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Veterinary journal (London, England : 1997)2018; 245; 49-54; doi: 10.1016/j.tvjl.2018.12.013

Genome-wide association study of equine herpesvirus type 1-induced myeloencephalopathy identifies a significant single nucleotide polymorphism in a platelet-related gene.

Abstract: Equine herpesvirus type 1 (EHV-1)-induced myeloencephalopathy (EHM) is a neurologic disease of horses that represents one outcome of infection. The neurologic form of disease occurs in a subset of infected horses when virus-induced endothelial cell damage triggers vasculitis and subsequent ischemic insult to the central nervous system. EHM causes considerable animal suffering and economic loss for the horse industry. Virus polymorphisms have been previously associated with disease outcome but cannot fully explain why only some horses develop EHM. This study investigated the role of host genetics in EHM. DNA samples were collected from 129 horses infected with EHV-1 (61 that developed EHM and 68 in which disease resolved without the development of neurologic signs) during natural outbreaks or experimental infections. A genome-wide association study (GWAS) was performed to investigate host genetic variations associated with EHM. Genotyping was performed using the Illumina SNP50 and SNP70 arrays and a custom Sequenom array. Mixed linear model (MLM) analysis using a recessive model identified one marker that surpassed the threshold for genome-wide significance (P<0.001) after Bonferroni correction. The marker (BIEC2_946397) is in an intron of the tetraspanin 9 (TSPAN9) gene, which is expressed in endothelial cells and platelets. The GWAS identified a region in the horse genome that is associated with EHM in the sample population and thus warrants further exploration. Understanding the contribution of host genetic variation to the development of EHM will enhance our knowledge of disease pathophysiology, and lead to improved strategies for treating individual cases and managing outbreaks.
Publication Date: 2018-12-12 PubMed ID: 30819425DOI: 10.1016/j.tvjl.2018.12.013Google Scholar: Lookup
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  • Journal Article

Summary

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The research studied the genetic factors that influence the development of a neurologic disease in horses, caused by equine herpesvirus type 1 (EHV-1), known as myeloencephalopathy (EHM). The study detected a significant genetic marker associated with the disease.

Objective of the Research

  • The primary objective of the research was to investigate the influence of host, or horse, genetics on the development of Equine herpesvirus type 1-induced myeloencephalopathy (EHM). While previous research concluded that virus polymorphisms influenced disease outcome, they could not fully explain why only some horses developed EHM.

Research Methodology

  • DNA samples were collected from 129 horses infected with EHV-1 during both natural disease outbreaks and experimental infections. Some of these horses (61 out of 129) developed EHM while the rest (68 out of 129) recovered without showing any neurological signs of the disease.
  • A genome-wide association study (GWAS) was conducted to determine the host genetic variations associated with the seriousness of the disease.
  • The genotyping was performed using the Illumina SNP50 and SNP70 arrays and a custom Sequenom array.
  • Following this, a Mixed Linear Model (MLM) analysis was carried out using a recessive model to identify any genome-wide significance.

Key Findings

  • The MLM analysis identified one marker (BIEC2_946397) that showed genome-wide significance after a Bonferroni correction. This marker is found within an intron of the tetraspanin 9 (TSPAN9) gene, which is expressed in endothelial cells and platelets.
  • The association of this marker with EHM denotes that it warrants further exploration to fully understand its role in the disease’s development.

Implications of the Research

  • Understanding the genetic factors contributing to the development of EHM can enhance our knowledge of its pathophysiology, or how the disease develops.
  • This understanding could lead to improved treatment strategies for individual cases and enable better management of disease outbreaks.
  • The findings can yield significant economic and welfare benefits for the horse industry by contributing towards reducing cases of EHM.

Cite This Article

APA
Brosnahan MM, Al Abri MA, Brooks SA, Antczak DF, Osterrieder N. (2018). Genome-wide association study of equine herpesvirus type 1-induced myeloencephalopathy identifies a significant single nucleotide polymorphism in a platelet-related gene. Vet J, 245, 49-54. https://doi.org/10.1016/j.tvjl.2018.12.013

Publication

ISSN: 1532-2971
NlmUniqueID: 9706281
Country: England
Language: English
Volume: 245
Pages: 49-54
PII: S1090-0233(18)30776-7

Researcher Affiliations

Brosnahan, M M
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States; College of Veterinary Medicine, Midwestern University, Glendale, AZ 85308, United States. Electronic address: mbrosn@midwestern.edu.
Al Abri, M A
  • Department of Animal Science, Cornell University, Ithaca, NY 14853, United States; Department of Animal and Veterinary Sciences, College of Agriculture and Marine Sciences, Sultan Qaboos University, Muscat, Oman.
Brooks, S A
  • Department of Animal Science, Cornell University, Ithaca, NY 14853, United States; University of Florida, Gainsville, FL 32611, United States.
Antczak, D F
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States.
Osterrieder, N
  • Institut fur Virologie, Freie Universität, 14163 Berlin, Germany.

MeSH Terms

  • Animals
  • Blood Platelets / metabolism
  • Encephalomyelitis, Equine / genetics
  • Encephalomyelitis, Equine / virology
  • Gene Expression
  • Genome-Wide Association Study
  • Genotype
  • Herpesviridae Infections / complications
  • Herpesviridae Infections / veterinary
  • Herpesvirus 1, Equid
  • Horse Diseases / genetics
  • Horses
  • Polymorphism, Single Nucleotide / genetics
  • Tetraspanins / genetics

Citations

This article has been cited 6 times.
  1. Finno CJ. Science-in-brief: Genomic and transcriptomic approaches to the investigation of equine diseases. Equine Vet J 2022 Mar;54(2):444-448.
    doi: 10.1111/evj.13549pubmed: 35133024google scholar: lookup
  2. Zarski LM, Weber PSD, Lee Y, Soboll Hussey G. Transcriptomic Profiling of Equine and Viral Genes in Peripheral Blood Mononuclear Cells in Horses during Equine Herpesvirus 1 Infection. Pathogens 2021 Jan 7;10(1).
    doi: 10.3390/pathogens10010043pubmed: 33430330google scholar: lookup
  3. Dunuwille WMB, YousefiMashouf N, Balasuriya UBR, Pusterla N, Bailey E. Genome-wide association study for host genetic factors associated with equine herpesvirus type-1 induced myeloencephalopathy. Equine Vet J 2020 Nov;52(6):794-798.
    doi: 10.1111/evj.13261pubmed: 32153055google scholar: lookup
  4. Stokol T, Soboll Hussey G. Editorial: Current Research in Equid Herpesvirus Type-1 (EHV-1). Front Vet Sci 2019;6:492.
    doi: 10.3389/fvets.2019.00492pubmed: 31998768google scholar: lookup
  5. Garvey M, Lyons R, Hector RD, Walsh C, Arkins S, Cullinane A. Molecular Characterisation of Equine Herpesvirus 1 Isolates from Cases of Abortion, Respiratory and Neurological Disease in Ireland between 1990 and 2017. Pathogens 2019 Jan 15;8(1).
    doi: 10.3390/pathogens8010007pubmed: 30650561google scholar: lookup
  6. Divilov K, Merz N, Schoolfield B, Green TJ, Langdon C. Genome-wide allele frequency studies in Pacific oyster families identify candidate genes for tolerance to ostreid herpesvirus 1 (OsHV-1). BMC Genomics 2023 Oct 23;24(1):631.
    doi: 10.1186/s12864-023-09744-0pubmed: 37872508google scholar: lookup