Predicting the rate of inbreeding in populations undergoing four-path selection on genomically enhanced breeding values.

OBJECTIVE: A formula is needed that is practical for current livestock breeding methods and that predicts the approximate rate of inbreeding (∆F) in populations where selection is performed according to four-path programs (sires to breed sons, sires to breed daughters, dams to breed sons, and dams to breed daughters). The formula widely used to predict inbreeding neglects selection, we need to develop a new formula that can be applied with or without selection. METHODS: The core of the prediction is to incorporate the long-tern genetic influence of the selected parents in four-selection paths executed as sires to breed sons, sires to breed daughters, dams to breed sons, and dams to breed daughters. The rate of inbreeding was computed as the magnitude that is proportional to the sum of squared long-term genetic contributions of the parents of four-selection paths to the selected offspring. RESULTS: We developed a formula to predict the rate of inbreeding in populations undergoing four-path selection on genomically enhanced breeding values and with discrete generations. The new formula can be applied with or without selection. Neglecting the effects of selection led to underestimation of the rate of inbreeding by 40% to 45%. CONCLUSION: The formula we developed here would be highly useful as a practical method for predicting the approximate rate of inbreeding (ΔF) in populations where selection is performed according to four-path programs.

Identification of deleterious recessive haplotypes and candidate deleterious recessive mutations in Japanese Black cattle.

Intensive use of a few elite sires has increased the risk of the manifestation of deleterious recessive traits in cattle. Substantial genotyping data gathered using single-nucleotide polymorphism (SNP) arrays have identified the haplotypes with homozygous deficiency, which may compromise survival. We developed Japanese Black cattle haplotypes (JBHs) using SNP array data (4843 individuals) and identified deleterious recessive haplotypes using exome sequencing of 517 sires. We identified seven JBHs with homozygous deficiency. JBH_10 and JBH_17 were associated with the resuming of estrus after artificial insemination, indicating that these haplotypes carried deleterious mutations affecting embryonic survival. The exome data of 517 Japanese Black sires revealed that AC_000165.1:g.85341291C>G of IARS in JBH_8_2, AC_000174.1:g.74743512G>T of CDC45 in JBH_17, and a copy variation region (CNVR_27) of CLDN16 in JBH_1_1 and JBH_1_2 were the candidate mutations. A novel variant AC_000174.1:g.74743512G>T of CDC45 in JBH_17 was located in a splicing donor site at a distance of 5 bp, affecting pre-mRNA splicing. Mating between heterozygotes of JBH_17 indicated that homozygotes carrying the risk allele died around the blastocyst stage. Analysis of frequency of the CDC45 risk allele revealed that its carriers were widespread throughout the tested Japanese Black cattle population. Our approach can effectively manage the inheritance of recessive risk alleles in a breeding population.

Genome-wide association study and genomic evaluation of feed efficiency traits in Japanese Black cattle using single-step genomic best linear unbiased prediction method.

The objectives of this study were to better understand the genetic architecture and the possibility of genomic evaluation for feed efficiency traits by (i) performing genome-wide association studies (GWAS), and (ii) assessing the accuracy of genomic evaluation for feed efficiency traits, using single-step genomic best linear unbiased prediction (ssGBLUP)-based methods. The analyses were performed in residual feed intake (RFI), residual body weight gain (RG), and residual intake and body weight gain (RIG) during three different fattening periods. The phenotypes from 4,578 Japanese Black steers, which were progenies of 362 progeny-tested bulls and the genotypes from the bulls were used in this study. The results of GWAS showed that a total of 16, 8, and 12 gene ontology terms were related to RFI, RG, and RIG, respectively, and the candidate genes identified in RFI and RG were involved in olfactory transduction and the phosphatidylinositol signaling system, respectively. The realized reliabilities of genomic estimated breeding values were low to moderate in the feed efficiency traits. In conclusion, ssGBLUP-based method can lead to understand some biological functions related to feed efficiency traits, even with small population with genotypes, however, an alternative strategy will be needed to enhance the reliability of genomic evaluation.

