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The welfare of calves is important to both farmers and consumers. Practices that increase the proportion of calves born alive and enable them to thrive through to weaning contribute to improved sustainability. Stillbirths (SB) are calvings where the calf dies at birth or within 24 h after birth. Preweaning mortality (PWM) refers to calves that die after the first day of life but before weaning based on termination data. Both SB and PWM are binary traits characterized by low heritability. Data collection for these traits is incomplete, compared with traits such as milk yield in cows. Despite these challenges, genetic variation can be measured and used to produce breeding tools, such as EBVs, to reduce calf mortality over time. The aim of this study was to compare the performance of various linear models to predict SB and PWM traits in Holstein and Jersey cattle and evaluate their applicability for industry-wide use in the Australian dairy industry. Calving records from around 2.25 million Holstein and Jersey dams were obtained from DataGene's Central Data Repository from the year 2000 onward, to calculate genetic parameters. About 7% of calves were recorded as SB in the period from 2000 to 2021 (n = 1.48 million calvings). The prevalence of PWM was much lower than SB during the same period at 2% (n = 0.89 million calves). Genetic parameters were estimated for SB direct, SB maternal, and PWM using bivariate linear models with calving ease (CE) as the second trait in the model. The heritability of these calf traits was low and varied between 1% and 5% depending on the breed, trait, and model. In Holstein cattle, heritabilities were 2% for PWM and SB direct and 1% for SB maternal, whereas in Jersey cattle heritabilities were 5% for PWM, 2% for SB direct, and 1% for SB maternal. The genetic trends for both SB direct and SB maternal in Holstein cattle indicate improvement in both traits, whereas there was no apparent increase or decrease in PWM in the past 2 decades. The coefficient of genetic variation for SB direct and PWM was between 11.7% and 23.0% in Holstein and Jersey cattle, demonstrating considerable genetic variation in calf survival traits as a first step to using genetic selection to increase the proportion of calves born alive and calves weaned. A focus on improved calf and calving recording practices is expected to increase the reliability of genetic predictions.
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Natimorto , Desmame , Animais , Bovinos/genética , Natimorto/veterinária , Natimorto/genética , Feminino , Cruzamento , Austrália , GravidezRESUMO
Fertility in dairy cattle has declined as an unintended consequence of single-trait selection for high milk yield. The unfavorable genetic correlation between milk yield and fertility is now well documented; however, the underlying physiological mechanisms are still uncertain. To understand the relationship between these traits, we developed a method that clusters variants with similar patterns of effects and, after the integration of gene expression data, identifies the genes through which they are likely to act. Biological processes that are enriched in the genes of each cluster were then identified. We identified several clusters with unique patterns of effects. One of the clusters included variants associated with increased milk yield and decreased fertility, where the "archetypal" variant (i.e., the one with the largest effect) was associated with the GC gene, whereas others were associated with TRIM32, LRRK2, and U6-associated snRNA. These genes have been linked to transcription and alternative splicing, suggesting that these processes are likely contributors to the unfavorable relationship between the 2 traits. Another cluster, with archetypal variant near DGAT1 and including variants associated with CDH2, BTRC, SFRP2, ZFHX3, and SLITRK5, appeared to affect milk yield but have little effect on fertility. These genes have been linked to insulin, adipose tissue, and energy metabolism. A third cluster with archetypal variant near ZNF613 and including variants associated with ROBO1, EFNA5, PALLD, GPC6, and PTPRT were associated with fertility but not milk yield. These genes have been linked to GnRH neuronal migration, embryonic development, or ovarian function. The use of archetypal clustering to group variants with similar patterns of effects may assist in identifying the biological processes underlying correlated traits. The method is hypothesis generating and requires experimental confirmation. However, we have uncovered several novel mechanisms potentially affecting milk production and fertility such as GnRH neuronal migration. We anticipate our method to be a starting point for experimental research into novel pathways, which have been previously unexplored within the context of dairy production.
