DNA modifications are epigenetic mechanisms that regulate gene activity, cell differentiation and function. Attachment of methyl groups to cytosine bases in DNA is carried out by enzymes DNA methyltransferases. The resulting 5-methylcytosine can then be oxidized by TET enzymes. The activity of these enzymes and their disorders have broad pleiotropic effects.
Mutations in the DNA methyltransferase DNMT3A gene are associated with a rare genetic disease - Tatton-Brown-Rahman syndrome (TBRS), which is relatively understudied. One of the goals of this project would be analysis of cell-free DNA isolated from the blood samples of TBRS patients (in cooperation with the Faculty of Medicine) by nanopore sequencing in order to determine the profiles of DNA modifications and nucleosome arrangement. This will help to better understand the etiology of TBRS and contribute to future solutions for diagnostics and treatment.