Header

UZH-Logo

Maintenance Infos

Analytical developments based on mass spectrometry to detect and quantify DNA mutations


Probst, Jean-Christophe. Analytical developments based on mass spectrometry to detect and quantify DNA mutations. 2013, University of Zurich, Faculty of Science.

Abstract

Epigenetic modifications, as e.g. methylation of histones and DNA, regulate gene expression. However, misregulation of this methylation can lead to very dangerous diseases as cancers, neurological disorders or autoimmune diseases. DNA also undergoes simply changes in the genomic sequence called mutations. They can be classified in advantageous, neutral and lethal processes. Advantageous mutations can contribute to evolutionary changes due to environmental influences. In contrast, lethal damages of the genomic sequence in cellular processes arising from DNA methylation, replication errors, ionizing radiation, or UV-irradiations, frequently result in cancers.
These important concepts necessary for the macromolecular machinery of life are presented in the first part of Chapter 1. They include also the flow of genetic information in a cell, primary, secondary, and tertiary structures of DNA, as well as packaging of DNA in a cell by proteins called histones.
As the rate of DNA mutation and relative binding affinities of small molecules to DNA will be considered in this thesis, the second part of Chapter 1 deals with quantitative determinations. Aspects of calibration, systematic and random errors, limit of detection, limit of quantification, dynamic range, and linearity are discussed. Combination of chromatography with mass spectrometry is often the method of choice used in quantification. Regarding the sample properties, criteria for selecting the most appropriate analytical method are developed, including chromatography, ionization modes, and mass analyzers.

Abstract

Epigenetic modifications, as e.g. methylation of histones and DNA, regulate gene expression. However, misregulation of this methylation can lead to very dangerous diseases as cancers, neurological disorders or autoimmune diseases. DNA also undergoes simply changes in the genomic sequence called mutations. They can be classified in advantageous, neutral and lethal processes. Advantageous mutations can contribute to evolutionary changes due to environmental influences. In contrast, lethal damages of the genomic sequence in cellular processes arising from DNA methylation, replication errors, ionizing radiation, or UV-irradiations, frequently result in cancers.
These important concepts necessary for the macromolecular machinery of life are presented in the first part of Chapter 1. They include also the flow of genetic information in a cell, primary, secondary, and tertiary structures of DNA, as well as packaging of DNA in a cell by proteins called histones.
As the rate of DNA mutation and relative binding affinities of small molecules to DNA will be considered in this thesis, the second part of Chapter 1 deals with quantitative determinations. Aspects of calibration, systematic and random errors, limit of detection, limit of quantification, dynamic range, and linearity are discussed. Combination of chromatography with mass spectrometry is often the method of choice used in quantification. Regarding the sample properties, criteria for selecting the most appropriate analytical method are developed, including chromatography, ionization modes, and mass analyzers.

Statistics

Downloads

17 downloads since deposited on 10 Apr 2019
17 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Dissertation (monographical)
Referees:Bienz Stefan, Bigler Laurent, Sigel Roland
Communities & Collections:UZH Dissertations
Dewey Decimal Classification:Unspecified
Language:English
Place of Publication:Zürich
Date:2013
Deposited On:10 Apr 2019 12:24
Last Modified:07 Apr 2020 07:17
Number of Pages:153
OA Status:Green
Related URLs:https://www.recherche-portal.ch/primo-explore/fulldisplay?docid=ebi01_prod010046248&context=L&vid=ZAD&search_scope=default_scope&tab=default_tab&lang=de_DE (Library Catalogue)

Download

Green Open Access

Download PDF  'Analytical developments based on mass spectrometry to detect and quantify DNA mutations'.
Preview
Content: Published Version
Language: English
Filetype: PDF
Size: 14MB