Heritability estimates and predictive ability for pig meat quality traits using identity-by-state and identity-by-descent relationships in an F2 population.

Genomic relationships can be computed with dense genome-wide genotypes through different methods, either based on identity-by-state (IBS) or identity-by-descent (IBD). The latter has been shown to increase the accuracy of both estimated relationships and predicted breeding values. However, it is not clear whether an IBD approach would achieve greater heritability ( h 2 ) and predictive ability ( r ̂ y , y ̂ ) than its IBS counterpart for data with low-depth pedigrees. Here, we compare both approaches in terms of the estimated of h 2 and r ̂ y , y ̂ , using data on meat quality and carcass traits recorded in experimental crossbred pigs, with a pedigree constrained to only three generations. Three animal models were fitted which differed on the relationship matrix: an IBS model ( G IBS ), an IBD (defined within the known pedigree) model ( G IBD ), and a pedigree model ( A 22 ). In 9 of 20 traits, the range of increase for the estimates of σ u 2 and h 2 was 1.2-2.9 times greater with G IBS and G IBD models than with A 22 . Whereas for all traits, both parameters were similar between genomic models. The r ̂ y , y ̂ of the genomic models was higher compared to A 22 . A scarce increment in r ̂ y , y ̂ was found with G IBS when compared to G IBD , most likely due to the former recovering sizeable relationships among founder F0 animals.

Causal inference for the covariance between breeding values under identity disequilibrium.

BACKGROUND: The covariance matrix of breeding values is at the heart of prediction methods. Prediction of breeding values can be formulated using either an "observed" or a theoretical covariance matrix, and a major argument for choosing one or the other is the reduction of the computational burden for inverting such a matrix. In this regard, covariance matrices that are derived from Markov causal models possess properties that deliver sparse inverses. RESULTS: By using causal Markov models, we express the breeding value of an individual as a linear regression on ancestral breeding values, plus a residual term, which we call residual breeding value (RBV). The latter is a noise term that accounts for the uncertainty in prediction due to lack of fit of the linear regression. A notable property of these models is the parental Markov condition, through which the multivariate distribution of breeding values is uniquely determined by the distribution of the mutually independent RBV. Animal breeders have long been relying on a causal Markov model, while using the additive relationship matrix as the covariance matrix structure of breeding values, which is calculated assuming gametic equilibrium. However, additional covariances among breeding values arise due to identity disequilibrium, which is defined as the difference between the covariance matrix under the multi-loci probability of identity-by-descent ([Formula: see text]) and its expectation under gametic phase equilibrium, i.e., A. The disequilibrium term [Formula: see text]-A is considered in the model for predicting breeding values called the "ancestral regression" (AR), a causal Markov model. Here, we introduce the "ancestral regression to parents" (PAR) causal Markov model, which reduces the computational burden of the AR approach. By taking advantage of the conditional independence property of the PAR Markov model, we derive covariances between the breeding values of grandparents and grand-offspring and between parents and offspring. In addition, we obtain analytical expressions for the covariance between collateral relatives under the PAR model, as well as for the inbreeding coefficient. CONCLUSIONS: We introduced the causal PAR Markov model that captures identity disequilibrium in the covariances among breeding values and produces a sparse inverse covariance matrix to build and solve a set of mixed model equations.

Estimating inbreeding depression for growth and reproductive traits using pedigree and genomic methods in Argentinean Brangus cattle.

