Jee-Soo Lee

Abstract Short-read sequencing (SRS)-based disease-targeted NGS gene panels have revolutionized rare disease diagnostics but often leave autosomal recessive cases unsolved when only one pathogenic allele is detected. Missing variants may reside in deep intronic regions or involve structural variants (SVs) undetectable by SRS.

Abstract Global developmental delay (GDD) and intellectual disability (ID) are frequently caused by genetic factors, yet many patients remain undiagnosed even after whole exome sequencing (WES). This study aimed to apply Optical Genome Mapping (OGM) and Illumina Complete Long Reads (ICLR) in pediatric patients with unexplained GDD/ID after WES and propose a practical diagnostic strategy for clinical implementation.

Abstract Paralogous genes challenge short-read sequencing (SRS) due to high sequence similarity. Although long-read sequencing (LRS) improves resolution, the extent to which it resolves paralogous genes remains unclear. This study evaluates the capability of LRS by integrating in silico mappability-based predictions with clinical data to generate SRS- and LRS-unresolved gene lists, and by assessing whether a paralog-specific phasing, Paraphase, can overcome remaining limitations.