509 results on '"Varona Luis"'
Search Results
2. Bayes factor between Student t and Gaussian mixed models within an animal breeding context
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García-Cortés Luis, Ibáñez-Escriche Noelia, Casellas Joaquim, and Varona Luis
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Bayes factor ,Gaussian distribution ,mixed model ,Student t distribution ,preferential treatment ,Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Abstract
Abstract The implementation of Student t mixed models in animal breeding has been suggested as a useful statistical tool to effectively mute the impact of preferential treatment or other sources of outliers in field data. Nevertheless, these additional sources of variation are undeclared and we do not know whether a Student t mixed model is required or if a standard, and less parameterized, Gaussian mixed model would be sufficient to serve the intended purpose. Within this context, our aim was to develop the Bayes factor between two nested models that only differed in a bounded variable in order to easily compare a Student t and a Gaussian mixed model. It is important to highlight that the Student t density converges to a Gaussian process when degrees of freedom tend to infinity. The twomodels can then be viewed as nested models that differ in terms of degrees of freedom. The Bayes factor can be easily calculated from the output of a Markov chain Monte Carlo sampling of the complex model (Student t mixed model). The performance of this Bayes factor was tested under simulation and on a real dataset, using the deviation information criterion (DIC) as the standard reference criterion. The two statistical tools showed similar trends along the parameter space, although the Bayes factor appeared to be the more conservative. There was considerable evidence favoring the Student t mixed model for data sets simulated under Student t processes with limited degrees of freedom, and moderate advantages associated with using the Gaussian mixed model when working with datasets simulated with 50 or more degrees of freedom. For the analysis of real data (weight of Pietrain pigs at six months), both the Bayes factor and DIC slightly favored the Student t mixed model, with there being a reduced incidence of outlier individuals in this population.
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- 2008
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3. Bayes factor for testing between different structures of random genetic groups: A case study using weaning weight in Bruna dels Pirineus beef cattle
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Varona Luis, Piedrafita Jesús, and Casellas Joaquim
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Bayes factor ,genetic groups ,beef cattle ,weaning weight ,Bruna dels Pirineus ,Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Abstract
Abstract The implementation of genetic groups in BLUP evaluations accounts for different expectations of breeding values in base animals. Notwithstanding, many feasible structures of genetic groups exist and there are no analytical tools described to compare them easily. In this sense, the recent development of a simple and stable procedure to calculate the Bayes factor between nested competing models allowed us to develop a new approach of that method focused on compared models with different structures of random genetic groups. The procedure is based on a reparameterization of the model in terms of intraclass correlation of genetic groups. The Bayes factor can be easily calculated from the output of a Markov chain Monte Carlo sampling by averaging conditional densities at the null intraclass correlation. It compares two nested models, a model with a given structure of genetic groups against a model without genetic groups. The calculation of the Bayes factor between different structures of genetic groups can be quickly and easily obtained from the Bayes factor between the nested models. We applied this approach to a weaning weight data set of the Bruna dels Pirineus beef cattle, comparing several structures of genetic groups, and the final results showed that the preferable structure was an only group for unknown dams and different groups for unknown sires for each year of calving.
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- 2007
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4. A Bayesian analysis of the effect of selection for growth rate on growth curves in rabbits
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Piles Miriam, Blasco Agustín, and Varona Luis
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growth curves ,selection ,rabbits ,Bayesian analysis ,Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Abstract
Abstract Gompertz growth curves were fitted to the data of 137 rabbits from control (C) and selected (S) lines. The animals came from a synthetic rabbit line selected for an increased growth rate. The embryos from generations 3 and 4 were frozen and thawed to be contemporary of rabbits born in generation 10. Group C was the offspring of generations 3 and 4, and group S was the contemporary offspring of generation 10. The animals were weighed individually twice a week during the first four weeks of life, and once a week thereafter, until 20 weeks of age. Subsequently, the males were weighed weekly until 40 weeks of age. The random samples of the posterior distributions of the growth curve parameters were drawn by using Markov Chain Monte Carlo (MCMC) methods. As a consequence of selection, the selected animals were heavier than the C animals throughout the entire growth curve. Adult body weight, estimated as a parameter of the Gompertz curve, was 7% higher in the selected line. The other parameters of the Gompertz curve were scarcely affected by selection. When selected and control growth curves are represented in a metabolic scale, all differences disappear.
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- 2003
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5. Test for positional candidate genes for body composition on pig chromosome 6
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Pérez-Enciso Miguel, Sánchez Armand, Toro Miguel, Rodríguez Carmen, Varona Luis, Barragán Carmen, Clop Alex, Noguera José, Oliver Angels, Cristina Óvilo, and Silió Luis
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candidate gene ,H-FABP ,LEPR ,QTL ,pigs ,Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Abstract
Abstract One QTL affecting backfat thickness (BF), intramuscular fat content (IMF) and eye muscle area (MA) was previously localized on porcine chromosome 6 in an F2 cross between Iberian and Landrace pigs. This work was done to study the effect of two positional candidate genes on these traits: H-FABP and LEPR genes. The QTL mapping analysis was repeated with a regression method using genotypes for seven microsatellites and two PCR-RFLPs in the H-FABP and LEPR genes. H-FABP and LEPR genes were located at 85.4 and 107 cM respectively, by linkage analysis. The effects of the candidate gene polymorphisms were analyzed in two ways. When an animal model was fitted, both genes showed significant effects on fatness traits, the H-FABP polymorphism showed significant effects on IMF and MA, and the LEPR polymorphism on BF and IMF. But when the candidate gene effect was included in a QTL regression analysis these associations were not observed, suggesting that they must not be the causal mutations responsible for the effects found. Differences in the results of both analyses showed the inadequacy of the animal model approach for the evaluation of positional candidate genes in populations with linkage disequilibrium, when the probabilities of the parental origin of the QTL alleles are not included in the model.
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- 2002
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6. Bayes factors for detection of Quantitative Trait Loci
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Pérez-Enciso Miguel, García-Cortés Luis, and Varona Luis
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Bayes factor ,Quantitative Trait Loci ,hypothesis testing ,Markov Chain Monte Carlo ,Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Abstract
Abstract A fundamental issue in quantitative trait locus (QTL) mapping is to determine the plausibility of the presence of a QTL at a given genome location. Bayesian analysis offers an attractive way of testing alternative models (here, QTL vs. no-QTL) via the Bayes factor. There have been several numerical approaches to computing the Bayes factor, mostly based on Markov Chain Monte Carlo (MCMC), but these strategies are subject to numerical or stability problems. We propose a simple and stable approach to calculating the Bayes factor between nested models. The procedure is based on a reparameterization of a variance component model in terms of intra-class correlation. The Bayes factor can then be easily calculated from the output of a MCMC scheme by averaging conditional densities at the null intra-class correlation. We studied the performance of the method using simulation. We applied this approach to QTL analysis in an outbred population. We also compared it with the Likelihood Ratio Test and we analyzed its stability. Simulation results were very similar to the simulated parameters. The posterior probability of the QTL model increases as the QTL effect does. The location of the QTL was also correctly obtained. The use of meta-analysis is suggested from the properties of the Bayes factor.