Inbreeding depression reduces the mean phenotypic value of important traits in livestock populations. The goal of this work was to estimate the level of inbreeding and inbreeding depression for growth and reproductive traits in Argentinean Brangus cattle, in order to obtain a diagnosis and monitor breed management. Data comprised 359,257 (from which 1,990 were genotyped for 40,678 single nucleotide polymorphisms [SNPs]) animals with phenotypic records for at least one of three growth traits: birth weight (BW), weaning weight (WW), and finishing weight (FW). For scrotal circumference (SC), 52,399 phenotypic records (of which 256 had genotype) were available. There were 530,938 animals in pedigree. Three methods to estimate inbreeding coefficients were used. Pedigree-based inbreeding coefficients were estimated accounting for missing parents. Inbreeding coefficients combining genotyped and nongenotyped animal information were also computed from matrix H of the single-step approach. Genomic inbreeding coefficients were estimated using homozygous segments obtained from a Hidden Markov model (HMM) approach. Inbreeding depression was estimated from the regression of the phenotype on inbreeding coefficients in a multiple-trait mixed model framework, either for the whole dataset or for the dataset of genotyped animals. All traits were unfavorably affected by inbreeding depression. A 10% increase in pedigree-based or combined inbreeding would result in a reduction of 0.34 to 0.39 kg in BW, 2.77 to 3.28 kg in WW, and 0.23 cm in SC. For FW, a 10% increase in pedigree-based, genomic, or combined inbreeding would result in a decrease of 8.05 to 11.57 kg. Genomic inbreeding based on the HMM was able to capture inbreeding depression, even in such a compressed genotyped dataset.

Estimation of direct and social effects of feeding duration in growing pigs using records from automatic feeding stations.

Automatic feeding systems in pig production allow for the recording of individual feeding behavior traits, which might be influenced by the social interactions among individuals. This study fitted mixed models to estimate the direct and social effects on visit duration at the feeder of group-housed pigs. The dataset included 74,413 records of each visit duration time (min) event at the automatic feeder from 135 pigs housed in 14 pens. The sequence of visits at the feeder was employed as a proxy for the social interaction between individuals. To estimate animal effects, the direct effect was apportioned to the animal feeding (feeding pig), and the social effect was apportioned to the animal that entered the feeder immediately after the feeding pig left the feeding station (follower). The data were divided into two subsets: "non-immediate replacement" time (NIRT, N = 6,256), where the follower pig occupied the feeder at least 600 s after the feeding pig left the feeder, and "immediate replacement" time (IRT, N = 58,255), where the elapsed time between replacements was less than or equal to 60 s. The marginal posterior distribution of the parameters was obtained by Bayesian method. Using the IRT subset, the posterior mean of the proportion of variance explained by the direct effect (PrpσTemefos) was 18% for all models. The proportion of variance explained by the follower social effect (Prpσ^f2) was 2%, and the residual variance (σ^e2) decreased, suggesting an improved model fit by including the follower effect. Fitting the models with the NIRT subset, the estimate of PrpσTemefos was 20% but the Prpσ^f2 was almost zero and σ^e2 was identical for all models. For the IRT subset, the predicted best linear unbiased predictor (BLUP) of direct (Direct BLUP) and social (Follower BLUP) random effects on visit duration at the feeder of an animal was calculated. Feeder visit duration time was not correlated with traits, such as weight gain or average feed intake (P > 0.05), whereas for the daily feeder occupation time, the estimated correlation was positive with the Direct BLUP (r^ = 0.51, P < 0.05) and negative with the Follower BLUP (r^= -0.26, P < 0.05). The results suggest that the visit duration of an animal at the single-space feeder was influenced by both direct and social effects when the replacement time between visits was less than 1 min. Finally, animals that spent a longer time per day at the feeder seemed to do so by shortening the meal length of the preceding individual at the feeder.

Estimating dominance genetic variances for growth traits in American Angus males using genomic models.

