Looking for the Telltale Gene

Are we ready for this knowledge? A Columbia study looks for answers.

Columbia Magazine’s Spring 2013 issue includes a feature article about a National Institutes of Health-funded multicenter study, led by Ronald Wapner, MD, director of reproductive genetics at Columbia University Medical Center and vice chairman for research in the Department of Obstetrics and Gynecology, which provided thousands of pregnant women with microarray analysis, a powerful new genetic test, for prenatal testing. The purpose of his study was to determine if this test generates information that is useful to doctors and parents, and therefore should be offered to all expectant mothers. As written in the article by Claudia Kalb:

Prenatal genetic testing emerged in the 1970s, when obstetricians started to recommend amniocentesis for pregnant women over the age of thirty-five. The first common condition that scientists learned to preemptively diagnose was Down syndrome, which stood out because it is caused by the presence of a whole extra chromosome. Soon, they were also spotting the large chromosomal anomalies that cause Tay-Sachs disease, sickle-cell anemia, and several disorders of the neural tube, which is the embryo’s precursor to the brain and spinal cord.

Wapner, a sixty-five-year-old obstetrician who came to Columbia from Drexel University in 2005, has been trying to improve prenatal diagnosis his entire career. In the early 1980s, he was instrumental in developing chorionic villus sampling (CVS), a procedure in which fetal cells are extracted from a woman’s placenta rather than from her amniotic fluid. CVS can be done at an earlier stage of pregnancy — in the first trimester, versus the second — and is now a popular alternative to amniocentesis, although some women still get amniocentesis because it is easier for physicians to administer and is more widely available.

Wapner’s most important contribution, though, may turn out to be his advancement of microarray analysis, the genetic test that Bermudez underwent last summer. The idea is simple: rather than limiting oneself to what can be spotted visually, why not use computers to identify the minutest discrepancies in a baby’s DNA? The technology is not new. By the time Wapner proposed examining fetal tissue this way in 2006, physicians had been analyzing the DNA of sick children by microarray for a few years. The technique was especially useful in spotting rare disorders that pediatricians had trouble diagnosing any other way.

“Say you have a youngster with a seemingly random combination of learning difficulties and physical problems, like a heart defect and cleft palate,” says Wapner. “If you do the microarray, you may discover he has a small piece of chromosome 22 missing. That indicates it’s DiGeorge syndrome. And it means he’s got a 25 percent chance of developing schizophrenia. So now you can be on the lookout for that, too.”

With such a sophisticated tool, however, came thorny ethical questions. Obstetricians knew from experience that many pregnant women who opt for genetic testing are those who, after having received a troubling result on an ultrasound, are considering abortion. The method of analysis using microscopes, which is called karyotyping, was generally considered a useful tool for helping them to make this decision because it identified large, clearly defined genetic defects. The microarray test, on the other hand, would detect not only the genetic signatures of rare diseases like DiGeorge syndrome but also many other DNA flaws whose impact on the body were not yet fully understood.

 “Imagine if parents and doctors knew from day one that a child was going to be susceptible to autism,” Wapner says. “They might catch it sooner and provide him early intervention, which can be critical. There are all sorts of things a physician can do with this information.”