Analysis of copy number variations in Holstein cows identify potential mechanisms contributing to differences in residual feed intake

Abstract

Genomic structural variation is an important and abundant source of genetic and phenotypic variation. In this study, we performed an initial analysis of copy number variations (CNVs) using BovineHD SNP genotyping data from 147 Holstein cows identified as having high or low feed efficiency as estimated by residual feed intake (RFI). We detected 443 candidate CNV regions (CNVRs) that represent 18.4 Mb (0.6 %) of the genome. To investigate the functional impacts of CNVs, we created two groups of 30 individual animals with extremely low or high estimated breeding values (EBVs) for RFI, and referred to these groups as low intake (LI; more efficient) or high intake (HI; less efficient), respectively. We identified 240 (~9.0 Mb) and 274 (~10.2 Mb) CNVRs from LI and HI groups, respectively. Approximately 30-40 % of the CNVRs were specific to the LI group or HI group of animals. The 240 LI CNVRs overlapped with 137 Ensembl genes. Network analyses indicated that the LI-specific genes were predominantly enriched for those functioning in the inflammatory response and immunity. By contrast, the 274 HI CNVRs contained 177 Ensembl genes. Network analyses indicated that the HI-specific genes were particularly involved in the cell cycle, and organ and bone development. These results relate CNVs to two key variables, namely immune response and organ and bone development. The data indicate that greater feed efficiency relates more closely to immune response, whereas cattle with reduced feed efficiency may have a greater capacity for organ and bone development.

Invited review: Improving feed efficiency in dairy production: challenges and possibilities

“…Factors including differences in rumen microbial populations (Rius et al, 2012), feeding behaviour (Williams et al, 2011;Connor et al, 2013;Green et al, 2013), physical activity (Connor et al, 2013) and variation in gene copy numbers (Hou et al, 2012) between dairy cattle that are divergent for RFI have been examined, which are described below.…”

“…These structural variations contribute to differences among cattle breeds and affect gene expression, multiple dairy production traits and complex traits including disease susceptibility and parasite resistance . Thus, to gain a better understanding of the genetic basis of variation in RFI, Hou et al (2012) identified and compared CNV regions between lactating Holstein cows with low v. high EBV for RFI. The genes associated with the CNV regions were then assembled into functional pathways and networks using specialised computing software to gain insight into biological mechanisms contributing to observed differences in RFI.…”

“…The genes associated with the CNV regions were then assembled into functional pathways and networks using specialised computing software to gain insight into biological mechanisms contributing to observed differences in RFI. Of interest, Hou et al (2012) found that among cows with extremely low EBV for RFI (efficient), CNV regions overlapped genes that primarily participate in inflammation and immunity, whereas among cows with extremely high EBV for RFI (inefficient), there were unique CNV regions that overlapped with genes enriched for functions in cell proliferation and organ and bone development.…”

“…Based on these findings, Hou et al (2012) suggested that differences in immune function, such as superior surveillance or ability to elicit an immune response to infection, may contribute to greater net efficiency of dairy cattle. Alternatively, among inefficient cows, genetic differences promoting greater organ and bone development may raise overall animal maintenance costs and reduce their net efficiency.…”

Biological mechanisms related to differences in residual feed intake in dairy cows

“…Although no significant differences in SCC were detected between high and low RFI cows, we found a positive phenotypic correlation between SCC and RFI, indicating that differences in SCC might partly explained variation observed in the efficiency of feed conversion to milk production among cows. Moreover, Hou et al (2012) studied genetic differences between cows with high and low estimated breeding values for RFI and found that that more efficient cows exhibit copy number variations in genes associated with immunity and the inflammatory response, which could impact their ability to elicit a response to an immune challenge. Therefore, assuming that SCC is an indicator of mastitis susceptibility, this result supported the hypothesis that differences in susceptibility to mastitis exist between low-and high-RFI cows.…”