Estimates of dominance variance for growth traits in beef cattle based on pedigree data vary considerably across studies, and the proportion of genetic variance explained by dominance deviations remains largely unknown. The potential benefits of including nonadditive genetic effects in the genomic model combined with the increasing availability of large genomic data sets have recently renewed the interest in including nonadditive genetic effects in genomic evaluation models. The availability of genomic information enables the computation of covariance matrices of dominant genomic relationships among animals, similar to matrices of additive genomic relationships, and in a more straightforward manner than the pedigree-based dominance relationship matrix. Data from 19,357 genotyped American Angus males were used to estimate additive and dominant variance components for 3 growth traits: birth weight, weaning weight, and postweaning gain, and to evaluate the benefit of including dominance effects in beef cattle genomic evaluations. Variance components were estimated using 2 models: the first one included only additive effects (MG) and the second one included both additive and dominance effects (MGD). The dominance deviation variance ranged from 3% to 8% of the additive variance for all 3 traits. Gibbs sampling and REML estimates showed good concordance. Goodness of fit of the models was assessed by a likelihood ratio test. For all traits, MG fitted the data as well as MGD as assessed either by the likelihood ratio test or by the Akaike information criterion. Predictive ability of both models was assessed by cross-validation and did not improve when including dominance effects in the model. There was little evidence of nonadditive genetic variation for growth traits in the American Angus male population as only a small proportion of genetic variation was explained by nonadditive effects. A genomic model including the dominance effect did not improve the model fit. Consequently, including nonadditive effects in the genomic evaluation model is not beneficial for growth traits in the American Angus male population.

Estimation of indirect social genetic effects for skin lesion count in group-housed pigs by quantifying behavioral interactions1.

Mixing of pigs into new social groups commonly induces aggressive interactions that result in skin lesions on the body of the animals. The relationship between skin lesions and aggressive behavioral interactions in group-housed pigs can be analyzed within the framework of social genetic effects (SGE). This study incorporates the quantification of aggressive interactions between pairs of animals in the modeling of SGE for skin lesions in different regions of the body in growing pigs. The dataset included 792 pigs housed in 59 pens. Skin lesions in the anterior, central, and caudal regions of the body were counted 24 h after pig mixing. Animals were video-recorded for 9 h postmixing and trained observers recorded the type and duration of aggressive interactions between pairs of animals. The number of seconds that pairs of pigs spent engaged in reciprocal fights and unilateral attack behaviors were used to parametrize the intensity of social interactions (ISI). Three types of models were fitted: direct genetic additive model (DGE), traditional social genetic effect model (TSGE) assuming uniform interactions between dyads, and an intensity-based social genetic effect model (ISGE) that used ISI to parameterize SGE. All models included fixed effects of sex, replicate, lesion scorer, weight at mixing, premixing lesion count, and the total time that the animal spent engaged in aggressive interactions (reciprocal fights and unilateral attack behaviors) as a covariate; a random effect of pen; and a random direct genetic effect. The ISGE models recovered more direct genetic variance than DGE and TSGE, and the estimated heritabilities (h^D2) were highest for all traits (P < 0.01) for the ISGE with ISI parametrized with unilateral attack behavior. The TSGE produced estimates that did not differ significantly from DGE (P > 0.5). Incorporating the ISI into ISGE, even in a small dataset, allowed separate estimation of the genetic parameters for direct and SGE, as well as the genetic correlation between direct and SGE (rs), which was positive for all lesion traits. The estimates from ISGE suggest that if behavioral observations are available, selection incorporating SGE may reduce the consequences of aggressive behaviors after mixing pigs.

Lidocaine protects neurons of the spinal cord in an excitotoxicity model.

Motor Neuron Disease disorders, described in domestic animals, are characterized by neuronal degeneration at the spinal cord. Excitotoxicity is a crucial factor for the selective loss of these neurons, being the fundamental processes involved in lesion progression after spinal cord injury, where glutamate is one of the main neurotransmitters involved. Kainic acid (KA) resembles the effects induced by the pathological release of glutamate. Lidocaine administered by different routes exerts some neuroprotective effects in the CNS. The aim of the present work was to determine whether lidocaine simultaneously injected with KA into the spinal cord could prevent the excitotoxic effects of the latter. Sprague-Dawley rats were injected by intraparenchymal route with KA or with KA plus 0.5% lidocaine into the C5 segment. Sham rats were injected with saline. Animals were motor and sensory tested at 0, 1, 2, 3, 7 and 14 post-injection days and then euthanized. Sections of the C5 segment were used for histological and immunohistochemical analysis. No KA-induced motor and sensitive impairments were observed when lidocaine was simultaneously injected with KA. Moreover, neuronal counting was statistically higher when compared with KA-injected animals. Thus, lidocaine could be considered as a neuroprotective drug in diseases and models involving excitotoxicity.

