Validation of an STR peak area model

Abstract

In analyzing a DNA mixture sample, the measured peak areas of alleles of STR markers amplified using the polymerase chain-reaction (PCR) technique provide valuable information concerning the relative amounts of DNA originating from each contributor to the mixture. This information can be exploited for the purpose of trying to predict the genetic profiles of those contributors whose genetic profiles are not known. The task is non-trivial, in part due to the need to take into account the stochastic nature of peak area values. Various methods have been proposed suggesting ways in which this may be done. One recent suggestion is a probabilistic expert system model that uses gamma distributions to model the size and stochastic variation in peak area values. In this paper we carry out a statistical analysis of the gamma distribution assumption, testing the assumption against synthetic peak area values computer generated using an independent model that simulates the PCR amplification process. Our analysis shows the gamma assumption works very well when allelic dropout is not present, but performs less and less well as dropout becomes more and more of an issue, such as occurs, for example, in Low Copy Template amplifications.