A graphical simulation model of the entire DNA process associated with the analysis of short tandem repeat loci.
The use of expert systems to interpret short tandem repeat DNA profiles in forensic, medical and ancient DNA applications is becoming increasingly prevalent as high-throughput analytical systems generate large amounts of data that are time-consuming to process. With special reference to low copy number (LCN) applications, we use a graphical model to simulate stochastic variation associated with the entire DNA process starting with extraction of sample, followed by the processing associated with the preparation of a PCR reaction mixture and PCR itself. Each part of the process is modelled with input efficiency parameters. Then, the key output parameters that define the characteristics of a DNA profile are derived, namely heterozygote balance (Hb) and the probability of allelic drop-out p(D). The model can be used to estimate the unknown efficiency parameters, such as pi(extraction). 'What-if' scenarios can be used to improve and optimize the entire process, e.g. by increasing the aliquot forwarded to PCR, the improvement expected to a given DNA profile can be reliably predicted. We demonstrate that Hb and drop-out are mainly a function of stochastic effect of pre-PCR molecular selection. Whole genome amplification is unlikely to give any benefit over conventional PCR for LCN.
Gill
Peter
P
Forensic Science Service, Birmingham UK. dnapgill@compuserve.com
Curran
James
J
Elliot
Keith
K
D003196:Computer Graphics; D003198:Computer Simulation; D004247:DNA / Q000302:isolation & purification; D006238:Haploidy; D006579:Heterozygote; D015233:Models, Statistical; D009010:Monte Carlo Method; D016133:Polymerase Chain Reaction / Q000379:methods*; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA / Q000379:methods*; D013269:Stochastic Processes; D020080:Tandem Repeat Sequences
D004247:DNA