{
  "abstract": "Schizophrenia is a complex and multifactorial brain disorder that impacts ~1% of the U.S. population. The genetic architecture of schizophrenia includes 10 large rare structural variants (SVs) ~10 exonic variants, and over 250 common variants. Previously we combined whole genome sequencing (WGS) with brain-specific epigenomic data and found an excess of ultrarare SVs in schizophrenia localizing to the boundaries of topologically associated domains (TADs). Alterations in TAD boundaries (TAD-b) may lead to disarrangement of enhancer-promoter contacts and dysregulation of gene expression and have been associated with several human diseases. Our study sought to functionally characterize two of these TAD-b SVs using chromatin conformation capture (e.g., Hi-C) and RNA sequencing, to unveil mechanistic insight into the effects of these variants on 3D-genome organization and gene expression. To achieve this, we genetically engineered these two TAD-b SVs in isogenic induced pluripotent stem cells (iPSCs) using CRISPR/Cas9. iPSCs were differentiated into neuronal precursor cells, excitatory glutamatergic neurons, and medium spiny neurons. We found that these TAD-boundary-disrupting SVs could reshape the 3D-genome and transcriptional networks in a cell-type-specific manner.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Psychiatry, University of Florida College of Medicine, Gainesville, FL, USA",
    "Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA",
    "Department of Genetic and Genome Sciences, University of Connecticut Health Center, Farmington, CT, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Luz M. Porras",
      "orcid": "0000-0002-0162-4494"
    },
    {
      "affs": [
        1
      ],
      "name": "Martilias Farrell",
      "orcid": "0000-0002-9520-6209"
    },
    {
      "affs": [
        0
      ],
      "name": "Isabelle Rodriguez-Lausell",
      "orcid": "0009-0004-4691-6599"
    },
    {
      "affs": [
        0
      ],
      "name": "Gabriel A. Iglesias-Maldonado"
    },
    {
      "affs": [
        0
      ],
      "name": "Emily Val F. Tuliao",
      "orcid": "0009-0003-0892-4144"
    },
    {
      "affs": [
        0
      ],
      "name": "Elizabeth Wright",
      "orcid": "0009-0001-2164-2112"
    },
    {
      "affs": [
        0
      ],
      "name": "Amphitreatte Kreiman"
    },
    {
      "affs": [
        1
      ],
      "name": "NaEshia Ancalade",
      "orcid": "0000-0002-4844-129X"
    },
    {
      "affs": [
        2
      ],
      "name": "Christopher Stoddard"
    },
    {
      "affs": [
        1
      ],
      "name": "Jin P. Szatkiewicz",
      "orcid": "0000-0002-4898-7401"
    },
    {
      "affs": [
        0
      ],
      "name": "Paola Giusti-Rodríguez",
      "orcid": "0000-0002-1921-1305"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a0k89z7yms24k.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.26.761993",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761993v1.full",
  "id": "a0k89z7yms24k",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761993v1",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genomics"
    ],
    [
      "heading",
      "Article"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761993v1.full.pdf",
  "pmcid": "PMC13733917",
  "pmid": "42990398",
  "published": "2026-10-26",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/a0k89z7yms24k.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:30:18Z",
      "native_id": "10.64898/2026.10.26.761993",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761993v1"
    },
    {
      "first_seen": "2026-11-08T12:23:36Z",
      "native_id": "PMC13733917",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.26.761993"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "3D-genome impacts of TAD-boundary-disrupting ultra-rare structural variants identified in schizophrenia",
  "title_text": "3D-genome impacts of TAD-boundary-disrupting ultra-rare structural variants identified in schizophrenia",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:36Z",
  "url": "https://research.draconitic.com/paper/a0k89z7yms24k",
  "venue": "bioRxiv",
  "versions": []
}