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Host genetic influence on papillomavirus-induced tumors in the horse.
Abstract: The common equine skin tumors known as sarcoids have been causally associated with infection by bovine papillomavirus (BPV). Additionally, there is evidence for host genetic susceptibility to sarcoids. We investigated the genetic basis of susceptibility to sarcoid tumors on a cohort of 82 affected horses and 270 controls genotyped on a genome-wide platform and two custom panels. A Genome Wide Association Study (GWAS) identified candidate regions on six chromosomes. Bayesian probability analysis of the same dataset verified only the regions on equine chromosomes (ECA) 20 and 22. Fine mapping using custom-produced SNP arrays for ECA20 and ECA22 regions identified two marker loci with high levels of significance: SNP BIEC2-530826 (map position 32,787,619) on ECA20 in an intron of the DQA1 gene in the Major Histocompatibility Complex (MHC) class II region (p = 4.6e-06), and SNP BIEC2-589604 (map position 25,951,536) on ECA22 in a 200 kb region containing four candidate genes: PROCR, EDEM2, EIF6 and MMP24 (p = 2.14e-06). The marker loci yielded odds ratios of 5.05 and 4.02 for ECA20 and ECA22, respectively. Associations between genetic MHC class II variants and papillomavirus-induced tumors have been reported for human papillomavirus and cottontail rabbit papillomavirus infections. This suggests a common mechanism for susceptibility to tumor progression that may involve subversion of the host immune response. This study also identified a genomic region other than MHC that influenced papillomavirus-induced tumor development in the studied population.
© 2016 UICC.
Publication Date: 2016-05-06 PubMed ID: 27037728DOI: 10.1002/ijc.30120Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates the role of genetics in the susceptibility of horses to sarcoid skin tumors, associated with bovine papillomavirus (BPV) infection. The study identified two particular genetic locations of significance, one of which is within the Major Histocompatibility Complex related to human papillomavirus and cottontail rabbit papillomavirus infections, suggesting a common susceptibility mechanism involving the immune response. It also revealed a non-MHC genomic region affecting tumor development.
Research Background and Study Approach
- This research is based on the evidence showing a link between bovine papillomavirus (BPV) infection and equine sarcoid skin tumors, and the associated host genetic susceptibility. It aims to understand the genetic factors influencing a horse’s susceptibility to develop these tumors.
- For this purpose, a Genome Wide Association Study (GWAS) was carried out on a cohort of 82 affected horses and 270 controls that were genotyped on a genome-wide platform and two custom panels. This allowed researchers to identify possible regions within the equine genome associated with tumor susceptibility.
Research Findings
- Candidate regions on six chromosomes were identified through GWAS. Further Bayesian probability analysis confirmed regions on two equine chromosomes (namely ECA20 and ECA22) as associated with sarcoid tumor susceptibility.
- Further investigation into these two chromosomes using custom-produced single nucleotide polymorphism (SNP) arrays led to the identification of two marker loci with high significance for tumor susceptibility.
- The first SNP (BIEC2-530826) on ECA20 is located in an intron of the DQA1 gene in the Major Histocompatibility Complex (MHC) class II region. The second SNP (BIEC2-589604) on ECA22 is located in a 200 kb region containing four candidate genes: PROCR, EDEM2, EIF6 and MMP24.
Ideas on Mechanisms and Implications
- The identification of a key SNP within MHC mirrors similar findings in human and cottontail rabbit papillomavirus infections. This suggests a potential shared mechanism for tumor susceptibility which could involve the immune response being manipulated by the virus.
- The study also found a non-MHC genomic region on ECA22 influencing tumor development, suggesting that susceptibility is also affected by other genomic factors, opening up avenues for further research.
Cite This Article
APA
Staiger EA, Tseng CT, Miller D, Cassano JM, Nasir L, Garrick D, Brooks SA, Antczak DF.
(2016).
Host genetic influence on papillomavirus-induced tumors in the horse.
Int J Cancer, 139(4), 784-792.
https://doi.org/10.1002/ijc.30120 Publication
Researcher Affiliations
- Department of Animal Science, Cornell University, Ithaca, NY.
- Baker Institute for Animal Health, Cornell University, Ithaca, NY.
- Baker Institute for Animal Health, Cornell University, Ithaca, NY.
- Baker Institute for Animal Health, Cornell University, Ithaca, NY.
- MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
- Department of Animal Science, Iowa State University, Ames, IA.
- Department of Animal Science, University of Florida, Gainesville, FL.
- Baker Institute for Animal Health, Cornell University, Ithaca, NY.
MeSH Terms
- Alleles
- Animals
- Case-Control Studies
- Chromosome Mapping
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Horse Diseases / epidemiology
- Horse Diseases / etiology
- Horses
- Linkage Disequilibrium
- Neoplasms / veterinary
- Odds Ratio
- Papillomavirus Infections / complications
- Papillomavirus Infections / virology
- Polymorphism, Single Nucleotide
- Skin Neoplasms / epidemiology
- Skin Neoplasms / etiology
Citations
This article has been cited 17 times.- Vasoya D, Tzelos T, Benedictus L, Karagianni AE, Pirie S, Marr C, Oddsdóttir C, Fintl C, Connelley T. High-Resolution Genotyping of Expressed Equine MHC Reveals a Highly Complex MHC Structure. Genes (Basel) 2023 Jul 10;14(7).