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- 2001
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7. Hypothesis testing for the genetic background of quantitative traits
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Moreno Carlos, Cabrillo Carlos, García-Cortés Luis, and Varona Luis
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animal breeding ,prior distribution ,Bayes factor ,hypothesis testing ,heritability ,Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Abstract
Abstract The testing of Bayesian point null hypotheses on variance component models have resulted in a tough assignment for which no clear and generally accepted method exists. In this work we present what we believe is a succeeding approach to such a task. It is based on a simple reparameterization of the model in terms of the total variance and the proportion of the additive genetic variance with respect to it, as well as on the explicit inclusion on the prior probability of a discrete component at origin. The reparameterization was used to bypass an arbitrariness related to the impropriety of uninformative priors onto unbounded variables while the discrete component was necessary to overcome the zero probability assigned to sets of null measure by the usual continuous variable models. The method was tested against computer simulations with appealing results.
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- 2001
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8. Computation of identity by descent probabilities conditional on DNA markers via a Monte Carlo Markov Chain method
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Pérez-Enciso Miguel, Varona Luis, and Rothschild Max F
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DNA markers ,identity by descent probability ,Monte Carlo Markov Chain ,Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Abstract
Abstract The accurate estimation of the probability of identity by descent (IBD) at loci or genome positions of interest is paramount to the genetic study of quantitative and disease resistance traits. We present a Monte Carlo Markov Chain method to compute IBD probabilities between individuals conditional on DNA markers and on pedigree information. The IBDs can be obtained in a completely general pedigree at any genome position of interest, and all marker and pedigree information available is used. The method can be split into two steps at each iteration. First, phases are sampled using current genotypic configurations of relatives and second, crossover events are simulated conditional on phases. Internal track is kept of all founder origins and crossovers such that the IBD probabilities averaged over replicates are rapidly obtained. We illustrate the method with some examples. First, we show that all pedigree information should be used to obtain line origin probabilities in F2 crosses. Second, the distribution of genetic relationships between half and full sibs is analysed in both simulated data and in real data from an F2 cross in pigs.
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- 2000
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9. Medulla oblongata transcriptome changes during presymptomatic natural scrapie and their association with prion-related lesions
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Filali Hicham, Martin-Burriel Inmaculada, Harders Frank, Varona Luis, Serrano Carmen, Acín Cristina, Badiola Juan J, Bossers Alex, and Bolea Rosa
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Natural scrapie ,Preclinical sheep ,Microarray ,Genetic expression ,Real time PCR ,Prion ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background The pathogenesis of natural scrapie and other prion diseases is still poorly understood. Determining the variations in the transcriptome in the early phases of the disease might clarify some of the molecular mechanisms of the prion-induced pathology and allow for the development of new biomarkers for diagnosis and therapy. This study is the first to focus on the identification of genes regulated during the preclinical phases of natural scrapie in the ovine medulla oblongata (MO) and the association of these genes with prion deposition, astrocytosis and spongiosis. Results A custom microarray platform revealed that 86 significant probes had expression changes greater than 2-fold. From these probes, we identified 32 genes with known function; the highest number of regulated genes was included in the phosphoprotein-encoding group. Genes encoding extracellular marker proteins and those involved in the immune response and apoptosis were also differentially expressed. In addition, we investigated the relationship between the gene expression profiles and the appearance of the main scrapie-associated brain lesions. Quantitative Real-time PCR was used to validate the expression of some of the regulated genes, thus showing the reliability of the microarray hybridization technology. Conclusions Genes involved in protein and metal binding and oxidoreductase activity were associated with prion deposition. The expression of glial fibrillary acidic protein (GFAP) was associated with changes in the expression of genes encoding proteins with oxidoreductase and phosphatase activity, and the expression of spongiosis was related to genes encoding extracellular matrix components or transmembrane transporters. This is the first genome-wide expression study performed in naturally infected sheep with preclinical scrapie. As in previous studies, our findings confirm the close relationship between scrapie and other neurodegenerative diseases.
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- 2012
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10. Carcass conformation and fat cover scores in beef cattle: A comparison of threshold linear models vs grouped data models
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Piedrafita Jesús, Varona Luis, Fina Marta, and Tarrés Joaquim
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Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Abstract
Abstract Background Beef carcass conformation and fat cover scores are measured by subjective grading performed by trained technicians. The discrete nature of these scores is taken into account in genetic evaluations using a threshold model, which assumes an underlying continuous distribution called liability that can be modelled by different methods. Methods Five threshold models were compared in this study: three threshold linear models, one including slaughterhouse and sex effects, along with other systematic effects, with homogeneous thresholds and two extensions with heterogeneous thresholds that vary across slaughterhouses and across slaughterhouse and sex and a generalised linear model with reverse extreme value errors. For this last model, the underlying variable followed a Weibull distribution and was both a log-linear model and a grouped data model. The fifth model was an extension of grouped data models with score-dependent effects in order to allow for heterogeneous thresholds that vary across slaughterhouse and sex. Goodness-of-fit of these models was tested using the bootstrap methodology. Field data included 2,539 carcasses of the Bruna dels Pirineus beef cattle breed. Results Differences in carcass conformation and fat cover scores among slaughterhouses could not be totally captured by a systematic slaughterhouse effect, as fitted in the threshold linear model with homogeneous thresholds, and different thresholds per slaughterhouse were estimated using a slaughterhouse-specific threshold model. This model fixed most of the deficiencies when stratification by slaughterhouse was done, but it still failed to correctly fit frequencies stratified by sex, especially for fat cover, as 5 of the 8 current percentages were not included within the bootstrap interval. This indicates that scoring varied with sex and a specific sex per slaughterhouse threshold linear model should be used in order to guarantee the goodness-of-fit of the genetic evaluation model. This was also observed in grouped data models that avoided fitting deficiencies when slaughterhouse and sex effects were score-dependent. Conclusions Both threshold linear models and grouped data models can guarantee the goodness-of-fit of the genetic evaluation for carcass conformation and fat cover, but our results highlight the need for specific thresholds by sex and slaughterhouse in order to avoid fitting deficiencies.
