Baby’s genome sequenced before birth

An ultrasound of a baby. Image: Simon Pederson/Shutterstock

A new, non-invasive method of screening for genetic disorders.

Scientists from the University of Washington in the US have devised a method that can accurately predict a fetus’ genome sequence without using invasive procedures. Using plasma samples that had been taken during a past pregnancy, they were able to reconstruct the baby’s entire genome.

By using plasma samples taken from the expectant mother, the scientists were able to avoid tapping into the fetus’ protective fluid sac and taking fluid from the uterus. If this method can be brought to the clinic, it may broaden the availability of genetic screening to more patients and screen for much larger panels of disorders than can currently be detected, according to Jacob Kitzman, one of the authors of the study published in Science Translational Medicine.

Just a few weeks after conception, a pregnant woman’s blood plasma contains cell-free DNA from her developing fetus. This concentration usually rises during gestation, with about 10 per cent of the cell-free DNA in a pregnant woman’s blood plasma coming from her fetus, and vanishes after the baby arrives.

There is no method to physically separate the DNA fragments, making it difficult to detect any genetic disorders such as Down Syndrome. “We sequenced the father’s and mother’s genomes, and then looked for sequence differences in their DNA that we used to distinguish whether the plasma DNA sequences were fetal or maternal in origin,” Kiztman says.

As a result, the scientists were able to assess more subtle variations in DNA than could be seen in previous tests. “The improved resolution is like going from being able to see that two books are stuck together to being able to notice one word misspelled on a page.”

The plasma samples used had been donated 18 weeks into a past pregnancy and stored in a repository. These samples were more accurate than samples donated by another couple eight weeks into a pregnancy, as they enabled the scientists to reconstruct the entire genome, primarily because more data was collected.

However, Kitzman thinks that this method will be feasible at earlier time points by sequencing the plasma DNA more deeply. “Currently, doing so is quite expensive, but the rapid improvements in cost and accuracy of DNA sequencing technologies will help to make this feasible in the near future.”

If the approach can be streamlined, it could enable non-invasive and comprehensive genetic screens for Mendelian disorders.