Legacies of domestication, trade and herder mobility shape extant male zebu cattle diversity in South Asia and Africa.

All tropically adapted humped cattle (Bos indicus or "zebu"), descend from a domestication process that took place >8,000 years ago in South Asia. Here we present an intercontinental survey of Y-chromosome diversity and a comprehensive reconstruction of male-lineage zebu cattle history and diversity patterns. Phylogenetic analysis revealed that all the zebu Y-chromosome haplotypes in our dataset group within three different lineages: Y3A, the most predominant and cosmopolitan lineage; Y3B, only observed in West Africa; and Y3C, predominant in South and Northeast India. The divergence times estimated for these three Zebu-specific lineages predate domestication. Coalescent demographic models support either de novo domestication of genetically divergent paternal lineages or more complex process including gene flow between wild and domestic animals. Our data suggest export of varied zebu lineages from domestication centres through time. The almost exclusive presence of Y3A haplotypes in East Africa is consistent with recent cattle restocking in this area. The cryptic presence of Y3B haplotypes in West Africa, found nowhere else, suggests that these haplotypes might represent the oldest zebu lineage introduced to Africa ca. 3,000 B.P. and subsequently replaced in most of the world. The informative ability of Interspersed Multilocus Microsatellites and Y-specific microsatellites to identify genetic structuring in cattle populations is confirmed.

Effects of an Intraparenchymal Injection of Lidocaine in the Rat Cervical Spinal Cord.

Lidocaine effects in the spinal cord have been extensively investigated over the years. Although the intrathecal route is usually used to treat insults occurring in the spinal cord, the local delivery drug via intraparenchymal infusions has gained increasing favor for the treatment of some neurodegenerative disorders. The aim of the present study was to evaluate the behavioral and tissue effects of the intraparenchymal injection of different concentrations of lidocaine into the rat cervical spinal cord. Young male Sprague-Dawley rats were intraparenchymally injected with 0.5%, 1% or 2% lidocaine at the C5 segment of the spinal cord. Other rats were injected with saline solution (sham group). Hot plate test was determined at 0, 1, 2, 3, 7 and 14 post-injection (pi) days. Rats of each experimental group were euthanized either at 1, 2, 3, 7 or 14 pi days. Intact animals were used as controls. Sections of the C5 segment were used for histological, immunohistochemical or immunofluorescence analysis. Injection of 0.5% lidocaine did not affect neuronal counting, did not evoke an inflammatory reaction, nor induce astrocyte activation. Therefore, a concentration of 0.5% lidocaine is suggested to promote anti-inflammatory effects after injury.

The effect of the H-1 scaling factors τ and ω on the structure of H in the single-step procedure.

BACKGROUND: The single-step covariance matrix H combines the pedigree-based relationship matrix [Formula: see text] with the more accurate information on realized relatedness of genotyped individuals represented by the genomic relationship matrix [Formula: see text]. In particular, to improve convergence behavior of iterative approaches and to reduce inflation, two weights [Formula: see text] and [Formula: see text] have been introduced in the definition of [Formula: see text], which blend the inverse of a part of [Formula: see text] with the inverse of [Formula: see text]. Since the definition of this blending is based on the equation describing [Formula: see text], its impact on the structure of [Formula: see text] is not obvious. In a joint discussion, we considered the question of the shape of [Formula: see text] for non-trivial [Formula: see text] and [Formula: see text]. RESULTS: Here, we present the general matrix [Formula: see text] as a function of these parameters and discuss its structure and properties. Moreover, we screen for optimal values of [Formula: see text] and [Formula: see text] with respect to predictive ability, inflation and iterations up to convergence on a well investigated, publicly available wheat data set. CONCLUSION: Our results may help the reader to develop a better understanding for the effects of changes of [Formula: see text] and [Formula: see text] on the covariance model. In particular, we give theoretical arguments that as a general tendency, inflation will be reduced by increasing [Formula: see text] or by decreasing [Formula: see text].

