Genetic and nongenetic profiling of milk pregnancy-associated glycoproteins in Holstein cattle

Authors: SANTOS, DANIEL - University Of Maryland; Cole, John; Null, Daniel; BYREM, TODD - Antel Biosystems, Inc; MA, LI - University Of Maryland

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/23/2018
Publication Date: 11/1/2018
Citation: Santos, D.A., Cole, J.B., Null, D.J., Byrem, T.M., Ma, L. 2018. Genetic and nongenetic profiling of milk pregnancy-associated glycoproteins in Holstein cattle. Journal of Dairy Science. 101(11):9987-10000. https://doi.org/10.3168/jds.2018-14682.
DOI: https://doi.org/10.3168/jds.2018-14682

Interpretive Summary: Milk pregnancy-associated glycoproteins are secreted by the trophoblast, and are commonly used to determine a cow’s pregnancy status. However, little is known about the genetic control of these proteins. Data from commerical tests used to measure milk pregnancy-asociated glycoprotein levels were combined with pedigree information, genotypes, and production information to study this trait, and its relationship to other economically importante phenotypes in US Holstein cattle. Results show that the trait is under moderate genetic control, and identified several genomic regions that appear to play important roles in regulating milk pregnancy-associatd glycoprotein levels.

Technical Abstract: Pregnancy-associated glycoproteins (PAG) are secreted by the trophoblast and are detectable in maternal circulation around the time of attachment of the fetal placenta, as well as in blood and milk throughout gestation. The understanding of the genetic mechanisms controlling PAG levels can confer advantages for a breeding program given the precocity and the ease of obtaining this phenotype from routine pregnancy diagnosis. The aim of this study is to characterize PAG levels by estimating genetic parameters and correlations with other dairy traits. In addition, a genome-wide association study was conducted to identify genomic regions and candidate genes associated with PAG levels in the maternal circulation. The data consisted of pregnancy diagnoses using commercial PAG assays collected from 2012 to 2017. Genotype data consisted of 54,123 SNP, including both autosomal and X-chromosome markers, for 2,352 individuals (embryos and dams). The model included contemporary group (herd, year, and season) as a fixed effect, embryo age as a covariate, and random embryonic (direct) and maternal (indirect) genetic effects. Using genomic data, the estimated h2 for direct and maternal genetic effects were 0.23 ± 0.05 and 0.11 ± 0.05, respectively. The genetic correlation between these effects was almost zero (0.001 ± 0.6). Low to moderate correlations of PAG levels with dairy traits were observed. The genome-wide association analysis was performed using two approaches: single-marker GWAS and single-step GWAS using all markers. Four genomic regions with direct genetic effects were detected on BTA6, BTA7, BTA19, and BTA29 of the embryonic genome. The BTA29 locus was within the bovine PAG gene cluster, suggesting a cis-regulatory QTL on the expression of PAG. However, other associations, without an obvious link to PAG expression, could be related to transportation and circulation of PAG protein from placenta to milk. Only one region, on BTA4, had a significant maternal effect, where WNT2 is a candidate gene related to placenta vascularization and gestation health. In sum, our results suggest that there is moderate genetic control of PAG levels, which can be useful in breeding programs as a measure of fertility.