Bayesian mixed model analysis uncovered 21 risk loci for chronic kidney disease in boxer dogs.

Chronic kidney disease (CKD) affects 10% of the human population, with only a small fraction genetically defined. CKD is also common in dogs and has been diagnosed in nearly all breeds, but its genetic basis remains unclear. Here, we performed a Bayesian mixed model genome-wide association analysis for canine CKD in a boxer population of 117 canine cases and 137 controls, and identified 21 genetic regions associated with the disease. At the top markers from each CKD region, the cases carried an average of 20.2 risk alleles, significantly higher than controls (15.6 risk alleles). An ANOVA test showed that the 21 CKD regions together explained 57% of CKD phenotypic variation in the population. Based on whole genome sequencing data of 20 boxers, we identified 5,206 variants in LD with the top 50 BayesR markers. Following comparative analysis with human regulatory data, 17 putative regulatory variants were identified and tested with electrophoretic mobility shift assays. In total four variants, three intronic variants from the MAGI2 and GALNT18 genes, and one variant in an intergenic region on chr28, showed alternative binding ability for the risk and protective alleles in kidney cell lines. Many genes from the 21 CKD regions, RELN, MAGI2, FGFR2 and others, have been implicated in human kidney development or disease. The results from this study provide new information that may enlighten the etiology of CKD in both dogs and humans.

Experimental Schistosomiasis japonica in the pig: immunohistology of the hepatic egg granuloma.

Use of the pig as an animal model in schistosomiasis research is increasing, but knowledge of the porcine immune response to schistosome infection is still very limited. We investigated the immunohistology of different maturation stages of the Schistosoma japonicum egg granuloma in pigs. Liver sections from pigs experimentally infected with S.japonicum for 9, 12 or 21 weeks were examined by immunohistochemistry using a three-step streptavidin-biotin-complex/immunoperoxidase method or a two-step alkaline phosphatase-mediated system. All granulomas showed marked expression of major histocompatibility complex (MHC) class II in epithelioid macrophages and were dominated by T lymphocytes, comprising both CD4+ and CD8+ phenotypes, with consistently higher proportions noted for CD8+ cells. B lymphocytes, as identified by expression of CD21, were confined to lymphoid nodular structures primarily associated with mature granulomas. Early and mature granulomas contained numerous immunoglobulin (Ig)G+ plasma cells. Significant differences in immunohistology related to duration of infection were not observed. The results indicate that all stages of the hepatic S.japonicum egg granuloma in the pig manifests MHC class II-dependent CD4+ T cell activity concomitant with infiltration of CD8+ T cells. B cell activity preceding the effector cell stage appears to occur in granuloma-associated lymphoid nodules, whereas antibody, mainly IgG, is produced within the granuloma.