Prenatal Genetic Test Analyzes DNA from Fetal Cells
Hughes researcher Yuet Wai Kan and his colleagues have designed a prenatal blood test to diagnose fetuses at risk for developing sickle cell anemia and thalassemias.
Hughes researchers have designed a prenatal blood test to diagnose a fetus at risk for developing sickle cell anemia or β-thalassemia.
To test a fetus for a genetic disorder, doctors collect fetal cells that may contain DNA with telltale disease-causing mutations. Getting these fetal cells is tricky. Today's techniquesamniocentesis and chorionic villus sampling (CVS)require physicians to use a needle to gather fetal cells on or in the amniotic sac surrounding the fetus. These invasive procedures carry a small risk for the fetus.
For years, researchers have studied ways to isolate fetal cells that leak into a mother's bloodstream during pregnancy. Until now, technical hurdleslike finding the right kind of fetal cell and gathering enough to studyhampered these efforts. But Yuet Wai Kan, a Hughes investigator at the University of California in San Francisco, and colleagues have now overcome the hurdles.
Kan's team zeroed in on the fetal erythroblast, a short-lived nucleated red blood cell that migrates into a mother's bloodstream. Using blood drawn from two pregnant women whose fetuses were at risk for β-thalassemia and sickle cell anemia, the researchers separated maternal and fetal erythroblasts from other cells based on certain physical properties of the cell. Next, they applied an antibody that recognizes fetal or embryonic hemoglobin and turns the fetal cell red. HHMI research associate Mei-Chi Cheung then pooled the red cells and amplified their DNA for analysis. According to Kan's test, neither fetus was affected by diseasea diagnosis independently confirmed by CVS. The results were reported in the November, 1996 issue of Nature Genetics.
Kan has been a pioneer in the field of hematology. In 1975, he discovered that a single missing gene causes α-thalassemia, a heritable blood disorder. Months later, his team developed the first prenatal DNA test for α-thalassemia.
In both thalassemias, a defective gene produces too little hemoglobin, resulting in anemia. People with thalassemia often descend from the Mediterranean region or Asia. In the United States, sickle cell anemia is more common, affecting about 80,000 people, most of African-American descent. In this disease, a defective gene produces abnormal rod-like hemoglobin molecules that plug blood vessels, restricting blood and oxygen supply. As a result, patients suffer bouts of severe pain, organ damage or stroke.
Like most geneticists, Kan isn't content merely to diagnose disease He wants to treat it. "Genetic therapy is the real challenge," he says. "That's the next area of research." Kan and colleagues have designed a retroviral vector, or carrier, to shuttle healthy globin genes into a patient's cells. His vector strictly targets cells in which the gene is mutatedan improvement over most gene therapy vectors, which enter many cells, including healthy ones.