Predicting pathway perturbations in Down syndrome

  • K. Gardiner
Part of the Journal of Neural Transmission Supplement 67 book series (NEURAL SUPPL, volume 67)


Comparative annotation of human chromosome 21 genomic sequence with homologous regions of mouse chromosomes 16, 17 and 10 has identified 170 orthologous gene pairs. Functional annotation of these genes, based on literature reports and computationally-derived predictions, shows that a broad range of cellular processes are represented. A goal of Down syndrome research is to determine which of these processes are perturbed by overexpression of chromosome 21 genes, and which may, therefore, contribute to the cognitive deficits that characterize Down syndrome. Eleven chromosome 21 genes are annotated to interact with or be affected by components of the MAP Kinase pathway and eight are involved in Ca2+/calcineurin signaling. Both pathways are critical for normal neurological function, and consequently their perturbations are proposed as candidates for phenotypic relevance. We present evidence suggesting that the MAP Kinase pathway is perturbed in the Ts65Dn mouse model of Down syndrome at 4–6 months of age. Analysis is complicated by the observation that overexpression of chromosome 21 genes in trisomy may be affected by method of detection, organism, tissue or brain region, and/or developmental age.


Nerve Growth Factor Down Syndrome Ts65Dn Mouse Orthologous Gene Pair Calcineurin Signaling 
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 2003

Authors and Affiliations

  • K. Gardiner
    • 1
    • 2
    • 3
    • 4
  1. 1.Eleanor Roosevelt InstituteUniversity of DenverDenverUSA
  2. 2.Department of Biochemistry and GeneticsUniversity of Colorado Health Sciences CenterDenverUSA
  3. 3.Eleanor Roosevelt InstituteUniversity of DenverDenverUSA
  4. 4.Department of Biochemistry and GeneticsUniversity of Colorado Health Sciences CenterDenverUSA

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