Long-read Genome Sequencing for the Molecular Diagnosis of Neurodevelopmental Disorders

Precise diagnosis of neurodevelopmental disorders (NDDs), which often have genetic causes, is a challenging and important problem.  Here we describe the results of a recent pilot study using PacBio CCS sequencing reads, which are both long and accurate the basepair level, to analyze 6 proband-parent trios affected by an NDD that remains undiagnosed after extensive testing, including short-read genome sequencing.  Our results suggest that long-read genomes may reveal biologically and clinically relevant information in many families affected by unexplained NDDs.

Learning Objectives:

1. Understand the role of genome sequencing for neurodevelopmental disorder diagnosis

2. Define the types of genetic variation that can be uncovered more effectively by long reads than short reads