Synchronized long-read genome, methylome, epigenome, and transcriptome for resolving a Mendelian condition.

ABSTRACT: Resolving the molecular basis of a Mendelian condition (MC) 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, and 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 (UDN) participant with a chromosome X;13 balanced translocation of uncertain significance revealed that this translocation disrupted the fun

SUBMITTER: Vollger MR 

PROVIDER: S-EPMC10557686 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature