Study of extracellular nucleic acids in maternal circulation in the cases of pathological and physiological pregnancies

In 1997, Prof. Dennis Lo discovered the presence of cell-free fetal DNA (cffDNA) in the maternal plasma and serum of pregnant women. This finding started the development of new non-invasive prenatal diagnosis methods, which are currently in the forefront of the advanced care of mother and fetus. Non-invasive genetic tests based on the detection of paternally inherited alleles, including determination of fetal sex in cases at risk of X-linked disorders or congenital adrenal hyperplasia and RHD or RHCE genotyping in alloimunized pregnancies, were quickly introduced into routine practice. This thesis focuses on the basic characteristics of cffDNA and fetal cells in maternal circulation and its usage for non-invasive prenatal diagnosis, especially in cases of placental insufficiency related complications, e.g. preeclampsia and IUGR. This severe disorder is characterized by placental dysfunction with an abnormal invasion of trophoblasts and a defect in the transformation of maternal spiral arteries, leading to placental ischemia followed by increased apoptosis of trophoblast associated with an elevated concentration of cell-free nucleic acids in maternal circulation. Until recently, cffDNA quantification studies were mostly done using amplification of SRY or DYS-14 genes localized on chromosome Y, and..