Mousavi, N., Shleizer-Burko, S., Yanicky, R. & Gymrek, M. Profiling the genome-wide landscape of tandem repeat expansions. Nucleic Acids Res. 47, e90 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shortt, J. A., Ruggiero, R. P., Cox, C., Wacholder, A. C. & Pollock, D. D. Finding and extending ancient simple sequence repeat-derived regions in the human genome. Mob. DNA 11, 11 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Willems, T. et al. The landscape of human STR variation. Genome Res. 24, 1894–1904 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Halman, A., Dolzhenko, E. & Oshlack, A. STRipy: a graphical application for enhanced genotyping of pathogenic short tandem repeats in sequencing data. Hum. Mutat. 43, 859–868 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhou, Z.-D., Jankovic, J., Ashizawa, T. & Tan, E.-K. Neurodegenerative diseases associated with non-coding CGG tandem repeat expansions. Nat. Rev. Neurol. 18, 145–157 (2022).

Article  CAS  PubMed  Google Scholar 

Hannan, A. J. Tandem repeats mediating genetic plasticity in health and disease. Nat. Rev. Genet. 19, 286–298 (2018).

Article  CAS  PubMed  Google Scholar 

Depienne, C. & Mandel, J.-L. 30 years of repeat expansion disorders: what have we learned and what are the remaining challenges? Am. J. Hum. Genet. 108, 764–785 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gall-Duncan, T., Sato, N., Yuen, R. K. C. & Pearson, C. E. Advancing genomic technologies and clinical awareness accelerates discovery of disease-associated tandem repeat sequences. Genome Res. 32, 1–27 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Malik, I., Kelley, C. P., Wang, E. T. & Todd, P. K. Molecular mechanisms underlying nucleotide repeat expansion disorders. Nat. Rev. Mol. Cell Biol. 22, 589–607 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Opal, P. & Ashizawa, T. Spinocerebellar ataxia type 1. In GeneReviews (eds Adam, M. P. et al.) https://www.ncbi.nlm.nih.gov/books/NBK1184/ (2023).

Wright, G. E. B. et al. Length of uninterrupted CAG, independent of polyglutamine size, results in increased somatic instability, hastening onset of Huntington disease. Am. J. Hum. Genet. 104, 1116–1126 (2019). This study showed that the absence of CAA interruptions in the (CAG)nCAA CAG repeat segment of HTT alleles is associated with earlier onset of Huntington disease, while duplication of the CAA CAG sequence is associated with later onset.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wright, G. E. B. et al. Interrupting sequence variants and age of onset in Huntington’s disease: clinical implications and emerging therapies. Lancet Neurol. 19, 930–939 (2020).

Article  CAS  PubMed  Google Scholar 

Latham, G. J., Coppinger, J., Hadd, A. G. & Nolin, S. L. The role of AGG interruptions in fragile X repeat expansions: a twenty-year perspective. Front. Genet. 5, 244 (2014).

Article  PubMed  PubMed Central  Google Scholar 

Perez, B. A. et al. CCG•CGG interruptions in high-penetrance SCA8 families increase RAN translation and protein toxicity. EMBO Mol. Med. 13, e14095 (2021). This study showed the association between CCG•CGG interruptions and higher SCA8 penetrance and earlier onset of symptoms, and outlined the effects of interruptions on repeat mRNA and protein-mediated toxicities.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang, X.-R., Tang, B.-S., Jin, P. & Guo, J.-F. The phenotypes and mechanisms of NOTCH2NLC-related GGC repeat expansion disorders: a comprehensive review. Mol. Neurobiol. 59, 523–534 (2022).

Article  CAS  PubMed  Google Scholar 

Schüle, B. et al. Parkinson’s disease associated with pure ATXN10 repeat expansion. NPJ Park. Dis. 3, 27 (2017).

Article  Google Scholar 

Stevanovski, I. et al. Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing. Sci. Adv. 8, eabm5386 (2022). Using the Oxford Nanopore Technologies ReadUntil function, a single assay for parallel genotyping, repeat sequence composition and methylation analyses of all known disease-associated STR loci was developed and validated. This study reported several novel and complex sequence configurations of normal and pathogenic STR alleles.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dolzhenko, E. et al. ExpansionHunter: a sequence-graph-based tool to analyze variation in short tandem repeat regions. Bioinformatics 35, 4754–4756 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dolzhenko, E. et al. REViewer: haplotype-resolved visualization of read alignments in and around tandem repeats. Genome Med. 14, 84 (2022). This study reports Repeat Expansion Viewer, a computational method for visualizing alignments of short (NGS) reads around STR regions. By generating haplotype-resolved alignments, this tool helps with the identification of sequence composition changes.

Article  PubMed  PubMed Central  Google Scholar 

Xi, J. et al. 5′ UTR CGG repeat expansion in GIPC1 is associated with oculopharyngodistal myopathy. Brain 144, 601–614 (2021).

