Genome-wide association analysis and pathways enrichment for lactation persistency in Canadian Holstein cattle
Citation
Do, D.N., Bissonnette, N., Lacasse, P., Miglior, F., Sargolzaei, M., Zhao, X., Ibeagha-Awemu, E.M. (2017). Genome-wide association analysis and pathways enrichment for lactation persistency in Canadian Holstein cattle. Journal of Dairy Science (JDS), [online] 100(3), 1955-1970. http://dx.doi.org/10.3168/jds.2016-11910
Plain language summary
The objective of this study was to find genetic markers (biomarkers) associated with the persistency of lactation. Lactation persistency is the ability to maintain high milk yield after peak milk production. This study was part of a large study with aim to reshape the lactation curve in order to improve milk production. This study specifically focused on the detection of biomarkers for improvement of lactation persistency. Lactation persistency information for 3,796 Canadian Holstein cows was calculated from first, second and third parity lactation records. Fifty thousand biomarkers scattered all over the bovine (cow) genome (genetic material) were associated with lactation persistency information using statistical methods. The study found potential candidate biomarkers and genes for lactation persistency, and the biological pathways implicated in the biology of lactation persistency. This information can be used to select cows with higher lactation persistency (or higher milk yield). This study has provided baseline information for exploring the biology of lactation persistency. It also added to the list of biomarkers for lactation persistency which can be used for validation and for integration in selection programs for high lactation persistency.
Abstract
Lactation persistency (LP), defined as the rate of declining milk yield after milk peak, is an economically important trait for dairy cattle. Improving LP is considered a good alternative method for increasing overall milk production because it does not cause the negative energy balance and other health issues that cows experience during peak milk production. However, little is known about the biology of LP. A genome-wide association study (GWAS) and pathway enrichment were used to explore the genetic mechanisms underlying LP. The GWAS was performed using a univariate regression mixed linear model on LP data of 3,796 cows and 44,100 single nucleotide polymorphisms (SNP). Eight and 47 SNP were significantly and suggestively associated with LP, respectively. The 2 most important quantitative trait loci regions for LP were (1) a region from 106 to 108 Mb on Bos taurus autosome (BTA) 5, where the most significant SNP (ARS-BFGL-NGS-2399) was located and also formed a linkage disequilibrium block with 3 other SNP; and (2) a region from 29.3 to 31.3 Mb on BTA 20, which contained 3 significant SNP. Based on physical positions, MAN1C1, MAP3K5, HCN1, TSPAN9, MRPS30, TEX14, and CCL28 are potential candidate genes for LP because the significant SNP were located in their intronic regions. Enrichment analyses of a list of 536 genes in 0.5-Mb flanking regions of significant and suggestive SNP indicates that synthesis of milk components, regulation of cell apoptosis processes and insulin, and prolactin signaling pathways are important for LP. Upstream regulators relevant for LP positional candidate genes were prolactin (PRL), peroxisome proliferator-activated receptor gamma (PPARG), and Erb-B2 receptor tyrosine kinase 2 (ERBB2). Several networks related to cellular development, proliferation and death were significantly enriched for LP positional candidate genes. In conclusion, this study detected several SNP, genes, and interesting regions for fine mapping and validation of candidate genes and SNP for potential use in selection for improved LP. This study also provided further insights on the biology of LP which will help to prioritize selected candidate genes for functional validation and application.