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The Forensic Epigenetic Landscape: Current Applications, Persistent Challenges, and Future Horizons

Abstract

The fundamentals of modern forensic science rely on the analysis of short tandem repeats (STRs) to determine individual identity .Although highly effective in identification, this methodology is limited in nature and does not provide any information regarding the donor’s age, tissue origin, or environmental exposure. This critical gap in investigative information has led to the exploration of epigenetics-genetic changes in gene expression without altering the underlying DNA sequence-as the next frontier in forensic analysis. Epigenetic modifications, particularly DNA methylation, non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), and histone modifications, are dynamic, tissue-specific, and responsive to environmental factors, making them powerful biomarkers. DNA methylation, the most stable of these markers, is of particular value due to its predicted changes with age, forming the basis for highly accurate “epigenetic clocks” with a mean absolute deviation (MAD) of approximately 3-5 years. Furthermore, distinct methylation patterns across different cell types (Differential Methylation Regions or DMRs) allow for the accurate identification of body fluids such as blood, saliva, and seminal fluid, a crucial step in crime scene reconstruction. MicroRNA molecules offer an added advantage, particularly in degraded samples, due to their exceptional stability and strong histologically specific expression patterns. These small molecules are successfully used not only to characterize body fluids but also to estimate the Post-Mortem Interval (PMI), providing a molecular clock of the time elapsed since death. This comprehensive review details the significant forensic importance of epigenetics, with a focus on these well-established applications. We are studying methodological developments, including next-generation sequencing (NGS) platforms such as whole-genome bisulfite sequencing (WGBS) and emerging, non-destructive nanopore technology, which enable high-throughput multi-analysis of these markers. Developing integrated tests capable of simultaneously identifying age, source of body fluids, and potential lifestyle factors from a single small sample represents a major future trend in the field of criminal intelligence. Finally, we critically examine the ongoing challenges that hinder the transfer of this technology to routine casework. These factors include the impact of sample degradation on the analysis, the urgent need for international standardization and validation of label plates and statistical models for court acceptance, and the complex ethical and legal considerations surrounding the inference of sensitive information relating to phenotype and lifestyle. Overcoming these obstacles is essential for the successful transition of epigenetic analysis from a promising research tool to a routine, scientifically robust, and legally defensible forensic practice.

Authors

1 Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi Arabia

2 Department of Natural and Life Sciences, Faculty of Sciences, University of M’sila, Université de M’Sila, Bordj Bou Arreridj Road, 28000, Algeria

3 Laboratory of Ethnobotany and Natural Substances, Department of Natural Sciences, Ecole Normale Supérieure(ENS), Alger, 16308, Algeria

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