دورية أكاديمية
A novel nonsense variant in SUPT20H gene associated with Rheumatoid Arthritis identified by Whole Exome Sequencing of multiplex families
| العنوان: | A novel nonsense variant in SUPT20H gene associated with Rheumatoid Arthritis identified by Whole Exome Sequencing of multiplex families |
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| المؤلفون: | Veyssière, Maeva, Perea, Javier, Michou, Laétitia, Boland, Anne, Caloustian, Christophe, Olaso, Robert, E, Deleuze, Jean-François, Cornelis, Francois, Petit-Teixeira, Elisabeth, Chaudru, Valérie |
| المساهمون: | Laboratoire de recherche européen pour la polyarthrite rhumatoïde (GenHotel), Université d'Évry-Val-d'Essonne (UEVE), CHU de Québec–Université Laval, Université Laval Québec (ULaval), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), GenHotel-Auvergne (GenHotel), Université d'Auvergne - Clermont-Ferrand I (UdA) |
| المصدر: | ISSN: 1932-6203. |
| بيانات النشر: | HAL CCSD Public Library of Science |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Rheumatoid arthritis, Genetic loci, Principal component analysis, Genomic databases, Autoimmune Diseases, Genetics of disease, Permutation, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system |
| الوصف: | International audience ; 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/30845214; hal-02075447; https://univ-evry.hal.science/hal-02075447Test; https://univ-evry.hal.science/hal-02075447/documentTest; https://univ-evry.hal.science/hal-02075447/file/journal.pone.0213387.pdfTest; PUBMED: 30845214 |
| DOI: | 10.1371/journal.pone.0213387 |
| الإتاحة: | https://doi.org/10.1371/journal.pone.0213387Test https://univ-evry.hal.science/hal-02075447Test https://univ-evry.hal.science/hal-02075447/documentTest https://univ-evry.hal.science/hal-02075447/file/journal.pone.0213387.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.41C4BAE6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pone.0213387 |
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