Source of genome-wide deleterious variation in a global cattle cohort
Background Identifying deleterious DNA changes underpins efforts to improve animal health, welfare, and sustainable breeding. In cattle, current variant prioritization focuses on coding changes, uses single annotation types, and gives limited resolution in non-coding sequence. Results We developed BovCADD (bovine Combined Annotation-Dependent Depletion), a nucleotide-level deleteriousness score…
A new tool called BovCADD has been developed to assess the detrimental effects of DNA changes across the entire genome in cattle. This nucleotide-level scoring system, applicable to both Bos taurus and Bos indicus cattle, integrates various factors such as evolutionary constraints, sequence context, epigenetic annotations, and gene/protein features.
By training on 41.9 million high-frequency derived alleles from approximately 3,700 cattle and comparing them to simulated variants, BovCADD can accurately differentiate known pathogenic variants from the general genetic variation. Notably, it can distinguish variants within the same consequence class and even score sites in introns and intergenic regions.
The aggregate scores have been used to identify genes harboring rare deleterious variations, highlighting elevated genetic load at trait-relevant loci and in bottlenecked, intensively selected cattle populations. This genome-wide, nucleotide-resolution measure of deleteriousness marks a significant advancement in animal health and breeding efforts, providing a comprehensive tool for variant interpretation in non-coding sequences. All precomputed scores for every possible substitution are publicly accessible through BovCADD.
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