title: Gene expression analysis in pregnant women and their infants identifies unique fetal biomarkers that circulate in maternal blood.
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 antepartum 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.
authors: Department of Pediatrics, Tufts--New England Medical Center, Boston, Massachusetts, USA. jmaron@tufts-nemc.org
authors: Jill L
authors: JL
authors: Maron
authors: Kirby L
authors: KL
authors: Johnson
authors: Donna
authors: D
authors: Slonim
authors: Chao-Qiang
authors: CQ
authors: Lai
authors: Marco
authors: M
authors: Ramoni
authors: Gil
authors: G
authors: Alterovitz
authors: Zina
authors: Z
authors: Jarrah
authors: Zinger
authors: Z
authors: Yang
authors: Diana W
authors: DW
authors: Bianchi
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D005333:Fetus / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007231:Infant, Newborn; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy / Q000235:genetics*; D037841:Pregnant People; D012333:RNA, Messenger / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger