Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease
Autoimmune disorders display complex phenotypes with clinically diverse manifestations, which together with complex genetic inheritance and environmental factors triggering the disease may complicate the diagnosis and investigation of the disease mechanism. The use of dog breeds may facilitate the analysis of genetic factors based on genetic homogeneity within a breed. We performed genetic analysis of two diseases common in dogs, immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA) that are similar to human SLE and a group of vasulitides such as Kawasaki disease, Henoch-Schönlein purpura and Behçet’s disease, correspondingly. We identified eleven genes along with specific alleles and genotypes for the major histocompatibility complex II involved in susceptibility, and studied their expression. The genes shared between the two diseases may be involved in the common immune signaling pathways and hence account for the common clinical signs, whereas the phenotype-specific genes may be implicated in particular pathways active in certain tissues and organs, and thereby may be responsible for characteristic manifestations seen only in one of the diseases. Further, the similarity between human and dog SLE at the genetic and functional levels demonstrated by the association of the BANK1 gene in both species indicates the common cross-species mechanisms of autoimmunity and may help identification of novel disease genes and pathways.
Vyšlo v časopise:
Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005248
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1005248
Souhrn
Autoimmune disorders display complex phenotypes with clinically diverse manifestations, which together with complex genetic inheritance and environmental factors triggering the disease may complicate the diagnosis and investigation of the disease mechanism. The use of dog breeds may facilitate the analysis of genetic factors based on genetic homogeneity within a breed. We performed genetic analysis of two diseases common in dogs, immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA) that are similar to human SLE and a group of vasulitides such as Kawasaki disease, Henoch-Schönlein purpura and Behçet’s disease, correspondingly. We identified eleven genes along with specific alleles and genotypes for the major histocompatibility complex II involved in susceptibility, and studied their expression. The genes shared between the two diseases may be involved in the common immune signaling pathways and hence account for the common clinical signs, whereas the phenotype-specific genes may be implicated in particular pathways active in certain tissues and organs, and thereby may be responsible for characteristic manifestations seen only in one of the diseases. Further, the similarity between human and dog SLE at the genetic and functional levels demonstrated by the association of the BANK1 gene in both species indicates the common cross-species mechanisms of autoimmunity and may help identification of novel disease genes and pathways.
Zdroje
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