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Fertilidade , Lactação , Leite , Animais , Bovinos/genética , Bovinos/fisiologia , Fertilidade/genética , Leite/metabolismo , Feminino , Lactação/genéticaRESUMO
The longevity of dairy cattle has economic, animal welfare, and health implications and is influenced by the frequency of mortality on the farm and sale for slaughter. In this study cows removed from the herd due to death or slaughter during the lactation were coded 1 and cows that were not terminated were coded 0. Genetic parameters for mortality rates (MR) and slaughter rates (SR) were estimated for Holstein (H) and Jersey (J) breeds by applying both linear (LM) and threshold (TM) sire models using about 1.2 million H and 286,000 J cows. Estimated breeding values (EBV) for MR and SR were predicted using animal models to assess the opportunity for selection and genetic trends. Cow termination data, recorded between 1990 and 2020 on a voluntary basis by Australian dairy farmers, were analyzed. Cow MR has increased from below 1% in the 1990s to 4.1% and 3.6% in recent years in H and J cows, respectively. Most dead cows (â¼36%) left the herd before 120 d of lactation, while cows that were slaughtered left the herd toward the end of the lactation. Using the LM, heritability (h2) estimates for MR were lower (1%) than those for SR (2%-3.5%). When h2 were estimated using a TM, the estimates for both traits varied between 4% and 20%, suggesting that the difference in incidence level is one of the reasons for the difference in the h2 values between MR and SR. Early test-day milk yield (MY) and 305-d MY (305-d MY) have unfavorable genetic correlations (0.32-0.41) with MR in both breeds. The genetic correlations of calving interval with MR were stronger (0.54-0.68) than with SR (0.28-0.45) suggesting that poor fertility can serve as an early indicator of poor cow health that may lead to increased risk of death. High early test-day somatic cell count is genetically associated with increased likelihood of slaughter (0.24-0.46), but not with increased likelihood of death. In H, 305-d protein yield (PY) had the strongest genetic correlation (-0.34 to -0.40) with SR whereas in J, both 305-d PY and fat yield showed high genetic (-0.64 to -0.70) and moderate environmental (-0.35 to -0.37) correlations with SR. The genetic correlation of removal from the herd due to death and slaughter was negative (-0.3) in J and zero in H. Strong selection for improved fertility and survival and less selection emphasis for MY, has led to an improvement in the genetic trend for cow MR in H and the trend in J has stabilized. Although genetic evaluations for cow MR are feasible, the reliabilities of the EBV are low and the level of cow MR in Australia are relatively low compared with similar countries. Therefore, genetic evaluation for survival based on mortality and slaughter data could be sufficient in the current selection circumstances where breeding objectives are broadly defined. Nevertheless, all Australian farmers should be encouraged to continue recording mortality and slaughter data for monitoring of the trends and for future development of genetic evaluations.
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We conducted a retrospective cohort study to validate the efficacy of the Australian multitrait fertility estimated breeding value (EBV). We did this by determining its associations with phenotypic measures of reproductive performance (i.e., submission rate, first service conception rate, and early calving). Our secondary aim was to report the associations between these reproductive outcomes and management and climate-related factors hypothesized to affect fertility. Our study population included 38 pasture-based dairy herds from the northern Victorian irrigation region in Australia. We collected records for 86,974 cows with 219,156 lactations and 438,578 mating events from the date on which managers started herd recording until December 2016, comprising both fertility-related data such as insemination records, calving dates, and pregnancy test results, and systems-related data such as production, herd size, and calving pattern. We also collected hourly data from 2004 to 2017 from the closest available weather station to account for climate-related factors (i.e., temperature humidity index; THI). Multilevel Cox proportional hazard models were used to analyze time-to-event outcomes (days to first service, days to cow calving following the planned herd calving start date), and multilevel logistic regression models for binomial outcomes (conception to first service) in the Holstein-Friesian and Jersey breeds. A 1-unit increase in daughter fertility EBV was associated with a 5.4 and 8.2% increase in the daily hazard of calving in the Holstein-Friesian and Jersey breeds respectively. These are relative increases (i.e., a Holstein-Friesian herd with a 60% 6-wk in-calf rate would see an improvement to 63.2% with a 1-unit increase in herd fertility EBV). Similar results were obtained for submission and conception rate. Associations between 120-d milk yield and reproductive outcome were complicated by interactions with 120-d protein percentage and calving age, depending on the breed and outcome. In general, we found that the reproductive performance of high milk-yielding animals deteriorated faster with age than low milk-yielding animals, and high protein percentage exacerbated the differences between low and high milk-yielding animals. Climate-related factors were also associated with fertility, with a 1-unit increase in maximum THI decreasing first service conception rate by 1.2% for Holstein-Friesians but having no statistically significant association in the Jersey breed. However, THI had a negative association in both breeds on the daily hazard of calving. Our study validates the efficacy of the daughter fertility EBV for improving herd reproductive performance and identifies significant associations between 120-d milk and protein yields and THI on the fertility of Australian dairy cows.
