, Volume 3, Issue 3, pp 396–406

The cognitive phenotype of Down syndrome: Insights from intracellular network analysis



Down syndrome (DS) is caused by trisomy of chromosome 21. All individuals with DS exhibit some level of cognitive dysfunction. It is generally accepted that these abnormalities are a result of the upregulation of genes encoded by chromosome 21. Many chromosome 21 proteins are known or predicted to function in critical neurological processes, but typically they function as modulators of these processes, not as key regulators. Thus, upregulation in DS is expected to cause only modest perturbations of normal processes. Systematic approaches such as intracellular network construction and analysis have not been generally applied in DS research. Networks can be assembled from high-throughput experiments or by text-mining of experimental literature. We survey some new developments in constructing such networks, focusing on newly developed network analysis methodologies. We propose how these methods could be integrated with creation and manipulation of mouse models of DS to advance our understanding of the perturbed cell signaling pathways in DS. This understanding could lead to potential therapeutics.

Key Words

Down syndrome systems biology graph theory text-mining Bayesian networks qualitative modeling 


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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2006

Authors and Affiliations

  • Avi Ma’ayan
    • 1
  • Katheleen Gardiner
    • 2
  • Ravi Iyengar
    • 1
  1. 1.Department of Pharmacology and Biological ChemistryMount Sinai School of MedicineNew York
  2. 2.Eleanor Roosevelt Institute at the University of DenverUniversity of Colorado at Denver and the Health Sciences CenterDenver

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