Metafounders are related to F st fixation indices and reduce bias in single-step genomic evaluations.

BACKGROUND: Metafounders are pseudo-individuals that encapsulate genetic heterozygosity and relationships within and across base pedigree populations, i.e. ancestral populations. This work addresses the estimation and usefulness of metafounder relationships in single-step genomic best linear unbiased prediction (ssGBLUP). RESULTS: We show that ancestral relationship parameters are proportional to standardized covariances of base allelic frequencies across populations, such as [Formula: see text] fixation indexes. These covariances of base allelic frequencies can be estimated from marker genotypes of related recent individuals and pedigree. Simple methods for their estimation include naïve computation of allele frequencies from marker genotypes or a method of moments that equates average pedigree-based and marker-based relationships. Complex methods include generalized least squares (best linear unbiased estimator (BLUE)) or maximum likelihood based on pedigree relationships. To our knowledge, methods to infer [Formula: see text] coefficients from marker data have not been developed for related individuals. We derived a genomic relationship matrix, compatible with pedigree relationships, that is constructed as a cross-product of {-1,0,1} codes and that is equivalent (apart from scale factors) to an identity-by-state relationship matrix at genome-wide markers. Using a simulation with a single population under selection in which only males and youngest animals are genotyped, we observed that generalized least squares or maximum likelihood gave accurate and unbiased estimates of the ancestral relationship parameter (true value: 0.40) whereas the naïve method and the method of moments were biased (average estimates of 0.43 and 0.35). We also observed that genomic evaluation by ssGBLUP using metafounders was less biased in terms of estimates of genetic trend (bias of 0.01 instead of 0.12), resulted in less overdispersed (0.94 instead of 0.99) and as accurate (0.74) estimates of breeding values than ssGBLUP without metafounders and provided consistent estimates of heritability. CONCLUSIONS: Estimation of metafounder relationships can be achieved using BLUP-like methods with pedigree and markers. Inclusion of metafounder relationships reduces bias of genomic predictions with no loss in accuracy.

Genomic prediction with epistasis models: on the marker-coding-dependent performance of the extended GBLUP and properties of the categorical epistasis model (CE).

BACKGROUND: Epistasis marker effect models incorporating products of marker values as predictor variables in a linear regression approach (extended GBLUP, EGBLUP) have been assessed as potentially beneficial for genomic prediction, but their performance depends on marker coding. Although this fact has been recognized in literature, the nature of the problem has not been thoroughly investigated so far. RESULTS: We illustrate how the choice of marker coding implicitly specifies the model of how effects of certain allele combinations at different loci contribute to the phenotype, and investigate coding-dependent properties of EGBLUP. Moreover, we discuss an alternative categorical epistasis model (CE) eliminating undesired properties of EGBLUP and show that the CE model can improve predictive ability. Finally, we demonstrate that the coding-dependent performance of EGBLUP offers the possibility to incorporate prior experimental information into the prediction method by adapting the coding to already available phenotypic records on other traits. CONCLUSION: Based on our results, for EGBLUP, a symmetric coding {-1,1} or {-1,0,1} should be preferred, whereas a standardization using allele frequencies should be avoided. Moreover, CE can be a valuable alternative since it does not possess the undesired theoretical properties of EGBLUP. However, which model performs best will depend on characteristics of the data and available prior information. Data from previous experiments can for instance be incorporated into the marker coding of EGBLUP.

Longitudinal data analysis of polymorphisms in the κ-casein and ß-lactoglobulin genes shows differential effects along the trajectory of the lactation curve in tropical dairy goats.

