HIERARCHICAL BAYESIAN METHODS TO MODEL HETEROGENEITY IN COW- AND HERD-LEVEL RELATIONSHIPS BETWEEN MILK PRODUCTION AND REPRODUCTION IN DAIRY COWS

Two of the most important broad classifications of phenotypes for successful dairy production are milk yield and fertility. The nature of the relationship between milk production and reproductive performance of dairy cows is uncertain due to conflicting results reported in many studies. A common deficiency in many such studies is an underappreciation of the dual dimension of the production-reproduction relationship, as defined by herd (random or u) level and cow (residual or e) level sources of (co)variation. Our overall hypothesis is that the e- and u- level relationships between milk production and reproduction in dairy cows are heterogeneous and depend upon various herd-related and management factors. Our objective is to develop hierarchical Bayesian extensions that capture heterogeneity in the relationships between traits by mixed effects modeling of u level and e level covariances between traits of interest. We specify a bivariate Bayesian model to jointly model two continuous traits and we apply a square-root free Cholesky decomposition to the variance-covariance matrices of the residuals (cow-level) and random effects (herd-level). As a result, the e- and u-level covariances among the traits are reparameterized into unconstrained and easily interpretable e- and u- regression parameters, respectively. These regression parameters specify the cow- and herd-level relationships, respectively, between the traits and can be easily modeled as functions of relevant fixed and random effects, thereby providing a mixed model extension of Pourahmadi’s method. We validate our method using a simulation study and apply it to data on 305-day milk yield and calving interval of Michigan dairy cows

Genotype imputation accuracy in a F2 pig population using high density and low density SNP panels

Background: F2 resource populations have been used extensively to map QTL segregating between pig breeds. A limitation associated with the use of these resource populations for fine mapping of QTL is the reduced number of founding individuals and recombinations of founding haplotypes occurring in the population. These limitations, however, become advantageous when attempting to impute unobserved genotypes using within family segregation information. A trade-off would be to re-type F2 populations using high density SNP panels for founding individuals and low density panels (tagSNP) in F2 individuals followed by imputation. Subsequently a combined meta-analysis of several populations would provide adequate power and resolution for QTL mapping, and could be achieved at relatively low cost. Such a strategy allows the wealth of phenotypic information that has previously been obtained on experimental resource populations to be further mined for QTL identification. In this study we used experimental and simulated high density genotypes (HD-60K) from an F2 cross to estimate imputation accuracy under several genotyping scenarios. Results: Selection of tagSNP using physical distance or linkage disequilibrium information produced similar imputation accuracies. In particular, tagSNP sets averaging 1 SNP every 2.1 Mb (1,200 SNP genome-wide) yielded imputation accuracies (IA) close to 0.97. If instead of using custom panels, the commercially available 9K chip is used in the F2, IA reaches 0.99. In order to attain such high imputation accuracy the F0 and F1 generations should be genotyped at high density. Alternatively, when only the F0 is genotyped at HD, while F1 and F2 are genotyped with a 9K panel, IA drops to 0.90. Conclusions: Combining 60K and 9K panels with imputation in F2 populations is an appealing strategy to re-genotype existing populations at a fraction of the cost.Fil: Gualdron Duarte, Jose Luis. Michigan State University; Estados Unidos. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bates, Ronald O.. Michigan State University; Estados UnidosFil: Ernst, Catherine W.. Michigan State University; Estados UnidosFil: Raney, Nancy E.. Michigan State University; Estados UnidosFil: Cantet, Rodolfo Juan Carlos. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Steibel, Juan P.. Michigan State University; Estados Unido

Differential Gene Expression Segregates Cattle Confirmed Positive for Bovine Tuberculosis from Antemortem Tuberculosis Test-False Positive Cattle Originating from Herds Free of Bovine Tuberculosis

