Complex structural variants resolved by short-read and long-read whole genome sequencing in Mendelian disorders
About Alba Sanchis-Juan
Alba Sanchis-Juan studied Biochemistry and Biomedicine at University of Valencia, Spain. She is a PhD student and works at the Department of Haematology, University of Cambridge. Her study has been focused on the use of next-generation sequencing for clinical research and diagnosis. Currently, she performs data analysis of whole genome sequence data of individuals with neurodevelopmental disorders.
Sanchis-Juan, A. et al. Complex structural variants resolved by short-read and long-read whole genome sequencing in Mendelian disorders. bioRxiv 281683 (2018). doi:10.1101/281683
Complex structural variants (cxSVs) are genomic rearrangements comprising multiple structural variants, typically involving three or more breakpoint junctions. They contribute to human genomic variation and can cause Mendelian disease, however they are not typically considered during genetic testing. We investigated the role of cxSVs in Mendelian disease using short-read whole genome sequencing (WGS) data from 1,324 individuals with neurodevelopmental or retinal disorders from the NIHR BioResource project. We identified four cases of individuals with a cxSV affecting Mendelian disease-associated genes. We used nanopore sequencing to resolve the mechanism of one of the variants. Our results show cxSVs are an important, although rare cause of Mendelian disease, and we therefore recommend their consideration during research and clinical investigations.