PLoS Genetics (Jun 2015)

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

  • Maria Wilbe,
  • Sergey V Kozyrev,
  • Fabiana H G Farias,
  • Hanna D Bremer,
  • Anna Hedlund,
  • Gerli R Pielberg,
  • Eija H Seppälä,
  • Ulla Gustafson,
  • Hannes Lohi,
  • Örjan Carlborg,
  • Göran Andersson,
  • Helene Hansson-Hamlin,
  • Kerstin Lindblad-Toh

DOI
https://doi.org/10.1371/journal.pgen.1005248
Journal volume & issue
Vol. 11, no. 6
p. e1005248

Abstract

Read online

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.