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Long-Read Sequencing and Analysis of Variable Number Tandem Repeats

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Genomic Structural Variants in Nervous System Disorders

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

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Abstract

Tandem repeats are among the most dynamic regions of the genome and a major source of human biological variation; however, tandem repeats larger than 6 bp in repeat unit size, termed variable number tandem repeats (VNTRs), have remained understudied. This lack of characterization is primarily because many VNTRs are in noncoding or intergenic regions and because their size often exceeds the sequence length of short-read sequencing technologies commonly used for whole genome sequencing. Fortunately, new technologies like long-read sequencing now allow us to resolve these regions in detail and have already revealed insights into the role of VNTRs in human evolution, disease, and gene expression. Here, we outline methods for sequencing VNTRs using single-molecule, real-time long-read sequencing, and aligning, phasing, and analyzing them using a bioinformatics pipeline. Together, these methods describe a novel and powerful framework for studying VNTR function and evolution.

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Notes

  1. 1.

    Editor’s note: see Chap. 7.

  2. 2.

    Editor’s note: see Chap. 8.

  3. 3.

    Editor’s note: see Chap. 7.

  4. 4.

    Editor’s note: see Chap. 2.

  5. 5.

    Editor’s note: see Chap. 6 for an example targeting short tandem repeats.

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Acknowledgments

This work is supported by the Robert F. Schoeni Award for Research from the Ann Arbor Active Against ALS (to P.N.V.) and the National Institute of General Medical Sciences (5T32GM007454-38 to M.M.C.).

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Authors and Affiliations

  1. Division of Medical Genetics, University of Washington School of Medicine, Seattle, WA, USA

    Meredith M. Course, Kathryn Gudsnuk & Paul N. Valdmanis

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  1. Meredith M. Course
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  2. Kathryn Gudsnuk
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  3. Paul N. Valdmanis
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Correspondence to Paul N. Valdmanis .

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Editors and Affiliations

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

    Christos Proukakis

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Course, M.M., Gudsnuk, K., Valdmanis, P.N. (2022). Long-Read Sequencing and Analysis of Variable Number Tandem Repeats. 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_5

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  • DOI: https://doi.org/10.1007/978-1-0716-2357-2_5

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