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- 2011
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11. Changes in HSP gene and protein expression in natural scrapie with brain damage
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Serrano Carmen, Bolea Rosa, Lyahyai Jaber, Filali Hicham, Varona Luis, Marcos-Carcavilla Ane, Acín Cristina, Calvo Jorge H, Serrano Magdalena, Badiola Juan J, Zaragoza Pilar, and Martín-Burriel Inmaculada
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Veterinary medicine ,SF600-1100 - Abstract
Abstract Heat shock proteins (Hsp) perform cytoprotective functions such as apoptosis regulation and inflammatory response control. These proteins can also be secreted to the extracellular medium, acting as inflammatory mediators, and their chaperone activity permits correct folding of proteins and avoids the aggregation of anomalous isoforms. Several studies have proposed the implication of Hsp in prion diseases. We analysed the gene expression and protein distribution of different members of the Hsp27, Hsp70, and Hsp90 families in the central nervous system of sheep naturally infected with scrapie. Different expression profiles were observed in the areas analysed. Whereas changes in transcript levels were not observed in the cerebellum or medulla oblongata, a significant decrease in HSP27 and HSP90 was detected in the prefrontal cortex. In contrast, HSP73 was over-expressed in diencephalons of scrapie animals. Western blotting did not reveal significant differences in Hsp90 and Hsp70 protein expression between scrapie and control animals. Expression rates identified by real-time RT-PCR and western blotting were compared with the extent of classical scrapie lesions using stepwise regression. Changes in Hsp gene and protein expression were associated with prion protein deposition, gliosis and spongiosis rather than with apoptosis. Finally, immunohistochemistry revealed intense Hsp70 and Hsp90 immunolabelling in Purkinje cells of scrapie sheep. In contrast, controls displayed little or no staining in these cells. The observed differences in gene expression and protein distribution suggest that the heat shock proteins analysed play a role in the natural form of the disease.
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- 2011
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12. A note on mate allocation for dominance handling in genomic selection
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Toro Miguel A and Varona Luis
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Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Abstract
Abstract Estimation of non-additive genetic effects in animal breeding is important because it increases the accuracy of breeding value prediction and the value of mate allocation procedures. With the advent of genomic selection these ideas should be revisited. The objective of this study was to quantify the efficiency of including dominance effects and practising mating allocation under a whole-genome evaluation scenario. Four strategies of selection, carried out during five generations, were compared by simulation techniques. In the first scenario (MS), individuals were selected based on their own phenotypic information. In the second (GSA), they were selected based on the prediction generated by the Bayes A method of whole-genome evaluation under an additive model. In the third (GSD), the model was expanded to include dominance effects. These three scenarios used random mating to construct future generations, whereas in the fourth one (GSD + MA), matings were optimized by simulated annealing. The advantage of GSD over GSA ranges from 9 to 14% of the expected response and, in addition, using mate allocation (GSD + MA) provides an additional response ranging from 6% to 22%. However, mate selection can improve the expected genetic response over random mating only in the first generation of selection. Furthermore, the efficiency of genomic selection is eroded after a few generations of selection, thus, a continued collection of phenotypic data and re-evaluation will be required.
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- 2010
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13. A bi-dimensional genome scan for prolificacy traits in pigs shows the existence of multiple epistatic QTL
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Bidanel Jean P, Arqué Meritxell, Barragán Carmen, Ramírez Oscar, Muñoz Gloria, Tomàs Anna, Varona Luis, Rodríguez Carmen, Noguera José L, Amills Marcel, Ovilo Cristina, and Sánchez Armand
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Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Prolificacy is the most important trait influencing the reproductive efficiency of pig production systems. The low heritability and sex-limited expression of prolificacy have hindered to some extent the improvement of this trait through artificial selection. Moreover, the relative contributions of additive, dominant and epistatic QTL to the genetic variance of pig prolificacy remain to be defined. In this work, we have undertaken this issue by performing one-dimensional and bi-dimensional genome scans for number of piglets born alive (NBA) and total number of piglets born (TNB) in a three generation Iberian by Meishan F2 intercross. Results The one-dimensional genome scan for NBA and TNB revealed the existence of two genome-wide highly significant QTL located on SSC13 (P < 0.001) and SSC17 (P < 0.01) with effects on both traits. This relative paucity of significant results contrasted very strongly with the wide array of highly significant epistatic QTL that emerged in the bi-dimensional genome-wide scan analysis. As much as 18 epistatic QTL were found for NBA (four at P < 0.01 and five at P < 0.05) and TNB (three at P < 0.01 and six at P < 0.05), respectively. These epistatic QTL were distributed in multiple genomic regions, which covered 13 of the 18 pig autosomes, and they had small individual effects that ranged between 3 to 4% of the phenotypic variance. Different patterns of interactions (a × a, a × d, d × a and d × d) were found amongst the epistatic QTL pairs identified in the current work. Conclusions The complex inheritance of prolificacy traits in pigs has been evidenced by identifying multiple additive (SSC13 and SSC17), dominant and epistatic QTL in an Iberian × Meishan F2 intercross. Our results demonstrate that a significant fraction of the phenotypic variance of swine prolificacy traits can be attributed to first-order gene-by-gene interactions emphasizing that the phenotypic effects of alleles might be strongly modulated by the genetic background where they segregate.
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- 2009
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14. Between-groups within-gene heterogeneity of residual variances in microarray gene expression data
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Varona Luis and Casellas Joaquim
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Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background The analysis of microarray gene expression data typically tries to identify differential gene expression patterns in terms of differences of the mathematical expectation between groups of arrays (e.g. treatments or biological conditions). Nevertheless, the differential expression pattern could also be characterized by group-specific dispersion patterns, although little is known about this phenomenon in microarray data. Commonly, a homogeneous gene-specific residual variance is assumed in hierarchical mixed models for gene expression data, although it could result in substantial biases if this assumption is not true. Results In this manuscript, a hierarchical mixed model with within-gene heterogeneous residual variances is proposed to analyze gene expression data from non-competitive hybridized microarrays. Moreover, a straightforward Bayes factor is adapted to easily check within-gene (between groups) heterogeneity of residual variances when samples are grouped in two different treatments. This Bayes factor only requires the analysis of the complex model (hierarchical mixed model with between-groups heterogeneous residual variances for all analyzed genes) and gene-specific Bayes factors are provided from the output of a simple Markov chain Monte Carlo sampling. Conclusion This statistical development opens new research possibilities within the gene expression framework, where heterogeneity in residual variability could be viewed as an alternative and plausible characterization of differential expression patterns.
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- 2008
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15. Identification of genomic regions associated with reproductive longevity in the Rubia Gallega beef cattle breed using a censored threshold model
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Martínez-Castillero, María, López-Carbonell, David, Srihi, Houssemeddine, Hervás-Rivero, Carlos, Altarriba, Juan, Martínez, Paulino, Hermida, Miguel, and Varona, Luis
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- 2023
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16. Equivalence of variance components between standard and recursive genetic models using LDL' transformations
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European Commission, Varona, Luis [0000-0001-6256-5478], López-Carbonell, David [0000-0003-0964-9212], Srihi, Houssemeddine [0000-0002-9249-3070], Hervás-Rivero, Carlos [0009-0004-9561-9048], González Recio, Oscar [0000-0002-9106-4063], Altarriba, Juan [0000-0002-3042-2250], Varona, Luis, López-Carbonell, David, Srihi, Houssemeddine, Hervás-Rivero, Carlos, González Recio, Oscar, Altarriba, Juan, European Commission, Varona, Luis [0000-0001-6256-5478], López-Carbonell, David [0000-0003-0964-9212], Srihi, Houssemeddine [0000-0002-9249-3070], Hervás-Rivero, Carlos [0009-0004-9561-9048], González Recio, Oscar [0000-0002-9106-4063], Altarriba, Juan [0000-0002-3042-2250], Varona, Luis, López-Carbonell, David, Srihi, Houssemeddine, Hervás-Rivero, Carlos, González Recio, Oscar, and Altarriba, Juan
- Abstract
Recursive models are a category of structural equation models that propose a causal relationship between traits. These models are more parameterized than multiple trait models, and they require imposing restrictions on the parameter space to ensure statistical identification. Nevertheless, in certain situations, the likelihood of recursive models and multiple trait models are equivalent. Consequently, the estimates of variance components derived from the multiple trait mixed model can be converted into estimates under several recursive models through LDL' or block-LDL' transformations.
