Genetic analysis of Parkinson's disease using Next-generation sequencing

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dc.contributor.advisor Gasser, Thomas (Prof. Dr.) Giri, Anamika 2019-04-17T07:41:33Z 2019-04-17T07:41:33Z 2019-04-17
dc.identifier.other 1663363919 de_DE
dc.identifier.uri de_DE
dc.description.abstract Neurological diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Epilepsy and Multiple Sclerosis are included in the Global burden of disease study as these disorders have a high impact on public health. Lack of effective treatment has motivated the researchers to perform early diagnostics, by identifying new gene mutations, which can improve the therapies. The aim of this thesis was a genetic analysis of PD using next-generation sequencing data. In this thesis, whole genome sequencing (WGS) and whole exome sequencing (WES) using DNA from familial PD patients and healthy individuals was performed in order to identify the PD causal genes. A large repository of sporadic PD WES data and a genotyping array was used to replicate our findings. The PD patients from Germany were stratified for clinical trials on the basis of mitochondrial endo-phenotype by performing risk profiling of associated Single Nucleotide Polymorphisms (SNPs) using exome genotyping array. The sporadic PD WES and genotyping array data from International Parkinson’s disease Genomics Consortium was used to perform association tests, to determine the burden of rare variants in candidate genes of interest. Furthermore, mRNA sequencing of all the genes under the PD GWAS loci after knockdown with short hairpin RNAs was performed, to identify the actual genes contributing to PD risk and the novel pathways involved in PD. Finally, an epistatic interaction of a Mendelian PD gene and associated locus was performed to understand the joint contribution to PD risk. Taking everything into account, we identified pathogenic variants in known and some novel genes causing PD in families. On the basis of risk profiling some of the German PD patients will undergo clinical trials with coenzyme Q10 and vitamin K2. The association tests using sporadic PD data helped to identify some novel genes significantly associated with PD risk. The knockdown experiments facilitated the identification of genes contributing to PD risk in some of the PD GWAS loci. en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podok de_DE
dc.rights.uri de_DE
dc.rights.uri en
dc.subject.classification Bioinformatik , Genomik , Parkinson-Krankheit de_DE
dc.subject.ddc 000 de_DE
dc.subject.ddc 500 de_DE
dc.subject.ddc 570 de_DE
dc.subject.ddc 610 de_DE
dc.subject.other Bioinformatics en
dc.subject.other Genomics en
dc.subject.other Next-generation sequencing en
dc.subject.other Parkinson's disease en
dc.title Genetic analysis of Parkinson's disease using Next-generation sequencing en
dc.type PhDThesis de_DE
dcterms.dateAccepted 2019-03-19
utue.publikation.fachbereich Medizin de_DE
utue.publikation.fakultaet 4 Medizinische Fakultät de_DE


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