HiFi long-read genomes for difficult-to-detect, clinically relevant variants.

ABSTRACT: Clinical short-read exome and genome sequencing approaches have positively impacted diagnostic testing for rare diseases. Yet, technical limitations associated with short reads challenge their use for the detection of disease-associated variation in complex regions of the genome. Long-read sequencing (LRS) technologies may overcome these challenges, potentially qualifying as a first-tier test for all rare diseases. To test this hypothesis, we performed LRS (30× high-fidelity [HiFi] genomes) for 100 samples with 145 known clinically relevant germline variants that are challenging to detect using short-read sequencing and necessitate a broad range of complementary test modalities in diagnostic laboratories. We show that relevant variant callers readily re-identified the majority of variants

SUBMITTER: Hops W 

PROVIDER: S-EPMC11866944 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature