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dc.contributor.authorVigeland, Maria Dehli
dc.date.accessioned2014-07-06T22:00:10Z
dc.date.issued2014
dc.identifier.citationVigeland, Maria Dehli. Exploring the functional relevance of genetic regions associated with rheumatoid arthritis. Master thesis, University of Oslo, 2014
dc.identifier.urihttp://hdl.handle.net/10852/39319
dc.description.abstractRheumatoid arthritis (RA) is a chronic autoimmune disease affecting nearly 1% of the western population. The disease is characterized by a systematic inflammatory process in the synovial joints initiated by the immune system, resulting in joint destruction and loss of articular cartilage. This cause pain, disability and reduced life quality for the patients. RA is a typical complex disease, with several genetic and environmental factors involved in disease susceptibility. At the initiation of this project, polymorphisms in 46 genetic regions had been identified as risk variants for RA. The causalities of these genetic susceptibility loci are generally unknown, but a common characteristic is that they map near immunologically important genes and reside in intergenic regions. With the publication of an extensive amount of functional data from the ENCODE (Encyclopedia of DNA elements) project in September 2012, new information about intergenic and regulatory regions became available. During this project, SNPs in linkage disequilibrium with the established RA risk loci were integrated with data from ENCODE to find potential causal variants responsible for the disease association signal. Thirteen new candidates were identified and tested for association in the Norwegian RA population in a case-control study of 944 RA patients and 1121 healthy controls. Five of the new SNPs were found significantly associated, and in the CD40 locus the association was significantly stronger towards the new candidate SNP than the original risk SNP. Expression quantitative trait loci analysis using genotype and gene expression data available from 42 Norwegian thymuses supported the plausible functional roles of the new candidate SNP in the CD40 locus. Because of its earlier demonstrated relevance in RA development, the CCR6 locus was selected for further functional investigation. Through DNA sequencing, a novel SNP believed to play a role in RA joint inflammation was confirmed as nonexistent in the Norwegian population. An investigation of cell specific CCR6 expression and its different transcripts was carried out on B and T cell populations extracted from a Norwegian control person, and new potential splice variants were detected. More research is needed to uncover the high proportion of missing heritability in RA, to understand the underlying functionality of the already established risk loci and to develop new, effective treatments.eng
dc.language.isoeng
dc.subjectrheumatoid
dc.subjectarthritis
dc.subjectassociation
dc.subjectanalysis
dc.subjectENCODE
dc.titleExploring the functional relevance of genetic regions associated with rheumatoid arthritiseng
dc.typeMaster thesis
dc.date.updated2014-07-06T22:00:10Z
dc.creator.authorVigeland, Maria Dehli
dc.date.embargoenddate3014-03-30
dc.rights.termsDette dokumentet er ikke elektronisk tilgjengelig etter ønske fra forfatter. Tilgangskode/Access code A
dc.identifier.urnURN:NBN:no-44171
dc.type.documentMasteroppgave
dc.rights.accessrightsclosedaccess
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/39319/1/Maria_masteroppgave.pdf


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