As submitted by the proposer:
While current techniques and technologies provide for reliable reporting of mitochondrial (mt) DNA haplotypes, the methods in place today do not effectively identify heteroplasmic variants (especially low-level variants). Even when heteroplasmy is observed at high levels, the information is typically not used during a forensic investigation. The ability to identify, report, and leverage the discrimination potential of heteroplasmy will significantly enhance the value of mtDNA analysis in forensic casework; including differentiation of individuals within the same maternal lineage. A next generation DNA sequencing (NGS) approach will allow the community to achieve this goal. We recently measured the rate of heteroplasmy in the control region (CR) of the mtgenome using a MiSeq approach. Rates were assessed on an individual and per nucleotide basis for people of European ancestry and across different age groups. To address a previous limitation, we also worked with a software company to develop a tool for researchers and practitioners to better align NGS data associated with mtDNA sequence, and to provide reporting practices consistent with forensic interests. Given our understanding of the diverse nature of mtDNA haplotypes across different population groups, and that mutations resulting in low-level heteroplasmy may be associated with local sequence and their effects on the replication process, the goals of this research are to measure the rate of heteroplasmy for people of African, East Asian and Latino ancestry, and compare the rates across all population groups; including Europeans. Rates of heteroplasmy will be measured for approximately 250 individuals in each population group. Findings will be used to help guide the refinement of best practices regarding the reporting of mtDNA heteroplasmy; including statistical analysis. The collective findings will help forensic laboratories as they prepare to report heteroplasmy in casework, significantly enhancing the discrimination potential of mtDNA testing. This outcome may also serve as motivation for a broader range of laboratories to adopt mtDNA analysis using an NGS approach.
Note: This project contains a research and/or development component, as defined in applicable law.