Many pregnant women have their unborn children screened for genetic abnormalities, such as Down syndrome. But standard tests cannot identify all problems, and many extremely serious conditions go undetected until birth. In a new study, researchers from the Baylor College of Medicine in Houston used DNA chips to test unborn babies for more than 270 genetic syndromes. They found that this procedure provided a more detailed and accurate view of the fetus’s genetic profile than the approach commonly used today.
The process normally used for prenatal diagnosis is karyotyping, which looks at the overall size and shape of chromosomes to identify problems. Sau Wai Cheung, director of Baylor’s Cytogenetics Laboratory and one of the leaders of the new study, says the new research shows that DNA chips can reliably detect far smaller chromosomal abnormalities than karyotyping allows. And while these abnormalities may be small in size, they can have a big impact. “A lot of the diseases that we tested for [in this study] cause mental delays and problems with physical development,” said Cheung. Angelman syndrome, for example, can result in significant developmental problems and seizures.
Arthur Beaudet, who led the study with Cheung and is chair of Baylor’s Department of Molecular and Human Genetics, says some parents want an early diagnosis so they can decide whether or not to terminate a pregnancy. Others simply want the information to prepare for their child’s special needs.
The DNA chip used in the study performs a process known as array comparative genomic hybridization (aCGH), which involves looking for an abnormal number of copies of particular segments of DNA. Normally, humans have two copies of each segment. Having extra or missing copies can result in serious medical problems. Each DNA chip contains hundreds of single-stranded DNA segments, each embedded in a piece of glass at a precise location. The researchers then add single-stranded, fetal DNA segments, usually taken from amniotic fluid. These strands are labeled red. Single-stranded DNA reference segments, which act as a control group and are labeled green, are also added to the chip. Once the fetal and control strands are bound with the embedded DNA, the arrangement of colors on the chip is imaged and analyzed by a computer.
“Basically we measured the color signal intensity,” said Cheung. If the fetus has an extra copy of a particular segment of DNA, then the spot on the chip that corresponds to that DNA segment will appear more red than green. If the fetus is missing a DNA segment, the corresponding spot on the chip will appear more green than red. And if the fetus has the correct number of copies of the DNA segment, then the spot should appear yellow.
Beaudet says that aCGH is already used in pediatric medicine with great success, but it has only recently been investigated for prenatal diagnostics. While the Baylor study sample was small–only 300 cases–the researchers say it is the largest of its kind to date. In the study, published in the current issue of Prenatal Diagnosis, the researchers identified seven cases where the aCGH results provided new information about the risk of disease, including two cases that would otherwise have been missed.