Antemortem tests for bovine tuberculosis (bTB) currently used in the US measure cell-mediated immune responses against Mycobacterium bovis. Postmortem tests for bTB rely on observation of gross and histologic lesions of bTB, followed by bacterial isolation or molecular diagnostics. Cumulative data from the state of Michigan indicates that 98 to 99% of cattle that react positively in antemortem tests are not confirmed positive for bTB at postmortem examination. Understanding the fundamental differences in gene regulation between antemortem test-false positive cattle and cattle that have bTB may allow identification of molecular markers that can be exploited to better separate infected from noninfected cattle. An immunospecific cDNA microarray was used to identify altered gene expression (P ≤ 0.01) of 122 gene features between antemortem test-false positive cattle and bTB-infected cattle following a 4-hour stimulation of whole blood with tuberculin. Further analysis using quantitative real-time PCR assays validated altered expression of 8 genes that had differential power (adj  P ≤ 0.05) to segregate cattle confirmed positive for bovine tuberculosis from antemortem tuberculosis test-false positive cattle originating from herds free of bovine tuberculosis

Estimation of linkage disequilibrium in four US pig breeds

<p>Abstract</p> <p>Background</p> <p>The success of marker assisted selection depends on the amount of linkage disequilibrium (LD) across the genome. To implement marker assisted selection in the swine breeding industry, information about extent and degree of LD is essential. The objective of this study is to estimate LD in four US breeds of pigs (Duroc, Hampshire, Landrace, and Yorkshire) and subsequently calculate persistence of phase among them using a 60 k SNP panel. In addition, we report LD when using only a fraction of the available markers, to estimate persistence of LD over distance.</p> <p>Results</p> <p>Average <it>r²</it>between adjacent SNP across all chromosomes was 0.36 for Landrace, 0.39 for Yorkshire, 0.44 for Hampshire and 0.46 for Duroc. For markers 1 Mb apart, <it>r²</it>ranged from 0.15 for Landrace to 0.20 for Hampshire. Reducing the marker panel to 10% of its original density, average <it>r²</it>ranged between 0.20 for Landrace to 0.25 for Duroc. We also estimated persistence of phase as a measure of prediction reliability of markers in one breed by those in another and found that markers less than 10 kb apart could be predicted with a maximal accuracy of 0.92 for Landrace with Yorkshire.</p> <p>Conclusions</p> <p>Our estimates of LD, although in good agreement with previous reports, are more comprehensive and based on a larger panel of markers. Our estimates also confirmed earlier findings reporting higher LD in pigs than in American Holstein cattle, especially at increasing marker distances (> 1 Mb). High average LD (<it>r²</it>> 0.4) between adjacent SNP found in this study is an important precursor for the implementation of marker assisted selection within a livestock species.</p> <p>Results of this study are relevant to the US purebred pig industry and critical for the design of programs of whole genome marker assisted evaluation and selection. In addition, results indicate that a more cost efficient implementation of marker assisted selection using low density panels with genotype imputation, would be feasible for these breeds.</p

Rapid screening for phenotype-genotype associations by linear transformations of genomic evaluations

Background: Currently, association studies are analysed using statistical mixed models, with marker effects estimated by a linear transformation of genomic breeding values. The variances of marker effects are needed when performing the tests of association. However, approaches used to estimate the parameters rely on a prior variance or on a constant estimate of the additive variance. Alternatively, we propose a standardized test of association using the variance of each marker effect, which generally differ among each other. Random breeding values from a mixed model including fixed effects and a genomic covariance matrix are linearly transformed to estimate the marker effects. Results: The standardized test was neither conservative nor liberal with respect to type I error rate (false-positives), compared to a similar test using Predictor Error Variance, a method that was too conservative. Furthermore, genomic predictions are solved efficiently by the procedure, and the p-values are virtually identical to those calculated from tests for one marker effect at a time. Moreover, the standardized test reduces computing time and memory requirements. The following steps are used to locate genome segments displaying strong association. The marker with the highest − log(p-value) in each chromosome is selected, and the segment is expanded one Mb upstream and one Mb downstream of the marker. A genomic matrix is calculated using the information from those markers only, which is used as the variance-covariance of the segment effects in a model that also includes fixed effects and random genomic breeding values. The likelihood ratio is then calculated to test for the effect in every chromosome against a reduced model with fixed effects and genomic breeding values. In a case study with pigs, a significant segment from chromosome 6 explained 11% of total genetic variance. Conclusions: The standardized test of marker effects using their own variance helps in detecting specific genomic regions involved in the additive variance, and in reducing false positives. Moreover, genome scanning of candidate segments can be used in meta-analyses of genome-wide association studies, as it enables the detection of specific genome regions that affect an economically relevant trait when using multiple populations.Fil: Gualdron Duarte, Jose Luis. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cantet, Rodolfo Juan Carlos. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bates, Ronald O.. Michigan State University; Estados UnidosFil: Ernst, Catherine W.. Michigan State University; Estados UnidosFil: Raney, Nancy E.. Michigan State University; Estados UnidosFil: Steibel, Juan P.. Michigan State University; Estados Unido

