Digital PCR for Noninvasive Detection of Aneuploidy: Power Analysis Equations for FeasibilityEvans M.I.a · Wright D.A.d · Pergament E.c · Cuckle H.S.b · Nicolaides K.H.e
aPrenatal Diagnosis, Comprehensive Genetics, bObstetrics and Gynecology, Columbia University, New York, N.Y., cGenetics, Northwestern Reproductive Genetics, Chicago, Ill., USA; dMathematics, University of Plymouth, Plymouth, and eFetal Medicine, Fetal Medicine Foundation, London, UK
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Objective: To determine the feasibility of digital PCR analysis for noninvasive prenatal diagnosis of trisomy 21. Methods: Through power equations, we modeled the number of wells necessary to determine the feasibility of digital PCR as a practical method for trisomy 21 risk assessment. Results: The number of wells needed is a direct correlate of the ability to isolate free fetal DNA. If a 20% fetal DNA enhancement can be achieved, then 2,609 counts would be sufficient to achieve a 99% detection rate for a 1% false-positive rate and potentially feasible with readily available plates. However, if only a 2% increase is seen, then 220,816 counts will be necessary, and over 110,000 would be needed just to achieve 95% for a 5% false-positive rate – both far beyond current commercially available technology. Conclusion: There are several noninvasive prenatal diagnostic methods which may reach commercialization; all have differing potential advantages and disadvantages. Digital PCR is potentially a cheaper methodology for trisomy 21, but it is too early to determine the optimal method.
© 2012 S. Karger AG, Basel
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