1. |
- Nelson, Ronald, et al.
(author)
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qtl.outbred: Interfacing outbred line cross data with the R/qtl mapping software
- 2011
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In: BMC Research Notes. - : BioMed Central. - 1756-0500. ; 4:154
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Journal article (peer-reviewed)abstract
- Backgroundqtl.outbred is an extendible interface in the statistical environment, R, for combining quantitative trait loci (QTL) mapping tools. It is built as an umbrella package that enables outbred genotype probabilities to be calculated and/or imported into the software package R/qtl.FindingsUsing qtl.outbred, the genotype probabilities from outbred line cross data can be calculated by interfacing with a new and efficient algorithm developed for analyzing arbitrarily large datasets (included in the package) or imported from other sources such as the web-based tool, GridQTL.Conclusionqtl.outbred will improve the speed for calculating probabilities and the ability to analyse large future datasets. This package enables the user to analyse outbred line cross data accurately, but with similar effort than inbred line cross data.
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2. |
- LeBlanc, Neil, et al.
(author)
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A novel combination of TaqMan RT-PCR and a suspension microarray assay for the detection and species identification of pestiviruses
- 2010
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In: Veterinary Microbiology. - : Elsevier BV. - 0378-1135 .- 1873-2542. ; 142:1-2, s. 81-86
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Journal article (peer-reviewed)abstract
- The genus pestivirus contains four recognized species: classical swine fever virus, border disease virus, bovine viral diarrhoea virus types 1 and 2. All are economically important and globally distributed but classical swine fever is the most serious, concerning losses and control measures. It affects both domestic pigs and wild boars. Outbreaks of this disease in domestic pigs call for the most serious measures of disease control, including a stamping out policy in Europe. Since all the members of the pestivirus genus can infect swine, differential diagnosis using traditional methods poses some problems. Antibody tests may lack specificity due to cross-reactions, antigen capture ELISAs may have low sensitivity, and virus isolation may take several days or even longer time to complete. PCR-based tests overcome these problems for the most part, but in general lack the multiplexing capability to detect and differentiate all the pestiviruses simultaneously. The assay platform described here addresses all of these issues by combining the advantages of real-time PCR with the multiplexing capability of microarray technology. The platform includes a TaqMan real-time PCR designed for the universal detection of pestiviruses and a microarray assay that can use the amplicons produced in the real-time PCR to identify the specific pestivirus.
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3. |
- Shen, Xia, et al.
(author)
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Hierarchical likelihood opens a new way of estimating genetic values using genome-wide dense marker maps
- 2011
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In: BMC Proceedings. - 1753-6561. ; :5(Suppl 3)
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Journal article (peer-reviewed)abstract
- Background Genome-wide dense markers have been used to detect genes and estimate relative genetic values. Among many methods, Bayesian techniques have been widely used and shown to be powerful in genome-wide breeding value estimation and association studies. However, computation is known to be intensive under the Bayesian framework, and specifying a prior distribution for each parameter is always required for Bayesian computation. We propose the use of hierarchical likelihood to solve such problems. Results Using double hierarchical generalized linear models, we analyzed the simulated dataset provided by the QTLMAS 2010 workshop. Marker-specific variances estimated by double hierarchical generalized linear models identified the QTL with large effects for both the quantitative and binary traits. The QTL positions were detected with very high accuracy. For young individuals without phenotypic records, the true and estimated breeding values had Pearson correlation of 0.60 for the quantitative trait and 0.72 for the binary trait, where the quantitative trait had a more complicated genetic architecture involving imprinting and epistatic QTL. Conclusions Hierarchical likelihood enables estimation of marker-specific variances under the likelihoodist framework. Double hierarchical generalized linear models are powerful in localizing major QTL and computationally fast.
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4. |
- Rönnegård, Lars, et al.
