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Analysis of NGS data for study of transposon activity in cancer cells
Hrazdilová, Ivana ; Čegan,, Radim (referee) ; Eduard, Kejnovský (advisor)
Theoretical part of this diploma thesis gives a brief characteristic of human mobile elements (transposons), which represents nearly 50% of human genome. It provides basic transposon clasification and describes types of transposons present in hunam genome, as well as mobilization, activation and regulation mechanisms. The work also deals with the domestication of transposons, describes the ways in which TE contribute to DNA damage and summarizes the diseases caused by mutagenic activity of transposons in the human genome. Conclusion of theoretical part describes next-generation sequencing technologies (NGS). As practical part, data from RNA-seq experimet were analyzed in order to compare differen transposon activity in normal and cancer cells from prostate and colorectal tissues. As like as publicly available sophisticated tools (TopHat), new scripts were created to analyze these data. The results show that cancer cells exhibit overexpression of transposons. This corresponds with the published results and suggests a connection of transposon activation with cancer development.
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Analysis of the spectrum of genetic variants associated with development of Parkinson's disease
Stočesová, Lucie ; Hirschfeldová, Kateřina (advisor) ; Fajkusová, Lenka (referee)
Parkinson's disease (PD) is one of the most common neurodegenerative disease in humans. It affects all age categories and the number of patients with this disease is still growing. However, the genetic cause of PD is not yet very clear and new and new candidate genes are constantly being discovered. The aim of the thesis is to perform a mutation analysis in a group of patients and controls from the Czech population and thus find possible genetic causes of parkinsonism in a cohort of researched patients. The second aim is to evaluate data correlation obtained by different methods. Next generation sequencing was used for this purpose. The results of this sequencing were verified with methods such as MLPA (Multiplex Ligation-Dependent Probe Amplification), analysis of short tandem repeats and Sanger sequencing. Using these methods, we obtained a wide range of possible genetic causes of parkinsonism in the studied group of patients. Patogenic or risk variants were found not only in classical candidate genes typical for PD (called PARK), but also in genes associated with other neurodegenerative diseases. For less than half of the patients (42,64 %), the genetic cause of parkinsonism was not found. Using several methods, we found that next generation sequencing is a very precise method, that can well...
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Study of genome and transcriptome variability employing data processing from massive parallel DNA sequencing.
Vojta, Petr ; Hajdúch, Marián (advisor) ; Budinská, Eva (referee) ; Mokrejš, Martin (referee)
Massive parallel sequencing (MPS) data analysis tasks are often computationally demanding and their execution time would take too long using standard computing machines. Thus there is a need for parallelization of this tasks and ability to execute them on a sufficiently powerful computing machines. In the first chapter we describe a newly created platform for resequencing analysis of MPS data - MOLDIMED and novel annotation tool, which is ready to deploy on HPC infrastructure. The second chapter describes MPS approaches in Diamond-Blackfan anaemia (DBA), which is predominantly underlined by mutations in genes encoding ribosomal proteins (RP); however, its etiology remains unexplained in approximately 25% of patients. We performed panel sequencing of all ribosomal genes in DBA patient without previously known molecular pathology. A novel heterozygous RPS7 mutation coding RPS7 p.V134F was found in one female patient and subsequently confirmed in two asymptomatic family members, in whom mild anemia were detected on further examination. Subsequently, we performed whole transcriptome analysis in all family members and patient with RPS7 mutation in comparison with healthy control group and with DBA patients with known mutation in RPS19. We observed dysregulation mainly in signal pathways of translation,...
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Analysis of NGS data for study of transposon activity in cancer cells
Hrazdilová, Ivana ; Čegan,, Radim (referee) ; Eduard, Kejnovský (advisor)
Theoretical part of this diploma thesis gives a brief characteristic of human mobile elements (transposons), which represents nearly 50% of human genome. It provides basic transposon clasification and describes types of transposons present in hunam genome, as well as mobilization, activation and regulation mechanisms. The work also deals with the domestication of transposons, describes the ways in which TE contribute to DNA damage and summarizes the diseases caused by mutagenic activity of transposons in the human genome. Conclusion of theoretical part describes next-generation sequencing technologies (NGS). As practical part, data from RNA-seq experimet were analyzed in order to compare differen transposon activity in normal and cancer cells from prostate and colorectal tissues. As like as publicly available sophisticated tools (TopHat), new scripts were created to analyze these data. The results show that cancer cells exhibit overexpression of transposons. This corresponds with the published results and suggests a connection of transposon activation with cancer development.
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