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- 2024
17. Characterization of microbiota signatures in Iberian pig strains using machine learning algorithms.
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Azouggagh, Lamiae, Ibáñez-Escriche, Noelia, Martínez-Álvaro, Marina, Varona, Luis, Casellas, Joaquim, Negro, Sara, and Casto-Rebollo, Cristina
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MACHINE learning ,SHORT-chain fatty acids ,FEATURE selection ,SUPPORT vector machines ,PHENOTYPIC plasticity ,GUT microbiome - Abstract
Background: There is a growing interest in uncovering the factors that shape microbiome composition due to its association with complex phenotypic traits in livestock. Host genetic variation is increasingly recognized as a major factor influencing the microbiome. The Iberian pig breed, known for its high-quality meat products, includes various strains with recognized genetic and phenotypic variability. However, despite the microbiome's known impact on pigs' productive phenotypes such as meat quality traits, comparative analyses of gut microbial composition across Iberian pig strains are lacking. This study aims to explore the gut microbiota of two Iberian pig strains, Entrepelado (n = 74) and Retinto (n = 63), and their reciprocal crosses (n = 100), using machine learning (ML) models to identify key microbial taxa relevant for distinguishing their genetic backgrounds, which holds potential application in the pig industry. Nine ML algorithms, including tree-based, kernel-based, probabilistic, and linear algorithms, were used. Results: Beta diversity analysis on 16 S rRNA microbiome data revealed compositional divergence among genetic, age and batch groups. ML models exploring maternal, paternal and heterosis effects showed varying levels of classification performance, with the paternal effect scenario being the best, achieving a mean Area Under the ROC curve (AUROC) of 0.74 using the Catboost (CB) algorithm. However, the most genetically distant animals, the purebreds, were more easily discriminated using the ML models. The classification of the two Iberian strains reached the highest mean AUROC of 0.83 using Support Vector Machine (SVM) model. The most relevant genera in this classification performance were Acetitomaculum, Butyricicoccus and Limosilactobacillus. All of which exhibited a relevant differential abundance between purebred animals using a Bayesian linear model. Conclusions: The study confirms variations in gut microbiota among Iberian pig strains and their crosses, influenced by genetic and non-genetic factors. ML models, particularly CB and RF, as well as SVM in certain scenarios, combined with a feature selection process, effectively classified genetic groups based on microbiome data and identified key microbial taxa. These taxa were linked to short-chain fatty acids production and lipid metabolism, suggesting microbial composition differences may contribute to variations in fat-related traits among Iberian genetic groups. [ABSTRACT FROM AUTHOR]
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- 2025
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18. Genetic inbreeding load and its individual prediction for milk yield in French dairy sheep.
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Antonios, Simona, Rodríguez-Ramilo, Silvia T., Legarra, Andres, Astruc, Jean-Michel, Varona, Luis, and Vitezica, Zulma G.
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GENETIC load ,LIKELIHOOD ratio tests ,MILK yield ,INBREEDING ,LIFE sciences ,GENETICS - Abstract
Background: The magnitude of inbreeding depression depends on the recessive burden of the individual, which can be traced back to the hidden (recessive) inbreeding load among ancestors. However, these ancestors carry different alleles at potentially deleterious loci and therefore there is individual variability of this inbreeding load. Estimation of the additive genetic value for inbreeding load is possible using a decomposition of inbreeding in partial inbreeding components due to ancestors. Both the magnitude of variation in partial inbreeding components and the additive genetic variance of inbreeding loads are largely unknown. Our study had three objectives. First, based on substitution effect under non-random matings, we showed analytically that inbreeding load of an ancestor can be expressed as an additive genetic effect. Second, we analysed the structure of individual inbreeding by examining the contributions of specific ancestors/founders using the concept of partial inbreeding coefficients in three French dairy sheep populations (Basco-Béarnaise, Manech Tête Noire and Manech Tête Rousse). Third, we included these coefficients in a mixed model as random regression covariates, to predict genetic variance and breeding values of the inbreeding load for milk yield in the same breeds. Results: Pedigrees included 190,276, 166,028 and 633,655 animals of Basco-Béarnaise, Manech Tête Noire and Manech Tête Rousse, respectively, born between 1985 and 2021. A fraction of 99.1% of the partial inbreeding coefficients were lower than 0.01 in all breeds, meaning that in practice inbreeding occurs in pedigree loops that span several generations backwards. Less than 5% ancestors generate inbreeding, because mating is essentially between unrelated individuals. Inbreeding load estimations involved 658,731, 541,180 and 2,168,454 records of yearly milk yield from 178,123, 151,863 and 596,586 females in Basco-Béarnaise, Manech Tête Noire and Manech Tête Rousse, respectively. Adding the inbreeding load effect to the model improved the fitting (values of the statistic Likelihood Ratio Test between 132 and 383) for milk yield in the three breeds. The inbreeding load variances were equal to 11,804 and 9435 L squared of milk yield for a fully inbred (100%) descendant in Manech Tête Noire and Manech Tête Rousse. In Basco-Béarnaise, the estimate of the inbreeding load variance (11,804) was not significantly different from zero. The correlations between (direct effect) additive genetic and inbreeding load effects were − 0.09, − 0.08 and − 0.12 in Basco-Béarnaise, Manech Tête Noire and Manech Tête Rousse. Conclusions: The decomposition of inbreeding in partial coefficients in these populations shows that inbreeding is mostly due to several small contributions of ancestors (lower than 0.001) going back several generations (5 to 7 generations), which is according to the policy of avoiding close matings. There is variation of inbreeding load among animals, although its magnitude does not seem enough to warrant selection based on this criterion. [ABSTRACT FROM AUTHOR]