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Lactação , Reprodução , Gravidez , Bovinos , Animais , Feminino , Estudos Retrospectivos , Austrália , Fertilidade , Leite/metabolismo , Indústria de Laticínios/métodosRESUMO
Although selection for increased milk production traits has led to a genetic increase in body weight (BW), the genetic gain in milk production has exceeded the gain in BW, so gross feed efficiency has improved. Nonetheless, greater gains may be possible by directly selecting for a measure of feed efficiency. Australia first introduced Feed Saved (FS) estimated breeding value (EBV) in 2015. Feed Saved combines residual feed intake (RFI) genomic EBV and maintenance requirements calculated from mature BW EBV. The FS EBV was designed to enable the selection of cows for reduced energy requirements with similar milk production. In this study, we used a reference population of 3,711 animals in a multivariate analysis including Australian heifers (AUSh), Australian cows (AUSc), and overseas cows (OVEc) to update the Australian EBV for lifetime RFI (i.e., a breeding value that incorporated RFI in growing and lactating cows) and to recalculate the FS EBV in Australian Holstein bulls (AUSb). The estimates of genomic heritabilities using univariate (only AUSc or AUSh) to trivariate (including the OVEc) analyses were similar. Genomic heritabilities for RFI were estimated as 0.18 for AUSc, 0.27 for OVEc, and 0.36 for AUSh. The genomic correlation for RFI between AUSc and AUSh was 0.47 and that between AUSc and OVEc was 0.94, but these estimates were associated with large standard errors (range: 0.18-0.28). The reliability of lifetime RFI (a component of FS) in the trivariate analysis (i.e., including OVEc) increased from 11% to 20% compared with the 2015 model and was greater, by 12%, than in a bivariate analysis in which the reference population included only AUSc and AUSh. By applying the prediction equation of the 2020 model, the average reliability of the FS EBV in 20,816 AUSb that were born between 2010 and 2020 improved from 33% to 43%. Previous selection strategies-that is, using the predecessor of the Balanced Performance Index (Australian Profit Ranking index) that did not include FS-have resulted in an unfavorable genetic trend in FS. However, this unfavorable trend has stabilized since 2015, when FS was included in the Balanced Performance Index, and is expected to move in a favorable direction with selection on Balanced Performance Index or the Health Weighted Index. Doubling the reference population, particularly by incorporating international data for feed efficiency, has improved the reliability of the FS EBV. This could lead to increased genetic gain for feed efficiency in the Australian industry.
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[This corrects the article DOI: 10.3168/jdsc.2021-0150.].
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Methane is a greenhouse gas of high interest to the dairy industry, with 57% of Australia's dairy emissions attributed to enteric methane. Enteric methane emissions also constitute a loss of approximately 6.5% of ingested energy. Genetic selection offers a unique mitigation strategy to decrease the methane emissions of dairy cattle, while simultaneously improving their energy efficiency. Breeding objectives should focus on improving the overall sustainability of dairy cattle by reducing methane emissions without negatively affecting important economic traits. Common definitions for methane production, methane yield, and methane intensity are widely accepted, but there is not yet consensus for the most appropriate method to calculate residual methane production, as the different methods have not been compared. In this study, we examined 9 definitions of residual methane production. Records of individual cow methane, dry matter intake (DMI), and energy corrected milk (ECM) were obtained from 379 animals and measured over a 5-d period from 12 batches across 5 yr using the SF6 tracer method and an electronic feed recording system, respectively. The 9 methods of calculating residual methane involved genetic and phenotypic regression of methane production on a combination of DMI and ECM corrected for days in milk, parity, and experimental batch using phenotypes or direct genomic values. As direct genomic values (DGV) for DMI are not routinely evaluated in Australia at this time, DGV for FeedSaved, which is derived from DGV for residual feed intake and estimated breeding value for bodyweight, were used. Heritability estimates were calculated using univariate models, and correlations were estimated using bivariate models corrected for the fixed effects of year-batch, days in milk, and lactation number, and fitted using a genomic relationship matrix. Residual methane production candidate traits had low to moderate heritability (0.10 ± 0.09 to 0.21 ± 0.10), with residual methane production corrected for ECM being the highest. All definitions of residual methane were highly correlated phenotypically (>0.87) and genetically (>0.79) with one another and moderately to highly with other methane candidate traits (>0.59), with high standard errors. The results suggest that direct selection for a residual methane production trait would result in indirect, favorable improvement in all other methane traits. The high standard errors highlight the importance of expanding data sets by measuring more animals for their methane emissions and DMI, or through exploration of proxy traits and combining data via international collaboration.
