Abstract in lingua inglese The development of the proposal is based on the collaboration of the group directed by. Prof Rossella Tupler at the University of Modena and Reggio Emilia (UNIMORE) with the group directed by Professor Matteo Chiara at the University of Milan. Professor Tupler has accrued a long-term experience on the molecular mechanism at the basis of facioscapulohumeral muscular dystrophy. Prof. Tupler is the Curator of the Italian National Registry for FSHD27 with the collection of over 4,000 individuals carrying the FSHD molecular defect. Professor Matteo Chiara has a strong record in the analysis of genomic data produced by modern NGS sequencing technologies, and has documented experience with the assembly of LRS data. He coordinates the Federated Human data community of the Italian node of the ELIXIR platform and is directly involved in the H2020 projects B1MG and GDI. His expertise will be also highly valued for the correct handling and processing of sensitive human data. The scientific collaboration between the groups directed by Professor Tupler and Professor Chiara has already produced a novel analysis on D4Z4 structure, distribution based on the T2T genome assembly and on genomes from the Human Pan-Genome project, and its epigenetic status (medRxiv 2023.06.13.23291337; https://doi.org/10.1101/2023.06.13.23291337) showing the critical importance of a close collaboration between between medical geneticists, molecular biologists and bioinformaticians to generate valid data for a rapid translation to clinics. For the proposal development in all phases of implementation, we will count on the continuative dialogue between key collaborators. Prof. Matteo Chiara’s group (University of Milan), will provide bioinformatics analyses supporting Specific Aim 1 1.2, Specific Aim 2, and Specific Aim 3.1. Activities will be monitored by weekly meetings in order to facilitate the continuous communication with the groups involved. Ideas exchange and discussion based on methodological approach and data interpretation will be the basis of our collaboration which is mainly focused on the analysis, integration and interpretation of molecular and bioinformatics data. To further boost data management and analysis the PhD student which will be selected to Pre-submission Cariplo Telethon Alliance GJC2023 Reference: Telethon_5275 Date submitted: - Page 4 of 48 focus his/her research project on this topic, will be expected to to spend 6 months at in the lab of our collaborator Prof. Chiara at UNIMI to acquire fundamental knowledge in data analysis and computational biology and learning appropriate independent action.