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    Genome Wide Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross

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    Author
    Gralinski, L.E.
    Ferris, M.T.
    Frieman, M.B.
    Date
    2015
    Journal
    PLoS Genetics
    Publisher
    Public Library of Science
    Type
    Article
    
    Metadata
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    See at
    https://doi.org/10.1371/journal.pgen.1005504
    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, Trim55, an E3 ubiquitin ligase with a role in muscle fiber maintenance. Lung pathology and transcriptomic data from mice genetically deficient in Trim55 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.
    Sponsors
    Lineberger Comprehensive Cancer Center, University of North Carolina; National Cancer Institute, NCI; National Institute of Allergy and Infectious Diseases, NIAID; National Institutes of Health, NIH: U01CA134240; National Institutes of Health, NIH: U19 AI100625; National Institutes of Health, NIH: U54AI081680
    Keyword
    SARS-CoV
    genetic mapping
    SARS Virus
    Coronavirus Infections
    Genome
    Collaborative Cross Mice
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-84946606810&doi=10.1371%2fjournal.pgen.1005504&partnerID=40&md5=a61cbd21f395f0f1cf613b050ecf2336; http://hdl.handle.net/10713/12409
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pgen.1005504
    Scopus Count
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    UMB Coronavirus Publications

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