Heralding a future in which a child’s entire genetic blueprint can be examined for traits and defects — noninvasively — long before birth, researchers have announced that they have reconstructed the whole genome of a fetus by using only a blood sample from its mother and a saliva sample from its father. The work was published today in Science Translational Medicine1. The feat relies on the fact that when a woman is pregnant, her blood contains DNA fragments both from her own genome and that of her unborn child. Depending on the individual woman and the stage of her pregnancy, more than 10% of the free floating DNA — called ‘cell-free DNA’ — in her blood may come from the fetus. The challenge facing those wishing to glean information from this fetal DNA is to figure out how to distinguish it from the mother's genetic signal.
Jay Shendure, a geneticist at the University of Washington in Seattle, and his coleagues isolated 5 nanograms of cell-free DNA from a maternal blood sample taken after 18.5 weeks of gestation. They performed 'deep sequencing' on the DNA, which involves sampling fragments about 78 times. The researchers also constructed the mother’s genome using her blood cells, and they worked out how her variants grouped together into blocks or haplotypes. The results from the deep sequencing were then compared to a computationally predicted ratio of haplotypes expected to come from the mother. Where the ratio of haplotypes diverged from the prediction, the researchers surmised they might be reading some of the genetic material from the fetus.