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- 2025
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19. Use of Bayes factors to evaluate the effects of host genetics, litter and cage on the rabbit cecal microbiota
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Velasco-Galilea, María, Piles, Miriam, Ramayo-Caldas, Yuliaxis, Varona, Luis, and Sánchez, Juan Pablo
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- 2022
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20. Safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis (the REFALS study): a randomised, double-blind, placebo-controlled phase 3 trial
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Kiernan, Matthew, Mathers, Susan, Henderson, Robert, Needham, Merrilee, Schultz, David, Löscher, Wolfgang, Mitrovic, Nenad, Rath, Jakob, Damme, Philip Van, De Bleecker, Jan L., Delstanche, Stéphanie, Johnston, Wendy, Zinman, Lorne, O'Connell, Colleen, Matte, Genevieve, Dionne, Annie, Korngut, Lawrence, Turnbull, John, Laaksovirta, Hannu, Jokela, Manu, Tapiola, Tero, Soriani, Marie-Hélène, Couratier, Philippe, Camu, William, Corcia, Philippe, Ludolph, Albert, Großkreutz, Julian, Meyer, Thomas, Boentert, Matthias, Schrank, Berthold, Prudlo, Johannes, Untucht, Robert, Hardiman, Orla, Siciliano, Gabriele, Chio', Adriano, Mazzini, Letizia, Inghilleri, Maurizio, Caponnetto, Claudia, Mora, Gabriele, Mora Pardina, Jesús S, Farrero Munoz, Eva, Vázquez Costa, Juan F, Aguera Morales, Eduardo, Varona, Luis, Andersen, Peter, Ingre, Caroline, Johansson, Rune, Radunovic, Aleksandar, Young, Carolyn, Babu, Suma, Shaibani, Aziz, Staff, Nathan, Vu, Tuan, Rivner, Michael, Scelsa, Stephen, Sivakumar, Kumaraswamy, Waheed, Waqar, Heitzman, Daragh, Rana, Sandeep, Pattee, Gary, Ajroud-Driss, Senda, Bayat, Elham, Kasarskis, Edward, Lange, Dale J, Elliott, Michael, Harris, Brent, Felice, Kevin, Pulley, Michael T, Kwan, Justin, Brown, Martin, Ravits, John, Burford, Matthew, Karam, Chafic, Miller, Timothy, Andrews, Jinsy, Levine, Todd, Locatelli, Eduardo, Wymer, James, Bedlack, Richard, Fee, Dominic, Goyal, Namita, Oskarsson, Bjorn, McCluskey, Leo, Caress, James, Weiss, Michael, Quick, Adam, Bromberg, Mark, Lacomis, David, Goutman, Stephen, Rezania, Kourosh, Guliani, Gaurav, Goslin, Kimberly, Katz, Jonathan S, Cudkowicz, Merit, Genge, Angela, Maragakis, Nicholas, Petri, Susanne, van den Berg, Leonard, Aho, Valtteri V, Sarapohja, Toni, Kuoppamäki, Mikko, Garratt, Chris, and Al-Chalabi, Ammar
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- 2021
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21. Bayesian inference of the inbreeding load variance for fertility traits in Brown Swiss cattle
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Martinez-Castillero, Maria, Varona, Luis, Pegolo, Sara, Rossoni, Attilio, and Cecchinato, Alessio
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- 2021
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22. A dimensional reduction approach to modulate the core ruminal microbiome associated with methane emissions via selective breeding
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Saborío-Montero, Alejandro, López-García, Adrían, Gutiérrez-Rivas, Mónica, Atxaerandio, Raquel, Goiri, Idoia, García-Rodriguez, Aser, Jiménez-Montero, José A., González, Carmen, Tamames, Javier, Puente-Sánchez, Fernando, Varona, Luis, Serrano, Magdalena, Ovilo, Cristina, and González-Recio, Oscar
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- 2021
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23. Genomic Prediction Methods Accounting for Nonadditive Genetic Effects
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Varona, Luis, primary, Legarra, Andres, additional, Toro, Miguel A., additional, and Vitezica, Zulma G., additional
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- 2022
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24. Correction to: Genomic Prediction Methods Accounting for Nonadditive Genetic Effects
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Varona, Luis, primary, Legarra, Andres, additional, Toro, Miguel A., additional, and Vitezica, Zulma G., additional
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- 2022
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25. Economic growth and the foreign sector: Peru 1821–2020.
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Varona, Luis, Gonzales, Jorge R, García, Benjamín, and Gismera, Laura
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INVESTMENT policy ,FOREIGN exchange ,ECONOMIC expansion ,INTERNATIONAL markets ,HUMAN capital ,ENDOGENOUS growth (Economics) ,NATURAL capital - Abstract
Thirlwall Model shows evidence in Latin American countries, as well as for the Peruvian economy, with an economic growth rate of balance of payments equilibrium, which is explained by causal variables that present a long-term cointegration relationship. These variables are exports with little added value, imports that reinforce technological dependence, external income, relative prices or the real exchange rate, the institutions, and the volatility of exports. Investment policies are prescribed in innovative, physical, financial, natural, and social human capital that tend to reduce the restriction of foreign exchange, technological dependence and the international market. Therefore, endogenous, dynamic, sustained, inclusive economic growth is generated, low in carbon as a means for sustainable human development, within the framework of a new growth and development strategy that involves balancing the participation of the market, state and civil society. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Food import demand in Peru, 1980-2021.
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Gonzales, Jorge R. and Varona, Luis
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INVESTMENT policy ,FOREIGN exchange rates ,PRICES ,ORGANIC fertilizers ,FREE trade - Abstract
This study analyses and explains food imports from Peru: 1980-2021. The econometric method uses Autoregressive Distributed Lagged (ARDL) models. The result of the stationarity property of I (0) and I(1) of the variables suggests the use of the ARDL model. The Granger causality result shows that variables explain food imports. The bound test cointegration showed a long-run cointegration to exist between foot imports and income, the real exchange rate, relative prices, price of fertilizers, and institution. The short-run analysis shows positive effects of relative prices and the real exchange rate towards food imports. And in the long-run analysis, we have found a positive relationship between food imports and economic growth. Also, there is a negative relationship between food imports and the growth of the real exchange rate, the price of fertilizers, and the opening of the Free Trade Agreement. Policies for self-sufficiency are recommended through investment policies in human capital for research in fertilizers and alternative organic manures; in financial capital for access to credit for small producers; in social capital, with support for sectors with lower productivity in rural areas to reduce dependence on the international market and the growing demand for food imports that puts food security at risk. [ABSTRACT FROM AUTHOR]
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- 2024
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- View/download PDF
27. Usefulness of running animal models in absence of pedigrees: Estimation of genetic parameters for gastrointestinal parasite resistance traits in Djallonké sheep of Burkina Faso
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Álvarez, Isabel, Traoré, Amadou, Fernández, Iván, Cervantes, Isabel, Varona, Luis, Soudré, Albert, Kaboré, Adama, Menéndez-Arias, Nuria A., Sanou, Moumouni, Tamboura, Hamidou H., and Goyache, Félix
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- 2018
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28. A multivariate gametic model for the analysis of purebred and crossbred data. An example between two populations of Iberian pigs
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Srihi, Houssemeddine, primary, López‐Carbonell, David, additional, Ibáñez‐Escriche, Noelia, additional, Casellas, Joaquim, additional, Hernández, Pilar, additional, Negro, Sara, additional, and Varona, Luis, additional
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- 2023
- Full Text
- View/download PDF
29. Genomic Scanning of Inbreeding Depression for Litter Size in Two Varieties of Iberian Pigs
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Hervás-Rivero, Carlos, primary, Srihi, Houssemeddine, additional, López-Carbonell, David, additional, Casellas, Joaquim, additional, Ibáñez-Escriche, Noelia, additional, Negro, Sara, additional, and Varona, Luis, additional
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- 2023
- Full Text
- View/download PDF
30. Genomic Scan of the Inbreeding Depression for Litter Size in Two Varieties of Iberian Pigs
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Hervás-Rivero, Carlos, primary, Srihi, Houssemeddine, additional, Carbonell, David López, additional, Casellas, Joaquim, additional, Ibañez-Escriche, Noelia, additional, Negro, Sara, additional, and Varona, Luis, additional
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- 2023
- Full Text
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31. The influence of natural selection in breeding programs: A simulation study
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García-Ballesteros, Silvia, Gutiérrez, Juan Pablo, Varona, Luis, and Fernández, Jesús
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- 2017
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32. Bayesian analysis of pig growth curves combining pedigree and genomic information
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Lázaro, Sirlene Fernandes, Ibáñez-Escriche, Noelia, Varona, Luis, Silva, Fabyano Fonseca e, Brito, Lais Costa, Guimarães, Simone Eliza Facioni, and Lopes, Paulo Sávio
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- 2017
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33. A cross-specific multiplicative binomial recursive model for the analysis of perinatal mortality in a diallel cross among three varieties of Iberian pig
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Varona, Luis, Noguera, José Luis, Casellas, Joaquim, de Hijas, Melani Martín, Rosas, Juan Pablo, and Ibáñez-Escriche, Noelia
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- 2020
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34. Genetic inbreeding depression load for morphological traits and defects in the Pura Raza Española horse
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Poyato-Bonilla, Julia, Perdomo-González, Davinia I., Sánchez-Guerrero, María J., Varona, Luis, Molina, Antonio, Casellas, Joaquim, and Valera, Mercedes
- Published
- 2020
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35. A multivariate gametic model for the analysis of purebred and crossbred data. An example between two populations of Iberian pigs.
- Author
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Srihi, Houssemeddine, López‐Carbonell, David, Ibáñez‐Escriche, Noelia, Casellas, Joaquim, Hernández, Pilar, Negro, Sara, and Varona, Luis
- Subjects
SWINE ,GENOMIC imprinting ,CROSSBREEDING ,PIGLETS ,BAYESIAN analysis - Abstract
Crossbreeding plays a pivotal role within pig breeding programmes, aiming to maximize heterosis and improve reproductive traits in crossbred maternal lines. Nevertheless, there is evidence indicating that the performance of reciprocal crosses between two genetic lines might exhibit variability. These variations in performance can be attributed to differences in the correlations between gametic effects, acting as either sire or dam, within purebred and crossbred populations. To address this issue, we propose a multivariate gametic model that incorporates up to four correlated gametic effects for each parental population. The model is employed on a data set comprising litter size data (total number of piglets born—TNB‐ and number of piglets born alive—NBA‐) derived from a reciprocal cross involving two Iberian pig populations: Entrepelado and Retinto. The data set comprises 6933 records from 1564 purebred Entrepelado (EE) sows, 4995 records from 1015 Entrepelado × Retinto (ER) crosses, 2977 records from 756 Retinto × Entrepelado (RE) crosses and 7497 records from 1577 purebred Retinto (RR) sows. The data set is further supplemented by a pedigree encompassing 6007 individual‐sire‐dam entries. The statistical model also included the order of parity (with six levels), the breed of the service sire (five levels) and the herd‐year‐season effects (141 levels). Additionally, the model integrates random dominant and permanent environmental sow effects. The analysis employed a Bayesian approach, and the results revealed all the posterior estimates of the gametic correlations to be positive. The range of the posterior mean estimates of the correlations varied across different gametic effects and traits, with a range between 0.04 (gametic correlation between the paternal effects for purebred and the maternal for crossbred in Retinto) and 0.53 (gametic correlation between the paternal effects for purebred and the paternal for crossbred in Entrepelado). Furthermore, the posterior mean variance estimates of the maternal gametic effects were consistently surpassed those for paternal effects within all four populations. The results suggest the possible influence of imprinting effects on the genetic control of litter size, and underscore the importance of incorporating crossbred data into the breeding value predictions for purebred individuals. [ABSTRACT FROM AUTHOR]
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- 2024
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36. A multivariate analysis with direct additive and inbreeding depression load effects
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Varona, Luis, Altarriba, Juan, Moreno, Carlos, Martínez-Castillero, María, and Casellas, Joaquim
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- 2019
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37. Characterizing SOD1 mutations in Spain. The impact of genotype, age, and sex in the natural history of the disease
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Instituto de Salud Carlos III, European Commission, Comunidad de Madrid, Ministerio de Sanidad (España), Centro de Investigación Biomédica en Red Enfermedades Raras (España), Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Pérez-Tur, Jordi [0000-0002-9111-1712], Vázquez-Costa, Juan F., Borrego-Hernández, Daniel, Paradas, Carmen, Gómez-Caravaca, María Teresa, Rojas-García, Ricardo, Varona, Luis, Povedano, Mónica, García-Sobrino, Tania, Jericó Pascual, Ivonne, Gutierrez, Antonio, Riancho, Javier, Turón-Sans, Janina, Assialioui, Abdelilah, Pérez-Tur, Jordi, Sevilla, Teresa, Esteban Pérez, Jesús, García-Redondo, Alberto, Instituto de Salud Carlos III, European Commission, Comunidad de Madrid, Ministerio de Sanidad (España), Centro de Investigación Biomédica en Red Enfermedades Raras (España), Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Pérez-Tur, Jordi [0000-0002-9111-1712], Vázquez-Costa, Juan F., Borrego-Hernández, Daniel, Paradas, Carmen, Gómez-Caravaca, María Teresa, Rojas-García, Ricardo, Varona, Luis, Povedano, Mónica, García-Sobrino, Tania, Jericó Pascual, Ivonne, Gutierrez, Antonio, Riancho, Javier, Turón-Sans, Janina, Assialioui, Abdelilah, Pérez-Tur, Jordi, Sevilla, Teresa, Esteban Pérez, Jesús, and García-Redondo, Alberto
- Abstract
Introduction: The aim of this study is to describe the frequency and distribution of SOD1 mutations in Spain, and to explore those factors contributing to their phenotype and prognosis. Methods: Seventeen centres shared data on amyotrophic lateral sclerosis (ALS) patients carrying pathogenic or likely pathogenic SOD1 variants. Multivariable models were used to explore prognostic modifiers. Results: In 144 patients (from 88 families), 29 mutations (26 missense, 2 deletion/insertion and 1 frameshift) were found in all 5 exons of SOD1, including 7 novel mutations. 2.6% of ALS patients (including 17.7% familial and 1.3% sporadic) were estimated to carry SOD1 mutations. Its frequency varied considerably between regions, due to founder events. The most frequent mutation was p.Gly38Arg (n = 58), followed by p.Glu22Gly (n = 11), p.Asn140His (n = 10), and the novel p.Leu120Val (n = 10). Most mutations were characterized by a protracted course, and some of them by atypical phenotypes. Older age of onset was independently associated with faster disease progression (exp(Estimate) = 1.03 [0.01, 0.05], p = 0.001) and poorer survival (HR = 1.05 [1.01, 1.08], p = 0.007), regardless of the underlying mutation. Female sex was independently associated to faster disease progression (exp(Estimate) = 2.1 [1.23, 3.65], p = 0.012) in patients carrying the p.Gly38Arg mutation, resulting in shorter survival compared with male carriers (236 vs 301 months). Conclusions: These data may help to evaluate the efficacy of SOD1 targeted treatments, and to expand the number of patients that might benefit from these treatments.
