New prenatal test for down syndrome less risky than amniocentesis, Stanford/Packard scientists say

October 06, 2008

STANFORD, Calif. -- Pregnant women worried about their babies' genetic health face a tough decision: get prenatal gene testing and risk miscarriage, or skip the tests and miss the chance to learn of genetic defects before birth.

But a new prenatal test could make this dilemma obsolete. The new method, developed by scientists at Stanford University, the Howard Hughes Medical Institute and Lucile Packard Children's Hospital, requires only a maternal blood sample to spot chromosomal disorders such as Down syndrome.

"Right now, people are risking their pregnancies to get this information," said Yair Blumenfeld, MD, a postdoctoral medical fellow in obstetrics and gynecology and co-author of a paper describing the technique. Current prenatal gene tests, such as amniocentesis and chorionic villus sampling, require inserting a needle in the uterus and carry a miscarriage risk of around half a percent.

"Non-invasive testing will be much safer than current approaches," said Stephen Quake, PhD, professor of bioengineering and the study's senior author. The new technique, which takes advantage of fragments of fetal DNA in the woman's blood, will be published online the week of Oct. 6 in the Proceedings of the National Academy of Sciences. Safety may not be the only gain. Quake hopes the test will spot genetic problems much earlier in gestation than the other methods.

The new method scans for fetal aneuploidy, an abnormality in the number of fetal 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.

The Stanford/Packard team developed a way to count chromosomes using bits of fetal DNA in a pregnant woman's blood. Other scientists had struggled to tease these tiny genetic clues apart from a mom's DNA, said Quake, who is also an HHMI investigator. His team made an ingenious simplification: their new method has no need to distinguish between maternal and fetal DNA.

First, using samples from 12 women with aneuploid pregnancies and six with normal pregnancies, the researchers separated maternal blood into cells and plasma. They discarded the blood cells, focusing on the liquid plasma's DNA fragments, which come from both the mom and the fetus. They counted the number of DNA fragments and used DNA sequencing to read each one.

"You randomly sequence whatever is there," explained Christina Fan, a doctoral student in bioengineering who was the study's lead author. The DNA fragments are 25-30 base pairs long, she said, long enough to match each fragment to a specific chromosome. The researchers tallied 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. Other forms of aneuploidy could be detected, too.

Because fetal DNA shows up in maternal blood quite early in pregnancy, the team says their technique could provide a much earlier diagnosis for fetal aneuploidy than is now available.

"The earlier you know you've got a fetus with Down syndrome, the better able you are to prepare," Quake said, noting that the benefit holds both for women who keep and those who terminate such pregnancies.

The next step, the scientists say, is to repeat their study in a larger number of women. If their technique holds up in further research, they expect that it would be simple and inexpensive to use in clinical settings, especially as other forms of genetic testing also become popular. Quake expects it will take the new test two to three years to reach the clinic, assuming that the larger trial is successful.

"This technique is on the leading edge of a flood of different ways that rapid DNA sequencing will be used in medicine," Quake said.
Stanford is filing a patent application for the new technique, and Quake consults for two potential licensees. In addition to Fan and Blumenfeld, Quake's team included Usha Chitkara, MD, professor of obstetrics and gynecology at Stanford and Packard Children's, and Louanne Hudgins, MD, director of perinatal genetics at Packard Children's and professor of pediatrics. The study was funded by the Wallace H. Coulter Foundation and the NIH Director's Pioneer Award. Stanford University Medical Center integrates research, medical education and patient care at its three institutions -- Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at

Ranked as one of the best pediatric hospitals in the nation by U.S. News & World Report and Child magazine, Lucile Packard Children's Hospital at Stanford is a 272-bed hospital devoted to the care of children and expectant mothers. Providing pediatric and obstetric medical and surgical services and associated with the Stanford University School of Medicine, Packard Children's offers patients locally, regionally and nationally the full range of health care programs and services -- from preventive and routine care to the diagnosis and treatment of serious illness and injury. For more information, visit

Stanford University Medical Center

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to