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

Abstract

R-loops are critical for gene regulation but their contribution to human Mendelian disorders has not been explored. We show that in rare disease cohorts de novo variants are highly prevalent in genomic regions which form R-loops. Using this insight, we demonstrate that variants in two novel disorder genes, RNU2-2P and RNU5B-1, together with the recently described RNU4-2 provide a genetic explanation for an exceptionally large proportion of individuals with suspected rare Mendelian disorders.