Prenatal Test Can Detect Sickle-Cell, Other Illness
A new genetic engineering technique for the prenatal diagnosis of sickle-cell disease has been developed by scientists at Cetus Corp. in Emeryville, Calif. The technique is at least 100 times more sensitive than existing tests, is much faster, and can be performed more cheaply.
The advance, reported in the most recent issue of the journal Science, can also be applied to the detection of other genetic diseases and, perhaps most important, to the diagnosis of infectious diseases.
The test is based on two independent technologies that can be separately used, but are most effective when used together.
The first technology, developed by Kary Mullis and Fred Faloona of Cetus, provides a way to greatly increase the amount of DNA--deoxyribonucleic acid, the material of which genes are composed--in a sample. This step is especially effective because only the DNA of interest, such as a portion of a particular gene, is increased in quantity.
The second technology, developed by Henry Erlich and his colleagues, uses a small piece of synthetic DNA, called a DNA probe, to bind to the DNA of interest. When the probe and the bound DNA are treated with specific enzymes that break the DNA into smaller pieces, characteristic fragments are produced.
Fragments Identified
These fragments can be separated and identified to determine if, for example, a specific defective gene is present in DNA obtained from fetal cells or if DNA from a specific microorganism is present in fluids from an infected patient.
The important thing about his technique, Erlich said in a telephone interview, is that the process can be easily automated.
In the case of the sickle-cell disease, scientists are looking for a defective gene that serves as a blueprint for an abnormal protein called Hemoglobin S. Normal hemoglobin carries oxygen through the blood. Hemoglobin S also carries oxygen, but much less effectively, so that the victim is deprived of oxygen during stress periods.
A victim of sickle-cell disease has two genes that code for Hemoglobin S. A carrier of the disease--who does not exhibit any symptoms--has one gene for Hemoglobin S and one for normal hemoglobin. A healthy individual has two normal genes. About 70,000 Americans suffer from sickle-cell disease.
For prenatal detection, the Cetus scientists first obtain a small sample of DNA from the fetus, either from cells in the amniotic fluid surrounding the fetus or with a newer technique called chorionic villi sampling. Mullis’ and Faloona’s technique is then used to increase the amount of the DNA of interest, specifically the portion of the hemoglobin gene that contains the defect, by a factor of more than 200,000.
This “amplified DNA” is treated with the DNA probe technology and the resulting fragments are analyzed. If two Hemoglobin S genes are present, one characteristic pattern is produced. If one normal and one Hemoglobin S gene are present a second pattern is produced. If two normal genes are present, a third pattern is produced.
Erlich and his colleagues have tested about 60 DNA samples with the technique and have found that all results agree with those obtained conventionally. The conventional test, however, costs about $500 and takes at least five days. The new technique, in contrast, may eventually cost only $50 to $100 and produces results overnight.
Commercialization of this new approach could give Cetus “a premier position” in the rapidly growing field of disease detection and diagnosis, according to Robert Kupor, an analyst for the Seattle firm of Cable, Howse & Ragen Inc.
Erlich’s group has also cooperated with local physicians to perform two actual prenatal diagnoses.
“In both cases,” he said, “the test showed the fetuses to be carriers of the sickle trait rather than victims of the disease. Neither fetus has been born yet, however, so we haven’t published those results.”
The test would be similarly applied for screening for other genetic diseases, and Cetus is already working on probes for such diseases.
Testing for disease might be more complicated, however. If a specific disease is thought to be present, the test could be used to confirm the microorganism’s presence. More often, however, it would be necessary to screen the patient for a number of different microorganisms to precisely identify the disease. Cetus is developing a machine that would automatically perform such screening.
“The chief advantage of Cetus’s approach,” Kupor said, “is that it would identify the disease-causing organism much more quickly than currently used techniques and thus would allow appropriate treatment to be begun sooner.”
