heritable disorder that results in painful skeletal muscle cramping with exercise in up to 10% of all Thoroughbred racehorses. Here, we report a genome-wide association study with 48 282 SNPs analyzed among 48 case and 37 control Thoroughbreds. The most significant SNPs spanned approximately 13 Mb on ECA16, and the P-value of the most significant SNP after correcting for population structure was 8.0 × 10(-6) . This region on ECA16 was further evaluated by genotyping 247 SNPs in both the initial population and a second population of 34 case and 98 control Thoroughbreds. Several SNPs across the 13-Mb region on ECA16 showed significance when each population was analyzed separately; however, the exact positions of the most significant SNPs within this region on ECA16 varied between populations. This variability in location may be attributed to lack of power owing to insufficient sample sizes within each population individually, or to the relative distribution of long, conserved haplotypes, characteristic of the Thoroughbred breed. Future genome-wide association studies with additional horses would likely improve the power to resolve casual loci located on ECA16 and increase the likelihood of detecting any additional loci on other chromosomes contributing to disease susceptibility.
© 2012 The Authors, Animal Genetics © 2012 Stichting International Society for Animal Genetics.
Publication Date: 2012-03-23 PubMed ID: 22497487PubMed Central: PMC3665002DOI: 10.1111/j.1365-2052.2012.02351.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
- Comparative Study
- Diagnosis
- Disease Diagnosis
- Disease Etiology
- Epidemiology
- Equine Diseases
- Equine Health
- Exercise
- Genetics
- Genomics
- Genotyping
- Heritability
- Horse Breeds
- In Vivo
- Musculoskeletal System
- Population Dynamics
- Recurrent Exertional Rhabdomyolysis
- Thoroughbreds
- Veterinary Care
- Veterinary Medicine
- Veterinary Research
Summary
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The research article examines the genetic mapping of the recurrent exertional rhabdomyolysis (RER) disorder within a population of North American Thoroughbred horses. The study, through a genome-wide association study, pinpoints the disorder’s genetic link to the ECA16 region of the Thoroughbred genome.
Introduction to Recurrent Exertional Rhabdomyolysis
- Recurrent exertional rhabdomyolysis (RER) is a genetically inherited disorder common in Thoroughbred racehorses, which induces painful skeletal muscle cramping during exercise. This ailment affects up to 10% of the breed’s population.
- This study focuses on understanding the genetic origins of this disorder through comprehensive genetic mapping of the Thoroughbred genome.
The Genome-Wide Association Study (GWAS)
- Conducted to identify the specific areas (loci) of the genome that are associated with RER, the genome-wide association study (GWAS) focused on 48,282 SNPs (Single Nucleotide Polymorphisms), essentially the most common type of genetic variation among individuals of a particular species.
- The study was performed on a population sample of 48 case Thoroughbreds (those suffering from RER) and 37 control Thoroughbreds (those showing no signs of RER).
Findings of the Research
- The most significant SNPs were found spanning approximately a 13 Mb region on ECA16, and the most influential SNP’s P-value (a measure of statistical significance) was 8.0 × 10(-6) even after correcting for population structure.
- A larger survey of 247 SNPs in the same ECA16 region was conducted in both the initial population and a second population of 34 case and 98 control Thoroughbreds.
Variability in SNP Significance
- While several SNPs on ECA16 showed significance in both populations, the top-ranking SNPs’ positions within this region varied.
- This variance might be due to inadequate sample sizes affecting the power of the study or the distribution of long, conserved haplotypes innate to the Thoroughbred breed.
Scope for Future Research
- The researchers suggest that future genome-wide association studies with larger sample sizes could improve the power to accurately pinpoint the causative loci on ECA16 and possibly detect other chromosomes contributing to RER susceptibility.
Cite This Article
APA
Fritz KL, McCue ME, Valberg SJ, Rendahl AK, Mickelson JR.
(2012).
Genetic mapping of recurrent exertional rhabdomyolysis in a population of North American Thoroughbreds.
Anim Genet, 43(6), 730-738.
https://doi.org/10.1111/j.1365-2052.2012.02351.x Publication
Researcher Affiliations
- Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108, USA. klfritz@umn.edu
MeSH Terms
- Animals
- Chromosome Mapping / veterinary
- Chromosomes, Mammalian / genetics
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study / veterinary
- Genotype
- Horse Diseases / genetics
- Horses
- Male
- Muscle, Skeletal / pathology
- Physical Exertion
- Polymorphism, Single Nucleotide
- Rhabdomyolysis / genetics
- Rhabdomyolysis / veterinary
Grant Funding
- T32 AR007612 / NIAMS NIH HHS
- K08 AR055713 / NIAMS NIH HHS
- 1K08AR055713-01A2 / NIAMS NIH HHS
- 5T32AR007612-09 / NIAMS NIH HHS
- T32-AR0076I2 / NIAMS NIH HHS
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