Analysis of fetal DNA in maternal plasma with markers designed for forensic DNA mixture resolution

Abstract

PurposeWith the description of circulating fetal DNA in maternal blood,noninvasive prenatal diagnostics became theoretically possible. As the presenceof background maternal DNA interferes with the detection of fetal DNA,analytical methods require genetic markers capable of distinguishing byquantitative or targeted approaches the minor population of DNA molecules of thefetus. Here we evaluate the feasibility of analyzing fetal DNA with novelDIP-STR genetic markers, designed for the investigation of forensic mixedbiological evidence. MethodsThe DIP-STR molecular approach is based on sequence-specificanalysis of paternally inherited fetal alleles. These sequences are biallelicdeletion/insertion polymorphisms (DIPs) located very close to short tandemrepeat (STR) markers, for combined analysis. In this study, 48 women were testedwith 28 DIP-STRs during the first, second, and third trimester ofpregnancy. ResultsPositive results were obtained across markers, including longer ones(386 base-pairs) and with blood samples collected during early pregnancy, suchas 10 weeks of gestational age. ConclusionThese data show that DIP-STR markers can be used to amplify specificgenomic regions of circulating fetal DNA to obtain targeted genetic information.This method may contribute to developments in noninvasive prenatal paternitytesting and diagnosis of certain genetic diseases.