Evaluating genome sequencing strategies: trio, singleton, and standard testing in rare disease diagnosis.

ABSTRACT:

Background

Short-read genome sequencing (GS) is among the most comprehensive genetic testing methods available, capable of detecting single-nucleotide variants, copy-number variants, mitochondrial variants, repeat expansions, and structural variants in a single assay. Despite its technical advantages, the full clinical utility of GS in real-world diagnostic settings remains to be fully established.

Methods

This study systematically compared singleton GS (sGS), trio GS (tGS), and exome sequencing-based standard-of-care (SoC) genetic testing in 416 patients with rare diseases in a blinded, prospective study. Three independent teams with divergent baseline expertise evaluated the diagnostic yield of GS as a unifying first-tier test and directly compared its variant detection ca

SUBMITTER: Kaschta D 

PROVIDER: S-EPMC12445032 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature