Alla ricerca delle basi molecolari del Diabete di Tipo 1: sequenziamento di ultima generazione in gemelli monozigoti concordanti e discordanti per la malattia

During my three years of PhD, I worked on a project which aims to clarify the molecular basis of Type 1 Diabetes (T1D), an autoimmune chronic disease showing a strikingly and, when compared to other Mediterranean regions, anomalously high incidence in the isolated founder population from Sardinia. The project, supervised by Prof. Francesco Cucca, involves the transcriptome, metilome and TCR repertoire analysis in CD4+ and CD8+ cells fromSardinian monozygotic twins (MZ), both concordant and discordant for T1D.The aim, during my PhD course, was to clarify how changes in transcriptional activity may contribute to the disease. CD4+ and CD8+ cells were collected from 3 concordant and 2 discordant Sardinian twin pairs, andtotal RNAwas isolated. The polyadenilated fraction was then sequenced and reads were mapped to the human genome, normalized, and scaled for library size and gene length. Gene expression levels were then quantified. Samples were sequenced with a mean coverage of ~60 millions of clusters, reads composition showed the expected behavior for PolyA(+) libraries. Nine genes were found differentially expressed between discordant MZ only in CD8+ cells. Results needs to be validated in a larger sample and further studied to confirm and understand the putative role of the 9 genes in T1D. The transcriptome, the metilome and TCR repertoire analysis in studies with MZ pairs concordant and discordant could contribute to the understanding of the pathogenesis of T1D