Structural variants from donor-specific assemblies affect recurrent chromatin contact divergence in humans
- 1Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA; Howard Hughes Medical Institute, University of Washington, Seattle
Abstract
Structural variants (SVs) are a major source of human genetic diversity, yet their contribution to three-dimensional (3D) genome organization remains difficult to resolve using a standard reference genome. Here, we integrate haplotype-resolved chromatin interaction maps across 354 human and 12 nonhuman ape haplotypes with matched genome assemblies and long-read transcriptomes to determine how inherited SVs influence chromatin organization. We observe significant improvements in contact mapping, with 13.2% of cis Hi-C contacts showing >25 kbp changes in inferred genomic separation and an additional 2.8% of valid contact pairs recovered when using donor-specific assemblies instead of standard references. We show that haplotype-specific chromatin differences are highly selective rather than pervasive, concentrating within 1,790 recurrent contact difference hotspots associated with a restricted subset of SVs. We identified 2,495 chromatin-structure-associated SVs that are enriched in regulatory genomic contexts and are linked to expression variation. Notably, more than 90% of these SVs are derived in the human lineage, consistent with recent remodeling of regulatory architecture at the population level. These findings highlight the importance of incorporating haplotype diversity from pangenomes into studies of chromatin organization and provide a framework for understanding how inherited genomic differences are linked to functional consequences across populations and evolution.
Related
- Genome-wide associations of structural variants with human traits through imputation from long-read assemblies
- An expanded evolutionary landscape of H3 histones with variants that destabilize nucleosomes and promote chromatin accessibility
- Reversible chromatin remodeling enables Prosopis cineraria survival under recurrent heat extremes.
- Chromatin compartment shifting is recurrent and associated with epigenetic reprogramming in prostate cancer
- Population-scale Y chromosome assemblies reveal recurrent remodeling within constrained architectures
BibTeX
@misc{ni2026structural,
title = {{Structural variants from donor-specific assemblies affect recurrent chromatin contact divergence in humans}},
author = {L. Ni and J. Lin and D. Yoo and T. Mack and I. Wong and J. Wertz and K. M. Munson and K. Hoekzema and Human Pangenome Reference Consortium (HPRC) and X. Shi and J. Ma and W. S. Noble and E. E. Eichler},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.756789},
url = {https://www.biorxiv.org/content/10.64898/2026.10.05.756789v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Structural variants from donor-specific assemblies affect recurrent chromatin contact divergence in humans
AU - L. Ni
AU - J. Lin
AU - D. Yoo
AU - T. Mack
AU - I. Wong
AU - J. Wertz
AU - K. M. Munson
AU - K. Hoekzema
AU - Human Pangenome Reference Consortium (HPRC)
AU - X. Shi
AU - J. Ma
AU - W. S. Noble
AU - E. E. Eichler
PY - 2026
DA - 2026/10/05
PB - bioRxiv
DO - 10.64898/2026.10.05.756789
UR - https://www.biorxiv.org/content/10.64898/2026.10.05.756789v1
AB - Structural variants (SVs) are a major source of human genetic diversity, yet their contribution to three-dimensional (3D) genome organization remains difficult to resolve using a standard reference genome. Here, we integrate haplotype-resolved chromatin interaction maps across 354 human and 12 nonhuman ape haplotypes with matched genome assemblies and long-read transcriptomes to determine how inherited SVs influence chromatin organization. We observe significant improvements in contact mapping, with 13.2% of cis Hi-C contacts showing >25 kbp changes in inferred genomic separation and an additional 2.8% of valid contact pairs recovered when using donor-specific assemblies instead of standard references. We show that haplotype-specific chromatin differences are highly selective rather than pervasive, concentrating within 1,790 recurrent contact difference hotspots associated with a restricted subset of SVs. We identified 2,495 chromatin-structure-associated SVs that are enriched in regulatory genomic contexts and are linked to expression variation. Notably, more than 90% of these SVs are derived in the human lineage, consistent with recent remodeling of regulatory architecture at the population level. These findings highlight the importance of incorporating haplotype diversity from pangenomes into studies of chromatin organization and provide a framework for understanding how inherited genomic differences are linked to functional consequences across populations and evolution.
ER -