Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease

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Wilbe , M , Kozyrev , S V , Farias , F H G , Bremer , H D , Hedlund , A , Pielberg , G R , Seppala , E H , Gustafson , U , Lohi , H , Carlborg , O , Andersson , G , Hansson-Hamlin , H & Lindblad-Toh , K 2015 , ' Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease ' , PLoS Genetics , vol. 11 , no. 6 , 1005248 . https://doi.org/10.1371/journal.pgen.1005248

Title: Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease
Author: Wilbe, Maria; Kozyrev, Sergey V.; Farias, Fabiana H. G.; Bremer, Hanna D.; Hedlund, Anna; Pielberg, Gerli R.; Seppala, Eija H.; Gustafson, Ulla; Lohi, Hannes; Carlborg, Orjan; Andersson, Goran; Hansson-Hamlin, Helene; Lindblad-Toh, Kerstin
Contributor: University of Helsinki, Hannes Tapani Lohi / Principal Investigator
University of Helsinki, Research Programs Unit
Date: 2015-06
Language: eng
Number of pages: 27
Belongs to series: PLoS Genetics
ISSN: 1553-7390
URI: http://hdl.handle.net/10138/162492
Abstract: The complexity of clinical manifestations commonly observed in autoimmune disorders poses a major challenge to genetic studies of such diseases. Systemic lupus erythematosus (SLE) affects humans as well as other mammals, and is characterized by the presence of antinuclear antibodies (ANA) in patients' sera and multiple disparate clinical features. Here we present evidence that particular sub-phenotypes of canine SLE-related disease, based on homogenous (ANA(H)) and speckled ANA (ANA(S)) staining pattern, and also steroid-responsive meningitis-arteritis (SRMA) are associated with different but overlapping sets of genes. In addition to association to certain MHC alleles and haplotypes, we identified 11 genes (WFDC3, HOMER2, VRK1, PTPN3, WHAMM, BANK1, AP3B2, DAPP1, LAM-TOR3, DDIT4L and PPP3CA) located on five chromosomes that contain multiple risk haplotypes correlated with gene expression and disease sub-phenotypes in an intricate manner. Intriguingly, the association of BANK1 with both human and canine SLE appears to lead to similar changes in gene expression levels in both species. Our results suggest that molecular definition may help unravel the mechanisms of different clinical features common between and specific to various autoimmune disease phenotypes in dogs and humans.
Subject: SYSTEMIC-LUPUS-ERYTHEMATOSUS
RESPONSIVE MENINGITIS-ARTERITIS
DOMAIN-PEPTIDE COMPLEX
BANK1 GENE
REVISED CRITERIA
WIDE ASSOCIATION
KAWASAKI-DISEASE
PAIN SYNDROME
SUSCEPTIBILITY
VARIANTS
3111 Biomedicine
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