"But there is a big difference between showing something can be done and doing it", says Jay Shendure, genome scientist at the University of Washington. In the new study, he and his team sequenced DNA from the plasma-blood minus the cells-of a woman who was 18.5 weeks pregnant. Comparing that DNA with genome sequences obtained from the father's saliva and the mother's blood allowed the researchers to identify fetal DNA sequences that they could computationally piece together into the child's genome. Comparison with the baby's genome sequence determined after birth showed the team's predictions to be more than 98% accurate.
"This is the first time that a fetus has been sequenced noninvasively," says Shendure, whose team reports its findings online last week in Science Translational Medicine. The researchers also successfully repeated the experiment on a second, younger fetus-it was 8.2 weeks after conception, a time when less fetal DNA is in the mother's blood.
The scientists also tried to find new mutations in the child that neither the father nor the mother carried but that arose during the reproductive process as sperm and egg were created, or as their DNA meshed during fertilization. Such de novo mutations are important because some of the most severe genetic diseases arise this way, and parents and physicians would typically have no hint that a child will be affected until after birth. For the initial child in the study, 44 de novo mutations were identified after birth-none of which were anticipated to cause severe disease. While the fetal DNA analysis had predicted 39 of those, it also wrongly predicted 25 million other potential de novo mutations. This huge false positive rate could suggest that a fetus has a genetic disorder it doesn't.
"You only worry the mother or the father a lot," says Lo. That part will need a lot of improvement, Shendure acknowledges. "The upside is: It shows that it is actually possible to predict these mutations."