Associated effects of copy number variants on economically important traits in Spanish Holstein dairy cattle

Copy number variants (CNV) are structural variants consisting of duplications or deletions of genomic fragments longer than 1 kb that present variability in the population and are heritable. The objective of this study was to identify CNV regions (CNVR) associated with 7 economically important traits (production, functional, and type traits) in Holstein cattle: fat yield, protein yield, somatic cell count, days open, stature, foot angle, and udder depth. Copy number variants were detected by using deep-sequencing data from 10 sequenced bulls and the Bovine SNP chip array hybridization signals. To reduce the number of false-positive calls, only CNV identified by both sequencing and Bovine SNP chip assays were kept in the final data set. This resulted in 823 CNVR. After filtering by minor allele frequency >0.01, a total of 90 CNVR appeared segregating in the bulls that had phenotypic data. Linear and quadratic CNVR effects were estimated using Bayesian approaches. A total of 15 CNVR were associated with the traits included in the analysis. One CNVR was associated with fat and protein yield, another 1 with fat yield, 3 with stature, 1 with foot angle, 7 with udder depth, and only 1 with days open. Among the genes located within these regions, highlighted were the MTHFSD gene that belongs to the folate metabolism genes, which play critical roles in regulating milk protein synthesis; the SNRPE gene that is related to several morphological pathologies; and the NF1 gene, which is associated with potential effects on fertility traits. The results obtained in the current study revealed that these CNVR segregate in the Holstein population, and therefore some potential exists to increase the frequencies of the favorable alleles in the population after independent validation of results in this study. However, genetic variance explained by the variants reported in this study was small.