Recent developments in noninvasive prenatal diagnosis using cell-free fetal nucleic acids in maternal plasma
Circulating cell-free fetal DNA was first demonstrated in maternal plasma in 1997. Since then many diagnostic applications using this noninvasive source of fetal DNA have been described, including applications to sex-linked diseases, fetal RhD blood group genotyping, analysis of paternally-inherited mutations, etc. Important biological information regarding such circulating fetal DNA has also been obtained, including the variations in circulating fetal DNA concentrations with gestational age and with disease states, its rapid clearance following delivery and size analysis of circulating DNA.
Two new developments in the field have recently opened up new areas of investigation. The first is the demonstration that fetal epigenetic signatures could be used as markers of fetal DNA in maternal plasma. This development has led to the development of markers that are gender- and polymorphism-independent. The second is the demonstration that placental mRNA is detectable in maternal plasma. The latter discovery has greatly increased the number of fetal markers that could be developed for noninvasive prenatal diagnosis and opened up interesting possibilities for noninvasive prenatal gene expression profiling.