Complex interaction between HNRNPD mutations and risk polymorphisms is associated with discordant Crohn’s disease in monozygotic twins
Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) affecting the lining of digestive tracts of the colon and ileum. To investigate the reasons behind the presence of CD phenotype in one of the monozygotic (MZ) twins, we utilized the whole exome sequence (WES) datasets of CD tissue bi...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-07-01
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| Series: | Autoimmunity |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/08916934.2017.1300883 |
| _version_ | 1797684773750046720 |
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| author | Tejaswini Prakash Avinash Veerappa Nallur B. Ramachandra |
| author_facet | Tejaswini Prakash Avinash Veerappa Nallur B. Ramachandra |
| author_sort | Tejaswini Prakash |
| collection | DOAJ |
| description | Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) affecting the lining of digestive tracts of the colon and ileum. To investigate the reasons behind the presence of CD phenotype in one of the monozygotic (MZ) twins, we utilized the whole exome sequence (WES) datasets of CD tissue biopsy and CD blood of affected twin and the exome dataset of blood from healthy twin. We report the presence of discordant and rare damaging mutation in HNRNPD and other risk polymorphisms such as, rs12103, rs2241880, rs3810936, rs7076156, rs1042058 and rs1292053. HNRNPD was found carrying two novel heterozygous mutations – a stop gain mutation that truncated the protein at 249th and 268th amino acid position and a single base missense mutation replacing Aspartate with Valine at 300th amino acid. The identified risk polymorphisms were found conferring susceptibility to CD and IBD. Discordant deleterious and damaging mutation was detected in HNRNPD that have been implicated in inflammatory pathways. Integrating these variants led to the elucidation of pathophysiology of CD in the affected twin involving the causal processes of macrophage activation, tissue death, autophagy, immune response, cell-migration and T-cell activation. |
| first_indexed | 2024-03-12T00:34:38Z |
| format | Article |
| id | doaj.art-ef7e541c99614fcbbc3f11f5fce5b0ab |
| institution | Directory Open Access Journal |
| issn | 0891-6934 1607-842X |
| language | English |
| last_indexed | 2024-03-12T00:34:38Z |
| publishDate | 2017-07-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autoimmunity |
| spelling | doaj.art-ef7e541c99614fcbbc3f11f5fce5b0ab2023-09-15T10:01:07ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2017-07-0150527527610.1080/08916934.2017.13008831300883Complex interaction between HNRNPD mutations and risk polymorphisms is associated with discordant Crohn’s disease in monozygotic twinsTejaswini Prakash0Avinash Veerappa1Nallur B. Ramachandra2University of MysoreUniversity of MysoreUniversity of MysoreCrohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) affecting the lining of digestive tracts of the colon and ileum. To investigate the reasons behind the presence of CD phenotype in one of the monozygotic (MZ) twins, we utilized the whole exome sequence (WES) datasets of CD tissue biopsy and CD blood of affected twin and the exome dataset of blood from healthy twin. We report the presence of discordant and rare damaging mutation in HNRNPD and other risk polymorphisms such as, rs12103, rs2241880, rs3810936, rs7076156, rs1042058 and rs1292053. HNRNPD was found carrying two novel heterozygous mutations – a stop gain mutation that truncated the protein at 249th and 268th amino acid position and a single base missense mutation replacing Aspartate with Valine at 300th amino acid. The identified risk polymorphisms were found conferring susceptibility to CD and IBD. Discordant deleterious and damaging mutation was detected in HNRNPD that have been implicated in inflammatory pathways. Integrating these variants led to the elucidation of pathophysiology of CD in the affected twin involving the causal processes of macrophage activation, tissue death, autophagy, immune response, cell-migration and T-cell activation.http://dx.doi.org/10.1080/08916934.2017.1300883crohn's diseaseautoimmunityinflammationhnrnpdmz twins |
| spellingShingle | Tejaswini Prakash Avinash Veerappa Nallur B. Ramachandra Complex interaction between HNRNPD mutations and risk polymorphisms is associated with discordant Crohn’s disease in monozygotic twins Autoimmunity crohn's disease autoimmunity inflammation hnrnpd mz twins |
| title | Complex interaction between HNRNPD mutations and risk polymorphisms is associated with discordant Crohn’s disease in monozygotic twins |
| title_full | Complex interaction between HNRNPD mutations and risk polymorphisms is associated with discordant Crohn’s disease in monozygotic twins |
| title_fullStr | Complex interaction between HNRNPD mutations and risk polymorphisms is associated with discordant Crohn’s disease in monozygotic twins |
| title_full_unstemmed | Complex interaction between HNRNPD mutations and risk polymorphisms is associated with discordant Crohn’s disease in monozygotic twins |
| title_short | Complex interaction between HNRNPD mutations and risk polymorphisms is associated with discordant Crohn’s disease in monozygotic twins |
| title_sort | complex interaction between hnrnpd mutations and risk polymorphisms is associated with discordant crohn s disease in monozygotic twins |
| topic | crohn's disease autoimmunity inflammation hnrnpd mz twins |
| url | http://dx.doi.org/10.1080/08916934.2017.1300883 |
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