ARS | Publication request: Gene expression analysis in pregnant women and their infants identifies unique fetal biomarkers that circulate in maternal blood

Submitted to: Journal of Clinical Investigation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 2, 2007
Publication Date: October 1, 2007
Citation: Maron, J.L., Johnson, K.L., Sionim, D., Lai, C., Ramoni, M., Alterovitz, G., Jerrah, Z., Yang, Z., Bianchi, D.W. 2007. Gene expression analysis in pregnant women and their infants identifies unique fetal biomarkers that circulate in maternal blood. Journal of Clinical Investigation. 117:3007-3019.

Interpretive Summary: The discovery of fetal mRNA transcripts in the maternal circulation holds great promise for noninvasive prenatal diagnosis. To identify potential fetal biomarkers in pregnant women’s blood, we studied gene expression pattern changes in 9-term pregnant women’s blood and their newborn. To do that, we isolated RNA from peripheral blood of 9-term pregnant and postpartum women (after childbirth), and umbilical blood of their newborns. The labeled RNA was hybridized to GeneChip microarrays for gene expression, from which paired Student’s t test and pathway analyses were performed. We identified 157 gene transcripts that met statistical significance, and were common in 9-term pregnant mother and their newborn, but absent or reduced in postpartum mothers. These unique fetal biomarkers included 27 developmental genes, 5 sensory perception genes, and 22 genes involved in neonatal physiology. Real-time RT-PCR amplification confirmed the presence of specific gene transcripts. Furthermore, SNP genotyping analysis demonstrated the presence of 3 fetal transcripts in maternal ante partum blood (pregnant mother’s blood), but not in maternal postpartum blood (after childbirth). Comparison of whole blood and plasma samples from the same pregnant woman suggested that placental genes are more easily detected in plasma. We conclude that fetal and placental mRNA circulates in the blood of pregnant women. In summary, this study identified a unique set of biologically diverse fetal genes and has a multitude of clinical applications.

Technical Abstract: The discovery of fetal mRNA transcripts in the maternal circulation holds great promise for noninvasive prenatal diagnosis. To identify potential fetal biomarkers, we studied whole blood and plasma gene transcripts that were common to 9 term pregnant women and their newborns but absent or reduced in the mothers postpartum. RNA was isolated from peripheral or umbilical blood and hybridized to gene expression arrays. Gene expression, paired Student’s t test, and pathway analyses were performed. In whole blood, 157 gene transcripts met statistical significance. These fetal biomarkers included 27 developmental genes, 5 sensory perception genes, and 22 genes involved in neonatal physiology. Transcripts were predominantly expressed or restricted to the fetus, the embryo, or the neonate. Real-time RT-PCR amplification confirmed the presence of specific gene transcripts; SNP analysis demonstrated the presence of 3 fetal transcripts in maternal ante partum blood. Comparison of whole blood and plasma samples from the same pregnant woman suggested that placental genes are more easily detected in plasma. We conclude that fetal and placental mRNA circulates in the blood of pregnant women. Transcriptional analysis of maternal whole blood identifies a unique set of biologically diverse fetal genes and has a multitude of clinical applications.