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PubMed | Institute of Animal Breeding and University of Hohenheim
Type: Journal Article | Journal: Genetics, selection, evolution : GSE | Year: 2016

Extending the reference set for genomic predictions in dairy cattle by adding large numbers of cows with genotypes and phenotypes has been proposed as a means to increase reliability of selection decisions for candidates.In this study, we explored the potential of increasing the reliability of breeding values of young selection candidates by genotyping a fixed number of first-crop daughters of each sire from one or two generations in a balanced and regular system of genotyping. Using stochastic simulation, we developed a basic population scenario that mimics the situation in dual-purpose Fleckvieh cattle with respect to important key parameters. Starting with a reference set consisting of only genotyped bulls, we extended this reference set by including increasing numbers of daughter genotypes and phenotypes. We studied the effects on model-derived reliabilities, validation reliabilities and unbiasedness of predicted values for selection candidates. We also illustrate and discuss the effects of a selected sample and an unbalanced sampling of daughters. Furthermore, we quantified the role of selection with respect to the influence on validation reliabilities and contrasted these to model-derived reliabilities.In the most extended design, with 200 daughters per sire genotyped from two generations, single nucleotide polymorphism (SNP) effects were estimated from a reference set of 420,000 cows and 4200 bulls. For this design, the validation reliabilities for candidates reached 80% or more, thereby exceeding the reliabilities that were achieved in traditional progeny-testing designs for a trait with moderate to high heritability. We demonstrate that even a moderate number of 25 genotyped daughters per sire will lead to considerable improvement in the reliability of predicted breeding values for selection candidates. Our results illustrate that the strategy applied to sample females for genotyping has a large impact on the benefits that can be achieved.


Groebner A.E.,TU Munich | Schulke K.,TU Munich | Unterseer S.,TU Munich | Reichenbach H.D.,Institute of Animal Breeding | And 5 more authors.
Placenta | Year: 2010

Bovine trophoblast cells release interferon-τ (IFNT), a type I IFN, as the pregnancy recognition signal. Since type I IFNs exert growth inhibitory and proapoptotic actions, the effect of the conceptus on components of the apoptosis pathways was determined in the bovine endometrium during the periimplantation period. Uteri of Simmental heifers were flushed post mortem at days 12, 15, and 18 of cycle or pregnancy for the recovery of conceptuses and the sampling of ipsilateral endometrial tissue at slaughter for quantitative RT-PCR, immunohistochemistry, caspase activity and TUNEL assays. Endometrium samples of pregnant animals revealed increased transcript levels for the proapoptotic genes XAF1 (day 15: 2.9-fold; day 18: 15.1-fold; p = 0.005) and CASP8 (day 18: 2.4-fold; p = 0.007). The mRNA expression increased significantly with the day of the cycle for the proapoptotic genes FASLG, TNFSF10, TNF and TNFSF1A (p = 0.004, p = 0.006, p = 0.001 and p = 0.007) and the antiapoptotic gene BIRC4 (p = 0.03). We detected high amounts of FASLG transcripts in day 18 conceptuses (16-fold higher than day 18 endometria). This finding was validated at the protein level by immunohistochemistry. To further analyse the endometrial activation of the caspase cascade, the activities of initiator caspase 8 and effector caspases 3/7 were determined luminometrically. No difference between pregnant and cyclic animals was found for either caspase activity. Additionally, a TUNEL assay showed no increase of apoptotic cells in the pregnant endometrium. In conclusion, although the bovine conceptus induces the expression of proapoptotic genes, neither an activation of a caspase cascade nor an increase of apoptotic cells was noticed. These results suggest inhibitory mechanisms preventing endometrial cells from programmed cell death. © 2009 Elsevier Ltd. All rights reserved.


Martini J.W.R.,University of Gottingen | Wimmer V.,Einbeck | Erbe M.,University of Gottingen | Erbe M.,Institute of Animal Breeding | Simianer H.,University of Gottingen
Theoretical and Applied Genetics | Year: 2016

Key message: Models based on additive marker effects and on epistatic interactions can be translated into genomic relationship models. This equivalence allows to perform predictions based on complex gene interaction models and reduces computational effort significantly.Abstract: In the theory of genome-assisted prediction, the equivalence of a linear model based on independent and identically normally distributed marker effects and a model based on multivariate Gaussian distributed breeding values with genomic relationship as covariance matrix is well known. In this work, we demonstrate equivalences of marker effect models incorporating epistatic interactions and corresponding mixed models based on relationship matrices and show how to exploit these equivalences computationally for genome-assisted prediction. In particular, we show how models with epistatic interactions of higher order (e.g., three-factor interactions) translate into linear models with certain covariance matrices and demonstrate how to construct epistatic relationship matrices for the linear mixed model, if we restrict the model to interactions defined a priori. We illustrate the practical relevance of our results with a publicly available data set on grain yield of wheat lines growing in four different environments. For this purpose, we select important interactions in one environment and use this knowledge on the network of interactions to increase predictive ability of grain yield under other environmental conditions. Our results provide a guide for building relationship matrices based on knowledge on the structure of trait-related gene networks. © 2016 Springer-Verlag Berlin Heidelberg


PubMed | Institute of Animal Breeding and Leibniz Institute for Farm Animal Biology
Type: | Journal: BMC genomics | Year: 2016

MHC class I genotyping is essential for a wide range of biomedical, immunological and biodiversity applications. Whereas in human a comprehensive MHC class I allele catalogue is available, respective data in non-model species is scarce in spite of decades of research.Taking advantage of the new high-throughput RNA sequencing technology (RNAseq), we developed a novel RNAseq-assisted method (RAMHCIT) for MHC class I typing at nucleotide level. RAMHCIT is performed on white blood cells, which highly express MHC class I molecules enabling reliable discovery of new alleles and discrimination of closely related alleles due to the high coverage of alleles with reads. RAMHCIT is more comprehensive than previous methods, because no targeted PCR pre-amplification of MHC loci is necessary, which avoids preselection of alleles as usually encountered, when amplification with MHC class I primers is performed prior to sequencing. In addition to allele identification, RAMHCIT also enables quantification of MHC class I expression at allele level, which was remarkably consistent across individuals.Successful application of RAMHCIT is demonstrated on a data set from cattle with different phenotype regarding a lethal, vaccination-induced alloimmune disease (bovine neonatal pancytopenia), for which MHC class I alleles had been postulated as causal agents.


Gotz K.-U.,Institute of Animal Breeding | Luntz B.,Institute of Animal Breeding | Robeis J.,Institute of Animal Breeding | Edel C.,Institute of Animal Breeding | And 4 more authors.
Livestock Science | Year: 2015

Systematic breeding of polled Fleckvieh (Simmental) cattle in Bavaria dates back until 1974 when the first polled cow was purchased for breeding purposes. Until 1985 three polled bulls and two more polled dams were purchased and from 1984 on the first homozygous bulls were produced via embryo transfer. Until 1990 the polled allele was only common in beef strains of the Fleckvieh breed. At the beginning of the 1990s the first polled alleles were introduced into the dairy herd of the State Research Farm in Grub. This research farm acted as the nucleus for the introgression of the polled allele in the dual-purpose lines of the Fleckvieh breed. Since 2003 polled calves in all herds under milk recording were systematically recorded and the polled phenotype was regularly examined by employees of the Bavarian State Research Institute for Agriculture. At the same time a systematic cooperation with Bavarian herdbook organizations and AI-stations was established. Between 2000 and 2011 in total 193 polled bulls were raised at the Bavarian State Research Institute for Agriculture (LfL), of which 37 entered AI-stations. Currently the dual-purpose population of Fleckvieh comprises 7055 polled cows and 175 polled AI-sires. In 2013 and 2014 approximately 22,000 and 32,000 polled calves were born per year. The analysis of relationships showed that the polled bulls are less related to the horned population and that until now the introgression has caused negligible amounts of additional inbreeding. It is expected that in 2021 the proportion of polled cows in the Fleckvieh dual-purpose population will be at 10.5% of all cows if the progression of polledness continues linearly. However, it can be expected that the progression will accelerate due to the new possibilities offered by genomic preselection of polled AI-bulls. First experiences with genomically preselected polled bulls show a very good acceptance among breeders. © 2015 Elsevier B.V.


