Journal Article

Applications of long-read sequencing to Mendelian genetics

Mastrorosa, Francesco Kumara, Eichler, Evan E., Miller, Danny E.

2023

Overview

Advances in clinical genetic testing, including the introduction of exome sequencing, have uncovered the molecular etiology for many rare and previously unsolved genetic disorders, yet more than half of individuals with a suspected genetic disorder remain unsolved after complete clinical evaluation. A precise genetic diagnosis may guide clinical treatment plans, allow families to make informed care decisions, and permit individuals to participate in N-of-1 trials; thus, there is high interest in developing new tools and techniques to increase the solve rate. Long-read sequencing (LRS) is a promising technology for both increasing the solve rate and decreasing the amount of time required to make a precise genetic diagnosis. Here, we summarize current LRS technologies, give examples of how they have been used to evaluate complex genetic variation and identify missing variants, and discuss future clinical applications of LRS. As costs continue to decrease, LRS will find additional utility in the clinical space fundamentally changing how pathological variants are discovered and eventually acting as a single-data source that can be interrogated multiple times for clinical service.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Accuracy / Applications of technology in health and disease / Bioinformatics / Biomedical and Life Sciences / Biomedicine / Cancer Research / Clinical trials / Diagnosis / Discovery tools / DNA methylation / DNA polymerase / Genetic disorders / Genetic diversity / Genetic screening / Genetic Testing / Genetic variation / Genetics / Genomes / Human Genetics / Humans / Long-read sequencing / Medical genetics / Medicine/Public Health / Mendelian disorders / Metabolomics / Review / Sequence Analysis, DNA / Structural variation / Systems Biology / Technology / Technology application