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- 2023
38. Invited review: Recursive models in animal breeding: Interpretation, limitations, and extensions
- Author
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Varona, L. [0000-0001-6256-5478], González Recio, Oscar [0000-0002-9106-4063], Varona, Luis, González Recio, Oscar, Varona, L. [0000-0001-6256-5478], González Recio, Oscar [0000-0002-9106-4063], Varona, Luis, and González Recio, Oscar
- Abstract
Structural equation models allow causal effects between 2 or more variables to be considered and can postulate unidirectional (recursive models; RM) or bidirectional (simultaneous models) causality between variables. This review evaluated the properties of RM in animal breeding and how to interpret the genetic parameters and the corresponding estimated breeding values. In many cases, RM and mixed multitrait models (MTM) are statistically equivalent, although subject to the assumption of variance-covariance matrices and restrictions imposed for achieving model identification. Inference under RM requires imposing some restrictions on the (co)variance matrix or on the location parameters. The estimates of the variance components and the breeding values can be transformed from RM to MTM, although the biological interpretation differs. In the MTM, the breeding values predict the full influence of the additive genetic effects on the traits and should be used for breeding purposes. In contrast, the RM breeding values express the additive genetic effect while holding the causal traits constant. The differences between the additive genetic effect in RM and MTM can be used to identify the genomic regions that affect the additive genetic variation of traits directly or causally mediated for another trait or traits. Furthermore, we presented some extensions of the RM that are useful for modeling quantitative traits with alternative assumptions. The equivalence of RM and MTM can be used to infer causal effects on sequentially expressed traits by manipulating the residual (co)variance matrix under the MTM. Further, RM can be implemented to analyze causality between traits that might differ among subgroups or within the parametric space of the independent traits. In addition, RM can be expanded to create models that introduce some degree of regularization in the recursive structure that aims to estimate a large number of recursive parameters. Finally, RM can be used in some cases
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- 2023
39. Evaluación de algoritmos de clasificación para la identificación de la deforestación en el resguardo indígena Llanos del Yarí Yaguara II.
- Author
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Cumbe Loaiza, Laura Camila, Guerrero Varona, Luis Miguel, and Medina Daza, Rubén Javier
- Subjects
LAND use mapping ,CLASSIFICATION algorithms ,DEFORESTATION ,SUPPORT vector machines ,IMAGE recognition (Computer vision) - Abstract
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- 2024
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40. A Bayesian Multivariate Gametic Model in a Reciprocal Cross with Genomic Information: An Example with Two Iberian Varieties
- Author
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Srihi, Houssemeddine, primary, López-Carbonell, David, additional, Ibáñez-Escriche, Noelia, additional, Casellas, Joaquim, additional, Hernández, Pilar, additional, Negro, Sara, additional, and Varona, Luis, additional
- Published
- 2023
- Full Text
- View/download PDF
41. Food import demand in Peru, 1980-2021
- Author
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Gonzales, Jorge R., primary and Varona, Luis, additional
- Published
- 2023
- Full Text
- View/download PDF
42. Correlaciones genéticas entre caracteres morfológicos y caracteres reproductivos, de crecimiento y calidad de la canal en la raza bovina Pirenaica
- Author
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Lopez-Carbonell, David, primary, Altarriba, Juan, additional, Ramírez, Marco Aurelio, additional, Srihi, Houssemeddine, additional, and Varona, Luis, additional
- Published
- 2023
- Full Text
- View/download PDF
43. APPENDIX_A.docx
- Author
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Varona, Luis and Gonzalez-Recio, Oscar
- Abstract
R code for the calculation of Figures 2 and 3 of the manuscript: Invited review: Recursive models in animal breeding: Interpretation, limitations, and extensions L. Varona and O. González-Recio (2023) https://doi.org/10.3168/jds.2022-22578
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- 2023
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44. Genomic information in pig breeding: Science meets industry needs
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Ibáñez-Escriche, Noelia, Forni, Selma, Noguera, Jose Luis, and Varona, Luis
- Published
- 2014
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45. Quantitative analysis of parent‐of‐origin effect in reproductive and morphological selection criteria in the Pura Raza Española horse.
