Study: NCT06796751

Intervention type: GENETIC
Group type: OTHER
Intervention: DNA/RNA sequencing and bioinformatic data analysis
Description: DNA will be extracted from peripheral blood or from somatic tissues. In some cases (reported mosaicism on blood) a skin biopsy will be performed to obtain fibroblasts for further analysis (DNA/RNA extraction and preparation of cell culture for Hi-C).~LRS will be performed on extracted DNA using Oxford Nanopore Technology by two different approaches:~* Target, in samples with monoallelic alterations in genes related to autosomal recessive disease;~* Genomic in other cases. Sequencing data will be analyzed through a dedicated bioinformatics pipeline. LRS data analysis will include sequence alignment and variant quality checks, producing a per-sample quality report to ensure elimination of technical noise and to obtain a harmonized jointly-called dataset for downstream analyses. Mean depth of coverage, a general indicator of LRS sensitivity, will be achieved at 30X to guarantee 95% of callable genomic positions \>20x.~To reconstruct the tridimensional structure of chromatin and the regions

Intervention type: GENETIC
Group type: OTHER
Intervention: DNA/RNA sequencing and bioinformatic data analysis
Description: DNA will be extracted from peripheral blood or from somatic tissues. In some cases (reported mosaicism on blood) a skin biopsy will be performed to obtain fibroblasts for further analysis (DNA/RNA extraction and preparation of cell culture for Hi-C).~LRS will be performed on extracted DNA using Oxford Nanopore Technology by two different approaches:~* Target, in samples with monoallelic alterations in genes related to autosomal recessive disease;~* Genomic in other cases. Sequencing data will be analyzed through a dedicated bioinformatics pipeline. LRS data analysis will include sequence alignment and variant quality checks, producing a per-sample quality report to ensure elimination of technical noise and to obtain a harmonized jointly-called dataset for downstream analyses. Mean depth of coverage, a general indicator of LRS sensitivity, will be achieved at 30X to guarantee 95% of callable genomic positions \>20x.~To reconstruct the tridimensional structure of chromatin and the regions

Intervention type: GENETIC
Group type: OTHER
Intervention: DNA/RNA sequencing and bioinformatic data analysis
Description: DNA will be extracted from peripheral blood or from somatic tissues. In some cases (reported mosaicism on blood) a skin biopsy will be performed to obtain fibroblasts for further analysis (DNA/RNA extraction and preparation of cell culture for Hi-C).~LRS will be performed on extracted DNA using Oxford Nanopore Technology by two different approaches:~* Target, in samples with monoallelic alterations in genes related to autosomal recessive disease;~* Genomic in other cases. Sequencing data will be analyzed through a dedicated bioinformatics pipeline. LRS data analysis will include sequence alignment and variant quality checks, producing a per-sample quality report to ensure elimination of technical noise and to obtain a harmonized jointly-called dataset for downstream analyses. Mean depth of coverage, a general indicator of LRS sensitivity, will be achieved at 30X to guarantee 95% of callable genomic positions \>20x.~To reconstruct the tridimensional structure of chromatin and the regions

Intervention type: GENETIC
Group type: OTHER
Intervention: DNA/RNA sequencing and bioinformatic data analysis
Description: DNA will be extracted from peripheral blood or from somatic tissues. In some cases (reported mosaicism on blood) a skin biopsy will be performed to obtain fibroblasts for further analysis (DNA/RNA extraction and preparation of cell culture for Hi-C).~LRS will be performed on extracted DNA using Oxford Nanopore Technology by two different approaches:~* Target, in samples with monoallelic alterations in genes related to autosomal recessive disease;~* Genomic in other cases. Sequencing data will be analyzed through a dedicated bioinformatics pipeline. LRS data analysis will include sequence alignment and variant quality checks, producing a per-sample quality report to ensure elimination of technical noise and to obtain a harmonized jointly-called dataset for downstream analyses. Mean depth of coverage, a general indicator of LRS sensitivity, will be achieved at 30X to guarantee 95% of callable genomic positions \>20x.~To reconstruct the tridimensional structure of chromatin and the regions