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DNA Methylation Patterns in patients with Neurodevelopmental Disorders
Vítková, Magdalena ; Steiner Mrázová, Lenka (advisor) ; Krejčík, Zdeněk (referee)
Neurodevelopmental disorders (NDDs) are diseases characterized by abnormal development of the central nervous system and brain. Simultaneously, the NDDs may also be associated with specific changes in DNA methylation. The rapid development of sequencing techniques, particularly whole genome sequencing (WGS) and whole exome sequencing (WES), has helped to uncover a number of genes associated with NDDs. Determining the pathogenicity of the variants found remains a challenge in the diagnosis of patients with NDDs. Finding the DNA methylation patterns by microarray or methylation sequencing in patients with NDDs carrying a variant of uncertain significance (VUS) may provide valuable information to address this problem. This thesis demonstrates the feasibility of using these approaches to functionally classify found variants in the KDM5C, ARID1B, ATRX, and BRWD3 genes. The aim was to determine whether there are changes in the DNA methylation patterns of patients with NDDs compared to probands and healthy controls, which could be used to confirm the diagnosis. Key words: DNA methylation patterns, DNA methylation, histone modifications, NDDs, KDM5C, ARID1B, ATRX, BRWD3
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Cytologická studie modelů DNA metylace a metylace histonů u lidských buněčných linií
Skalníková, M. ; Bártová, Eva ; Kozubek, Stanislav ; Kozubek, Michal
Epigenetic processes are defined as heritable changes in genome function that occur without a change in DNA sequence. Gene expression, chromosome segregation, DNA replication, repair, and recombination all act, not on DNA alone, but on the chromatin template. DNA methylation, along with histone lysine methylation, establishes the framework for long-term epigenetic maintenance. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed epigenetic mechanisms that considerably extend the information potential of the genetic code. In mammals, heterochromatin is characterised by DNA methylation at CpG dinucleotides and methylation at lysine 9 of histone 3 (H3-K9), whereas euchromatin is associated with methylation at lysine 4 of histone 3 (H3-K4).
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