(author)
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Genetic heterogeneity of residual variance - estimation of variance components using double hierarchical generalized linear models
- 2010
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In: Genetics Selection Evolution. - : Springer Science and Business Media LLC. - 0999-193X .- 1297-9686. ; 42
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Journal article (peer-reviewed)abstract
- Background: The sensitivity to microenvironmental changes varies among animals and may be under genetic control. It is essential to take this element into account when aiming at breeding robust farm animals. Here, linear mixed models with genetic effects in the residual variance part of the model can be used. Such models have previously been fitted using EM and MCMC algorithms.Results: We propose the use of double hierarchical generalized linear models (DHGLM), where the squared residuals are assumed to be gamma distributed and the residual variance is fitted using a generalized linear model. The algorithm iterates between two sets of mixed model equations, one on the level of observations and one on the level of variances. The method was validated using simulations and also by re-analyzing a data set on pig litter size that was previously analyzed using a Bayesian approach. The pig litter size data contained 10,060 records from 4,149 sows. The DHGLM was implemented using the ASReml software and the algorithm converged within three minutes on a Linux server. The estimates were similar to those previously obtained using Bayesian methodology, especially the variance components in the residual variance part of the model.Conclusions: We have shown that variance components in the residual variance part of a linear mixed model can be estimated using a DHGLM approach. The method enables analyses of animal models with large numbers of observations. An important future development of the DHGLM methodology is to include the genetic correlation between the random effects in the mean and residual variance parts of the model as a parameter of the DHGLM.
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5. |
- Besnier, Francois, et al.
(author)
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Fine mapping and replication of QTL in outbred chicken advanced intercross lines
- 2011
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In: Genetics Selection Evolution. - Paris : Springer Science and Business Media LLC. - 0999-193X .- 1297-9686. ; 43, s. 3-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Linkage mapping is used to identify genomic regions affecting the expression of complex traits. However, when experimental crosses such as F2 populations or backcrosses are used to map regions containing a Quantitative Trait Locus (QTL), the size of the regions identified remains quite large, i.e. 10 or more Mb. Thus, other experimental strategies are needed to refine the QTL locations. Advanced Intercross Lines (AIL) are produced by repeated intercrossing of F2 animals and successive generations, which decrease linkage disequilibrium in a controlled manner. Although this approach is seen as promising, both to replicate QTL analyses and fine-map QTL, only a few AIL datasets, all originating from inbred founders, have been reported in the literature.METHODS: We have produced a nine-generation AIL pedigree (n = 1529) from two outbred chicken lines divergently selected for body weight at eight weeks of age. All animals were weighed at eight weeks of age and genotyped for SNP located in nine genomic regions where significant or suggestive QTL had previously been detected in the F2 population. In parallel, we have developed a novel strategy to analyse the data that uses both genotype and pedigree information of all AIL individuals to replicate the detection of and fine-map QTL affecting juvenile body weight.RESULTS: Five of the nine QTL detected with the original F2 population were confirmed and fine-mapped with the AIL, while for the remaining four, only suggestive evidence of their existence was obtained. All original QTL were confirmed as a single locus, except for one, which split into two linked QTL.CONCLUSIONS: Our results indicate that many of the QTL, which are genome-wide significant or suggestive in the analyses of large intercross populations, are true effects that can be replicated and fine-mapped using AIL. Key factors for success are the use of large populations and powerful statistical tools. Moreover, we believe that the statistical methods we have developed to efficiently study outbred AIL populations will increase the number of organisms for which in-depth complex traits can be analyzed.
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6. |
- Rönnegård, Lars, et al.
(author)
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Hglm: A package for fitting hierarchical generalized linear models
- 2010
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In: The R Journal. - 2073-4859. ; 2:2, s. 20-28
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Journal article (peer-reviewed)abstract
- We present the hglm package for fitting hierarchical generalized linear models. It can be used for linear mixed models and generalized linear mixed models with random effects for a variety of links and a variety of distributions for both the outcomes and the random effects. Fixed effects can also be fitted in the dispersion part of the model.
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7. |
- Rönnegård, Lars, et al.