Pimentel E.C.G.,Institute of Animal Breeding | Edel C.,Institute of Animal Breeding | Emmerling R.,Institute of Animal Breeding | Gotz K.-U.,Institute of Animal Breeding
Journal of Dairy Science | Year: 2015

The objective of this study was to investigate in detail the biasing effects of imputation errors on genomic predictions. Direct genomic values (DGV) of 3,494 Brown Swiss selection candidates for 37 production and conformation traits were predicted using either their observed 50K genotypes or their 50K genotypes imputed from a mimicked 6K chip. Changes in DGV caused by imputation errors were shown to be systematic. The DGV of top animals were, on average, underestimated and that of bottom animals were, on average, overestimated when imputed genotypes were used instead of observed genotypes. This pattern might be explained by the fact that imputation algorithms will usually suggest the most frequent haplotype from the sample whenever a haplotype cannot be determined unambiguously. That was empirically shown to cause an advantage for the bottom animals and a disadvantage for the top animals. © 2015 American Dairy Science Association.


Fritscher-Ravens A.,University of Kiel | Milla P.,University College London | Ellrichmann M.,University of Kiel | Hellwig I.,University of Kiel | And 3 more authors.
Gastrointestinal Endoscopy | Year: 2013

Background: Many GI motility disorders are associated with underlying GI neuromuscular pathology, which requires full-thickness biopsies (FTB) for histopathologic diagnosis. Currently, none of the endoscopy-based attempts to obtain FTB specimens have proven suitable for routine use. This study evaluated a novel endoscopic prototype device (ED) for this purpose. Objective: To determine (1) the ability of the ED to obtain suitable FTB specimens, (2) associated complications, (3) feasibility of reliable defect closure, and (4) ability to evaluate intramural neuromuscular components. Design: Preclinical proof-of-concept study in 30 pigs. Setting: Animal laboratory. Intervention: Gastric FTB specimens were obtained with a circular cutter and anchor. The defect was closed by over-the-scope clips/T-tags. The resection site was inspected via laparoscopy. After 2 to 4 weeks, necropsy was carried out to evaluate late complications. Main Outcome Measurements: Feasibility, safety, and closure rate of the procedure. FTB specimens were assessed by histology/immunohistochemistry to visualize enteric neuromusculature. Results: A total of 29 of 30 procedures were successfully performed; one hemorrhage required endoscopic treatment. A total of 29 of 30 FTB specimens (mean diameter 9.1 mm) were retrieved in 7.1 ± 0.4 minutes (range 3.0-12.5 minutes), displaying optimal tissue quality. Defect closure took 10.8 ± 0.9 minutes (range 7.2-32 minutes). Laparoscopy did not reveal damage to adjacent organs. Necropsy showed well-healed scars at the resection site and no complications, peritonitis, or abscess formation. Histology showed smooth muscle layers and submucosal and myenteric ganglia. Limitations: Survival animal pilotstudy, no patients. Conclusion: The novel ED enabled safe harvesting of well-preserved FTB specimens. Defect closure proved to be reliable. All neuromuscular structures relevant for histopathologic evaluation of GI neuromuscular pathology were demonstrated. Further studies are needed to verify the efficacy of this prototype device in the entire gut and in humans. © 2013 American Society for Gastrointestinal Endoscopy.


