{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:48:25Z","timestamp":1785433705620,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,3]]},"group-title":"Genomics","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"crossref","award":["ZIAHG200398"],"award-info":[{"award-number":["ZIAHG200398"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["ZIAAG000534"],"award-info":[{"award-number":["ZIAAG000534"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["ZIAAG000538"],"award-info":[{"award-number":["ZIAAG000538"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"crossref","award":["ZIC MH002903"],"award-info":[{"award-number":["ZIC MH002903"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]},{"award":["T32HG012344"],"award-info":[{"award-number":["T32HG012344"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Transposable elements (TEs) are mobile DNA sequences that shape genome architecture and gene regulation, yet their roles in the human brain remain largely unresolved. Short-read sequencing lacks the resolution to accurately map TE insertions, detect associated structural variants, and resolve highly repetitive regions. Here, we leverage long-read whole-genome sequencing to profile germline TE insertions in postmortem brain tissue from two ancestrally diverse cohorts: the North American Brain Expression Consortium (NABEC; European ancestry,\n                  <jats:italic>n<\/jats:italic>\n                  = 205) and the Human Brain Collection Core (HBCC; African and African-admixed ancestry,\n                  <jats:italic>n<\/jats:italic>\n                  = 146). We identified 2,842 and 1,660 high-confidence non-reference insertions in HBCC and NABEC, respectively, spanning\n                  <jats:italic>Alu<\/jats:italic>\n                  , LINE-1, and SVA elements. We then also further characterized complex short tandem repeat and variable number tandem repeat variation within reference SVA and\n                  <jats:italic>Alu<\/jats:italic>\n                  loci. Reference TEs were also found to mediate complex structural variants at loci implicated in brain development and neurodegenerative disease, with several showing ancestry-specific patterns. Integration of bulk RNA-sequencing data identified TE expression quantitative trait loci, including insertions that modulate neuronal gene expression. Single-nucleus RNA sequencing revealed cell-type-specific effects of TE regulation across cortical populations. Long-read methylation profiling further demonstrated age-associated epigenetic regulation of both reference and non-reference\n                  <jats:italic>Alu<\/jats:italic>\n                  elements. As a community resource, we release a catalog of TE insertions, allele frequencies, and ancestry-specific distributions to enable future functional and disease-focused investigations. Together, these findings highlight the widespread regulatory and epigenetic influence of TEs in the human brain and establish long-read sequencing as a powerful approach for uncovering cell-type- and population-specific TE dynamics.\n                <\/jats:p>","DOI":"10.64898\/2026.07.02.735893","type":"posted-content","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T07:35:11Z","timestamp":1783150511000},"source":"Crossref","is-referenced-by-count":0,"title":["Long-read sequencing maps transposable element variation and its regulatory and epigenetic effects in the human brain"],"prefix":"10.64898","author":[{"given":"Alexis","family":"Ayuketah","sequence":"first","affiliation":[{"name":"Center for Alzheimer\u2019s and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 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P.","family":"Chaisson","sequence":"additional","affiliation":[{"name":"Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Middlehurst","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivien J.","family":"Bubb","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Price","sequence":"additional","affiliation":[{"name":"Molecular Pathology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew B.","family":"Singleton","sequence":"additional","affiliation":[{"name":"Center for Alzheimer\u2019s and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"},{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miten","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Department of Physics, Northeastern University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis","family":"Blauwendraat","sequence":"additional","affiliation":[{"name":"Center for Alzheimer\u2019s and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"},{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Nalls","sequence":"additional","affiliation":[{"name":"Center for Alzheimer\u2019s and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"},{"name":"DataTecnica LLC, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R","family":"Cookson","sequence":"additional","affiliation":[{"name":"Center for Alzheimer\u2019s and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"},{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xylena","family":"Reed","sequence":"additional","affiliation":[{"name":"Center for Alzheimer\u2019s and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fritz J.","family":"Sedlazeck","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA"},{"name":"Center for Cancer Research, National Cancer Institute, National Institutes of Health, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8034-5559","authenticated-orcid":false,"given":"Cl\u00e9ment","family":"Goubert","sequence":"additional","affiliation":[{"name":"R. 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