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Additional file 6. Expression profiles of the 4 most expressed LINE. A) and C) LINE2A and LINE2C1 have similar expression profiles and are mostly expressed in EMS cell (4-cell stage) and in MSx2 cell (16-cell stage). B) LINE2B is expressed in 8-cell E, in AB cells and in MSx1 cell of the 16-cell stage. D) LINE2F is expressed ~ 5-fold with respect to LINE 2A, 2B and 2C1 and its expression seems to be related to 16-cell stage Ea and Ep cells.

Additional file 1. TE occupancy in C. elegans, Drosophila, mouse and human reference genomes. Genomic occupancy of the 5 TE classes (DNA – light red, RC - ochre, LINE – light green, LTR - cyan and SINE - purple) in C. elegans, D. melanogaster, M. musculus and H. sapiens genomes. More than 70% of C. elegans TE are DNA transposons, ~ 60% of Drosophila TE are annotated as LTR and intriguingly Drosophila genome completely lacks SINE, ~ 40% of mouse TE are annotated as SINE and ~ 45% of human TE are LINE. TE annotation files for the 5 species have been retrieved from UCSC database (https://genome.ucsc.edu).

Additional file 5. CER1 and LTRCER1 expression profiles in the C. elegans early embryo. A) CER1 and B) LTRCER1 expression profiles. CER1 and LTRCER1 are the most expressed LTR elements. The two LTR are expressed in the 1-, 2-, 4- and 8-cell stages while their expression in the 16-cell stage is very low. Their expression profiles recapitulate the global expression pattern of LTR elements.

Additional file 7. Expression profiles of the 4 most expressed DNA transposons. A) CEMUDR1 has an LTR-like expression profile: it is expressed in the 1-, 2-, 4- and 8-cell stages and not in the 16-cell stage. B) Chapaev-1 has a constant expression profile that recapitulates the general DNA transposon class profile of expression. C) and D) PALTA3 and PALTTTAAA3 have a non-LTR-like profile of expression: these TE are mostly expressed in 16-cell stage AB cells.

Additional file 4. TE expression profiles in the C. elegans early embryo. For each TE belonging to DNA, LTR, LINE and SINE classes (rows) are reported the log10(RPM) expression values of each replicate of the 31 cells analyzed (columns). Black color means no expression, green low and red high expression. The horizontal color band above the picture corresponds to different stages (1-, 2-, 4-, 8- and 16-cell stages – left to right), while the vertical color band on the left side of the picture indicates the TE classes (DNA, LTR, LINE, SINE – top to bottom).

Additional file 6. Expression profiles of the 4 most expressed LINE. A) and C) LINE2A and LINE2C1 have similar expression profiles and are mostly expressed in EMS cell (4-cell stage) and in MSx2 cell (16-cell stage). B) LINE2B is expressed in 8-cell E, in AB cells and in MSx1 cell of the 16-cell stage. D) LINE2F is expressed ~ 5-fold with respect to LINE 2A, 2B and 2C1 and its expression seems to be related to 16-cell stage Ea and Ep cells.

Down syndrome (DS) - also known as Trisomy 21 - is a genetic disorder caused by an extra copy of all or part of human chromosome 21 (HSA21). DS is a complex genetic condition characterized by over 80 clinically different phenotypes of variable penetrance and expressivity. Individuals with DS show alterations - both structural and functional - affecting distinct organs and systems, which suggest that a perturbation of embryogenesis occurs in individuals with Down syndrome, due to Trisomy 21. Large-scale gene expression studies have revealed a more complex scenario, highlighting a global transcriptional deregulation, extended also to genes mapping outside the DS Critical Region (DSCR) on HSA21, as well as on the other chromosomes. In this context, it is clear that direct and/or indirect interactions between gene products of HSA21 and those from the other chromosomes can better explain the complexity of the clinical manifestations of the disorder. Recent studies have pointed out a previously unexpected role of non-coding RNA (ncRNAs), such as pseudogenes and lincRNAs, on gene expression regulation. In particular, a new crosstalk mediated by the competition for the binding to specific miRNAs has been demonstrated between messenger RNAs and ncRNAs. Such a regulatory crosstalk represents a new and interesting "RNA language" through which different mRNAs regulate each other by competing for miRNAs' availability. Given these recent findings and considering that Trisomy 21-induced gene imbalance perturbs the entire transcriptome and occurs throughout the embryogenesis, the above-described regulatory crosstalk may be altered by HSA21 trisomy in DS fetuses. The pathological overexpression of HSA21 genes may perturb gene expression during embryogenesis through the alteration of the crosstalk mediated by the interaction with specific miRNAs. In turn, it would cause typical multisystem clinical manifestations of Down syndrome. Thus, the aim of this PhD project is to deeply explore the global gene deregulation, and the potential role of microRNAs' "sponges" played by HSA21 genes that are overexpressed in DS during embryonic development. Taking advantage of publicly available mRNA and miRNA expression datasets of human embryos (4-6 weeks), a regulatory miRNA/mRNA network in these crucial weeks of the human embryonic development was established. A significant fraction of genes within the network belong to developmental-related pathways. Afterwards, HSA21 genes overexpressed in DS embryos that belong to this network were identified using RNA-Seq datasets from DS and euploid matched chorionic villi. HUNK gene was computationally selected as the best candidate to be an HSA21-derived miRNAs' sponge. Experimental studies confirmed that the overexpression of its 3'UTR induces an increased expression of genes involved in embryonic development, including BCL2, CLIC5, EPHA5, ERBB4, HIPK2, MECP2, ONECUT2, and WNT5A, and a reduction of the expression of correlated miRNAs, including miR-17, miR-20a, miR-20b, miR-128 and miR-200c. Although further studies are still in progress, the results of both the computational and the experimental studies strongly suggest that the overexpression of HSA21 genes may perturb the physiologic regulatory miRNA/mRNA network during DS embryos' development. This would explain, at least in part, the multisystemic nature of the alterations the typically occur in individuals with the syndrome.

Inherited retinal diseases (IRDs) are the leading cause of vision loss in the working-age population. We performed a retrospective epidemiological study to determine the genetic basis of IRDs in a large Italian cohort (n = 2790) followed at a single referral center. We provided, mainly by next generation sequencing, potentially conclusive molecular diagnosis for 2036 patients (from 1683 unrelated families). We identified a total of 1319 causative sequence variations in 132 genes, including 353 novel variants, and 866 possibly actionable genotypes for therapeutic approaches. ABCA4 was the most frequently mutated gene (n = 535; 26.3% of solved cases), followed by USH2A (n = 228; 11.2%) and RPGR (n = 102; 5.01%). The other 129 genes had a lower contribution to IRD pathogenesis (e.g. CHM 3.5%, RHO 3.5%; MYO7A 3.4%; CRB1 2.7%; RPE65 2%, RP1 1.8%; GUCY2D 1.7%). Seventy-eight genes were mutated in five patients or less. Mitochondrial DNA variants were responsible for 2.1% of cases. Our analysis confirms the complex genetic etiology of IRDs and reveals the high prevalence of ABCA4 and USH2A mutations. This study also uncovers genetic associations with a spectrum of clinical subgroups and highlights a valuable number of cases potentially eligible for clinical trials and, ultimately, for molecular therapies.