Groebner A.E.,TU Munich | Rubio-Aliaga I.,TU Munich | Schulke K.,TU Munich | Reichenbach H.D.,Institute of Animal Breeding | And 4 more authors.
Reproduction | Year: 2011

Amino acids (AAs) are crucial for the developing conceptus prior to implantation. To provide insights into the requirements of the bovine embryo, we determined the AA composition of the uterine fluid. At days 12, 15, and 18 post-estrus, the uteri of synchronized pregnant and non-pregnant Simmental heifers were flushed for the analysis of 41 AAs and their derivatives by liquid chromatography-tandem mass spectrometry. The ipsilateral endometrium was sampled for quantitative PCR. In addition to a pregnancy-dependent increase of the essential AAs (P<0.01), we detected elevated concentrations for most non-essential proteinogenic AAs. Histidine (His) and the expression of the His/peptide transporter solute carrier 15A3 (SLC15A3) were significantly increased at day 18 of pregnancy in vivo. In addition, SLC15A3 was predominantly stimulated by trophoblast-derived interferon-τ in stroma cells of an in vitro co-culture model of endometrial cells. Our results show an increased concentration of AAs most likely to optimally provide the elongating pre-attachment conceptus with nutrients. © 2011 Society for Reproduction and Fertility.


Awad A.,Ludwig Maximilians University of Munich | Russ I.,Tierzuchtforschung E.V. Munich | Emmerling R.,Institute of Animal Breeding | Forster M.,Ludwig Maximilians University of Munich | And 2 more authors.
Animal Genetics | Year: 2010

We analysed a QTL affecting milk yield (MY), milk protein yield (PY) and milk fat yield (FY) in the dual purpose cattle breed Fleckvieh on BTA5. Twenty-six microsatellite markers covering 135 cM were selected to analyse nine half-sib families containing 605 sons in a granddaughter design. We thereby assigned two new markers to the public linkage map using the CRI-MAP program. Phenotypic records were daughter yield deviations (DYD) originating from the routinely performed genetic evaluations of breeding animals. To determine the position of the QTL, three different approaches were applied: Interval mapping (IM), linkage analysis by variance component analysis (LAVC), and combined linkage disequilibrium (LD) and linkage (LDL) analysis. All three methods mapped the QTL in the same marker interval (BM2830-ETH152) with the greatest test-statistic value at 118, 119.33 and 119.33 cM respectively. The positive QTL allele simultaneously increases DYD in the first lactation by 272 kg milk, 7.1 kg milk protein and 7.0 kg milk fat. Although the mapping accuracy and the significance of a QTL effect increased from IM over LAVC to LDL, the confidence interval was large (13, 20 and 24 cM for FY, MY and PY respectively) for the positional cloning of the causal gene. The estimated averages of pair wise marker LD with a distance <5 cM were low (0.107) and reflect the large effective population size of the Fleckvieh subpopulation analysed. This low level of LD suggests a need for increase in marker density in following fine mapping steps. © 2009 Stichting International Foundation for Animal Genetics.


PubMed | Institute of Animal Breeding
Type: Journal Article | Journal: Journal of dairy science | Year: 2016

In this study we investigate the potential of enlarging the reference population for genomic prediction in dairy cattle by routinely genotyping a random sample of the first-crop daughters of every AI bull in the breeding program. We analyzed small nuclear pedigrees, each consisting of a genotyped selection candidate and 3 generations of genotyped male ancestors. Genotypes were taken from the genomic routine evaluation of Fleckvieh cattle in Germany and Austria. The phenotypic information of a daughter of any one male in each of these pedigrees was either considered to be part of the daughter yield deviation of the corresponding sire, or was assumed to be an individually observed genotyped daughter of this sire. Daughter genotypes in this case were simulated from phased haplotypes of their sires and random maternal gametes drawn from a haplotype library. We measured the gain from genotyping daughters as the increase in model-based theoretical reliability of the genomic prediction for a putative selection candidate. We expressed the improvements as a marginal increase, corresponding to an increase in reliability at a reliability baseline level of zero, to simplify comparisons. Results were encouraging with 2 to 40% of marginal reliability increase for selection candidates depending on the assumed heritability of the trait and the number of daughters modeled to be genotyped in the design.

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