Chapter 32 - Noninvasive prenatal testing/screening by circulating cell-free DNA

Abstract

The first prenatal genetic test was performed in 1968. Since then, fetal genetic testing has required either amniocentesis or chorion villus sampling. Those invasive methods are technically difficult and are associated with procedure-related miscarriages. Noninvasive prenatal screening has therefore long been considered the “holy grail” of prenatal genetic diagnosis [1]. Circulating cell-free fetal DNA was discovered in the maternal blood plasma in 1997 [2]. With this discovery, cell-free DNA (cfDNA) analysis became a reality. The advent of massive parallel sequencing has enabled the noninvasive prenatal screening (NIPS) of fetal aneuploidy, fetal gender, and NIPT for rhesus status and monogenic disorders [2–6]. The main aim of prenatal cfDNA testing has been the identification of pregnancies at risk for trisomy 21, 18, and 13. Yet, with the availability of genome-wide fetal and maternal sequence data, it is possible to interrogate the whole fetal and maternal genome. As a consequence, the scope of cfDNA analysis is currently being extended beyond the detection of the three most common trisomies. This chapter will elaborate on the different clinical applications of prenatal cfDNA analysis.