Circadian Forensics: Estimating blood trace deposition time using rhythmic biomarkers

markdownabstractThe main objectives of criminal investigation are to determine the who, the how and the when of the crime. Who was the perpetrator that committed the criminal offense; how did the crime happen; and when or at what time did the crime happen. Currently, there are methods which allow the researchers and investigators to answer the first two questions, the who and the how. The when, however, is still in need of developing reliable and precise tests. Research presented in this thesis aimed at unravelling one of the aspect of the when – what time during the day or night a biological trace was left at the crime scene – by applying the insights from circadian biology to an open forensic problem. The first chapter of this thesis gives a brief introduction into the circadian systems and their involvement with other physiological processes in humans. The second chapter describes research undertaken to determine the utility of miRNA markers miR-142-5p and miR-541, which were previously proposed for forensic time of death determination (Odriozola et al., 2013), for blood stain deposition timing. Contrary, we did not find these particular miRNA markers suitable for estimating blood trace deposition time. In the next chapter, the assessment of expression patterns of genes, that were implied to be rhythmic mostly in animal models or in various human peripheral tissues, in human blood from healthy volunteers subjected to sleep laboratory protocols, is presented. In this study, the rhythmicity of several clock-controlled genes in humans was established, and the most informative ones were subsequently tested to determine their potential to predict time of day for forensic purposes, as reported in the following fourth chapter. The fifth chapter describes a study on the rhythmicity of metabolites tested in human blood samples. In this project metabolites with robust, 24 hour rhythms were identified, and their suitability for blood trace deposition timing was determined. The final chapter provides a general discussion on the research presented in this thesis, including elaboration on ongoing as well as future studies on this subject