A Safer Test for Down Syndrome

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Quake and his colleagues took blood samples from pregnant women who were considered at high risk of carrying a baby with aneuploidy and used high-throughput sequencing to amplify fragments of DNA from both the mother and fetus and to map its chromosomes. They then looked at the amount of material from each chromosome. An overabundance of any particular chromosome pointed to a genetic disorder. The results, Quake says, "can be as precise as you want simply by sequencing more fragments."

"It's a step forward," adds James Egan, chairman of the Department of Obstetrics and Gynecology at the University of Connecticut Health Center. "It has great potential, but it's not ready for prime time yet." Egan did not contribute to the Stanford study. Quake's team is now planning a larger study of several hundred pregnant women.

The cost of the sequencing used in the study was $700 per sample, but Quake says that it has since slipped to $300, as the cost of the technology continues to drop. "If it truly can be performed for $700, it could revolutionize the field," Simpson says.

Quake's team tested women in their second trimester of pregnancy, although he believes that the test could be used as early as 10 weeks into a pregnancy. A first-trimester test for Down syndrome would be preferable, so that parents have more time to decide if they wish to terminate the pregnancy, or to prepare for the birth of a baby with the disorder.

Quake's method is one of several different approaches to the problem of using fetal DNA in a noninvasive diagnostic test for genetic disorders like Down syndrome.

Sequenom, based in San Diego, is developing a test based on genes on chromosome 21 that code for fetal-specific RNA. Those markers can be used to count copies of the chromosome."There are thousands of genetic disorders that can easily be diagnosed with genetic screening," says Ravinder Dhallan, founder and CEO of Ravgen, a Columbia, MD-based biotech company that's developing diagnostic tests using fetal DNA. "Some are treatable today and many more may be treatable in the future.

It's not yet clear which method--or methods--will ultimately pay off. "It's like CDs or DVDs or thumb drives," says the University of Connecticut's Egan. "They're all different ways of approaching a problem. One or all will catch the imagination of the medical community and become a very useful clinical tool."