Synchronized long-read genome, methylome, epigenome and transcriptome profiling resolve a Mendelian condition.

ABSTRACT: Resolving the molecular basis of a Mendelian condition remains challenging owing to the diverse mechanisms by which genetic variants cause disease. To address this, we developed a synchronized long-read genome, methylome, epigenome and transcriptome sequencing approach, which enables accurate single-nucleotide, insertion-deletion and structural variant calling and diploid de novo genome assembly. This permits the simultaneous elucidation of haplotype-resolved CpG methylation, chromatin accessibility and full-length transcript information in a single long-read sequencing run. Application of this approach to an Undiagnosed Diseases Network participant with a chromosome X;13-balanced translocation of uncertain significance revealed that this translocation disrupted the functioning of four sep

SUBMITTER: Vollger MR 

PROVIDER: S-EPMC12077378 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature