Fetal DNA circulating in a pregnant mother’s blood can be used to detect a wide variety of genetic abnormalities before birth, opening the door for noninvasive testing for more conditions.
By sequencing DNA that escapes into women’s bloodstreams, scientists were able to detect disease-causing mutations that are now normally found by piercing a mother’s womb with a needle to get amniotic fluid, according to a study in the American Journal of Human Genetics.
Amniocentesis, the standard procedure for prenatally testing for genetic conditions such as Down syndrome, carries a low risk of miscarriage. Obtaining DNA from a blood sample from the mother carries virtually no risk, and may enable doctors to expand their reach and accuracy as they look for genetic disease, said Cynthia Morton, a Harvard Medical School geneticist who performs prenatal tests at Brigham & Women’s Hospital in Boston.
“This could largely replace invasive testing,” she said in a telephone interview, “and, no doubt, is an exciting next step in the future of prenatal testing.”
The study was done by scientists at Tufts Medical Center in Boston and Verinata Health Inc. in Redwood City, California. Illumina Inc., the biggest maker of DNA sequencers, said this week that it will buy Verinata for $350 million plus as much as $100 million in milestone payments through 2015.
Interest in sequencing fetuses and newborns is increasing as more laboratories are showing that DNA analysis can quickly diagnose rare diseases that once took years to unravel. The U.S. National Human Genome Research Institute and the National Institute of Child Health and Newborn Development have set aside $25 million to study questions related to sequencing newborns over the next five years.
Verinata and other companies already offer blood tests that analyze circulating fetal DNA to diagnose Down syndrome, a genetic condition in which a baby is born with three copies of chromosome 21, instead of the normal two. The same tests can detect other conditions in which the fetus has too many copies of certain chromosomes, which are the packages that hold large amounts of DNA within the cell’s nucleus.
In the study published today, the team showed that they can detect far smaller genetic flaws that affect just portions of chromosomes. The test was able to find abnormalities involving as little as 100 kilobases of DNA, a fraction of the millions of chemical bases that each chromosome normally contains.
The price of sequencing DNA is falling quickly, and as it does, the scientists are using the procedure to replace and expand on established medical tests. In a study released yesterday in the journal Science Translational Medicine, for example, researchers showed that DNA analysis of the Pap smear for cervical cancer can also identify malignancies of the ovaries and endometrium.
Currently, doctors who believe a fetus may harbor a genetic condition analyze chromosomes and DNA taken by amniocentesis.
Sequencing fetal DNA from the mother’s bloodstream costs about as much to perform as conventional amniocentesis techniques, said Richard Rava, Verinata’s chief science officer and one of the investigators on the study. While the blood test isn’t available commercially yet, he said the company will give “serious consideration” to making it a product.
“It won’t be tomorrow,” he said. “The study shows that this is no longer a technical issue for us. Now it’s more of a question of how does the market want to drive forward with this.”
Some mutations that can be found by standard testing may not be detectable with the Verinata technique, Morton said. For example, in certain cases, two chromosomes may exchange equal-size portions of their DNA, a defect called a balanced translocation. Some data suggests that at least 6 percent of balanced translocations can lead to illnesses that appear at or near birth, Morton said.
“You wouldn’t to miss them,” in testing, Morton said.
Doctors may want to use noninvasive techniques first, and then turn to invasive techniques later if needed, Rava said.