<p>Genomic structural variants (SVs) contribute substantially to genetic diversity and human diseases<sup><CitationRef AdditionalCitationIDS="CR2 CR3" CitationID="CR1">1</CitationRef>–<CitationRef CitationID="CR4">4</CitationRef></sup>, yet remain under-characterized in population-scale cohorts<sup><CitationRef CitationID="CR5">5</CitationRef></sup>. Here we conducted long-read sequencing<sup><CitationRef CitationID="CR6">6</CitationRef></sup> 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<sup><CitationRef CitationID="CR7">7</CitationRef></sup>, advancing SV characterization over short-read-based population-scale surveys<sup><CitationRef CitationID="CR3">3</CitationRef>,<CitationRef CitationID="CR4">4</CitationRef></sup>. 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<sup><CitationRef CitationID="CR8">8</CitationRef>,<CitationRef CitationID="CR9">9</CitationRef></sup> 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.</p>

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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

摘要

Genomic structural variants (SVs) contribute substantially to genetic diversity and human diseases14, 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.