RNA-seq Analysis in Huntington's disease (HD) peripheral blood mononuclear cell samples

Huntington'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.