Genome-wide association study among four horse breeds identifies a common haplotype associated with in vitro CD3+ T cell susceptibility/resistance to equine arteritis virus infection.
Abstract: Previously, we have shown that horses could be divided into susceptible and resistant groups based on an in vitro assay using dual-color flow cytometric analysis of CD3+ T cells infected with equine arteritis virus (EAV). Here, we demonstrate that the differences in in vitro susceptibility of equine CD3+ T lymphocytes to EAV infection have a genetic basis. To investigate the possible hereditary basis for this trait, we conducted a genome-wide association study (GWAS) to compare susceptible and resistant phenotypes. Testing of 267 DNA samples from four horse breeds that had a susceptible or a resistant CD3+ T lymphocyte phenotype using both Illumina Equine SNP50 BeadChip and Sequenom's MassARRAY system identified a common, genetically dominant haplotype associated with the susceptible phenotype in a region of equine chromosome 11 (ECA11), positions 49572804 to 49643932. The presence of a common haplotype indicates that the trait occurred in a common ancestor of all four breeds, suggesting that it may be segregated among other modern horse breeds. Biological pathway analysis revealed several cellular genes within this region of ECA11 encoding proteins associated with virus attachment and entry, cytoskeletal organization, and NF-κB pathways that may be associated with the trait responsible for the in vitro susceptibility/resistance of CD3+ T lymphocytes to EAV infection. The data presented in this study demonstrated a strong association of genetic markers with the trait, representing de facto proof that the trait is under genetic control. To our knowledge, this is the first GWAS of an equine infectious disease and the first GWAS of equine viral arteritis.
Publication Date: 2011-10-12 PubMed ID: 21994447PubMed Central: PMC3233183DOI: 10.1128/JVI.06068-11Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research study investigates the genetic basis behind the varying susceptibility of horses to equine arteritis virus (EAV), revealing that specific genetic traits linked to a common ancestor across four horse breeds can influence a horse’s in vitro resistance or susceptibility to the virus.
Objective and Methodology
- The objective of this study was to explore whether the varying susceptibility of CD3+ T lymphocytes (a type of white blood cell) in horses to EAV infection has a genetic basis.
- To ascertain this, the researchers executed a genome-wide association study (GWAS), an approach that involves rapidly scanning markers across complete sets of DNA, or genomes, in many individuals to find genetic variations associated with a particular disease.
- The study involved the testing of 267 DNA samples procured from four horse breeds, using the Illumina Equine SNP50 BeadChip and Sequenom’s MassARRAY system.
Key Findings
- The study successfully identified a common, genetically dominant haplotype associated with susceptibility to EAV. A ‘haplotype’ is a set of DNA variations, or polymorphisms, that are typically inherited together.
- This common haplotype was found in a region of equine chromosome 11 (ECA11), indicated that it likely originated from a common ancestor of all four horse breeds studied. The researchers suggest that this trait might also be present in other modern horse breeds.
- Upon analyzing the genes within this region, it was found that they are linked with cellular processes, such as virus attachment and entry, cytoskeletal organization, and the NF-κB pathway, all of which might influence the susceptibility/resistance of CD3+ T lymphocytes to EAV infection.
Significance of the Study
- This study offers crucial evidence that the varying susceptibility/resistance of horses to EAV has a genetic underpinning.
- This is the first GWAS of an equine infectious disease and specifically of equine viral arteritis, thereby offering a novel perspective on the genetic influences on equine diseases.
- The findings lay the groundwork for further studies investigating the genetic control of susceptibility to infectious diseases in horses and potentially other species.
Cite This Article
APA
Go YY, Bailey E, Cook DG, Coleman SJ, Macleod JN, Chen KC, Timoney PJ, Balasuriya UB.
(2011).
Genome-wide association study among four horse breeds identifies a common haplotype associated with in vitro CD3+ T cell susceptibility/resistance to equine arteritis virus infection.
J Virol, 85(24), 13174-13184.
https://doi.org/10.1128/JVI.06068-11 Publication
Researcher Affiliations
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546-0099, USA.
MeSH Terms
- Animals
- Arterivirus Infections / genetics
- Arterivirus Infections / immunology
- Arterivirus Infections / veterinary
- Arterivirus Infections / virology
- CD3 Complex / analysis
- Equartevirus / immunology
- Equartevirus / pathogenicity
- Genetic Markers
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Haplotypes
- Horse Diseases / genetics
- Horse Diseases / immunology
- Horse Diseases / virology
- Horses
- T-Lymphocyte Subsets / chemistry
- T-Lymphocyte Subsets / immunology
- T-Lymphocyte Subsets / virology
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