Genome Wide Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross
Identifieur interne : 001315 ( Main/Exploration ); précédent : 001314; suivant : 001316Genome Wide Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross
Auteurs : Lisa E. Gralinski [États-Unis] ; Martin T. Ferris [États-Unis] ; David L. Aylor [États-Unis] ; Alan C. Whitmore [États-Unis] ; Richard Green [États-Unis] ; Matthew B. Frieman [États-Unis] ; Damon Deming [États-Unis] ; Vineet D. Menachery [États-Unis] ; Darla R. Miller [États-Unis] ; Ryan J. Buus [États-Unis] ; Timothy A. Bell [États-Unis] ; Gary A. Churchill [États-Unis] ; David W. Threadgill [États-Unis] ; Michael G. Katze [États-Unis] ; Leonard Mcmillan [États-Unis] ; William Valdar [États-Unis] ; Mark T. Heise [États-Unis] ; Fernando Pardo-Manuel De Villena [États-Unis] ; Ralph S. Baric [États-Unis]Source :
- PLoS Genetics [ 1553-7390 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Humains, Inflammation (anatomopathologie), Inflammation (génétique), Inflammation (virologie), Interactions hôte-pathogène, Modèles animaux de maladie humaine, Phénotype, Réplication virale (génétique), Souris, Susceptibilité à une maladie, Syndrome respiratoire aigu sévère (anatomopathologie), Syndrome respiratoire aigu sévère (génétique), Syndrome respiratoire aigu sévère (virologie), Virus du SRAS (génétique), Virus du SRAS (pathogénicité).
- MESH :
- anatomopathologie : Inflammation, Syndrome respiratoire aigu sévère.
- génétique : Inflammation, Réplication virale, Syndrome respiratoire aigu sévère, Virus du SRAS.
- pathogénicité : Virus du SRAS.
- virologie : Inflammation, Syndrome respiratoire aigu sévère.
- Animaux, Humains, Interactions hôte-pathogène, Modèles animaux de maladie humaine, Phénotype, Souris, Susceptibilité à une maladie.
English descriptors
- KwdEn :
- Animals, Disease Models, Animal, Disease Susceptibility, Host-Pathogen Interactions, Humans, Inflammation (genetics), Inflammation (pathology), Inflammation (virology), Mice, Phenotype, SARS Virus (genetics), SARS Virus (pathogenicity), Severe Acute Respiratory Syndrome (genetics), Severe Acute Respiratory Syndrome (pathology), Severe Acute Respiratory Syndrome (virology), Virus Replication (genetics).
- MESH :
- genetics : Inflammation, SARS Virus, Severe Acute Respiratory Syndrome, Virus Replication.
- pathogenicity : SARS Virus.
- pathology : Inflammation, Severe Acute Respiratory Syndrome.
- virology : Inflammation, Severe Acute Respiratory Syndrome.
- Animals, Disease Models, Animal, Disease Susceptibility, Host-Pathogen Interactions, Humans, Mice, Phenotype.
