Noninvasive Whole-Genome Sequencing of a Human Fetus

This is the title of a manuscript published on June 6 on Science Translational Medicine.

For the first time researchers have decoded the entire genome of a 18 weeks fetus using only a blood sample from the mother and a saliva sample from the father.

Scientists have long known that a pregnant woman's blood plasma a few weeks after conception contains cell-free DNA from her developing fetus a few weeks after conception. About 10 percent of the cell-free DNA in a pregnant woman's blood plasma comes from her fetus although the concentration varies among individuals.

Comparing the woman's plasma 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.

To identify the fetal DNA, Shendure and colleagues first used a new technique to identify haplotypes that could be traced back to the mother’s genome. This information, along with data from the father’s DNA sample, allowed the researchers to determine which parts of the maternal and paternal genomes were inherited by the fetus.

Comparison with the baby's genome sequence determined after birth showed the team's predictions to be more than 98% accurate.

The scientists also successfully repeated the experiment on a second younger fetus at a time (8.2 weeks after conception) when less fetal DNA is in the mother's blood.

(Image credit: Shedure Lab)