- Author
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Perdomo‐González, Davinia I., Varona, Luis, Molina, Antonio, Laseca, Nora, and Valera, Mercedes
- Subjects
- *
PEARSON correlation (Statistics) , *HORSE breeds , *HORSES , *QUANTITATIVE genetics , *HORSE breeding , *MARES , *QUANTITATIVE research , *MENDEL'S law - Abstract
It is generally assumed that parents make a genetically equal contribution to their offspring, but this assumption might not always hold. This is because the expression of a gene can be blocked by methylation during gametogenesis, and the degree of methylation can depend on the origin of the parental gene (imprinting) or by preferential management associated with genetic merit. The first consequences of this for quantitative genetics is that the mean phenotypes of reciprocal heterozygotes need no longer be the same, as would be expected according to Mendelian heritage. We analysed three mare reproductive traits (reproductive efficiency, age at first foaling and foaling number) and three morphological traits (height at withers, thoracic circumference, and scapula‐ischial length) in the Pura Raza Española (PRE) horse population, which possesses a deep and reliable pedigree, making it a perfect breed for analysing the quantitative effect of parent‐of‐origin. The number of animals analysed ranged from 44,038 to 144,191, all of them with both parents known. The model comparison between a model without parent‐of‐origin effects and three different models with parent‐of‐origin effects revealed that both maternal and paternal gametic effects influence all the analysed traits. The maternal gametic effect had a higher influence on most traits, accounting for between 3% and 11% of the total phenotypic variance, while the paternal gametic effect accounted for a higher proportion of variance in one trait, age at first foaling (4%). As expected, the Pearson's correlations between additive breeding values of models that consider parent‐of‐origin and that do not consider parent‐of‐origin were very high; however, the percentage of coincident animals slightly decreases when comparing animals with the highest estimated breeding values. Ultimately, this work demonstrates that parent‐of‐origin effects exist in horse gene transmission from a quantitative point of view. Additionally, including an estimate of the parent‐of‐origin effect within the PRE horse breeding program could be a great tool for a better parent's selection and that could be of interest for breeders, as this value will determine whether the animals acquire genetic categories and are much more highly valued. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
46. Clinical trials in pediatric ALS: a TRICALS feasibility study
- Author
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Kliest, Tessa, Van Eijk, Ruben P.A., Al-Chalabi, Ammar, Albanese, Alberto, Andersen, Peter M., Amador, Maria Del Mar, Bråthen, Geir, Brunaud-Danel, Veronique, Brylev, Lev, Camu, William, De Carvalho, Mamede, Cereda, Cristina, Cetin, Hakan, Chaverri, Delia, Chiò, Adriano, Corcia, Philippe, Couratier, Philippe, De Marchi, Fabiola, Desnuelle, Claude, Van Es, Michael A., Esteban, JesÚs, Filosto, Massimiliano, GarcÍa Redondo, Alberto, Grosskreutz, Julian, Hanemann, Clemens O., Holmøy, Trygve, Høyer, Helle, Ingre, Caroline, Koritnik, Blaz, Kuzma-Kozakiewicz, Magdalena, Lambert, Thomas, Leigh, Peter N., Lunetta, Christian, Mandrioli, Jessica, Mcdermott, Christopher J., Meyer, Thomas, Mora, Jesus S., Petri, Susanne, Povedano, Mónica, Reviers, Evy, Riva, Nilo, Roes, Kit C.B., Rubio, Miguel Á., Salachas, François, Sarafov, Stayko, Sorarù, Gianni, Stevic, Zorica, Svenstrup, Kirsten, Møller, Anette Torvin, Turner, Martin R., Van Damme, Philip, Van Leeuwen, Lucie A.G., Varona, Luis, VÁzquez Costa, Juan F., Weber, Markus, Hardiman, Orla, Van Den Berg, Leonard H., Kliest, Tessa, Van Eijk, Ruben P.A., Al-Chalabi, Ammar, Albanese, Alberto, Andersen, Peter M., Amador, Maria Del Mar, Bråthen, Geir, Brunaud-Danel, Veronique, Brylev, Lev, Camu, William, De Carvalho, Mamede, Cereda, Cristina, Cetin, Hakan, Chaverri, Delia, Chiò, Adriano, Corcia, Philippe, Couratier, Philippe, De Marchi, Fabiola, Desnuelle, Claude, Van Es, Michael A., Esteban, JesÚs, Filosto, Massimiliano, GarcÍa Redondo, Alberto, Grosskreutz, Julian, Hanemann, Clemens O., Holmøy, Trygve, Høyer, Helle, Ingre, Caroline, Koritnik, Blaz, Kuzma-Kozakiewicz, Magdalena, Lambert, Thomas, Leigh, Peter N., Lunetta, Christian, Mandrioli, Jessica, Mcdermott, Christopher J., Meyer, Thomas, Mora, Jesus S., Petri, Susanne, Povedano, Mónica, Reviers, Evy, Riva, Nilo, Roes, Kit C.B., Rubio, Miguel Á., Salachas, François, Sarafov, Stayko, Sorarù, Gianni, Stevic, Zorica, Svenstrup, Kirsten, Møller, Anette Torvin, Turner, Martin R., Van Damme, Philip, Van Leeuwen, Lucie A.G., Varona, Luis, VÁzquez Costa, Juan F., Weber, Markus, Hardiman, Orla, and Van Den Berg, Leonard H.
- Abstract
Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA). Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe. Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS. Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS. Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information.
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- 2022
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47. Additional file 7 of Use of Bayes factors to evaluate the effects of host genetics, litter and cage on the rabbit cecal microbiota
- Author
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CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Velasco‐Galilea, María, Piles, Miriam, Ramayo-Caldas, Yuliaxis, Varona, Luis, Sánchez, Juan Pablo, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Velasco‐Galilea, María, Piles, Miriam, Ramayo-Caldas, Yuliaxis, Varona, Luis, and Sánchez, Juan Pablo
- Abstract
Additional file 7: Table S5. Mean (standard deviation) of Bayes factors and cage variance ratio estimates for OTU that are influenced by cage effects and adjusted with the normal LMM. Table S6. Mean (standard deviation) of Bayes factor and cage variance ratio estimates for OTU that are influenced by cage effect and adjusted with the ZIP model. Tables S7. Bayes factors, marginal posterior means (standard deviations) of cage variance ratio for genera and alpha-diversity indices that are influenced by cage effects.
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- 2022
48. Additional file 9 of Use of Bayes factors to evaluate the effects of host genetics, litter and cage on the rabbit cecal microbiota
- Author
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CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Velasco‐Galilea, María, Piles, Miriam, Ramayo-Caldas, Yuliaxis, Varona, Luis, Sánchez, Juan Pablo, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Velasco‐Galilea, María, Piles, Miriam, Ramayo-Caldas, Yuliaxis, Varona, Luis, and Sánchez, Juan Pablo
- Abstract
Additional file 9: Table S9. Bayes factors, marginal posterior means and standard deviations of litter variance ratio for OTU influenced by litter effects together with the associated probability of these estimates being higher than 0.10. The frequency among the rabbit samples and the taxonomic assignment are also provided for each OTU.
- Published
- 2022
49. Additional file 8 of Use of Bayes factors to evaluate the effects of host genetics, litter and cage on the rabbit cecal microbiota
- Author
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CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Velasco‐Galilea, María, Piles, Miriam, Ramayo-Caldas, Yuliaxis, Varona, Luis, Sánchez, Juan Pablo, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Velasco‐Galilea, María, Piles, Miriam, Ramayo-Caldas, Yuliaxis, Varona, Luis, and Sánchez, Juan Pablo
- Abstract
Additional file 8: Table S8. Bayes factors, marginal posterior means and standard deviations of heritability estimates for OTU under genetic control together with the associated probability of these estimates being higher than 0.10. The frequency among the rabbit samples and the taxonomic assignment are also provided for each OTU.
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- 2022
50. Additional file 10 of Use of Bayes factors to evaluate the effects of host genetics, litter and cage on the rabbit cecal microbiota
- Author
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CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Velasco‐Galilea, María, Piles, Miriam, Ramayo-Caldas, Yuliaxis, Varona, Luis, Sánchez, Juan Pablo, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Velasco‐Galilea, María, Piles, Miriam, Ramayo-Caldas, Yuliaxis, Varona, Luis, and Sánchez, Juan Pablo
- Abstract
Additional file 10: Table S10. Bayes factors, marginal posterior means and standard deviations of cage variance ratio for OTU influenced by cage effects together with the associated probability of these estimates being higher than 0.10. The frequency among the rabbit samples and the taxonomic assignment are also provided for each OTU.
- Published
- 2022
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