I-40: Non Invasive Prenatal Genetic Diagnosis;Current Status and The Future

Discovery of cell free fetal DNA in 1997 has deeply changed the outlook of prenatal diagnosis approaches as most of the clinically established screening tests are not sensitive/specific enough while the current practical diagnostic tests are also invasive in their nature. The most common prenatal screening test is routinely practiced for the diagnosis of Down syndrome (DS) which includes a 10% failure in diagnosis of pregnancies with DS, whilst 19 from 20 positive-screened are also falsely positive. In addition, definite diagnosis of DS pregnancies can be achieved by invasive procedures of amniocentesis and or CVS which will contain a risk of 0.5 to 1% for fetal loss. Non-invasive prenatal genetic diagnosis (NIPNGD) relies on genotyping of the fetus rather than phenotypic evaluations and is done through separation of fetal cells or nucleic acids from maternal blood. In the last 15 years, an increasing number of researches were done on NIPNGD which in turn have brought it to the edge of approval for clinical application at least in some prenatal conditions like DS. Nowadays, NIPNGD methods are broadly under investigation to determine their applicability in various fetomaternal conditions such as fetal sex determination, aneuploidies, single gene disorders, microdeletions and microduplications, Rhesus incompatibility, fetal growth restrictions, preeclampsia, preterm labor and so on. These approaches are mostly based on detecting fetal nucleic acids in maternal blood as the number of intact fetal cells and the methods for their separation from maternal blood are quietly limited. The two important obstacles that have hindered the use of cell free fetal DNA in NIPNGD are the very low ratio of fetal DNA in maternal blood (3 to 6%) and difficulty in distinguishing fetal DNA from maternal DNA. These difficulties are mostly affecting the result of conventional methods such as PCR and Sanger sequencing. Sophisticated and highly throughput new approaches such as array CGH and next generation sequencing (NGS) are promising to be able to overcome these drawbacks. At the present, NGS is going to be clinically applicable for screening trisomic pregnancies with 100% sensitivity and specificity. It is predictable that these methods can be extensively applied in the clinic for non-invasive prenatal diagnosis of various genetic conditions in the future.