Development of a structural growth curve model that considers the causal effect of initial phenotypes.

BACKGROUND: Growth curves have been widely used in genetic analyses to gain insights into the growth characteristics of both animals and plants. However, several questions remain unanswered, including how the initial phenotypes affect growth and what is the duration of any such impact. For beef cattle production in Japan, calves are procured from farms that specialize in reproduction and then moved to other farms where they are fattened to achieve their market/purchase value. However, the causal effect of growth, while calves are on the reproductive farms, on their growth during fattening remains unclear. To investigate this, we developed a model that combines a structural equation with a growth curve model. The causal effect was modeled with B-splines, which allows inference of the effect as a curve. We fitted the proposed structural growth curve model to repeated measures of body weight from a Japanese beef cattle population (n = 3831) to estimate the curve of the causal effect of the calves' initial weight on their trajectory of growth when they are on fattening farms. RESULTS: Maternal and reproduction farm effects explained 26% of the phenotypic variance of initial weight at fattening farms. The structural growth curve model was fitted to remove the effects of these factors in growth curve analysis at fattening farms. The estimated curve of causal effects remained at approximately 0.8 for 200 d after the calves entered the fattening farms, which means that 64% of the phenotypic variance was explained by the initial weight. Then, the effect decreased linearly and disappeared approximately 620 d after entering the fattening farms, which corresponded to an average age of 871.5 d. CONCLUSIONS: The proposed model is expected to provide more accurate estimates of genetic values for growth patterns because the confounding causal factors such as maternal and reproduction farm effects are removed. Moreover, examination of the inferred curve of the causal effect enabled us to estimate the effect of a calf's initial weight at arbitrary times during growth, which could provide suitable information for decision-making when shifting the time of slaughter, building models for genetic evaluation, and selecting calves for market.

Selection on milk production and conformation traits during the last two decades in Japan.

OBJECTIVE: The purpose of this study was to compare intended and actual yearly genetic gains for milk production and conformation traits and to investigate the simple selection criterion practiced among milk production and conformation traits during the last two decades in Japan. Learning how to utilize the information on intended and actual genetic gains during the last two decades into the genomic era is vital. METHODS: Genetic superiority for each trait for four paths of selection (sires to breed bulls [SB], sires to breed cows [SC], dams to breed bulls [DB], and dams to breed cows [DC]) was estimated. Actual practiced simple selection criteria were investigated among milk production and conformation traits and relative emphasis on milk production and conformation traits was compared. RESULTS: Selection differentials in milk production traits were greater than those of conformation traits in all four paths of selection. Realized yearly genetic gain was less than that intended for milk production traits. Actual annual genetic gain for conformation traits was equivalent to or greater than intended. Retrospective selection weights of milk production and conformation traits were 0.73:0.27 and 0.56:0.44 for intended and realized genetic gains, respectively. CONCLUSION: Selection was aimed more toward increasing genetic gain in milk production than toward conformation traits over the past two decades in Japan. In contrast, actual annual genetic gain for conformation traits was equivalent to or greater than intended. Balanced selection between milk production and conformation traits tended to be favored during actual selection. Each of four paths of selection (SB, SC, DB, and DC) has played an individual and important role. With shortening generation interval in the genomic era, a young sire arises before the completion of sire's daughters' milk production records. How to integrate these four paths of selection in the genomic era is vital.

Effects of preselection of genotyped animals on reliability and bias of genomic prediction in dairy cattle.

