Human Genetics

, Volume 131, Issue 11, pp 1751–1759

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

DOI: 10.1007/s00439-012-1195-x

Cite this article as:
Hui, L., Slonim, D.K., Wick, H.C. et al. Hum Genet (2012) 131: 1751. doi:10.1007/s00439-012-1195-x

Abstract

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.

Supplementary material

439_2012_1195_MOESM1_ESM.doc (868 kb)
Supplementary material 1 (DOC 867 kb)
439_2012_1195_MOESM2_ESM.doc (554 kb)
Supplementary material 2 (DOC 553 kb)
439_2012_1195_MOESM3_ESM.doc (108 kb)
Supplementary material 3 (DOC 108 kb)
439_2012_1195_MOESM4_ESM.doc (198 kb)
Supplementary material 4 (DOC 197 kb)
439_2012_1195_MOESM5_ESM.doc (141 kb)
Supplementary material 5 (DOC 141 kb)
439_2012_1195_MOESM6_ESM.doc (115 kb)
Supplementary material 6 (DOC 115 kb)
439_2012_1195_MOESM7_ESM.doc (88 kb)
Supplementary material 7 (DOC 88.5 kb)
439_2012_1195_MOESM8_ESM.doc (33 kb)
Supplementary material 8 (DOC 33.0 kb)
439_2012_1195_MOESM9_ESM.doc (78 kb)
Supplementary material 9 (DOC 78.5 kb)
439_2012_1195_MOESM10_ESM.doc (62 kb)
Supplementary material 10 (DOC 62 kb)

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

Personalised recommendations