On Thursday 5 March 2026 at 13:00, Oliver Kjærlund Hansen defends his PhD dissertation entitled "Modelling nucleotide context of mutational processes in germline”.

Every person’s DNA carries small changes, known as mutations. These mutations are essential for evolution, but they may also contribute to genetic disease. The biological processes that generate mutations in the human germline are not fully understood, particularly those that cause short insertions and deletions of DNA (InDels). Although it is important, it has not been clear why some parts of our DNA mutate more often than others. While many studies have reported on single DNA changes, depending on the adjacent DNA, few have attempted to disentangle the landscape in a larger DNA context, including for InDels.

InDels have been difficult to study due to classification challenges. Using a data-informed approach, five distinct InDel mutation signatures are identified across the human genome. These signatures reveal influences of DNA replication and transcription, including pronounced strand asymmetries in which mutation patterns differ depending on the direction of these processes.
Utilising human germline mutations, we developed statistical models to explain how DNA sequence context and broader genomic properties shape mutation rates. By using extended stretches of DNA surrounding each mutation, together with features such as DNA methylation, replication timing, and recombination, the work provides improved estimates of mutation rates at single-site resolution. These models outperform existing approaches and can be used to quantify the extent to which genes are constrained against harmful mutations, an important step towards understanding genetic disease risk.

The summary is written by the PhD student.

The defence is public and takes place in Auditorium, Ground floor, Building D/E, Department of Molecular Medicine, Aarhus University Hospital. Please see the press release for more information. 

Contact

PhD student Oliver Kjærlund Hansen
Mail: oliver@clin.au.dk
Phone: +45 20434305

Read full press release