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  Gene expression variation in Down's syndrome mice allows prioritization of candidate genes

Sultan, M., Piccini, I., Balzereit, D., Herwig, R., Saran, N. G., Lehrach, H., et al. (2007). Gene expression variation in Down's syndrome mice allows prioritization of candidate genes. Genome Biology, 8(5), R91-R91. doi:10.1186/gb-2007-8-5-r91.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-81FF-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8200-C
Genre: Journal Article
Alternative Title : Genome Biol

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 Creators:
Sultan, Marc1, Author              
Piccini, Ilaria2, Author
Balzereit, Daniela1, Author              
Herwig, Ralf3, Author              
Saran, Nidhi G., Author
Lehrach, Hans4, Author              
Reeves, Roger H., Author
Yaspo, Marie-Laure1, Author              
Affiliations:
1Human Chromosome 21 (Marie-Laure Yaspo), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479652              
2Max Planck Society, ou_persistent13              
3Bioinformatics (Ralf Herwig), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479648              
4Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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 Abstract: Background Down's syndrome (DS), or trisomy 21, is a complex developmental disorder that exhibits many clinical signs that vary in occurrence and severity among patients. The molecular mechanisms responsible for DS have thus far remained elusive. We argue here that normal variation in gene expression in the population contributes to the heterogeneous clinical picture of DS, and we estimated the amplitude of this variation in 50 mouse orthologs of chromosome 21 genes in brain regions of Ts65Dn (a mouse model of DS). We analyzed the RNAs of eight Ts65Dn and eight euploid mice by real-time polymerase chain reaction. Results In pooled RNAs, we confirmed that trisomic/euploid gene expression ratios were close to 1.5. However, we observed that inter-individual gene expression levels spanned a broad range of values. We identified three categories of genes: genes with expression levels consistently higher in Ts65Dn than in euploids (9, 17, and 7 genes in cerebellum, cortex, and midbrain, respectively); genes whose expression levels partially overlap between the two groups (10, 9, and 14 genes); and genes with intermingled expression, which cannot be used to differentiate trisomics from euploids (12, 5 and 9 genes). Of the genes in the first category, App, Cbr1, and Mrps6 exhibited tight regulation in the three tissues and are therefore attractive candidates for further research. Conclusion This is the first analysis addressing inter-individual gene expression levels as a function of trisomy. We propose a strategy allowing discrimination between candidates for the constant features of DS and those genes that may contribute to the partially penetrant signs of DS.

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Language(s): eng - English
 Dates: 2007-05
 Publication Status: Published in print
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Title: Genome Biology
  Alternative Title : Genome Biol
Source Genre: Journal
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Pages: - Volume / Issue: 8 (5) Sequence Number: - Start / End Page: R91 - R91 Identifier: ISSN: 1465-6906