(author)
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How to deal with genotype uncertainty in variance component quantitative trait loci analyses
- 2011
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In: Genetics Research. - : Cambridge University Press. - 0016-6723 .- 1469-5073. ; 93, s. 333-342
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Journal article (peer-reviewed)abstract
- Dealing with genotype uncertainty is an ongoing issue in genetic analyses of complex traits. Here we consider genotype uncertainty in quantitative trait loci (QTL) analyses for large crosses in variance component models, where the genetic information is included in identity-by-descent (IBD) matrices. An IBD matrix is one realization from a distribution of potential IBD matrices given available marker information. In QTL analyses, its expectation is normally used resulting in potentially reduced accuracy and loss of power. Previously, IBD distributions have been included in models for small human full-sib families. We develop an Expectation-Maximization (EM) algorithm for estimating a full model based on Monte Carlo imputation for applications in large animal pedigrees. Our simulations show that the bias of variance component estimates using traditional expected IBD matrix can be adjusted by accounting for the distribution and that the calculations are computationally feasible for large pedigrees.
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8. |
- Strandberg, Erling, et al.
(author)
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Statistical tools to select for robustness and milk quality
- 2013
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In: Advances in Animal Biosciences. - : Cambridge University Press. - 2040-4700 .- 2040-4719. ; 4:3, s. 606-611
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Journal article (peer-reviewed)abstract
- This work was part of the EU RobustMilk project. In this work package, we have focused on two aspects of robustness, micro- and macro-environmental sensitivity and applied these to somatic cell count (SCC), one aspect of milk quality. We showed that it is possible to combine both categorical and continuous descriptions of the environment in one analysis of genotype by environment interaction. We also developed a method to estimate genetic variation in residual variance and applied it to both simulated and a large field data set of dairy cattle. We showed that it is possible to estimate genetic variation in both micro- and macro-environmental sensitivity in the same data, but that there is a need for good data structure. In a dairy cattle example, this would mean at least 100 bulls with at least 100 daughters each. We also developed methods for improved genetic evaluation of SCC. We estimated genetic variance for some alternative SCC traits, both in an experimental herd data and in field data. Most of them were highly correlated with subclinical mastitis (>0.9) and clinical mastitis (0.7 to 0.8), and were also highly correlated with each other. We studied whether the fact that animals in different herds are differentially exposed to mastitis pathogens could be a reason for the low heritabilities for mastitis, but did not find strong evidence for that. We also created a new model to estimate breeding values not only for the probability of getting mastitis but also for recovering from it. In a progeny-testing situation, this approach resulted in accuracies of 0.75 and 0.4 for these two traits, respectively, which means that it is possible to also select for cows that recover more quickly if they get mastitis.
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10. |
- Jonsdottir, Rakel J., et al.
(author)
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Effects of nutrient loading and fertilization at planting on growth and nutrient status of Lutz spruce (Picea x lutzii) seedlings during the first growing season in Iceland
- 2013
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In: Scandinavian Journal of Forest Research. - : Taylor & Francis. - 0282-7581 .- 1651-1891. ; 28:7, s. 631-641
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Journal article (peer-reviewed)abstract
- The low availability of nitrogen (N) is believed to be one of the major limiting factors of forest regeneration inIceland and frequently under Boreal conditions. Lutz spruce (Picea x lutzii Littl.) seedlings were nutrient loadedusing four fertilization regimes in the end of nursery rotation in autumn 2008 and planted in the following spring,with or without a single dose of fertilizer, on two treeless sites in N-Iceland with contrasting soil fertility.Measurements were made after one growing season. The highest loading level without additional field fertilizationincreased new needle mass by 122% and 152%, for the poor and more fertile site, respectively. The highest loadinglevel with field fertilization increased new needle mass equally, by 188% and 189%, for the poor and more fertilesite, respectively. Retranslocation of N, from old needles to current needles, increased with more loading.However, it was clear that nutrient loading could not replace field fertilization, as the seedlings generally showedan additive response to field fertilization and nutrient loading; doing both always gave the best results in seedlingperformance. As the study only covers field establishment during the first year, the long-term effect of nutrientloading of Lutz spruce cannot be predicted. However, it was concluded that loading might provide an additionalinput for faster plantation establishment during the first growing season after planting.
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