Genotype-by-environment interaction in Holstein heifer fertility traits using single-step genomic reaction norm models.

BACKGROUND: The effect of heat stress on livestock production is a worldwide issue. Animal performance is influenced by exposure to harsh environmental conditions potentially causing genotype-by-environment interactions (G × E), especially in highproducing animals. In this context, the main objectives of this study were to (1) detect the time periods in which heifer fertility traits are more sensitive to the exposure to high environmental temperature and/or humidity, (2) investigate G × E due to heat stress in heifer fertility traits, and, (3) identify genomic regions associated with heifer fertility and heat tolerance in Holstein cattle. RESULTS: Phenotypic records for three heifer fertility traits (i.e., age at first calving, interval from first to last service, and conception rate at the first service) were collected, from 2005 to 2018, for 56,998 Holstein heifers raised in 15 herds in the Beijing area (China). By integrating environmental data, including hourly air temperature and relative humidity, the critical periods in which the heifers are more sensitive to heat stress were located in more than 30 days before the first service for age at first calving and interval from first to last service, or 10 days before and less than 60 days after the first service for conception rate. Using reaction norm models, significant G × E was detected for all three traits regarding both environmental gradients, proportion of days exceeding heat threshold, and minimum temperature-humidity index. Through single-step genome-wide association studies, PLAG1, AMHR2, SP1, KRT8, KRT18, MLH1, and EOMES were suggested as candidate genes for heifer fertility. The genes HCRTR1, AGRP, PC, and GUCY1B1 are strong candidates for association with heat tolerance. CONCLUSIONS: The critical periods in which the reproductive performance of heifers is more sensitive to heat stress are trait-dependent. Thus, detailed analysis should be conducted to determine this particular period for other fertility traits. The considerable magnitude of G × E and sire re-ranking indicates the necessity to consider G × E in dairy cattle breeding schemes. This will enable selection of more heat-tolerant animals with high reproductive efficiency under harsh climatic conditions. Lastly, the candidate genes identified to be linked with response to heat stress provide a better understanding of the underlying biological mechanisms of heat tolerance in dairy cattle.

Unraveling the actual background of second litter syndrome in pigs: based on Large White data.

Second litter syndrome (SLS) in sows is when fertility performance is lower in the second parity than in the first parity. The causes of SLS have been associated with lactation weight loss, premature first insemination, short lactation length, short weaning to insemination interval, season, and farm of farrowing. There is little known about the genetic background of SLS or if it is a real biological problem or just a statistical issue. Thus, we aimed to evaluate risk factors, investigate genetic background of SLS, and estimate the probability of SLS existing due to the statistical properties of the trait. The records of 246 799 litters (total number born, TNB) from 46 218 Large White sows were used. A total of 15 398 sows had SLS. Two traits were defined: first a binominal trait if a sow had SLS or not (biSLS) and second a continuous trait (Range) created by subtracting the total number of piglets born in the first parity (TNB1) from the piglets born in the second parity (TNB2). Lactation length, farm, and season of the farrowing had significant effects on SLS traits when tested as fixed effects in the genetic model. These effects are farm management-related factors. The age at first insemination and weaning to insemination interval were significant only for other reproduction traits (e.g., TNB1, TNB2, litter weight in parity 1 and 2). The heritability of biSLS was 0.05 (on observed scale), whereas heritability of Range was 0.03. To verify the existence of SLS data with records of 50 000 sows and 9 parities was simulated. The simulations showed that the average expected frequency of SLS across all the parities was 0.49 (±0.05) while the observed frequency in the actual data was 0.46 (±0.04). We compared this to SLS frequencies in 67 farms and only 2 farms had more piglets born in the first parity compared to the second. Therefore, on the individual sow level SLS is likely due to statistical properties of the trait, whereas on the farm level SLS is likely due to farm management. Thus, SLS should not be considered an abnormality nor a syndrome if on average the herd litter size in parity 2 is larger than in parity 1.

