Wilbe, Maria and Kozyrev, Sergey V. and Farias, F.H.G. and Bremer, Hanna and Hedlund, Anna and Pielberg, Gerli and Seppälä, Eija H. and Gustafson, Ulla and Lohi, Hannes and Carlborg, Örjan and Andersson, Göran and Hamlin, Helene and Lindblad-Toh, Kerstin
(2015).
Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease.
PLoS genetics. 11
, 1-27
[Research article]
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Official URL: http://dx.doi.org/10.1371/journal.pgen.1005248
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 (ANAH) and speckled ANA (ANAS) 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/Creators: | Wilbe, Maria and Kozyrev, Sergey V. and Farias, F.H.G. and Bremer, Hanna and Hedlund, Anna and Pielberg, Gerli and Seppälä, Eija H. and Gustafson, Ulla and Lohi, Hannes and Carlborg, Örjan and Andersson, Göran and Hamlin, Helene and Lindblad-Toh, Kerstin | ||||||
|---|---|---|---|---|---|---|---|
| Title: | Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease | ||||||
| Series Name/Journal: | PLoS genetics | ||||||
| Year of publishing : | 2015 | ||||||
| Volume: | 11 | ||||||
| Page range: | 1-27 | ||||||
| Number of Pages: | 27 | ||||||
| Publisher: | Public Library of Science | ||||||
| ISSN: | 1553-7404 | ||||||
| Language: | English | ||||||
| Publication Type: | Research article | ||||||
| Refereed: | Yes | ||||||
| Article category: | Scientific peer reviewed | ||||||
| Version: | Published version | ||||||
| Copyright: | Creative Commons: Attribution 4.0 | ||||||
| Full Text Status: | Public | ||||||
| Subjects: | (A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Other Veterinary Science (A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 404 Agricultural Biotechnology > Genetics and Breeding | ||||||
| Agrovoc terms: | autoimmune diseases, genetic disorders | ||||||
| Keywords: | Systemic-Lupus-Erythematosus, responsive meningitis-arteritis, Domain-peptide complex, BANK1 gene, Kawasaki-disease, Pain syndrome, Susceptibility | ||||||
| URN:NBN: | urn:nbn:se:slu:epsilon-e-4899 | ||||||
| Permanent URL: | http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-4899 | ||||||
| Additional ID: |
| ||||||
| ID Code: | 15490 | ||||||
| Faculty: | VH - Faculty of Veterinary Medicine and Animal Science | ||||||
| Department: | (VH) > Dept. of Clinical Sciences (VH) > Dept. of Animal Breeding and Genetics | ||||||
| Deposited By: | SLUpub Connector | ||||||
| Deposited On: | 25 May 2018 09:04 | ||||||
| Metadata Last Modified: | 09 Sep 2020 14:17 |
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