Researchers at the University of Washington, Seattle, lead by Dr. Jay Shendure, published a study in Science Translational Medicine where they sequenced the entire genome of a fetus just with DNA obtained from the mother's blood. This accomplishment is a huge leap forward for non-invasive prenatal genetic testing.
Within months after the launch of the first prenatal genetic tests using maternal blood to detect uneven representation of easily identified large chromosomal pieces that cause Down's syndrome and similar disorders, the Seattle researchers have shown that a similar approach can be used to determine the complete sequence of the A, T, C, G bases in the whole fetal genome. This capacity enables detection of virtually any known congenital genetic disease since it can detect all types of DNA mutations.
Recent advances in DNA sequencing technology continue to make easier sequencing of individuals' genomic DNA. However, sequencing fetal DNA in an expectant mother's blood is difficult because it is hard to differentiate maternal and fetal DNA comingling in the blood. There are some slight differences between the two types of DNA, however, in the four base A, T, C, G sequence since only half of the child's DNA is from the mother. The other half is from the father.
Generally, high throughput DNA sequencing is done piecemeal so that lots of small fragments are sequenced randomly, then pieced together like a linear puzzle based on overlapping portions that match. Eventually, the whole sequence is aligned as one long strand (about 3 feet of DNA for the human genome!). As the DNA from the mother is sequenced over-and-over and the overlapping fragments are matched and assembled together to tease out the full sequence, two similar but distinct DNA strands form. One strand comprises the mother's and one the child's genomes. To determine which of the two sequences from the mother was the child's, the researchers sequenced the father's DNA too. The child's DNA, of course, is more similar to the father's, since half of it is from the father.
It will be at least a couple years before this technology will be ready to use in routine fetal testing. When the group checked their results with blood from the baby after birth, the researchers confirmed they were able to sequence the fetal DNA 98% correctly using DNA in the mother's blood. While exceptionally impressive, routine prenatal testing will require better results that are proven to be consistently repeatable. However, this study confirms the practical feasibility of this approach for prenatal diagnostics and also helps validate the utility of the recently approved more limited non-invasive fetal genetic tests that also rely on maternal blood.
To read more about this study, you can review the summary on the Science website.