Genetics and genomics of uniformity and resilience in livestock and aquaculture species: A review.

Genetic control of residual variance offers opportunities to increase uniformity and resilience of livestock and aquaculture species. Improving uniformity and resilience of animals will improve health and welfare of animals and lead to more homogenous products. Our aims in this review were to summarize the current models and methods to study genetic control of residual variance, genetic parameters and genomic results for residual variance and discuss future research directions. Typically, the genetic coefficient of variation is high (median = 0.27; range 0-0.86) and the heritability of residual variance is low (median = 0.01; range 0-0.10). Higher heritabilities can be achieved when increasing the number of records per animal. Divergent selection experiments have supported the feasibility of selecting for high or low residual variance. Genomic studies have revealed associations in regions related to stress, including those from the heat shock protein family. Although the number of studies is growing, genetic control of residual variance is still poorly understood, but big data and genomics offer great opportunities.

The Impact of Genomic and Traditional Selection on the Contribution of Mutational Variance to Long-Term Selection Response and Genetic Variance.

De novo mutations (DNM) create new genetic variance and are an important driver for long-term selection response. We hypothesized that genomic selection exploits mutational variance less than traditional selection methods such as mass selection or selection on pedigree-based breeding values, because DNM in selection candidates are not captured when the selection candidates' own phenotype is not used in genomic selection, DNM are not on SNP chips and DNM are not in linkage disequilibrium with the SNP on the chip. We tested this hypothesis with Monte Carlo simulation. From whole-genome sequence data, a subset of ∼300,000 variants was used that served as putative markers, quantitative trait loci or DNM. We simulated 20 generations with truncation selection based on breeding values from genomic best linear unbiased prediction without (GBLUP_no_OP) or with own phenotype (GBLUP_OP), pedigree-based BLUP without (BLUP_no_OP) or with own phenotype (BLUP_OP), or directly on phenotype. GBLUP_OP was the best strategy in exploiting mutational variance, while GBLUP_no_OP and BLUP_no_OP were the worst in exploiting mutational variance. The crucial element is that GBLUP_no_OP and BLUP_no_OP puts no selection pressure on DNM in selection candidates. Genetic variance decreased faster with GBLUP_no_OP and GBLUP_OP than with BLUP_no_OP, BLUP_OP or mass selection. The distribution of mutational effects, mutational variance, number of DNM per individual and nonadditivity had a large impact on mutational selection response and mutational genetic variance, but not on ranking of selection strategies. We advocate that more sustainable genomic selection strategies are required to optimize long-term selection response and to maintain genetic diversity.

Selecting for changes in average "parity curve" pattern of litter size in Large White pigs.

This study aimed to analyse genetic background of variation in reproductive performance between parities of a sow and to investigate selection strategies to change the "parity curve". Total number born (TNB) recorded in Large White sows was provided by Topigs Norsvin. Analysis with basic (BM) and random regression (RRM) models was done in ASReml 4.1. The BM included only a fixed "parity curve", while RRM included 3rd order polynomials for additive genetic and permanent sow effects. Parameters from RRM were used in simulations in SelAction 2.1. Based on Akaike information criterion, RRM was a better model for TNB data. Genetic variance and heritability estimates of TNB from BM and RRM were increasing with parity from parity 2. Genetically, parity 1 is the most different from parities 7 to 10, whereas most similar to parities 2 and 3. This indicates presence of genetic variation to change the "parity curve". Based on simulations, the selection to increase litter size in parity 1 only increases TNB in all parities, but does not change the observed shape of "parity curve", whereas selection for increased TNB in parity 1 and reduced TNB in parity 5 decreases differences between parities, but also reduces overall TNB in all parities. Changing the "parity curve" will be difficult as the genetic and phenotypic relationships between the parities are hard to overcome even when selecting for one parity.

Genomic regions underlying uniformity of yearling weight in Nellore cattle evaluated under different response variables.

