Long-read sequencing and structural variant characterization in 1,019 samples from the 1000 Genomes Project

Area of Science:

• Genomics
• Human Genetics
• Bioinformatics

Background:

• Structural variants (SVs) are crucial for human genetic diversity and disease but are difficult to resolve with short-read sequencing.
• Previous population genomics studies have limitations in capturing the full spectrum of SVs at nucleotide resolution.

Approach:

• Leveraged nanopore sequencing for an intermediate coverage resource of 1,019 long-read genomes from 26 human populations.
• Integrated linear and graph-based approaches with pangenome graph-augmentation for SV analysis.
• Uncovered 167,291 sequence-resolved SVs, advancing characterization compared to short-read studies.

Key Points:

• Detailed diverse SV classes (deletions, duplications, insertions, inversions) at a population scale.
• Identified LINE-1 and SVA retrotransposition mediating transductions of unique sequences.
• Found evidence for a continuum of homology-mediated rearrangement processes and SV recurrence involving repeat sequences.

Conclusions:

• The open-access dataset highlights the impact of long-read sequencing on characterizing polymorphic genomic architectures.
• Provides a resource for prioritizing variants in future long-read sequencing-based disease studies.