Circulating Fetal DNA/RNA in Maternal Plasma for Aneuploidy Detection

Abstract

The discovery of cell-free fetal DNA in maternal plasma has offered new possibilities for non-invasive prenatal diagnosis and monitoring. The co-existence of fetal DNA as a minor fraction with a major background of maternal DNA in maternal plasma has posed a challenge for non-invasive prenatal detection of fetal chromosomal aneuploidies. The early approaches focus on the detection of fetal-specific RNA or DNA molecules to develop strategies for chromosome dosage determination, such as the RNA-single nucleotide polymorphism (SNP), epigenetic allelic ratio, and the epigenetic-genetic chromosome dosage approaches. While the detection of polymorphism is involved in these methods, a polymorphism-independent method has been developed with the highly precise digital polymerase chain reaction (PCR) platform. The power of single molecule counting technology is further demonstrated by the massively parallel sequencing platform for the direct detection of fetal chromosomal aneuploidies from maternal plasma. The analytical power of the latter approach with an unprecedented sensitivity, specificity, accuracy and precision has made it the most promising strategy for the clinical implementation of non-invasive prenatal diagnosis.