title: Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease.
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, LAMTOR3, 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.
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Wilbe
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Kozyrev
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Fabiana H G
authors.initials: FH
authors.lastname: Farias
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
authors.forename: Hanna D
authors.initials: HD
authors.lastname: Bremer
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Hedlund
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Gerli R
authors.initials: GR
authors.lastname: Pielberg
authors.affiliation: Research Programs Unit, Molecular Neurology; Department of Veterinary Biosciences, University of Helsinki and Folkhälsan Research Center, Helsinki, Finland.
authors.forename: Eija H
authors.initials: EH
authors.lastname: Seppälä
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
authors.forename: Ulla
authors.initials: U
authors.lastname: Gustafson
authors.affiliation: Research Programs Unit, Molecular Neurology; Department of Veterinary Biosciences, University of Helsinki and Folkhälsan Research Center, Helsinki, Finland.
authors.forename: Hannes
authors.initials: H
authors.lastname: Lohi
authors.affiliation: Department of Clinical Sciences, Division of Computational Genetics, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
authors.forename: Örjan
authors.initials: Ö
authors.lastname: Carlborg
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Andersson
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
authors.forename: Helene
authors.initials: H
authors.lastname: Hansson-Hamlin
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Broad Institute, Cambridge, Cambridge, Massachusetts, United States of America.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D004285:Dogs; D056426:Genetic Loci; D016678:Genome; D006239:Haplotypes; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000662:veterinary; D010641:Phenotype