Hepatic Gene Expression Profiling to Predict Future Lactation Performance in Dairy Cattle

An experiment was conducted to obtain a hepatic gene expression dataset from postpubertal dairy heifers that could be fit to a computational model capable of predicting future lactation performance values. The initial animal experiment was conducted to characterize the hepatic transcriptional response to 24-hour total feed withdrawal in one-hundred and two postpubertal Holstein dairy heifers using an 8329-gene oligonucleotide microarray in a randomized block design. Plasma concentration of non-esterified fatty acids was significantly higher, while levels of beta-hydroxybutyrate, triacylglycerol, and glucose were significantly lower with the 24-hour total feed withdrawal. In total, 505 differentially expressed genes were identified and microarray results were confirmed by real-time PCR. Upregulation of key gluconeogenic genes occurred despite diminished dietary substrate and lower hepatic glucose synthesis. Downregulation of ketogenic genes was contrary to the non-ruminant response to feed withdrawal, but was consistent with a lower ruminal supply of short-chain fatty acids as precursors. Following the microarray experiment, the first series of regression analyses was employed to identify relationships between gene expression signal and lactation performance measurements taken over the first lactation of 81 of the subjects from the original study. Regression models were evaluated using mean square prediction error (MSPE) and concordance correlation coefficient (CCC) analysis. The strongest validated stepwise regression models were constructed for milk protein percentage (r = 0.04) and lactation persistency (r = 0.09). To determine if another type of regression analysis would better predict lactation performance, partial least squares (PLS) regression analysis was then applied. Selection of gene expression data was based on an assessment of the linear dependence of all genes in normalized datasets for 81 subjects against 18 dairy herd index (DHI) variables using Pearson correlation analysis. Results were distributed into two lists based on correlation coefficient. Each gene expression dataset was used to construct PLS models for the purpose of predicting lactation performance. The strongest predictive models were generated for protein percentage (r = 0.46), 305-d milk yield (r = 0.44), and 305-d protein yield (r = 0.47). These results demonstrate the suitability of using hepatic gene expression in young animals to quantitatively predict future lactation performance.