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AuthorSchäfer, Nadjadc.contributor.author
Date of accession2016-03-15T10:41:38Zdc.date.accessioned
Available in OPARU since2016-03-15T10:41:38Zdc.date.available
Year of creation2014dc.date.created
AbstractThe major elements associated with the autoimmune disease Type 1 Diabetes (T1D) are the highly polymorphic genes of the human leukocyte antigen (HLA), which are located on chromosome 6p21.3. The major risk of HLA encoded susceptibility to T1D is mediated by the alleles of the HLA-class-II-genes HLA-DRB1, HLA-DQA1 and HLA-DQB1. Predisposing as well as protective HLA-haplotypes have been identified. The protective HLA-haplotype DR2-DQ6.2 dominates over the predisposing HLA-haplotypes DR4-DQ8 and DR3-DQ2, because individuals heterozygous for the protective and one of these predisposing haplotypes have a significantly reduced disease risk. In this study expression levels of HLA-class-II-genes that are involved in developing T1D were determined. Therefore, lymphoblastoid B cell lines (B-LCLs) of probands with different HLA-constellations, which are differently associated with T1D, were used. We demonstrate that expression levels of HLA-DQA1 and HLA-DQB1 differ in B-LCLs of probands with different HLA-constellations. Furthermore, we found differences in expression of distinct alleles of HLA-DQA1 and HLA-DQB1 in heterozygous probands carrying different HLA-haplotypes. These results indicate that in addition to structural differences in HLA-class-II molecules, quantitative differences could be critical for developing T1D. Furthermore, since microRNAs (miRNAs) are important negative-regulators for gene expression, they are likely to contribute to regulating HLA-class-II genes. In this study we show that some miRNAs were expressed differently between probands with distinct HLA-constellations. This result could be an evidence for the regulatory role of miRNAs in HLA-class-II expression. In summary, our data have strengthened previous findings of allelic differences in expression of HLA-DQA1 and HLA-DQB1 genes. Our findings suggest a dose dependent effect of HLA-class-II molecules in the context of developing T1D.dc.description.abstract
Languagededc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandard (ohne Print-On-Demand)dc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_opod_v1dc.rights.uri
Keyword6p21dc.subject
KeywordAutoimmunerkrankungdc.subject
KeywordHLA-Haplotypdc.subject
KeywordLymphoblastoide B-Zellliniendc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHAutoimmune diseasesdc.subject.mesh
MeSHCytokinesdc.subject.mesh
MeSHDiabetes mellitus, Type 1dc.subject.mesh
MeSHHaplotypesdc.subject.mesh
MeSHHLA-DQA1 antigendc.subject.mesh
MeSHHLA-DQB1 antigendc.subject.mesh
MeSHMicroRNAsdc.subject.mesh
TitleIdentifikation differentiell exprimierter Gene im Kontext krankheitsassoziierter HLA-Haplotypen bei Typ 1 Diabetesdc.title
Resource typeDissertationdc.type
DOIhttp://dx.doi.org/10.18725/OPARU-3453dc.identifier.doi
PPN798746378dc.identifier.ppn
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-vts-92427dc.identifier.urn
GNDAntigenpräsentationdc.subject.gnd
GNDCytokinedc.subject.gnd
GNDHLAdc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
Date of activation2014-10-13T13:24:22Zuulm.freischaltungVTS
Peer reviewneinuulm.peerReview
Shelfmark print versionW: W-H 13.817uulm.shelfmark
DCMI TypeTextuulm.typeDCMI
VTS-ID9242uulm.vtsID
CategoryPublikationenuulm.category
University Bibliographyjauulm.unibibliographie


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