Analysis of social interactions in group-housed animals using dyadic linear models

Understanding factors affecting social interactions among animals is important for applied animal behavior research. Thus, there is a need to elicit statistical models to analyze data collected from pairwise behavioral interactions. In this study, we propose treating social interaction data as dyadic observations and propose a statistical model for their analysis. We performed posterior predictive checks of the model through different validation strategies: stratified 5-fold random cross-validation, block-by-social-group cross-validation, and block-by-focal-animals validation. The proposed model was applied to a pig behavior dataset collected from 797 growing pigs freshly remixed into 59 social groups that resulted in 10,032 records of directional dyadic interactions. The response variable was the duration in seconds that each animal spent delivering attacks on another group mate. Generalized linear mixed models were fitted. Fixed effects included sex, individual weight, prior nursery mate experience, and prior littermate experience of the two pigs in the dyad. Random effects included aggression giver, aggression receiver, dyad, and social group. A Bayesian framework was utilized for parameter estimation and posterior predictive model checking. Prior nursery mate experience was the only significant fixed effect. In addition, a weak but significant correlation between the random giver effect and the random receiver effect was obtained when analyzing the attacking duration. The predictive performance of the model varied depending on the validation strategy, with substantially lower performance from the block-by-social-group strategy than other validation strategies. Collectively, this paper demonstrates a statistical model to analyze interactive animal behaviors, particularly dyadic interactions

Identification of Carcass and Meat Quality QTL in an F2 Duroc × Pietrain Pig Resource Population Using Different Least-Squares Analysis Models

A three-generation resource population was constructed by crossing pigs from the Duroc and Pietrain breeds. In this study, 954 F2 animals were used to identify quantitative trait loci (QTL) affecting carcass and meat quality traits. Based on results of the first scan analyzed with a line-cross (LC) model using 124 microsatellite markers and 510 F2 animals, 9 chromosomes were selected for genotyping of additional markers. Twenty additional markers were genotyped for 954 F2 animals and 20 markers used in the first scan were genotyped for 444 additional F2 animals. Three different Mendelian models using least-squares for QTL analysis were applied for the second scan: a LC model, a half-sib (HS) model, and a combined LC and HS model. Significance thresholds were determined by false discovery rate (FDR). In total, 50 QTL using the LC model, 38 QTL using the HS model, and 3 additional QTL using the combined LC and HS model were identified (q < 0.05). The LC and HS models revealed strong evidence for QTL regions on SSC6 for carcass traits (e.g., 10th-rib backfat; q < 0.0001) and on SSC15 for meat quality traits (e.g., tenderness, color, pH; q < 0.01), respectively. QTL for pH (SSC3), dressing percent (SSC7), marbling score and moisture percent (SSC12), CIE a* (SSC16), and carcass length and spareribs weight (SSC18) were also significant (q < 0.01). Additional marker and animal genotypes increased the statistical power for QTL detection, and applying different analysis models allowed confirmation of QTL and detection of new QTL

Application of alternative models to identify QTL for growth traits in an F2 Duroc x Pietrain pig resource population

