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Detecting Tandem Repeat Expansions Using Short-Read Sequencing for Clinical Use

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Genomic Structural Variants in Nervous System Disorders

Part of the book series: Neuromethods ((NM,volume 182))

Abstract

Repeat expansion disorders are a unique class of genetic diseases caused by expansions of short tandem repeats. Until recently, these pathogenic variations were detected with locus-by-locus lab-based methods leading to underascertainment and were thought to be undetectable by short-read sequencing. Repeat expansion disorders present with a diverse set of phenotypes including overlap with several common complex neurological disorders; hence, the importance of their detection is becoming increasingly recognized.

Recently bioinformatic methods have been developed that can detect both known and novel repeat expansions in standard short-read whole exome and whole genome sequencing data. In this chapter, we review how these methods work, why they need to be incorporated into all whole genome sequencing pipelines, and future directions in repeat expansion disorder genomic analysis.

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Acknowledgments

This work was supported by the Victorian Government’s Operational Infrastructure Support Program and the National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme. MFB was supported by a Taking Flight Award from CURE Epilepsy. AT is supported by the Medical Research Council as Clinician Scientist (MR/S006753/1). MB was supported by an Australian National Health and Medical Research Council Senior Research Fellowship (1102971).

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Authors and Affiliations

  1. Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

    Mark F. Bennett & Melanie Bahlo

  2. Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia

    Mark F. Bennett & Melanie Bahlo

  3. Department of Medicine, Epilepsy Research Centre, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia

    Mark F. Bennett

  4. William Harvey Research Institute, Queen Mary University of London, London, UK

    Arianna Tucci

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  1. Mark F. Bennett
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  2. Arianna Tucci
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Correspondence to Arianna Tucci .

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  1. Queen Square Institute of Neurology, University College London, London, UK

    Christos Proukakis

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Bennett, M.F., Tucci, A., Bahlo, M. (2022). Detecting Tandem Repeat Expansions Using Short-Read Sequencing for Clinical Use. In: Proukakis, C. (eds) Genomic Structural Variants in Nervous System Disorders. Neuromethods, vol 182. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2357-2_2

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