Part of the problem, says Ravgen’s founder and CEO, Ravinder Dhallan, is that the baby’s signal is so low: previous studies had estimated that fetal DNA accounts for a mere 3 percent of DNA in the blood. So the Ravgen group developed a simple way to boost the signal. It believes the mother’s DNA is much more abundant because maternal blood cells burst when a blood sample is processed, spilling the woman’s DNA into the surrounding plasma. But if the blood sample is treated immediately with formaldehyde, which causes cells to harden, the proportion of fetal DNA in the plasma jumps to about 25 percent.
The scientists at Ravgen then scan the DNA samples for common variations in genetic sequence, called single nucleotide polymorphisms (SNPs). “We look at many variable sites in the mother’s DNA and compare it to variable sites in the fetal DNA, and we find sites where mother and the baby differ,” Dhallan says. This allows the researchers to piece together two separate genetic signals. They can then compare the level of the fetal signal at chromosome 21 to another chromosome; an abnormally high level indicates an extra copy of chromosome 21.
Dennis Lo, a scientist at the Chinese University of Hong Kong who first discovered fetal-DNA fragments in maternal blood, says that this method and the company’s results must be reproduced by other groups, but that the research bodes well for the prospects of a noninvasive prenatal test. He is developing a competing technique that uses pieces of fetal RNA to detect Down’s syndrome.
Deborah Driscoll, a reproductive geneticist at University of Pennsylvania who authored the revised guidelines for Down’s syndrome testing, says that while current diagnostic tests are accurate, they cannot be performed until 15 weeks into a pregnancy. “People are looking for technological advances that will provide a high detection rate, will be noninvasive, and can be done early in pregnancy,” she says.