Detecting and characterizing copy number variation in a large commercial U.S. Holstein cattle population

Copy number variations (CNVs) are an important source of genomic variation that play an active role in modulating biological processes by altering gene expression and dosage. These structural variants involve duplications and deletions of segments usually exceeding 1 kilobase in size, dispersed throughout the genome of humans and livestock individuals. We mapped CNVs from high-density single-nucleotide polymorphism (SNP) genotyping array data on 3,601 Holsteins. Following, we explored their association with reported quantitative trait loci (QTLs), genes, and biological pathways, unveiling the potential biological contributions of CNVs to economically important traits in the dairy industry and breeding programs.

We identified 4,113 non-redundant high-confidence CNVs, of which 78% were deletions and 22% duplications, distributed across all bovine autosomal chromosomes (BTA). Out of the 1,184 compiled CNV regions (CNVRs) covering 3.02% of the autosomal genome, 199 novel CNVRs were mapped. QTLs overlapping with CNVRs detected in this study were enriched for 140 economically important traits, such as milk yield, conception and pregnancy rates, susceptibility to diseases and length of productive life, indicating that CNVs likely underlie productive, reproductive and health performance in Holstein dairy cattle. Moreover, detected CNVRs overlapped with 2,788 annotated genes, including those linked to milk production, fertility, and immune response in cattle, such as DGAT1, AFF1, and ADAMTS13 genes. Furthermore, the gene set analysis revealed GO terms related to metabolic processes, immune system, response to stimulus, and cellular binding activities. Notably, enriched GO terms highlighted relevant genes to cattle health and reproduction overlapping CNVRs, such as DEFB4A, GATA3, GNB1, and PPP1R1B.

We mapped and demonstrated the characteristics of genome-wide distributed CNVs in a large commercial Holstein population genotyped with a high-density SNP array. Collectively, the results emphasize the role of CNVs as a valuable resource of genetic variation and contribute to better understand the genetic architecture of economic complex traits in dairy cattle. Furthermore, these findings may provide opportunities for the development of novel and enhanced genomic selection strategies in Holstein cattle.