{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:11:52Z","timestamp":1793293912776,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS003130"],"award-info":[{"award-number":["NS003130"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Human endogenous retroviruses (HERV) represent nearly 8% of the human genome. Of these, HERV-K subtype HML-2 is a transposable element that plays a critical role in embryonic development and in the pathogenesis of several diseases. Quantification and characterization of these multiple HML-2 insertions in the human chromosome has been challenging due to their size, sequence homology with each other, and their repetitive nature. We examined a cohort of 222 individuals for HML-2 proviruses 6q14.1 and 7p22.1a, two loci that are capable of producing full-length viral proteins and have been previously implicated in several cancers, autoimmune disorders and neurodegenerative diseases, using long-read DNA sequencing. While the reference genome for both regions suggests these two loci are structurally dissimilar, we found that for both loci about 5% of individuals have a unique tandem repeat-like sequence (three long terminal repeat sequences sandwiching two internal, potentially protein coding sequences), while most individuals have a standard proviral structure (one internal region sandwiched by two long terminal repeats). Moreover, both proviruses can make full-length, or nearly full-length, HERV-K proteins in multiple transcription orientations. The amino acid sequences from different loci in the same transcriptional orientation share sequence homology with each other. These results demonstrate a clear, previously unreported, relationship between HML-2 loci 6q14.1 and 7p22.1a and highlight the utility of long-read sequencing to study repetitive elements. Future studies need to determine if these polymorphisms determine genetic susceptibility to diseases that are associated with them.<\/jats:p>","DOI":"10.3389\/fgene.2025.1498978","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T06:40:19Z","timestamp":1737960019000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterization of novel human endogenous retrovirus structures on chromosomes 6 and 7"],"prefix":"10.3389","volume":"16","author":[{"given":"Nicholas","family":"Pasternack","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Paulsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avindra","family":"Nath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13059-020-1935-5","article-title":"Opportunities and challenges in long-read sequencing data analysis","volume":"21","author":"Amarasinghe","year":"2020","journal-title":"Genome Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"D523","DOI":"10.1093\/nar\/gkac1052","article-title":"UniProt: the universal protein Knowledgebase in 2023","volume":"51","author":"Bateman","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"9437","DOI":"10.1128\/JVI.02216-06","article-title":"Rate of recombinational deletion among human endogenous retroviruses","volume":"81","author":"Belshaw","year":"2007","journal-title":"J. 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