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Bovinos/metabolismo , Metano/metabolismo , Animais , Austrália , Peso Corporal/genética , Bovinos/genética , Indústria de Laticínios , Dieta/veterinária , Feminino , Genoma , Gases de Efeito Estufa , Lactação , Leite , Fenótipo , Gravidez , Seleção ArtificialRESUMO
The objectives of this study were (1) to evaluate the computational feasibility of the multitrait test-day single-step SNP-BLUP (ssSNP-BLUP) model using phenotypic records of genotyped and nongenotyped animals, and (2) to compare accuracies (coefficient of determination; R2) and bias of genomic estimated breeding values (GEBV) and de-regressed proofs as response variables in 3 Australian dairy cattle breeds (i.e., Holstein, Jersey, and Red breeds). Additive genomic random regression coefficients for milk, fat, protein yield and somatic cell score were predicted in the first, second, and third lactation. The predicted coefficients were used to derive 305-d GEBV and were compared with the traditional parent averages obtained from a BLUP model without genomic information. Cow fertility traits were evaluated from the 5-trait repeatability model (i.e., calving interval, days from calving to first service, pregnancy diagnosis, first service nonreturn rate, and lactation length). The de-regressed proofs were only for calving interval. Our results showed that ssSNP-BLUP using multitrait test-day model increased reliability and reduced bias of breeding values of young animals when compared with parent average from traditional BLUP in Australian Holsten, Jersey, and Red breeds. The use of a custom selection of approximately 46,000 SNP (custom XT SNP list) increased the reliability of GEBV compared with the results obtained using the commercial Illumina 50K chip (Illumina, San Diego, CA). The use of the second preconditioner substantially improved the convergence rate of the preconditioned conjugate gradient method, but further work is needed to improve the efficiency of the computation of the Kronecker matrix product by vector. Application of ssSNP-BLUP to multitrait random regression models is computationally feasible.
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Bovinos/genética , Fertilidade/genética , Genoma/genética , Leite/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Animais , Austrália , Cruzamento , Feminino , Genômica , Genótipo , Lactação , Modelos Lineares , Análise de Sequência com Séries de Oligonucleotídeos/veterinária , Fenótipo , Gravidez , Reprodutibilidade dos TestesRESUMO
The aim of this study was to investigate the feasibility of using mid-infrared (MIR) spectroscopy analysis of milk samples to increase the power and precision of genome-wide association studies (GWAS) for milk composition and to better distinguish linked quantitative trait loci (QTL). To achieve this goal, we analyzed phenotypic data of milk composition traits, related MIR spectra, and genotypic data comprising 626,777 SNP on 5,202 Holstein, Jersey, and crossbred cows. We performed a conventional GWAS on protein, lactose, fat, and fatty acid concentrations in milk, a GWAS on individual MIR wavenumbers, and a partial least squares regression (PLS), which is equivalent to a multi-trait GWAS, exploiting MIR data simultaneously to predict SNP genotypes. The PLS detected most of the QTL identified using single-trait GWAS, usually with a higher significance value, as well as previously undetected QTL for milk composition. Each QTL tends to have a different pattern of effects across the MIR spectrum and this explains the increased power. Because SNP tracking different QTL tend to have different patterns of effect, it was possible to distinguish closely linked QTL. Overall, the results of this study suggest that using MIR data through either GWAS or PLS analysis applied to genomic data can provide a powerful tool to distinguish milk composition QTL.
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Bovinos/fisiologia , Estudo de Associação Genômica Ampla/veterinária , Leite/química , Locos de Características Quantitativas/genética , Animais , Bovinos/genética , Ácidos Graxos/análise , Feminino , Genótipo , Glicolipídeos/análise , Glicoproteínas/análise , Raios Infravermelhos , Lactose/análise , Gotículas Lipídicas , Leite/efeitos da radiação , Proteínas do Leite/análise , FenótipoRESUMO
BACKGROUND: Identifying causative mutations or genes through which quantitative trait loci (QTL) act has proven very difficult. Using information such as gene expression may help to identify genes and mutations underlying QTL. Our objective was to identify regions associated both with production traits or fertility and with gene expression, in dairy cattle. We used three different approaches to discover QTL that are also expression QTL (eQTL): 1) estimate the correlation between local genomic estimated breeding values (GEBV) and gene expression, 2) investigate whether the 300 intervals explaining most genetic variance for a trait contain more eQTL than 300 randomly selected intervals, and 3) a colocalisation analysis. Phenotypes and genotypes up to sequence level of 35,775 dairy bulls and cows were used for QTL mapping, and gene expression and genotypes of 131 cows were used to identify eQTL. RESULTS: With all three approaches, we identified some overlap between eQTL and QTL, though the majority of QTL in our dataset did not seem to be eQTL. The most significant associations between QTL and eQTL were found for intervals on chromosome 18, where local GEBV for all traits showed a strong association with the expression of the FUK and DDX19B. Intervals whose local GEBV for a trait correlated highly significantly with the expression of a nearby gene explained only a very small part of the genetic variance for that trait. It is likely that part of these correlations were due to linkage disequilibrium (LD) in the interval. While the 300 intervals explaining most genetic variance explained most of the GEBV variance, they contained only slightly more eQTL than 300 randomly selected intervals that explained a minimal portion of the GEBV variance. Furthermore, some variants showed a high colocalisation probability, but this was only the case for few variants. CONCLUSIONS: Several reasons may have contributed to the low level of overlap between QTL and eQTL detected in our study, including a lack of power in the eQTL study and long-range LD making it difficult to separate QTL and eQTL. Furthermore, it may be that eQTL explain only a small fraction of QTL.
