Beyond the exome: utility of long-read whole genome sequencing in exome-negative autosomal recessive diseases.

ABSTRACT:

Background

Long-read whole genome sequencing (lrWGS) has the potential to address the technical limitations of exome sequencing in ways not possible by short-read WGS. However, its utility in autosomal recessive Mendelian diseases is largely unknown.

Methods

In a cohort of 34 families in which the suspected autosomal recessive diseases remained undiagnosed by exome sequencing, lrWGS was performed on the Pacific Bioscience Sequel IIe platform.

Results

Likely causal variants were identified in 13 (38%) of the cohort. These include (1) a homozygous splicing SV in TYMS as a novel candidate gene for lethal neonatal lactic acidosis, (2) a homozygous non-coding SV that we propose impacts STK25 expression and causes a novel neurodevelopmental disorder, (3) a compound heterozy

SUBMITTER: AlAbdi L 

PROVIDER: S-EPMC10720148 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature