Pangenome variation analysis uncovers the impacts of SNP-independent structural variations in modern European cattle breeding.

While pangenome studies emphasize structural variations (SVs), their functional significance beyond single-nucleotide polymorphisms (SNPs) in cattle remains unexplored. We established a comprehensive variation map for 1379 European cattle from nine breeds using a pangenome graph. Although SV and SNP distributions were similar genome-wide, 19.3% of SVs exhibited low linkage disequilibrium (r² < 0.2) with nearby SNPs. These non-SNP-tagged SVs are preferentially localized to chromosome ends and promoters, and play crucial roles in artificial selection for production traits. Integrated analyses of large-scale chromosomal recombination data and transposon-mediated SV events revealed that terminal chromosomal recombination and strong selection on recurrent young SVs are likely to prevent SNP tagging. For SVs tagged by SNPs, they were found to play a dominant role in haplotype diversity and inter-population differences. Genome-wide association studies of over 50,000 dairy bulls using imputed SV + SNP data identified functional SVs missed by standard analysis, including an SV (chr6:32,772,14-32,772,409) showing strong milk yield association (p < 1 × 10- 10) and divergent selection between dairy and beef breeds, demonstrating SVs' unique contribution to complex trait architecture. Overall, our study illustrates the independent or dominant roles of SV in the breeding processes of the European cattle, facilitating the use of pangenome SVs to recover missing heritability from SNP-based research.