title: 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.
authors.affiliation: Agriculture and Agri-Food Canada, Sherbrooke Research and Development Centre, Sherbrooke, QC, J1M 0C8, Canada; Department of Animal Science, McGill University, Ste-Anne-de-Bellevue, QC, H9X 3V9, Canada.
authors.forename: D N
authors.initials: DN
authors.lastname: Do
authors.affiliation: Agriculture and Agri-Food Canada, Sherbrooke Research and Development Centre, Sherbrooke, QC, J1M 0C8, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Bissonnette
authors.affiliation: Agriculture and Agri-Food Canada, Sherbrooke Research and Development Centre, Sherbrooke, QC, J1M 0C8, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Lacasse
authors.affiliation: Centre for Genetic Improvement of Livestock, Department of Animal Biosciences, University of Guelph, Guelph, ON, N1G 2W1, Canada; Canadian Dairy Network, Guelph, ON, N1K 1E5, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Miglior
authors.affiliation: Centre for Genetic Improvement of Livestock, Department of Animal Biosciences, University of Guelph, Guelph, ON, N1G 2W1, Canada; Semex Alliance, Guelph, ON, N1H 6J2, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Sargolzaei
authors.affiliation: Department of Animal Science, McGill University, Ste-Anne-de-Bellevue, QC, H9X 3V9, Canada.
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Agriculture and Agri-Food Canada, Sherbrooke Research and Development Centre, Sherbrooke, QC, J1M 0C8, Canada. Electronic address: eveline.ibeagha-awemu@agr.gc.ca.
authors.forename: E M
authors.initials: EM
authors.lastname: Ibeagha-Awemu
mesh_terms: D000818:Animals; D002170:Canada; D002417:Cattle; D005260:Female; D055106:Genome-Wide Association Study; D007774:Lactation / Q000235:genetics*; D015810:Linkage Disequilibrium; D008892:Milk / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
keywords: cows; genome-wide association study; lactation persistency; pathways; single nucleotide polymorphism