Long-read genome sequencing and variant reanalysis increase diagnostic yield in neurodevelopmental disorders.

ABSTRACT: Variant detection from long-read genome sequencing (lrGS) has proven to be considerably more accurate and comprehensive than variant detection from short-read genome sequencing (srGS). However, the rate at which lrGS can increase molecular diagnostic yield for rare disease is not yet precisely characterized. We performed lrGS using Pacific Biosciences "HiFi" technology on 96 short-read-negative probands with rare disease that were suspected to be genetic. We generated hg38-aligned variants and de novo phased genome assemblies, and subsequently annotated, filtered, and curated variants using clinical standards. New disease-relevant or potentially relevant genetic findings were identified in 16/96 (16.7%) probands, eight of which (8/96, 8.33%) harbored pathogenic or likely pathogenic

SUBMITTER: Hiatt SM 

PROVIDER: S-EPMC10996728 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature