| http://purl.uniprot.org/citations/22970191 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22970191 | http://www.w3.org/2000/01/rdf-schema#comment | "BackgroundMice that are deficient for glutathione peroxidases 1 and 2 (GPX) show large variations in the penetrance and severity of colitis in C57BL/6J and 129S1/SvImJ backgrounds. We mapped a locus contributing to this difference to distal chromosome 2 (∼119-133 mbp) and named it glutathione peroxidase-deficiency-associated colitis 1 (Gdac1). The aim of this study was to identify the best gene candidates within the Gdac1 locus contributing to the murine colitis phenotype.Method/principal findingsWe refined the boundaries of Gdac1 to 118-125 mbp (95% confidence interval) by increasing sample size and marker density across the interval. The narrowed region contains 128 well-annotated protein coding genes but it excludes Fermt1, a human inflammatory bowel disease candidate that was within the original boundaries of Gdac1. The locus we identified may be the Cdcs3 locus mapped by others studying IL10-knockout mice. Using in silico analysis of the 128 genes, based on published colon expression data, the relevance of pathways to colitis, gene mutations, presence of non-synonymous-single-nucleotide polymorphisms (nsSNPs) and whether the nsSNPs are predicted to have an impact on protein function or expression, we excluded 42 genes. Based on a similar analysis, twenty-five genes from the remaining 86 genes were analyzed for expression-quantitative-trait loci, and another 15 genes were excluded.Conclusion/significanceAmong the remaining 10 genes, we identified Pla2g4f and Duox2 as the most likely colitis gene candidates, because GPX metabolizes PLA2G4F and DUOX2 products. Pla2g4f is a phospholipase A2 that has three potentially significant nsSNP variants and showed expression differences across mouse strains. PLA2G4F produces arachidonic acid, which is a substrate for lipoxygenases and, in turn, for GPXs. DUOX2 produces H(2)O(2) and may control microbial populations. DUOX-1 and -2 control microbial populations in mammalian lung and in the gut of several insects and zebrafish. Dysbiosis is a phenotype that differentiates 129S1/SvImJ from C57BL/6J and may be due to strain differences in DUOX2 activity."xsd:string |
| http://purl.uniprot.org/citations/22970191 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0044262"xsd:string |
| http://purl.uniprot.org/citations/22970191 | http://purl.uniprot.org/core/author | "Leto T.L."xsd:string |
| http://purl.uniprot.org/citations/22970191 | http://purl.uniprot.org/core/author | "Kim B.W."xsd:string |
| http://purl.uniprot.org/citations/22970191 | http://purl.uniprot.org/core/author | "Doroshow J.H."xsd:string |
| http://purl.uniprot.org/citations/22970191 | http://purl.uniprot.org/core/author | "Chu F.F."xsd:string |
| http://purl.uniprot.org/citations/22970191 | http://purl.uniprot.org/core/author | "Esworthy R.S."xsd:string |
| http://purl.uniprot.org/citations/22970191 | http://purl.uniprot.org/core/author | "Rivas G.E."xsd:string |
| http://purl.uniprot.org/citations/22970191 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22970191 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/22970191 | http://purl.uniprot.org/core/pages | "e44262"xsd:string |
| http://purl.uniprot.org/citations/22970191 | http://purl.uniprot.org/core/title | "Analysis of candidate colitis genes in the Gdac1 locus of mice deficient in glutathione peroxidase-1 and -2."xsd:string |
| http://purl.uniprot.org/citations/22970191 | http://purl.uniprot.org/core/volume | "7"xsd:string |
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