Scott, B. | bioRxiv Science

bioRxiv2018

Repeat elements organize 3D genome structure and mediate transcription in the filamentous fungus Epichloë festucae

Structural features of genomes, including the three-dimensional arrangement of DNA in the nucleus, are increasingly seen as key contributors to the regulation of gene expression. However, studies on how genome structure and nuclear organization influence transcription have so far been limited to a handful of model species. This narrow focus limits our ability to draw general conclusions about the ways in which three-dimensional structures are encoded, and to integrate information from three-dimensional data to address a broader gamut of biological questions. Here, we generate a complete and gapless genome sequence for the filamentous fungus, Epichloe festucae. Coupling it with RNAseq and HiC data, we investigate how the structure of the genome contributes to the suite of transcriptional changes that an Epichloe species needs to maintain symbiotic relationships with its grass host. Our results reveal a unique \"patchwork\" genome, in which repeat-rich blocks of DNA with discrete boundaries are interspersed by gene-rich sequences. In contrast to other species, the three-dimensional structure of the genome is anchored by these repeat blocks, which act to isolate transcription in neighbouring gene-rich regions. Genes that are differentially expressed in planta are enriched near the boundaries of these repeat-rich blocks, suggesting that their three-dimensional orientation partly encodes and regulates the symbiotic relationship formed by this organism.

genomics↗

bioRxiv2017

Rare Variant Burden in Known Dystonia Genes in Population Controls and Sporadic Dystonia Patients

BackgroundRare mutations in genes associated with Mendelian forms of disease are a potential mechanism for sporadic disease. The need to assess the clinical significance of such variants is increasing as personalized medicine and genome sequencing increases.\n\nObjectiveTo evaluate the rate of rare, functional variants in dystonia genes in the general population to improve interpretation of the clinical relevance of potentially pathogenic variants in dystonia cases.\n\nMethodsWe performed an \"aggregated\" collapsing analysis of exome sequence that considered rare coding variants in genes previously associated with dystonia, a rare neurological movement disorder, on 2,372 population controls of European ethnicity. We then performed a pilot study in sporadic dystonia to assess whether there was a substantially greater incidence of individuals with rare variation in dystonia genes.\n\nResultsNearly half of population controls had a rare coding variant when 148 genes associated with a dystonia phenotype were considered. When the subset of genes causing isolated dystonia (14 genes) was evaluated, 3-4% of controls harbored rare qualifying variants. Our pilot study of case exomes was powered to identify a five-fold higher or greater rate of qualifying variants in isolated dystonia genes in sporadic dystonia cases compared to population controls; we did not find such an enrichment.\n\nConclusionsWe provide the first systematic analysis of rare variation in dystonia genes considered collectively. Our findings emphasize the need to consider the overall frequency of variants in rare disease-related genes in the general population when considering their potential role in clinical presentations.

genomics↗