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Variant origin |
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Variant description |
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Mapping and Phenotype information for this QTL, its variants and associated markersJ:276529In the immunocompromised host, invasive infection with the fungal pathogen Candida albicans is associated with high morbidity and mortality. Sporadic cases in otherwise normal individuals are rare, and they are thought to be associated with genetic predisposition. Using a mouse model of systemic infection with C. albicans, the authors identified the SM/J mouse strain as unusually susceptible to infection. A total of 150 (C57BL/6J x SM/J)F2 male mice were genotyped at the McGill University and Genome Quebec Innovation Centre (Montreal, QC, Canada) using Sequenome iPlex Gold technology and a custom panel that contained 126 informative SNPs distributed evenly across the genome. Nine additional microsatellite markers annotated in the Mouse Genome Informatics Database were used for gap filling and fine mapping.Genetic linkage analysis in R/qtl was performed using Haley-Knott regression. Linkage studies in informative (C57BL/6J x SM/J)F2 mice identified a major locus on distal chromosome 15, given the appellation Carg5, that regulates C. albicans replication in SM/J mice. Studies in additional F2 progeny (204 female, 40 male) validated the effect of Carg5 (peak LOD = 6.09) and delineated a minimal Bayesian interval (95% confidence limit).QTL Carg5 (Candida albicans resistance gene 5) maps to Chr15: 97.8 - 103.1 Mb with a peak LOD score of 6.09 at D15Mit77. Carg5 explains 11.3% of the phenotypic variance, and homozygosity for SM/J alleles is associated with higher kidney fungal load at Carg5. Experimental evidence indicates that Carg5-regulated susceptibility in SM/J is associated with a complex defect in the myeloid compartment of these mice, and susceptibility alleles are inherited in a recessive fashion. |
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References |
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 12/10/2024 MGI 6.24 |
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