BACKGROUND: In livestock, residual variance has been studied because of the interest to improve uniformity of production. Several studies have provided evidence that residual variance is partially under genetic control; however, few investigations have elucidated genes that control it. The aim of this study was to identify genomic regions associated with within-family residual variance of yearling weight (YW; N = 423) in Nellore bulls with high density SNP data, using different response variables. For this, solutions from double hierarchical generalized linear models (DHGLM) were used to provide the response variables, as follows: a DGHLM assuming non-null genetic correlation between mean and residual variance (rmv ≠ 0) to obtain deregressed EBV for mean (dEBVm) and residual variance (dEBVv); and a DHGLM assuming rmv = 0 to obtain two alternative response variables for residual variance, dEBVv_r0 and log-transformed variance of estimated residuals (ln_[Formula: see text]). RESULTS: The dEBVm and dEBVv were highly correlated, resulting in common regions associated with mean and residual variance of YW. However, higher effects on variance than the mean showed that these regions had effects on the variance beyond scale effects. More independent association results between mean and residual variance were obtained when null rmv was assumed. While 13 and 4 single nucleotide polymorphisms (SNPs) showed a strong association (Bayes Factor > 20) with dEBVv and ln_[Formula: see text], respectively, only suggestive signals were found for dEBVv_r0. All overlapping 1-Mb windows among top 20 between dEBVm and dEBVv were previously associated with growth traits. The potential candidate genes for uniformity are involved in metabolism, stress, inflammatory and immune responses, mineralization, neuronal activity and bone formation. CONCLUSIONS: It is necessary to use a strategy like assuming null rmv to obtain genomic regions associated with uniformity that are not associated with the mean. Genes involved not only in metabolism, but also stress, inflammatory and immune responses, mineralization, neuronal activity and bone formation were the most promising biological candidates for uniformity of YW. Although no clear evidence of using a specific response variable was found, we recommend consider different response variables to study uniformity to increase evidence on candidate regions and biological mechanisms behind it.

Genetic Selection to Enhance Animal Welfare Using Meat Inspection Data from Slaughter Plants.

Animal health and welfare are monitored during meat inspection in many slaughter plants around the world. Carcasses are examined by meat inspectors and remarks are made with respect to different diseases, injuries, and other abnormalities. This is a valuable data resource for disease prevention and enhancing animal welfare, but it is rarely used for this purpose. Records on carcass remarks on 140,375 finisher pigs were analyzed to investigate the possibility of genetic selection to reduce the risk of the most prevalent diseases and indicators of suboptimal animal welfare. As part of this, effects of some non-genetic factors such as differences between farms, sexes, and growth rates were also examined. The most frequent remarks were pneumonia (15.4%), joint disorders (9.8%), pleuritis (4.7%), pericarditis (2.3%), and liver lesions (2.2%). Joint disorders were more frequent in boars than in gilts. There were also significant differences between farms. Pedigree records were available for 142,324 pigs from 14 farms and were used for genetic analysis. Heritability estimates for pneumonia, pleuritis, pericarditis, liver lesions, and joint disorders were 0.10, 0.09, 0.14, 0.24, and 0.17 on the liability scale, respectively, suggesting the existence of substantial genetic variation. This was further confirmed though genome wide associations using deregressed breeding values as phenotypes. The genetic correlations between these remarks and finishing traits were small but mostly negative, suggesting the possibility of enhancing pig health and welfare simultaneously with genetic improvement in finishing traits. A selection index based on the breeding values for these traits and their economic values was developed. This index is used to enhance animal welfare in pig farms.

Heritable environmental variance causes nonlinear relationships between traits: application to birth weight and stillbirth of pigs.

There is recent evidence from laboratory experiments and analysis of livestock populations that not only the phenotype itself, but also its environmental variance, is under genetic control. Little is known about the relationships between the environmental variance of one trait and mean levels of other traits, however. A genetic covariance between these is expected to lead to nonlinearity between them, for example between birth weight and survival of piglets, where animals of extreme weights have lower survival. The objectives were to derive this nonlinear relationship analytically using multiple regression and apply it to data on piglet birth weight and survival. This study provides a framework to study such nonlinear relationships caused by genetic covariance of environmental variance of one trait and the mean of the other. It is shown that positions of phenotypic and genetic optima may differ and that genetic relationships are likely to be more curvilinear than phenotypic relationships, dependent mainly on the environmental correlation between these traits. Genetic correlations may change if the population means change relative to the optimal phenotypes. Data of piglet birth weight and survival show that the presence of nonlinearity can be partly explained by the genetic covariance between environmental variance of birth weight and survival. The framework developed can be used to assess effects of artificial and natural selection on means and variances of traits and the statistical method presented can be used to estimate trade-offs between environmental variance of one trait and mean levels of others.

Strategic test-day recording regimes to estimate lactation yield in tropical dairy animals.

BACKGROUND: In developing dairy sectors, genetic improvement programs have limited resources and recording of herds is minimal. This study evaluated different methods to estimate lactation yield and sampling schedules with fewer test-day records per lactation to determine recording regimes that (1) estimate lactation yield with a minimal impact on the accuracy of selection and (2) optimise the available resources. METHODS: Using Sahiwal cattle as a tropical dairy breed example, weekly milk records from 464 cows were used in a simulation study to generate different shaped lactation curves. The daily milk yields from these simulated lactation curves were subset to equally spaced (weekly, monthly and quarterly) and unequally spaced (with four, five or six records per lactation) test-day intervals. Lactation yield estimates were calculated from these subsets using two methods: the test-interval method and Wood's (Nature 216:164-165, 1967) lactation curve model. Using the resulting lactation yields, breeding values were predicted and comparisons were made between the sampling regimes and estimation methods. RESULTS: The results show that, based on the mean square error of prediction, use of Wood's lactation curve model to estimate total yield was more accurate than use of the test-interval method. However, the differences in the ranking of animals were small, i.e. a 1 to 5% difference in accuracy. Comparisons between the different test-day sampling regimes showed that, with the same number of records per lactation (for example, quarterly and four test-days), strategically timed test-days can result in more accurate estimates of lactation yield than test-days at equal intervals. CONCLUSIONS: An important outcome of these results is that combining Wood's model for lactation yield estimation and as few as four, five or six strategically placed test-day records can produce estimates of lactation yield that are comparable with estimates based on monthly test-day records using the test-interval method. Furthermore, calculations show that although using fewer test-days results in a decrease in the accuracy of selection, it does provide an opportunity to progeny-test more sires. Thus, using strategically timed test-days and Wood's model to estimate lactation yield, can lead to a more efficient use of the allocated resources.

Identification of proteomic biomarkers in M. Longissimus dorsi as potential predictors of pork quality.

Meat quality traits have low heritability and large environmental influences. To predict, improve and manage meat quality, proteomic biomarkers are superior to genetic markers. The objectives of this research were (1) to find associations between proteome profiles of longissimus muscle at slaughter and meat quality accuracies of prediction of traits ranged from 20 up to 80%. Differentially expressed proteins related to drip loss and ultimate pH were identified by NanoLC-FTMSMS. The proteins highlight biological mechanisms that may explain how these traits develop biologically and how they are related to each other.

Gene expression patterns in four brain areas associate with quantitative measure of estrous behavior in dairy cows.

