Transcriptome analysis of human autosomal trisomy
Transcriptome analysis of human autosomal trisomy
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DOI：
10.1093/hmg/11.26.3249
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发表时间：
2002-12-15
影响因子：
3.5
通讯作者：
Hastie, ND
中科院分区：
文献类型：
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作者：
FitzPatrick, DR;Ramsay, J;Hastie, ND
我们对患有21三体（t21）和13三体（t13）的妊娠人胎儿细胞的原代培养物进行转录组分析。将t21和t13例的合并mRNA样本与正常细胞的合并mRNA cDNA阵列进行比较杂交。当将阵列cdna按染色体位置分组时，可以清楚地识别出相关的三体染色体表现出最显著的失调。阵列分析显示，与正常细胞相比，三体染色体上的平均转录水平仅增加了约1.1倍。由于核型可以通过转录组准确预测，这为检测未知位置的畸形提供了一种新的方法。随后对个体病例的分析表明，如果不汇集或使用具有较高比例的所有人类cdna的阵列，每一类样本之间转录谱的差异使得转录核型分析变得困难。有趣的是，染色体之间相对表达水平的一致差异被检测到，这表明基因组控制机制可能比之前认为的作用距离更大。大多数(bbb95 %) > +/-2SD失调基因没有映射到三体染色体上，显著的失调在t13比t21更常见。这些数据支持三体染色体上基因的微妙的初级上调模式，导致继发性的，普遍的和更极端的转录失调。在大多数非整倍体中，这种失调的程度似乎决定了表型的严重程度。
We present transcriptome analyses of primary cultures of human fetal cells from pregnancies affected with trisomy 21 (t21) and trisomy 13 (t13). Pooled mRNA samples from t21 and t13 cases were used for comparative hybridizations to cDNA arrays with pooled mRNA from normal cells. When the array cDNAs were grouped by chromosomal location the relevant trisomic chromosome could be clearly identified as showing the most significant misregulation. The average level of transcription on the trisomic chromosome was increased only similar to1.1-fold compared to normal cells on array analysis. Since the karyotype could be accurately predicted by the transcriptome this could provide a novel method of detecting aneusomy of unknown position. Subsequent analysis of individuals cases demonstrated that variation in transcriptional profiles between samples within each class made transcriptional karyotyping difficult without pooling or the use of arrays with a higher proportion of all human cDNAs. Interestingly, consistent differences in the relative expression levels between chromosomes were detected suggesting that genomic control mechanisms may act over larger distances than previously thought. Most (>95%) > +/-2SD misregulated genes did not map to the trisomic chromosome and significant misregulation was more common in t13 than t21. These data support a mode of a subtle primary upregulation of genes on the trisomic chromosome resulting in a secondary, generalized and more extreme transcriptional misregulation. It seems likely that the degree of this misregulation determines the severity of the phenotype in most aneuploidy.