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Bovinos/genética , Bovinos/fisiologia , Indústria de Laticínios , Fertilidade/genética , Locos de Características Quantitativas/genética , Animais , Bovinos/metabolismo , Variação Genética , Estudo de Associação Genômica AmplaRESUMO
Genomic prediction is widely used to select candidates for breeding. Size and composition of the reference population are important factors influencing prediction accuracy. In Holstein dairy cattle, large reference populations are used, but this is difficult to achieve in numerically small breeds and for traits that are not routinely recorded. The prediction accuracy is usually estimated using cross-validation, requiring the full data set. It would be useful to have a method to predict the benefit of multibreed reference populations that does not require the availability of the full data set. Our objective was to study the effect of the size and breed composition of the reference population on the accuracy of genomic prediction using genomic BLUP and Bayes R. We also examined the effect of trait heritability and validation breed on prediction accuracy. Using these empirical results, we investigated the use of a formula to predict the effect of the size and composition of the reference population on the accuracy of genomic prediction. Phenotypes were simulated in a data set containing real genotypes of imputed sequence variants for 22,752 dairy bulls and cows, including Holstein, Jersey, Red Holstein, and Australian Red cattle. Different reference populations were constructed, varying in size and composition, to study within-breed, multibreed, and across-breed prediction. Phenotypes were simulated varying in heritability, number of chromosomes, and number of quantitative trait loci. Genomic prediction was carried out using genomic BLUP and Bayes R. We used either the genomic relationship matrix (GRM) to estimate the number of independent chromosomal segments and subsequently to predict accuracy, or the accuracies obtained from single-breed reference populations to predict the accuracies of larger or multibreed reference populations. Using the GRM overestimated the accuracy; this overestimation was likely due to close relationships among some of the reference animals. Consequently, the GRM could not be used to predict the accuracy of genomic prediction reliably. However, a method using the prediction accuracies obtained by cross-validation using a small, single-breed reference population predicted the accuracy using a multibreed reference population well and slightly overestimated the accuracy for a larger reference population of the same breed, but gave a reasonably close estimate of the accuracy for a multibreed reference population. This method could be useful for making decisions regarding the size and composition of the reference population.
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Bovinos/genética , Animais , Teorema de Bayes , Cruzamento , Bovinos/fisiologia , Feminino , Genômica , Genótipo , Masculino , Modelos Genéticos , Fenótipo , Locos de Características QuantitativasRESUMO
Cost-effective high-density (HD) genotypes of livestock species can be obtained by genotyping a proportion of the population using a HD panel and the remainder using a cheaper low-density panel, and then imputing the missing genotypes that are not directly assayed in the low-density panel. The efficacy of genotype imputation can largely be affected by the structure and history of the specific target population and it should be checked before incorporating imputation in routine genotyping practices. Here, we investigated the efficacy of imputation in crossbred dairy cattle populations of East Africa using 4 different commercial single nucleotide polymorphisms (SNP) panels, 3 reference populations, and 3 imputation algorithms. We found that Minimac and a reference population, which included a mixture of crossbred and ancestral purebred animals, provided the highest imputation accuracy compared with other scenarios of imputation. The accuracies of imputation, measured as the correlation between real and imputed genotypes averaged across SNP, were around 0.76 and 0.94 for 7K and 40K SNP, respectively, when imputed up to a 770K panel. We also presented a method to maximize the imputation accuracy of low-density panels, which relies on the pairwise (co)variances between SNP and the minor allele frequency of SNP. The performance of the developed method was tested in a 5-fold cross-validation process where various densities of SNP were selected using the (co)variance method and also by alternative SNP selection methods and then imputed up to the HD panel. The (co)variance method provided the highest imputation accuracies at almost all marker densities, with accuracies being up to 0.19 higher than the random selection of SNP. The accuracies of imputation from 7K and 40K panels selected using the (co)variance method were around 0.80 and 0.94, respectively. The presented method also achieved higher accuracy of genomic prediction at lower densities of selected SNP. The squared correlation between genomic breeding values estimated using imputed genotypes and those from the real 770K HD panel was 0.95 when the accuracy of imputation was 0.64. The presented method for SNP selection is straightforward in its application and can ensure high accuracies in genotype imputation of crossbred dairy populations in East Africa.
