Structural variants in the bovine genome

Genome and environment together greatly influence how an organism develops and functions. Cattle is a livestock species with high economic significance; thus, deciphering how its genome and genomic information relates to its phenotype is crucial. Nevertheless, our understanding of bovine genomes is incomplete: investigation of bovine genomes thus far has mainly focused on single-nucleotide variants, leaving less tractable and complex variants, such as structural variants, underexplored. In this thesis, I present a comprehensive and in-depth investigation of structural variants in bovine genomes. Two structural variant catalogues, generated from genotyping data and deeply sequenced bovine genomes, revealed ~32 and ~5,000 SVs per genome, respectively. Furthermore, I integrated statistical associations and ~omics data, and delineated a 12-Kb copy number variant (CNV) as the likely causal variant of a major clinical mastitis QTL. This CNV encompasses an enhancer that targets the group-specific component gene, which encodes a vitamin D binding protein. Lastly, I investigated the emergence of de novo structural variants by exploiting 127 multi-generational deeply sequenced genomes. The pedigree-based germline mutation rate corresponded to one de novo structural variant per 8.5 births. The de novo structural variants were strongly biased towards male germlines and in vitro produced animals, unravelling sex and reproductive technology effects. Together, this thesis highlights a broad spectrum of bovine structural variants: from extremely rare de novo mutations to population variants, highlighting one that exerts strong effects on economically important traits. This thesis contributes to advancing our understanding of bovine structural variation.