Nicky Whiffin is an Associate Professor, Sir Henry Dale Fellow, and the co-lead of the research theme in Genomics at the University of Oxford’s Big Data Institute. She is also a research fellow at St Anne’s College and a visiting scholar at the Broad Institute of MIT and Harvard. Nicky’s research uses computational approaches to interpret the role of genetic variants in rare diseases, and to understand how gene regulation can be modified therapeutically. She is an expert in annotation and interpretation of variants in non-coding regions of the genome, for which she has led the creation of clinical guidelines. Nicky was awarded a 2024 Lister Institute Research Prize and the 2025 Balfour Lecture from the UK Genetics Society.

Small nuclear RNAs in rare disease

Small nuclear RNAs (snRNAs) are key non-coding components on the spliceosome. An increasing number are being shown to have important roles in rare neurodevelopmental disorders (NDD). These include RNU4-2, which encodes the U4 snRNA. Variants in RNU4-2 cause a highly prevalent NDD called ReNU syndrome, which is predicted to affect ~100,000 individuals worldwide. In this talk, I will describe the discovery of ReNU syndrome using the Genomics England dataset and global collaboration. I will also describe a saturation genome editing experiment, encompassing variants across the entire RNU4-2 gene which provides valuable insight into ReNU syndrome, resolves variant pathogenicity, and led to the discovery of a recessive NDD also associated with variants in RNU4-2.