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Research of Down syndrome-related genes

  Research of Down syndrome-related genes is based on studying the genes located on chromosome 21. In general, this leads to an overexpression of the genes.[1] [2] Understanding the genes involved may help to target medical treatment to individuals with Down syndrome. It is estimated that chromosome 21 contains 200 to 250 genes.[3] Recent research has identified a region of the chromosome that contains the main genes responsible for the pathogenesis of Down syndrome,[4] located proximal to 21q22.3. The search for major genes involved in Down syndrome characteristics is normally in the region 21q21–21q22.3.

Some suspected genes involved in features of Down syndrome are given in the Table 1:

Table 1: Some genes located on the long arm of chromosome 21[3]
Gene OMIM Reference Location Purported Function
APP 104760 21q21 Amyloid beta A4 precursor protein. Suspected to have a major role in cognitive difficulties. One of the first genes studied with transgenic mice with Down syndrome.[5]
SOD1 147450 21q22.1 Superoxide dismutase. Possible role in Alzheimer's disease. Anti-oxidant as well as possible affects on the immuno-system.
DYRK 600855 21q22.1 Dual-specificity Tyrosine Phosphorylation-Regulated Kinase 1A. May have an effect on mental development through abnormal neurogenesis. [6]
IFNAR 107450 21q22.1 Interferon, Alpha, Beta, and Omega, Receptor. Responsible for the expression of interferon, which affects the immuno-system.
DSCR1 602917 21q22.1–21q22.2 Down Syndrome Critical Region Gene 1. Possibly part of a signal transduction pathway involving both heart and brain.[7]
COL6A1 120220 21q22.3 Collagen, type I, alpha 1 gene. May have an effect on heart disease.
ETS2 164740 21q22.3 Avian Erythroblastosis Virus E26 Oncogene Homolog 2. Researchers have "demonstrated that overexpression of ETS2 results in apoptosis. Transgenic mice overexpressing ETS2 developed a smaller thymus and lymphocyte abnormalities, similar to features observed in Down syndrome."[8]
CRYA1 123580 21q22.3 Crystallin, Alpha-A. Involved in the synthesis of Crystallin, a major component of the lens in eyes. May be cause of cataracts.


Specific genes

Amyloid beta (APP)

  One chromosome 21 gene that might predispose Down syndrome individuals to develop Alzheimer's pathology is the gene that encodes the precursor of the amyloid protein. Neurofibrillary tangles and amyloid plaques are commonly found in both Down syndrome and Alzheimer's individuals. Layer II of the entorhinal cortex and the subiculum, both critical for memory consolidation, are among the first affected by the damage. A gradual decrease in the number of nerve cells throughout the cortex follows. A few years ago, Johns Hopkins scientists created a genetically engineered mouse called Ts65Dn (segmental trisomy 16 mouse) as an excellent model for studying the Down syndrome. Ts65Dn mouse has genes on chromosomes 16 that are very similar to the human chromosome 21 genes. Recently, researchers have used this transgenic mouse to connect APP to cognitive problems among the mice.[5]

Superoxide dismutase (SOD1)

  Some (but not all) studies have shown that the activity of the superoxide dismutase enzyme is elevated in Down syndrome. SOD converts oxygen radicals to hydrogen peroxide and water. Oxygen radicals produced in cells can be damaging to cellular structures, hence the important role of SOD. However, the hypothesis says that once SOD activity increases disproportionately to enzymes responsible for removal of hydrogen peroxide (e.g., glutathione peroxidase), the cells will suffer from a peroxide damage. Some scientists believe that the treatment of Down syndrome neurons with free radical scavengers can substantially prevent neuronal degeneration. Oxidative damage to neurons results in rapid brain aging similar to that of Alzheimer's disease.


  1. ^ R Mao, CL Zielke, HR Zielke, J Pevsner (2003). "Global up-regulation of chromosome 21 gene expression in the developing Down syndrome brain". Genomics 81 (5): 457-467.
  2. ^ Rong Mao, X Wang, EL Spitznagel, LP Frelin, JC Ting, H Ding, J Kim, I Ruczinski, TJ Downey, J Pevsner (2005). "Primary and secondary transcriptional effects in the developing human Down syndrome brain and heart". Genome Biology 6 (13): R107.
  3. ^ a b See Leshin, L. (2003). Trisomy 21: The Story of Down Syndrome. Retrieved on 2006-05-21.
  4. ^ Zohra Rahmani, Jean-Louis Blouin, Nicole Créau-Goldberg, Paul C. Watkins, Jean-François Mattei, Marc Poissonnier, Marguerite Prieur, Zoubida Chettouh, Annie Nicole, Alain Aurias, Pierre-Marie Sinet, Jean-Maurice Delabar (2005). "Down syndrome critical region around D21S55 on proximal 21q22.3". American Journal of Medical Genetics 37 (S2): 98-103.
  5. ^ a b Chandra Shekhar (6 July 2006). Down syndrome traced to one gene. The Scientist. Retrieved on 2006-07-11.
  6. ^ Song, W.-J., Sternberg, L. R., Kasten-Sportes, C., Van Keuren, M. L., Chung, S.-H., Slack, A. C., Miller, D. E., Glover, T. W., Chiang, P.-W., Lou, L.; Kurnit, D. M. (1996). "Isolation of human and murine homologues of the Drosophila minibrain gene: human homologue maps to 21q22.2 in the Down syndrome 'critical region". Genomics 38: 331-339.
  7. ^ Fuentes JJ, Pritchard MA, Planas AM, Bosch A, Ferrer I, Estivill X (1995). "A new human gene from the Down syndrome critical region encodes a proline-rich protein highly expressed in fetal brain and heart". Hum Mol Genet 4 (10): 1935-1944.
  8. ^ OMIM, NIH. V-ETS Avian Erythroblastosis virus E26 Oncogene Homolog 2. Retrieved on 2006-06-29.

See also

Down syndrome

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Research_of_Down_syndrome-related_genes". A list of authors is available in Wikipedia.
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