Applications of long-read sequencing to Mendelian genetics

Genome Medicine

Review

Francesco Kumara Mastrorosa¹  Evan E. Eichler²  Danny E. Miller³ 

[1] Department of Genome Sciences, University of Washington School of Medicine, 98195, Seattle, WA, USA;Department of Genome Sciences, University of Washington School of Medicine, 98195, Seattle, WA, USA;Howard Hughes Medical Institute, University of Washington, 98195, Seattle, WA, USA;Division of Genetic Medicine, Department of Pediatrics, University of Washington and Seattle Children’s Hospital, 98195, Seattle, WA, USA;Department of Laboratory Medicine and Pathology, University of Washington, 98195, Seattle, WA, USA;Brotman Baty Institute for Precision Medicine, University of Washington, 98195, Seattle, WA, USA;

关键词: Long-read sequencing;    Genetic variation;    Medical genetics;    Structural variation;    Mendelian disorders;   

DOI  :  10.1186/s13073-023-01194-3

 received in 2022-12-08, accepted in 2023-05-18,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2023

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