Targeted long-read sequencing with adaptive sampling enables the integrated genomic and epigenomic profiling of imprinting disorders.

Targeted long-read sequencing (Oxford Nanopore, adaptive sampling) detecting methylation, CNVs and sequence variants in a single assay at the 11p15.5 locus

Molecular diagnosis of imprinting disorders relies on sequential assays that are expensive, slow and often insufficient for detecting mosaicism. The authors present a targeted long-read sequencing strategy detecting DNA methylation, CNVs and sequence variants in a single assay for the Beckwith-Wiedemann spectrum (alterations of imprinting control regions IC1/IC2 at 11p15.5). Three Oxford Nanopore workflows are evaluated in three patients, including two with mosaic paternal uniparental disomy and one with IC2 loss of methylation. Adaptive sampling on P2 achieves the best target coverage, with good concordance to Illumina short-read.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A strong example of diagnostic integration: a single long-read assay captures methylation, CNVs and sequence variants where multiple analyses were previously needed, with a clear advantage for detecting mosaicism. Validation is still limited (three cases), but the approach is directly transferable to imprinting disorder diagnostics.

Analysis by Dr Thibaut Benquey