Altered gene expression in fetal Down Syndrome brain as revealed by the gene hunting technique of subtractive hybridization

  • E. Kitzmueller
  • O. Labudova
  • H. Rink
  • N. Cairns
  • G. Lubec
Conference paper


Information on gene expression in brain of patients with Down Syndrome (DS, trisomy 21) is limited and molecular biological research is focussing on mapping and sequencing chromosome 21. The information on gene expression in DS available follows the current concept of a gene dosage effect due to a third copy of chromosome 21 claiming overexpression of genes encoded on this chromosome.

Based upon the availability of fetal brain and recent technology of gene hunting, we decided to use subtractive hybridization to evaluate differences in gene expression between DS and control brains.

Subtractive hybridization was applied on two fetal brains with DS and two age and sex matched controls, 23rd week of gestation, and mRNA steady state levels were evaluated generating a subtractive library. Subtracted sequences were identified by gene bank and assigned by alignments to individual genes.

We found a series of up-and downregulated sequences consisting of chromosomal transcripts, enzymes of intermediary metabolism, hormones, transporters / channels and transcription factors (TFs).

We show that trisomy 21 or aneuploidy leads to the deterioration of gene expression and the derangement of transcripts describes the impairment of transport, carriers, channels, signaling, known metabolic and hormone imbalances. The dys-coordinated expression of transcription factors including homeobox genes, POU-domain TFs, helix-loop-helix-motifs, LIM domain containing TFs, leucine zippers, forkhead genes, maybe of pathophysiological significance for abnormal brain development and wiring found in patients with DS. This is the first description of the concomitant expression of a large series of sequences indicating disruption of the concerted action of genes in this disorder.


Down Syndrome Down Syndrome Patient Subtractive Library Down Syndrome Brain Gene Hunting 
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.


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Copyright information

© Springer-Verlag Wien 1999

Authors and Affiliations

  • E. Kitzmueller
    • 1
  • O. Labudova
    • 1
  • H. Rink
    • 2
  • N. Cairns
    • 3
  • G. Lubec
    • 1
  1. 1.Department of PediatricsUniversity of ViennaViennaAustria
  2. 2.Department of RadiobiologyUniversity of BonnFederal Republic of Germany
  3. 3.Brain Bank, Institute of PsychiatryUniversity of LondonUK

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