# Applications of long-read sequencing to Mendelian genetics

## TL;DR

Long-read sequencing is a promising technology that can help solve more genetic disorders by identifying complex and previously missed variants.

## Contribution

The paper reviews how long-read sequencing can improve the diagnosis of genetic disorders by uncovering complex genetic variations.

## Key findings

- Long-read sequencing can identify complex genetic variations that are missed by traditional methods.
- As costs decrease, long-read sequencing will become more widely used in clinical settings.
- LRS has the potential to act as a single-data source for multiple clinical investigations.

## Abstract

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.

The online version contains supplementary material available at 10.1186/s13073-023-01194-3.