Building on the latest developments in DNA science, Stanford University researchers have designed a prenatal genetic test that appears to be just as accurate as — but much safer than — methods like amniocentesis.
Currently, pregnant women worried about their babies' genetic health face a tough choice: Get prenatal gene testing and risk miscarriage, or skip the tests and miss the chance to learn of genetic defects before birth.
The new method, which was published in a study Monday and still needs to undergo a larger clinical trial, requires only a single sample of the mother's blood to spot chromosomal disorders such as Down syndrome. Current prenatal gene tests, such as amniocentesis and chorionic villus sampling (CVS), require inserting a needle in the uterus and carry a miscarriage risk of around half a percent.
Safety may not be the only gain. Researchers hope the test will spot Down syndrome — the most common genetic cause of developmental disabilities and mental retardation — much earlier in gestation than the other methods. And it may be able to detect other genetic disorders, such as Edwards syndrome and Patau syndrome.
The method exploits the ability of new and improved DNA technologies to reveal more detailed genetic information. "I am extraordinarily excited,'' said Stephen Quake, a Stanford professor of bioengineering and the study's senior author. "I got into this because I have a family, with two kids. With the first kid, we used amnio. With the second, we used CVS. Both were nerve-wracking experiences."
A description of the new technique, which counts chromosomes using bits of fetal DNA in a pregnant woman's blood, was published online Monday in the Proceedings of the National Academy of Sciences. The new method was developed by scientists at Stanford, the Howard Hughes Medical Institute and Lucile Packard Children's Hospital.
"The ability to diagnose fetal chromosomal disorders from maternal blood would be an important advance in the area of prenatal diagnosis,'' said test expert Dr. James Goldberg of the San Francisco-based Perinatal Associates. A founding fellow of the American College of Medical Genetics, Goldberg said the approach "would eliminate the small risk of fetal loss associated with invasive procedures such as amniocentesis and chorionic villus sampling."
But because other promising approaches have not held up after further testing, Goldberg remains cautious until the findings are confirmed in a large study. If the further trial is successful, doctors might be able to use the new method in as few as two years.
The new method scans for aneuploidy, an abnormality in the number of chromosomes. Humans typically inherit 46 chromosomes, half from each parent. Errors in chromosome number cause serious problems in physical and mental development. Down syndrome, for example, arises from an extra copy of chromosome 21.
First, using samples from 12 women with aneuploid pregnancies and six with normal pregnancies, the researchers separated maternal blood into cells and plasma. They focused on the plasma, seeking free-floating DNA fragments, which come from both the mother and the fetus.
They counted the number of DNA fragments and used DNA sequencing to read each one. Then the researchers counted how many gene fragments originated from each chromosome. Women with Down syndrome pregnancies had more chromosome-21 fragments in their blood than women with normal pregnancies.
"Right now, people are risking their pregnancies to get this information," said Dr. Yair Blumenfeld, a Stanford postdoctoral medical fellow in obstetrics and gynecology and co-author of the paper describing the technique.
This elegant but simple mathematical approach relied on recent innovations in science, Quake said. "This would not have been practical even three years ago,'' said Quake, citing technological breakthroughs that allowed researchers to quickly sequence large amounts of DNA and also the Human Genome Project. "Without that data," he said, "it wouldn't have worked.''
Contact Lisa Krieger at firstname.lastname@example.org or (408) 920-5565.