BACKGROUND: The decline noticed in several fertility traits of dairy cattle over the past few decades is of major concern. Understanding of the genomic factors underlying fertility, which could have potential applications to improve fertility, is very limited. Here, we aimed to identify and study those genes that associated with a key fertility trait namely estrous behavior, among genes expressed in four bovine brain areas (hippocampus, amygdala, dorsal hypothalamus and ventral hypothalamus), either at the start of estrous cycle, or at mid cycle, or regardless of the phase of cycle. RESULTS: An average heat score was calculated for each of 28 primiparous cows in which estrous behavior was recorded for at least two consecutive estrous cycles starting from 30 days post-partum. Gene expression was then measured in brain tissue samples collected from these cows, 14 of which were sacrificed at the start of estrus and 14 around mid cycle. For each brain area, gene expression was modeled as a function of the orthogonally transformed average heat score values using a Bayesian hierarchical mixed model. Genes whose expression patterns showed significant linear or quadratic relationships with heat scores were identified. These included genes expected to be related to estrous behavior as they influence states like socio-sexual behavior, anxiety, stress and feeding motivation (OXT, AVP, POMC, MCHR1), but also genes whose association with estrous behavior is novel and warrants further investigation. CONCLUSIONS: Several genes were identified whose expression levels in the bovine brain associated with the level of expression of estrous behavior. The genes OXT and AVP play major roles in regulating estrous behavior in dairy cows. Genes related to neurotransmission and neuronal plasticity are also involved in estrous regulation, with several genes and processes expressed in mid-cycle probably contributing to proper expression of estrous behavior in the next estrus. Studying these genes and the processes they control improves our understanding of the genomic regulation of estrous behavior expression.

Genetic heterogeneity of residual variance - estimation of variance components using double hierarchical generalized linear models.

BACKGROUND: The sensitivity to microenvironmental changes varies among animals and may be under genetic control. It is essential to take this element into account when aiming at breeding robust farm animals. Here, linear mixed models with genetic effects in the residual variance part of the model can be used. Such models have previously been fitted using EM and MCMC algorithms. RESULTS: We propose the use of double hierarchical generalized linear models (DHGLM), where the squared residuals are assumed to be gamma distributed and the residual variance is fitted using a generalized linear model. The algorithm iterates between two sets of mixed model equations, one on the level of observations and one on the level of variances. The method was validated using simulations and also by re-analyzing a data set on pig litter size that was previously analyzed using a Bayesian approach. The pig litter size data contained 10,060 records from 4,149 sows. The DHGLM was implemented using the ASReml software and the algorithm converged within three minutes on a Linux server. The estimates were similar to those previously obtained using Bayesian methodology, especially the variance components in the residual variance part of the model. CONCLUSIONS: We have shown that variance components in the residual variance part of a linear mixed model can be estimated using a DHGLM approach. The method enables analyses of animal models with large numbers of observations. An important future development of the DHGLM methodology is to include the genetic correlation between the random effects in the mean and residual variance parts of the model as a parameter of the DHGLM.

Fear of movement/(re)injury in chronic low back pain: education or exposure in vivo as mediator to fear reduction?

Clinical research of graded exposure in vivo with behavioral experiments in patients with chronic low back pain who reported fear of movement/(re)injury shows abrupt changes in self-reported pain-related fears and cognitions. The abrupt changes are more characteristics of insight learning rather than the usual gradual progression of trial and error learning. The educational session at the start of the exposure might have contributed to this insight. The current study examines the contribution of education and graded exposure versus graded activity in the reduction of pain-related fear and associated disability and physical activity. Six consecutive patients with chronic low back pain who reported substantial fear of movement/(re)injury were included in the study. After a no-treatment baseline measurement period, all the patients received a single educational session, followed again by a no-treatment period. Patients were then randomly assigned to either a graded exposure with behavioral experiments or an operant graded activity program. A diary was used to assess daily changes in pain intensity, pain-related fear, pain catastrophizing, and activity goal achievement. Standardized questionnaires of pain-related fear, pain vigilance, pain intensity, and pain disability were administered before and after each intervention and at the 6-month follow-up. An activity monitor was carried at baseline, during the interventions, and 1 week at 6-month follow-up. Randomization tests of the daily measures showed that improvements in pain-related fear and catastrophizing occurred after the education was introduced. The results also showed a further improvement when exposure in vivo followed the no-treatment period after the education and not during the operant graded activity program. Performance of relevant daily activities, however, were not affected by the educational session and improved significantly only in the exposure in vivo condition. All improvements remained at half-year follow-up only in patients receiving the exposure in vivo. These patients also reported a significant decrease in pain intensity at follow-up.