Detection of Fetal-derived Paternally Inherited X-Chromosome Polymorphisms in Maternal Plasma

Abstract

The recent demonstration of the presence of cell-free fetal DNA in the plasma and serum of pregnant women opens up new possibilities for noninvasive prenatal diagnosis (1)(2)(3)(4)(5). However, many published reports have used Y-chromosomal sequences that are present in a male fetus as a marker (1)(6)(7), an approach that is not applicable to the 50% of pregnancies that involve a female fetus. A marker allowing the positive identification of DNA from a female fetus in maternal plasma would be useful for the investigation of sex-linked genetic disorders and for the extension of studies on pathologies involving fetal DNA abnormalities (7)(8) to pregnancies involving female fetuses. We reason that because the female fetus would have inherited a paternally derived copy of the X-chromosome, short tandem repeat (STR) polymorphisms on this chromosome could potentially be used as a fetus-specific marker for female fetal DNA. In this study, we tested this hypothesis using a panel of STRs on the X-chromosome. Blood samples from pregnant women were collected into tubes containing EDTA. Plasma was harvested as described previously (9). We studied samples from 25 women with female fetuses as ascertained at delivery. Informed consent was obtained, and the study was approved by the Clinical Research Ethics Committee. In 10 cases, samples were collected during the second trimester (mean gestational age, 18 weeks; range, 16–19 weeks) just before amniocentesis. …