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Bovinos/genética , Genômica , Genótipo , Polimorfismo de Nucleotídeo Único , África Oriental , Animais , Cruzamento , GenomaRESUMO
Genomic prediction is applicable to individuals of different breeds. Empirical results to date, however, show limited benefits in using information on multiple breeds in the context of genomic prediction. We investigated a multitask Bayesian model, presented previously by others, implemented in a Bayesian stochastic search variable selection (BSSVS) model. This model allowed for evidence of quantitative trait loci (QTL) to be accumulated across breeds or for both QTL that segregate across breeds and breed-specific QTL. In both cases, single nucleotide polymorphism effects were estimated with information from a single breed. Other models considered were a single-trait and multitrait genomic residual maximum likelihood (GREML) model, with breeds considered as different traits, and a single-trait BSSVS model. All single-trait models were applied to each of the 2 breeds separately and to the pooled data of both breeds. The data used included a training data set of 6,278 Holstein and 722 Jersey bulls, as well as 374 Jersey validation bulls. All animals had genotypes for 474,773 single nucleotide polymorphisms after editing and phenotypes for milk, fat, and protein yields. Using the same training data, BSSVS consistently outperformed GREML. The multitask BSSVS, however, did not outperform single-trait BSSVS, which used pooled Holstein and Jersey data for training. Thus, the rigorous assumption that the traits are the same in both breeds yielded a slightly better prediction than a model that had to estimate the correlation between the breeds from the data. Adding the Holstein data significantly increased the accuracy of the single-trait GREML and BSSVS in predicting the Jerseys for milk and protein, in line with estimated correlations between the breeds of 0.66 and 0.47 for milk and protein yields, whereas only the BSSVS model significantly improved the accuracy for fat yield with an estimated correlation between breeds of only 0.05. The relatively high genetic correlations for milk and protein yields, and the superiority of the pooling strategy, is likely the result of the observed admixture between both breeds in our data. The Bayesian model was able to detect several QTL in Holsteins, which likely enabled it to outperform GREML. The inability of the multitask Bayesian models to outperform a simple pooling strategy may be explained by the fact that the pooling strategy assumes equal effects in both breeds; furthermore, this assumption may be valid for moderate- to large-sized QTL, which are important for multibreed genomic prediction.
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Bovinos/genética , Animais , Teorema de Bayes , Cruzamento , Bovinos/metabolismo , Feminino , Genoma , Genômica/métodos , Genótipo , Funções Verossimilhança , Masculino , Leite/metabolismo , Modelos Genéticos , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características QuantitativasAssuntos
Cruzamento , Genoma , Gado/genética , Seleção Genética , Animais , Simulação por Computador , Genômica , Genótipo , Modelos Genéticos , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
We compared the outcome of mating programs based on different evaluation models that included nonadditive genetic effects (dominance and heterozygosity) in addition to additive effects. The additive and dominance marker effects and the values of regression on average heterozygosity were estimated using 632,003 single nucleotide polymorphisms from 7,902 and 7,510 Holstein cows with calving interval and production (milk, fat, and protein yields) records, respectively. Expected progeny values were computed based on the estimated genetic effects and genotype probabilities of hypothetical progeny from matings between the available genotyped cows and the top 50 young genomic bulls. An index combining the traits based on their economic values was developed and used to evaluate the performance of different mating scenarios in terms of dollar profit. We observed that mating programs with nonadditive genetic effects performed better than a model with only additive effects. Mating programs with dominance and heterozygosity effects increased milk, fat, and protein yields by up to 38, 1.57, and 1.21 kg, respectively. The inclusion of dominance and heterozygosity effects decreased calving interval by up to 0.70 d compared with random mating. The average reduction in progeny inbreeding by the inclusion of nonadditive genetic effects in matings compared with random mating was between 0.25 to 1.57 and 0.64 to 1.57 percentage points for calving interval and production traits, respectively. The reduction in inbreeding was accompanied by an average of A$8.42 (Australian dollars) more profit per mating for a model with additive, dominance, and heterozygosity effects compared with random mating. Mate allocations that benefit from nonadditive genetic effects can improve progeny performance only in the generation where it is being implemented, and the gain from specific combining abilities cannot be accumulated over generations. Continuous updating of genomic predictions and mate allocation programs are required to benefit from nonadditive genetic effects in the long term.
