Phased-assembly-driven pangenome graphs for structural variant genotyping and complex trait mapping in dairy cattle.

Yang, Liu; Gao, Yahui; Kuhn, Kristen L; Bhowmik, Nayan; Li, Wenli; Zanton, Geoffrey; Fang, Lingzhao; Cole, John B et al. · Nat Commun · 2026

basic_science · Level V

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Abstract

Structural variants are an underexplored source of genetic diversity. As part of the FarmGTEx Project, here we report a Holstein breed-specific pangenome graph (H20D) using Minigraph-Cactus and 40 phased haploid assemblies from 20 cows. H20D outperforms both assembly- and read-based long-read callers, and far exceeds short-read approaches, identifying over 10,000 additional structural variants per sample. It also significantly improves structural variant detection and genotyping relative to graphs built across breeds or from fewer/unphased assemblies, with particular advantages in complex regions. Using H20D, we genotype variants in 173 cattle and performed a GWAS, where a larger fraction of structural variants than SNPs reach genome-wide significance, implicating them as potential causal variants. Together, these results demonstrate the power of phased, within-breed pangenome graphs for accurate SV genotyping and trait mapping in dairy cattle.

Medical subject headings