alexa Isolating fetal cells from maternal blood. Advances in prenatal diagnosis through molecular technology.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Health & Medical Informatics

Author(s): Simpson JL, Elias S

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Abstract OBJECTIVES: To review the rationale for and progress toward the goal of isolating and analyzing fetal cells circulating in maternal blood, and to explore the feasibility of this method in providing noninvasive prenatal cytogenetic diagnosis. DATA SOURCES: Critical review of data published since the first report (1969) of fetal metaphases in maternal blood. Emphasis is placed on data since the demonstration by polymerase chain reaction (PCR) in 1989 and 1990 that fetal cells indeed exist in maternal blood. DATA SYNTHESIS: Clinical evaluations have not yet been conducted, but it is already clear that molecular technologies have allowed the unequivocal demonstration of fetal cells in maternal blood. Using PCR, our own group and others have demonstrated Y sequences and single gene sequences (eg, hemoglobin LeporeBoston) in maternal blood. Thus, fetal DNA sequences indeed exist in maternal blood. Among the various candidate cells, the most promising appear to be fetal nucleated red blood cells. We isolated nucleated red blood cells on the basis of flow-sorting for the transferrin receptor and glycophorin-A. Enriched samples were then subjected to fluorescence in situ hybridization with chromosome-specific probes. This approach allowed us to detect trisomy 21 and trisomy 18, work later confirmed by others. CONCLUSIONS: Isolating and analyzing fetal cells from maternal blood is clearly possible. Several key biologic questions remain--the optimal cells for isolation, frequency of cells in maternal blood, timing during gestation for maternal blood sampling, and the likelihood of persistence of fetal cells after delivery. Clinical evaluations planned by the National Institute of Child Health and Human Development will determine the sensitivity and specificity of this method and its precise role in prenatal cytogenetic diagnosis.
This article was published in JAMA and referenced in Journal of Health & Medical Informatics

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