{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:25:34Z","timestamp":1790774734420,"version":"4.1.0"},"reference-count":102,"publisher":"Portland Press Ltd.","issue":"3","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,12,14]]},"abstract":"<jats:p>Approximately half of the human genome includes repetitive sequences, and these DNA sequences (as well as their transcribed repetitive RNA and translated amino-acid repeat sequences) are known as the repeatome. Within this repeatome there are a couple of million tandem repeats, dispersed throughout the genome. These tandem repeats have been estimated to constitute \u223c8% of the entire human genome. These tandem repeats can be located throughout exons, introns and intergenic regions, thus potentially affecting the structure and function of tandemly repetitive DNA, RNA and protein sequences. Over more than three decades, more than 60 monogenic human disorders have been found to be caused by tandem-repeat mutations. These monogenic tandem-repeat disorders include Huntington's disease, a variety of ataxias, amyotrophic lateral sclerosis and frontotemporal dementia, as well as many other neurodegenerative diseases. Furthermore, tandem-repeat disorders can include fragile X syndrome, related fragile X disorders, as well as other neurological and psychiatric disorders. However, these monogenic tandem-repeat disorders, which were discovered via their dominant or recessive modes of inheritance, may represent the \u2018tip of the iceberg\u2019 with respect to tandem-repeat contributions to human disorders. A previous proposal that tandem repeats may contribute to the \u2018missing heritability\u2019 of various common polygenic human disorders has recently been supported by a variety of new evidence. This includes genome-wide studies that associate tandem-repeat mutations with autism, schizophrenia, Parkinson's disease and various types of cancers. In this article, I will discuss how tandem-repeat mutations and polymorphisms could contribute to a wide range of common disorders, along with some of the many major challenges of tandem-repeat biology and medicine. Finally, I will discuss the potential of tandem repeats to be therapeutically targeted, so as to prevent and treat an expanding range of human disorders.<\/jats:p>","DOI":"10.1042\/etls20230075","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T15:24:15Z","timestamp":1702481055000},"page":"239-247","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Expanding horizons of tandem repeats in biology and medicine: Why \u2018genomic dark matter\u2019 matters"],"prefix":"10.1042","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7532-8922","authenticated-orcid":false,"given":"Anthony J.","family":"Hannan","sequence":"additional","affiliation":[{"name":"1Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia"},{"name":"2Department of Anatomy and Physiology, University of Melbourne, Parkville, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"key":"2023121411240761800_ETLS-2023-0075CC1","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1126\/science.abj6987","article-title":"The complete sequence of a human genome","volume":"376","year":"2022","journal-title":"Science"},{"key":"2023121411240761800_ETLS-2023-0075CC2","doi-asserted-by":"publisher","DOI":"10.1101\/2023.10.29.564632","article-title":"Benchmarking of small and large variants across tandem repeats","year":"2023","journal-title":"bioRxiv"},{"key":"2023121411240761800_ETLS-2023-0075CC3","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.tig.2009.11.008","article-title":"Tandem repeat polymorphisms: modulators of disease susceptibility and candidates for \u2018missing heritability\u2019","volume":"26","year":"2010","journal-title":"Trends Genet."},{"key":"2023121411240761800_ETLS-2023-0075CC4","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s13059-022-02697-9","article-title":"Open problems in human trait genetics","volume":"23","year":"2022","journal-title":"Genome Biol."},{"key":"2023121411240761800_ETLS-2023-0075CC5","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/nmeth.4267","article-title":"Genome-wide profiling of heritable and de novo STR variations","volume":"14","year":"2017","journal-title":"Nat. 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