Differentiating Monozygotic Twins with DNA Methylation Technology

As submitted by the proposer: Prosecuting cases with physical evidence from an identical - or monozygotic (MZ) - twin remains a challenge in criminal justice because current genetic technology cannot differentiate persons with identical genomes. As the rate of twin births are on the rise, the incidence of forensic evidence samples originating from an MZ twin will likely also increase and result in further unsolved cases due to a lack of cost effective and accurate forensic analysis methods for MZ twins. Fortunately, new tools in genome analysis and bioinformatics are opening doors to explore the epigenetic landscape and may provide new biomarkers to the forensic community for challenging samples such as MZ twins. The aim of this study is to investigate one particular component of epigenetics, DNA methylation, in an applied research project to differentiate MZ twins of different ages and from evidence types of different tissue sources. This research will statistically probe differentially methylated sites in the human genome, using deep coverage methylation profiling microarrays for identification of a panel of methylation markers with high association to MZ twin differentiation. The first goal targets the discovery of methylation markers based on the analysis of over 850,000 CpG sites in samples collected from multiple twin pairs. Samples will be analyzed based on three criteria: (i) temporal sampling of the twin pairs, (ii) multiple tissue types, and (iii) varying biological ages. Comprehensive statistical evaluation of these data across multiple parameters will result in a down selection to a target panel of markers (150-200 CpG sites). At the conclusion of the study, all laboratory methods and results will be made available as open source resources for the criminal justice community. While Short Tandem Repeats (STRs) will likely always remain the gold standard in human identification, the epigenetic methylation markers discovered in this study and the laboratory method could help resolve a vast number of cases involving MZ twins and also open door to further forensic genomic applications stemming from epigenetic approaches. Note: This project contains a research and/or development component, as defined in applicable law, and complies with Part 200 Uniform Requirements � 2 CFR 200.210(a)(14). ca/ncf