Analysis of R-loop forming regions identifies RNU2-2 and RNU5B-1 as neurodevelopmental disorder genes

Date: Monday 23rd of June at 11:00 in Askja, room N-132

Title: Analysis of R-loop forming regions identifies RNU2-2 and RNU5B-1 as neurodevelopmental disorder genes

Speaker: Siddhart Banka, Professor of Genomic Medicine and Rare Diseases at the University of Manchester, England

Abstract: R-loops are DNA–RNA hybrid structures that may promote mutagenesis. However, their contribution to human Mendelian disorders is unexplored. Here we show excess de novo variants in genomic regions that form R-loops (henceforth, ‘R-loop regions’) and demonstrate enrichment of R-loop region variants (RRVs) in ribozyme, snoRNA and snRNA genes, specifically in rare disease cohorts. Using this insight, we report neurodevelopmental disorders (NDDs) caused by rare variants in two major spliceosomal RNA encoding genes, RNU2-2 and RNU5B-1. These, along with the recently described RNU4-2-related ReNU syndrome, provide a genetic explanation for a substantial proportion of individuals with NDDs.

Bio: Sid is a Professor of Genomic Medicine and Rare Diseases at the University of Manchester, a Consultant Clinical Geneticist at the Manchester Centre for Genomic Medicine and Clinical Director of the Manchester Rare Conditions Centre. His research programs focus on novel disease-gene discovery; improving diagnosis through innovative data analysis and multi-omic approaches; understanding mechanisms and natural history of developmental diseases; and performing therapeutic clinical trials. He co-leads the Rare Conditions theme of the NIHR Manchester Biomedical Research Centre, the EpiGenRare node of the MRC UK Rare Disease Research Platform, and NHSE Rare Disease Genomics Network of Excellence.