Bjarne Gjerde

Hepatic gene expression profiling reveals protective responses in Atlantic salmon vaccinated against furunculosis

BackgroundFurunculosis, a disease caused with gram negative bacteria Aeromonas salmonicida produces heavy losses in aquaculture. Vaccination against furunculosis reduces mortality of Atlantic salmon but fails to eradicate infection. Factors that determine high individual variation of vaccination efficiency remain unknown. We used gene expression analyses to search for the correlates of vaccine protection against furunculosis in Atlantic salmon.ResultsNaïve and vaccinated fish were challenged by co-habitance. Fish with symptoms of furunculosis at the onset of mass mortality (LR - low resistance) and survivors (HR - high resistance) were sampled. Hepatic gene expression was analyzed with microarray (SFA2.0 - immunochip) and real-time qPCR. Comparison of LR and HR indicated changes associated with the protection and results obtained with naïve fish were used to find and filter the vaccine-independent responses. Genes involved in recruitment and migration of immune cells changed expression in both directions with greater magnitude in LR. Induction of the regulators of immune responses was either equal (NFkB) or greater (Jun) in LR. Expression levels of proteasome components and extracellular proteases were higher in LR while protease inhibitors were up-regulated in HR. Differences in chaperones and protein adaptors, scavengers of reactive oxygen species and genes for proteins of iron metabolism suggested cellular and oxidative stress in LR. Reduced levels of free iron and heme can be predicted in LR by gene expression profiles with no protection against pathogen. The level of complement regulation was greater in HR, which showed up-regulation of the components of membrane attack complex and the complement proteins that protect the host against the auto-immune damages. HR fish was also characterized with up-regulation of genes for proteins involved in the protection of extracellular matrix, lipid metabolism and clearance of endogenous and exogenous toxic compounds. A number of genes with marked expression difference between HR and LR can be considered as positive and negative correlates of vaccine protection against furunculosis.ConclusionEfficiency of vaccination against furunculosis depends largely on the ability of host to neutralize the negative impacts of immune responses combined with efficient clearance and prevention of tissue damages.

Quantitative genetics of taura syndrome resistance in pacific white shrimp (penaeus vannamei): a cure model approach

BackgroundIn aquaculture breeding, resistance against infectious diseases is commonly assessed as time until death under exposure to a pathogen. For some diseases, a fraction of the individuals may appear as cured (non-susceptible), and the resulting survival time may thus be a result of two confounded underlying traits, i.e., endurance (individual hazard) and susceptibility (whether at risk or not), which may be accounted for by fitting a cure survival model. We applied a cure model to survival data of Pacific white shrimp (Penaeus vannamei) challenged with the Taura syndrome virus, which is one of the major pathogens of Panaeid shrimp species.MethodsIn total, 15,261 individuals of 513 full-sib families from three generations were challenge-tested in 21 separate tests (tanks). All challenge-tests were run until mortality naturally ceased. Time-until-event data were analyzed with a mixed cure survival model using Gibbs sampling, treating susceptibility and endurance as separate genetic traits.ResultsOverall mortality at the end of test was 28%, while 38% of the population was considered susceptible to the disease. The estimated underlying heritability was high for susceptibility (0.41 ± 0.07), but low for endurance (0.07 ± 0.03). Furthermore, endurance and susceptibility were distinct genetic traits (rg = 0.22 ± 0.25). Estimated breeding values for endurance and susceptibility were only moderately correlated (0.50), while estimated breeding values from classical models for analysis of challenge-test survival (ignoring the cured fraction) were closely correlated with estimated breeding values for susceptibility, but less correlated with estimated breeding values for endurance.ConclusionsFor Taura syndrome resistance, endurance and susceptibility are apparently distinct genetic traits. However, genetic evaluation of susceptibility based on the cure model showed clear associations with standard genetic evaluations that ignore the cure fraction for these data. Using the current testing design, genetic variation in observed survival time and absolute survival at the end of test were most likely dominated by genetic variation in susceptibility. If the aim is to reduce susceptibility, earlier termination of the challenge-test or back-truncation of the follow-up period should be avoided, as this may shift focus of selection towards endurance rather than susceptibility.

A sequential threshold cure model for genetic analysis of time-to-event data1

In analysis of time-to-event data, classical survival models ignore the presence of potential nonsusceptible (cured) individuals, which, if present, will invalidate the inference procedures. Existence of nonsusceptible individuals is particularly relevant under challenge testing with specific pathogens, which is a common procedure in aquaculture breeding schemes. A cure model is a survival model accounting for a fraction of nonsusceptible individuals in the population. This study proposes a mixed cure model for time-to-event data, measured as sequential binary records. In a simulation study survival data were generated through 2 underlying traits: susceptibility and endurance (risk of dying per time-unit), associated with 2 sets of underlying liabilities. Despite considerable phenotypic confounding, the proposed model was largely able to distinguish the 2 traits. Furthermore, if selection is for improved susceptibility rather than endurance, the error of applying a classical survival model was nonnegligible. The difference was most pronounced for scenarios with substantial underlying genetic variation in endurance and when the 2 underlying traits were lowly genetically correlated. In the presence of nonsusceptible individuals, the method provides a novel and more accurate tool for utilization of time-to-event data, and has also been proven successful when applied to zero-inflated longitudinal binary data.