Genome-wide association analysis and pathways enrichment for lactation persistency in Canadian Holstein cattle

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.

RETRACTED ARTICLE: Dissecting closely linked association signals in combination with the mammalian phenotype database can identify candidate genes in dairy cattle

“…The second most significant association signal was at BTA20:29996719 (rs43116343), which is close to MRPS30 . A recent study showed MRPS30 to be associated with lactation persistence in Canadian Holstein cattle [ 19 ]. This lead SNP is also close to the growth hormone receptor, GHR [ 20 ].…”

Genome‐wide association for milk production and lactation curve parameters in Holstein dairy cows

“…per lactation, peak yield and persistency are considered as among the economically most important production traits in dairy cows (Dekkers, Ten Hag, & Weersink, 1998;Do et al, 2017;Tekerli, Akinci, Dogan, & Akcan, 2000). There is a considerable variation between animals in terms of the shape of the lactation curve, which can be attributed to factors such as genetic background, parity, diet, health status and other environmental factors (Atashi, Zamiri, & Dadpasand, 2013;Hostens, Ehrlich, Van Ranst, & Opsomer, 2012;Rekaya, Carabano, & Toro, 2000;Tekerli et al, 2000).…”

Transcriptome signature of the lactation process, identified by meta-analysis of microarray and RNA-Seq data

“…It enhances the mammary gland's defense system during mastitis induced by Escherichia coli infection in goats (Zhu et al, 2007). A study performed on Canadian Holstein cattle on the enrichment of lactation persistency resulted in the identification of the cytochrome b5 reductase 3 (CYB5R3 ) gene (Do et al, 2017). Interestingly, in our research, the CYB5R3 gene showed a high co-expression with the GSN gene (Table S4 and Table S7).…”