A novel nonsense variant in SUPT20H gene associated with Rheumatoid Arthritis identified by Whole Exome Sequencing of multiplex families.
The triggering and development of Rheumatoid Arthritis (RA) is conditioned by environmental and genetic factors. Despite the identification of more than one hundred genetic variants associated with the disease, not all the cases can be explained. Here, we performed Whole Exome Sequencing in 9 multip...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0213387 |
| _version_ | 1819142796515213312 |
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| author | Maëva Veyssiere Javier Perea Laetitia Michou Anne Boland Christophe Caloustian Robert Olaso Jean-François Deleuze François Cornelis Elisabeth Petit-Teixeira Valérie Chaudru |
| author_facet | Maëva Veyssiere Javier Perea Laetitia Michou Anne Boland Christophe Caloustian Robert Olaso Jean-François Deleuze François Cornelis Elisabeth Petit-Teixeira Valérie Chaudru |
| author_sort | Maëva Veyssiere |
| collection | DOAJ |
| description | The triggering and development of Rheumatoid Arthritis (RA) is conditioned by environmental and genetic factors. Despite the identification of more than one hundred genetic variants associated with the disease, not all the cases can be explained. Here, we performed Whole Exome Sequencing in 9 multiplex families (N = 30) to identify rare variants susceptible to play a role in the disease pathogenesis. We pre-selected 77 genes which carried rare variants with a complete segregation with RA in the studied families. Follow-up linkage and association analyses with pVAAST highlighted significant RA association of 43 genes (p-value < 0.05 after 106 permutations) and pinpointed their most likely causal variant. We re-sequenced the 10 most significant likely causal variants (p-value ≤ 3.78*10-3 after 106 permutations) in the extended pedigrees and 9 additional multiplex families (N = 110). Only one SNV in SUPT20H: c.73A>T (p.Lys25*), presented a complete segregation with RA in an extended pedigree with early-onset cases. In summary, we identified in this study a new variant associated with RA in SUPT20H gene. This gene belongs to several biological pathways like macro-autophagy and monocyte/macrophage differentiation, which contribute to RA pathogenesis. In addition, these results showed that analyzing rare variants using a family-based approach is a strategy that allows to identify RA risk loci, even with a small dataset. |
| first_indexed | 2024-12-22T12:16:02Z |
| format | Article |
| id | doaj.art-0b0551b40c3c4cafae528e7dfbade9cd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T12:16:02Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0b0551b40c3c4cafae528e7dfbade9cd2022-12-21T18:26:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01143e021338710.1371/journal.pone.0213387A novel nonsense variant in SUPT20H gene associated with Rheumatoid Arthritis identified by Whole Exome Sequencing of multiplex families.Maëva VeyssiereJavier PereaLaetitia MichouAnne BolandChristophe CaloustianRobert OlasoJean-François DeleuzeFrançois CornelisElisabeth Petit-TeixeiraValérie ChaudruThe triggering and development of Rheumatoid Arthritis (RA) is conditioned by environmental and genetic factors. Despite the identification of more than one hundred genetic variants associated with the disease, not all the cases can be explained. Here, we performed Whole Exome Sequencing in 9 multiplex families (N = 30) to identify rare variants susceptible to play a role in the disease pathogenesis. We pre-selected 77 genes which carried rare variants with a complete segregation with RA in the studied families. Follow-up linkage and association analyses with pVAAST highlighted significant RA association of 43 genes (p-value < 0.05 after 106 permutations) and pinpointed their most likely causal variant. We re-sequenced the 10 most significant likely causal variants (p-value ≤ 3.78*10-3 after 106 permutations) in the extended pedigrees and 9 additional multiplex families (N = 110). Only one SNV in SUPT20H: c.73A>T (p.Lys25*), presented a complete segregation with RA in an extended pedigree with early-onset cases. In summary, we identified in this study a new variant associated with RA in SUPT20H gene. This gene belongs to several biological pathways like macro-autophagy and monocyte/macrophage differentiation, which contribute to RA pathogenesis. In addition, these results showed that analyzing rare variants using a family-based approach is a strategy that allows to identify RA risk loci, even with a small dataset.https://doi.org/10.1371/journal.pone.0213387 |
| spellingShingle | Maëva Veyssiere Javier Perea Laetitia Michou Anne Boland Christophe Caloustian Robert Olaso Jean-François Deleuze François Cornelis Elisabeth Petit-Teixeira Valérie Chaudru A novel nonsense variant in SUPT20H gene associated with Rheumatoid Arthritis identified by Whole Exome Sequencing of multiplex families. PLoS ONE |
| title | A novel nonsense variant in SUPT20H gene associated with Rheumatoid Arthritis identified by Whole Exome Sequencing of multiplex families. |
| title_full | A novel nonsense variant in SUPT20H gene associated with Rheumatoid Arthritis identified by Whole Exome Sequencing of multiplex families. |
| title_fullStr | A novel nonsense variant in SUPT20H gene associated with Rheumatoid Arthritis identified by Whole Exome Sequencing of multiplex families. |
| title_full_unstemmed | A novel nonsense variant in SUPT20H gene associated with Rheumatoid Arthritis identified by Whole Exome Sequencing of multiplex families. |
| title_short | A novel nonsense variant in SUPT20H gene associated with Rheumatoid Arthritis identified by Whole Exome Sequencing of multiplex families. |
| title_sort | novel nonsense variant in supt20h gene associated with rheumatoid arthritis identified by whole exome sequencing of multiplex families |
| url | https://doi.org/10.1371/journal.pone.0213387 |
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