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Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy

BACKGROUND: The Down syndrome phenotype has been attributed to overexpression of chromosome 21 (Hsa21) genes. However, the expression profile of Hsa21 genes in trisomic human subjects as well as their effects on genes located on different chromosomes are largely unknown. Using oligonucleotide microa...

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Autores principales: Conti, Anna, Fabbrini, Floriana, D'Agostino, Paola, Negri, Rosa, Greco, Dario, Genesio, Rita, D'Armiento, Maria, Olla, Carlo, Paladini, Dario, Zannini, Mariastella, Nitsch, Lucio
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1964766/
https://www.ncbi.nlm.nih.gov/pubmed/17683628
http://dx.doi.org/10.1186/1471-2164-8-268
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author Conti, Anna
Fabbrini, Floriana
D'Agostino, Paola
Negri, Rosa
Greco, Dario
Genesio, Rita
D'Armiento, Maria
Olla, Carlo
Paladini, Dario
Zannini, Mariastella
Nitsch, Lucio
author_facet Conti, Anna
Fabbrini, Floriana
D'Agostino, Paola
Negri, Rosa
Greco, Dario
Genesio, Rita
D'Armiento, Maria
Olla, Carlo
Paladini, Dario
Zannini, Mariastella
Nitsch, Lucio
author_sort Conti, Anna
collection PubMed
description BACKGROUND: The Down syndrome phenotype has been attributed to overexpression of chromosome 21 (Hsa21) genes. However, the expression profile of Hsa21 genes in trisomic human subjects as well as their effects on genes located on different chromosomes are largely unknown. Using oligonucleotide microarrays we compared the gene expression profiles of hearts of human fetuses with and without Hsa21 trisomy. RESULTS: Approximately half of the 15,000 genes examined (87 of the 168 genes on Hsa21) were expressed in the heart at 18–22 weeks of gestation. Hsa21 gene expression was globally upregulated 1.5 fold in trisomic samples. However, not all genes were equally dysregulated and 25 genes were not upregulated at all. Genes located on other chromosomes were also significantly dysregulated. Functional class scoring and gene set enrichment analyses of 473 genes, differentially expressed between trisomic and non-trisomic hearts, revealed downregulation of genes encoding mitochondrial enzymes and upregulation of genes encoding extracellular matrix proteins. There were no significant differences between trisomic fetuses with and without heart defects. CONCLUSION: We conclude that dosage-dependent upregulation of Hsa21 genes causes dysregulation of the genes responsible for mitochondrial function and for the extracellular matrix organization in the fetal heart of trisomic subjects. These alterations might be harbingers of the heart defects associated with Hsa21 trisomy, which could be based on elusive mechanisms involving genetic variability, environmental factors and/or stochastic events.
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spelling pubmed-19647662007-09-05 Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy Conti, Anna Fabbrini, Floriana D'Agostino, Paola Negri, Rosa Greco, Dario Genesio, Rita D'Armiento, Maria Olla, Carlo Paladini, Dario Zannini, Mariastella Nitsch, Lucio BMC Genomics Research Article BACKGROUND: The Down syndrome phenotype has been attributed to overexpression of chromosome 21 (Hsa21) genes. However, the expression profile of Hsa21 genes in trisomic human subjects as well as their effects on genes located on different chromosomes are largely unknown. Using oligonucleotide microarrays we compared the gene expression profiles of hearts of human fetuses with and without Hsa21 trisomy. RESULTS: Approximately half of the 15,000 genes examined (87 of the 168 genes on Hsa21) were expressed in the heart at 18–22 weeks of gestation. Hsa21 gene expression was globally upregulated 1.5 fold in trisomic samples. However, not all genes were equally dysregulated and 25 genes were not upregulated at all. Genes located on other chromosomes were also significantly dysregulated. Functional class scoring and gene set enrichment analyses of 473 genes, differentially expressed between trisomic and non-trisomic hearts, revealed downregulation of genes encoding mitochondrial enzymes and upregulation of genes encoding extracellular matrix proteins. There were no significant differences between trisomic fetuses with and without heart defects. CONCLUSION: We conclude that dosage-dependent upregulation of Hsa21 genes causes dysregulation of the genes responsible for mitochondrial function and for the extracellular matrix organization in the fetal heart of trisomic subjects. These alterations might be harbingers of the heart defects associated with Hsa21 trisomy, which could be based on elusive mechanisms involving genetic variability, environmental factors and/or stochastic events. BioMed Central 2007-08-07 /pmc/articles/PMC1964766/ /pubmed/17683628 http://dx.doi.org/10.1186/1471-2164-8-268 Text en Copyright © 2007 Conti et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Conti, Anna
Fabbrini, Floriana
D'Agostino, Paola
Negri, Rosa
Greco, Dario
Genesio, Rita
D'Armiento, Maria
Olla, Carlo
Paladini, Dario
Zannini, Mariastella
Nitsch, Lucio
Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy
title Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy
title_full Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy
title_fullStr Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy
title_full_unstemmed Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy
title_short Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy
title_sort altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1964766/
https://www.ncbi.nlm.nih.gov/pubmed/17683628
http://dx.doi.org/10.1186/1471-2164-8-268
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