{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:24:10Z","timestamp":1790774650397,"version":"4.1.0"},"reference-count":16,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes for Health","doi-asserted-by":"crossref","award":["R01HL145175"],"award-info":[{"award-number":["R01HL145175"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Short Tandem Repeats (STRs) have been found to play a role in a myriad of complex traits and genetic diseases. We examined the variability in the lengths of over 850,000 STR loci in 996 children with suspected genetic disorders and 1,178 parents across six separate ancestral groups: Africans, Europeans, East Asians, Admixed Americans, Non-admixed Americans, and Pacific Islanders. For each STR locus we compared allele length between and within each ancestry group. In relation to Europeans, admixed Americans had the most similar STR lengths with only 623 positions either significantly expanded or contracted, while the divergence was highest in Africans, with 4,933 chromosomal positions contracted or expanded. We also examined probands to identify STR expansions at known pathogenic loci. The genes <jats:italic>TCF4<\/jats:italic>, <jats:italic>AR<\/jats:italic>, and <jats:italic>DMPK<\/jats:italic> showed significant expansions with lengths 250% greater than their various average allele lengths in 49, 162, and 11 individuals respectively. All 49 individuals containing an expansion in <jats:italic>TCF4<\/jats:italic> and six individuals containing an expansion in <jats:italic>DMPK<\/jats:italic> presented with allele lengths longer than the known pathogenic length for these genes. Next, we identified individuals with significant expansions in highly conserved loci across all ancestries. Eighty loci in conserved regions met criteria for divergence. Two of these individuals were found to have exonic STR expansions: one in <jats:italic>ZBTB4<\/jats:italic> and the other in <jats:italic>SLC9A7<\/jats:italic>, which is associated with X-linked mental retardation. Finally, we used parent-child trios to detect and analyze <jats:italic>de novo<\/jats:italic> mutations. In total, we observed 3,219 <jats:italic>de novo<\/jats:italic> expansions, where proband allele lengths are greater than twice the longest parental allele length. This work helps lay the foundation for understanding STR lengths genome-wide across ancestries and may help identify new disease genes and novel mechanisms of pathogenicity in known disease genes.<\/jats:p>","DOI":"10.1371\/journal.pone.0279430","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T18:36:32Z","timestamp":1674758192000},"page":"e0279430","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Genomic landscape of short tandem repeats across multiple ancestries"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7661-236X","authenticated-orcid":true,"given":"Prashanth","family":"Vijayaraghavan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Batalov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Sanford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen F.","family":"Kingsmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Dimmock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Hobbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Bainbridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,1,26]]},"reference":[{"key":"pone.0279430.ref001","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S1672-0229(07)60009-6","article-title":"A Brief Review of Short Tandem Repeat Mutation","volume":"5","author":"H. 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Zhao","year":"2020","journal-title":"NAR Genomics and Bioinformatics"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0279430","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T18:37:00Z","timestamp":1674758220000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0279430"}},"subtitle":[],"editor":[{"given":"Alvaro","family":"Galli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,1,26]]},"references-count":16,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0279430","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,26]]}}}