Retrospective Single Nucleotide Polymorphism Analysis of Host Resistance and Susceptibility to Ovine Johne’s Disease Using Restored FFPE DNA

dc.contributor.authorKravitz, Amandaen
dc.contributor.authorLiao, Mingsien
dc.contributor.authorMorota, Gotaen
dc.contributor.authorTyler, Ronen
dc.contributor.authorCockrum, Rebeccaen
dc.contributor.authorManohar, B. Muralien
dc.contributor.authorRonald, B. Samuel Masilamonien
dc.contributor.authorCollins, Michael T.en
dc.contributor.authorSriranganathan, Nammalwaren
dc.date.accessioned2024-07-29T13:25:50Zen
dc.date.available2024-07-29T13:25:50Zen
dc.date.issued2024-07-15en
dc.date.updated2024-07-26T12:29:03Zen
dc.description.abstractJohne&rsquo;s disease (JD), also known as paratuberculosis, is a chronic, untreatable gastroenteritis of ruminants caused by <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> (MAP) infection. Evidence for host genetic resistance to disease progression exists, although it is limited due to the extended incubation period (years) and diagnostic challenges. To overcome this, previously restored formalin-fixed paraffin embedded tissue (FFPE) DNA from archived FFPE tissue cassettes was utilized for a novel retrospective case-control genome-wide association study (GWAS) on ovine JD. Samples from known MAP-infected flocks with ante- and postmortem diagnostic data were used. Cases (N = 9) had evidence of tissue infection, compared to controls (N = 25) without evidence of tissue infection despite positive antemortem diagnostics. A genome-wide efficient mixed model analysis (GEMMA) to conduct a GWAS using restored FFPE DNA SNP results from the Illumina Ovine SNP50 Bead Chip, identified 10 SNPs reaching genome-wide significance of <i>p</i> &lt; 1 &times; 10<sup>&minus;6</sup> on chromosomes 1, 3, 4, 24, and 26. Pathway analysis using PANTHER and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was completed on 45 genes found within 1 Mb of significant SNPs. Our work provides a framework for the novel use of archived FFPE tissues for animal genetic studies in complex diseases and further evidence for a genetic association in JD.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationKravitz, A.; Liao, M.; Morota, G.; Tyler, R.; Cockrum, R.; Manohar, B.M.; Ronald, B.S.M.; Collins, M.T.; Sriranganathan, N. Retrospective Single Nucleotide Polymorphism Analysis of Host Resistance and Susceptibility to Ovine Johne&rsquo;s Disease Using Restored FFPE DNA. Int. J. Mol. Sci. 2024, 25, 7748.en
dc.identifier.doihttps://doi.org/10.3390/ijms25147748en
dc.identifier.urihttps://hdl.handle.net/10919/120731en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleRetrospective Single Nucleotide Polymorphism Analysis of Host Resistance and Susceptibility to Ovine Johne&rsquo;s Disease Using Restored FFPE DNAen
dc.title.serialInternational Journal of Molecular Scienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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