Characterization of novel human endogenous retrovirus structures on chromosomes 6 and 7
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 insertio...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1498978/full |
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| author | Nicholas Pasternack Nicholas Pasternack Ole Paulsen Avindra Nath |
| author_facet | Nicholas Pasternack Nicholas Pasternack Ole Paulsen Avindra Nath |
| author_sort | Nicholas Pasternack |
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| description | 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. |
| format | Article |
| id | doaj-art-534a221bd2af4aa3807c6f462fa7624c |
| institution | Kabale University |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-534a221bd2af4aa3807c6f462fa7624c2025-01-27T06:40:05ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-01-011610.3389/fgene.2025.14989781498978Characterization of novel human endogenous retrovirus structures on chromosomes 6 and 7Nicholas Pasternack0Nicholas Pasternack1Ole Paulsen2Avindra Nath3Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD, United StatesDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomSection of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD, United StatesHuman 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.https://www.frontiersin.org/articles/10.3389/fgene.2025.1498978/fullDNA sequencingHERV-KHML-2long-read sequencingstructural variantstandem repeat |
| spellingShingle | Nicholas Pasternack Nicholas Pasternack Ole Paulsen Avindra Nath Characterization of novel human endogenous retrovirus structures on chromosomes 6 and 7 Frontiers in Genetics DNA sequencing HERV-K HML-2 long-read sequencing structural variants tandem repeat |
| title | Characterization of novel human endogenous retrovirus structures on chromosomes 6 and 7 |
| title_full | Characterization of novel human endogenous retrovirus structures on chromosomes 6 and 7 |
| title_fullStr | Characterization of novel human endogenous retrovirus structures on chromosomes 6 and 7 |
| title_full_unstemmed | Characterization of novel human endogenous retrovirus structures on chromosomes 6 and 7 |
| title_short | Characterization of novel human endogenous retrovirus structures on chromosomes 6 and 7 |
| title_sort | characterization of novel human endogenous retrovirus structures on chromosomes 6 and 7 |
| topic | DNA sequencing HERV-K HML-2 long-read sequencing structural variants tandem repeat |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1498978/full |
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