The κ-casein (CSN-3) and ß-lactoglobulin (BLG) genes are extensively polymorphic in ruminants. Several association studies have estimated the effects of polymorphisms in these genes on milk yield, milk composition, and cheese-manufacturing properties. Usually, these results are based on production integrated over the lactation curve or on cross-sectional studies at specific days in milk (DIM). However, as differential expression of milk protein genes occurs over lactation, the effect of the polymorphisms may change over time. In this study, we fitted a mixed-effects regression model to test-day records of milk yield and milk quality traits (fat, protein, and total solids yields) from Colombian tropical dairy goats. We used the well-characterized A/B polymorphisms in the CSN-3 and BLG genes. We argued that this approach provided more efficient estimators than cross-sectional designs, given the same number and pattern of observations, and allowed exclusion of between-subject variation from model error. The BLG genotype AA showed a greater performance than the BB genotype for all traits along the whole lactation curve, whereas the heterozygote showed an intermediate performance. We observed no such constant pattern for the CSN-3 gene between the AA homozygote and the heterozygote (the BB genotype was absent from the sample). The differences among the genotypic effects of the BLG and the CSN-3 polymorphisms were statistically significant during peak and mid lactation (around 40-160 DIM) for the BLG gene and only for mid lactation (80-145 DIM) for the CSN-3 gene. We also estimated the additive and dominant effects of the BLG locus. The locus showed a statistically significant additive behavior along the whole lactation trajectory for all quality traits, whereas for milk yield the effect was not significant at later stages. In turn, we detected a statistically significant dominance effect only for fat yield in the early and peak stages of lactation (at about 1-45 DIM). The longitudinal analysis of test-day records allowed us to estimate the differential effects of polymorphisms along the lactation curve, pointing toward stages that could be affected by the gene.

Quality control of genotypes using heritability estimates of gene content at the marker.

Quality control filtering of single-nucleotide polymorphisms (SNPs) is a key step when analyzing genomic data. Here we present a practical method to identify low-quality SNPs, meaning markers whose genotypes are wrongly assigned for a large proportion of individuals, by estimating the heritability of gene content at each marker, where gene content is the number of copies of a particular reference allele in a genotype of an animal (0, 1, or 2). If there is no mutation at the marker, gene content has an additive heritability of 1 by construction. The method uses restricted maximum likelihood (REML) to estimate heritability of gene content at each SNP and also builds a likelihood-ratio test statistic to test for zero error variance in genotyping. As a by-product, estimates of the allele frequencies of markers at the base population are obtained. Using simulated data with 10% permutation error (4% actual error) in genotyping, the method had a specificity of 0.96 (4% of correct markers are rejected) and a sensitivity of 0.99 (1% of wrong markers are accepted) if markers with heritability lower than 0.975 are discarded. Checking of Mendelian errors resulted in a lower sensitivity (0.84) for the same simulation. The proposed method is further illustrated with a real data set with genotypes from 3534 animals genotyped for 50,433 markers from the Illumina PorcineSNP60 chip and a pedigree of 6473 individuals; those markers underwent very little quality control. A total of 4099 markers with P-values lower than 0.01 were discarded based on our method, with associated estimates of heritability as low as 0.12. Contrary to other techniques, our method uses all information in the population simultaneously, can be used in any population with markers and pedigree recordings, and is simple to implement using standard software for REML estimation. Scripts for its use are provided.

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.

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

BACKGROUND: F(2) 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 F(2) populations using high density SNP panels for founding individuals and low density panels (tagSNP) in F(2) 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 F(2) 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 F(2), IA reaches 0.99. In order to attain such high imputation accuracy the F(0) and F(1) generations should be genotyped at high density. Alternatively, when only the F(0) is genotyped at HD, while F(1) and F(2) are genotyped with a 9K panel, IA drops to 0.90. CONCLUSIONS: Combining 60K and 9K panels with imputation in F(2) populations is an appealing strategy to re-genotype existing populations at a fraction of the cost.

Reduced faecal shedding of Escherichia coli O157:H7 in cattle following systemic vaccination with γ-intimin C280 and EspB proteins.