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Cruzamento , Fazendas , Modelos Genéticos , Animais , Austrália , Bovinos , Feminino , Endogamia , Masculino , Leite/metabolismoRESUMO
Improving feed efficiency in cattle is important because it increases profitability by reducing costs, and it also shrinks the environmental footprint of cattle production by decreasing manure and greenhouse gas emissions. Residual feed intake (RFI) is 1 measurement of feed efficiency and is the difference between actual and predicted feed intake. Residual feed intake is a complex trait with moderate heritability, but the genes and biological processes associated with its variation still need to be found. We explored the variation in expression of genes using RNA sequencing to find genes whose expression was associated with RFI and then investigated the pathways that are enriched for these genes. In this study, we used samples from growing Angus bulls (muscle and liver tissues) and lactating Holstein cows (liver tissue and white blood cells) divergently selected for low and high RFI. Within each breed-tissue combination, the correlation between the expression of genes and RFI phenotypes, as well as GEBV, was calculated to determine the genes whose expression was correlated with RFI. There were 16,039 genes expressed in more than 25% of samples in 1 or more tissues. The expression of 6,143 genes was significantly associated with RFI phenotypes, and expression of 2,343 genes was significantly associated with GEBV for RFI ( < 0.05) in at least 1 tissue. The genes whose expression was correlated with RFI phenotype (or GEBV) within each breed-tissue combination were enriched for 158 (78) biological processes (Fisher Exact Statistics for gene-enrichment analysis, EASE score < 0.1) and associated with 13 (13) Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways ( < 0.05 and fold enrichment > 2). These biological processes were related to regulation of transcription, translation, energy generation, cell cycling, apoptosis, and proteolysis. However, the direction of the correlation between RFI and gene expression in some cases reversed between tissues. For instance, low levels of proteolysis in muscle were associated with high efficiency in growing bulls, but high levels of proteolysis in white blood cells were associated with efficiency of milk production in lactating cows.
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Bovinos/genética , Ingestão de Alimentos , Fertilidade , Genoma/genética , Ração Animal/análise , Animais , Teorema de Bayes , Cruzamento , Bovinos/sangue , Bovinos/fisiologia , Feminino , Lactação , Fígado/metabolismo , Masculino , Músculos , Fenótipo , Análise de Sequência de RNA/veterináriaRESUMO
BACKGROUND: Polymorphisms underlying complex traits often explain a small part (less than 1 %) of the phenotypic variance (σ2P). This makes identification of mutations underling complex traits difficult and usually only a subset of large-effect loci are identified. One approach to identify more loci is to increase sample size of experiments but here we propose an alternative. The aim of this paper is to use secondary phenotypes for genetically simple traits during the QTL discovery phase for complex traits. We demonstrate this approach in a dairy cattle data set where the complex traits were milk production phenotypes (fat, milk and protein yield; fat and protein percentage in milk) measured on thousands of individuals while secondary (potentially genetically simpler) traits are detailed milk composition traits (measurements of individual protein abundance, mineral and sugar concentrations; and gene expression). RESULTS: Quantitative trait loci (QTL) were identified using 11,527 Holstein cattle with milk production records and up to 444 cows with milk composition traits. There were eight regions that contained QTL for both milk production and a composition trait, including four novel regions. One region on BTAU1 affected both milk yield and phosphorous concentration in milk. The QTL interval included the gene SLC37A1, a phosphorous antiporter. The most significant imputed sequence variants in this region explained 0.001 σ2P for milk yield, and 0.11 σ2P for phosphorus concentration. Since the polymorphisms were non-coding, association mapping for SLC37A1 gene expression was performed using high depth mammary RNAseq data from a separate group of 371 lactating cows. This confirmed a strong eQTL for SLC37A1, with peak association at the same imputed sequence variants that were most significant for phosphorus concentration. Fitting any of these variants as covariables in the association analysis removed the QTL signal for milk production traits. Plausible causative mutations in the casein complex region were also identified using a similar strategy. CONCLUSIONS: Milk production traits in dairy cows are typical complex traits where polymorphisms explain only a small portion of the phenotypic variance. However, here we show that these mutations can have larger effects on secondary traits, such as concentrations of minerals, proteins and sugars in the milk, and expression levels of genes in mammary tissue. These larger effects were used to successfully map variants for milk production traits. Genetically simple traits also provide a direct biological link between possible causal mutations and the effect of these mutations on milk production.
