Related Experiment Video
Updated: May 25, 2026
Semiconductor Sequencing for Preimplantation Genetic Testing for Aneuploidy
Published on: August 25, 2019
Single molecule sequencing of free DNA from maternal plasma for noninvasive trisomy 21 detection
Jessica M E van den Oever1, Sahila Balkassmi, E Joanne Verweij
1Center for Human and Clinical Genetics, Laboratory for Diagnostic Genome Analysis, Leiden University Medical Center, Leiden, the Netherlands.
Background:
Noninvasive fetal aneuploidy detection by use of free DNA from maternal plasma has recently been shown to be achievable by whole genome shotgun sequencing. The high-throughput next-generation sequencing platforms previously tested use a PCR step during sample preparation, which results in amplification bias in GC-rich areas of the human genome. To eliminate this bias, and thereby experimental noise, we have used single molecule sequencing as an alternative method.
Methods:
For noninvasive trisomy 21 detection, we performed single molecule sequencing on the Helicos platform using free DNA isolated from maternal plasma from 9 weeks of gestation onwards. Relative sequence tag density ratios were calculated and results were directly compared to the previously described Illumina GAII platform.
Results:
Sequence data generated without an amplification step show no GC bias. Therefore, with the use of single molecule sequencing all trisomy 21 fetuses could be distinguished more clearly from euploid fetuses.
Conclusions:
This study shows for the first time that single molecule sequencing is an attractive and easy to use alternative for reliable noninvasive fetal aneuploidy detection in diagnostics. With this approach, previously described experimental noise associated with PCR amplification, such as GC bias, can be overcome.
