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G3 (Bethesda, Md.)2022; 12(10); jkac179; doi: 10.1093/g3journal/jkac179

Selection signature analyses and genome-wide association reveal genomic hotspot regions that reflect differences between breeds of horse with contrasting risk of degenerative suspensory ligament desmitis.

Abstract: Degenerative suspensory ligament desmitis is a progressive idiopathic condition that leads to scarring and rupture of suspensory ligament fibers in multiple limbs in horses. The prevalence of degenerative suspensory ligament desmitis is breed related. Risk is high in the Peruvian Horse, whereas pony and draft breeds have low breed risk. Degenerative suspensory ligament desmitis occurs in families of Peruvian Horses, but its genetic architecture has not been definitively determined. We investigated contrasts between breeds with differing risk of degenerative suspensory ligament desmitis and identified associated risk variants and candidate genes. We analyzed 670k single nucleotide polymorphisms from 10 breeds, each of which was assigned one of the four breed degenerative suspensory ligament desmitis risk categories: control (Belgian, Icelandic Horse, Shetland Pony, and Welsh Pony), low risk (Lusitano, Arabian), medium risk (Standardbred, Thoroughbred, Quarter Horse), and high risk (Peruvian Horse). Single nucleotide polymorphisms were used for genome-wide association and selection signature analysis using breed-assigned risk levels. We found that the Peruvian Horse is a population with low effective population size and our breed contrasts suggest that degenerative suspensory ligament desmitis is a polygenic disease. Variant frequency exhibited signatures of positive selection across degenerative suspensory ligament desmitis breed risk groups on chromosomes 7, 18, and 23. Our results suggest degenerative suspensory ligament desmitis breed risk is associated with disturbances to suspensory ligament homeostasis where matrix responses to mechanical loading are perturbed through disturbances to aging in tendon (PIN1), mechanotransduction (KANK1, KANK2, JUNB, SEMA7A), collagen synthesis (COL4A1, COL5A2, COL5A3, COL6A5), matrix responses to hypoxia (PRDX2), lipid metabolism (LDLR, VLDLR), and BMP signaling (GREM2). Our results do not suggest that suspensory ligament proteoglycan turnover is a primary factor in disease pathogenesis.
© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.
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Publication Date: 2022-07-23 PubMed ID: 35866615PubMed Central: PMC9526059DOI: 10.1093/g3journal/jkac179Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The researchers studied the genetic factors contributing to a horse disease called degenerative suspensory ligament desmitis and found certain gene variants associated with a higher risk of the disease, particularly in the Peruvian horse breed.

Research Context

  • The research focused on degenerative suspensory ligament desmitis (DSLD), a disease that damages the suspensory ligaments in horse legs leading to lameness. The occurrence of this disease is discovered to be breed-specific, making it prevalent amongst Peruvian Horses and scarce in pony and draft breeds.
  • The disease is known to occur in families of Peruvian Horses, implying possible genetic factors.
  • DSLD’s exact genetic composition remained undefined before this study, making it the researchers’ primary objective.

Methodology

  • The study was conducted analyzing 670k single nucleotide polymorphisms (SNPs), variations at a single position in a DNA sequence, across 10 horse breeds. The breeds were categorized according to their risk of developing DSLD: control, low risk, medium risk, and high risk.
  • The researchers used these SNPs for a genome-wide association and selection signature analysis, utilizing the assigned breed risk levels.

Key Findings

  • Peruvian Horse, a breed with a high risk of DSLD, was found to have a low effective population size, implying that this breed has less genetic diversity.
  • DSLD was identified as a polygenic disease, meaning it is influenced by multiple genes.
  • The study identified potential disease-related SNPs on chromosomes 7, 18, and 23, showing signs of positive selection, meaning these variations were advantageous due to the influence of natural selection.
  • The genetic variants suggested a disturbance in the homeostasis of the suspensory ligament, affecting numerous functions such as collagen synthesis, lipid metabolism, aging in tendon, matrix responses to mechanical loading and hypoxia, and BMP signaling.
  • Proteoglycan turnover in suspensory ligament, however, was not implicated as a significant factor in the disease’s development.

Implications

  • The findings provide a better understanding of the genetic architecture of DSLD, paving the way for further research into prevention and treatment measures.
  • The study also offers valuable insights into how genetic factors can contribute to breed-specific diseases in horses, highlighting the importance of genetic diversity.

Cite This Article

APA
Momen M, Brounts SH, Binversie EE, Sample SJ, Rosa GJM, Davis BW, Muir P. (2022). Selection signature analyses and genome-wide association reveal genomic hotspot regions that reflect differences between breeds of horse with contrasting risk of degenerative suspensory ligament desmitis. G3 (Bethesda), 12(10), jkac179. https://doi.org/10.1093/g3journal/jkac179

Publication

G3 (Bethesda, Md.)
ISSN: 2160-1836
NlmUniqueID: 101566598
Country: England
Language: English
Volume: 12
Issue: 10
PII: jkac179

Researcher Affiliations

Momen, Mehdi
  • Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Brounts, Sabrina H
  • Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Binversie, Emily E
  • Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Sample, Susannah J
  • Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Rosa, Guilherme J M
  • Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Davis, Brian W
  • Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
Muir, Peter
  • Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.

MeSH Terms

  • Animals
  • Genome-Wide Association Study
  • Genomics
  • Horse Diseases / genetics
  • Horse Diseases / pathology
  • Horses / genetics
  • Ligaments / metabolism
  • Ligaments / pathology
  • Mechanotransduction, Cellular
  • Muscular Diseases / metabolism
  • Proteoglycans / metabolism

Grant Funding

  • R21 AR073301 / NIAMS NIH HHS
  • T15 LM007359 / NLM NIH HHS
  • T32 OD010423 / NIH HHS

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