OBJECTIVE: Models for genomic selection assume that the reference population is an unselected population. However, in practice, genotyped individuals, such as progeny-tested bulls, are highly selected, and the reference population is created after preselection. In dairy cattle, the intensity of selection is higher in males than in females, suggesting that cows can be added to the reference population with less bias and loss of accuracy. The objective is to develop formulas applied to any genomic prediction studies or practice with preselected animals as reference population. METHODS: We developed formulas for calculating the reliability and bias of genomically enhanced breeding values (GEBV) in the reference population where individuals are preselected on estimated breeding values. Based on the formulas presented, deterministic simulation was conducted by varying heritability, preselection percentage, and the reference population size. RESULTS: The number of bulls equal to a cow regarding the reliability of GEBV was expressed through a simple formula for the reference population consisting of preselected animals. The bull population was vastly superior to the cow population regarding the reliability of GEBV for low-heritability traits. However, the superiority of reliability from the bull reference population over the cow population decreased as heritability increased. Bias was greater for bulls than cows. Bias and reduction in reliability of GEBV due to preselection was alleviated by expanding reference population. CONCLUSION: Cows are easier in expanding reference population size compared with bulls and alleviate bias and reduction in reliability of GEBV of bulls which are highly preselected than cows by expanding the cow reference population.

Evaluation of feed efficiency traits for genetic improvement in Japanese Black cattle.

We evaluated the genetic relationships (1) among feed efficiency traits with different fattening periods, (2) between feed efficiency traits and growth traits, and (3) between feed efficiency traits and carcass traits, to determine the influence of genetic factors on feed efficiency traits. In total, 4,578 Japanese Black cattle from a progeny testing program were used. Residual feed intake (RFI), residual BW gain (RG), and residual intake and BW gain (RIG) were defined as feed efficiency traits, and were measured for the first half (approximately 9 to 15 months of age), latter half (approximately 15 to 21 months of age), and total period of fattening (approximately 9 to 21 months of age). A single-trait animal model for estimating heritability and a two-trait animal model for estimating genetic and phenotypic correlations were used. The heritability estimates for RFI, RG, and RIG were different in each fattening period, ranging from 0.36 to 0.46, 0.19 to 0.28, and 0.28 to 0.34, respectively, and the heritability estimates for the total fattening period were greater than those for the first and latter halves separately. RIG showed the greatest preferred genetic correlation, with a greater feed conversion ratio than the other feed efficiency traits (ranging from -0.84 to -0.96). RG in the first and latter halves of the fattening period had different genetic correlations with the growth starting point (0.82 and -0.06, respectively) and maturity rate (0.49 and -0.51, respectively) of the Gompertz growth curve parameters, and is strongly dependent on the different fattening periods. Feed efficiency traits in different fattening periods had low genetic correlations with the carcass traits (from -0.05 to 0.19 for RFI; from 0.02 to 0.31 for RG; and from -0.11 to 0.20 for RIG). This study indicated the possibility for genetic improvement through the selection of high-RIG animals to decrease feed intake and increase BW gain without any unfavorable correlated responses affecting mature (asymptotic) weight and carcass grade.

Effects of selection index coefficients that ignore reliability on economic weights and selection responses during practical selection.

OBJECTIVE: In practical breeding, selection is often performed by ignoring the accuracy of evaluations and applying economic weights directly to the selection index coefficients of genetically standardized traits. The denominator of the standardized component trait of estimated genetic evaluations in practical selection varies with its reliability. Whereas theoretical methods for calculating the selection index coefficients of genetically standardized traits account for this variation, practical selection ignores reliability and assumes that it is equal to unity for each trait. The purpose of this study was to clarify the effects of ignoring the accuracy of the standardized component trait in selection criteria on selection responses and economic weights in retrospect. METHODS: Theoretical methods were presented accounting for reliability of estimated genetic evaluations for the selection index composed of genetically standardized traits. RESULTS: Selection responses and economic weights in retrospect resulting from practical selection were greater than those resulting from theoretical selection accounting for reliability when the accuracy of the estimated breeding value (EBV) or genomically enhanced breeding value (GEBV) was lower than those of the other traits in the index, but the opposite occurred when the accuracy of the EBV or GEBV was greater than those of the other traits. This trend was more conspicuous for traits with low economic weights than for those with high weights. CONCLUSION: Failure of the practical index to account for reliability yielded economic weights in retrospect that differed from those obtained with the theoretical index. Our results indicated that practical indices that ignore reliability delay genetic improvement. Therefore, selection practices need to account for reliability, especially when the reliabilities of the traits included in the index vary widely.