Combining long-read DNA and RNA sequencing to enhance molecular understanding of structural variations leading to copy gains.

ABSTRACT: Structural variants (SVs) significantly contribute to human disease, but their complexity often makes accurate characterization difficult with conventional methods. Advances in long-read sequencing (LRS) offer potential by spanning kilobases and directly resolving SVs. In this study, we examined two individuals with unresolved SVs. LRS on both DNA and cDNA provided single-base resolution of all breakpoint junctions, revealing detailed rearrangement structures and underlying mechanisms. Transcriptomic analyses identified abnormal fusion transcripts and clarified their functional consequences, including haploinsufficiency and potential dominant-negative effects. In one case, a triplication affecting the ZMYM2 gene was precisely mapped, revealing a truncated variant that may escape non

SUBMITTER: Fauqueux J 

PROVIDER: S-EPMC12104687 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature