Abstract
Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, current studies on SVs have failed to provide a global view of the full spectrum of SVs and to integrate them into reference panels of genetic variation.
Here, we analyzed 769 individuals from 250 Dutch families, whole-genome sequenced at an average coverage of 14.5x, and provide a haplotype-resolved map of 1.9 million genome variants across 9 different variant classes, including novel forms of complex indels and retrotransposition-mediated insertions of mobile elements and processed RNAs. A large proportion of the structural variants (36%) were discovered in the size range of 21 - 100bp, a size range which remains under reported in many studies. Furthermore, we detected 4 megabases of novel sequence, extending the human pangenome with 11 new active transcripts. Finally, we show 191 known, trait-associated SNPs to be in strong linkage disequilibrium with a structural variant and demonstrate that our panel facilitates accurate imputation of SVs into unrelated individuals, which is essential for future genome-wide association studies.