biostudies-arrayexpressGiovanna VentolaHomo sapiensCutadapt, STAR, Rhttps://www.ebi.ac.uk/biostudies/studies/E-MTAB-14696Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of the CAG nucleotide repeat in the first exon of the huntingtin (HTT) gene, with an onset between the second and third decades of life and slow progression. The pathogenesis of several of HD involves dysregulation of gene expression, which depends on several molecular processes ranging from transcription to protein stability. To elucidate potential variations in gene expression in HD, a transcriptome study was conducted on 15 HD subjects and 15 controls, all of Sicilian origin, starting from peripheral blood mononuclear cell samples. A total of 7179 different statistically significant genes were identified between the two cohorts. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) terms were employed to explore the pathways influenced by differentially expressed mRNAs. GSEA revealed GO pathways strongly associated with HD, i.e. all GO biological process terms encompassing ribosome functions and structure are all highly negatively expressed phenotypes, with a large number of genes being dysregulated. This leads to the hypothesis that the processing chain leading to protein translation (via ribosomes) from mRNA is somehow impaired. In addition, genes and non-coding RNAs (ncRNAs) that play a regulatory role in various transcriptional processes were dysregulated. We can hypothesize that the whole process, from transcription to translation, is somehow compromised in HD subjects who have been genetically diagnosed with the expansion of the CAG triplet of the first exon of the HTT gene.biostudies-arrayexpressSample Collection - RNA analysis on peripheral blood mononuclear cells (PBMCs) was performed by RNA-seq in 30 subjects, including 15 HD subjects and 15 controls, all of Sicilian origin.Nucleic Acid Extraction - RNA was extracted using Qiasymphony PAXgene blood RNA kiT.Library Construction - Indexed libraries were prepared from 700ng/ea purified RNA with Illumina Stranded mRNA (mRNA-Prep-Ligation) Library Prep,Ligation Kit according to the manufacturer’s instructions. For library quantifications, TapeStation 4200 (Agilent Technologies) and Qubit (Thermo Fischer) was used.Sequencing - Indexed libraries were pooled in equimolar amounts with a final concentration of 2 nM. Illumina NovaSeq 6000 System was used to sequence the pooled samples in a 2 × 101 paired-end format.OrganizationMINSEQE ScoreAssays and DataProcessed DataMAGE-TAB FilesData Transformation - The read-count for the genes of interest was normalized considering all genes expressed in the samples, using DESeq2, with standard parameter, using the median of ratio, to perform the differential expression analysis.UnknownTranscriptomicsGenomicsProteomicsIllumina NovaSeq 6000RNA-seq of coding RNAHomo sapiensGiovanna VentolafalseRNA-seq Analysis in Huntington's disease (HD) peripheral blood mononuclear cell samplesHuntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of the CAG nucleotide repeat in the first exon of the huntingtin (HTT) gene, with an onset between the second and third decades of life and slow progression. The pathogenesis of several of HD involves dysregulation of gene expression, which depends on several molecular processes ranging from transcription to protein stability. To elucidate potential variations in gene expression in HD, a transcriptome study was conducted on 15 HD subjects and 15 controls, all of Sicilian origin, starting from peripheral blood mononuclear cell samples. A total of 7179 different statistically significant genes were identified between the two cohorts. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) terms were employed to explore the pathways influenced by differentially expressed mRNAs. GSEA revealed GO pathways strongly associated with HD, i.e. all GO biological process terms encompassing ribosome functions and structure are all highly negatively expressed phenotypes, with a large number of genes being dysregulated. This leads to the hypothesis that the processing chain leading to protein translation (via ribosomes) from mRNA is somehow impaired. In addition, genes and non-coding RNAs (ncRNAs) that play a regulatory role in various transcriptional processes were dysregulated. We can hypothesize that the whole process, from transcription to translation, is somehow compromised in HD subjects who have been genetically diagnosed with the expansion of the CAG triplet of the first exon of the HTT gene.2025-06-03T00:00:00Z2024-12-16T11:53:37.158Z2024-12-16T11:53:37.158ZE-MTAB-14696ERP167210EFO_0002944EFO_0004170EFO_0005518EFO_0003816EFO_0003738EFO_0004184