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

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New emerging pathogens are a significant threat to human health with at least six highly pathogenic viruses, including four respiratory viruses, having spread from animal hosts into the human population within the past 15 years. With the emergence of new pathogens, new and better animal models are needed in order to better understand the disease these pathogens cause; to assist in the rapid development of therapeutics; and importantly to evaluate the role of natural host genetic variation in regulating disease outcome. We used incipient lines of the Collaborative Cross, a newly available recombinant inbred mouse panel, to identify polymorphic host genes that contribute to SARS-CoV pathogenesis. We discovered new animal models that better capture the range of disease found in human SARS patients and also found four novel susceptibility loci governing various aspects of SARS-induced pathogenesis. By integrating statistical, genetic and bioinformatic approaches we were able to narrow candidate genome regions to highly likely candidate genes. We narrowed one locus to a single candidate gene, Trim55, and confirmed its role in the inflammatory response to SARS-CoV infection through the use of knockout mice. This work identifies a novel function for Trim55 and also demonstrates the utility of the CC as a platform for identifying the genetic contributions of complex traits.

Vyšlo v časopise: Genome Wide Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005504
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005504

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