Development of Linkage Phase Analysis Software for Resolving mtDNA Mixtures

A mixture of different mitochondrial DNA (mtDNA) molecules in a single sample presents a significant obstacle to successful mtDNA analyses by standard methods. Under Award 2003-IJ-CX-K104, the University of Denver developed and validated a Denaturing High-Performance Liquid Chromatography (DHPLC) method for the accurate, rapid and low-cost analysis of mtDNA mixtures. Coupled with a concept called 'linkage phase analysis', DHPLC can reliably determine the mtDNA types of the individual contributors to the mixture. While the statistical confidence of resolving mixtures using this approach typically exceeds 99.9%, the computationally intensive nature of the underlying mathematics of linkage phase analysis is prohibitively time consuming. The goal of the current project is to develop, test and release a solidly reliable software application for performing linkage phase analysis. The impact of doing so will enable investigators to obtain potentially probative information from samples that historically have not been amenable to analysis by traditional DNA sequencing methods. ca/ncf