A plea to implement robustness into a breeding goal: poultry as an example

The combination of breeding for increased production and the intensification of housing conditions have resulted in increased occurrence of behavioral, physiological, and immunological disorders. These disorders affect health and welfare of production animals negatively. For future livestock systems, it is important to consider how to manage and breed production animals. In this paper, we will focus on selective breeding of laying hens. Selective breeding should not only be defined in terms of production, but should also include traits related to animal health and welfare. For this we like to introduce the concept of robustness. The concept of robustness includes individual traits of an animal that are relevant for health and welfare. Improving robustness by selective breeding will increase (or restore) the ability of animals to interact successfully with the environment and thereby to make them more able to adapt to an appropriate husbandry system. Application of robustness into a breeding goal will result in animals with improved health and welfare without affecting their integrity. Therefore, in order to be ethically acceptable, selective breeding in animal production should accept robustness as a breeding goa

Purkinje cell-specific ablation of CaV2.1 Channels is sufficient to cause cerebellar ataxia in mice

The Cacna1a gene encodes the α1A subunit of voltage-gated CaV2.1 Ca2+ channels that are involved in neurotransmission at central synapses. CaV2.1-α1- knockout (α1KO) mice, which lack CaV2.1 channels in all neurons, have a very severe phenotype of cerebellar ataxia and dystonia, and usually die around postnatal day 20. This early lethality, combined with the wide expression of CaV2.1 channels throughout the cerebellar cortex and nuclei, prohibited determination of the contribution of particular cerebellar cell types to the development of the severe neurobiological phenotype in Cacna1a mutant mice. Here, we crossed conditional Cacna1a mice with transgenic mice expressing Cre recombinase, driven by the Purkinje cell-specific Pcp2 promoter, to specifically ablate the CaV2.1- α1A subunit and thereby CaV2.1 channels in Purkinje cells. Purkinje cell CaV2.1-α1A-knockout (PCα1KO) mice aged without difficulties, rescuing the lethal phenotype seen in α1KO mice. PCα1KO mice exhibited cerebellar ataxia starting around P12, much earlier than the first signs of progressive Purkinje cell loss, which appears in these mice between P30 and P45. Secondary cell loss was observed in the granular and molecular layers of the cerebellum and the volume of all individual cerebellar nuclei was reduced. In this mouse model with a cell type-specific ablation of CaV2.1 channels, we show that ablation of CaV2.1 channels restricted to Purkinje cells is sufficient to cause cerebellar ataxia. We demonstrate that spatial ablation of CaV2.1 channels may help in unraveling mechanisms of human disease

Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice

Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. To date, targeting these translocations to mouse B cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1(+)Lin(-) hematopoietic stem/progenitor cells, which showed NF-κB activation and early lymphoid priming, being selectively skewed toward B-cell differentiation. These cells accumulated in extranodal tissues and gave rise to clonal tumors recapitulating the principal clinical, biological, and molecular genetic features of MALT lymphoma. Deletion of p53 gene accelerated tumor onset and induced transformation of MALT lymphoma to activated B-cell diffuse large-cell lymphoma (ABC-DLBCL). Treatment of MALT1-induced lymphomas with a specific inhibitor of MALT1 proteolytic activity decreased cell viability, indicating that endogenous Malt1 signaling was required for tumor cell survival. Our study shows that human-like lymphomas can be modeled in mice by targeting MALT1 expression to hematopoietic stem/progenitor cells, demonstrating the oncogenic role of MALT1 in lymphomagenesis. Furthermore, this work establishes a molecular link between MALT lymphoma and ABC-DLBCL, and provides mouse models to test MALT1 inhibitors. Finally, our results suggest that hematopoietic stem/progenitor cells may be involved in the pathogenesis of human mature B-cell lymphomas

Genetics of survival in cannibalistic laying hens: The contribution of social effects

Mortality due to cannibalism in laying hens is a worldwide economic and welfare problem occurring in all types of commercial poultry housing systems. Due to prohibition of beak-trimming and the traditional battery system in the European Union in the near future, mortality due to cannibalism in laying hens may increase. To reduce mortality in laying hens, it is possible to use genetic selection. Mortality due to cannibalism, however, depends on social interactions between group members. Traditional selection methods neglect these social interactions, meaning that they ignore the genetic effect an individual has on its group members. These methods are, therefore, not very effective. The main aim of this thesis is to investigate the effect of social interactions on the heritable variance in mortality due to cannibalism in laying hens and to develop a selection method that takes into account social interactions. To investigate the effect of social interactions on the heritable variance in mortality due to cannibalism, genetic parameters for direct and associative effects on survival time in three layer lines were estimated. For all three layer lines it was found that social interactions contribute approximately two-third of the heritable variation in survival time. The heritable variation in survival time is, therefore, substantially larger than suggested by the traditional methods currently used in poultry breeding. To improve traits affected by social interactions in laying hens, a solution is to select individually housed candidates based on the performance of their full sibs kept in family groups. Theoretical results suggest that this selection method offers good opportunities to improve traits affected by social interactions. A selection experiment was applied aiming to improve mortality due to cannibalism in laying hens using selection based on relatives. After one generation, mortality was 10% lower in the selection line compared to the control. In the second generation, no significant effect was found, which seemed to be related to environmental factors. Results in this thesis suggest that prospects for reducing mortality due to cannibalism by means of genetic selection are good. Using selection methods that incorporate social interactions may lead to substantial reduction of one of the major welfare problems in egg production. Further research is needed to investigate the effect of group size and kin recognition on social interactions. <br/