- Cappelli K, Ciucis CG, Mecocci S, Nervo T, Crescio MI, Pepe M, Gialletti R, Pietrucci D, Migone LF, Turco S, Mechelli L, Passamonti F, Drago C, Donato GG, Varello K, Modesto P, Chillemi G, Ghelardi A, Razzuoli E. Detection of Equus Caballus Papillomavirus Type-2 in Asymptomatic Italian Horses. Viruses 2022 Jul 31;14(8).
- Hamza E, Cosandey J, Gerber V, Koch C, Unger L. The potential of three whole blood microRNAs to predict outcome and monitor treatment response in sarcoid-bearing equids. Vet Res Commun 2023 Jan;47(1):87-98.
- Cosandey J, Hamza E, Gerber V, Ramseyer A, Leeb T, Jagannathan V, Blaszczyk K, Unger L. Diagnostic and prognostic potential of eight whole blood microRNAs for equine sarcoid disease. PLoS One 2021;16(12):e0261076.
- Jindra C, Hainisch EK, Rümmele A, Wolschek M, Muster T, Brandt S. Influenza virus vector iNS1 expressing bovine papillomavirus 1 (BPV1) antigens efficiently induces tumour regression in equine sarcoid patients. PLoS One 2021;16(11):e0260155.
- Longeri M, Russo V, Strillacci MG, Perillo A, Carisetti M, Cozzi MC, Neola B, Roperto S. Association Between BoLA-DRB3.2 Polymorphism and Bovine Papillomavirus Infection for Bladder Tumor Risk in Podolica Cattle. Front Vet Sci 2021;8:630089.
- Weber LA, Funtan A, Paschke R, Delarocque J, Kalbitz J, Meißner J, Feige K, Kietzmann M, Cavalleri JV. In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer. PLoS One 2020;15(11):e0241448.
- Raudsepp T, Finno CJ, Bellone RR, Petersen JL. Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post-genome era. Anim Genet 2019 Dec;50(6):569-597.
- Unger L, Jagannathan V, Pacholewska A, Leeb T, Gerber V. Differences in miRNA differential expression in whole blood between horses with sarcoid regression and progression. J Vet Intern Med 2019 Jan;33(1):241-250.
- Kalbfleisch TS, Rice ES, DePriest MS Jr, Walenz BP, Hestand MS, Vermeesch JR, O Connell BL, Fiddes IT, Vershinina AO, Saremi NF, Petersen JL, Finno CJ, Bellone RR, McCue ME, Brooks SA, Bailey E, Orlando L, Green RE, Miller DC, Antczak DF, MacLeod JN. Improved reference genome for the domestic horse increases assembly contiguity and composition. Commun Biol 2018;1:197.
- Sadeghi R, Moradi-Shahrbabak M, Miraei Ashtiani SR, Miller DC, Antczak DF. MHC haplotype diversity in Persian Arabian horses determined using polymorphic microsatellites. Immunogenetics 2018 May;70(5):305-315.
- Viļuma A, Mikko S, Hahn D, Skow L, Andersson G, Bergström TF. Genomic structure of the horse major histocompatibility complex class II region resolved using PacBio long-read sequencing technology. Sci Rep 2017 Mar 31;7:45518.
- Miller D, Tallmadge RL, Binns M, Zhu B, Mohamoud YA, Ahmed A, Brooks SA, Antczak DF. Polymorphism at expressed DQ and DR loci in five common equine MHC haplotypes. Immunogenetics 2017 Mar;69(3):145-156.
- Beermann A, Hamza E, Reinhard S, Koch C, Oberhänsli T, Unger L. Selected microRNAs as biomarkers in sarcoid-affected horses under immunotherapy with a mistletoe extract. J Vet Diagn Invest 2026 Jan;38(1):33-40.
- Vychodilova L, Plasil M, Futas J, Kopecka A, Molinkova D, Wijacki T, Jahn P, Knoll A, Horin P. Genetic susceptibility to sarcoid in Arabian horses: associations with MHC class II and compound MHC class I/KLRA genotypes. Vet Res Commun 2025 May 1;49(3):184.
- Quatember H, Nell B, Richter B, Rigler D, Dolezal M, Sykora S, Wallner B. Studying the Impact of the DDB2 T338M Missense Mutation on the Development of Equine Squamous Cell Carcinoma and Sarcoid. Animals (Basel) 2025 Mar 22;15(7).
- Beermann A, Clottu O, Reif M, Biegel U, Unger L, Koch C. A randomized placebo-controlled double-blinded study comparing oral and subcutaneous administration of mistletoe extract for the treatment of equine sarcoid disease. J Vet Intern Med 2024 May-Jun;38(3):1815-1824.
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