Abstract
BackgroundCopy number variation (CNV) is an important type of genetic variation contributing to phenotypic differences among mammals and may serve as an alternative molecular marker to single nucleotide polymorphism (SNP) for genome-wide association study (GWAS). Recently, GWAS analysis using CNV has been applied in livestock, although few studies have focused on Holstein cattle.ResultsWe describe 191 CNV detected using intensity data from over 700,000 SNP genotypes generated with the BovineHD Genotyping BeadChip (Illumina, San Diego, CA) in 528 Holstein cows. The CNV were used for GWAS analysis of 10 important production traits of 473 cattle related to feed intake, milk quality, and female fertility, as well as 2 composite traits of net merit and productive life. In total, we detected 57 CNV associated (P < 0.05 after false discovery rate correction) with at least one of the 10 phenotypes. Focusing on feed efficiency and intake-related phenotypes of residual feed intake and dry matter intake, we detected a single CNV associated with both traits which overlaps a predicted olfactory receptor gene OR2A2 (LOC787786). Additionally, 2 CNV within the RXFP4 (relaxin/insulin like family peptide receptor 4) and 2 additional olfactory receptor gene regions, respectively, were associated with residual feed intake. The RXFP4 gene encodes a receptor for an orexigenic peptide, insulin-like peptide 5 produced by intestinal L cells, which is expressed by enteric neurons. Olfactory receptors are critical for transmitting the effects of odorants, contributing to the sense of smell, and have been implicated in participating in appetite regulation.ConclusionsOur results identify CNV for genomic evaluation in Holstein cattle, and provide candidate genes, such as RXFP4, contributing to variation in feed efficiency and feed intake-related traits. These results indicate potential novel targets for manipulating feed intake-related traits of livestock.
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