Human Genetics

, Volume 131, Issue 11, pp 1751–1759 | Cite as

Novel neurodevelopmental information revealed in amniotic fluid supernatant transcripts from fetuses with trisomies 18 and 21

  • Lisa Hui
  • Donna K. Slonim
  • Heather C. Wick
  • Kirby L. Johnson
  • Keiko Koide
  • Diana W. Bianchi
Original Investigation


Trisomies 18 and 21 are the two most common live born autosomal aneuploidies in humans. While the anatomic abnormalities in affected fetuses are well documented, the dysregulated biological pathways associated with the development of the aneuploid phenotype are less clear. Amniotic fluid (AF) cell-free RNA is a valuable source of biological information obtainable from live fetuses. In this study, we mined gene expression data previously produced by our group from mid-trimester AF supernatant samples. We identified the euploid, trisomy 18 and trisomy 21 AF transcriptomes, and analyzed them with a particular focus on the nervous system. We used multiple bioinformatics resources, including DAVID, Ingenuity Pathway Analysis, and the BioGPS Gene Expression Atlas. Our analyses confirmed that AF supernatant from aneuploid fetuses is enriched for nervous system gene expression and neurological disease pathways. Tissue analysis showed that fetal brain cortex and Cajal–Retzius cells were significantly enriched for genes contained in the AF transcriptomes. We also examined AF transcripts known to be dysregulated in aneuploid fetuses compared with euploid controls and identified several brain-specific transcripts among them. Many of these genes play critical roles in nervous system development. NEUROD2, which was downregulated in trisomy 18, induces neurogenic differentiation. SOX11, downregulated in trisomy 21, is a transcription factor that is essential for pan-neuronal protein expression and axonal growth of sensory neurons. Our results show that whole transcriptome analysis of cell-free RNA in AF from live pregnancies permits discovery of biomarkers of abnormal human neurodevelopment and advances our understanding of the pathophysiology of aneuploidy.


Down Syndrome Amniotic Fluid Ingenuity Pathway Analysis Amniotic Fluid Sample Retzius Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank Janet Cowan, PhD, and Uma Tantravahi, PhD, who provided the AF supernatant samples. Financial support was provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD 42053-09 to Dr Bianchi and R01 HD 058880 to Dr Slonim); the University of Sydney Medical School (Albert S. McKern Research Scholarship to Dr Hui); and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists Research Foundation (Fotheringham Fellowship to Dr Hui). The authors declare that they have no conflicts of interest to disclose. This study complies with current laws of the United States of America.

Supplementary material

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Lisa Hui
    • 1
    • 2
  • Donna K. Slonim
    • 3
    • 4
  • Heather C. Wick
    • 3
  • Kirby L. Johnson
    • 1
  • Keiko Koide
    • 1
  • Diana W. Bianchi
    • 1
  1. 1.Mother Infant Research Institute and the Division of Genetics, Department of PediatricsThe Floating Hospital for Children at Tufts Medical CenterBostonUSA
  2. 2.The Department of Obstetrics, Gynecology and NeonatalogyUniversity of SydneySydneyAustralia
  3. 3.Department of Computer ScienceTufts UniversityMedfordUSA
  4. 4.Department of PathologyTufts University School of MedicineBostonUSA

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