Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Via Belmeloro 8, 40126, Bologna, BO, Italy.
Current Address: Department of Molecular and Translational Medicine (DMMT), University of Brescia, Viale Europa 11, 24123, Brescia, BS, Italy.
Hum Genomics. 2021 May 1;15(1):25. doi: 10.1186/s40246-021-00325-4.
Trisomy 21 (T21) is a genetic alteration characterised by the presence of an extra full or partial human chromosome 21 (Hsa21) leading to Down syndrome (DS), the most common form of intellectual disability (ID). It is broadly agreed that the presence of extra genetic material in T21 gives origin to an altered expression of genes located on Hsa21 leading to DS phenotype. The aim of this study was to analyse T21 and normal control blood cell gene expression profiles obtained by total RNA sequencing (RNA-Seq).
The results were elaborated by the TRAM (Transcriptome Mapper) software which generated a differential transcriptome map between human T21 and normal control blood cells providing the gene expression ratios for 17,867 loci. The obtained gene expression profiles were validated through real-time reverse transcription polymerase chain reaction (RT-PCR) assay and compared with previously published data. A post-analysis through transcriptome mapping allowed the identification of the segmental (regional) variation of the expression level across the whole genome (segment-based analysis of expression). Interestingly, the most over-expressed genes encode for interferon-induced proteins, two of them (MX1 and MX2 genes) mapping on Hsa21 (21q22.3). The altered expression of genes involved in mitochondrial translation and energy production also emerged, followed by the altered expression of genes encoding for the folate cycle enzyme, GART, and the folate transporter, SLC19A1.
The alteration of these pathways might be linked and involved in the manifestation of ID in DS.
唐氏综合征（DS）是一种由额外的完整或部分人类 21 号染色体（Hsa21）引起的遗传改变，是最常见的智力障碍（ID）形式。人们普遍认为，T21 中额外的遗传物质导致 Hsa21 上基因表达的改变，从而导致 DS 表型。本研究旨在通过总 RNA 测序（RNA-Seq）分析 T21 和正常对照血细胞的基因表达谱。
通过 TRAM（转录组映射器）软件对结果进行了详细分析，该软件生成了人类 T21 和正常对照血细胞之间的差异转录组图谱，提供了 17867 个基因的表达比值。通过实时逆转录聚合酶链反应（RT-PCR）检测对获得的基因表达谱进行了验证，并与先前发表的数据进行了比较。通过转录组映射的后分析，确定了整个基因组中表达水平的片段（区域）变化（基于片段的表达分析）。有趣的是，表达最上调的基因编码干扰素诱导蛋白，其中两个（MX1 和 MX2 基因）位于 Hsa21（21q22.3）上。还出现了参与线粒体翻译和能量产生的基因表达改变，随后是编码叶酸循环酶 GART 和叶酸转运蛋白 SLC19A1 的基因表达改变。
这些途径的改变可能与 DS 中 ID 的表现有关。
