Next-Generation–Sequencing-Based Noninvasive Prenatal Diagnosis

Abstract

Prenatal diagnosis is important part of obstetric practice (Tounta et al. 2011). Traditionally, fetal DNA is obtained by invasive techniques, namely, amniocentesis and chorionic villus sampling. Such invasive procedure leads to a miscarriage rate of about 1 % and is reserved only for high risk pregnancies for specific genetic conditions which include fetal chromosomal aneuploidies and monogenic disorders with relatively high prevalence in the relevant populations. The ultimate goal for early prenatal diagnosis, while decreasing the miscarriage rate, is to employ noninvasive testing using maternal peripheral blood as a source of fetal genetic material (Tounta et al. 2011). Multiple studies indicate that both intact fetal cells and cell-free fetal nucleic acids (cffNA) cross the placenta and can be found in the maternal circulation. Intact fetal cells present an attractive target for noninvasive prenatal diagnosis (NIPD) of fetal chromosomal abnormalities (Lo et al. 1996). Isolation and analysis of fetal cells from maternal circulation have been extensively investigated and several methods for fetal cell enrichment have been developed (Bianchi 1999; Jackson 2003; Sekizawa et al. 2007). However, due to the lack of cells in the maternal circulation and low efficiency of enrichment methods results have not been promising. In addition, it has been challenging to perform Fluorescent In Situ Hybridization (FISH) because of the presence of apoptotic nuclei of fetal cells (Bianchi et al. 1997).