Impact and characterization of serial structural variations across humans and great apes
Modern sequencing technology enables the systematic detection of complex structural variation (SV) across genomes. However, extensive DNA rearrangements arising through a series of mutations, a phenomenon we refer to as serial SV (sSV), remain underexplored, posing a challenge for SV discovery. Here, we present NAHRwhals ( https://github.com/WHops/NAHRwhals ), a method to infer repeat-mediated series of SVs in long-read genomic assemblies. Applying NAHRwhals to haplotype-resolved human genomes from 28 individuals reveals 37 sSV loci of various length and complexity. These sSVs explain otherwise cryptic variation in medically relevant regions such as the TPSAB1 gene, 8p23.1, 22q11 and Sotos syndrome regions. Comparisons with great ape assemblies indicate that most human sSVs formed recently, after the human-ape split, and involved non-repeat-mediated processes in addition to non-allelic homologous recombination. NAHRwhals reliably discovers and characterizes sSVs at scale and independent of species, uncovering their genomic abundance and suggesting broader implications for disease.
Authors
- Fritz Joachim Sedlazeck (ORCID: https://orcid.org/0000-0001-6040-2691)
- Tobias Rausch (ORCID: https://orcid.org/0000-0001-5773-5620)
- Michael Jendrusch (ORCID: https://orcid.org/0000-0003-2385-6103)
- Wolfram Höps
Institutions
- QB3 (US)
- University of Maryland, Baltimore (US)
- BC Cancer Agency (CA)
- European Bioinformatics Institute (GB)
- University of Alabama (US)
- German Cancer Research Center (DE)
- Baylor College of Medicine (US)
- University of Washington (US)
- Heidelberg University (DE)
- University of Michigan (US)
- Yale University (US)
- Düsseldorf University Hospital (DE)
- Biologie Computationnelle, Quantitative et Synthétique (FR)
- BioNano Genomics (United States) (US)
- Jackson Laboratory (US)
- European Molecular Biology Laboratory (DE)
- New York Genome Center (US)
- European Molecular Biology Laboratory (DE)
- Heinrich Heine University Düsseldorf (DE)
- Rice University (US)
- University of Pennsylvania (US)
- Clemson University (US)
- Temple University (US)
- Xi'an Jiaotong University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-12
- DOI
- https://doi.org/10.1038/s41467-024-52027-9
- Citations
- 10
- Primary Topic
- Genomics and Phylogenetic Studies
- Type
- article
- Field-Weighted Citation Impact
- 2.10
Funders
- Bundesministerium für Bildung und Forschung
- National Institutes of Health