Vollger et al. (2025) Synchronized long-read genome, methylome, epigenome, and transcriptome profiling resolve a Mendelian condition
Simultaneous profiling of the genome, methylome, epigenome, and transcriptome using single-molecule chromatin fiber sequencing and multiplexed arrays isoform sequencing identifies the genetic and molecular basis of an undiagnosed Mendelian disease case with an X;13-balanced translocation. Our multi-omics approach revealed this single variant disrupted the function of four genes previously associated with Mendelian conditions, including fusion transcript formation, enhancer adoption, transcriptional readthrough silencing, and inappropriate X inactivation. Contributing consortia: Undiagnosed Diseases Network, University of Washington Center for Rare Disease Research