X chromosome inactivation in female predisposition to autoimmunity

Simple item page
buir.advisorÖzçelik, Tayfun
dc.contributor.authorUz, Elif
dc.date.accessioned2016-01-08T18:06:12Z
dc.date.available2016-01-08T18:06:12Z
dc.date.issued2008
dc.descriptionAnkara : The Department of Molecular Biology and Genetics and the Institute of Engineering and Science of Bilkent University, 2008.en_US
dc.descriptionThesis (Ph.D.] -- Bilkent University, 2008.en_US
dc.descriptionIncludes bibliographical references leaves 95-121.en_US
dc.description.abstractThe high female preponderance is thought to be important in identifying the etiological factors. Sex hormones, pregnancy related microchimerism, and environmental factors are investigated as likely candidates. Disturbed Xchromosome inactivation (XCI) is another candidate, which may contribute to the break-down of self-tolerance. In this study, we tested the hypothesis that “loss of mosaicism” for X-linked gene expression may contribute to autoimmune disease etiology. Therefore, XCI status of healthy individuals and patients diagnosed with scleroderma (SSc), autoimmune thyroiditis (AITDs), Sjogren’s syndrome (SICCA), and juvenile idiopathic arthritis (JIA) in the Turkish population were analyzed by genotyping the methylation status of a CAG polymorphism in the androgen receptor (AR) gene. Extremely skewed XCI was observed in a significant proportion of SSc (OR: 38.9; P<0.0001), AITDs (OR: 9.6; P<0.0001), and JIA (OR: 4.4; P=0.0022). Further genotyping of AITDs in Tunisian and SSc in the US population supported the initial observations (OR: 3.8; P=0.0046; OR: 3.8; P<0.0001) respectively. Analysis of rheumatoid arthritis (RA) in the Tunisian population suggests that extremely skewed XCI (OR: 6.7; P<0.0001) could be involved in disease pathogenesis. Moreover, pre-eclampsia, a disease in which autoimmunity may be important, skewed XCI was observed (OR; 11.7; P=0.0005). However, in SICCA random patterns of XCI was observed suggesting that extreme skewing is not a common feature of all female prevalent autoimmune disorders. In conclusion, our results suggest that extremely skewed XCI may be important factor in autoimmune disease pathogenesis.en_US
dc.description.provenanceMade available in DSpace on 2016-01-08T18:06:12Z (GMT). No. of bitstreams: 1 0003589.pdf: 3932820 bytes, checksum: 95344a52ea08072d1b57bc63f7d791bf (MD5)en
dc.description.statementofresponsibilityUz, Elifen_US
dc.format.extentxxiii, 136 leaves, [28] leaves, illustrations, graphsen_US
dc.identifier.urihttp://hdl.handle.net/11693/14728
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectautoimmune diseasesen_US
dc.subjectX-chromosome inactivationen_US
dc.subjectfemale predispositionen_US
dc.subjectHUMARA assayen_US
dc.subject.lccWD305 .U9 2008en_US
dc.subject.lcshAutoimmune diseases Genetic aspects.en_US
dc.subject.lcshAutoimmunity.en_US
dc.subject.lcshX chromosome.en_US
dc.titleX chromosome inactivation in female predisposition to autoimmunityen_US
dc.typeThesisen_US
thesis.degree.disciplineMolecular Biology and Genetics
thesis.degree.grantorBilkent University
thesis.degree.levelDoctoral
thesis.degree.namePh.D. (Doctor of Philosophy)

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
0003589.pdf
Size:
3.75 MB
Format:
Adobe Portable Document Format
Download

Collections

Graduate School of Engineering and Science