Structural variation in 1,019 diverse humans based on long-read sequencing

Abstract

Genomic structural variants (SVs) contribute substantially to genetic diversity and human diseases1-4, yet remain under-characterized in population-scale cohorts5. Here we conducted long-read sequencing6 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 repeats7, advancing SV characterization over short-read-based population-scale surveys3,4. 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 transduction8,9 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.