An in silico approach reveals associations between genetic and epigenetic factors within regulatory elements in B cells from primary Sjögren’s syndrome patients
Recent advances in genetics have highlighted several regions and candidate genes associated with primary Sjögren's syndrome (SS), a systemic autoimmune epithelitis that combines exocrine gland dysfunctions, and focal lymphocytic infiltrations. In addition to genetic factors, it is now clear tha...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00437/full |
| _version_ | 1818364342834298880 |
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| author | Orsia D. Konsta Orsia D. Konsta Christelle eLE DANTEC Amandine eCharras Wesley H. Brooks Marina I Arleevskaya Anne eBordron Yves eRenaudineau Yves eRenaudineau |
| author_facet | Orsia D. Konsta Orsia D. Konsta Christelle eLE DANTEC Amandine eCharras Wesley H. Brooks Marina I Arleevskaya Anne eBordron Yves eRenaudineau Yves eRenaudineau |
| author_sort | Orsia D. Konsta |
| collection | DOAJ |
| description | Recent advances in genetics have highlighted several regions and candidate genes associated with primary Sjögren's syndrome (SS), a systemic autoimmune epithelitis that combines exocrine gland dysfunctions, and focal lymphocytic infiltrations. In addition to genetic factors, it is now clear that epigenetic deregulations are present during SS and restricted to specific cell type subsets such as lymphocytes and salivary gland epithelial cells. In this study, 72 single nucleotide polymorphisms (SNPs) associated with 43 SS gene risk factors were selected from publicly available and peer reviewed literature for further in silico analysis. SS risk variant location was tested revealing a broad distribution in coding sequences (5.6%), intronic sequences (55.6%), upstream/downstream genic regions (30.5%), and intergenic regions (8.3%). Moreover, a significant enrichment of regulatory motifs (promoter, enhancer, insulator, DNAse peak and eQTL) characterizes SS risk variants (94.4%). Next, screening SNPs in high linkage disequilibrium (r2 ≥ 0.8 in Caucasians) revealed 645 new variants including 5 SNPs with missense mutations, and indicated an enrichment of transcriptionally active motifs according to the cell type (B cells > monocytes > T cells >> A549). Finally, we looked at SS risk variants for histone markers in B cells (GM12878), monocytes (CD14+) and epithelial cells (A548). Active histone markers were associated with SS risk variants at both promoters and enhancers in B cells, and within enhancers in monocytes. In conclusion and based on the obtained in silico results, that need further confirmation, associations were observed between SS genetic risk factors and epigenetic factors and these associations predominate in B cells such as those observed at the FAM167A-BLK locus. |
| first_indexed | 2024-12-13T22:02:51Z |
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| id | doaj.art-06dc75d8220c4ab6a50f67bea7a34e7c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T22:02:51Z |
| publishDate | 2015-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-06dc75d8220c4ab6a50f67bea7a34e7c2022-12-21T23:29:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242015-08-01610.3389/fimmu.2015.00437155827An in silico approach reveals associations between genetic and epigenetic factors within regulatory elements in B cells from primary Sjögren’s syndrome patientsOrsia D. Konsta0Orsia D. Konsta1Christelle eLE DANTEC2Amandine eCharras3Wesley H. Brooks4Marina I Arleevskaya5Anne eBordron6Yves eRenaudineau7Yves eRenaudineau8INSERMSchool of MedicineINSERMINSERMUniversity of South Florida TampaKazan State Medical AcademyINSERMBrest University Medical SchoolINSERMRecent advances in genetics have highlighted several regions and candidate genes associated with primary Sjögren's syndrome (SS), a systemic autoimmune epithelitis that combines exocrine gland dysfunctions, and focal lymphocytic infiltrations. In addition to genetic factors, it is now clear that epigenetic deregulations are present during SS and restricted to specific cell type subsets such as lymphocytes and salivary gland epithelial cells. In this study, 72 single nucleotide polymorphisms (SNPs) associated with 43 SS gene risk factors were selected from publicly available and peer reviewed literature for further in silico analysis. SS risk variant location was tested revealing a broad distribution in coding sequences (5.6%), intronic sequences (55.6%), upstream/downstream genic regions (30.5%), and intergenic regions (8.3%). Moreover, a significant enrichment of regulatory motifs (promoter, enhancer, insulator, DNAse peak and eQTL) characterizes SS risk variants (94.4%). Next, screening SNPs in high linkage disequilibrium (r2 ≥ 0.8 in Caucasians) revealed 645 new variants including 5 SNPs with missense mutations, and indicated an enrichment of transcriptionally active motifs according to the cell type (B cells > monocytes > T cells >> A549). Finally, we looked at SS risk variants for histone markers in B cells (GM12878), monocytes (CD14+) and epithelial cells (A548). Active histone markers were associated with SS risk variants at both promoters and enhancers in B cells, and within enhancers in monocytes. In conclusion and based on the obtained in silico results, that need further confirmation, associations were observed between SS genetic risk factors and epigenetic factors and these associations predominate in B cells such as those observed at the FAM167A-BLK locus.http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00437/fullAutoimmunityGeneticsepigeneticsB cellsHistone Modificationspolymorphism |
| spellingShingle | Orsia D. Konsta Orsia D. Konsta Christelle eLE DANTEC Amandine eCharras Wesley H. Brooks Marina I Arleevskaya Anne eBordron Yves eRenaudineau Yves eRenaudineau An in silico approach reveals associations between genetic and epigenetic factors within regulatory elements in B cells from primary Sjögren’s syndrome patients Frontiers in Immunology Autoimmunity Genetics epigenetics B cells Histone Modifications polymorphism |
| title | An in silico approach reveals associations between genetic and epigenetic factors within regulatory elements in B cells from primary Sjögren’s syndrome patients |
| title_full | An in silico approach reveals associations between genetic and epigenetic factors within regulatory elements in B cells from primary Sjögren’s syndrome patients |
| title_fullStr | An in silico approach reveals associations between genetic and epigenetic factors within regulatory elements in B cells from primary Sjögren’s syndrome patients |
| title_full_unstemmed | An in silico approach reveals associations between genetic and epigenetic factors within regulatory elements in B cells from primary Sjögren’s syndrome patients |
| title_short | An in silico approach reveals associations between genetic and epigenetic factors within regulatory elements in B cells from primary Sjögren’s syndrome patients |
| title_sort | in silico approach reveals associations between genetic and epigenetic factors within regulatory elements in b cells from primary sj 246 gren s syndrome patients |
| topic | Autoimmunity Genetics epigenetics B cells Histone Modifications polymorphism |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00437/full |
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