<p>Abstract</p> <p>Background</p> <p>A variety of analysis approaches have been applied to detect quantitative trait loci (QTL) in experimental populations. The initial genome scan of our Duroc x Pietrain F₂resource population included 510 F₂animals genotyped with 124 microsatellite markers and analyzed using a line-cross model. For the second scan, 20 additional markers on 9 chromosomes were genotyped for 954 F₂animals and 20 markers used in the first scan were genotyped for 444 additional F₂animals. Three least-squares Mendelian models for QTL analysis were applied for the second scan: a line-cross model, a half-sib model, and a combined line-cross and half-sib model.</p> <p>Results</p> <p>In total, 26 QTL using the line-cross model, 12 QTL using the half-sib model and 3 additional QTL using the combined line-cross and half-sib model were detected for growth traits with a 5% false discovery rate (FDR) significance level. In the line-cross analysis, highly significant QTL for fat deposition at 10-, 13-, 16-, 19-, and 22-wk of age were detected on SSC6. In the half-sib analysis, a QTL for loin muscle area at 19-wk of age was detected on SSC7 and QTL for 10th-rib backfat at 19- and 22-wk of age were detected on SSC15.</p> <p>Conclusions</p> <p>Additional markers and animals contributed to reduce the confidence intervals and increase the test statistics for QTL detection. Different models allowed detection of new QTL which indicated differing frequencies for alternative alleles in parental breeds.</p

Reassessing Design and Analysis of two-Colour Microarray Experiments Using Mixed Effects Models

Gene expression microarray studies have led to interesting experimental design and statistical analysis challenges. The comparison of expression profiles across populations is one of the most common objectives of microarray experiments. In this manuscript we review some issues regarding design and statistical analysis for two-colour microarray platforms using mixed linear models, with special attention directed towards the different hierarchical levels of replication and the consequent effect on the use of appropriate error terms for comparing experimental groups. We examine the traditional analysis of variance (ANOVA) models proposed for microarray data and their extensions to hierarchically replicated experiments. In addition, we discuss a mixed model methodology for power and efficiency calculations of different microarray experimental designs

Meta-analysis of genome-wide association from genomic prediction models

Genome-wide association (GWA) studies based on GBLUP models are a common practice in animal breeding. However, effect sizes of GWA tests are small, requiring larger sample sizes to enhance power of detection of rare variants. Because of difficulties in increasing sample size in animal populations, one alternative is to implement a meta-analysis (MA), combining information and results from independent GWA studies. Although this methodology has been used widely in human genetics, implementation in animal breeding has been limited. Thus, we present methods to implement a MA of GWA, describing the proper approach to compute weights derived from multiple genomic evaluations based on animal-centric GBLUP models. Application to real datasets shows that MA increases power of detection of associations in comparison with population-level GWA, allowing for population structure and heterogeneity of variance components across populations to be accounted for. Another advantage of MA is that it does not require access to genotype data that is required for a joint analysis. Scripts related to the implementation of this approach, which consider the strength of association as well as the sign, are distributed and thus account for heterogeneity in association phase between QTL and SNPs. Thus, MA of GWA is an attractive alternative to summarizing results from multiple genomic studies, avoiding restrictions with genotype data sharing, definition of fixed effects and different scales of measurement of evaluated traits.Fil: Bernal Rubio, Yeni Liliana. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentina. Michigan State University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gualdron Duarte, Jose Luis. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bates, R. O.. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; ArgentinaFil: Ernst, C. W.. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; ArgentinaFil: Nonneman, D.. United States Department of Agriculture. Agricultural Research Service; Estados UnidosFil: Rohrer, G. A.. United States Department of Agriculture. Agricultural Research Service; Estados UnidosFil: King, A.. United States Department of Agriculture. Agricultural Research Service; Estados UnidosFil: Shackelford, S. D.. United States Department of Agriculture. Agricultural Research Service; Estados UnidosFil: Wheeler, T. L.. United States Department of Agriculture. Agricultural Research Service; Estados UnidosFil: Cantet, Rodolfo Juan Carlos. Michigan State University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Steibel, J. P.. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentina. Michigan State University; Estados Unido