Abstract
New systems genetics approaches are needed to rapidly identify host genes and genetic networks that regulate complex disease outcomes. Using genetically diverse animals from incipient lines of the Collaborative Cross mouse panel, we demonstrate a greatly expanded range of phenotypes relative to classical mouse models of SARS-CoV infection including lung pathology, weight loss and viral titer. Genetic mapping revealed several loci contributing to differential disease responses, including an 8.5Mb locus associated with vascular cuffing on chromosome 3 that contained 23 genes and 13 noncoding RNAs. Integrating phenotypic and genetic data narrowed this region to a single gene,
Url:
DOI: 10.1371/journal.pgen.1005504
PubMed: 26452100
PubMed Central: 4599853
Affiliations:
- États-Unis
- Caroline du Nord, Maine (État), Texas, Washington (État)
- Seattle
- Université de Washington
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Le document en format XML
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Gralinski</name><affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>Department of Epidemiology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Ferris, Martin T" sort="Ferris, Martin T" uniqKey="Ferris M" first="Martin T." last="Ferris">Martin T. Ferris</name><affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Aylor, David L" sort="Aylor, David L" uniqKey="Aylor D" first="David L." last="Aylor">David L. Aylor</name><affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Whitmore, Alan C" sort="Whitmore, Alan C" uniqKey="Whitmore A" first="Alan C." last="Whitmore">Alan C. 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Menachery</name><affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>Department of Epidemiology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Miller, Darla R" sort="Miller, Darla R" uniqKey="Miller D" first="Darla R." last="Miller">Darla R. 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Buus</name><affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff004"><addr-line>Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Bell, Timothy A" sort="Bell, Timothy A" uniqKey="Bell T" first="Timothy A." last="Bell">Timothy A. Bell</name><affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff004"><addr-line>Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Churchill, Gary A" sort="Churchill, Gary A" uniqKey="Churchill G" first="Gary A." last="Churchill">Gary A. Churchill</name><affiliation wicri:level="2"><nlm:aff id="aff005"><addr-line>The Jackson Laboratory, Bar Harbor, Maine, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Jackson Laboratory, Bar Harbor, Maine</wicri:regionArea><placeName><region type="state">Maine (État)</region></placeName></affiliation></author><author><name sortKey="Threadgill, David W" sort="Threadgill, David W" uniqKey="Threadgill D" first="David W." last="Threadgill">David W. Threadgill</name><affiliation wicri:level="2"><nlm:aff id="aff006"><addr-line>Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G." last="Katze">Michael G. Katze</name><affiliation wicri:level="4"><nlm:aff id="aff003"><addr-line>Department of Microbiology, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Mcmillan, Leonard" sort="Mcmillan, Leonard" uniqKey="Mcmillan L" first="Leonard" last="Mcmillan">Leonard Mcmillan</name><affiliation wicri:level="2"><nlm:aff id="aff007"><addr-line>Department of Computer Science, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Computer Science, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Valdar, William" sort="Valdar, William" uniqKey="Valdar W" first="William" last="Valdar">William Valdar</name><affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Heise, Mark T" sort="Heise, Mark T" uniqKey="Heise M" first="Mark T." last="Heise">Mark T. Heise</name><affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Pardo Manuel De Villena, Fernando" sort="Pardo Manuel De Villena, Fernando" uniqKey="Pardo Manuel De Villena F" first="Fernando" last="Pardo-Manuel De Villena">Fernando Pardo-Manuel De Villena</name><affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff004"><addr-line>Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>Department of Epidemiology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author></analytic><series><title level="j">PLoS Genetics</title><idno type="ISSN">1553-7390</idno><idno type="eISSN">1553-7404</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Disease Susceptibility</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Inflammation (genetics)</term><term>Inflammation (pathology)</term><term>Inflammation (virology)</term><term>Mice</term><term>Phenotype</term><term>SARS Virus (genetics)</term><term>SARS Virus (pathogenicity)</term><term>Severe Acute Respiratory Syndrome (genetics)</term><term>Severe Acute Respiratory Syndrome (pathology)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Virus Replication (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Inflammation (anatomopathologie)</term><term>Inflammation (génétique)</term><term>Inflammation (virologie)</term><term>Interactions hôte-pathogène</term><term>Modèles animaux de maladie humaine</term><term>Phénotype</term><term>Réplication virale (génétique)</term><term>Souris</term><term>Susceptibilité à une maladie</term><term>Syndrome respiratoire aigu sévère (anatomopathologie)</term><term>Syndrome