Modelling effects of candidate genes on complex traits as variables over time

Abstract

In this study, changes in gene effects for milk production traits were analysed over time. Such changes can be expected by investigating daily milk production yields, which increase during the early phase of lactation and then decrease. Moreover, additive polygenic effects on milk production traits estimated in other studies differed throughout the 305 days of lactation, clearly indicating changes in the genetic determination of milk production throughout this period. Our study focused on particular candidate genes known to affect milk production traits and on the estimation of potential changes in the magnitude of their effects over time. With two independent data sets from Holstein-Friesian and Jersey breeds, we show that the effects of the DGAT1:p.Lys232Ala polymorphism on fat and protein content in milk change during lactation. The other candidate genes considered in this study (leptin receptor, leptin and butyrophilin, subfamily 1, member A1) exhibited effects that vary across time, but these could be observed in only one of the breeds. Longitudinal modelling of SNP effects enables more precise description of the genetic background underlying the variation of complex traits. A gene that changes the magnitude or even the sign of its effect cannot be detected by a time-averaged model. This was particularly evident when analysing the effect of butyrophilin, missed by many previous studies, which considered butyrophilin's effect as constant over time.

Effects of the DGAT1 polymorphism on test-day milk production traits throughout lactation

“…These results support the basic findings by Strucken et al (2011) and Szyda et al (2014); however, some differences exist on how effects of DGAT1 on milk production traits change throughout lactation. Strucken et al (2011) concluded that the characteristic DGAT1 genotypic effects occur after lactation d 40.…”

“…In the current study, we observed that the lactation stage at which the maximum difference between DGAT1 genotypes is reached differed between parities and traits and ranges between d 50 and 150 in lactation. Szyda et al (2014) concluded that effects of DGAT1 on fat and protein content increased during lactation, whereas we observed an increase in effects of DGAT1 on fat and protein content during the first 150 d in lactation, but later in lactation the effects stabilized for fat content and decreased for protein content. Furthermore, Szyda et al (2014) reported that effects of DGAT1 on milk yield were constant throughout lactation, whereas we observed a strong DGAT1 by lactation stage interaction for milk yield.…”

“…Kuehn et al (2007) detected significant dominance effects of the DGAT1 polymorphism on milk fat content, and recent studies by Strucken et al (2011) and Szyda et al (2014) suggest that effects of DGAT1 are not constant throughout lactation. Daughter yield deviations do not allow estimating dominance effects, and changes in gene effects throughout lactation remain unnoticed when effects are estimated based on 305-d production records.…”

The effect of DGAT1 polymorphism on milk production traits in dairycows depending on environmental temperature

“…In our previous study, the effect of this polymorphism on fat and protein contents in milk showed changes over time, being low in the first stage of lactation, and increased as lactation progressed (9). The significant impact of lactation stage on K232A Other reports suggest that the effect of DGAT1 may also depend on breed (8,13,16) and parity (15,16).…”

“…An ApA to GpC dinucleotide substitution located in exon 8 of the bovine DGAT1 gene that replaces lysine (K) by alanine (A) in encoded protein (K232A polymorphism) has been proven to have a pronounced influence on milk yield and composition, especially on fat percentage in milk (5-7). Although in many cattle populations DGAT1:p.K232A alleles affected individual milk traits in the same direction, the magnitude of effects was variable between breeds (8), and during lactation (9). Recently, Akbar et al (10) reported that the expression of this gene in the liver is reduced during the hot season.…”