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Advances in Down Syndrome Research pp 21–37Cite as

Predicting pathway perturbations in Down syndrome

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Part of the book series: Journal of Neural Transmission Supplement 67 ((NEURAL SUPPL,volume 67))

Summary

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.

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Authors and Affiliations

  1. Eleanor Roosevelt Institute, University of Denver, Denver, CO, USA

    Dr. K. Gardiner

  2. Department of Biochemistry and Genetics, University of Colorado Health Sciences Center, Denver, CO, USA

    Dr. K. Gardiner

  3. Eleanor Roosevelt Institute, University of Denver, 1899 Gaylord Street, Denver, Co, 80206, USA

    Dr. K. Gardiner

  4. Department of Biochemistry and Genetics, University of Colorado Health Sciences Center, 1899 Gaylord Street, Denver, Co, 80206, USA

    Dr. K. Gardiner

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Editors and Affiliations

  1. Department of Pediatrics, University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria

    G. Lubec

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© 2003 Springer-Verlag

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Gardiner, K. (2003). Predicting pathway perturbations in Down syndrome. In: Lubec, G. (eds) Advances in Down Syndrome Research. Journal of Neural Transmission Supplement 67, vol 67. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6721-2_2

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  • DOI: https://doi.org/10.1007/978-3-7091-6721-2_2

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  • Print ISBN: 978-3-211-40776-9

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