1. The transcriptome profile of human trisomy 21 blood cells
- Author
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Allison Piovesan, Chiara Locatelli, Francesca Catapano, Pierluigi Strippoli, Rossella Zenatelli, Giulia Guerri, Lorenza Vitale, Maria Chiara Pelleri, Guido Cocchi, Beatrice Vione, Alice Gori, Giuseppe Ramacieri, Maria Caracausi, Francesca Antonaros, Matteo Bertelli, Antonaros F., Zenatelli R., Guerri G., Bertelli M., Locatelli C., Vione B., Catapano F., Gori A., Vitale L., Pelleri M.C., Ramacieri G., Cocchi G., Strippoli P., Caracausi M., and Piovesan A.
- Subjects
Myxovirus Resistance Proteins ,0301 basic medicine ,Blood cells ,Trisomy 21 ,Chromosomes, Human, Pair 21 ,Mitochondrial translation ,Down syndrome ,Human chromosome 21 ,QH426-470 ,Biology ,Genome ,Transcriptome ,Reduced Folate Carrier Protein ,03 medical and health sciences ,0302 clinical medicine ,Intellectual Disability ,Drug Discovery ,Gene expression ,Genetics ,Humans ,Carbon-Nitrogen Ligases ,RNA-Seq ,Molecular Biology ,Gene ,Phosphoribosylglycinamide Formyltransferase ,Genome, Human ,Blood cell ,RNA sequencing ,Phenotype ,Mitochondria ,Reverse transcription polymerase chain reaction ,030104 developmental biology ,Gene Expression Regulation ,Medicine ,Molecular Medicine ,Energy Metabolism ,Primary Research ,Chromosome 21 ,Software ,030217 neurology & neurosurgery - Abstract
Background 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). Results 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. Conclusions The alteration of these pathways might be linked and involved in the manifestation of ID in DS.
- Published
- 2021