Nanopore sequencing to resolve structural variants causing antithrombin deficiency
About Alba Sanchis-Juan
Alba studied Biochemistry and Biomedicine and completed her Ph.D. in Biotechnology at University of Valencia, Spain, before working at the University of Cambridge as part of the NIHR Bioresource Project. Currently, she is a Postdoctoral Fellow at the Talkowski laboratory in the Broad Institute of Harvard and MIT, where she works on large-scale population and clinical genomics projects to systematically explore a variety of genomic variation and its implication for human disease.
The identification and characterization of structural variants (SVs) in clinical genetics have remained historically challenging. Here, we performed long-read whole-genome sequencing (LR-WGS) on 19 unrelated cases with antithrombin deficiency (ATD) where routine molecular tests were either negative, ambiguous, or not fully characterized. We developed an analysis workflow to identify disease-associated SVs and resolved 10 cases. For the first time, we identified a germline complex rearrangement and a novel SINE-VNTR-Alu (SVA) retroelement insertion involved in ATD. Our study underscores the utility of LR-WGS as a complementary diagnostic method to identify, characterize, and unveil the molecular mechanism of formation of disease-causing SVs.