respiratoire aigu sévère (génétique)</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (pathogénicité)</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Inflammation</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Inflammation</term><term>SARS Virus</term><term>Severe Acute Respiratory Syndrome</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Inflammation</term><term>Réplication virale</term><term>Syndrome respiratoire aigu sévère</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Inflammation</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Inflammation</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Inflammation</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Disease Susceptibility</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Mice</term><term>Phenotype</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Interactions hôte-pathogène</term><term>Modèles animaux de maladie humaine</term><term>Phénotype</term><term>Souris</term><term>Susceptibilité à une maladie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>New systems genetics approaches are needed to rapidly identify host genes and genetic networks that regulate complex disease outcomes. Using genetically diverse animals from incipient lines of the Collaborative Cross mouse panel, we demonstrate a greatly expanded range of phenotypes relative to classical mouse models of SARS-CoV infection including lung pathology, weight loss and viral titer. Genetic mapping revealed several loci contributing to differential disease responses, including an 8.5Mb locus associated with vascular cuffing on chromosome 3 that contained 23 genes and 13 noncoding RNAs. Integrating phenotypic and genetic data narrowed this region to a single gene, <italic>Trim55</italic>, an E3 ubiquitin ligase with a role in muscle fiber maintenance. Lung pathology and transcriptomic data from mice genetically deficient in <italic>Trim55</italic> were used to validate its role in SARS-CoV-induced vascular cuffing and inflammation. These data establish the Collaborative Cross platform as a powerful genetic resource for uncovering genetic contributions of complex traits in microbial disease severity, inflammation and virus replication in models of outbred populations.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author><author><name sortKey="Lai, St" uniqKey="Lai S">ST Lai</name></author><author><name sortKey="Poon, Ll" uniqKey="Poon L">LL Poon</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name></author><author><name sortKey="Yam, Ly" uniqKey="Yam L">LY Yam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Li, Ks" uniqKey="Li K">KS Li</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y 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(État)</li><li>Texas</li><li>Washington (État)</li></region><settlement><li>Seattle</li></settlement><orgName><li>Université de Washington</li></orgName></list><tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E." last="Gralinski">Lisa E. 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Churchill</name><name sortKey="Deming, Damon" sort="Deming, Damon" uniqKey="Deming D" first="Damon" last="Deming">Damon Deming</name><name sortKey="Ferris, Martin T" sort="Ferris, Martin T" uniqKey="Ferris M" first="Martin T." last="Ferris">Martin T. Ferris</name><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B." last="Frieman">Matthew B. Frieman</name><name sortKey="Green, Richard" sort="Green, Richard" uniqKey="Green R" first="Richard" last="Green">Richard Green</name><name sortKey="Heise, Mark T" sort="Heise, Mark T" uniqKey="Heise M" first="Mark T." last="Heise">Mark T. Heise</name><name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G." last="Katze">Michael G. Katze</name><name sortKey="Mcmillan, Leonard" sort="Mcmillan, Leonard" uniqKey="Mcmillan L" first="Leonard" last="Mcmillan">Leonard Mcmillan</name><name sortKey="Menachery, Vineet D" sort="Menachery, Vineet D" uniqKey="Menachery V" first="Vineet D." last="Menachery">Vineet D. Menachery</name><name sortKey="Miller, Darla R" sort="Miller, Darla R" uniqKey="Miller D" first="Darla R." last="Miller">Darla R. Miller</name><name sortKey="Miller, Darla R" sort="Miller, Darla R" uniqKey="Miller D" first="Darla R." last="Miller">Darla R. Miller</name><name sortKey="Pardo Manuel De Villena, Fernando" sort="Pardo Manuel De Villena, Fernando" uniqKey="Pardo Manuel De Villena F" first="Fernando" last="Pardo-Manuel De Villena">Fernando Pardo-Manuel De Villena</name><name sortKey="Pardo Manuel De Villena, Fernando" sort="Pardo Manuel De Villena, Fernando" uniqKey="Pardo Manuel De Villena F" first="Fernando" last="Pardo-Manuel De Villena">Fernando Pardo-Manuel De Villena</name><name sortKey="Threadgill, David W" sort="Threadgill, David W" uniqKey="Threadgill D" first="David W." last="Threadgill">David W. Threadgill</name><name sortKey="Valdar, William" sort="Valdar, William" uniqKey="Valdar W" first="William" last="Valdar">William Valdar</name><name sortKey="Whitmore, Alan C" sort="Whitmore, Alan C" uniqKey="Whitmore A" first="Alan C." last="Whitmore">Alan C. Whitmore</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|wiki= Sante
|area= SrasV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= PMC:4599853
|texte= Genome Wide Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross
}}
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