Cell-free nucleic acids in the body fluids of pregnant women
Our laboratory is actively involved in translational research towards development of new biomarkers for prenatal diagnosis using maternal body fluids. Cell-free fetal (cff) DNA can be studied using quantitative or qualitative analysis. Cff DNA is elevated in maternal plasma in preeclampsia, placental abnormalities, and aneuploidy. Amniotic fluid supernatant is a rich source of cell-free fetal DNA and RNA and can provide novel information about gene expression and functional development in the living fetus. In maternal plasma we have analyzed factors that will be important in the clinical interpretation of cff DNA levels, such as maternal weight, race, parity, smoking history, type of conception (natural or assisted), and placental volume. We are using specific disease models (such as congenital diaphragmatic hernia and twin-to-twin transfusion [TTTS]) to understand the effects of gestational age and specific pathology on fetal gene expression by analyzing cell-free mRNA levels in maternal plasma. By optimizing recovery of cell-free fetal nucleic acids in amniotic fluid we observe that there are significant size differences in the cff DNA fragments in samples obtained from normal and aneuploid fetuses. In addition we have successfully hybridized cff DNA in amniotic fluid to DNA microarrays, permitting rapid assessment of fetal molecular karyotype (Larrabee et al, Am J Hum Genet 2004;75:485-491). We also have preliminary data on fetal gene expression in amniotic fluid (Larrabee et al. JAMA 2005;293:836-842). This has led to the identification of novel genes and specific metabolic pathways involved in TTTS and fetal hydrops. Finally, we are actively involved in promoting noninvasive prenatal testing in the US, such as encouraging the use of fetal DNA for fetal Rhesus D assessment(see Bianchi DW et al, Obstet Gynecol 2005;106: 841-844). On the other hand, we are cautious and concerned about the availability of internet-based “at-home” kits for gender detection.