Retrospective Single Nucleotide Polymorphism Analysis of Host Resistance and Susceptibility to Ovine Johne’s Disease Using Restored FFPE DNA
| dc.contributor.author | Kravitz, Amanda | en |
| dc.contributor.author | Liao, Mingsi | en |
| dc.contributor.author | Morota, Gota | en |
| dc.contributor.author | Tyler, Ron | en |
| dc.contributor.author | Cockrum, Rebecca | en |
| dc.contributor.author | Manohar, B. Murali | en |
| dc.contributor.author | Ronald, B. Samuel Masilamoni | en |
| dc.contributor.author | Collins, Michael T. | en |
| dc.contributor.author | Sriranganathan, Nammalwar | en |
| dc.date.accessioned | 2024-07-29T13:25:50Z | en |
| dc.date.available | 2024-07-29T13:25:50Z | en |
| dc.date.issued | 2024-07-15 | en |
| dc.date.updated | 2024-07-26T12:29:03Z | en |
| dc.description.abstract | Johne’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> < 1 × 10<sup>−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.version | Published version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | Kravitz, 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’s Disease Using Restored FFPE DNA. Int. J. Mol. Sci. 2024, 25, 7748. | en |
| dc.identifier.doi | https://doi.org/10.3390/ijms25147748 | en |
| dc.identifier.uri | https://hdl.handle.net/10919/120731 | en |
| dc.language.iso | en | en |
| dc.publisher | MDPI | en |
| dc.rights | Creative Commons Attribution 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
| dc.subject | paratuberculosis | en |
| dc.subject | FFPE tissues | en |
| dc.subject | DNA repair | en |
| dc.subject | GWAS | en |
| dc.subject | host susceptibility | en |
| dc.title | Retrospective Single Nucleotide Polymorphism Analysis of Host Resistance and Susceptibility to Ovine Johne’s Disease Using Restored FFPE DNA | en |
| dc.title.serial | International Journal of Molecular Science | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |