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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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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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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