Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain: challenging the gene dosage effect hypothesis (Part I) |
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| Authors: | Cheon M S Kim S H Yaspo M-L Blasi F Aoki Y Melen K Lubec G |
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| Institution: | (1) Department of Pediatrics, University of Vienna, Vienna, Austria, AT;(2) Max Planck Institute for Molecular Genetics, Berlin, Germany, DE;(3) Molecular Genetics Unit, DIBIT, Università Vita-Salute S Raffaele, Milan, Italy, IT;(4) Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan, JP;(5) Department of Microbiology, National Public Health Institute, Helsinki, Finland, FI |
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| Abstract: | Summary. Down syndrome (DS) is the most significant genetic disorder with mental retardation and is caused by trisomy 21. The phenotype
of DS is thought to result from overexpression of a gene(s) located on the triplicated chromosome (region). An increasing
body of evidence that challenge this “gene dosage effect” hypothesis, however, has been reported indicating that this hypothesis
still remains to be elucidated. The availability of the complete sequence of genes on chromosome 21 could have an immediate
impact on DS research, but no conclusions can be drawn from nucleic acid levels. This made us evaluate protein levels of six
proteins, gene products, encoded on chromosome 21 (T-cell lymphoma invasion and metastasis inducing Tiam1 protein, holocarboxylase
synthetase, human interferon-regulated resistance GTP-binding protein MxA, Pbx regulating protein 1, autoimmune regulator,
and pericentrin) in fetal cortex from DS and controls at 18–19 weeks of gestational age using Western blot technique. None
of the investigated proteins showed overexpression in DS compared to controls. Our present data showing unaltered expression
of six proteins on chromosome 21 in fetal DS brain suggest that the existence of the trisomic state is not involved in abnormal
development of fetal DS brain and that the gene dosage effect hypothesis is not sufficient to fully explain the DS phenotype.
We are in the process of quantifying all gene products of chromosome 21 and our first results do not support the gene dosage
hypothesis.
Received June 27, 2002 Accepted July 19, 2002 Published online November 14, 2002
Authors' address: Prof. Dr. Gert Lubec, CChem, FRSC (UK), Department of Pediatrics, University of Vienna, Waehringer Guertel 18, A-1090 Vienna,
Austria, Fax: +43-1-40400-3194, E-mail: gert.lubec@akh-wien.ac.at
Abbreviations: AIRE, autoimmune regulator; DS, Down syndrome; HCS, holocarboxylase synthetase; Prep1, Pbx regulating protein 1; Tiam1, T-cell
lymphoma invasion and metastasis 1 |
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| Keywords: | : AIRE Chromosome 21 Down syndrome HCS MxA Pericentrin Prep1 protein expression Tiam1 |
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