Article  PubMed  Google Scholar 

Gymrek, M. & Goren, A. Missing heritability may be hiding in repeats. Science 373, 1440–1441 (2021).

Article  ADS  CAS  PubMed  Google Scholar 

Burgunder, J.-M. Mechanisms underlying phenotypic variation in neurogenetic disorders. Nat. Rev. Neurol. 19, 363–370 (2023).

Article  CAS  PubMed  Google Scholar 

McGinty, R. J. & Mirkin, S. M. Cis- and trans-modifiers of repeat expansions: blending model systems with human genetics. Trends Genet. 34, 448–465 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cleary, J. D., Subramony, S. H. & Ranum L. P. W. Spinocerebellar ataxia type 8. In GeneReviews (eds Adam, M. P. et al.) https://www.ncbi.nlm.nih.gov/books/NBK1268/ (2021).

Paulson, H. & Shakkottai, V. Spinocerebellar ataxia type 3. In GeneReviews (eds Adam, M. P. et al.) https://www.ncbi.nlm.nih.gov/books/NBK1196/ (2020).

Bird, T. D. Myotonic dystrophy type 1. In GeneReviews (eds Adam, M. P. et al.) https://www.ncbi.nlm.nih.gov/books/NBK1165/ (2021).

Morales, F. et al. Longitudinal increases in somatic mosaicism of the expanded CTG repeat in myotonic dystrophy type 1 are associated with variation in age-at-onset. Hum. Mol. Genet. 29, 2496–2507 (2020).

Article  CAS  PubMed  Google Scholar 

Ishiura, H. et al. Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy. Nat. Genet. 50, 581–590 (2018). This study identified the TTTCA repeat expansion in the SAMD12 gene and that the expansions of the same motif in TNRC6A and RAPGEF2 genes contribute to FAME.

Article  CAS  PubMed  Google Scholar 

Schoser, B. Myotonic dystrophy type 2. In GeneReviews (eds Adam, M. P. et al.) https://www.ncbi.nlm.nih.gov/books/NBK1466/ (2020).

Hunter, J. E., Berry-Kravis, E., Hipp, H. & Todd P. K. FMR1 disorders. In GeneReviews (eds Adam, M. P. et al.) https://www.ncbi.nlm.nih.gov/books/NBK1384/ (2019).

Flavell, J., Franklin, C. & Nestor, P. J. A systematic review of fragile X-associated neuropsychiatric disorders. J. Neuropsychiatry Clin. Neurosci. 35, 110–120 (2023).

Article  PubMed  Google Scholar 

Nolin, S. L. et al. Fragile X AGG analysis provides new risk predictions for 45-69 repeat alleles. Am. J. Med. Genet. A 161A, 771–778 (2013).

Article  PubMed  Google Scholar 

Alonso, I. et al. Reduced penetrance of intermediate size alleles in spinocerebellar ataxia type 10. Neurology 66, 1602–1604 (2006).

Article  CAS  PubMed  Google Scholar 

Pulst, S. M. Spinocerebellar ataxia type 2. In GeneReviews (eds Adam, M. P. et al.) https://www.ncbi.nlm.nih.gov/books/NBK1275/ (2019).

Caron, N. S., Wright, G. E. B. & Hayden, M. R. In GeneReviews (eds Adam, M. P. et al.) https://www.ncbi.nlm.nih.gov/books/NBK1305/ (2020).

Steely, C. J., Watkins, W. S., Baird, L. & Jorde, L. B. The mutational dynamics of short tandem repeats in large, multigenerational families. Genome Biol. 23, 253 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gao, R. et al. Instability of expanded CAG/CAA repeats in spinocerebellar ataxia type 17. Eur. J. Hum. Genet. 16, 215–222 (2008).

Article  CAS  PubMed  Google Scholar 

Gossye, H., Engelborghs, S., Van Broeckhoven, C. & van der Zee, J. C9orf72 frontotemporal dementia and/or amyotrophic lateral sclerosis. In GeneReviews (eds Adam, M. P. et al.) https://www.ncbi.nlm.nih.gov/books/NBK268647/ (2020).

Nolin, S. L. et al. Expansions and contractions of the FMR1 CGG repeat in 5,508 transmissions of normal, intermediate, and premutation alleles. Am. J. Med. Genet. A 179, 1148–1156 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nolin, S. L. et al. Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles. Am. J. Hum. Genet. 72, 454–464 (2003).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nolin, S. L. et al. Fragile X full mutation expansions are inhibited by one or more AGG interruptions in premutation carriers. Genet. Med. 17, 358–364 (2015). Refs. 40–42laid the basis for assessing the probability or risk of expansions during the transmission of maternal FMR1 intermediate and premutation alleles with varying numbers of CGG repeats and AGG interruptions.

Article  CAS  PubMed  Google Scholar 

Ciosi, M. et al. A genetic association study of glutamine-encoding DNA sequence structures, somatic CAG expansion, and DNA repair gene variants, with Huntington disease clinical outcomes. EBioMedicine 48, 568–580 (2019).

Article