The impact of digital DNA counting technologies on noninvasive prenatal testing

Abstract

The discovery of cell-free DNA molecules in maternal plasma has opened up numerous opportunities for noninvasive prenatal testing. The advent of new digital counting technologies, including digital polymerase chain reaction and massive parallel sequencing, has provided the opportunity to quantify the cell-free DNA molecules in maternal plasma in an unprecedentedly precise manner. Powered by these technologies, prenatal testing of different kinds of hereditary conditions, ranging from monogenic diseases to chromosome aneuploidies, has been shown to be possible through the analysis of maternal plasma DNA. Discussed here are the principles of the approaches used in the noninvasive testing of different fetal conditions, with an emphasis on the impact that different digital DNA counting strategies have made on the development of these tests.

Keywords:

• cell-free fetal DNA
• digital PCR
• massive parallel sequencing
• maternal plasma
• NIPT

Financial & competing interests disclosure

This work was supported by the University Grants Committee of the Government of the Hong Kong Special Administration Region, China, under the Areas of Excellence Scheme (AoE/M-04/06). K Sun has filed patent applications on molecular diagnostics based on plasma DNA. KCA Chan has filed patent applications and holds patents on molecular diagnostics based on plasma DNA. KCA Chan holds equities of Sequenom and is a shareholder of Xcelom and Cirina, and is a director of Xcelom, Cirina and Sanomics. P Jiang has filed patent applications and holds patents on molecular diagnostics based on plasma DNA, and is a consultant for Xcelom. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Prenatal diagnosis is an essential part of modern obstetric care, while with the conventional invasive methods, there is a risk of losing the fetus; thus the noninvasive approaches are more favored and emerging.

• Digital DNA counting methods, including digital PCR and massive parallel sequencing, show significant advantages in accuracy and precision over the non-digital methods, for DNA quantification.

• Monogenic diseases, especially those potentially inherited from the mother, could be accurately detected by noninvasive prenatal diagnosis using digital PCR assays.

• Noninvasive fetal aneuploidy testing has now been routinely deployed in many countries using massive parallel sequencing technology.

• The fetal genome could be noninvasively reconstructed by analyzing the maternal plasma, demonstrating the great potential of digital counting methods in noninvasive prenatal diagnosis.

Notes