What lies beyond our genes
Applications of methylation analysis in forensic genetics
Charlotte Sutter, Zurich Institute of Forensic Medicine at the University of Zurich, Switzerland
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In my current work as a PhD student at the Zurich Institute of Forensic Medicine, I am focusing on DNA methylation for forensic applications. The potential of the epigenome for forensic purposes was recognized several years ago, and it is now utilized to answer a range of investigative questions.
My research centers on applying DNA methylation to estimate the age of a biological stain donor. This falls under the broader field of Forensic DNA phenotyping, where age estimation through DNA methylation is employed in cases where a donor cannot be identified using STR profiling. In these cases, phenotyping can help law enforcement by offering investigative leads, such as the approximate age of the stain donor.
Although there are many existing tools available for age estimation, some factors that contribute to inconsistencies in estimation accuracy remain unknown. My research primarily seeks to clarify some of these factors and inform the forensic community on how they influence the reliability of current age estimation tools.
One critical factor in methylation-based age estimation is the tissue and cell type specificity of methylation patterns. Because methylation plays a key role in gene regulation, patterns vary depending on the cell or tissue type being analyzed. Consequently, different CpG sites are targeted and distinct statistical models are generated and applied depending on the sample type. While considerable research has been conducted on forensically relevant sample types like blood, saliva, or semen, other sample types – such as bone or teeth – have received less attention in methylation studies.
In one of my projects, I am exploring age estimation in bone samples. Unlike morphological age estimation, methylation-based methods can provide age estimates even when only small bone fragments are available. My research focuses on determining whether different bone types within the same individual exhibit consistent methylation patterns and assessing how well existing bone age estimation tools perform in our laboratory.
Figure 1: Applications of methylation analysis in forensic genetics (upper half) and the laboratory steps that have to be performed from stain to analyzed data (lower half)
Another widely discussed issue in epigenomic research is the influence of environmental factors on epigenetic markers like methylation. Prior studies, both within and beyond the forensic field, have examined factors such as alcohol consumption, smoking, physical activity, and certain diseases as potential influences on methylation patterns. To contribute further to this area of research, I am investigating how various types of cancer may affect the accuracy of forensic age estimation tools in blood samples.
Beyond forensic age estimation, DNA methylation can be used for other applications, including body fluid identification or the differentiation of monozygotic siblings. Another potential future avenue I am exploring involves the use of DNA methylation as a risk marker to help clarify cases of sudden unexplained death. In instances where a young person dies unexpectedly without prior signs of heart disease, investigators may look for pathogenic genetic variants that could have contributed to the fatal cardiac event. However, such variants are only found in a fraction of cases. My project proposes that changes in the methylome could potentially also play a role in sudden unexplained death and may provide further insight into why this tragic event occurred.
An essential component of all my projects is collaboration. I am therefore grateful to have been selected as a student ambassador at ISHI35 this year, where I presented and discussed my bone age estimation project with both senior scientists and fellow students. It was a fantastic opportunity to network, receive constructive feedback, and exchange ideas with others in the field.
Charlotte Sutter
PhD student, Zurich Institute of Forensic Medicine at the University of Zurich
Charlotte Sutter earned her degree in Molecular Medicine from the Medical University of Innsbruck, Austria. For her Bachelor’s and Master’s theses, she focused on sequencing protocol optimization and forensic age estimation based on DNA methylation at the Institute of Legal Medicine in Innsbruck. Since 2022, she has been a PhD student at the Zurich Institute of Forensic Medicine at the University of Zurich, where her research centers on DNA methylation applications in forensic genetics. Her work includes methylation-based age estimation of stain donors and whole methylome analysis in cases of sudden unexplained death (SIDS and SUD). She was selected as one of five student ambassadors at ISHI35 in 2024.
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