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, Jesús 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 Jensen, Nikhil R. Podduturi, Jan Stutzki, Bernardo Rodríguez–Martín, Tobias Rausch, Tobias Marschall, Jan O. Korbel
Abstract
Abstract 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.