Structural variation in 1,019 diverse humans based on long-read sequencing
- Siegfried Schloissnig
- Samarendra Pani
- Jana Ebler
- Carsten Hain
- Vasiliki Tsapalou
- Arda Söylev
- Patrick Hüther
- Hufsah Ashraf
- Timofey Prodanov
- Mila Asparuhova
- Hugo Magalhães
- Wolfram Höps
- Jesus Emiliano Sotelo-Fonseca
- Tomas Fitzgerald
- Walter Santana-Garcia
- Ricardo Moreira-Pinhal
- Sarah Hunt
- Francy J. Pérez-Llanos
- Tassilo Erik Wollenweber
- Sugirthan Sivalingam
- Dagmar Wieczorek
- Mario Cáceres
- Christian Gilissen
- Ewan Birney
- Zhihao Ding
- Jan Nygaard Jensen
- Nikhil Podduturi
- Jan Stutzki
- Bernardo Rodriguez-Martin
- Tobias Rausch
- Tobias Marschall
- Jan O. Korbel
2025-07-23
Genomic structural variants (SVs) contribute substantially to genetic diversity and human diseases 1–4 , yet remain under-characterized in population-scale cohorts 5 . Here we conducted long-read sequencing 6 in 1,019 humans to construct an intermediate-coverage resource covering 26 populations from the 1000 Genomes Project. Integrating linear and graph genome-based analyses, we uncover over 100,000 sequence-resolved biallelic SVs and we genotype 300,000 multiallelic variable number of tandem repeats 7 , advancing SV characterization over short-read-based population-scale surveys 3,4 . We characterize deletions, duplications, insertions and inversions in distinct populations. Long interspersed nuclear element-1 (L1) and SINE-VNTR-Alu (SVA) retrotransposition activities mediate the transduction 8,9 of unique sequence stretches in 5′ or 3′, depending on source mobile element class and locus. SV breakpoint analyses point to a spectrum of homology-mediated processes contributing to SV formation and recurrent deletion events. Our open-access resource underscores the value of long-read sequencing in advancing SV characterization and enables guiding variant prioritization in patient genomes.