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dc.contributor.authorBeka, Sylvia
dc.date.accessioned2016-05-24T15:28:56Z
dc.date.available2016-05-24T15:28:56Z
dc.date.issued2016-05-24
dc.identifier.urihttp://hdl.handle.net/2299/17200
dc.description.abstractHuman complex diseases, like Diabetes and Cancer, affect many people worldwide today. Despite existing knowledge, many of these diseases are still not preventable. Complex diseases are known to be caused by a combination of genetic factors, as well as environmental and life style factors. The scope of this investigation covered the genomics of Type 1 Diabetes (T1D). There are 49 human genomic regions that are known to carry markers (disease-associated single nucleotide mutations) for T1D, and these were extensively studied in this research. The aim was to find out in how far this disease may be caused by problems in gene regulation rather than in gene coding. For this, the genetic factors associated with T1D, including the single point mutations and susceptibility regions, were characterised on the basis of their genomic attributes. Furthermore, mutations that occur in binding sites for transcription factors were analysed for change in the conspicuousness of their binding region, caused by allele substitution. This is called SNP (Single nucleotide polymorphism) sensitivity. From this study, it was found that the markers for T1D are mostly non-coding SNPs that occur in introns and non-coding gene transcripts, these are structures known to be involved in gene regulatory activity. It was also discovered that the T1D susceptibility regions contain an abundance of intronic, non-coding transcript and regulatory nucleotides, and that they can be split into three distinct groups on the basis of their structural and functional genomic contents. Finally, using an algorithm designed for this study, thirty-seven SNPs that change the representation of their surrounding region were identified. These regulatory mutations are non-associated T1D-SNPs that are mostly characterised by Cytosine to Thymine (C-T) transition mutations. They were found to be closer in average distance to the disease-associated SNPs than other SNPs in binding sites, and also to occur frequently in the binding motifs for the USF (Upstream stimulatory factor) protein family which is linked to problems in Type 2 diabetes.en_US
dc.language.isoenen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectSNPsen_US
dc.subjectPolymorphismsen_US
dc.subjectType 1 Diabetesen_US
dc.subjectComplex diseaseen_US
dc.subjectDNAen_US
dc.subjectSequencesen_US
dc.subjectSusceptibilityen_US
dc.subjectRegionen_US
dc.subjectRegulatoryen_US
dc.subjectSensitivityen_US
dc.subjectFunctionalen_US
dc.subjectTranscription factoren_US
dc.subjectTranscriptionen_US
dc.subjectBindingen_US
dc.subjectTFBSen_US
dc.subjectReference alleleen_US
dc.subjectMutant alleleen_US
dc.subjectGeneen_US
dc.subjectTranscripten_US
dc.subjectProtein-codingen_US
dc.subjectNon-codingen_US
dc.subjectRNA transcripten_US
dc.subjectOverlappingen_US
dc.subjectExpressionen_US
dc.subjectCluster analysisen_US
dc.subjectRepresentationen_US
dc.subjectBinding signalen_US
dc.subjectMotif changeen_US
dc.subjectProfileen_US
dc.subjectComplex diseaseen_US
dc.subjectGenomeen_US
dc.subjectGenetic factoren_US
dc.subjectEnsembleen_US
dc.subjectVEPen_US
dc.subjectT1Dbaseen_US
dc.subjectRavendbaseen_US
dc.subjectClustersen_US
dc.subjectProfilesen_US
dc.subjectFeaturesen_US
dc.subjectStructuralen_US
dc.subjectMutationen_US
dc.subjectAssociateden_US
dc.subjectNon-associateden_US
dc.titleThe Genomics of Type 1 Diabetes Susceptibility Regions and Effect of Regulatory SNPsen_US
dc.typeinfo:eu-repo/semantics/doctoralThesisen_US
dc.type.qualificationlevelDoctoralen_US
dc.type.qualificationnamePhDen_US
herts.preservation.rarelyaccessedtrue


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