Genetic solutions to reduce injurious pecking in laying hens

Survival of commercial laying hens is an important trait. Feather pecking has a large effect on the survival of birds. To improve survival it is important to use quantitative genetic methods that take into account both the direct genetic effect (victim effect) and the indirect genetic effect (actor effect). For survival time, we found that the victim effect contributes 13-64% of total heritable variation, while the actor effect contributes 36-87% of total heritable variation. Together, they explain 15-26% of total phenotypic variation in survival time. Here we compare different breeding programme designs to identify the optimum selection strategy against mortality due to feather pecking. Results show that mortality due to feather pecking can be reduced using genetic approaches, taking into account direct and indirect genetic effects. We performed a selection experiment using selection based on relatives. Using this method enables selection against mortality due to feather pecking in laying hens. However, selection intensities were small. Genomic selection can be a promising tool to select against mortality due to feather pecking. Model predictions show that genomic selection is expected to yield a rapid reduction of mortality due to feather pecking, but a challenge will be to reduce mortality due to feather pecking in large groups

Response to commentary on “Examples of overlooking common sense solutions: the domestication gene and selection against mortality”.

In a commentary in Frontiers, Van Rooijen (2014) states: “Today the developments in genetics are exciting. Perhaps this explains why geneticists sometimes seem to overlook common sense solutions. One example of this is the selection experiment done by Bijma et al. (2007a,b). ……As a result their selection seemed not very efficient.” In those two papers, however, we do not report a selection experiment. The first paper presents general quantitative genetic theory, showing how interactions among individuals alter heritable variation in traits, and how this can affect response to selection. The second paper presents general methodology to estimate the quantitative genetic parameters for such traits, and illustrates this methodology using a population of laying hens showing high mortality due to pecking behavior. Neither of those papers report results of a selection experiment

Using pooled data to estimate variance components and breeding values for traits affected by social interactions

Background Through social interactions, individuals affect one another’s phenotype. In such cases, an individual’s phenotype is affected by the direct (genetic) effect of the individual itself and the indirect (genetic) effects of the group mates. Using data on individual phenotypes, direct and indirect genetic (co)variances can be estimated. Together, they compose the total genetic variance that determines a population’s potential to respond to selection. However, it can be difficult or expensive to obtain individual phenotypes. Phenotypes on traits such as egg production and feed intake are, therefore, often collected on group level. In this study, we investigated whether direct, indirect and total genetic variances, and breeding values can be estimated from pooled data (pooled by group). In addition, we determined the optimal group composition, i.e. the optimal number of families represented in a group to minimise the standard error of the estimates. Methods This study was performed in three steps. First, all research questions were answered by theoretical derivations. Second, a simulation study was conducted to investigate the estimation of variance components and optimal group composition. Third, individual and pooled survival records on 12 944 purebred laying hens were analysed to investigate the estimation of breeding values and response to selection. Results Through theoretical derivations and simulations, we showed that the total genetic variance can be estimated from pooled data, but the underlying direct and indirect genetic (co)variances cannot. Moreover, we showed that the most accurate estimates are obtained when group members belong to the same family. Additional theoretical derivations and data analyses on survival records showed that the total genetic variance and breeding values can be estimated from pooled data. Moreover, the correlation between the estimated total breeding values obtained from individual and pooled data was surprisingly close to one. This indicates that, for survival in purebred laying hens, loss in response to selection will be small when using pooled instead of individual data. Conclusions Using pooled data, the total genetic variance and breeding values can be estimated, but the underlying genetic components cannot. The most accurate estimates are obtained when group members belong to the same family

Response to commentary on “Examples of overlooking common sense solutions: the domestication gene and selection against mortality”.

In a commentary in Frontiers, Van Rooijen (2014) states: “Today the developments in genetics are exciting. Perhaps this explains why geneticists sometimes seem to overlook common sense solutions. One example of this is the selection experiment done by Bijma et al. (2007a,b). ……As a result their selection seemed not very efficient.” In those two papers, however, we do not report a selection experiment. The first paper presents general quantitative genetic theory, showing how interactions among individuals alter heritable variation in traits, and how this can affect response to selection. The second paper presents general methodology to estimate the quantitative genetic parameters for such traits, and illustrates this methodology using a population of laying hens showing high mortality due to pecking behavior. Neither of those papers report results of a selection experiment