Genome-wide association study of equine herpesvirus type 1-induced myeloencephalopathy identifies a significant single nucleotide polymorphism in a platelet-related gene
•Only a small percentage of horses infected with equine herpesvirus type 1 (EHV-1) develop neurologic disease.•Polymorphisms in the viral genome account for some, but not all, of this difference.•Polymorphisms in host genome have never been investigated as a contributing factor.•Here we report the r...
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creator | Brosnahan, M.M. Al Abri, M.A. Brooks, S.A. Antczak, D.F. Osterrieder, N. |
description | •Only a small percentage of horses infected with equine herpesvirus type 1 (EHV-1) develop neurologic disease.•Polymorphisms in the viral genome account for some, but not all, of this difference.•Polymorphisms in host genome have never been investigated as a contributing factor.•Here we report the results of a genome-wide association study (GWAS).•A single nucleotide polymorphism (SNP) of significance was identified in an intron of a platelet-associated gene.
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 |
doi_str_mv | 10.1016/j.tvjl.2018.12.013 |
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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.</description><identifier>ISSN: 1090-0233</identifier><identifier>EISSN: 1532-2971</identifier><identifier>DOI: 10.1016/j.tvjl.2018.12.013</identifier><identifier>PMID: 30819425</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Equine ; Equine herpesvirus 1 ; Genome-wide association study ; Virology</subject><ispartof>The veterinary journal (1997), 2019-03, Vol.245, p.49-54</ispartof><rights>2018</rights><rights>Copyright © 2018. Published by Elsevier Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-21160c04284b6e8fe38c56d08d26b02286915bdaca02e53d778667fab331f44b3</citedby><cites>FETCH-LOGICAL-c356t-21160c04284b6e8fe38c56d08d26b02286915bdaca02e53d778667fab331f44b3</cites><orcidid>0000-0003-1708-3845 ; 0000-0003-0820-107X ; 0000-0002-4500-2689</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.tvjl.2018.12.013$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3541,27915,27916,45986</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30819425$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brosnahan, M.M.</creatorcontrib><creatorcontrib>Al Abri, M.A.</creatorcontrib><creatorcontrib>Brooks, S.A.</creatorcontrib><creatorcontrib>Antczak, D.F.</creatorcontrib><creatorcontrib>Osterrieder, N.</creatorcontrib><title>Genome-wide association study of equine herpesvirus type 1-induced myeloencephalopathy identifies a significant single nucleotide polymorphism in a platelet-related gene</title><title>The veterinary journal (1997)</title><addtitle>Vet J</addtitle><description>•Only a small percentage of horses infected with equine herpesvirus type 1 (EHV-1) develop neurologic disease.•Polymorphisms in the viral genome account for some, but not all, of this difference.•Polymorphisms in host genome have never been investigated as a contributing factor.•Here we report the results of a genome-wide association study (GWAS).•A single nucleotide polymorphism (SNP) of significance was identified in an intron of a platelet-associated gene.
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.</description><subject>Equine</subject><subject>Equine herpesvirus 1</subject><subject>Genome-wide association study</subject><subject>Virology</subject><issn>1090-0233</issn><issn>1532-2971</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u1DAURi0EoqXwAiyQl2yS-idxEokNqqBUqsQG1pZj38x45Nip7QzKI_GWOJrCkpW_xbnfle9B6D0lNSVU3J7qfD65mhHa15TVhPIX6Jq2nFVs6OjLkslAKsI4v0JvUjoRQoamYa_RFSc9HRrWXqPf9-DDDNUvawCrlIK2Ktvgccqr2XCYMDyt1gM-QlwgnW1cE87bAphW1ptVg8HzBi6A17AclQuLyscNlzqf7WQhYYWTPfiStfK5ZH9wgP2qHYS8b12C2-YQl6NNM7a-8ItTGRzkKsKeDD6Ah7fo1aRcgnfP7w36-fXLj7tv1eP3-4e7z4-V5q3IFaNUEE0a1jejgH4C3utWGNIbJkbCWC8G2o5GaUUYtNx0XS9EN6mRczo1zchv0MdL7xLD0wopy9kmDc4pD2FNktG-a9kgBlZQdkF1DClFmOQS7aziJimRuyJ5krsiuSuSlMmiqAx9eO5fxxnMv5G_Tgrw6QJA-eXZQpRJ2_28xkbQWZpg_9f_B31vpzY</recordid><startdate>201903</startdate><enddate>201903</enddate><creator>Brosnahan, M.M.</creator><creator>Al Abri, M.A.</creator><creator>Brooks, S.A.</creator><creator>Antczak, D.F.</creator><creator>Osterrieder, N.</creator><general>Elsevier Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1708-3845</orcidid><orcidid>https://orcid.org/0000-0003-0820-107X</orcidid><orcidid>https://orcid.org/0000-0002-4500-2689</orcidid></search><sort><creationdate>201903</creationdate><title>Genome-wide association study of equine herpesvirus type 1-induced myeloencephalopathy identifies a significant single nucleotide polymorphism in a platelet-related gene</title><author>Brosnahan, M.M. ; Al Abri, M.A. ; Brooks, S.A. ; Antczak, D.F. ; Osterrieder, N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-21160c04284b6e8fe38c56d08d26b02286915bdaca02e53d778667fab331f44b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Equine</topic><topic>Equine herpesvirus 1</topic><topic>Genome-wide association study</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brosnahan, M.M.</creatorcontrib><creatorcontrib>Al Abri, M.A.</creatorcontrib><creatorcontrib>Brooks, S.A.</creatorcontrib><creatorcontrib>Antczak, D.F.</creatorcontrib><creatorcontrib>Osterrieder, N.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The veterinary journal (1997)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brosnahan, M.M.</au><au>Al Abri, M.A.</au><au>Brooks, S.A.</au><au>Antczak, D.F.</au><au>Osterrieder, N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide association study of equine herpesvirus type 1-induced myeloencephalopathy identifies a significant single nucleotide polymorphism in a platelet-related gene</atitle><jtitle>The veterinary journal (1997)</jtitle><addtitle>Vet J</addtitle><date>2019-03</date><risdate>2019</risdate><volume>245</volume><spage>49</spage><epage>54</epage><pages>49-54</pages><issn>1090-0233</issn><eissn>1532-2971</eissn><abstract>•Only a small percentage of horses infected with equine herpesvirus type 1 (EHV-1) develop neurologic disease.•Polymorphisms in the viral genome account for some, but not all, of this difference.•Polymorphisms in host genome have never been investigated as a contributing factor.•Here we report the results of a genome-wide association study (GWAS).•A single nucleotide polymorphism (SNP) of significance was identified in an intron of a platelet-associated gene.
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.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30819425</pmid><doi>10.1016/j.tvjl.2018.12.013</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0003-1708-3845</orcidid><orcidid>https://orcid.org/0000-0003-0820-107X</orcidid><orcidid>https://orcid.org/0000-0002-4500-2689</orcidid></addata></record> |
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title | Genome-wide association study of equine herpesvirus type 1-induced myeloencephalopathy identifies a significant single nucleotide polymorphism in a platelet-related gene |
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