Biology and Diagnostic Applications of Cell-Free Fetal Nucleic Acids in Maternal Plasma

Abstract

The discovery of cell-free fetal nucleic acids in maternal plasma in 1997 has opened up new possibilities for noninvasive prenatal diagnosis. Since then, many of the fundamental biological parameters of this phenomenon have been elucidated, including the effects of gestational age, the size of the circulating nucleic acid molecules, and their rapid clearance following delivery. A variety of circulating fetal nucleic acid markers have also been developed, including fetal genetic, epigenetic, mRNA, and miRNA markers. A number of exciting new technologies have been developed for their analysis, including single molecule counting technologies, such as digital PCR and massively parallel sequencing. Together, these developments have culminated in a number of prenatal diagnostic applications, including fetal sexing, RhD blood group genotyping, monogenic disease analysis, and the detection of fetal chromosomal aneuploidies. It is hoped that such advances will ultimately make prenatal testing safer for pregnant women and their fetuses.