Assuntos
Estudos de Associação Genética , Variação Genética , Fenótipo , Característica Quantitativa Herdável , Animais , Bovinos , Expressão Gênica , Leite , Locos de Características Quantitativas , Análise de Sequência de DNARESUMO
Complex or quantitative traits are important in medicine, agriculture and evolution, yet, until recently, few of the polymorphisms that cause variation in these traits were known. Genome-wide association studies (GWAS), based on the ability to assay thousands of single nucleotide polymorphisms (SNPs), have revolutionized our understanding of the genetics of complex traits. We advocate the analysis of GWAS data by a statistical method that fits all SNP effects simultaneously, assuming that these effects are drawn from a prior distribution. We illustrate how this method can be used to predict future phenotypes, to map and identify the causal mutations, and to study the genetic architecture of complex traits. The genetic architecture of complex traits is even more complex than previously thought: in almost every trait studied there are thousands of polymorphisms that explain genetic variation. Methods of predicting future phenotypes, collectively known as genomic selection or genomic prediction, have been widely adopted in livestock and crop breeding, leading to increased rates of genetic improvement.
Assuntos
Estudos de Associação Genética , Modelos Genéticos , Fenótipo , Polimorfismo de Nucleotídeo Único , Cruzamento , Genômica , Modelos Estatísticos , Locos de Características QuantitativasRESUMO
BACKGROUND: We adapted Bayesian statistical learning strategies to the prognosis field to investigate if genome-wide common SNP improve the prediction ability of clinico-pathological prognosticators and applied it to non-muscle invasive bladder cancer (NMIBC) patients. METHODS: Adapted Bayesian sequential threshold models in combination with LASSO were applied to consider the time-to-event and the censoring nature of data. We studied 822 NMIBC patients followed-up >10 years. The study outcomes were time-to-first-recurrence and time-to-progression. The predictive ability of the models including up to 171,304 SNP and/or 6 clinico-pathological prognosticators was evaluated using AUC-ROC and determination coefficient. RESULTS: Clinico-pathological prognosticators explained a larger proportion of the time-to-first-recurrence (3.1 %) and time-to-progression (5.4 %) phenotypic variances than SNPs (1 and 0.01 %, respectively). Adding SNPs to the clinico-pathological-parameters model slightly improved the prediction of time-to-first-recurrence (up to 4 %). The prediction of time-to-progression using both clinico-pathological prognosticators and SNP did not improve. Heritability (h (2)) of both outcomes was <1 % in NMIBC. CONCLUSIONS: We adapted a Bayesian statistical learning method to deal with a large number of parameters in prognostic studies. Common SNPs showed a limited role in predicting NMIBC outcomes yielding a very low heritability for both outcomes. We report for the first time a heritability estimate for a disease outcome. Our method can be extended to other disease models.
Assuntos
Teorema de Bayes , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/genética , Progressão da Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/genéticaRESUMO
BACKGROUND: Dense SNP genotypes are often combined with complex trait phenotypes to map causal variants, study genetic architecture and provide genomic predictions for individuals with genotypes but no phenotype. A single method of analysis that jointly fits all genotypes in a Bayesian mixture model (BayesR) has been shown to competitively address all 3 purposes simultaneously. However, BayesR and other similar methods ignore prior biological knowledge and assume all genotypes are equally likely to affect the trait. While this assumption is reasonable for SNP array genotypes, it is less sensible if genotypes are whole-genome sequence variants which should include causal variants. RESULTS: We introduce a new method (BayesRC) based on BayesR that incorporates prior biological information in the analysis by defining classes of variants likely to be enriched for causal mutations. The information can be derived from a range of sources, including variant annotation, candidate gene lists and known causal variants. This information is then incorporated objectively in the analysis based on evidence of enrichment in the data. We demonstrate the increased power of BayesRC compared to BayesR using real dairy cattle genotypes with simulated phenotypes. The genotypes were imputed whole-genome sequence variants in coding regions combined with dense SNP markers. BayesRC increased the power to detect causal variants and increased the accuracy of genomic prediction. The relative improvement for genomic prediction was most apparent in validation populations that were not closely related to the reference population. We also applied BayesRC to real milk production phenotypes in dairy cattle using independent biological priors from gene expression analyses. Although current biological knowledge of which genes and variants affect milk production is still very incomplete, our results suggest that the new BayesRC method was equal to or more powerful than BayesR for detecting candidate causal variants and for genomic prediction of milk traits. CONCLUSIONS: BayesRC provides a novel and flexible approach to simultaneously improving the accuracy of QTL discovery and genomic prediction by taking advantage of prior biological knowledge. Approaches such as BayesRC will become increasing useful as biological knowledge accumulates regarding functional regions of the genome for a range of traits and species.