Absence of Maternal Contamination of Chorionic Villi Used for Fetal-Gene Analysis

Chorionic villi can be obtained by direct transcervical aspiration at 9 to 10 weeks' gestation and used for analysis of fetal DNA. However, for the method to be reliable, there must be no detectable contamination by maternal DNA. To investigate the question of contamination, we compared the DNA of chorionic villi from five fetuses with that obtained from maternal lymphocytes, using the restriction endonuclease Taq I and specific DNA probes for a pair of alleles on the X chromosome. The alleles yield fragments of different lengths when digested with Taq I (length polymorphism), which can be demonstrated by electrophoresis and hybridization with the radioactive DNA probes. If the pattern obtained with the chorionic DNA is different from that obtained with the maternal DNA, contamination is not present. In two cases the fetal DNA of the chorionic villi was shown to be uncontaminated by maternal tissue. In one of these cases the mother was heterozygous and the fetus was homozygous; in the other the mother was homozygous and the fetus was heterozygous. In three other cases no definitive conclusions could be drawn, because the genotypes of the fetus and mother were identical. We conclude that chorionic villi at 9 to 10 weeks' gestation are a source of fetal DNA that can be used for gene analysis, with no detectable contamination by maternal DNA. (N Engl J Med 1983; 308:1433–5.) In the first trimester of gestation, chorionic villi of the fetus are accessible by transcervical aspiration without anesthesia, as a source of trophoblasts for direct analysis of fetal DNA. 1 Although the method has been used for both the early diagnosis of hemoglobinopathies 2 and determination of fetal sex, 3 for its potential to be exploited, the chorionic tissue must be shown to be free of contaminating maternal tissue. Overgrowth by maternal cells is a documented risk. 4 In this article we show that chorionic villi obtained 9 to 10 weeks after the last menstrual period provide fetal DNA without detectable maternal contamination. The . . .