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Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease
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نویسنده
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wilbe m. ,kozyrev s.v. ,farias f.h.g. ,bremer h.d. ,hedlund a. ,pielberg g.r. ,seppälä e.h. ,department of veterinary biosciences university of helsinki and folkhälsan research center ,gustafson u. ,lohi h. ,department of veterinary biosciences university of helsinki and folkhälsan research center ,carlborg ö. ,andersson g. ,hansson-hamlin h. ,lindblad-toh k.
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منبع
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plos genetics - 2015 - دوره : 11 - شماره : 6
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چکیده
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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. © 2015 wilbe et al.
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آدرس
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department of animal breeding and genetics,swedish university of agricultural sciences (slu),uppsala,sweden,science for life laboratory,department of immunology,genetics and pathology,uppsala university,uppsala, Sweden, science for life laboratory,department of medical biochemistry and microbiology,uppsala university,uppsala, Sweden, science for life laboratory,department of medical biochemistry and microbiology,uppsala university,uppsala, Sweden, department of clinical sciences,swedish university of agricultural sciences (slu),uppsala, Sweden, department of animal breeding and genetics,swedish university of agricultural sciences (slu),uppsala, Sweden, science for life laboratory,department of medical biochemistry and microbiology,uppsala university,uppsala, Sweden, research programs unit, Molecular Neurology, helsinki,finland,blueprint genetics ltd,helsinki, Finland, department of animal breeding and genetics,swedish university of agricultural sciences (slu),uppsala, Sweden, research programs unit, Molecular Neurology, helsinki, Finland, department of clinical sciences,division of computational genetics,swedish university of agricultural sciences (slu),uppsala, Sweden, department of animal breeding and genetics,swedish university of agricultural sciences (slu),uppsala, Sweden, department of clinical sciences,swedish university of agricultural sciences (slu),uppsala, Sweden, science for life laboratory,department of medical biochemistry and microbiology,uppsala university,uppsala,sweden,broad institute,cambridge,cambridge,ma, United States
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Authors
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m. ,s.v. ,f.h.g. ,h.d. ,a. ,g.r. ,e.h. ,university of helsinki and folkhälsan research center ,u. ,h. ,university of helsinki and folkhälsan research center ,ö. ,g. ,h. ,k.
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