Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy
Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy
复制标题
DOI：
10.1186/1471-2164-8-268
复制
发表时间：
2007-08-07
期刊：
影响因子：
4.4
通讯作者：
Nitsch, Lucio
中科院分区：
文献类型：
--
作者：
Conti, Anna;Fabbrini, Floriana;Nitsch, Lucio
背景：唐氏综合征表型归因于21号染色体（Hsa21）基因的过度表达。然而，Hsa21基因在人类三体中的表达谱及其对位于不同染色体上的基因的影响在很大程度上是未知的。我们使用寡核苷酸微阵列比较了Hsa21三体和非Hsa21三体人胎儿心脏的基因表达谱。结果：15000个基因中约有一半（Hsa21上168个基因中的87个）在妊娠18-22周时在心脏中表达。在三体样本中，Hsa21基因表达全局上调1.5倍。然而，并不是所有的基因都同样失调，有25个基因完全没有上调。位于其他染色体上的基因也明显失调。对三体和非三体心脏差异表达的473个基因进行功能分类评分和基因集富集分析，发现编码线粒体酶的基因下调，编码细胞外基质蛋白的基因上调。有和没有心脏缺陷的三体胎儿之间没有显著差异。结论：Hsa21基因的剂量依赖性上调会导致三体胎儿心脏中负责线粒体功能和细胞外基质组织的基因失调。这些改变可能是与Hsa21三体相关的心脏缺陷的先兆，这可能基于涉及遗传变异、环境因素和/或随机事件的难以捉摸的机制。
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.