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 is the most prevalent EHEC serotype that has been recovered from patients with haemolytic uremic syndrome (HUS) worldwide. Vaccination of cattle, the main reservoir of EHEC O157:H7, could be a logical strategy to fight infection in humans. This study evaluated a vaccine based on the carboxyl-terminal fragment of 280 amino acids of γ-intimin (γ-intimin C280) and EspB, two key colonization factors of E. coli O157:H7. Intramuscular immunization elicited significantly high levels of serum IgG antibodies against both proteins. Antigen-specific IgA and IgG were also induced in saliva, but only the IgA response was significant. Following experimental challenge with E. coli O157:H7, a significant reduction in bacterial shedding was observed in vaccinated calves, compared to control group. These promising results suggest that systemic immunization of cattle with intimin and EspB could be a feasible strategy to reduce EHEC O157:H7 faecal shedding in cattle.

Equivalence of multibreed animal models and hierarchical Bayes analysis for maternally influenced traits.

BACKGROUND: It has been argued that multibreed animal models should include a heterogeneous covariance structure. However, the estimation of the (co)variance components is not an easy task, because these parameters can not be factored out from the inverse of the additive genetic covariance matrix. An alternative model, based on the decomposition of the genetic covariance matrix by source of variability, provides a much simpler formulation. In this study, we formalize the equivalence between this alternative model and the one derived from the quantitative genetic theory. Further, we extend the model to include maternal effects and, in order to estimate the (co)variance components, we describe a hierarchical Bayes implementation. Finally, we implement the model to weaning weight data from an Angus x Hereford crossbred experiment. METHODS: Our argument is based on redefining the vectors of breeding values by breed origin such that they do not include individuals with null contributions. Next, we define matrices that retrieve the null-row and the null-column pattern and, by means of appropriate algebraic operations, we demonstrate the equivalence. The extension to include maternal effects and the estimation of the (co)variance components through the hierarchical Bayes analysis are then straightforward. A FORTRAN 90 Gibbs sampler was specifically programmed and executed to estimate the (co)variance components of the Angus x Hereford population. RESULTS: In general, genetic (co)variance components showed marginal posterior densities with a high degree of symmetry, except for the segregation components. Angus and Hereford breeds contributed with 50.26% and 41.73% of the total direct additive variance, and with 23.59% and 59.65% of the total maternal additive variance. In turn, the contribution of the segregation variance was not significant in either case, which suggests that the allelic frequencies in the two parental breeds were similar. CONCLUSION: The multibreed maternal animal model introduced in this study simplifies the problem of estimating (co)variance components in the framework of a hierarchical Bayes analysis. Using this approach, we obtained for the first time estimates of the full set of genetic (co)variance components. It would be interesting to assess the performance of the procedure with field data, especially when interbreed information is limited.

Improving 2D-DIGE protein expression analysis by two-stage linear mixed models: assessing experimental effects in a melanoma cell study.

MOTIVATION: Difference in-gel electrophoresis (DIGE)-based protein expression analysis allows assessing the relative expression of proteins in two biological samples differently labeled (Cy5, Cy3 CyDyes). In the same gel, a reference sample is also used (Cy2 CyDye) for spot matching during image analysis and volume normalization. The standard statistical techniques to identify differentially expressed (DE) proteins are the calculation of fold-changes and the comparison of treatment means by the t-test. The analyses rarely accounts for other experimental effects, such as CyDye and gel effects, which could be important sources of noise while detecting treatment effects. RESULTS: We propose to identify DIGE DE proteins using a two-stage linear mixed model. The proposal consists of splitting the overall model for the measured intensity into two interconnected models. First, we fit a normalization model that accounts for the general experimental effects, such as gel and CyDye effects as well as for the features of the associated random term distributions. Second, we fit a model that uses the residuals from the first step to account for differences between treatments in protein-by-protein basis. The modeling strategy was evaluated using data from a melanoma cell study. We found that a heteroskedastic model in the first stage, which also account for CyDye and gel effects, best normalized the data, while allowing for an efficient estimation of the treatment effects. The Cy2 reference channel was used as a covariate in the normalization model to avoid skewness of the residual distribution. Its inclusion improved the detection of DE proteins in the second stage.